Surgery

In the 1990s, researchers found that patients undergoing any type of surgical procedure were more than twice as likely to die if they developed postsurgical infection.¹ Work to reduce surgical site infection (SSI) has and does continue, with perioperative antibiotics representing a good part of that effort. The American College of Obstetricians and Gynecologists currently recommends such antibiotic therapy for women undergoing laparotomy and laparoscopic hysterectomy.² ACOG does not, however, recommend prophylactic antibiotics for myomectomy procedures.³ Rates of infection for hysterectomy have been reported to be 3.9% for abdominal and 1.4% for minimally invasive approaches.⁴

To determine the current use of antibiotics during myomectomy and associated rates of SSI at their institutions, Dipti Banerjee, MD, and colleagues conducted a retrospective analysis of women undergoing laparoscopic or abdominal myomectomy between February 2013 and December 2017 at the University of California, Los Angeles and Hoag Memorial Hospital in Orange County, California. They presented their study results at AAGL’s 49th Global Congress on MIGS, held virtually November 6-14, 2020.³

Rate of SSI after myomectomy

A total of 620 women underwent laparoscopic myomectomy and 563 underwent open myomectomy during the study period. Antibiotics were used in 76.9% of cases. SSI developed within 6 weeks of surgery in 34 women (2.9%) overall. The women undergoing abdominal myomectomy without antibiotics were more likely to experience SSI than the women who received antibiotics (odds ratio [OR], 4.89; confidence interval [CI], 1.80–13.27; P = .0006). For laparoscopic myomectomy, antibiotic use did not affect the odds of developing SSI (OR, 1.08; CI, 0.35–3.35).

Antibiotics were more likely to be used in certain cases

Antibiotics were more likely to be administered for patients who:

• were obese (body mass index ≥30 kg/m²) (P = .009)
• underwent previous abdominal surgery (P = .001)
• underwent laparotomy (P <.0001)
• had endometrial cavity entry (P <.0001)
• had >1 fibroid (P = .0004) or an aggregate fibroid weight >500 g (P <.0001).

More data on antibiotics for myomectomy

In a retrospective study conducted at 2 academic hospitals in Boston, Massachusetts, 1,211 women underwent myomectomy from 2009 to 2016. (Exclusions were use of vaginal or hysteroscopic myomectomy, chromopertubation, or conversion to hysterectomy.) More than 92% of the women received perioperative antibiotics at the time of surgery. Although demographics were similar between women receiving and not receiving antibiotics, women who received antibiotics were more likely to have longer operative times (median 140 vs 85 min), a greater myoma burden (7 vs 2 myomas removed and weight 255 vs 53 g), and lose blood during the procedure (137 vs 50 mL). These women also were 4 times less likely to have surgical site infection (adjusted OR, 3.77; 95% CI, 1.30–10.97; P = .015).^5,6

Banerjee and colleagues say that their California study demonstrates “that the majority of surgeons elect to use antibiotics prophylactically” during myomectomy, despite current ACOG guidelines, and that their findings of benefit for abdominal myomectomy but not for laparoscopic myomectomy should inform future guidance on antibiotics for myomectomy surgery.³

In the 1990s, researchers found that patients undergoing any type of surgical procedure were more than twice as likely to die if they developed postsurgical infection.¹ Work to reduce surgical site infection (SSI) has and does continue, with perioperative antibiotics representing a good part of that effort. The American College of Obstetricians and Gynecologists currently recommends such antibiotic therapy for women undergoing laparotomy and laparoscopic hysterectomy.² ACOG does not, however, recommend prophylactic antibiotics for myomectomy procedures.³ Rates of infection for hysterectomy have been reported to be 3.9% for abdominal and 1.4% for minimally invasive approaches.⁴

To determine the current use of antibiotics during myomectomy and associated rates of SSI at their institutions, Dipti Banerjee, MD, and colleagues conducted a retrospective analysis of women undergoing laparoscopic or abdominal myomectomy between February 2013 and December 2017 at the University of California, Los Angeles and Hoag Memorial Hospital in Orange County, California. They presented their study results at AAGL’s 49th Global Congress on MIGS, held virtually November 6-14, 2020.³

Rate of SSI after myomectomy

A total of 620 women underwent laparoscopic myomectomy and 563 underwent open myomectomy during the study period. Antibiotics were used in 76.9% of cases. SSI developed within 6 weeks of surgery in 34 women (2.9%) overall. The women undergoing abdominal myomectomy without antibiotics were more likely to experience SSI than the women who received antibiotics (odds ratio [OR], 4.89; confidence interval [CI], 1.80–13.27; P = .0006). For laparoscopic myomectomy, antibiotic use did not affect the odds of developing SSI (OR, 1.08; CI, 0.35–3.35).

Antibiotics were more likely to be used in certain cases

Antibiotics were more likely to be administered for patients who:

• were obese (body mass index ≥30 kg/m²) (P = .009)
• underwent previous abdominal surgery (P = .001)
• underwent laparotomy (P <.0001)
• had endometrial cavity entry (P <.0001)
• had >1 fibroid (P = .0004) or an aggregate fibroid weight >500 g (P <.0001).

More data on antibiotics for myomectomy

In a retrospective study conducted at 2 academic hospitals in Boston, Massachusetts, 1,211 women underwent myomectomy from 2009 to 2016. (Exclusions were use of vaginal or hysteroscopic myomectomy, chromopertubation, or conversion to hysterectomy.) More than 92% of the women received perioperative antibiotics at the time of surgery. Although demographics were similar between women receiving and not receiving antibiotics, women who received antibiotics were more likely to have longer operative times (median 140 vs 85 min), a greater myoma burden (7 vs 2 myomas removed and weight 255 vs 53 g), and lose blood during the procedure (137 vs 50 mL). These women also were 4 times less likely to have surgical site infection (adjusted OR, 3.77; 95% CI, 1.30–10.97; P = .015).^5,6

Banerjee and colleagues say that their California study demonstrates “that the majority of surgeons elect to use antibiotics prophylactically” during myomectomy, despite current ACOG guidelines, and that their findings of benefit for abdominal myomectomy but not for laparoscopic myomectomy should inform future guidance on antibiotics for myomectomy surgery.³

In the 1990s, researchers found that patients undergoing any type of surgical procedure were more than twice as likely to die if they developed postsurgical infection.¹ Work to reduce surgical site infection (SSI) has and does continue, with perioperative antibiotics representing a good part of that effort. The American College of Obstetricians and Gynecologists currently recommends such antibiotic therapy for women undergoing laparotomy and laparoscopic hysterectomy.² ACOG does not, however, recommend prophylactic antibiotics for myomectomy procedures.³ Rates of infection for hysterectomy have been reported to be 3.9% for abdominal and 1.4% for minimally invasive approaches.⁴

To determine the current use of antibiotics during myomectomy and associated rates of SSI at their institutions, Dipti Banerjee, MD, and colleagues conducted a retrospective analysis of women undergoing laparoscopic or abdominal myomectomy between February 2013 and December 2017 at the University of California, Los Angeles and Hoag Memorial Hospital in Orange County, California. They presented their study results at AAGL’s 49th Global Congress on MIGS, held virtually November 6-14, 2020.³

Rate of SSI after myomectomy

A total of 620 women underwent laparoscopic myomectomy and 563 underwent open myomectomy during the study period. Antibiotics were used in 76.9% of cases. SSI developed within 6 weeks of surgery in 34 women (2.9%) overall. The women undergoing abdominal myomectomy without antibiotics were more likely to experience SSI than the women who received antibiotics (odds ratio [OR], 4.89; confidence interval [CI], 1.80–13.27; P = .0006). For laparoscopic myomectomy, antibiotic use did not affect the odds of developing SSI (OR, 1.08; CI, 0.35–3.35).

Antibiotics were more likely to be used in certain cases

Antibiotics were more likely to be administered for patients who:

• were obese (body mass index ≥30 kg/m²) (P = .009)
• underwent previous abdominal surgery (P = .001)
• underwent laparotomy (P <.0001)
• had endometrial cavity entry (P <.0001)
• had >1 fibroid (P = .0004) or an aggregate fibroid weight >500 g (P <.0001).

More data on antibiotics for myomectomy

In a retrospective study conducted at 2 academic hospitals in Boston, Massachusetts, 1,211 women underwent myomectomy from 2009 to 2016. (Exclusions were use of vaginal or hysteroscopic myomectomy, chromopertubation, or conversion to hysterectomy.) More than 92% of the women received perioperative antibiotics at the time of surgery. Although demographics were similar between women receiving and not receiving antibiotics, women who received antibiotics were more likely to have longer operative times (median 140 vs 85 min), a greater myoma burden (7 vs 2 myomas removed and weight 255 vs 53 g), and lose blood during the procedure (137 vs 50 mL). These women also were 4 times less likely to have surgical site infection (adjusted OR, 3.77; 95% CI, 1.30–10.97; P = .015).^5,6

Banerjee and colleagues say that their California study demonstrates “that the majority of surgeons elect to use antibiotics prophylactically” during myomectomy, despite current ACOG guidelines, and that their findings of benefit for abdominal myomectomy but not for laparoscopic myomectomy should inform future guidance on antibiotics for myomectomy surgery.³

A quality improvement plan incorporating vaginal cleansing and azithromycin significantly reduced surgical-site infections (SSIs) after cesarean deliveries, reported Johanna Quist-Nelson, MD, of the University of North Carolina, Chapel Hill.

“Surgical site infections after a cesarean delivery are more common if the patient is in labor or has ruptured membranes,” she said at the 2020 virtual meeting of the American College of Obstetricians and Gynecologists.. 

Two options to decrease the risk of SSIs after cesarean for those patients in labor or with ruptured membranes are vaginal cleansing and azithromycin, given in addition to preoperative antibiotics, Dr. Quist-Nelson said. She and her colleagues conducted a quality improvement study of the effects of a stepwise implementation of vaginal cleansing and azithromycin to reduce SSIs at cesarean delivery in this high-risk population. The data were collected from 2016 to 2019 at Thomas Jefferson University, Philadelphia.

“We aimed to decrease our SSI rate by 30% by adopting an intervention of cleansing followed by azithromycin,” she said.

The researchers added vaginal cleansing to the SSI prevention protocol in January 2017, with the addition of azithromycin in March 2018. Vaginal cleansing involved 30 seconds of anterior to posterior cleaning prior to urinary catheter placement. Azithromycin was given at a dose of 500 mg intravenously in addition to preoperative antibiotics and within an hour of cesarean delivery.

A total of 1,033 deliveries qualified for the study by being in labor or with ruptured membranes; of these 291 were performed prior to the interventions, 335 received vaginal cleansing only, and 407 received vaginal cleansing and azithromycin. The average age of the participants was 30 years; approximately 42% were Black, and 32% were White.
 

Cleansing protocol reduces SSIs

Overall, the rate of SSIs was 22% in the standard care group, 17% in the vaginal cleansing group, and 15% in the vaginal cleansing plus azithromycin group. When broken down by infection type, no deep SSI occurred in the vaginal cleansing or cleansing plus azithromycin group, compared with 2% of the standard care group (P = .009). In addition, endometritis, which is an organ-space SSI, was significantly lower in the cleansing group (10%) and the cleansing plus azithromycin group (11%), compared with the standard care group (16%).

The study findings were limited by factors including the use of EMRs for collection of data, and given that it is a quality improvement study, there is a potential lack of generalizability to other institutions. The study focused on patients at high risk for SSI and the use of the Plan-Do-Study-Act (PDSA) method of conducting the research, Dr. Quist-Nelson said. Compared with standard care, the implementation of vaginal cleansing reduced the SSI rate by 33%, with no significantly further change in SSI after the addition of azithromycin, she concluded.
 

Data sharing boosts compliance

In a question-and-answer session, Dr. Quist-Nelson noted that povidone iodine (Betadine) was chosen for vaginal cleansing because it was easily accessible at her institution, but that patients with allergies were given chlorhexidine. The cleansing itself was “primarily vaginal, not a full vulvar cleansing,” she clarified. The cleansing was performed immediately before catheter placement and included the urethra.

When asked about strategies to increase compliance, Dr. Quist-Nelson noted that sharing data was valuable, namely “reporting to our group the current compliance,” as well as sharing information by email and discussing it during multidisciplinary rounds.

The study was a quality improvement project and not a randomized trial, so the researchers were not able to tease out the impact of vaginal cleansing from the impact of azithromycin, Dr. Quist-Nelson said.

Based on her results, Dr. Quist-Nelson said she would recommend the protocol for use in patients who require cesarean delivery after being in labor or having ruptured membranes, and that “there are trials to support the use of both interventions.”

The results suggest opportunities for further randomized trials, including examination of the use of oral versus IV azithromycin, she added.

The study received no outside funding. Dr. Quist-Nelson had no financial conflicts to disclose.

A quality improvement plan incorporating vaginal cleansing and azithromycin significantly reduced surgical-site infections (SSIs) after cesarean deliveries, reported Johanna Quist-Nelson, MD, of the University of North Carolina, Chapel Hill.

“Surgical site infections after a cesarean delivery are more common if the patient is in labor or has ruptured membranes,” she said at the 2020 virtual meeting of the American College of Obstetricians and Gynecologists.. 

Two options to decrease the risk of SSIs after cesarean for those patients in labor or with ruptured membranes are vaginal cleansing and azithromycin, given in addition to preoperative antibiotics, Dr. Quist-Nelson said. She and her colleagues conducted a quality improvement study of the effects of a stepwise implementation of vaginal cleansing and azithromycin to reduce SSIs at cesarean delivery in this high-risk population. The data were collected from 2016 to 2019 at Thomas Jefferson University, Philadelphia.

“We aimed to decrease our SSI rate by 30% by adopting an intervention of cleansing followed by azithromycin,” she said.

The researchers added vaginal cleansing to the SSI prevention protocol in January 2017, with the addition of azithromycin in March 2018. Vaginal cleansing involved 30 seconds of anterior to posterior cleaning prior to urinary catheter placement. Azithromycin was given at a dose of 500 mg intravenously in addition to preoperative antibiotics and within an hour of cesarean delivery.

A total of 1,033 deliveries qualified for the study by being in labor or with ruptured membranes; of these 291 were performed prior to the interventions, 335 received vaginal cleansing only, and 407 received vaginal cleansing and azithromycin. The average age of the participants was 30 years; approximately 42% were Black, and 32% were White.
 

Cleansing protocol reduces SSIs

Overall, the rate of SSIs was 22% in the standard care group, 17% in the vaginal cleansing group, and 15% in the vaginal cleansing plus azithromycin group. When broken down by infection type, no deep SSI occurred in the vaginal cleansing or cleansing plus azithromycin group, compared with 2% of the standard care group (P = .009). In addition, endometritis, which is an organ-space SSI, was significantly lower in the cleansing group (10%) and the cleansing plus azithromycin group (11%), compared with the standard care group (16%).

The study findings were limited by factors including the use of EMRs for collection of data, and given that it is a quality improvement study, there is a potential lack of generalizability to other institutions. The study focused on patients at high risk for SSI and the use of the Plan-Do-Study-Act (PDSA) method of conducting the research, Dr. Quist-Nelson said. Compared with standard care, the implementation of vaginal cleansing reduced the SSI rate by 33%, with no significantly further change in SSI after the addition of azithromycin, she concluded.
 

Data sharing boosts compliance

In a question-and-answer session, Dr. Quist-Nelson noted that povidone iodine (Betadine) was chosen for vaginal cleansing because it was easily accessible at her institution, but that patients with allergies were given chlorhexidine. The cleansing itself was “primarily vaginal, not a full vulvar cleansing,” she clarified. The cleansing was performed immediately before catheter placement and included the urethra.

When asked about strategies to increase compliance, Dr. Quist-Nelson noted that sharing data was valuable, namely “reporting to our group the current compliance,” as well as sharing information by email and discussing it during multidisciplinary rounds.

The study was a quality improvement project and not a randomized trial, so the researchers were not able to tease out the impact of vaginal cleansing from the impact of azithromycin, Dr. Quist-Nelson said.

Based on her results, Dr. Quist-Nelson said she would recommend the protocol for use in patients who require cesarean delivery after being in labor or having ruptured membranes, and that “there are trials to support the use of both interventions.”

The results suggest opportunities for further randomized trials, including examination of the use of oral versus IV azithromycin, she added.

The study received no outside funding. Dr. Quist-Nelson had no financial conflicts to disclose.

A quality improvement plan incorporating vaginal cleansing and azithromycin significantly reduced surgical-site infections (SSIs) after cesarean deliveries, reported Johanna Quist-Nelson, MD, of the University of North Carolina, Chapel Hill.

“Surgical site infections after a cesarean delivery are more common if the patient is in labor or has ruptured membranes,” she said at the 2020 virtual meeting of the American College of Obstetricians and Gynecologists.. 

Two options to decrease the risk of SSIs after cesarean for those patients in labor or with ruptured membranes are vaginal cleansing and azithromycin, given in addition to preoperative antibiotics, Dr. Quist-Nelson said. She and her colleagues conducted a quality improvement study of the effects of a stepwise implementation of vaginal cleansing and azithromycin to reduce SSIs at cesarean delivery in this high-risk population. The data were collected from 2016 to 2019 at Thomas Jefferson University, Philadelphia.

“We aimed to decrease our SSI rate by 30% by adopting an intervention of cleansing followed by azithromycin,” she said.

The researchers added vaginal cleansing to the SSI prevention protocol in January 2017, with the addition of azithromycin in March 2018. Vaginal cleansing involved 30 seconds of anterior to posterior cleaning prior to urinary catheter placement. Azithromycin was given at a dose of 500 mg intravenously in addition to preoperative antibiotics and within an hour of cesarean delivery.

A total of 1,033 deliveries qualified for the study by being in labor or with ruptured membranes; of these 291 were performed prior to the interventions, 335 received vaginal cleansing only, and 407 received vaginal cleansing and azithromycin. The average age of the participants was 30 years; approximately 42% were Black, and 32% were White.
 

Cleansing protocol reduces SSIs

Overall, the rate of SSIs was 22% in the standard care group, 17% in the vaginal cleansing group, and 15% in the vaginal cleansing plus azithromycin group. When broken down by infection type, no deep SSI occurred in the vaginal cleansing or cleansing plus azithromycin group, compared with 2% of the standard care group (P = .009). In addition, endometritis, which is an organ-space SSI, was significantly lower in the cleansing group (10%) and the cleansing plus azithromycin group (11%), compared with the standard care group (16%).

The study findings were limited by factors including the use of EMRs for collection of data, and given that it is a quality improvement study, there is a potential lack of generalizability to other institutions. The study focused on patients at high risk for SSI and the use of the Plan-Do-Study-Act (PDSA) method of conducting the research, Dr. Quist-Nelson said. Compared with standard care, the implementation of vaginal cleansing reduced the SSI rate by 33%, with no significantly further change in SSI after the addition of azithromycin, she concluded.
 

Data sharing boosts compliance

In a question-and-answer session, Dr. Quist-Nelson noted that povidone iodine (Betadine) was chosen for vaginal cleansing because it was easily accessible at her institution, but that patients with allergies were given chlorhexidine. The cleansing itself was “primarily vaginal, not a full vulvar cleansing,” she clarified. The cleansing was performed immediately before catheter placement and included the urethra.

When asked about strategies to increase compliance, Dr. Quist-Nelson noted that sharing data was valuable, namely “reporting to our group the current compliance,” as well as sharing information by email and discussing it during multidisciplinary rounds.

The study was a quality improvement project and not a randomized trial, so the researchers were not able to tease out the impact of vaginal cleansing from the impact of azithromycin, Dr. Quist-Nelson said.

