A transmembrane glycoprotein labeled neuropilin-1 may be a diagnostic biomarker for hepatocellular carcinoma.

In a series of experiments using HCC tissues and cell lines, as well as serum samples from patients with other malignancies or hepatitis, Jiafei Lin, MD, from Shanghai Jiaotong University, Shanghai, China, and colleagues found that neuropilin-1 (NRP1) was up-regulated in hepatocellular carcinoma (HCC) and promotes tumor growth.

“Notably, the concentrations of serum NRP1 in the HCC patients were much higher than those of hepatitis B, hepatitis C, cirrhosis, breast cancer, colon cancer, gastric cancer, and lung cancer patients,” they wrote in the journal Clinica Chimica Acta.

They also found that NRP1 has a high degree of sensitivity and specificity for HCC, and suggested that NRP1 could replace alpha fetoprotein (AFP) for early clinical diagnosis of HCC.

They first showed that NRP1 was directly regulated by TEAD, a family of transcription factors essential for developmental processes. The experiments in HCC cell lines showed that messenger RNA levels of NRP1 were increased when TEAD was overexpressed, and decreased when TEAD was knocked down. The experiments also suggested that TEAD binds directly to the promoter of NRP1 to stimulate its transcription in HCC cells.

The investigators then sought to demonstrate that NRP1 promotes tumor development and growth in HCC by testing expression of the protein in both normal liver and HCC tissue samples.

“NRP1 was found highly up-regulated in HCC tissues compared to normal tissues. Moreover, NRP1 was recruited to the membrane in HCC tissues, whereas this protein was not detected in normal tissues,” they wrote.

Furthermore, when they zeroed in on NRP1 using two different short hairpin RNAs to silence its expression, they found that knocking down NRP1 suppressed the viability of tumor cells and inhibited colony formation while also ramping up programmed cell death. Taken together, the data indicate that NRP1 is highly expressed in HCC and promotes tumorigenesis.

They then showed that NRP1 serum concentrations were significantly higher in samples from patients with HCC than in those from healthy individuals or patients with hepatitis B, hepatitis C, cirrhosis, breast cancer, colon cancer, gastric cancer, or lung cancer. In addition, higher NRP1 concentrations were significantly associated with higher HCC tumor stages.

The investigators then looked at the relationship between serum NRP1 and standard liver function markers in HCC, and found that NRP1 serum levels significantly correlated with gamma-glutamyltransferase, albumin, bile acid, ALT, AST, AFP, and prealbumin levels, but not total bilirubin or total protein levels.

Finally, they demonstrated that serum NRP1 is a better diagnostic marker than AFP, with an area under the receiver operating characteristic curve of 0.971, compared with 0.862 for AFP. At an NRP1 cutoff of 68 pg/mL, NRP1 had a sensitivity of 93.7%, and a specificity of 98.7%. Combining NRP1 with AFP only slightly improved the diagnostic accuracy.

“These results indicate that the single use of NRP1 is a promising choice for the diagnosis of HCC,” the investigators wrote.

They noted that the most of the study subjects were of Han Chinese origin, and that the results need to be validated in people of other ethnicities.

The study was supported by the National Natural Science Foundation of China. Potential conflicts of interest were not reported.

SOURCE: Lin J et al. Clin Chim Acta. 2018;485:158-65.

A transmembrane glycoprotein labeled neuropilin-1 may be a diagnostic biomarker for hepatocellular carcinoma.

In a series of experiments using HCC tissues and cell lines, as well as serum samples from patients with other malignancies or hepatitis, Jiafei Lin, MD, from Shanghai Jiaotong University, Shanghai, China, and colleagues found that neuropilin-1 (NRP1) was up-regulated in hepatocellular carcinoma (HCC) and promotes tumor growth.

“Notably, the concentrations of serum NRP1 in the HCC patients were much higher than those of hepatitis B, hepatitis C, cirrhosis, breast cancer, colon cancer, gastric cancer, and lung cancer patients,” they wrote in the journal Clinica Chimica Acta.

They also found that NRP1 has a high degree of sensitivity and specificity for HCC, and suggested that NRP1 could replace alpha fetoprotein (AFP) for early clinical diagnosis of HCC.

They first showed that NRP1 was directly regulated by TEAD, a family of transcription factors essential for developmental processes. The experiments in HCC cell lines showed that messenger RNA levels of NRP1 were increased when TEAD was overexpressed, and decreased when TEAD was knocked down. The experiments also suggested that TEAD binds directly to the promoter of NRP1 to stimulate its transcription in HCC cells.

The investigators then sought to demonstrate that NRP1 promotes tumor development and growth in HCC by testing expression of the protein in both normal liver and HCC tissue samples.

“NRP1 was found highly up-regulated in HCC tissues compared to normal tissues. Moreover, NRP1 was recruited to the membrane in HCC tissues, whereas this protein was not detected in normal tissues,” they wrote.

Furthermore, when they zeroed in on NRP1 using two different short hairpin RNAs to silence its expression, they found that knocking down NRP1 suppressed the viability of tumor cells and inhibited colony formation while also ramping up programmed cell death. Taken together, the data indicate that NRP1 is highly expressed in HCC and promotes tumorigenesis.

They then showed that NRP1 serum concentrations were significantly higher in samples from patients with HCC than in those from healthy individuals or patients with hepatitis B, hepatitis C, cirrhosis, breast cancer, colon cancer, gastric cancer, or lung cancer. In addition, higher NRP1 concentrations were significantly associated with higher HCC tumor stages.