Based on her results, Dr. Quist-Nelson said she would recommend the protocol for use in patients who require cesarean delivery after being in labor or having ruptured membranes, and that “there are trials to support the use of both interventions.”

The results suggest opportunities for further randomized trials, including examination of the use of oral versus IV azithromycin, she added.

The study received no outside funding. Dr. Quist-Nelson had no financial conflicts to disclose.

Obesity and hypoxia at the time of hospital admission predicted more severe disease in children diagnosed with COVID-19, based on data from 281 patients at 8 locations.

Manifestations of COVID-19 in children include respiratory disease similar to that seen in adults, but the full spectrum of disease in children has been studied mainly in single settings or with a focus on one clinical manifestation, wrote Danielle M. Fernandes, MD, of Albert Einstein College of Medicine, New York, and colleagues.

In a study published in the Journal of Pediatrics, the researchers identified 281 children hospitalized with COVID-19 and/or multisystem inflammatory syndrome in children (MIS-C) at 8 sites in Connecticut, New Jersey, and New York. A total of 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations of illness including 32 patients with gastrointestinal problems, 21 infants with fever, 6 cases of neurologic disease, 6 cases of diabetic ketoacidosis, and 4 patients with other indications. The median age of the patients was 10 years, 60% were male, 51% were Hispanic, and 23% were non-Hispanic Black. The most common comorbidities were obesity (34%) and asthma (14%).
 

Independent predictors of disease severity in children found

After controlling for multiple variables, obesity and hypoxia at hospital admission were significant independent predictors of severe respiratory disease, with odds ratios of 3.39 and 4.01, respectively. In addition, lower absolute lymphocyte count (OR, 8.33 per unit decrease in 10⁹ cells/L) and higher C-reactive protein (OR, 1.06 per unit increase in mg/dL) were significantly predictive of severe MIS-C (P = .001 and P = .017, respectively).

“The association between weight and severe respiratory COVID-19 is consistent with the adult literature; however, the mechanisms of this association require further study,” Dr. Fernandes and associates noted.

Overall, children with MIS-C were significantly more likely to be non-Hispanic Black, compared with children with respiratory disease, an 18% difference. However, neither race/ethnicity nor socioeconomic status were significant predictors of disease severity, the researchers wrote.

During the study period, 7 patients (2%) died and 114 (41%) were admitted to the ICU.

“We found a wide array of clinical manifestations in children and youth hospitalized with SARS-CoV-2,” Dr. Fernandes and associates wrote. Notably, gastrointestinal symptoms, ocular symptoms, and dermatologic symptoms have rarely been noted in adults with COVID-19, but occurred in more than 30% of the pediatric patients.

“We also found that SARS-CoV-2 can be an incidental finding in a substantial number of hospitalized pediatric patients,” the researchers said.

The findings were limited by several factors including a population of patients only from Connecticut, New Jersey, and New York, and the possibility that decisions on hospital and ICU admission may have varied by location, the researchers said. In addition, approaches may have varied in the absence of data on the optimal treatment of MIS-C.

“This study builds on the growing body of evidence showing that mortality in hospitalized pediatric patients is low, compared with adults,” Dr. Fernandes and associates said. “However, it highlights that the young population is not universally spared from morbidity, and that even previously healthy children and youth can develop severe disease requiring supportive therapy.”
 

Findings confirm other clinical experience

The study was important to show that, “although most children are spared severe illness from COVID-19, some children are hospitalized both with acute COVID-19 respiratory disease, with MIS-C and with a range of other complications,” Adrienne Randolph, MD, of Boston Children’s Hospital and Harvard Medical School, Boston, said in an interview.

Dr. Randolph said she was not surprised by the study findings, “as we are also seeing these types of complications at Boston Children’s Hospital where I work.”

Additional research is needed on the outcomes of these patients, “especially the longer-term sequelae of having COVID-19 or MIS-C early in life,” she emphasized.

The take-home message to clinicians from the findings at this time is to be aware that children and adolescents can become severely ill from COVID-19–related complications, said Dr. Randolph. “Some of the laboratory values on presentation appear to be associated with disease severity.”

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Randolph disclosed funding from the Centers for Disease Control and Prevention to lead the Overcoming COVID-19 Study in U.S. Children and Adults.

SOURCE: Fernandes DM et al. J Pediatr. 2020 Nov 13. doi: 10.1016/j.jpeds.2020.11.016.

Obesity and hypoxia at the time of hospital admission predicted more severe disease in children diagnosed with COVID-19, based on data from 281 patients at 8 locations.

Manifestations of COVID-19 in children include respiratory disease similar to that seen in adults, but the full spectrum of disease in children has been studied mainly in single settings or with a focus on one clinical manifestation, wrote Danielle M. Fernandes, MD, of Albert Einstein College of Medicine, New York, and colleagues.

In a study published in the Journal of Pediatrics, the researchers identified 281 children hospitalized with COVID-19 and/or multisystem inflammatory syndrome in children (MIS-C) at 8 sites in Connecticut, New Jersey, and New York. A total of 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations of illness including 32 patients with gastrointestinal problems, 21 infants with fever, 6 cases of neurologic disease, 6 cases of diabetic ketoacidosis, and 4 patients with other indications. The median age of the patients was 10 years, 60% were male, 51% were Hispanic, and 23% were non-Hispanic Black. The most common comorbidities were obesity (34%) and asthma (14%).
 

Independent predictors of disease severity in children found

After controlling for multiple variables, obesity and hypoxia at hospital admission were significant independent predictors of severe respiratory disease, with odds ratios of 3.39 and 4.01, respectively. In addition, lower absolute lymphocyte count (OR, 8.33 per unit decrease in 10⁹ cells/L) and higher C-reactive protein (OR, 1.06 per unit increase in mg/dL) were significantly predictive of severe MIS-C (P = .001 and P = .017, respectively).

“The association between weight and severe respiratory COVID-19 is consistent with the adult literature; however, the mechanisms of this association require further study,” Dr. Fernandes and associates noted.

Overall, children with MIS-C were significantly more likely to be non-Hispanic Black, compared with children with respiratory disease, an 18% difference. However, neither race/ethnicity nor socioeconomic status were significant predictors of disease severity, the researchers wrote.

During the study period, 7 patients (2%) died and 114 (41%) were admitted to the ICU.

“We found a wide array of clinical manifestations in children and youth hospitalized with SARS-CoV-2,” Dr. Fernandes and associates wrote. Notably, gastrointestinal symptoms, ocular symptoms, and dermatologic symptoms have rarely been noted in adults with COVID-19, but occurred in more than 30% of the pediatric patients.

“We also found that SARS-CoV-2 can be an incidental finding in a substantial number of hospitalized pediatric patients,” the researchers said.

The findings were limited by several factors including a population of patients only from Connecticut, New Jersey, and New York, and the possibility that decisions on hospital and ICU admission may have varied by location, the researchers said. In addition, approaches may have varied in the absence of data on the optimal treatment of MIS-C.

“This study builds on the growing body of evidence showing that mortality in hospitalized pediatric patients is low, compared with adults,” Dr. Fernandes and associates said. “However, it highlights that the young population is not universally spared from morbidity, and that even previously healthy children and youth can develop severe disease requiring supportive therapy.”
 

Findings confirm other clinical experience

The study was important to show that, “although most children are spared severe illness from COVID-19, some children are hospitalized both with acute COVID-19 respiratory disease, with MIS-C and with a range of other complications,” Adrienne Randolph, MD, of Boston Children’s Hospital and Harvard Medical School, Boston, said in an interview.

Dr. Randolph said she was not surprised by the study findings, “as we are also seeing these types of complications at Boston Children’s Hospital where I work.”

Additional research is needed on the outcomes of these patients, “especially the longer-term sequelae of having COVID-19 or MIS-C early in life,” she emphasized.

The take-home message to clinicians from the findings at this time is to be aware that children and adolescents can become severely ill from COVID-19–related complications, said Dr. Randolph. “Some of the laboratory values on presentation appear to be associated with disease severity.”

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Randolph disclosed funding from the Centers for Disease Control and Prevention to lead the Overcoming COVID-19 Study in U.S. Children and Adults.

SOURCE: Fernandes DM et al. J Pediatr. 2020 Nov 13. doi: 10.1016/j.jpeds.2020.11.016.

Obesity and hypoxia at the time of hospital admission predicted more severe disease in children diagnosed with COVID-19, based on data from 281 patients at 8 locations.

Manifestations of COVID-19 in children include respiratory disease similar to that seen in adults, but the full spectrum of disease in children has been studied mainly in single settings or with a focus on one clinical manifestation, wrote Danielle M. Fernandes, MD, of Albert Einstein College of Medicine, New York, and colleagues.

In a study published in the Journal of Pediatrics, the researchers identified 281 children hospitalized with COVID-19 and/or multisystem inflammatory syndrome in children (MIS-C) at 8 sites in Connecticut, New Jersey, and New York. A total of 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations of illness including 32 patients with gastrointestinal problems, 21 infants with fever, 6 cases of neurologic disease, 6 cases of diabetic ketoacidosis, and 4 patients with other indications. The median age of the patients was 10 years, 60% were male, 51% were Hispanic, and 23% were non-Hispanic Black. The most common comorbidities were obesity (34%) and asthma (14%).
 

Independent predictors of disease severity in children found

After controlling for multiple variables, obesity and hypoxia at hospital admission were significant independent predictors of severe respiratory disease, with odds ratios of 3.39 and 4.01, respectively. In addition, lower absolute lymphocyte count (OR, 8.33 per unit decrease in 10⁹ cells/L) and higher C-reactive protein (OR, 1.06 per unit increase in mg/dL) were significantly predictive of severe MIS-C (P = .001 and P = .017, respectively).

“The association between weight and severe respiratory COVID-19 is consistent with the adult literature; however, the mechanisms of this association require further study,” Dr. Fernandes and associates noted.

Overall, children with MIS-C were significantly more likely to be non-Hispanic Black, compared with children with respiratory disease, an 18% difference. However, neither race/ethnicity nor socioeconomic status were significant predictors of disease severity, the researchers wrote.

During the study period, 7 patients (2%) died and 114 (41%) were admitted to the ICU.

“We found a wide array of clinical manifestations in children and youth hospitalized with SARS-CoV-2,” Dr. Fernandes and associates wrote. Notably, gastrointestinal symptoms, ocular symptoms, and dermatologic symptoms have rarely been noted in adults with COVID-19, but occurred in more than 30% of the pediatric patients.

“We also found that SARS-CoV-2 can be an incidental finding in a substantial number of hospitalized pediatric patients,” the researchers said.

The findings were limited by several factors including a population of patients only from Connecticut, New Jersey, and New York, and the possibility that decisions on hospital and ICU admission may have varied by location, the researchers said. In addition, approaches may have varied in the absence of data on the optimal treatment of MIS-C.

“This study builds on the growing body of evidence showing that mortality in hospitalized pediatric patients is low, compared with adults,” Dr. Fernandes and associates said. “However, it highlights that the young population is not universally spared from morbidity, and that even previously healthy children and youth can develop severe disease requiring supportive therapy.”
 

Findings confirm other clinical experience

The study was important to show that, “although most children are spared severe illness from COVID-19, some children are hospitalized both with acute COVID-19 respiratory disease, with MIS-C and with a range of other complications,” Adrienne Randolph, MD, of Boston Children’s Hospital and Harvard Medical School, Boston, said in an interview.

Dr. Randolph said she was not surprised by the study findings, “as we are also seeing these types of complications at Boston Children’s Hospital where I work.”

Additional research is needed on the outcomes of these patients, “especially the longer-term sequelae of having COVID-19 or MIS-C early in life,” she emphasized.

The take-home message to clinicians from the findings at this time is to be aware that children and adolescents can become severely ill from COVID-19–related complications, said Dr. Randolph. “Some of the laboratory values on presentation appear to be associated with disease severity.”

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Randolph disclosed funding from the Centers for Disease Control and Prevention to lead the Overcoming COVID-19 Study in U.S. Children and Adults.

SOURCE: Fernandes DM et al. J Pediatr. 2020 Nov 13. doi: 10.1016/j.jpeds.2020.11.016.

When cervical cancer recurs after radical hysterectomy, the likelihood of recurrence at certain sites and the timing of recurrence may be associated with the surgical approach, according to a retrospective study.

U.S. Air Force photo by Staff Sgt. Ciara Gosier

Recurrence tended to occur sooner after minimally invasive surgery than after open abdominal surgery for cervical cancer, according to a propensity-matched analysis of data from 105 patients with recurrence.

And recurrence in the pelvic cavity and peritoneal carcinomatosis were more common after laparoscopic hysterectomy than after open surgery. Overall survival was similar between the groups, however.

The different patterns of recurrence may relate to dissemination of the disease during colpotomy, but the reasons are unknown, study author Giorgio Bogani, MD, PhD, said at the meeting sponsored by AAGL.

To examine patterns of recurrence after laparoscopic and open abdominal radical hysterectomy for cervical cancer, Dr. Bogani of the department of gynecologic surgery at the National Cancer Institute in Milan and colleagues analyzed data from patients with cervical cancer who developed recurrence after surgery at two oncologic referral centers between 1990 and 2018 (Int J Gynecol Cancer. 2020 Jul. doi: 10.1136/ijgc-2020-001381).

The investigators applied a propensity-matching algorithm to reduce possible confounding factors. They matched 35 patients who had recurrence after laparoscopic hysterectomy to 70 patients who had recurrence after open surgery. The groups had similar baseline characteristics.

As in the Laparoscopic Approach to Cervical Cancer (LACC) trial, patients who had minimally invasive surgery were more likely to have a worse disease-free survival, compared with patients who had open surgery, Dr. Bogani said. Patients who underwent laparoscopic radical hysterectomy had a median progression-free survival of 8 months, whereas patients who underwent open abdominal procedures had a median progression-free survival of 15.8 months.

Although vaginal, lymphatic, and distant recurrences were similar between the groups, a greater percentage of patients in the laparoscopic hysterectomy group had recurrence in the pelvic cavity (74% vs. 34%) and peritoneal carcinomatosis (17% vs. 1.5%).

The LACC trial, which found significantly lower disease-free and overall survival with laparoscopic hysterectomy, sent a “shockwave through the gynecologic oncology community” when it was published in 2018, said Masoud Azodi, MD, in a discussion following Dr. Bogani’s presentation.

Researchers have raised questions about that trial’s design and validity, noted Dr. Azodi, director of minimally invasive and robotic surgery at Yale University in New Haven, Conn.

It could be that local recurrences are attributable to surgical technique, rather than to the minimally invasive approach in itself, Dr. Azodi said. Prior studies of laparoscopic hysterectomy for cervical cancer had indicated better surgical outcomes and equivalent oncologic results, relative to open surgery.

Before the LACC trial, Dr. Bogani used the minimally invasive approach for almost all surgeries. Since then, he has performed open surgeries. If he were to use a minimally invasive approach now, it would be in the context of a clinical trial, Dr. Bogani said.

Dr. Bogani and Dr. Azodi had no relevant financial disclosures.

[email protected]

SOURCE: Bogani G et al. J Minim Invasive Gynecol. 2020 Nov. doi: 10.1016/j.jmig.2020.08.069.

When cervical cancer recurs after radical hysterectomy, the likelihood of recurrence at certain sites and the timing of recurrence may be associated with the surgical approach, according to a retrospective study.

U.S. Air Force photo by Staff Sgt. Ciara Gosier

Recurrence tended to occur sooner after minimally invasive surgery than after open abdominal surgery for cervical cancer, according to a propensity-matched analysis of data from 105 patients with recurrence.

And recurrence in the pelvic cavity and peritoneal carcinomatosis were more common after laparoscopic hysterectomy than after open surgery. Overall survival was similar between the groups, however.

The different patterns of recurrence may relate to dissemination of the disease during colpotomy, but the reasons are unknown, study author Giorgio Bogani, MD, PhD, said at the meeting sponsored by AAGL.

To examine patterns of recurrence after laparoscopic and open abdominal radical hysterectomy for cervical cancer, Dr. Bogani of the department of gynecologic surgery at the National Cancer Institute in Milan and colleagues analyzed data from patients with cervical cancer who developed recurrence after surgery at two oncologic referral centers between 1990 and 2018 (Int J Gynecol Cancer. 2020 Jul. doi: 10.1136/ijgc-2020-001381).

The investigators applied a propensity-matching algorithm to reduce possible confounding factors. They matched 35 patients who had recurrence after laparoscopic hysterectomy to 70 patients who had recurrence after open surgery. The groups had similar baseline characteristics.

As in the Laparoscopic Approach to Cervical Cancer (LACC) trial, patients who had minimally invasive surgery were more likely to have a worse disease-free survival, compared with patients who had open surgery, Dr. Bogani said. Patients who underwent laparoscopic radical hysterectomy had a median progression-free survival of 8 months, whereas patients who underwent open abdominal procedures had a median progression-free survival of 15.8 months.

Although vaginal, lymphatic, and distant recurrences were similar between the groups, a greater percentage of patients in the laparoscopic hysterectomy group had recurrence in the pelvic cavity (74% vs. 34%) and peritoneal carcinomatosis (17% vs. 1.5%).

The LACC trial, which found significantly lower disease-free and overall survival with laparoscopic hysterectomy, sent a “shockwave through the gynecologic oncology community” when it was published in 2018, said Masoud Azodi, MD, in a discussion following Dr. Bogani’s presentation.

Researchers have raised questions about that trial’s design and validity, noted Dr. Azodi, director of minimally invasive and robotic surgery at Yale University in New Haven, Conn.

It could be that local recurrences are attributable to surgical technique, rather than to the minimally invasive approach in itself, Dr. Azodi said. Prior studies of laparoscopic hysterectomy for cervical cancer had indicated better surgical outcomes and equivalent oncologic results, relative to open surgery.

Before the LACC trial, Dr. Bogani used the minimally invasive approach for almost all surgeries. Since then, he has performed open surgeries. If he were to use a minimally invasive approach now, it would be in the context of a clinical trial, Dr. Bogani said.

Dr. Bogani and Dr. Azodi had no relevant financial disclosures.

[email protected]

SOURCE: Bogani G et al. J Minim Invasive Gynecol. 2020 Nov. doi: 10.1016/j.jmig.2020.08.069.

When cervical cancer recurs after radical hysterectomy, the likelihood of recurrence at certain sites and the timing of recurrence may be associated with the surgical approach, according to a retrospective study.

U.S. Air Force photo by Staff Sgt. Ciara Gosier

Recurrence tended to occur sooner after minimally invasive surgery than after open abdominal surgery for cervical cancer, according to a propensity-matched analysis of data from 105 patients with recurrence.

And recurrence in the pelvic cavity and peritoneal carcinomatosis were more common after laparoscopic hysterectomy than after open surgery. Overall survival was similar between the groups, however.

The different patterns of recurrence may relate to dissemination of the disease during colpotomy, but the reasons are unknown, study author Giorgio Bogani, MD, PhD, said at the meeting sponsored by AAGL.

To examine patterns of recurrence after laparoscopic and open abdominal radical hysterectomy for cervical cancer, Dr. Bogani of the department of gynecologic surgery at the National Cancer Institute in Milan and colleagues analyzed data from patients with cervical cancer who developed recurrence after surgery at two oncologic referral centers between 1990 and 2018 (Int J Gynecol Cancer. 2020 Jul. doi: 10.1136/ijgc-2020-001381).

The investigators applied a propensity-matching algorithm to reduce possible confounding factors. They matched 35 patients who had recurrence after laparoscopic hysterectomy to 70 patients who had recurrence after open surgery. The groups had similar baseline characteristics.