The investigators then looked at the relationship between serum NRP1 and standard liver function markers in HCC, and found that NRP1 serum levels significantly correlated with gamma-glutamyltransferase, albumin, bile acid, ALT, AST, AFP, and prealbumin levels, but not total bilirubin or total protein levels.

Finally, they demonstrated that serum NRP1 is a better diagnostic marker than AFP, with an area under the receiver operating characteristic curve of 0.971, compared with 0.862 for AFP. At an NRP1 cutoff of 68 pg/mL, NRP1 had a sensitivity of 93.7%, and a specificity of 98.7%. Combining NRP1 with AFP only slightly improved the diagnostic accuracy.

“These results indicate that the single use of NRP1 is a promising choice for the diagnosis of HCC,” the investigators wrote.

They noted that the most of the study subjects were of Han Chinese origin, and that the results need to be validated in people of other ethnicities.

The study was supported by the National Natural Science Foundation of China. Potential conflicts of interest were not reported.

SOURCE: Lin J et al. Clin Chim Acta. 2018;485:158-65.

A transmembrane glycoprotein labeled neuropilin-1 may be a diagnostic biomarker for hepatocellular carcinoma.

In a series of experiments using HCC tissues and cell lines, as well as serum samples from patients with other malignancies or hepatitis, Jiafei Lin, MD, from Shanghai Jiaotong University, Shanghai, China, and colleagues found that neuropilin-1 (NRP1) was up-regulated in hepatocellular carcinoma (HCC) and promotes tumor growth.

“Notably, the concentrations of serum NRP1 in the HCC patients were much higher than those of hepatitis B, hepatitis C, cirrhosis, breast cancer, colon cancer, gastric cancer, and lung cancer patients,” they wrote in the journal Clinica Chimica Acta.

They also found that NRP1 has a high degree of sensitivity and specificity for HCC, and suggested that NRP1 could replace alpha fetoprotein (AFP) for early clinical diagnosis of HCC.

They first showed that NRP1 was directly regulated by TEAD, a family of transcription factors essential for developmental processes. The experiments in HCC cell lines showed that messenger RNA levels of NRP1 were increased when TEAD was overexpressed, and decreased when TEAD was knocked down. The experiments also suggested that TEAD binds directly to the promoter of NRP1 to stimulate its transcription in HCC cells.

The investigators then sought to demonstrate that NRP1 promotes tumor development and growth in HCC by testing expression of the protein in both normal liver and HCC tissue samples.

“NRP1 was found highly up-regulated in HCC tissues compared to normal tissues. Moreover, NRP1 was recruited to the membrane in HCC tissues, whereas this protein was not detected in normal tissues,” they wrote.

Furthermore, when they zeroed in on NRP1 using two different short hairpin RNAs to silence its expression, they found that knocking down NRP1 suppressed the viability of tumor cells and inhibited colony formation while also ramping up programmed cell death. Taken together, the data indicate that NRP1 is highly expressed in HCC and promotes tumorigenesis.

They then showed that NRP1 serum concentrations were significantly higher in samples from patients with HCC than in those from healthy individuals or patients with hepatitis B, hepatitis C, cirrhosis, breast cancer, colon cancer, gastric cancer, or lung cancer. In addition, higher NRP1 concentrations were significantly associated with higher HCC tumor stages.

The investigators then looked at the relationship between serum NRP1 and standard liver function markers in HCC, and found that NRP1 serum levels significantly correlated with gamma-glutamyltransferase, albumin, bile acid, ALT, AST, AFP, and prealbumin levels, but not total bilirubin or total protein levels.

Finally, they demonstrated that serum NRP1 is a better diagnostic marker than AFP, with an area under the receiver operating characteristic curve of 0.971, compared with 0.862 for AFP. At an NRP1 cutoff of 68 pg/mL, NRP1 had a sensitivity of 93.7%, and a specificity of 98.7%. Combining NRP1 with AFP only slightly improved the diagnostic accuracy.

“These results indicate that the single use of NRP1 is a promising choice for the diagnosis of HCC,” the investigators wrote.

They noted that the most of the study subjects were of Han Chinese origin, and that the results need to be validated in people of other ethnicities.

The study was supported by the National Natural Science Foundation of China. Potential conflicts of interest were not reported.

SOURCE: Lin J et al. Clin Chim Acta. 2018;485:158-65.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that has a social and psychosocial impact on patients with skin of color.¹ It is characterized by recurrent abscesses, draining sinus tracts, and scarring in the intertriginous skin folds. The lesions are difficult to treat and present with considerable frustration for both patients and physicians. Although current treatment ladders can delay procedures and surgical intervention,¹ some believe that surgery should be introduced earlier in HS management.² In this article, we review current procedures for the management of HS, including cryoinsufflation, incision and drainage, deroofing, skin tissue–saving excision with electrosurgical peeling, and wide surgical excision, along with various closure techniques.