As in the Laparoscopic Approach to Cervical Cancer (LACC) trial, patients who had minimally invasive surgery were more likely to have a worse disease-free survival, compared with patients who had open surgery, Dr. Bogani said. Patients who underwent laparoscopic radical hysterectomy had a median progression-free survival of 8 months, whereas patients who underwent open abdominal procedures had a median progression-free survival of 15.8 months.

Although vaginal, lymphatic, and distant recurrences were similar between the groups, a greater percentage of patients in the laparoscopic hysterectomy group had recurrence in the pelvic cavity (74% vs. 34%) and peritoneal carcinomatosis (17% vs. 1.5%).

The LACC trial, which found significantly lower disease-free and overall survival with laparoscopic hysterectomy, sent a “shockwave through the gynecologic oncology community” when it was published in 2018, said Masoud Azodi, MD, in a discussion following Dr. Bogani’s presentation.

Researchers have raised questions about that trial’s design and validity, noted Dr. Azodi, director of minimally invasive and robotic surgery at Yale University in New Haven, Conn.

It could be that local recurrences are attributable to surgical technique, rather than to the minimally invasive approach in itself, Dr. Azodi said. Prior studies of laparoscopic hysterectomy for cervical cancer had indicated better surgical outcomes and equivalent oncologic results, relative to open surgery.

Before the LACC trial, Dr. Bogani used the minimally invasive approach for almost all surgeries. Since then, he has performed open surgeries. If he were to use a minimally invasive approach now, it would be in the context of a clinical trial, Dr. Bogani said.

Dr. Bogani and Dr. Azodi had no relevant financial disclosures.

[email protected]

SOURCE: Bogani G et al. J Minim Invasive Gynecol. 2020 Nov. doi: 10.1016/j.jmig.2020.08.069.

From the University of Alabama at Birmingham, Birmingham, AL.

Abstract

Objective: To review current challenges in the management of peptic ulcer disease.

Methods: Review of the literature.

Results: Peptic ulcer disease affects 5% to 10% of the population worldwide, with recent decreases in lifetime prevalence in high-income countries. Helicobacter pylori infection and nonsteroidal anti-inflammatory drug (NSAID) use are the most important drivers of peptic ulcer disease. Current management strategies for peptic ulcer disease focus on ulcer healing; management of complications such as bleeding, perforation, and obstruction; and prevention of ulcer recurrence. Proton pump inhibitors (PPIs) are the cornerstone of medical therapy for peptic ulcers, and complement testing for and treatment of H. pylori infection as well as elimination of NSAID use. Although advances have been made in the medical and endoscopic treatment of peptic ulcer disease and the management of ulcer complications, such as bleeding and obstruction, challenges remain.

Conclusion: Peptic ulcer disease is a common health problem globally, with persistent challenges related to refractory ulcers, antiplatelet and anticoagulant use, and continued bleeding in the face of endoscopic therapy. These challenges should be met with PPI therapy of adequate frequency and duration, vigilant attention to and treatment of ulcer etiology, evidence-based handling of antiplatelet and anticoagulant medications, and utilization of novel endoscopic tools to obtain improved clinical outcomes.

Keywords: H. pylori; nonsteroidal anti-inflammatory drugs; NSAIDs; proton pump inhibitor; PPI; bleeding; perforation; obstruction; refractory ulcer; salvage endoscopic therapy; transcatheter angiographic embolization.

A peptic ulcer is a fibrin-covered break in the mucosa of the digestive tract extending to the submucosa that is caused by acid injury (Figure 1). Most peptic ulcers occur in the stomach or proximal duodenum, though they may also occur in the esophagus or, less frequently, in a Meckel’s diverticulum.^1,2 The estimated worldwide prevalence of peptic ulcer disease is 5% to 10%, with an annual incidence of 0.1% to 0.3%¹; both rates are declining.³ The annual incidence of peptic ulcer disease requiring medical or surgical treatment is also declining, and currently is estimated to be 0.1% to 0.2%.⁴ The lifetime prevalence of peptic ulcers has been decreasing in high-income countries since the mid-20th century due to both the widespread use of medications that suppress gastric acid secretion and the declining prevalence of Helicobacter pylori infection.^1,3

Peptic ulcer disease in most individuals results from H. pylori infection, chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, or both. A combination of H. pylori factors and host factors lead to mucosal disruption in infected individuals who develop peptic ulcers. H. pylori–specific factors include the expression of virulence factors such as CagA and VacA, which interact with the host inflammatory response to cause mucosal injury. The mucosal inflammatory response is at least partially determined by polymorphisms in the host’s cytokine genes.^1,4 NSAIDs inhibit the production of cyclooxygenase-1-derived prostaglandins, with subsequent decreases in epithelial mucous formation, bicarbonate secretion, cell proliferation, and mucosal blood flow, all of which are key elements in the maintenance of mucosal integrity.^1,5 Less common causes of peptic ulcers include gastrinoma, adenocarcinoma, idiopathic ulcers, use of sympathomimetic drugs (eg, cocaine or methamphetamine), certain anticancer agents, and bariatric surgery.^4,6

This article provides an overview of current management principles for peptic ulcer disease and discusses current challenges in peptic ulcer management, including proton pump inhibitor (PPI) therapy, refractory ulcers, handling of antiplatelet and anticoagulants during and after peptic ulcer bleeding, and ulcer bleeding that continues despite salvage endoscopic therapy.

Methods

We searched MEDLINE using the term peptic ulcer disease in combination with the terms current challenges, epidemiology, bleeding, anticoagulant, antiplatelet, PPI potency, etiology, treatment, management, and refractory. We selected publications from the past 35 years that we judged to be relevant.

Current Management

The goals of peptic ulcer disease management are ulcer healing and prevention of recurrence. The primary interventions used in the management of peptic ulcer disease are medical therapy and implementation of measures that address the underlying etiology of the disease.

Medical Therapy

Introduced in the late 1980s, PPIs are the cornerstone of medical therapy for peptic ulcer disease.⁶ These agents irreversibly inhibit the H+/K+-ATPase pump in the gastric mucosa and thereby inhibit gastric acid secretion, promoting ulcer healing. PPIs improve rates of ulcer healing compared to H2-receptor antagonists.^4,7

Underlying Causes

The underlying cause of peptic ulcer disease should be addressed, in addition to initiating medical therapy. A detailed history of NSAID use should be obtained, and patients with peptic ulcers caused by NSAIDs should be counseled to avoid them, if possible. Patients with peptic ulcer disease who require long-term use of NSAIDs should be placed on long-term PPI therapy.⁶ Any patient with peptic ulcer disease, regardless of any history of H. pylori infection or treatment, should be tested for infection. Tests that identify active infection, such as urea breath test, stool antigen assay, or mucosal biopsy–based testing, are preferred to IgG antibody testing, although the latter is acceptable in the context of peptic ulcer disease with a high pretest probability of infection.⁸ Any evidence of active infection warrants appropriate treatment to allow ulcer healing and prevent recurrence.¹H. pylori infection is most often treated with clarithromycin triple therapy or bismuth quadruple therapy for 14 days, with regimens selected based on the presence or absence of penicillin allergy, prior antibiotic exposure, and local clarithromycin resistance rates, when known.^4,8

Managing Complications

An additional aspect of care in peptic ulcer disease is managing the complications of bleeding, perforation, and gastric outlet obstruction. Acute upper gastrointestinal bleeding (GIB) is the most common complication of peptic ulcer disease, which accounts for 40% to 60% of nonvariceal acute upper GIB.^1,6 The first step in the management of acute GIB from a peptic ulcer is fluid resuscitation to ensure hemodynamic stability. If there is associated anemia with a hemoglobin level < 8 g/dL, blood transfusion should be undertaken to target a hemoglobin level > 8 g/dL. In patients with peptic ulcer disease–related acute upper GIB and comorbid cardiovascular disease, the transfusion threshold is higher, with the specific cutoff depending on clinical status, type and severity of cardiovascular disease, and degree of bleeding. Endoscopic management should generally be undertaken within 24 hours of presentation and should not be delayed in patients taking anticoagulants.⁹ Combination endoscopic treatment with through-the-scope clips plus thermocoagulation or sclerosant injection is recommended for acutely bleeding peptic ulcers with high-risk stigmata.

Pharmacologic management of patients with bleeding peptic ulcers with high-risk stigmata includes PPI therapy, with an 80 mg intravenous (IV) loading dose followed by continuous infusion of 8 mg/hr for 72 hours to reduce rebleeding and mortality. Following completion of IV therapy, oral PPI therapy should be continued twice daily for 14 days, followed by once-daily dosing thereafter.⁹Patients with peptic ulcer perforation present with sudden-onset epigastric abdominal pain and have tenderness to palpation, guarding, and rigidity on examination, often along with tachycardia and hypotension.^1,4 Computed tomography (CT) of the abdomen is 98% sensitive for identifying and localizing a perforation. Most perforations occur in the duodenum or antrum.

Management of a peptic ulcer perforation requires consultation with a surgeon to determine whether a nonoperative approach may be employed (eg, a stable patient with a contained perforation), or if surgery is indicated. The surgical approach to peptic ulcer perforation has been impacted by the clinical success of gastric acid suppression with PPIs and H. pylori eradication, but a range of surgical approaches are still used to repair perforations, from omental patch repair with peritoneal drain placement, to more extensive surgeries such as wedge resection or partial gastrectomy.⁴ Perforation carries a high mortality risk, up to 20% to 30%, and is the leading cause of death in patients with peptic ulcer disease.^1,4

Gastric outlet obstruction, a rare complication of peptic ulcer disease, results from recurrent ulcer formation and scarring. Obstruction often presents with hypovolemia and metabolic alkalosis from prolonged vomiting. CT imaging with oral contrast is often the first diagnostic test employed to demonstrate obstruction. Upper endoscopy should be performed to evaluate the appearance and degree of obstruction as well as to obtain biopsies to evaluate for a malignant etiology of the ulcer disease. Endoscopic balloon dilation has become the cornerstone of initial therapy for obstruction from peptic ulcer disease, especially in the case of ulcers due to reversible causes. Surgery is now typically reserved for cases of refractory obstruction, after repeated endoscopic balloon dilation has failed to remove the obstruction. However, because nearly all patients with gastric outlet obstruction present with malnutrition, nutritional deficiencies should be addressed prior to the patient undergoing surgical intervention. Surgical options include pyloroplasty, antrectomy, and gastrojejunostomy.⁴

Current Challenges

Rapid Metabolism of PPIs

High-dose PPI therapy is a key component of therapy for peptic ulcer healing. PPIs are metabolized by the cytochrome P450 system, which is comprised of multiple isoenzymes. CYP2C19, an isoenzyme involved in PPI metabolism, has 21 polymorphisms, which have variable effects leading to ultra-rapid, extensive, intermediate, or poor metabolism of PPIs.¹⁰ With rapid metabolism of PPIs, standard dosing can result in inadequate suppression of acid secretion. Despite this knowledge, routine testing of CYP2C19 phenotype is not recommended due to the cost of testing. Instead, inadequate ulcer healing should prompt consideration of increased PPI dosing to 80 mg orally twice daily, which may be sufficient to overcome rapid PPI metabolism.¹¹

Relative Potency of PPIs

In addition to variation in PPI metabolism, the relative potency of various PPIs has been questioned. A review of all available clinical studies of the effects of PPIs on mean 24-hour intragastric pH reported a quantitative difference in the potency of 5 PPIs, with omeprazole as the reference standard. Potencies ranged from 0.23 omeprazole equivalents for pantoprazole to 1.82 omeprazole equivalents for rabeprazole.¹² An additional study of data from 56 randomized clinical trials confirmed that PPIs vary in potency, which was measured as time that gastric pH is less than 4. A linear increase in intragastric pH time less than 4 was observed from 9 to 64 mg omeprazole equivalents; higher doses yielded no additional benefit. An increase in PPI dosing from once daily to twice daily also increased the duration of intragastric pH time less than 4 from 15 to 21 hours.¹³ Earlier modeling of the relationship between duodenal ulcer healing and antisecretory therapy showed a strong correlation of ulcer healing with the duration of acid suppression, length of therapy, and the degree of acid suppression. Additional benefit was not observed after intragastric pH rose above 3.¹⁴ Thus, as the frequency and duration of acid suppression therapy are more important than PPI potency, PPIs can be used interchangeably.^13,14

Addressing Underlying Causes

Continued NSAID Use. Refractory peptic ulcers are defined as those that do not heal despite adherence to 8 to 12 weeks of standard acid-suppression therapy. A cause of refractory peptic ulcer disease that must be considered is continued NSAID use.^1,15 In a study of patients with refractory peptic ulcers, 27% of patients continued NSAID use, as determined by eventual disclosure by the patients or platelet cyclooxygenase activity assay, despite extensive counseling to avoid NSAIDs at the time of the diagnosis of their refractory ulcer and at subsequent visits.¹⁶ Pain may make NSAID cessation difficult for some patients, while others do not realize that over-the-counter preparations they take contain NSAIDs.¹⁵

Another group of patients with continued NSAID exposure are those who require long-term NSAID therapy for control of arthritis or the management of cardiovascular conditions. If NSAID therapy cannot be discontinued, the risk of NSAID-related gastrointestinal injury can be assessed based on the presence of multiple risk factors, including age > 65 years, high-dose NSAID therapy, a history of peptic ulcer, and concurrent use of aspirin, corticosteroids, or anticoagulants. Individuals with 3 or more of the preceding risk factors or a history of a peptic ulcer with a complication, especially if recent, are considered to be at high risk of developing an NSAID-related ulcer and possible subsequent complications.¹⁷ In these individuals, NSAID therapy should be continued with agents that have the lowest risk for gastrointestinal toxicity and at the lowest possible dose. A meta-analysis comparing nonselective NSAIDs to placebo demonstrated naproxen to have the highest risk of gastrointestinal complications, including GIB, perforation, and obstruction (adjusted rate ratio, 4.2), while diclofenac demonstrated the lowest risk (adjusted rate ratio, 1.89). High-dose NSAID therapy demonstrated a 2-fold increase in risk of peptic ulcer formation as compared to low-dose therapy.¹⁸

In addition to selecting the NSAID with the least gastrointestinal toxicity at the lowest possible dose, additional strategies to prevent peptic ulcer disease and its complications in chronic NSAID users include co-administration of a PPI and substitution of a COX-2 selective NSAID for nonselective NSAIDs.^1,9 Prior double-blind, placebo-controlled, randomized, multicenter trials with patients requiring daily NSAIDs demonstrated an up to 15% absolute reduction in the risk of developing peptic ulcers over 6 months while taking esomeprazole.¹⁹

Persistent Infection. Persistent H. pylori infection, due either to initial false-negative testing or ongoing infection despite first-line therapy, is another cause of refractory peptic ulcer disease.^1,15 Because antibiotics and PPIs can reduce the number of H. pylori bacteria, use of these medications concurrent with H. pylori testing can lead to false-negative results with several testing modalities. When suspicion for H. pylori is high, 2 or more diagnostic tests may be needed to effectively rule out infection.¹⁵

When H. pylori is detected, successful eradication is becoming more difficult due to an increasing prevalence of antibiotic resistance, leading to persistent infection in many cases and maintained risk of peptic ulcer disease, despite appropriate first-line therapy.⁸ Options for salvage therapy for persistent H. pylori, as well as information on the role and best timing of susceptibility testing, are beyond the scope of this review, but are reviewed by Lanas and Chan¹ and in the American College of Gastroenterology guideline on the treatment of H. pylori infection.⁸

Other Causes. In a meta-analysis of rigorously designed studies from North America, 20% of patients experienced ulcer recurrence at 6 months, despite successful H. pylori eradication and no NSAID use.²⁰ In addition, as H. pylori prevalence is decreasing, idiopathic ulcers are increasingly being diagnosed, and such ulcers may be associated with high rates of GIB and mortality.¹ In this subset of patients with non-H. pylori, non-NSAID ulcers, increased effort is required to further evaluate the differential diagnosis for rarer causes of upper GI tract ulcer disease (Table). Certain malignancies, including adenocarcinoma and lymphoma, can cause ulcer formation and should be considered in refractory cases. Repeat biopsy at follow-up endoscopy for persistent ulcers should always be obtained to further evaluate for malignancy.^1,15 Infectious diseases other than H. pylori infection, such as tuberculosis, syphilis, cytomegalovirus, and herpes simplex virus, are also reported as etiologies of refractory ulcers, and require specific antimicrobial treatment over and above PPI monotherapy. Special attention in biopsy sampling and sample processing is often required when infectious etiologies are being considered, as specific histologic stains and cultures may be needed for identification.¹⁵

Systemic conditions, including sarcoidosis,²¹ Behçet disease,²² and polyarteritis nodosa,^15,23 can also cause refractory ulcers. Approximately 15% of patients with Crohn disease have gastroduodenal involvement, which may include ulcers of variable sizes.^1,15,24 The increased gastric acid production seen in Zollinger-Ellison syndrome commonly presents as refractory peptic ulcers in the duodenum beyond the bulb that do not heal with standard doses of PPIs.^1,15 More rare causes of acid hypersecretion leading to refractory ulcers include idiopathic gastric acid hypersecretion and retained gastric antrum syndrome after partial gastrectomy with Billroth II anastomosis.¹⁵ Smoking is a known risk factor for impaired tissue healing throughout the body, and can contribute to impaired healing of peptic ulcers through decreased prostaglandin synthesis²⁵ and reduced gastric mucosal blood flow.²⁶ Smoking should always be addressed in patients with refractory peptic ulcers, and cessation should be strongly encouraged. Other less common causes of refractory upper GI tract ulcers include radiation therapy, crack cocaine use, and mesenteric ischemia.¹⁵

Managing Antiplatelet and Anticoagulant Medications

Use of antiplatelets and anticoagulants, alone or in combination, increases the risk of peptic ulcer bleeding. In patients who continue to take aspirin after a peptic ulcer bleed, recurrent bleeding occurs in up to 300 cases per 1000 person-years. The rate of GIB associated with aspirin use ranges from 1.1% to 2.5%, depending on the dose. Prior peptic ulcer disease, age greater than 70 years, and concurrent NSAID, steroid, anticoagulant, or dual antiplatelet therapy (DAPT) use increase the risk of bleeding while on aspirin. The rate of GIB while taking a thienopyridine alone is slightly less than that when taking aspirin, ranging from 0.5% to 1.6%. Studies to date have yielded mixed estimates of the effect of DAPT on the risk of GIB. Estimates of the risk of GIB with DAPT range from an odds ratio for serious GIB of 7.4 to an absolute risk increase of only 1.3% when compared to clopidogrel alone.²⁷

Many patients are also on warfarin or a direct oral anticoagulant (DOAC). In a study from the United Kingdom, the adjusted rate ratio of GIB with warfarin alone was 1.94, and this increased to 6.48 when warfarin was used with aspirin.²⁸ The use of warfarin and DAPT, often called triple therapy, further increases the risk of GIB, with a hazard ratio of 5.0 compared to DAPT alone, and 5.38 when compared to warfarin alone. DOACs are increasingly prescribed for the treatment and prevention of thromboembolism, and by 2014 were prescribed as often as warfarin for stroke prevention in atrial fibrillation in the United States. A meta-analysis showed the risk of major GIB did not differ between DOACs and warfarin or low-molecular-weight heparin, but among DOACs factor Xa inhibitors showed a reduced risk of GIB compared with dabigatran, a direct thrombin inhibitor.²⁹