Cryoinsufflation

First described in 2014, cryoinsufflation is a novel method for treating sinus tracts.³ Lesions initially are identified on physical examination. Prior to the procedure, local anesthesia is administered to the lesion.³ A 21-gauge needle is mounted onto a cryosurgical unit and inserted into the opening of the sinus tract. Liquid nitrogen is sprayed into the tract for 5 seconds, followed by a 3-second pause; the process is repeated 3 times. Patients return for treatment sessions monthly until the tract is obliterated. This procedure was first performed on 2 patients with satisfactory results.³

Since the initial report, the investigators made 2 changes to refine the procedure.⁴ First, systemic antibiotics should be prescribed 2 months prior to the procedure to clear the sinus tracts of infection. Furthermore, a 21-gauge, olive-tipped cannula is recommended in lieu of a 21-gauge needle to mitigate the risk of adverse events such as air embolism.⁴

Incision and Drainage

Incision and drainage provides rapid pain relief for tense fluctuant abscesses, but recurrence is common and the procedure costs are high.⁵ For drainage, wide circumferential local anesthesia is administered followed by incision.⁶ Pus is eliminated using digital pressure or saline rinses.² Following the elimination of pus, the wound may need gauze packing or placement of a wick for a few days.⁶ The general belief is that incision and drainage should be used, if necessary, to rapidly relieve the patient’s pain; however, other surgical options should be considered if the patient has had multiple incision and drainage procedures.⁷ Currently there are no randomized controlled trials (RCTs) on incision and drainage procedures in HS abscesses.

Deroofing

In 1959, Mullins et al⁸ first described the deroofing procedure, which was refined to preserve the floor of the sinus tract in the 1980s.^9,10 Culp¹⁰ and Brown et al⁹ theorized that preservation of the exposed floor of the sinus tract allowed for the epithelial cells from sweat glands and hair follicle remnants to rapidly reepithelialize the wound. In 2010, van der Zee et al¹¹ performed a prospective study of 88 deroofed lesions in which the investigators removed keratinous debris and epithelial remnants of the floor due to concern for recurrence in this area if the tissues remained. Only 17% (15/88) of the lesions recurred at a median follow-up of 34 months.¹¹

In Hurley stage I or II HS, deroofing remains the primary procedure for persistent nodules and sinus tracts.² The lesion is identified on physical examination and local anesthesia is administered, first to the area surrounding the lesion, then to the lesion itself.¹¹ A blunt probe is used to identify openings and search for connecting fistulas. After defining the sinus tract, the roof and wings created by the incision are removed.^11,12 The material on the floor of the tract is scraped away, and the wound is left to heal by secondary intention.¹¹ In general, deroofed lesions heal with cosmetically acceptable scars. We have used this procedure in skin of color patients with good results and no difficulties with healing. Controlled trials with long-term follow-up are lacking in this population.

Skin Tissue–Saving Excision With Electrosurgical Peeling

Skin tissue–saving excision with electrosurgical peeling was first introduced in 2015.¹³ Blok et al¹⁴ described the procedure as a promising alternative to wide surgical excision for Hurley stage II or III HS. The procedure saves healthy tissue while completely removing lesional tissue, leading to rapid wound healing, excellent cosmesis, and a low risk of contractures^2,14; however, recurrence rates are higher than those seen in wide surgical excision.¹⁵ There are no known RCTs with long-term follow-up for HS patients treated with skin tissue–saving excision with electrosurgical peeling.

The procedure typically is performed under general anesthesia.¹⁴ First, the sinus tract is palpated on physical examination and probed to delineate the extent of the tract. Next, the roof of the tract is incised electrosurgically with a wire loop tip coupled to an electrosurgical generator.¹⁴ Consecutive tangential excisions are made until the floor of the sinus tract is reached. The process of incising sinus tracts followed by tangential peeling off of tissue continues until the entire area is clear of lesional and fibrotic tissue. The wound margins are probed for the presence and subsequent removal of residual sinus tracts. Lastly, the electrosurgical generator is used to achieve hemostasis, steroids are injected to prevent the formation of hypergranulation tissue, and the wound is left to heal by secondary intention.¹⁴ Following intervention, recurrence rates appear to be similar to wide surgical excision.^13,14

Wide Surgical Excision

Wide excision is a widely established technique consisting of surgical excision of a lesion plus an area of surrounding disease-free tissue such as subcutaneous fat or a lateral margin of intertriginous skin.¹⁵ Similar to other surgical techniques, wide excision is considered in cases of severe disease when pharmacologic management cannot remedy extensive fibrosis or architectural loss. It typically is performed in Hurley stage II and III HS, with pathology extending to involve deeper structures inaccessible to more superficial surgical methods.² Prominent areas of use include gluteal, axillary, perineal, and perianal HS lesions on which conservative treatments have little effect and depend on wide excision to provide successful postoperative results.¹⁶ Although retrospective and prospective studies exist on wide excision in HS, there continues to be a dearth of RCTs. Based on the available literature, the primary motive for wide excision is lower recurrence rates (13% overall compared to 22% and 27% for local excision and deroofing, respectively) and longer asymptomatic periods compared to more local techniques.^7,17 Wide excision combined with continued aggressive medical management and dietary modifications currently is an efficacious treatment in providing functional long-term results.⁶ These benefits, however, are not without their drawbacks, as the more extensive nature of wide surgical excision predisposes patients to larger wounds, surgery-induced infection, and prolonged recovery periods.^6,15 If preoperative measurements are not wisely assessed, the excision also can extend to involve neurovascular bundles and other vital structures, contributing to greater postoperative morbidity.¹⁵ Ultrasonography provides useful anatomic information in HS, such as location and extent of fistulous tracts and fluid collections; these findings can assist in guiding the width and depth of the excision itself to ensure the entire area of HS involvement is removed.¹⁸ Published data revealed that 204 of 255 (80%) patients were markedly satisfied with postoperative outcomes of wide excision,¹⁹ which gives credence to the idea that although the complications of wide excision may not be as favorable, the long-lasting improvements in quality of life make wide surgical excision a suggested first-line treatment in all stages of HS.^16,20

Closure Techniques

The best skin closure method following surgical excision is controversial and not well established in literature. Options include healing by secondary intention, primary (suture-based) closure, skin grafts, and skin flaps. Each of these methods has had moderate success in multiple observational studies, and the choice should be made based on individualized assessment of the patient’s HS lesion characteristics, ability to adhere to recovery protocols, and relevant demographics. A systematic review by Mehdizadeh et al¹⁷ provided the following recurrence rates for techniques utilized after wide excision: primary closure, 15%; flaps, 8%; and grafting, 6%. Despite conflicting evidence, allowing wounds to heal by secondary intention is best, based on the author’s experience (I.H.H.).

Secondary Intention
Healing by secondary intention refers to a wound that is intentionally left open to be filled in with granulation tissue and eventual epithelization over time rather than being approximated and closed via sutures or staples as in primary intention. It is a well-established option in wound management and results in a longer but more comfortable period of convalescence in postsurgical HS management.²⁰ Patients can add regular moist wound dressings (eg, silastic foam dressing) to manage the wound at home and continue normal activities for most of the healing period; however, the recovery period can become excessively long and painful, and there is a high risk of formation of retractile scar bands at and around the healing site.¹² Strict adherence to wound-healing protocols is paramount to minimizing unwanted complications.²¹ Secondary intention often is used after wide local excision and has been demonstrated to yield positive functional and aesthetic results in multiple studies, especially in the more severe Hurley stage II or III cases.^21,22 It can be successfully employed after laser treatment and in surgical defects of all sizes with little to no contractures or reduced range of motion.⁶ Ultimately, the choice to heal via secondary intention should be made after thorough assessment of patient needs and with ample education to ensure compliance.

Primary Closure
Primary closure is the suture-mediated closing technique that is most often used in wound closure for lower-grade HS cases, especially smaller excisions. However, it is associated with potential complications. If HS lesions are not effectively excised, disease can then recur at the periphery of the excision and wound dehiscence can manifest more readily, especially as wound size increases.²³ Consequently, primary closure is associated with the highest recurrence rates among closure techniques.¹⁷ Avoiding primary closure in active disease also is recommended due to the potential of burying residual foci of inflammation.⁶ Finally, primary closures lack skin coverage and thus often are not viable options in most perianal and genital lesions that require more extensive reconstruction. Retrospective case series and case reports exist on primary excision, but further study is needed.

Skin Grafts
Skin grafting is a technique of surgically transplanting a piece of healthy skin from one body site to another. Skin grafts typically are used when primary closure or skin flaps are not feasible (eg, in large wounds) and also when shorter time to wound closure is a greater concern in patient recovery.^2,24 Additionally, skin grafts can be employed on large flat surfaces of the body, such as the buttocks or thighs, for timely wound closure when wound contraction is less effective or wound healing is slow via epithelization. Types of skin graft techniques include split-thickness skin graft (STSG), full-thickness skin graft, and recycled skin graft. All 3 types have demonstrated acceptable functional and aesthetic results in observational studies and case reports, and thus deciding which technique to use should include individualized assessment.^2,25 The STSG has several advantages over the full-thickness skin graft, including hairlessness (ie, without hair follicles), ease of harvest, and a less complicated transfer to contaminated lesional areas such as those in HS.²⁶ Additionally, STSGs allow for closure of even the largest wounds with minimal risk of serious infection. Split-thickness skin grafts are considered one of the most efficacious tools for axilla reconstruction; however, they require prolonged immobilization of the arm, result in sequelae in donor sites, and do not always prevent retractile scars.²⁶ The recycled skin graft technique can be used to treat chronic gluteal HS, but reliability and outcomes have not been reported. Skin grafting after excision is associated with increased pain, immobilization, prolonged hospitalization, and longer healing times compared to skin flaps.¹⁹ In a systematic review of wound healing techniques following wide excision, grafting was shown to have the lowest recurrence rate (6%) compared to skin flaps (8%) and primary closure (15%).¹⁷ The absence of hair follicles and sweat glands in STSGs may be advantageous in HS because both hair follicles and sweat glands are thought to play more roles in the pathogenesis of HS.^18,24 Most studies on skin grafts are limited to case reports.

Skin Flaps
Skin flaps are similar to skin grafts in that healthy skin is transplanted from one site to another; the difference is that flaps maintain an intact blood supply, whereas skin grafts depend on growth of new blood vessels.^12,13 The primary advantage of skin flaps is that they provide the best quality of skin due to the thick tissue coverage, which is an important concern, especially in aesthetic scenarios. Additionally, they have been shown to provide shorter healing times than grafts, primary closure, and secondary healing, which can be especially important when functional disability is a concern in the postoperative period.²⁶ However, their use should be limited due to several complications owing to their blood supply, as there is a high risk of ischemia to distant portions of flaps, which often can progress to necrosis and hemorrhage during the harvesting process.² Thus, skin flaps are incredibly difficult to use in larger wounds and often require debulking due to their thickness. Additionally, skin flaps are definitive by nature, which can pose an issue if HS recurs locally. Skin flaps are recommended only when their use is mandatory, such as in the coverage of important anatomic structures (eg, exposed neurovascular bundles and large vessels).² Advances have been made in flap construction, and now several types of flaps are employed in several body areas with differing indications and recommendations.^2,21 As with skin grafts, most studies in the literature are case reports; therefore, further investigation is needed.