The use of antiplatelets and anticoagulants in the context of peptic ulcer bleeding is a current management challenge. Data to guide decision-making in patients on antiplatelet and/or anticoagulant therapy who experience peptic ulcer bleeding are scarce. Decision-making in this group of patients requires balancing the severity and risk of bleeding with the risk of thromboembolism.^1,27 In patients on antiplatelet therapy for primary prophylaxis of atherothrombosis who develop bleeding from a peptic ulcer, the antiplatelet should generally be held and the indication for the medication reassessed. In patients on antiplatelet therapy for secondary prevention, the agent may be immediately resumed after endoscopy if bleeding is found to be due to an ulcer with low-risk stigmata. With bleeding resulting from an ulcer with high-risk stigmata, antiplatelet agents employed for secondary prevention may be held initially, with consideration given to early reintroduction, as early as day 3 after endoscopy.¹ In patients at high risk for atherothrombotic events, including those on aspirin for secondary prophylaxis, withholding aspirin leads to a 3-fold increase in the risk of a major adverse cardiac event, with events occurring as early as 5 days after aspirin cessation in some cases.²⁷ A randomized controlled trial of continuing low-dose aspirin versus withholding it for 8 weeks in patients on aspirin for secondary prophylaxis of cardiovascular events who experienced peptic ulcer bleeding that required endoscopic therapy demonstrated lower all-cause mortality (1.3% vs 12.9%), including death from cardiovascular or cerebrovascular events, among those who continued aspirin therapy, with a small increased risk of recurrent ulcer bleeding (10.3% vs 5.4%).³⁰ Thus, it is recommended that antiplatelet therapy, when held, be resumed as early as possible when the risk of a cardiovascular or cerebrovascular event is considered to be higher than the risk of bleeding.²⁷

When patients are on DAPT for a history of drug-eluting stent placement, withholding both antiplatelet medications should be avoided, even for a brief period of time, given the risk of in-stent thrombosis. When DAPT is employed for other reasons, it should be continued, if indicated, after bleeding that is found to be due to peptic ulcers with low-risk stigmata. If bleeding is due to a peptic ulcer with high-risk stigmata at endoscopy, then aspirin monotherapy should be continued and consultation should be obtained with a cardiologist to determine optimal timing to resume the second antiplatelet agent.¹ In patients on anticoagulants, anticoagulation should be resumed once hemostasis is achieved when the risk of withholding anticoagulation is thought to be greater than the risk of rebleeding. For example, anticoagulation should be resumed early in a patient with a mechanical heart valve to prevent thrombosis.^1,27 Following upper GIB from peptic ulcer disease, patients who will require long-term aspirin, DAPT, or anticoagulation with either warfarin or DOACs should be maintained on long-term PPI therapy to reduce the risk of recurrent bleeding.^9,27

Failure of Endoscopic Therapy to Control Peptic Ulcer Bleeding

Bleeding recurs in as many as 10% to 20% of patients after initial endoscopic control of peptic ulcer bleeding.^4,31 In this context, repeat upper endoscopy for hemostasis is preferred to surgery, as it leads to less morbidity while providing long-term control of bleeding in more than 70% of cases.^31,32 Two potential endoscopic rescue therapies that may be employed are over-the-scope clips (OTSCs) and hemostatic powder.^32,33

While through-the-scope (TTS) hemostatic clips are often used during endoscopy to control active peptic ulcer bleeding, their use may be limited in large or fibrotic ulcers due to the smaller size of the clips and method of application. OTSCs have several advantages over TTS clips; notably, their larger size allows the endoscopist to achieve deeper mucosal or submucosal clip attachment via suction of the targeted tissue into the endoscopic cap (Figure 2). In a systematic review of OTSCs, successful hemostasis was achieved in 84% of 761 lesions, including 75% of lesions due to peptic ulcer disease.³⁴ Some have argued that OTSCs may be preferred as first-line therapy over epinephrine with TTS clips for hemostasis in bleeding from high-risk peptic ulcers (ie, those with visualized arterial bleeding or a visible vessel) given observed decreases in rebleeding events.³⁵

Despite the advantages of OTSCs, endoscopists should be mindful of the potential complications of OTSC use, including luminal obstruction, particularly in the duodenum, and perforation, which occurs in 0.3% to 2% of cases. Additionally, retrieval of misplaced OTSCs presents a significant challenge. Careful decision-making with consideration of the location, size, and depth of lesions is required when deciding on OTSC placement.^34,36

A newer endoscopic tool developed for refractory bleeding from peptic ulcers and other causes is hemostatic powder. Hemostatic powders accelerate the coagulation cascade, leading to shortened coagulation times and enhanced clot formation.³⁷ A recent meta-analysis showed that immediate hemostasis could be achieved in 95% of cases of bleeding, including in 96% of cases of bleeding from peptic ulcer disease.³⁸ The primary limitation of hemostatic powders is the temporary nature of hemostasis, which requires the underlying etiology of bleeding to be addressed in order to provide long-term hemostasis. In the above meta-analysis, rebleeding occurred in 17% of cases after 30 days.³⁸

Hypotension and ulcer diameter ≥ 2 cm are independent predictors of failure of endoscopic salvage therapy.³¹ When severe bleeding is not controlled with initial endoscopic therapy or bleeding recurs despite salvage endoscopic therapy, transcatheter angiographic embolization (TAE) is the treatment of choice.⁴ Systematic reviews and meta-analyses of studies that compared TAE to surgery have shown that the rate of rebleeding may be higher with TAE, but with less morbidity and either decreased or equivalent rates of mortality, with no increased need for additional interventions.^4,32 In a case series examining 5 years of experience at a single medical center in China, massive GIB from duodenal ulcers was successfully treated with TAE in 27 of 29 cases (93% clinical success rate), with no mucosal ischemic necrosis observed.³⁹

If repeated endoscopic therapy has not led to hemostasis of a bleeding peptic ulcer and TAE is not available, then surgery is the next best option. Bleeding gastric ulcers may be excised, wedge resected, or oversewn after an anterior gastrostomy. Bleeding duodenal ulcers may require use of a Kocher maneuver and linear incision of the anterior duodenum followed by ligation of the gastroduodenal artery. Fortunately, such surgical management is rarely necessary given the availability of TAE at most centers.⁴

Conclusion

Peptic ulcer disease is a common health problem globally, with persistent challenges related to refractory ulcers, antiplatelet and anticoagulant use, and continued bleeding in the face of endoscopic therapy. These challenges should be met with adequate frequency and duration of PPI therapy, vigilant attention to and treatment of ulcer etiology, evidence-based handling of antiplatelet and anticoagulant medications, and utilization of novel endoscopic tools to obtain improved clinical outcomes.

Acknowledgment: We thank Dr. Nipun Reddy from our institution for providing the endoscopic images used in this article.

Corresponding author: Adam L. Edwards, MD, MS; [email protected].

Financial disclosures: None.

From the University of Alabama at Birmingham, Birmingham, AL.

Abstract

Objective: To review current challenges in the management of peptic ulcer disease.

Methods: Review of the literature.

Results: Peptic ulcer disease affects 5% to 10% of the population worldwide, with recent decreases in lifetime prevalence in high-income countries. Helicobacter pylori infection and nonsteroidal anti-inflammatory drug (NSAID) use are the most important drivers of peptic ulcer disease. Current management strategies for peptic ulcer disease focus on ulcer healing; management of complications such as bleeding, perforation, and obstruction; and prevention of ulcer recurrence. Proton pump inhibitors (PPIs) are the cornerstone of medical therapy for peptic ulcers, and complement testing for and treatment of H. pylori infection as well as elimination of NSAID use. Although advances have been made in the medical and endoscopic treatment of peptic ulcer disease and the management of ulcer complications, such as bleeding and obstruction, challenges remain.

Conclusion: Peptic ulcer disease is a common health problem globally, with persistent challenges related to refractory ulcers, antiplatelet and anticoagulant use, and continued bleeding in the face of endoscopic therapy. These challenges should be met with PPI therapy of adequate frequency and duration, vigilant attention to and treatment of ulcer etiology, evidence-based handling of antiplatelet and anticoagulant medications, and utilization of novel endoscopic tools to obtain improved clinical outcomes.

Keywords: H. pylori; nonsteroidal anti-inflammatory drugs; NSAIDs; proton pump inhibitor; PPI; bleeding; perforation; obstruction; refractory ulcer; salvage endoscopic therapy; transcatheter angiographic embolization.

A peptic ulcer is a fibrin-covered break in the mucosa of the digestive tract extending to the submucosa that is caused by acid injury (Figure 1). Most peptic ulcers occur in the stomach or proximal duodenum, though they may also occur in the esophagus or, less frequently, in a Meckel’s diverticulum.^1,2 The estimated worldwide prevalence of peptic ulcer disease is 5% to 10%, with an annual incidence of 0.1% to 0.3%¹; both rates are declining.³ The annual incidence of peptic ulcer disease requiring medical or surgical treatment is also declining, and currently is estimated to be 0.1% to 0.2%.⁴ The lifetime prevalence of peptic ulcers has been decreasing in high-income countries since the mid-20th century due to both the widespread use of medications that suppress gastric acid secretion and the declining prevalence of Helicobacter pylori infection.^1,3

Peptic ulcer disease in most individuals results from H. pylori infection, chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, or both. A combination of H. pylori factors and host factors lead to mucosal disruption in infected individuals who develop peptic ulcers. H. pylori–specific factors include the expression of virulence factors such as CagA and VacA, which interact with the host inflammatory response to cause mucosal injury. The mucosal inflammatory response is at least partially determined by polymorphisms in the host’s cytokine genes.^1,4 NSAIDs inhibit the production of cyclooxygenase-1-derived prostaglandins, with subsequent decreases in epithelial mucous formation, bicarbonate secretion, cell proliferation, and mucosal blood flow, all of which are key elements in the maintenance of mucosal integrity.^1,5 Less common causes of peptic ulcers include gastrinoma, adenocarcinoma, idiopathic ulcers, use of sympathomimetic drugs (eg, cocaine or methamphetamine), certain anticancer agents, and bariatric surgery.^4,6

This article provides an overview of current management principles for peptic ulcer disease and discusses current challenges in peptic ulcer management, including proton pump inhibitor (PPI) therapy, refractory ulcers, handling of antiplatelet and anticoagulants during and after peptic ulcer bleeding, and ulcer bleeding that continues despite salvage endoscopic therapy.

Methods

We searched MEDLINE using the term peptic ulcer disease in combination with the terms current challenges, epidemiology, bleeding, anticoagulant, antiplatelet, PPI potency, etiology, treatment, management, and refractory. We selected publications from the past 35 years that we judged to be relevant.

Current Management

The goals of peptic ulcer disease management are ulcer healing and prevention of recurrence. The primary interventions used in the management of peptic ulcer disease are medical therapy and implementation of measures that address the underlying etiology of the disease.

Medical Therapy

Introduced in the late 1980s, PPIs are the cornerstone of medical therapy for peptic ulcer disease.⁶ These agents irreversibly inhibit the H+/K+-ATPase pump in the gastric mucosa and thereby inhibit gastric acid secretion, promoting ulcer healing. PPIs improve rates of ulcer healing compared to H2-receptor antagonists.^4,7

Underlying Causes

The underlying cause of peptic ulcer disease should be addressed, in addition to initiating medical therapy. A detailed history of NSAID use should be obtained, and patients with peptic ulcers caused by NSAIDs should be counseled to avoid them, if possible. Patients with peptic ulcer disease who require long-term use of NSAIDs should be placed on long-term PPI therapy.⁶ Any patient with peptic ulcer disease, regardless of any history of H. pylori infection or treatment, should be tested for infection. Tests that identify active infection, such as urea breath test, stool antigen assay, or mucosal biopsy–based testing, are preferred to IgG antibody testing, although the latter is acceptable in the context of peptic ulcer disease with a high pretest probability of infection.⁸ Any evidence of active infection warrants appropriate treatment to allow ulcer healing and prevent recurrence.¹H. pylori infection is most often treated with clarithromycin triple therapy or bismuth quadruple therapy for 14 days, with regimens selected based on the presence or absence of penicillin allergy, prior antibiotic exposure, and local clarithromycin resistance rates, when known.^4,8

Managing Complications

An additional aspect of care in peptic ulcer disease is managing the complications of bleeding, perforation, and gastric outlet obstruction. Acute upper gastrointestinal bleeding (GIB) is the most common complication of peptic ulcer disease, which accounts for 40% to 60% of nonvariceal acute upper GIB.^1,6 The first step in the management of acute GIB from a peptic ulcer is fluid resuscitation to ensure hemodynamic stability. If there is associated anemia with a hemoglobin level < 8 g/dL, blood transfusion should be undertaken to target a hemoglobin level > 8 g/dL. In patients with peptic ulcer disease–related acute upper GIB and comorbid cardiovascular disease, the transfusion threshold is higher, with the specific cutoff depending on clinical status, type and severity of cardiovascular disease, and degree of bleeding. Endoscopic management should generally be undertaken within 24 hours of presentation and should not be delayed in patients taking anticoagulants.⁹ Combination endoscopic treatment with through-the-scope clips plus thermocoagulation or sclerosant injection is recommended for acutely bleeding peptic ulcers with high-risk stigmata.

Pharmacologic management of patients with bleeding peptic ulcers with high-risk stigmata includes PPI therapy, with an 80 mg intravenous (IV) loading dose followed by continuous infusion of 8 mg/hr for 72 hours to reduce rebleeding and mortality. Following completion of IV therapy, oral PPI therapy should be continued twice daily for 14 days, followed by once-daily dosing thereafter.⁹Patients with peptic ulcer perforation present with sudden-onset epigastric abdominal pain and have tenderness to palpation, guarding, and rigidity on examination, often along with tachycardia and hypotension.^1,4 Computed tomography (CT) of the abdomen is 98% sensitive for identifying and localizing a perforation. Most perforations occur in the duodenum or antrum.

Management of a peptic ulcer perforation requires consultation with a surgeon to determine whether a nonoperative approach may be employed (eg, a stable patient with a contained perforation), or if surgery is indicated. The surgical approach to peptic ulcer perforation has been impacted by the clinical success of gastric acid suppression with PPIs and H. pylori eradication, but a range of surgical approaches are still used to repair perforations, from omental patch repair with peritoneal drain placement, to more extensive surgeries such as wedge resection or partial gastrectomy.⁴ Perforation carries a high mortality risk, up to 20% to 30%, and is the leading cause of death in patients with peptic ulcer disease.^1,4

Gastric outlet obstruction, a rare complication of peptic ulcer disease, results from recurrent ulcer formation and scarring. Obstruction often presents with hypovolemia and metabolic alkalosis from prolonged vomiting. CT imaging with oral contrast is often the first diagnostic test employed to demonstrate obstruction. Upper endoscopy should be performed to evaluate the appearance and degree of obstruction as well as to obtain biopsies to evaluate for a malignant etiology of the ulcer disease. Endoscopic balloon dilation has become the cornerstone of initial therapy for obstruction from peptic ulcer disease, especially in the case of ulcers due to reversible causes. Surgery is now typically reserved for cases of refractory obstruction, after repeated endoscopic balloon dilation has failed to remove the obstruction. However, because nearly all patients with gastric outlet obstruction present with malnutrition, nutritional deficiencies should be addressed prior to the patient undergoing surgical intervention. Surgical options include pyloroplasty, antrectomy, and gastrojejunostomy.⁴

Current Challenges

Rapid Metabolism of PPIs

High-dose PPI therapy is a key component of therapy for peptic ulcer healing. PPIs are metabolized by the cytochrome P450 system, which is comprised of multiple isoenzymes. CYP2C19, an isoenzyme involved in PPI metabolism, has 21 polymorphisms, which have variable effects leading to ultra-rapid, extensive, intermediate, or poor metabolism of PPIs.¹⁰ With rapid metabolism of PPIs, standard dosing can result in inadequate suppression of acid secretion. Despite this knowledge, routine testing of CYP2C19 phenotype is not recommended due to the cost of testing. Instead, inadequate ulcer healing should prompt consideration of increased PPI dosing to 80 mg orally twice daily, which may be sufficient to overcome rapid PPI metabolism.¹¹

Relative Potency of PPIs

In addition to variation in PPI metabolism, the relative potency of various PPIs has been questioned. A review of all available clinical studies of the effects of PPIs on mean 24-hour intragastric pH reported a quantitative difference in the potency of 5 PPIs, with omeprazole as the reference standard. Potencies ranged from 0.23 omeprazole equivalents for pantoprazole to 1.82 omeprazole equivalents for rabeprazole.¹² An additional study of data from 56 randomized clinical trials confirmed that PPIs vary in potency, which was measured as time that gastric pH is less than 4. A linear increase in intragastric pH time less than 4 was observed from 9 to 64 mg omeprazole equivalents; higher doses yielded no additional benefit. An increase in PPI dosing from once daily to twice daily also increased the duration of intragastric pH time less than 4 from 15 to 21 hours.¹³ Earlier modeling of the relationship between duodenal ulcer healing and antisecretory therapy showed a strong correlation of ulcer healing with the duration of acid suppression, length of therapy, and the degree of acid suppression. Additional benefit was not observed after intragastric pH rose above 3.¹⁴ Thus, as the frequency and duration of acid suppression therapy are more important than PPI potency, PPIs can be used interchangeably.^13,14

Addressing Underlying Causes

Continued NSAID Use. Refractory peptic ulcers are defined as those that do not heal despite adherence to 8 to 12 weeks of standard acid-suppression therapy. A cause of refractory peptic ulcer disease that must be considered is continued NSAID use.^1,15 In a study of patients with refractory peptic ulcers, 27% of patients continued NSAID use, as determined by eventual disclosure by the patients or platelet cyclooxygenase activity assay, despite extensive counseling to avoid NSAIDs at the time of the diagnosis of their refractory ulcer and at subsequent visits.¹⁶ Pain may make NSAID cessation difficult for some patients, while others do not realize that over-the-counter preparations they take contain NSAIDs.¹⁵

Another group of patients with continued NSAID exposure are those who require long-term NSAID therapy for control of arthritis or the management of cardiovascular conditions. If NSAID therapy cannot be discontinued, the risk of NSAID-related gastrointestinal injury can be assessed based on the presence of multiple risk factors, including age > 65 years, high-dose NSAID therapy, a history of peptic ulcer, and concurrent use of aspirin, corticosteroids, or anticoagulants. Individuals with 3 or more of the preceding risk factors or a history of a peptic ulcer with a complication, especially if recent, are considered to be at high risk of developing an NSAID-related ulcer and possible subsequent complications.¹⁷ In these individuals, NSAID therapy should be continued with agents that have the lowest risk for gastrointestinal toxicity and at the lowest possible dose. A meta-analysis comparing nonselective NSAIDs to placebo demonstrated naproxen to have the highest risk of gastrointestinal complications, including GIB, perforation, and obstruction (adjusted rate ratio, 4.2), while diclofenac demonstrated the lowest risk (adjusted rate ratio, 1.89). High-dose NSAID therapy demonstrated a 2-fold increase in risk of peptic ulcer formation as compared to low-dose therapy.¹⁸

In addition to selecting the NSAID with the least gastrointestinal toxicity at the lowest possible dose, additional strategies to prevent peptic ulcer disease and its complications in chronic NSAID users include co-administration of a PPI and substitution of a COX-2 selective NSAID for nonselective NSAIDs.^1,9 Prior double-blind, placebo-controlled, randomized, multicenter trials with patients requiring daily NSAIDs demonstrated an up to 15% absolute reduction in the risk of developing peptic ulcers over 6 months while taking esomeprazole.¹⁹

Persistent Infection. Persistent H. pylori infection, due either to initial false-negative testing or ongoing infection despite first-line therapy, is another cause of refractory peptic ulcer disease.^1,15 Because antibiotics and PPIs can reduce the number of H. pylori bacteria, use of these medications concurrent with H. pylori testing can lead to false-negative results with several testing modalities. When suspicion for H. pylori is high, 2 or more diagnostic tests may be needed to effectively rule out infection.¹⁵