Combination Reconstructions
Combination reconstructions refer to the simultaneous use of multiple closure or healing techniques. By combining 2 or more methods, surgeons can utilize the advantages of each technique to provide an individualized approach that can substantially diminish wound surface area and accelerate wound healing.² For example, with the starlike technique, 5 equilateral triangles bordering a foci of axillary disease are excised in addition to the central foci, and the edges of each triangle are then sutured together to create a final scar of considerably smaller size. The starlike technique allows the wound to be partially sutured while leaving the remaining area to heal by secondary intention.² There are a small number of case series and prospective studies on combined reconstructions in HS but no RCTs.

Conclusion

Many procedures exist as options for treatment of patients with HS. Deroofing and cryoinsufflation are options for localized Hurley stage I or II disease. For more severe Hurley stage II or III disease, skin tissue–saving excision with electrosurgical peeling or wide surgical excisions are preferred. Following excision, there are many options for wound closure, but our preference is to allow the wound to heal by secondary intention. It is imperative that dermatologists are informed on the different techniques for treating this disease to determine the best route of care for their patients.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that has a social and psychosocial impact on patients with skin of color.¹ It is characterized by recurrent abscesses, draining sinus tracts, and scarring in the intertriginous skin folds. The lesions are difficult to treat and present with considerable frustration for both patients and physicians. Although current treatment ladders can delay procedures and surgical intervention,¹ some believe that surgery should be introduced earlier in HS management.² In this article, we review current procedures for the management of HS, including cryoinsufflation, incision and drainage, deroofing, skin tissue–saving excision with electrosurgical peeling, and wide surgical excision, along with various closure techniques.

Cryoinsufflation

First described in 2014, cryoinsufflation is a novel method for treating sinus tracts.³ Lesions initially are identified on physical examination. Prior to the procedure, local anesthesia is administered to the lesion.³ A 21-gauge needle is mounted onto a cryosurgical unit and inserted into the opening of the sinus tract. Liquid nitrogen is sprayed into the tract for 5 seconds, followed by a 3-second pause; the process is repeated 3 times. Patients return for treatment sessions monthly until the tract is obliterated. This procedure was first performed on 2 patients with satisfactory results.³

Since the initial report, the investigators made 2 changes to refine the procedure.⁴ First, systemic antibiotics should be prescribed 2 months prior to the procedure to clear the sinus tracts of infection. Furthermore, a 21-gauge, olive-tipped cannula is recommended in lieu of a 21-gauge needle to mitigate the risk of adverse events such as air embolism.⁴

Incision and Drainage

Incision and drainage provides rapid pain relief for tense fluctuant abscesses, but recurrence is common and the procedure costs are high.⁵ For drainage, wide circumferential local anesthesia is administered followed by incision.⁶ Pus is eliminated using digital pressure or saline rinses.² Following the elimination of pus, the wound may need gauze packing or placement of a wick for a few days.⁶ The general belief is that incision and drainage should be used, if necessary, to rapidly relieve the patient’s pain; however, other surgical options should be considered if the patient has had multiple incision and drainage procedures.⁷ Currently there are no randomized controlled trials (RCTs) on incision and drainage procedures in HS abscesses.

Deroofing

In 1959, Mullins et al⁸ first described the deroofing procedure, which was refined to preserve the floor of the sinus tract in the 1980s.^9,10 Culp¹⁰ and Brown et al⁹ theorized that preservation of the exposed floor of the sinus tract allowed for the epithelial cells from sweat glands and hair follicle remnants to rapidly reepithelialize the wound. In 2010, van der Zee et al¹¹ performed a prospective study of 88 deroofed lesions in which the investigators removed keratinous debris and epithelial remnants of the floor due to concern for recurrence in this area if the tissues remained. Only 17% (15/88) of the lesions recurred at a median follow-up of 34 months.¹¹

In Hurley stage I or II HS, deroofing remains the primary procedure for persistent nodules and sinus tracts.² The lesion is identified on physical examination and local anesthesia is administered, first to the area surrounding the lesion, then to the lesion itself.¹¹ A blunt probe is used to identify openings and search for connecting fistulas. After defining the sinus tract, the roof and wings created by the incision are removed.^11,12 The material on the floor of the tract is scraped away, and the wound is left to heal by secondary intention.¹¹ In general, deroofed lesions heal with cosmetically acceptable scars. We have used this procedure in skin of color patients with good results and no difficulties with healing. Controlled trials with long-term follow-up are lacking in this population.

Skin Tissue–Saving Excision With Electrosurgical Peeling

Skin tissue–saving excision with electrosurgical peeling was first introduced in 2015.¹³ Blok et al¹⁴ described the procedure as a promising alternative to wide surgical excision for Hurley stage II or III HS. The procedure saves healthy tissue while completely removing lesional tissue, leading to rapid wound healing, excellent cosmesis, and a low risk of contractures^2,14; however, recurrence rates are higher than those seen in wide surgical excision.¹⁵ There are no known RCTs with long-term follow-up for HS patients treated with skin tissue–saving excision with electrosurgical peeling.