When H. pylori is detected, successful eradication is becoming more difficult due to an increasing prevalence of antibiotic resistance, leading to persistent infection in many cases and maintained risk of peptic ulcer disease, despite appropriate first-line therapy.⁸ Options for salvage therapy for persistent H. pylori, as well as information on the role and best timing of susceptibility testing, are beyond the scope of this review, but are reviewed by Lanas and Chan¹ and in the American College of Gastroenterology guideline on the treatment of H. pylori infection.⁸

Other Causes. In a meta-analysis of rigorously designed studies from North America, 20% of patients experienced ulcer recurrence at 6 months, despite successful H. pylori eradication and no NSAID use.²⁰ In addition, as H. pylori prevalence is decreasing, idiopathic ulcers are increasingly being diagnosed, and such ulcers may be associated with high rates of GIB and mortality.¹ In this subset of patients with non-H. pylori, non-NSAID ulcers, increased effort is required to further evaluate the differential diagnosis for rarer causes of upper GI tract ulcer disease (Table). Certain malignancies, including adenocarcinoma and lymphoma, can cause ulcer formation and should be considered in refractory cases. Repeat biopsy at follow-up endoscopy for persistent ulcers should always be obtained to further evaluate for malignancy.^1,15 Infectious diseases other than H. pylori infection, such as tuberculosis, syphilis, cytomegalovirus, and herpes simplex virus, are also reported as etiologies of refractory ulcers, and require specific antimicrobial treatment over and above PPI monotherapy. Special attention in biopsy sampling and sample processing is often required when infectious etiologies are being considered, as specific histologic stains and cultures may be needed for identification.¹⁵

Systemic conditions, including sarcoidosis,²¹ Behçet disease,²² and polyarteritis nodosa,^15,23 can also cause refractory ulcers. Approximately 15% of patients with Crohn disease have gastroduodenal involvement, which may include ulcers of variable sizes.^1,15,24 The increased gastric acid production seen in Zollinger-Ellison syndrome commonly presents as refractory peptic ulcers in the duodenum beyond the bulb that do not heal with standard doses of PPIs.^1,15 More rare causes of acid hypersecretion leading to refractory ulcers include idiopathic gastric acid hypersecretion and retained gastric antrum syndrome after partial gastrectomy with Billroth II anastomosis.¹⁵ Smoking is a known risk factor for impaired tissue healing throughout the body, and can contribute to impaired healing of peptic ulcers through decreased prostaglandin synthesis²⁵ and reduced gastric mucosal blood flow.²⁶ Smoking should always be addressed in patients with refractory peptic ulcers, and cessation should be strongly encouraged. Other less common causes of refractory upper GI tract ulcers include radiation therapy, crack cocaine use, and mesenteric ischemia.¹⁵

Managing Antiplatelet and Anticoagulant Medications

Use of antiplatelets and anticoagulants, alone or in combination, increases the risk of peptic ulcer bleeding. In patients who continue to take aspirin after a peptic ulcer bleed, recurrent bleeding occurs in up to 300 cases per 1000 person-years. The rate of GIB associated with aspirin use ranges from 1.1% to 2.5%, depending on the dose. Prior peptic ulcer disease, age greater than 70 years, and concurrent NSAID, steroid, anticoagulant, or dual antiplatelet therapy (DAPT) use increase the risk of bleeding while on aspirin. The rate of GIB while taking a thienopyridine alone is slightly less than that when taking aspirin, ranging from 0.5% to 1.6%. Studies to date have yielded mixed estimates of the effect of DAPT on the risk of GIB. Estimates of the risk of GIB with DAPT range from an odds ratio for serious GIB of 7.4 to an absolute risk increase of only 1.3% when compared to clopidogrel alone.²⁷

Many patients are also on warfarin or a direct oral anticoagulant (DOAC). In a study from the United Kingdom, the adjusted rate ratio of GIB with warfarin alone was 1.94, and this increased to 6.48 when warfarin was used with aspirin.²⁸ The use of warfarin and DAPT, often called triple therapy, further increases the risk of GIB, with a hazard ratio of 5.0 compared to DAPT alone, and 5.38 when compared to warfarin alone. DOACs are increasingly prescribed for the treatment and prevention of thromboembolism, and by 2014 were prescribed as often as warfarin for stroke prevention in atrial fibrillation in the United States. A meta-analysis showed the risk of major GIB did not differ between DOACs and warfarin or low-molecular-weight heparin, but among DOACs factor Xa inhibitors showed a reduced risk of GIB compared with dabigatran, a direct thrombin inhibitor.²⁹

The use of antiplatelets and anticoagulants in the context of peptic ulcer bleeding is a current management challenge. Data to guide decision-making in patients on antiplatelet and/or anticoagulant therapy who experience peptic ulcer bleeding are scarce. Decision-making in this group of patients requires balancing the severity and risk of bleeding with the risk of thromboembolism.^1,27 In patients on antiplatelet therapy for primary prophylaxis of atherothrombosis who develop bleeding from a peptic ulcer, the antiplatelet should generally be held and the indication for the medication reassessed. In patients on antiplatelet therapy for secondary prevention, the agent may be immediately resumed after endoscopy if bleeding is found to be due to an ulcer with low-risk stigmata. With bleeding resulting from an ulcer with high-risk stigmata, antiplatelet agents employed for secondary prevention may be held initially, with consideration given to early reintroduction, as early as day 3 after endoscopy.¹ In patients at high risk for atherothrombotic events, including those on aspirin for secondary prophylaxis, withholding aspirin leads to a 3-fold increase in the risk of a major adverse cardiac event, with events occurring as early as 5 days after aspirin cessation in some cases.²⁷ A randomized controlled trial of continuing low-dose aspirin versus withholding it for 8 weeks in patients on aspirin for secondary prophylaxis of cardiovascular events who experienced peptic ulcer bleeding that required endoscopic therapy demonstrated lower all-cause mortality (1.3% vs 12.9%), including death from cardiovascular or cerebrovascular events, among those who continued aspirin therapy, with a small increased risk of recurrent ulcer bleeding (10.3% vs 5.4%).³⁰ Thus, it is recommended that antiplatelet therapy, when held, be resumed as early as possible when the risk of a cardiovascular or cerebrovascular event is considered to be higher than the risk of bleeding.²⁷

When patients are on DAPT for a history of drug-eluting stent placement, withholding both antiplatelet medications should be avoided, even for a brief period of time, given the risk of in-stent thrombosis. When DAPT is employed for other reasons, it should be continued, if indicated, after bleeding that is found to be due to peptic ulcers with low-risk stigmata. If bleeding is due to a peptic ulcer with high-risk stigmata at endoscopy, then aspirin monotherapy should be continued and consultation should be obtained with a cardiologist to determine optimal timing to resume the second antiplatelet agent.¹ In patients on anticoagulants, anticoagulation should be resumed once hemostasis is achieved when the risk of withholding anticoagulation is thought to be greater than the risk of rebleeding. For example, anticoagulation should be resumed early in a patient with a mechanical heart valve to prevent thrombosis.^1,27 Following upper GIB from peptic ulcer disease, patients who will require long-term aspirin, DAPT, or anticoagulation with either warfarin or DOACs should be maintained on long-term PPI therapy to reduce the risk of recurrent bleeding.^9,27

Failure of Endoscopic Therapy to Control Peptic Ulcer Bleeding

Bleeding recurs in as many as 10% to 20% of patients after initial endoscopic control of peptic ulcer bleeding.^4,31 In this context, repeat upper endoscopy for hemostasis is preferred to surgery, as it leads to less morbidity while providing long-term control of bleeding in more than 70% of cases.^31,32 Two potential endoscopic rescue therapies that may be employed are over-the-scope clips (OTSCs) and hemostatic powder.^32,33

While through-the-scope (TTS) hemostatic clips are often used during endoscopy to control active peptic ulcer bleeding, their use may be limited in large or fibrotic ulcers due to the smaller size of the clips and method of application. OTSCs have several advantages over TTS clips; notably, their larger size allows the endoscopist to achieve deeper mucosal or submucosal clip attachment via suction of the targeted tissue into the endoscopic cap (Figure 2). In a systematic review of OTSCs, successful hemostasis was achieved in 84% of 761 lesions, including 75% of lesions due to peptic ulcer disease.³⁴ Some have argued that OTSCs may be preferred as first-line therapy over epinephrine with TTS clips for hemostasis in bleeding from high-risk peptic ulcers (ie, those with visualized arterial bleeding or a visible vessel) given observed decreases in rebleeding events.³⁵

Despite the advantages of OTSCs, endoscopists should be mindful of the potential complications of OTSC use, including luminal obstruction, particularly in the duodenum, and perforation, which occurs in 0.3% to 2% of cases. Additionally, retrieval of misplaced OTSCs presents a significant challenge. Careful decision-making with consideration of the location, size, and depth of lesions is required when deciding on OTSC placement.^34,36

A newer endoscopic tool developed for refractory bleeding from peptic ulcers and other causes is hemostatic powder. Hemostatic powders accelerate the coagulation cascade, leading to shortened coagulation times and enhanced clot formation.³⁷ A recent meta-analysis showed that immediate hemostasis could be achieved in 95% of cases of bleeding, including in 96% of cases of bleeding from peptic ulcer disease.³⁸ The primary limitation of hemostatic powders is the temporary nature of hemostasis, which requires the underlying etiology of bleeding to be addressed in order to provide long-term hemostasis. In the above meta-analysis, rebleeding occurred in 17% of cases after 30 days.³⁸

Hypotension and ulcer diameter ≥ 2 cm are independent predictors of failure of endoscopic salvage therapy.³¹ When severe bleeding is not controlled with initial endoscopic therapy or bleeding recurs despite salvage endoscopic therapy, transcatheter angiographic embolization (TAE) is the treatment of choice.⁴ Systematic reviews and meta-analyses of studies that compared TAE to surgery have shown that the rate of rebleeding may be higher with TAE, but with less morbidity and either decreased or equivalent rates of mortality, with no increased need for additional interventions.^4,32 In a case series examining 5 years of experience at a single medical center in China, massive GIB from duodenal ulcers was successfully treated with TAE in 27 of 29 cases (93% clinical success rate), with no mucosal ischemic necrosis observed.³⁹

If repeated endoscopic therapy has not led to hemostasis of a bleeding peptic ulcer and TAE is not available, then surgery is the next best option. Bleeding gastric ulcers may be excised, wedge resected, or oversewn after an anterior gastrostomy. Bleeding duodenal ulcers may require use of a Kocher maneuver and linear incision of the anterior duodenum followed by ligation of the gastroduodenal artery. Fortunately, such surgical management is rarely necessary given the availability of TAE at most centers.⁴

Conclusion

Peptic ulcer disease is a common health problem globally, with persistent challenges related to refractory ulcers, antiplatelet and anticoagulant use, and continued bleeding in the face of endoscopic therapy. These challenges should be met with adequate frequency and duration of PPI therapy, vigilant attention to and treatment of ulcer etiology, evidence-based handling of antiplatelet and anticoagulant medications, and utilization of novel endoscopic tools to obtain improved clinical outcomes.

Acknowledgment: We thank Dr. Nipun Reddy from our institution for providing the endoscopic images used in this article.

Corresponding author: Adam L. Edwards, MD, MS; [email protected].

Financial disclosures: None.

From the University of Alabama at Birmingham, Birmingham, AL.

Abstract

Objective: To review current challenges in the management of peptic ulcer disease.

Methods: Review of the literature.

Results: Peptic ulcer disease affects 5% to 10% of the population worldwide, with recent decreases in lifetime prevalence in high-income countries. Helicobacter pylori infection and nonsteroidal anti-inflammatory drug (NSAID) use are the most important drivers of peptic ulcer disease. Current management strategies for peptic ulcer disease focus on ulcer healing; management of complications such as bleeding, perforation, and obstruction; and prevention of ulcer recurrence. Proton pump inhibitors (PPIs) are the cornerstone of medical therapy for peptic ulcers, and complement testing for and treatment of H. pylori infection as well as elimination of NSAID use. Although advances have been made in the medical and endoscopic treatment of peptic ulcer disease and the management of ulcer complications, such as bleeding and obstruction, challenges remain.

Conclusion: Peptic ulcer disease is a common health problem globally, with persistent challenges related to refractory ulcers, antiplatelet and anticoagulant use, and continued bleeding in the face of endoscopic therapy. These challenges should be met with PPI therapy of adequate frequency and duration, vigilant attention to and treatment of ulcer etiology, evidence-based handling of antiplatelet and anticoagulant medications, and utilization of novel endoscopic tools to obtain improved clinical outcomes.

Keywords: H. pylori; nonsteroidal anti-inflammatory drugs; NSAIDs; proton pump inhibitor; PPI; bleeding; perforation; obstruction; refractory ulcer; salvage endoscopic therapy; transcatheter angiographic embolization.

A peptic ulcer is a fibrin-covered break in the mucosa of the digestive tract extending to the submucosa that is caused by acid injury (Figure 1). Most peptic ulcers occur in the stomach or proximal duodenum, though they may also occur in the esophagus or, less frequently, in a Meckel’s diverticulum.^1,2 The estimated worldwide prevalence of peptic ulcer disease is 5% to 10%, with an annual incidence of 0.1% to 0.3%¹; both rates are declining.³ The annual incidence of peptic ulcer disease requiring medical or surgical treatment is also declining, and currently is estimated to be 0.1% to 0.2%.⁴ The lifetime prevalence of peptic ulcers has been decreasing in high-income countries since the mid-20th century due to both the widespread use of medications that suppress gastric acid secretion and the declining prevalence of Helicobacter pylori infection.^1,3

Peptic ulcer disease in most individuals results from H. pylori infection, chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, or both. A combination of H. pylori factors and host factors lead to mucosal disruption in infected individuals who develop peptic ulcers. H. pylori–specific factors include the expression of virulence factors such as CagA and VacA, which interact with the host inflammatory response to cause mucosal injury. The mucosal inflammatory response is at least partially determined by polymorphisms in the host’s cytokine genes.^1,4 NSAIDs inhibit the production of cyclooxygenase-1-derived prostaglandins, with subsequent decreases in epithelial mucous formation, bicarbonate secretion, cell proliferation, and mucosal blood flow, all of which are key elements in the maintenance of mucosal integrity.^1,5 Less common causes of peptic ulcers include gastrinoma, adenocarcinoma, idiopathic ulcers, use of sympathomimetic drugs (eg, cocaine or methamphetamine), certain anticancer agents, and bariatric surgery.^4,6

This article provides an overview of current management principles for peptic ulcer disease and discusses current challenges in peptic ulcer management, including proton pump inhibitor (PPI) therapy, refractory ulcers, handling of antiplatelet and anticoagulants during and after peptic ulcer bleeding, and ulcer bleeding that continues despite salvage endoscopic therapy.

Methods

We searched MEDLINE using the term peptic ulcer disease in combination with the terms current challenges, epidemiology, bleeding, anticoagulant, antiplatelet, PPI potency, etiology, treatment, management, and refractory. We selected publications from the past 35 years that we judged to be relevant.

Current Management

The goals of peptic ulcer disease management are ulcer healing and prevention of recurrence. The primary interventions used in the management of peptic ulcer disease are medical therapy and implementation of measures that address the underlying etiology of the disease.

Medical Therapy

Introduced in the late 1980s, PPIs are the cornerstone of medical therapy for peptic ulcer disease.⁶ These agents irreversibly inhibit the H+/K+-ATPase pump in the gastric mucosa and thereby inhibit gastric acid secretion, promoting ulcer healing. PPIs improve rates of ulcer healing compared to H2-receptor antagonists.^4,7

Underlying Causes

The underlying cause of peptic ulcer disease should be addressed, in addition to initiating medical therapy. A detailed history of NSAID use should be obtained, and patients with peptic ulcers caused by NSAIDs should be counseled to avoid them, if possible. Patients with peptic ulcer disease who require long-term use of NSAIDs should be placed on long-term PPI therapy.⁶ Any patient with peptic ulcer disease, regardless of any history of H. pylori infection or treatment, should be tested for infection. Tests that identify active infection, such as urea breath test, stool antigen assay, or mucosal biopsy–based testing, are preferred to IgG antibody testing, although the latter is acceptable in the context of peptic ulcer disease with a high pretest probability of infection.⁸ Any evidence of active infection warrants appropriate treatment to allow ulcer healing and prevent recurrence.¹H. pylori infection is most often treated with clarithromycin triple therapy or bismuth quadruple therapy for 14 days, with regimens selected based on the presence or absence of penicillin allergy, prior antibiotic exposure, and local clarithromycin resistance rates, when known.^4,8

Managing Complications

An additional aspect of care in peptic ulcer disease is managing the complications of bleeding, perforation, and gastric outlet obstruction. Acute upper gastrointestinal bleeding (GIB) is the most common complication of peptic ulcer disease, which accounts for 40% to 60% of nonvariceal acute upper GIB.^1,6 The first step in the management of acute GIB from a peptic ulcer is fluid resuscitation to ensure hemodynamic stability. If there is associated anemia with a hemoglobin level < 8 g/dL, blood transfusion should be undertaken to target a hemoglobin level > 8 g/dL. In patients with peptic ulcer disease–related acute upper GIB and comorbid cardiovascular disease, the transfusion threshold is higher, with the specific cutoff depending on clinical status, type and severity of cardiovascular disease, and degree of bleeding. Endoscopic management should generally be undertaken within 24 hours of presentation and should not be delayed in patients taking anticoagulants.⁹ Combination endoscopic treatment with through-the-scope clips plus thermocoagulation or sclerosant injection is recommended for acutely bleeding peptic ulcers with high-risk stigmata.

Pharmacologic management of patients with bleeding peptic ulcers with high-risk stigmata includes PPI therapy, with an 80 mg intravenous (IV) loading dose followed by continuous infusion of 8 mg/hr for 72 hours to reduce rebleeding and mortality. Following completion of IV therapy, oral PPI therapy should be continued twice daily for 14 days, followed by once-daily dosing thereafter.⁹Patients with peptic ulcer perforation present with sudden-onset epigastric abdominal pain and have tenderness to palpation, guarding, and rigidity on examination, often along with tachycardia and hypotension.^1,4 Computed tomography (CT) of the abdomen is 98% sensitive for identifying and localizing a perforation. Most perforations occur in the duodenum or antrum.