The procedure typically is performed under general anesthesia.¹⁴ First, the sinus tract is palpated on physical examination and probed to delineate the extent of the tract. Next, the roof of the tract is incised electrosurgically with a wire loop tip coupled to an electrosurgical generator.¹⁴ Consecutive tangential excisions are made until the floor of the sinus tract is reached. The process of incising sinus tracts followed by tangential peeling off of tissue continues until the entire area is clear of lesional and fibrotic tissue. The wound margins are probed for the presence and subsequent removal of residual sinus tracts. Lastly, the electrosurgical generator is used to achieve hemostasis, steroids are injected to prevent the formation of hypergranulation tissue, and the wound is left to heal by secondary intention.¹⁴ Following intervention, recurrence rates appear to be similar to wide surgical excision.^13,14

Wide Surgical Excision

Wide excision is a widely established technique consisting of surgical excision of a lesion plus an area of surrounding disease-free tissue such as subcutaneous fat or a lateral margin of intertriginous skin.¹⁵ Similar to other surgical techniques, wide excision is considered in cases of severe disease when pharmacologic management cannot remedy extensive fibrosis or architectural loss. It typically is performed in Hurley stage II and III HS, with pathology extending to involve deeper structures inaccessible to more superficial surgical methods.² Prominent areas of use include gluteal, axillary, perineal, and perianal HS lesions on which conservative treatments have little effect and depend on wide excision to provide successful postoperative results.¹⁶ Although retrospective and prospective studies exist on wide excision in HS, there continues to be a dearth of RCTs. Based on the available literature, the primary motive for wide excision is lower recurrence rates (13% overall compared to 22% and 27% for local excision and deroofing, respectively) and longer asymptomatic periods compared to more local techniques.^7,17 Wide excision combined with continued aggressive medical management and dietary modifications currently is an efficacious treatment in providing functional long-term results.⁶ These benefits, however, are not without their drawbacks, as the more extensive nature of wide surgical excision predisposes patients to larger wounds, surgery-induced infection, and prolonged recovery periods.^6,15 If preoperative measurements are not wisely assessed, the excision also can extend to involve neurovascular bundles and other vital structures, contributing to greater postoperative morbidity.¹⁵ Ultrasonography provides useful anatomic information in HS, such as location and extent of fistulous tracts and fluid collections; these findings can assist in guiding the width and depth of the excision itself to ensure the entire area of HS involvement is removed.¹⁸ Published data revealed that 204 of 255 (80%) patients were markedly satisfied with postoperative outcomes of wide excision,¹⁹ which gives credence to the idea that although the complications of wide excision may not be as favorable, the long-lasting improvements in quality of life make wide surgical excision a suggested first-line treatment in all stages of HS.^16,20

Closure Techniques

The best skin closure method following surgical excision is controversial and not well established in literature. Options include healing by secondary intention, primary (suture-based) closure, skin grafts, and skin flaps. Each of these methods has had moderate success in multiple observational studies, and the choice should be made based on individualized assessment of the patient’s HS lesion characteristics, ability to adhere to recovery protocols, and relevant demographics. A systematic review by Mehdizadeh et al¹⁷ provided the following recurrence rates for techniques utilized after wide excision: primary closure, 15%; flaps, 8%; and grafting, 6%. Despite conflicting evidence, allowing wounds to heal by secondary intention is best, based on the author’s experience (I.H.H.).

Secondary Intention
Healing by secondary intention refers to a wound that is intentionally left open to be filled in with granulation tissue and eventual epithelization over time rather than being approximated and closed via sutures or staples as in primary intention. It is a well-established option in wound management and results in a longer but more comfortable period of convalescence in postsurgical HS management.²⁰ Patients can add regular moist wound dressings (eg, silastic foam dressing) to manage the wound at home and continue normal activities for most of the healing period; however, the recovery period can become excessively long and painful, and there is a high risk of formation of retractile scar bands at and around the healing site.¹² Strict adherence to wound-healing protocols is paramount to minimizing unwanted complications.²¹ Secondary intention often is used after wide local excision and has been demonstrated to yield positive functional and aesthetic results in multiple studies, especially in the more severe Hurley stage II or III cases.^21,22 It can be successfully employed after laser treatment and in surgical defects of all sizes with little to no contractures or reduced range of motion.⁶ Ultimately, the choice to heal via secondary intention should be made after thorough assessment of patient needs and with ample education to ensure compliance.

Primary Closure
Primary closure is the suture-mediated closing technique that is most often used in wound closure for lower-grade HS cases, especially smaller excisions. However, it is associated with potential complications. If HS lesions are not effectively excised, disease can then recur at the periphery of the excision and wound dehiscence can manifest more readily, especially as wound size increases.²³ Consequently, primary closure is associated with the highest recurrence rates among closure techniques.¹⁷ Avoiding primary closure in active disease also is recommended due to the potential of burying residual foci of inflammation.⁶ Finally, primary closures lack skin coverage and thus often are not viable options in most perianal and genital lesions that require more extensive reconstruction. Retrospective case series and case reports exist on primary excision, but further study is needed.

Skin Grafts
Skin grafting is a technique of surgically transplanting a piece of healthy skin from one body site to another. Skin grafts typically are used when primary closure or skin flaps are not feasible (eg, in large wounds) and also when shorter time to wound closure is a greater concern in patient recovery.^2,24 Additionally, skin grafts can be employed on large flat surfaces of the body, such as the buttocks or thighs, for timely wound closure when wound contraction is less effective or wound healing is slow via epithelization. Types of skin graft techniques include split-thickness skin graft (STSG), full-thickness skin graft, and recycled skin graft. All 3 types have demonstrated acceptable functional and aesthetic results in observational studies and case reports, and thus deciding which technique to use should include individualized assessment.^2,25 The STSG has several advantages over the full-thickness skin graft, including hairlessness (ie, without hair follicles), ease of harvest, and a less complicated transfer to contaminated lesional areas such as those in HS.²⁶ Additionally, STSGs allow for closure of even the largest wounds with minimal risk of serious infection. Split-thickness skin grafts are considered one of the most efficacious tools for axilla reconstruction; however, they require prolonged immobilization of the arm, result in sequelae in donor sites, and do not always prevent retractile scars.²⁶ The recycled skin graft technique can be used to treat chronic gluteal HS, but reliability and outcomes have not been reported. Skin grafting after excision is associated with increased pain, immobilization, prolonged hospitalization, and longer healing times compared to skin flaps.¹⁹ In a systematic review of wound healing techniques following wide excision, grafting was shown to have the lowest recurrence rate (6%) compared to skin flaps (8%) and primary closure (15%).¹⁷ The absence of hair follicles and sweat glands in STSGs may be advantageous in HS because both hair follicles and sweat glands are thought to play more roles in the pathogenesis of HS.^18,24 Most studies on skin grafts are limited to case reports.