Management of a peptic ulcer perforation requires consultation with a surgeon to determine whether a nonoperative approach may be employed (eg, a stable patient with a contained perforation), or if surgery is indicated. The surgical approach to peptic ulcer perforation has been impacted by the clinical success of gastric acid suppression with PPIs and H. pylori eradication, but a range of surgical approaches are still used to repair perforations, from omental patch repair with peritoneal drain placement, to more extensive surgeries such as wedge resection or partial gastrectomy.⁴ Perforation carries a high mortality risk, up to 20% to 30%, and is the leading cause of death in patients with peptic ulcer disease.^1,4

Gastric outlet obstruction, a rare complication of peptic ulcer disease, results from recurrent ulcer formation and scarring. Obstruction often presents with hypovolemia and metabolic alkalosis from prolonged vomiting. CT imaging with oral contrast is often the first diagnostic test employed to demonstrate obstruction. Upper endoscopy should be performed to evaluate the appearance and degree of obstruction as well as to obtain biopsies to evaluate for a malignant etiology of the ulcer disease. Endoscopic balloon dilation has become the cornerstone of initial therapy for obstruction from peptic ulcer disease, especially in the case of ulcers due to reversible causes. Surgery is now typically reserved for cases of refractory obstruction, after repeated endoscopic balloon dilation has failed to remove the obstruction. However, because nearly all patients with gastric outlet obstruction present with malnutrition, nutritional deficiencies should be addressed prior to the patient undergoing surgical intervention. Surgical options include pyloroplasty, antrectomy, and gastrojejunostomy.⁴

Current Challenges

Rapid Metabolism of PPIs

High-dose PPI therapy is a key component of therapy for peptic ulcer healing. PPIs are metabolized by the cytochrome P450 system, which is comprised of multiple isoenzymes. CYP2C19, an isoenzyme involved in PPI metabolism, has 21 polymorphisms, which have variable effects leading to ultra-rapid, extensive, intermediate, or poor metabolism of PPIs.¹⁰ With rapid metabolism of PPIs, standard dosing can result in inadequate suppression of acid secretion. Despite this knowledge, routine testing of CYP2C19 phenotype is not recommended due to the cost of testing. Instead, inadequate ulcer healing should prompt consideration of increased PPI dosing to 80 mg orally twice daily, which may be sufficient to overcome rapid PPI metabolism.¹¹

Relative Potency of PPIs

In addition to variation in PPI metabolism, the relative potency of various PPIs has been questioned. A review of all available clinical studies of the effects of PPIs on mean 24-hour intragastric pH reported a quantitative difference in the potency of 5 PPIs, with omeprazole as the reference standard. Potencies ranged from 0.23 omeprazole equivalents for pantoprazole to 1.82 omeprazole equivalents for rabeprazole.¹² An additional study of data from 56 randomized clinical trials confirmed that PPIs vary in potency, which was measured as time that gastric pH is less than 4. A linear increase in intragastric pH time less than 4 was observed from 9 to 64 mg omeprazole equivalents; higher doses yielded no additional benefit. An increase in PPI dosing from once daily to twice daily also increased the duration of intragastric pH time less than 4 from 15 to 21 hours.¹³ Earlier modeling of the relationship between duodenal ulcer healing and antisecretory therapy showed a strong correlation of ulcer healing with the duration of acid suppression, length of therapy, and the degree of acid suppression. Additional benefit was not observed after intragastric pH rose above 3.¹⁴ Thus, as the frequency and duration of acid suppression therapy are more important than PPI potency, PPIs can be used interchangeably.^13,14

Addressing Underlying Causes

Continued NSAID Use. Refractory peptic ulcers are defined as those that do not heal despite adherence to 8 to 12 weeks of standard acid-suppression therapy. A cause of refractory peptic ulcer disease that must be considered is continued NSAID use.^1,15 In a study of patients with refractory peptic ulcers, 27% of patients continued NSAID use, as determined by eventual disclosure by the patients or platelet cyclooxygenase activity assay, despite extensive counseling to avoid NSAIDs at the time of the diagnosis of their refractory ulcer and at subsequent visits.¹⁶ Pain may make NSAID cessation difficult for some patients, while others do not realize that over-the-counter preparations they take contain NSAIDs.¹⁵

Another group of patients with continued NSAID exposure are those who require long-term NSAID therapy for control of arthritis or the management of cardiovascular conditions. If NSAID therapy cannot be discontinued, the risk of NSAID-related gastrointestinal injury can be assessed based on the presence of multiple risk factors, including age > 65 years, high-dose NSAID therapy, a history of peptic ulcer, and concurrent use of aspirin, corticosteroids, or anticoagulants. Individuals with 3 or more of the preceding risk factors or a history of a peptic ulcer with a complication, especially if recent, are considered to be at high risk of developing an NSAID-related ulcer and possible subsequent complications.¹⁷ In these individuals, NSAID therapy should be continued with agents that have the lowest risk for gastrointestinal toxicity and at the lowest possible dose. A meta-analysis comparing nonselective NSAIDs to placebo demonstrated naproxen to have the highest risk of gastrointestinal complications, including GIB, perforation, and obstruction (adjusted rate ratio, 4.2), while diclofenac demonstrated the lowest risk (adjusted rate ratio, 1.89). High-dose NSAID therapy demonstrated a 2-fold increase in risk of peptic ulcer formation as compared to low-dose therapy.¹⁸

In addition to selecting the NSAID with the least gastrointestinal toxicity at the lowest possible dose, additional strategies to prevent peptic ulcer disease and its complications in chronic NSAID users include co-administration of a PPI and substitution of a COX-2 selective NSAID for nonselective NSAIDs.^1,9 Prior double-blind, placebo-controlled, randomized, multicenter trials with patients requiring daily NSAIDs demonstrated an up to 15% absolute reduction in the risk of developing peptic ulcers over 6 months while taking esomeprazole.¹⁹

Persistent Infection. Persistent H. pylori infection, due either to initial false-negative testing or ongoing infection despite first-line therapy, is another cause of refractory peptic ulcer disease.^1,15 Because antibiotics and PPIs can reduce the number of H. pylori bacteria, use of these medications concurrent with H. pylori testing can lead to false-negative results with several testing modalities. When suspicion for H. pylori is high, 2 or more diagnostic tests may be needed to effectively rule out infection.¹⁵

When H. pylori is detected, successful eradication is becoming more difficult due to an increasing prevalence of antibiotic resistance, leading to persistent infection in many cases and maintained risk of peptic ulcer disease, despite appropriate first-line therapy.⁸ Options for salvage therapy for persistent H. pylori, as well as information on the role and best timing of susceptibility testing, are beyond the scope of this review, but are reviewed by Lanas and Chan¹ and in the American College of Gastroenterology guideline on the treatment of H. pylori infection.⁸

Other Causes. In a meta-analysis of rigorously designed studies from North America, 20% of patients experienced ulcer recurrence at 6 months, despite successful H. pylori eradication and no NSAID use.²⁰ In addition, as H. pylori prevalence is decreasing, idiopathic ulcers are increasingly being diagnosed, and such ulcers may be associated with high rates of GIB and mortality.¹ In this subset of patients with non-H. pylori, non-NSAID ulcers, increased effort is required to further evaluate the differential diagnosis for rarer causes of upper GI tract ulcer disease (Table). Certain malignancies, including adenocarcinoma and lymphoma, can cause ulcer formation and should be considered in refractory cases. Repeat biopsy at follow-up endoscopy for persistent ulcers should always be obtained to further evaluate for malignancy.^1,15 Infectious diseases other than H. pylori infection, such as tuberculosis, syphilis, cytomegalovirus, and herpes simplex virus, are also reported as etiologies of refractory ulcers, and require specific antimicrobial treatment over and above PPI monotherapy. Special attention in biopsy sampling and sample processing is often required when infectious etiologies are being considered, as specific histologic stains and cultures may be needed for identification.¹⁵

Systemic conditions, including sarcoidosis,²¹ Behçet disease,²² and polyarteritis nodosa,^15,23 can also cause refractory ulcers. Approximately 15% of patients with Crohn disease have gastroduodenal involvement, which may include ulcers of variable sizes.^1,15,24 The increased gastric acid production seen in Zollinger-Ellison syndrome commonly presents as refractory peptic ulcers in the duodenum beyond the bulb that do not heal with standard doses of PPIs.^1,15 More rare causes of acid hypersecretion leading to refractory ulcers include idiopathic gastric acid hypersecretion and retained gastric antrum syndrome after partial gastrectomy with Billroth II anastomosis.¹⁵ Smoking is a known risk factor for impaired tissue healing throughout the body, and can contribute to impaired healing of peptic ulcers through decreased prostaglandin synthesis²⁵ and reduced gastric mucosal blood flow.²⁶ Smoking should always be addressed in patients with refractory peptic ulcers, and cessation should be strongly encouraged. Other less common causes of refractory upper GI tract ulcers include radiation therapy, crack cocaine use, and mesenteric ischemia.¹⁵

Managing Antiplatelet and Anticoagulant Medications

Use of antiplatelets and anticoagulants, alone or in combination, increases the risk of peptic ulcer bleeding. In patients who continue to take aspirin after a peptic ulcer bleed, recurrent bleeding occurs in up to 300 cases per 1000 person-years. The rate of GIB associated with aspirin use ranges from 1.1% to 2.5%, depending on the dose. Prior peptic ulcer disease, age greater than 70 years, and concurrent NSAID, steroid, anticoagulant, or dual antiplatelet therapy (DAPT) use increase the risk of bleeding while on aspirin. The rate of GIB while taking a thienopyridine alone is slightly less than that when taking aspirin, ranging from 0.5% to 1.6%. Studies to date have yielded mixed estimates of the effect of DAPT on the risk of GIB. Estimates of the risk of GIB with DAPT range from an odds ratio for serious GIB of 7.4 to an absolute risk increase of only 1.3% when compared to clopidogrel alone.²⁷

Many patients are also on warfarin or a direct oral anticoagulant (DOAC). In a study from the United Kingdom, the adjusted rate ratio of GIB with warfarin alone was 1.94, and this increased to 6.48 when warfarin was used with aspirin.²⁸ The use of warfarin and DAPT, often called triple therapy, further increases the risk of GIB, with a hazard ratio of 5.0 compared to DAPT alone, and 5.38 when compared to warfarin alone. DOACs are increasingly prescribed for the treatment and prevention of thromboembolism, and by 2014 were prescribed as often as warfarin for stroke prevention in atrial fibrillation in the United States. A meta-analysis showed the risk of major GIB did not differ between DOACs and warfarin or low-molecular-weight heparin, but among DOACs factor Xa inhibitors showed a reduced risk of GIB compared with dabigatran, a direct thrombin inhibitor.²⁹

The use of antiplatelets and anticoagulants in the context of peptic ulcer bleeding is a current management challenge. Data to guide decision-making in patients on antiplatelet and/or anticoagulant therapy who experience peptic ulcer bleeding are scarce. Decision-making in this group of patients requires balancing the severity and risk of bleeding with the risk of thromboembolism.^1,27 In patients on antiplatelet therapy for primary prophylaxis of atherothrombosis who develop bleeding from a peptic ulcer, the antiplatelet should generally be held and the indication for the medication reassessed. In patients on antiplatelet therapy for secondary prevention, the agent may be immediately resumed after endoscopy if bleeding is found to be due to an ulcer with low-risk stigmata. With bleeding resulting from an ulcer with high-risk stigmata, antiplatelet agents employed for secondary prevention may be held initially, with consideration given to early reintroduction, as early as day 3 after endoscopy.¹ In patients at high risk for atherothrombotic events, including those on aspirin for secondary prophylaxis, withholding aspirin leads to a 3-fold increase in the risk of a major adverse cardiac event, with events occurring as early as 5 days after aspirin cessation in some cases.²⁷ A randomized controlled trial of continuing low-dose aspirin versus withholding it for 8 weeks in patients on aspirin for secondary prophylaxis of cardiovascular events who experienced peptic ulcer bleeding that required endoscopic therapy demonstrated lower all-cause mortality (1.3% vs 12.9%), including death from cardiovascular or cerebrovascular events, among those who continued aspirin therapy, with a small increased risk of recurrent ulcer bleeding (10.3% vs 5.4%).³⁰ Thus, it is recommended that antiplatelet therapy, when held, be resumed as early as possible when the risk of a cardiovascular or cerebrovascular event is considered to be higher than the risk of bleeding.²⁷

When patients are on DAPT for a history of drug-eluting stent placement, withholding both antiplatelet medications should be avoided, even for a brief period of time, given the risk of in-stent thrombosis. When DAPT is employed for other reasons, it should be continued, if indicated, after bleeding that is found to be due to peptic ulcers with low-risk stigmata. If bleeding is due to a peptic ulcer with high-risk stigmata at endoscopy, then aspirin monotherapy should be continued and consultation should be obtained with a cardiologist to determine optimal timing to resume the second antiplatelet agent.¹ In patients on anticoagulants, anticoagulation should be resumed once hemostasis is achieved when the risk of withholding anticoagulation is thought to be greater than the risk of rebleeding. For example, anticoagulation should be resumed early in a patient with a mechanical heart valve to prevent thrombosis.^1,27 Following upper GIB from peptic ulcer disease, patients who will require long-term aspirin, DAPT, or anticoagulation with either warfarin or DOACs should be maintained on long-term PPI therapy to reduce the risk of recurrent bleeding.^9,27

Failure of Endoscopic Therapy to Control Peptic Ulcer Bleeding

Bleeding recurs in as many as 10% to 20% of patients after initial endoscopic control of peptic ulcer bleeding.^4,31 In this context, repeat upper endoscopy for hemostasis is preferred to surgery, as it leads to less morbidity while providing long-term control of bleeding in more than 70% of cases.^31,32 Two potential endoscopic rescue therapies that may be employed are over-the-scope clips (OTSCs) and hemostatic powder.^32,33

While through-the-scope (TTS) hemostatic clips are often used during endoscopy to control active peptic ulcer bleeding, their use may be limited in large or fibrotic ulcers due to the smaller size of the clips and method of application. OTSCs have several advantages over TTS clips; notably, their larger size allows the endoscopist to achieve deeper mucosal or submucosal clip attachment via suction of the targeted tissue into the endoscopic cap (Figure 2). In a systematic review of OTSCs, successful hemostasis was achieved in 84% of 761 lesions, including 75% of lesions due to peptic ulcer disease.³⁴ Some have argued that OTSCs may be preferred as first-line therapy over epinephrine with TTS clips for hemostasis in bleeding from high-risk peptic ulcers (ie, those with visualized arterial bleeding or a visible vessel) given observed decreases in rebleeding events.³⁵

Despite the advantages of OTSCs, endoscopists should be mindful of the potential complications of OTSC use, including luminal obstruction, particularly in the duodenum, and perforation, which occurs in 0.3% to 2% of cases. Additionally, retrieval of misplaced OTSCs presents a significant challenge. Careful decision-making with consideration of the location, size, and depth of lesions is required when deciding on OTSC placement.^34,36

A newer endoscopic tool developed for refractory bleeding from peptic ulcers and other causes is hemostatic powder. Hemostatic powders accelerate the coagulation cascade, leading to shortened coagulation times and enhanced clot formation.³⁷ A recent meta-analysis showed that immediate hemostasis could be achieved in 95% of cases of bleeding, including in 96% of cases of bleeding from peptic ulcer disease.³⁸ The primary limitation of hemostatic powders is the temporary nature of hemostasis, which requires the underlying etiology of bleeding to be addressed in order to provide long-term hemostasis. In the above meta-analysis, rebleeding occurred in 17% of cases after 30 days.³⁸

Hypotension and ulcer diameter ≥ 2 cm are independent predictors of failure of endoscopic salvage therapy.³¹ When severe bleeding is not controlled with initial endoscopic therapy or bleeding recurs despite salvage endoscopic therapy, transcatheter angiographic embolization (TAE) is the treatment of choice.⁴ Systematic reviews and meta-analyses of studies that compared TAE to surgery have shown that the rate of rebleeding may be higher with TAE, but with less morbidity and either decreased or equivalent rates of mortality, with no increased need for additional interventions.^4,32 In a case series examining 5 years of experience at a single medical center in China, massive GIB from duodenal ulcers was successfully treated with TAE in 27 of 29 cases (93% clinical success rate), with no mucosal ischemic necrosis observed.³⁹

If repeated endoscopic therapy has not led to hemostasis of a bleeding peptic ulcer and TAE is not available, then surgery is the next best option. Bleeding gastric ulcers may be excised, wedge resected, or oversewn after an anterior gastrostomy. Bleeding duodenal ulcers may require use of a Kocher maneuver and linear incision of the anterior duodenum followed by ligation of the gastroduodenal artery. Fortunately, such surgical management is rarely necessary given the availability of TAE at most centers.⁴

Conclusion

Peptic ulcer disease is a common health problem globally, with persistent challenges related to refractory ulcers, antiplatelet and anticoagulant use, and continued bleeding in the face of endoscopic therapy. These challenges should be met with adequate frequency and duration of PPI therapy, vigilant attention to and treatment of ulcer etiology, evidence-based handling of antiplatelet and anticoagulant medications, and utilization of novel endoscopic tools to obtain improved clinical outcomes.

Acknowledgment: We thank Dr. Nipun Reddy from our institution for providing the endoscopic images used in this article.

Corresponding author: Adam L. Edwards, MD, MS; [email protected].

Financial disclosures: None.

A two-layer vaginal cuff closure during total laparoscopic hysterectomy is associated with fewer postoperative complications, compared with a standard one-layer closure, according to a retrospective study of approximately 3,000 patients.

The difference is driven by fewer vaginal cuff complications among patients whose surgeons used the two-layer technique, said Ann Peters, MD, of Magee-Womens Hospital at the University of Pittsburgh Medical Center.

In light of these findings, Dr. Peters switched to using a two-layer closure. More surgeons may adopt this method, she said at the annual meeting sponsored by AAGL, held virtually this year.
 

Modifiable factors

Complications after total laparoscopic hysterectomy may be associated with modifiable surgical risk factors such as surgical volume, expertise, and suture material. The method of vaginal cuff closure also plays an important role, but few studies have compared multilayer and single-layer vaginal cuff closure, Dr. Peters said.

To investigate this question, Dr. Peters and colleagues analyzed data from 2,973 women who underwent total laparoscopic hysterectomy for benign indications during a 6-year period at their institution.

The analysis included 1,760 patients (59%) who underwent single-layer closure and 1,213 (41%) who underwent two-layer closure. The closure method was a matter of surgeon preference. Aside from the closure technique, other aspects of the surgeries were standardized.

The primary outcome was the rate of 30-day postoperative complications. Secondary outcomes included vaginal cuff complications during 6 months of follow-up.

The groups generally had similar baseline characteristics, although patients in the two-layer group had lower body mass index and were less likely to use tobacco.

Intraoperative complications and postoperative readmissions did not differ between the groups. The rate of postoperative complications, however, was lower in the two-layer group: 3.5% versus 5.6%. Likewise, the rate of vaginal cuff complications was lower in the two-layer group: 0.9% versus 2.5%.

No instances of vaginal cuff dehiscence or mucosal separation occurred in the two-layer group, whereas 12 cases of dehiscence and 4 cases of mucosal separation occurred in the one-layer group.

Two-layer closure was associated with a decreased likelihood of complications, with an odds ratio of 0.36. Although the study is limited by its retrospective design, the surgeons had similar training and many variables, including the sutures used, were equal or standardized, Dr. Peters noted.

Avoiding rare complications

Grace M. Janik, MD, of Reproductive Specialty Center in Milwaukee, has long theorized that two-layer closure may be beneficial. This study provides data to support that theory, Dr. Janik said in a discussion following the research presentation.

Given that hysterectomy is a common procedure, “any optimization ... has implications for a large number of women,” Dr. Janik said. Although rare outcomes such as dehiscence are difficult to study, the large number of patients in this analysis allowed the investigators to detect differences between the groups.

Studies of vaginal cuff closure have yielded mixed results. For example, various studies have suggested that laparoscopic closure may be inferior to, equal to, or superior to vaginal closure. Together, the findings indicate that “what we are doing is probably more important than the route,” said Dr. Janik.

Along with multilayer closure, the use of delayed absorbable sutures and adequate tissue bites are other factors that may lead to fewer complications, Dr. Janik noted.

Dr. Peters and Dr. Janik had no relevant financial disclosures. A study coauthor is a consultant for Medtronic and Olympus. The statistical analysis was supported by the National Institutes of Health.

[email protected]

SOURCE: Ali R et al. J Minim Invasive Gynecol. 2020 Nov. doi: 10.1016/j.jmig.2020.08.603.

A two-layer vaginal cuff closure during total laparoscopic hysterectomy is associated with fewer postoperative complications, compared with a standard one-layer closure, according to a retrospective study of approximately 3,000 patients.