Skin Flaps
Skin flaps are similar to skin grafts in that healthy skin is transplanted from one site to another; the difference is that flaps maintain an intact blood supply, whereas skin grafts depend on growth of new blood vessels.^12,13 The primary advantage of skin flaps is that they provide the best quality of skin due to the thick tissue coverage, which is an important concern, especially in aesthetic scenarios. Additionally, they have been shown to provide shorter healing times than grafts, primary closure, and secondary healing, which can be especially important when functional disability is a concern in the postoperative period.²⁶ However, their use should be limited due to several complications owing to their blood supply, as there is a high risk of ischemia to distant portions of flaps, which often can progress to necrosis and hemorrhage during the harvesting process.² Thus, skin flaps are incredibly difficult to use in larger wounds and often require debulking due to their thickness. Additionally, skin flaps are definitive by nature, which can pose an issue if HS recurs locally. Skin flaps are recommended only when their use is mandatory, such as in the coverage of important anatomic structures (eg, exposed neurovascular bundles and large vessels).² Advances have been made in flap construction, and now several types of flaps are employed in several body areas with differing indications and recommendations.^2,21 As with skin grafts, most studies in the literature are case reports; therefore, further investigation is needed.

Combination Reconstructions
Combination reconstructions refer to the simultaneous use of multiple closure or healing techniques. By combining 2 or more methods, surgeons can utilize the advantages of each technique to provide an individualized approach that can substantially diminish wound surface area and accelerate wound healing.² For example, with the starlike technique, 5 equilateral triangles bordering a foci of axillary disease are excised in addition to the central foci, and the edges of each triangle are then sutured together to create a final scar of considerably smaller size. The starlike technique allows the wound to be partially sutured while leaving the remaining area to heal by secondary intention.² There are a small number of case series and prospective studies on combined reconstructions in HS but no RCTs.

Conclusion

Many procedures exist as options for treatment of patients with HS. Deroofing and cryoinsufflation are options for localized Hurley stage I or II disease. For more severe Hurley stage II or III disease, skin tissue–saving excision with electrosurgical peeling or wide surgical excisions are preferred. Following excision, there are many options for wound closure, but our preference is to allow the wound to heal by secondary intention. It is imperative that dermatologists are informed on the different techniques for treating this disease to determine the best route of care for their patients.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that has a social and psychosocial impact on patients with skin of color.¹ It is characterized by recurrent abscesses, draining sinus tracts, and scarring in the intertriginous skin folds. The lesions are difficult to treat and present with considerable frustration for both patients and physicians. Although current treatment ladders can delay procedures and surgical intervention,¹ some believe that surgery should be introduced earlier in HS management.² In this article, we review current procedures for the management of HS, including cryoinsufflation, incision and drainage, deroofing, skin tissue–saving excision with electrosurgical peeling, and wide surgical excision, along with various closure techniques.

Cryoinsufflation

First described in 2014, cryoinsufflation is a novel method for treating sinus tracts.³ Lesions initially are identified on physical examination. Prior to the procedure, local anesthesia is administered to the lesion.³ A 21-gauge needle is mounted onto a cryosurgical unit and inserted into the opening of the sinus tract. Liquid nitrogen is sprayed into the tract for 5 seconds, followed by a 3-second pause; the process is repeated 3 times. Patients return for treatment sessions monthly until the tract is obliterated. This procedure was first performed on 2 patients with satisfactory results.³

Since the initial report, the investigators made 2 changes to refine the procedure.⁴ First, systemic antibiotics should be prescribed 2 months prior to the procedure to clear the sinus tracts of infection. Furthermore, a 21-gauge, olive-tipped cannula is recommended in lieu of a 21-gauge needle to mitigate the risk of adverse events such as air embolism.⁴

Incision and Drainage

Incision and drainage provides rapid pain relief for tense fluctuant abscesses, but recurrence is common and the procedure costs are high.⁵ For drainage, wide circumferential local anesthesia is administered followed by incision.⁶ Pus is eliminated using digital pressure or saline rinses.² Following the elimination of pus, the wound may need gauze packing or placement of a wick for a few days.⁶ The general belief is that incision and drainage should be used, if necessary, to rapidly relieve the patient’s pain; however, other surgical options should be considered if the patient has had multiple incision and drainage procedures.⁷ Currently there are no randomized controlled trials (RCTs) on incision and drainage procedures in HS abscesses.