The difference is driven by fewer vaginal cuff complications among patients whose surgeons used the two-layer technique, said Ann Peters, MD, of Magee-Womens Hospital at the University of Pittsburgh Medical Center.

In light of these findings, Dr. Peters switched to using a two-layer closure. More surgeons may adopt this method, she said at the annual meeting sponsored by AAGL, held virtually this year.
 

Modifiable factors

Complications after total laparoscopic hysterectomy may be associated with modifiable surgical risk factors such as surgical volume, expertise, and suture material. The method of vaginal cuff closure also plays an important role, but few studies have compared multilayer and single-layer vaginal cuff closure, Dr. Peters said.

To investigate this question, Dr. Peters and colleagues analyzed data from 2,973 women who underwent total laparoscopic hysterectomy for benign indications during a 6-year period at their institution.

The analysis included 1,760 patients (59%) who underwent single-layer closure and 1,213 (41%) who underwent two-layer closure. The closure method was a matter of surgeon preference. Aside from the closure technique, other aspects of the surgeries were standardized.

The primary outcome was the rate of 30-day postoperative complications. Secondary outcomes included vaginal cuff complications during 6 months of follow-up.

The groups generally had similar baseline characteristics, although patients in the two-layer group had lower body mass index and were less likely to use tobacco.

Intraoperative complications and postoperative readmissions did not differ between the groups. The rate of postoperative complications, however, was lower in the two-layer group: 3.5% versus 5.6%. Likewise, the rate of vaginal cuff complications was lower in the two-layer group: 0.9% versus 2.5%.

No instances of vaginal cuff dehiscence or mucosal separation occurred in the two-layer group, whereas 12 cases of dehiscence and 4 cases of mucosal separation occurred in the one-layer group.

Two-layer closure was associated with a decreased likelihood of complications, with an odds ratio of 0.36. Although the study is limited by its retrospective design, the surgeons had similar training and many variables, including the sutures used, were equal or standardized, Dr. Peters noted.

Avoiding rare complications

Grace M. Janik, MD, of Reproductive Specialty Center in Milwaukee, has long theorized that two-layer closure may be beneficial. This study provides data to support that theory, Dr. Janik said in a discussion following the research presentation.

Given that hysterectomy is a common procedure, “any optimization ... has implications for a large number of women,” Dr. Janik said. Although rare outcomes such as dehiscence are difficult to study, the large number of patients in this analysis allowed the investigators to detect differences between the groups.

Studies of vaginal cuff closure have yielded mixed results. For example, various studies have suggested that laparoscopic closure may be inferior to, equal to, or superior to vaginal closure. Together, the findings indicate that “what we are doing is probably more important than the route,” said Dr. Janik.

Along with multilayer closure, the use of delayed absorbable sutures and adequate tissue bites are other factors that may lead to fewer complications, Dr. Janik noted.

Dr. Peters and Dr. Janik had no relevant financial disclosures. A study coauthor is a consultant for Medtronic and Olympus. The statistical analysis was supported by the National Institutes of Health.

[email protected]

SOURCE: Ali R et al. J Minim Invasive Gynecol. 2020 Nov. doi: 10.1016/j.jmig.2020.08.603.

A two-layer vaginal cuff closure during total laparoscopic hysterectomy is associated with fewer postoperative complications, compared with a standard one-layer closure, according to a retrospective study of approximately 3,000 patients.

The difference is driven by fewer vaginal cuff complications among patients whose surgeons used the two-layer technique, said Ann Peters, MD, of Magee-Womens Hospital at the University of Pittsburgh Medical Center.

In light of these findings, Dr. Peters switched to using a two-layer closure. More surgeons may adopt this method, she said at the annual meeting sponsored by AAGL, held virtually this year.
 

Modifiable factors

Complications after total laparoscopic hysterectomy may be associated with modifiable surgical risk factors such as surgical volume, expertise, and suture material. The method of vaginal cuff closure also plays an important role, but few studies have compared multilayer and single-layer vaginal cuff closure, Dr. Peters said.

To investigate this question, Dr. Peters and colleagues analyzed data from 2,973 women who underwent total laparoscopic hysterectomy for benign indications during a 6-year period at their institution.

The analysis included 1,760 patients (59%) who underwent single-layer closure and 1,213 (41%) who underwent two-layer closure. The closure method was a matter of surgeon preference. Aside from the closure technique, other aspects of the surgeries were standardized.

The primary outcome was the rate of 30-day postoperative complications. Secondary outcomes included vaginal cuff complications during 6 months of follow-up.

The groups generally had similar baseline characteristics, although patients in the two-layer group had lower body mass index and were less likely to use tobacco.

Intraoperative complications and postoperative readmissions did not differ between the groups. The rate of postoperative complications, however, was lower in the two-layer group: 3.5% versus 5.6%. Likewise, the rate of vaginal cuff complications was lower in the two-layer group: 0.9% versus 2.5%.

No instances of vaginal cuff dehiscence or mucosal separation occurred in the two-layer group, whereas 12 cases of dehiscence and 4 cases of mucosal separation occurred in the one-layer group.

Two-layer closure was associated with a decreased likelihood of complications, with an odds ratio of 0.36. Although the study is limited by its retrospective design, the surgeons had similar training and many variables, including the sutures used, were equal or standardized, Dr. Peters noted.

Avoiding rare complications

Grace M. Janik, MD, of Reproductive Specialty Center in Milwaukee, has long theorized that two-layer closure may be beneficial. This study provides data to support that theory, Dr. Janik said in a discussion following the research presentation.

Given that hysterectomy is a common procedure, “any optimization ... has implications for a large number of women,” Dr. Janik said. Although rare outcomes such as dehiscence are difficult to study, the large number of patients in this analysis allowed the investigators to detect differences between the groups.

Studies of vaginal cuff closure have yielded mixed results. For example, various studies have suggested that laparoscopic closure may be inferior to, equal to, or superior to vaginal closure. Together, the findings indicate that “what we are doing is probably more important than the route,” said Dr. Janik.

Along with multilayer closure, the use of delayed absorbable sutures and adequate tissue bites are other factors that may lead to fewer complications, Dr. Janik noted.

Dr. Peters and Dr. Janik had no relevant financial disclosures. A study coauthor is a consultant for Medtronic and Olympus. The statistical analysis was supported by the National Institutes of Health.

[email protected]

SOURCE: Ali R et al. J Minim Invasive Gynecol. 2020 Nov. doi: 10.1016/j.jmig.2020.08.603.

Students have similar confidence levels during a simulated laparoscopic vaginal cuff suturing task whether they train with the current standard laparoscopic simulator or a newer gynecology-specific simulator, a randomized trial found.

Participants who trained on the gynecology-specific simulator, known as Essentials in Minimally Invasive Gynecology (EMIG), reported higher confidence scores, but differences between the groups were not statistically significant, a researcher reported at the annual meeting sponsored by AAGL, held virtually this year.

The study compared EMIG with Fundamentals of Laparoscopic Surgery (FLS), a laparoscopic simulator that general surgeons launched in 2004.

In 2018, the American Board of Obstetrics and Gynecology announced an FLS requirement for residents graduating after May 31, 2020. The same year, the AAGL began validating EMIG. AAGL developed the simulator in response to a growing trend for minimally invasive approaches and to provide a training tool geared toward gynecologists, said Emily G. Lin, MD, an obstetrics and gynecology resident at McGaw Medical Center at Northwestern University in Chicago.
 

A comparison of the two simulators

The simulators use different port placement and operator positioning. The operating fields within the box trainers also differ. In EMIG, laparoscopic tasks take place within a bowl that simulates a confined workspace similar to a pelvis, whereas FLS tasks take place in an open box trainer environment, Dr. Lin said.

To compare students’ self-reported confidence levels after performing a laparoscopic vaginal cuff suturing task after training with EMIG or FLS, Dr. Lin and colleagues conducted a randomized controlled trial.

The researchers recruited 45 participants who were preclinical medical students or premedical college students without prior training experience. Participants were randomized to EMIG or FLS training. After watching instructional videos about their simulator tasks and the vaginal cuff suturing task, they attempted the vaginal cuff suturing task as a pretest.

They then trained for about 2 hours on their assigned simulator. Training for both groups included practicing peg transfer and intracorporeal knot tying. In addition, the EMIG group trained on a running suture task, and the FLS group trained on a ligating loop task.

After training, participants retried the vaginal cuff suturing task. Participants subsequently rated their confidence during each simulation task on a 5-point Likert scale.

Confidence levels on the peg transfer (4.13 with EMIG vs. 4.10 with FLS), intracorporeal knot tying (3.0 with EMIG vs. 2.86 with FLS) and vaginal cuff suturing (2.46 with EMIG vs. 2.05 with FLS) were similar for both groups.

The study was small, included only one training session, and included only three of the five tasks for each simulator because of time and cost constraints, Dr. Lin noted.
 

Using simulation in residency training

The study was well designed and sheds light on inevitable comparisons between FLS and EMIG, Ido Sirota, MD, MHA, of New York-Presbyterian Queens, said in a discussion following the research presentation.

“The field of medical simulation has developed tremendously in the past decade,” Dr. Sirota said. “The paradigm that used to be common in our field – of see one, do one, teach one – belongs to the past. ... Current trainees need extensive practice on their surgical skills in a simulation setting before” entering the operating room.

A 2017 review found that simulation may be a useful adjunct to residency training.

And in a pilot study, EMIG’s laparoscopic and hysteroscopic simulation systems were considered to have good face validity, Dr. Sirota noted.

Using a gynecology-specific simulation may have advantages.

“In this day and age when we are trying to differentiate ourselves as a subspecialty, there is a great value to developing our own simulation-based curricula to validate our surgical skills during training, as well as for maintenance throughout our career,” Dr. Sirota said. “We as a subspecialty need specific tests tailored to our surgical procedures.”

Dr. Sirota disclosed consulting for Medtronic, Activ Surgical, Heracure, and HT, and he is on the speakers bureau for Medtronic. Dr. Lin had no relevant financial disclosures.

[email protected]

SOURCE: Lin E et al. J Minim Invasive Gynecol. 2020 Nov. doi: 10.1016/j.jmig.2020.08.593.

Students have similar confidence levels during a simulated laparoscopic vaginal cuff suturing task whether they train with the current standard laparoscopic simulator or a newer gynecology-specific simulator, a randomized trial found.

Participants who trained on the gynecology-specific simulator, known as Essentials in Minimally Invasive Gynecology (EMIG), reported higher confidence scores, but differences between the groups were not statistically significant, a researcher reported at the annual meeting sponsored by AAGL, held virtually this year.

The study compared EMIG with Fundamentals of Laparoscopic Surgery (FLS), a laparoscopic simulator that general surgeons launched in 2004.

In 2018, the American Board of Obstetrics and Gynecology announced an FLS requirement for residents graduating after May 31, 2020. The same year, the AAGL began validating EMIG. AAGL developed the simulator in response to a growing trend for minimally invasive approaches and to provide a training tool geared toward gynecologists, said Emily G. Lin, MD, an obstetrics and gynecology resident at McGaw Medical Center at Northwestern University in Chicago.
 

A comparison of the two simulators

The simulators use different port placement and operator positioning. The operating fields within the box trainers also differ. In EMIG, laparoscopic tasks take place within a bowl that simulates a confined workspace similar to a pelvis, whereas FLS tasks take place in an open box trainer environment, Dr. Lin said.

To compare students’ self-reported confidence levels after performing a laparoscopic vaginal cuff suturing task after training with EMIG or FLS, Dr. Lin and colleagues conducted a randomized controlled trial.

The researchers recruited 45 participants who were preclinical medical students or premedical college students without prior training experience. Participants were randomized to EMIG or FLS training. After watching instructional videos about their simulator tasks and the vaginal cuff suturing task, they attempted the vaginal cuff suturing task as a pretest.

They then trained for about 2 hours on their assigned simulator. Training for both groups included practicing peg transfer and intracorporeal knot tying. In addition, the EMIG group trained on a running suture task, and the FLS group trained on a ligating loop task.

After training, participants retried the vaginal cuff suturing task. Participants subsequently rated their confidence during each simulation task on a 5-point Likert scale.

Confidence levels on the peg transfer (4.13 with EMIG vs. 4.10 with FLS), intracorporeal knot tying (3.0 with EMIG vs. 2.86 with FLS) and vaginal cuff suturing (2.46 with EMIG vs. 2.05 with FLS) were similar for both groups.

The study was small, included only one training session, and included only three of the five tasks for each simulator because of time and cost constraints, Dr. Lin noted.
 

Using simulation in residency training

The study was well designed and sheds light on inevitable comparisons between FLS and EMIG, Ido Sirota, MD, MHA, of New York-Presbyterian Queens, said in a discussion following the research presentation.

“The field of medical simulation has developed tremendously in the past decade,” Dr. Sirota said. “The paradigm that used to be common in our field – of see one, do one, teach one – belongs to the past. ... Current trainees need extensive practice on their surgical skills in a simulation setting before” entering the operating room.

A 2017 review found that simulation may be a useful adjunct to residency training.

And in a pilot study, EMIG’s laparoscopic and hysteroscopic simulation systems were considered to have good face validity, Dr. Sirota noted.

Using a gynecology-specific simulation may have advantages.

“In this day and age when we are trying to differentiate ourselves as a subspecialty, there is a great value to developing our own simulation-based curricula to validate our surgical skills during training, as well as for maintenance throughout our career,” Dr. Sirota said. “We as a subspecialty need specific tests tailored to our surgical procedures.”

Dr. Sirota disclosed consulting for Medtronic, Activ Surgical, Heracure, and HT, and he is on the speakers bureau for Medtronic. Dr. Lin had no relevant financial disclosures.

[email protected]

SOURCE: Lin E et al. J Minim Invasive Gynecol. 2020 Nov. doi: 10.1016/j.jmig.2020.08.593.

Students have similar confidence levels during a simulated laparoscopic vaginal cuff suturing task whether they train with the current standard laparoscopic simulator or a newer gynecology-specific simulator, a randomized trial found.

Participants who trained on the gynecology-specific simulator, known as Essentials in Minimally Invasive Gynecology (EMIG), reported higher confidence scores, but differences between the groups were not statistically significant, a researcher reported at the annual meeting sponsored by AAGL, held virtually this year.

The study compared EMIG with Fundamentals of Laparoscopic Surgery (FLS), a laparoscopic simulator that general surgeons launched in 2004.

In 2018, the American Board of Obstetrics and Gynecology announced an FLS requirement for residents graduating after May 31, 2020. The same year, the AAGL began validating EMIG. AAGL developed the simulator in response to a growing trend for minimally invasive approaches and to provide a training tool geared toward gynecologists, said Emily G. Lin, MD, an obstetrics and gynecology resident at McGaw Medical Center at Northwestern University in Chicago.
 

A comparison of the two simulators

The simulators use different port placement and operator positioning. The operating fields within the box trainers also differ. In EMIG, laparoscopic tasks take place within a bowl that simulates a confined workspace similar to a pelvis, whereas FLS tasks take place in an open box trainer environment, Dr. Lin said.

To compare students’ self-reported confidence levels after performing a laparoscopic vaginal cuff suturing task after training with EMIG or FLS, Dr. Lin and colleagues conducted a randomized controlled trial.

The researchers recruited 45 participants who were preclinical medical students or premedical college students without prior training experience. Participants were randomized to EMIG or FLS training. After watching instructional videos about their simulator tasks and the vaginal cuff suturing task, they attempted the vaginal cuff suturing task as a pretest.

They then trained for about 2 hours on their assigned simulator. Training for both groups included practicing peg transfer and intracorporeal knot tying. In addition, the EMIG group trained on a running suture task, and the FLS group trained on a ligating loop task.

After training, participants retried the vaginal cuff suturing task. Participants subsequently rated their confidence during each simulation task on a 5-point Likert scale.

Confidence levels on the peg transfer (4.13 with EMIG vs. 4.10 with FLS), intracorporeal knot tying (3.0 with EMIG vs. 2.86 with FLS) and vaginal cuff suturing (2.46 with EMIG vs. 2.05 with FLS) were similar for both groups.

The study was small, included only one training session, and included only three of the five tasks for each simulator because of time and cost constraints, Dr. Lin noted.
 

Using simulation in residency training

The study was well designed and sheds light on inevitable comparisons between FLS and EMIG, Ido Sirota, MD, MHA, of New York-Presbyterian Queens, said in a discussion following the research presentation.

“The field of medical simulation has developed tremendously in the past decade,” Dr. Sirota said. “The paradigm that used to be common in our field – of see one, do one, teach one – belongs to the past. ... Current trainees need extensive practice on their surgical skills in a simulation setting before” entering the operating room.

A 2017 review found that simulation may be a useful adjunct to residency training.

And in a pilot study, EMIG’s laparoscopic and hysteroscopic simulation systems were considered to have good face validity, Dr. Sirota noted.

Using a gynecology-specific simulation may have advantages.

“In this day and age when we are trying to differentiate ourselves as a subspecialty, there is a great value to developing our own simulation-based curricula to validate our surgical skills during training, as well as for maintenance throughout our career,” Dr. Sirota said. “We as a subspecialty need specific tests tailored to our surgical procedures.”

Dr. Sirota disclosed consulting for Medtronic, Activ Surgical, Heracure, and HT, and he is on the speakers bureau for Medtronic. Dr. Lin had no relevant financial disclosures.

[email protected]

SOURCE: Lin E et al. J Minim Invasive Gynecol. 2020 Nov. doi: 10.1016/j.jmig.2020.08.593.

Background: Heart failure is a known risk factor for postoperative mortality and complications. Many of the studies used to establish this association, however, have focused on major high-risk surgeries and not on outpatient surgeries. Improved medical care has increased the survival rate of patients with heart failure and an increasing number of these patients are undergoing elective surgical procedures. This has led to an increasing need to better understand the degree to which heart failure affects preoperative risk in the outpatient setting.

Study design: A retrospective cohort study.

Setting: Multiple Veteran’s Affairs Hospitals using data from the VA Surgical Quality Improvement Program (VASQIP) and the VA Corporate Data Warehouse.

Synopsis: A total of 355,121 patients who underwent outpatient surgeries were analyzed. 19,353 patients had heart failure and 334,768 did not. Patients with heart failure had a higher risk of 90-day mortality with an adjusted odds ratio of 1.95 (95% confidence interval, 1.69-2.44), and this risk progressively increased as the ejection fraction decreased. The risk of 30-day complication also increased in patients with heart failure with an adjusted OR of 1.10 (95% CI, 1.02-1.19).

Limitations of this study include the patient population, which were all veterans and mostly male. The nature of the inclusion criteria was limiting as well, in that all the patients in this study were deemed fit for surgery. There were no data available for patients who had been considered but ultimately did not undergo surgery or for patients who were considered for ambulatory surgery but ultimately underwent inpatient surgery. These limitations may have resulted in a selection bias, which limited the generalizability of the study’s findings when assessing patients for ambulatory surgery.

Bottom line: Patients with heart failure had a higher risk of 90-day postoperative mortality and 30-day postoperative complication in ambulatory noncardiac surgery. The risk of postoperative mortality increased as systolic function decreased.

Citation: Lerman BJ et al. Association between heart failure and postoperative mortality among patients undergoing ambulatory noncardiac surgery. JAMA Surg. 2019 Jul 10. doi: 10.1001/jamasurg.2019.2110.

Dr. Cheatham is a hospitalist and clinical educator at St. Louis University School of Medicine.

Background: Heart failure is a known risk factor for postoperative mortality and complications. Many of the studies used to establish this association, however, have focused on major high-risk surgeries and not on outpatient surgeries. Improved medical care has increased the survival rate of patients with heart failure and an increasing number of these patients are undergoing elective surgical procedures. This has led to an increasing need to better understand the degree to which heart failure affects preoperative risk in the outpatient setting.

Study design: A retrospective cohort study.

Setting: Multiple Veteran’s Affairs Hospitals using data from the VA Surgical Quality Improvement Program (VASQIP) and the VA Corporate Data Warehouse.

Synopsis: A total of 355,121 patients who underwent outpatient surgeries were analyzed. 19,353 patients had heart failure and 334,768 did not. Patients with heart failure had a higher risk of 90-day mortality with an adjusted odds ratio of 1.95 (95% confidence interval, 1.69-2.44), and this risk progressively increased as the ejection fraction decreased. The risk of 30-day complication also increased in patients with heart failure with an adjusted OR of 1.10 (95% CI, 1.02-1.19).

Limitations of this study include the patient population, which were all veterans and mostly male. The nature of the inclusion criteria was limiting as well, in that all the patients in this study were deemed fit for surgery. There were no data available for patients who had been considered but ultimately did not undergo surgery or for patients who were considered for ambulatory surgery but ultimately underwent inpatient surgery. These limitations may have resulted in a selection bias, which limited the generalizability of the study’s findings when assessing patients for ambulatory surgery.

Bottom line: Patients with heart failure had a higher risk of 90-day postoperative mortality and 30-day postoperative complication in ambulatory noncardiac surgery. The risk of postoperative mortality increased as systolic function decreased.

Citation: Lerman BJ et al. Association between heart failure and postoperative mortality among patients undergoing ambulatory noncardiac surgery. JAMA Surg. 2019 Jul 10. doi: 10.1001/jamasurg.2019.2110.

Dr. Cheatham is a hospitalist and clinical educator at St. Louis University School of Medicine.

Background: Heart failure is a known risk factor for postoperative mortality and complications. Many of the studies used to establish this association, however, have focused on major high-risk surgeries and not on outpatient surgeries. Improved medical care has increased the survival rate of patients with heart failure and an increasing number of these patients are undergoing elective surgical procedures. This has led to an increasing need to better understand the degree to which heart failure affects preoperative risk in the outpatient setting.

Study design: A retrospective cohort study.

Setting: Multiple Veteran’s Affairs Hospitals using data from the VA Surgical Quality Improvement Program (VASQIP) and the VA Corporate Data Warehouse.

Synopsis: A total of 355,121 patients who underwent outpatient surgeries were analyzed. 19,353 patients had heart failure and 334,768 did not. Patients with heart failure had a higher risk of 90-day mortality with an adjusted odds ratio of 1.95 (95% confidence interval, 1.69-2.44), and this risk progressively increased as the ejection fraction decreased. The risk of 30-day complication also increased in patients with heart failure with an adjusted OR of 1.10 (95% CI, 1.02-1.19).

Limitations of this study include the patient population, which were all veterans and mostly male. The nature of the inclusion criteria was limiting as well, in that all the patients in this study were deemed fit for surgery. There were no data available for patients who had been considered but ultimately did not undergo surgery or for patients who were considered for ambulatory surgery but ultimately underwent inpatient surgery. These limitations may have resulted in a selection bias, which limited the generalizability of the study’s findings when assessing patients for ambulatory surgery.

Bottom line: Patients with heart failure had a higher risk of 90-day postoperative mortality and 30-day postoperative complication in ambulatory noncardiac surgery. The risk of postoperative mortality increased as systolic function decreased.

Citation: Lerman BJ et al. Association between heart failure and postoperative mortality among patients undergoing ambulatory noncardiac surgery. JAMA Surg. 2019 Jul 10. doi: 10.1001/jamasurg.2019.2110.

Dr. Cheatham is a hospitalist and clinical educator at St. Louis University School of Medicine.

Doctors commonly perform pelvic examinations approximately 6 weeks following hysterectomy to assess the integrity of the vaginal cuff. But this practice may not be necessary if patients do not have symptoms, a study suggests.

“The 6-week posthysterectomy pelvic examination in asymptomatic women may not be necessary, as it neither detected cuff dehiscence nor negated future risk for dehiscence,” Ritchie Mae Delara, MD, said at the meeting sponsored by AAGL, held virtually this year.

Dr. Delara, of the Mayo Clinic in Phoenix, and colleagues conducted a retrospective cohort study of data from more than 2,000 patients to assess the utility of the 6-week posthysterectomy pelvic examination in detecting cuff dehiscence in asymptomatic women.
 

An unpredictable complication

Vaginal cuff dehiscence is a rare complication of hysterectomy that can occur days or decades after surgery, which makes “identifying an optimal time for cuff evaluation difficult,” Dr. Delara said. “Currently there is neither evidence demonstrating benefit of routine posthysterectomy examination in detecting vaginal cuff dehiscence, nor data demonstrating the best time to perform posthysterectomy examination.”

For their study, which was also published in the Journal of Minimally Invasive Gynecology, the researchers examined data from 2,051 women who underwent hysterectomy at a single institution during a 6-year period. Patients received at least one postoperative evaluation within 90 days of surgery. Examination of the vaginal cuff routinely was performed approximately 6 weeks after hysterectomy. Patients’ posthysterectomy symptoms and pelvic examination findings were recorded.

About 80% of patients were asymptomatic at the 6-week visit.

Asymptomatic patients were more likely to have normal pelvic examination findings, compared with patients with posthysterectomy symptoms (86.4% vs. 54.3%).

In all, 13 patients experienced complete cuff dehiscence. All of them had an intact vaginal cuff at their 6-week examination. Three had symptoms at that time, including vaginal bleeding in one patient and pelvic pain in two patients.

One patient experienced a complete cuff dehiscence that was provoked by intercourse prior to her examination. The patient subsequently developed two additional episodes of dehiscence provoked by intercourse.

Dehiscence may present differently after benign and oncologic hysterectomies, the study indicated.

Eight patients who experienced complete cuff dehiscence after benign hysterectomy had symptoms such as pelvic pain and vaginal bleeding at the time of presentation for dehiscence, which mainly occurred after intercourse.

Five patients who experienced dehiscence after oncologic hysterectomy were more likely to present without symptoms or provocation.

The median time to dehiscence after benign hysterectomy was about 19 weeks, whereas the median time to dehiscence after oncologic hysterectomy was about 81 weeks.

Surgeons should educate patients about symptoms of dehiscence and the potential for events such as coitus to provoke its occurrence, and patients should promptly seek evaluation if symptoms occur, Dr. Delara said.

Patients with risk factors such as malignancy may benefit from continued routine evaluation, she added.

Timely research

The findings may be especially relevant during the COVID-19 pandemic, when states have issued shelter-in-place orders and doctors have increased their use of telemedicine to reduce in-person visits, Dr. Delara noted.

In that sense, the study is “extremely timely” and may inform and support practice changes, commented Emad Mikhail, MD, in a discussion following the research presentation.

Whether the results generalize to other centers, including smaller centers that perform fewer surgeries, is unclear, said Dr. Mikhail, of the University of South Florida, Tampa.

“It takes vision and critical thinking to challenge these traditional practices,” he said. “I applaud Dr. Delara for challenging one of these.”

Dr. Delara and Dr. Mikhail had no relevant disclosures.

[email protected]

SOURCE: Delara RMM et al. J Minim Invasive Gynecol. 2020 Nov 1. doi: 10.1016/j.jmig.2020.08.306.

Doctors commonly perform pelvic examinations approximately 6 weeks following hysterectomy to assess the integrity of the vaginal cuff. But this practice may not be necessary if patients do not have symptoms, a study suggests.

“The 6-week posthysterectomy pelvic examination in asymptomatic women may not be necessary, as it neither detected cuff dehiscence nor negated future risk for dehiscence,” Ritchie Mae Delara, MD, said at the meeting sponsored by AAGL, held virtually this year.

Dr. Delara, of the Mayo Clinic in Phoenix, and colleagues conducted a retrospective cohort study of data from more than 2,000 patients to assess the utility of the 6-week posthysterectomy pelvic examination in detecting cuff dehiscence in asymptomatic women.
 

An unpredictable complication

Vaginal cuff dehiscence is a rare complication of hysterectomy that can occur days or decades after surgery, which makes “identifying an optimal time for cuff evaluation difficult,” Dr. Delara said. “Currently there is neither evidence demonstrating benefit of routine posthysterectomy examination in detecting vaginal cuff dehiscence, nor data demonstrating the best time to perform posthysterectomy examination.”

For their study, which was also published in the Journal of Minimally Invasive Gynecology, the researchers examined data from 2,051 women who underwent hysterectomy at a single institution during a 6-year period. Patients received at least one postoperative evaluation within 90 days of surgery. Examination of the vaginal cuff routinely was performed approximately 6 weeks after hysterectomy. Patients’ posthysterectomy symptoms and pelvic examination findings were recorded.

About 80% of patients were asymptomatic at the 6-week visit.

Asymptomatic patients were more likely to have normal pelvic examination findings, compared with patients with posthysterectomy symptoms (86.4% vs. 54.3%).

In all, 13 patients experienced complete cuff dehiscence. All of them had an intact vaginal cuff at their 6-week examination. Three had symptoms at that time, including vaginal bleeding in one patient and pelvic pain in two patients.

One patient experienced a complete cuff dehiscence that was provoked by intercourse prior to her examination. The patient subsequently developed two additional episodes of dehiscence provoked by intercourse.

Dehiscence may present differently after benign and oncologic hysterectomies, the study indicated.

Eight patients who experienced complete cuff dehiscence after benign hysterectomy had symptoms such as pelvic pain and vaginal bleeding at the time of presentation for dehiscence, which mainly occurred after intercourse.

Five patients who experienced dehiscence after oncologic hysterectomy were more likely to present without symptoms or provocation.

The median time to dehiscence after benign hysterectomy was about 19 weeks, whereas the median time to dehiscence after oncologic hysterectomy was about 81 weeks.

Surgeons should educate patients about symptoms of dehiscence and the potential for events such as coitus to provoke its occurrence, and patients should promptly seek evaluation if symptoms occur, Dr. Delara said.

Patients with risk factors such as malignancy may benefit from continued routine evaluation, she added.

Timely research

The findings may be especially relevant during the COVID-19 pandemic, when states have issued shelter-in-place orders and doctors have increased their use of telemedicine to reduce in-person visits, Dr. Delara noted.

In that sense, the study is “extremely timely” and may inform and support practice changes, commented Emad Mikhail, MD, in a discussion following the research presentation.

Whether the results generalize to other centers, including smaller centers that perform fewer surgeries, is unclear, said Dr. Mikhail, of the University of South Florida, Tampa.

“It takes vision and critical thinking to challenge these traditional practices,” he said. “I applaud Dr. Delara for challenging one of these.”

Dr. Delara and Dr. Mikhail had no relevant disclosures.

[email protected]

SOURCE: Delara RMM et al. J Minim Invasive Gynecol. 2020 Nov 1. doi: 10.1016/j.jmig.2020.08.306.

Doctors commonly perform pelvic examinations approximately 6 weeks following hysterectomy to assess the integrity of the vaginal cuff. But this practice may not be necessary if patients do not have symptoms, a study suggests.

“The 6-week posthysterectomy pelvic examination in asymptomatic women may not be necessary, as it neither detected cuff dehiscence nor negated future risk for dehiscence,” Ritchie Mae Delara, MD, said at the meeting sponsored by AAGL, held virtually this year.

Dr. Delara, of the Mayo Clinic in Phoenix, and colleagues conducted a retrospective cohort study of data from more than 2,000 patients to assess the utility of the 6-week posthysterectomy pelvic examination in detecting cuff dehiscence in asymptomatic women.
 

An unpredictable complication

Vaginal cuff dehiscence is a rare complication of hysterectomy that can occur days or decades after surgery, which makes “identifying an optimal time for cuff evaluation difficult,” Dr. Delara said. “Currently there is neither evidence demonstrating benefit of routine posthysterectomy examination in detecting vaginal cuff dehiscence, nor data demonstrating the best time to perform posthysterectomy examination.”

For their study, which was also published in the Journal of Minimally Invasive Gynecology, the researchers examined data from 2,051 women who underwent hysterectomy at a single institution during a 6-year period. Patients received at least one postoperative evaluation within 90 days of surgery. Examination of the vaginal cuff routinely was performed approximately 6 weeks after hysterectomy. Patients’ posthysterectomy symptoms and pelvic examination findings were recorded.

About 80% of patients were asymptomatic at the 6-week visit.

Asymptomatic patients were more likely to have normal pelvic examination findings, compared with patients with posthysterectomy symptoms (86.4% vs. 54.3%).

In all, 13 patients experienced complete cuff dehiscence. All of them had an intact vaginal cuff at their 6-week examination. Three had symptoms at that time, including vaginal bleeding in one patient and pelvic pain in two patients.

One patient experienced a complete cuff dehiscence that was provoked by intercourse prior to her examination. The patient subsequently developed two additional episodes of dehiscence provoked by intercourse.

Dehiscence may present differently after benign and oncologic hysterectomies, the study indicated.

Eight patients who experienced complete cuff dehiscence after benign hysterectomy had symptoms such as pelvic pain and vaginal bleeding at the time of presentation for dehiscence, which mainly occurred after intercourse.

Five patients who experienced dehiscence after oncologic hysterectomy were more likely to present without symptoms or provocation.

The median time to dehiscence after benign hysterectomy was about 19 weeks, whereas the median time to dehiscence after oncologic hysterectomy was about 81 weeks.

Surgeons should educate patients about symptoms of dehiscence and the potential for events such as coitus to provoke its occurrence, and patients should promptly seek evaluation if symptoms occur, Dr. Delara said.

Patients with risk factors such as malignancy may benefit from continued routine evaluation, she added.

Timely research

The findings may be especially relevant during the COVID-19 pandemic, when states have issued shelter-in-place orders and doctors have increased their use of telemedicine to reduce in-person visits, Dr. Delara noted.

In that sense, the study is “extremely timely” and may inform and support practice changes, commented Emad Mikhail, MD, in a discussion following the research presentation.

Whether the results generalize to other centers, including smaller centers that perform fewer surgeries, is unclear, said Dr. Mikhail, of the University of South Florida, Tampa.

“It takes vision and critical thinking to challenge these traditional practices,” he said. “I applaud Dr. Delara for challenging one of these.”

Dr. Delara and Dr. Mikhail had no relevant disclosures.

[email protected]

SOURCE: Delara RMM et al. J Minim Invasive Gynecol. 2020 Nov 1. doi: 10.1016/j.jmig.2020.08.306.

As far as the pandemic is concerned, it seems like a pretty small thing. A difference of just 0.3%. Children now represent 11.8% of all COVID-19 cases that have occurred since the beginning of the pandemic, compared with 11.5% 1 week ago, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Hiding behind that 0.3%, however, is a much larger number: 144,145. That is the number of new child cases that occurred during the week that ended Nov. 19, and it’s the highest weekly figure yet, eclipsing the previous high of 111,946 from the week of Nov. 12, the AAP and the CHA said in their latest COVID-19 report. For the week ending Nov. 19, children represented 14.1% of all new cases, up from 14.0% the week before.

In the United States, more than 1.18 million children have been infected by the coronavirus since the beginning of the pandemic, with the total among all ages topping 10 million in 49 states (New York is not providing age distribution), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP/CHA data show. That works out to 11.8% of all cases.

The overall rate of child COVID-19 cases is now up to 1,573 per 100,000 children nationally, with considerable variation seen among the states. The lowest rates can be found in Vermont (344 per 100,000), Maine (452), and Hawaii (675), and the highest in North Dakota (5,589), South Dakota (3,993), and Wisconsin (3,727), the AAP and CHA said in the report.

Comparisons between states are somewhat problematic, though, because “each state makes different decisions about how to report the age distribution of COVID-19 cases, and as a result the age range for reported cases varies by state. … It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states at this time,” the two organizations noted.

Five more COVID-19–related deaths in children were reported during the week of Nov. 19, bringing the count to 138 and holding at just 0.06% of the total for all ages, based on data from 43 states and New York City. Children’s share of hospitalizations increased slightly in the last week, rising from 1.7% to 1.8% in the 24 states (and NYC) that are reporting such data. The total number of child hospitalizations in those jurisdictions is just over 6,700, the AAP and CHA said.

[email protected]

As far as the pandemic is concerned, it seems like a pretty small thing. A difference of just 0.3%. Children now represent 11.8% of all COVID-19 cases that have occurred since the beginning of the pandemic, compared with 11.5% 1 week ago, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Hiding behind that 0.3%, however, is a much larger number: 144,145. That is the number of new child cases that occurred during the week that ended Nov. 19, and it’s the highest weekly figure yet, eclipsing the previous high of 111,946 from the week of Nov. 12, the AAP and the CHA said in their latest COVID-19 report. For the week ending Nov. 19, children represented 14.1% of all new cases, up from 14.0% the week before.

In the United States, more than 1.18 million children have been infected by the coronavirus since the beginning of the pandemic, with the total among all ages topping 10 million in 49 states (New York is not providing age distribution), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP/CHA data show. That works out to 11.8% of all cases.

The overall rate of child COVID-19 cases is now up to 1,573 per 100,000 children nationally, with considerable variation seen among the states. The lowest rates can be found in Vermont (344 per 100,000), Maine (452), and Hawaii (675), and the highest in North Dakota (5,589), South Dakota (3,993), and Wisconsin (3,727), the AAP and CHA said in the report.

Comparisons between states are somewhat problematic, though, because “each state makes different decisions about how to report the age distribution of COVID-19 cases, and as a result the age range for reported cases varies by state. … It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states at this time,” the two organizations noted.

Five more COVID-19–related deaths in children were reported during the week of Nov. 19, bringing the count to 138 and holding at just 0.06% of the total for all ages, based on data from 43 states and New York City. Children’s share of hospitalizations increased slightly in the last week, rising from 1.7% to 1.8% in the 24 states (and NYC) that are reporting such data. The total number of child hospitalizations in those jurisdictions is just over 6,700, the AAP and CHA said.

[email protected]

As far as the pandemic is concerned, it seems like a pretty small thing. A difference of just 0.3%. Children now represent 11.8% of all COVID-19 cases that have occurred since the beginning of the pandemic, compared with 11.5% 1 week ago, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Hiding behind that 0.3%, however, is a much larger number: 144,145. That is the number of new child cases that occurred during the week that ended Nov. 19, and it’s the highest weekly figure yet, eclipsing the previous high of 111,946 from the week of Nov. 12, the AAP and the CHA said in their latest COVID-19 report. For the week ending Nov. 19, children represented 14.1% of all new cases, up from 14.0% the week before.

In the United States, more than 1.18 million children have been infected by the coronavirus since the beginning of the pandemic, with the total among all ages topping 10 million in 49 states (New York is not providing age distribution), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP/CHA data show. That works out to 11.8% of all cases.

The overall rate of child COVID-19 cases is now up to 1,573 per 100,000 children nationally, with considerable variation seen among the states. The lowest rates can be found in Vermont (344 per 100,000), Maine (452), and Hawaii (675), and the highest in North Dakota (5,589), South Dakota (3,993), and Wisconsin (3,727), the AAP and CHA said in the report.

Comparisons between states are somewhat problematic, though, because “each state makes different decisions about how to report the age distribution of COVID-19 cases, and as a result the age range for reported cases varies by state. … It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states at this time,” the two organizations noted.

Five more COVID-19–related deaths in children were reported during the week of Nov. 19, bringing the count to 138 and holding at just 0.06% of the total for all ages, based on data from 43 states and New York City. Children’s share of hospitalizations increased slightly in the last week, rising from 1.7% to 1.8% in the 24 states (and NYC) that are reporting such data. The total number of child hospitalizations in those jurisdictions is just over 6,700, the AAP and CHA said.

[email protected]