Deroofing

In 1959, Mullins et al⁸ first described the deroofing procedure, which was refined to preserve the floor of the sinus tract in the 1980s.^9,10 Culp¹⁰ and Brown et al⁹ theorized that preservation of the exposed floor of the sinus tract allowed for the epithelial cells from sweat glands and hair follicle remnants to rapidly reepithelialize the wound. In 2010, van der Zee et al¹¹ performed a prospective study of 88 deroofed lesions in which the investigators removed keratinous debris and epithelial remnants of the floor due to concern for recurrence in this area if the tissues remained. Only 17% (15/88) of the lesions recurred at a median follow-up of 34 months.¹¹

In Hurley stage I or II HS, deroofing remains the primary procedure for persistent nodules and sinus tracts.² The lesion is identified on physical examination and local anesthesia is administered, first to the area surrounding the lesion, then to the lesion itself.¹¹ A blunt probe is used to identify openings and search for connecting fistulas. After defining the sinus tract, the roof and wings created by the incision are removed.^11,12 The material on the floor of the tract is scraped away, and the wound is left to heal by secondary intention.¹¹ In general, deroofed lesions heal with cosmetically acceptable scars. We have used this procedure in skin of color patients with good results and no difficulties with healing. Controlled trials with long-term follow-up are lacking in this population.

Skin Tissue–Saving Excision With Electrosurgical Peeling

Skin tissue–saving excision with electrosurgical peeling was first introduced in 2015.¹³ Blok et al¹⁴ described the procedure as a promising alternative to wide surgical excision for Hurley stage II or III HS. The procedure saves healthy tissue while completely removing lesional tissue, leading to rapid wound healing, excellent cosmesis, and a low risk of contractures^2,14; however, recurrence rates are higher than those seen in wide surgical excision.¹⁵ There are no known RCTs with long-term follow-up for HS patients treated with skin tissue–saving excision with electrosurgical peeling.

The procedure typically is performed under general anesthesia.¹⁴ First, the sinus tract is palpated on physical examination and probed to delineate the extent of the tract. Next, the roof of the tract is incised electrosurgically with a wire loop tip coupled to an electrosurgical generator.¹⁴ Consecutive tangential excisions are made until the floor of the sinus tract is reached. The process of incising sinus tracts followed by tangential peeling off of tissue continues until the entire area is clear of lesional and fibrotic tissue. The wound margins are probed for the presence and subsequent removal of residual sinus tracts. Lastly, the electrosurgical generator is used to achieve hemostasis, steroids are injected to prevent the formation of hypergranulation tissue, and the wound is left to heal by secondary intention.¹⁴ Following intervention, recurrence rates appear to be similar to wide surgical excision.^13,14

Wide Surgical Excision

Wide excision is a widely established technique consisting of surgical excision of a lesion plus an area of surrounding disease-free tissue such as subcutaneous fat or a lateral margin of intertriginous skin.¹⁵ Similar to other surgical techniques, wide excision is considered in cases of severe disease when pharmacologic management cannot remedy extensive fibrosis or architectural loss. It typically is performed in Hurley stage II and III HS, with pathology extending to involve deeper structures inaccessible to more superficial surgical methods.² Prominent areas of use include gluteal, axillary, perineal, and perianal HS lesions on which conservative treatments have little effect and depend on wide excision to provide successful postoperative results.¹⁶ Although retrospective and prospective studies exist on wide excision in HS, there continues to be a dearth of RCTs. Based on the available literature, the primary motive for wide excision is lower recurrence rates (13% overall compared to 22% and 27% for local excision and deroofing, respectively) and longer asymptomatic periods compared to more local techniques.^7,17 Wide excision combined with continued aggressive medical management and dietary modifications currently is an efficacious treatment in providing functional long-term results.⁶ These benefits, however, are not without their drawbacks, as the more extensive nature of wide surgical excision predisposes patients to larger wounds, surgery-induced infection, and prolonged recovery periods.^6,15 If preoperative measurements are not wisely assessed, the excision also can extend to involve neurovascular bundles and other vital structures, contributing to greater postoperative morbidity.¹⁵ Ultrasonography provides useful anatomic information in HS, such as location and extent of fistulous tracts and fluid collections; these findings can assist in guiding the width and depth of the excision itself to ensure the entire area of HS involvement is removed.¹⁸ Published data revealed that 204 of 255 (80%) patients were markedly satisfied with postoperative outcomes of wide excision,¹⁹ which gives credence to the idea that although the complications of wide excision may not be as favorable, the long-lasting improvements in quality of life make wide surgical excision a suggested first-line treatment in all stages of HS.^16,20

Closure Techniques

The best skin closure method following surgical excision is controversial and not well established in literature. Options include healing by secondary intention, primary (suture-based) closure, skin grafts, and skin flaps. Each of these methods has had moderate success in multiple observational studies, and the choice should be made based on individualized assessment of the patient’s HS lesion characteristics, ability to adhere to recovery protocols, and relevant demographics. A systematic review by Mehdizadeh et al¹⁷ provided the following recurrence rates for techniques utilized after wide excision: primary closure, 15%; flaps, 8%; and grafting, 6%. Despite conflicting evidence, allowing wounds to heal by secondary intention is best, based on the author’s experience (I.H.H.).

Secondary Intention
Healing by secondary intention refers to a wound that is intentionally left open to be filled in with granulation tissue and eventual epithelization over time rather than being approximated and closed via sutures or staples as in primary intention. It is a well-established option in wound management and results in a longer but more comfortable period of convalescence in postsurgical HS management.²⁰ Patients can add regular moist wound dressings (eg, silastic foam dressing) to manage the wound at home and continue normal activities for most of the healing period; however, the recovery period can become excessively long and painful, and there is a high risk of formation of retractile scar bands at and around the healing site.¹² Strict adherence to wound-healing protocols is paramount to minimizing unwanted complications.²¹ Secondary intention often is used after wide local excision and has been demonstrated to yield positive functional and aesthetic results in multiple studies, especially in the more severe Hurley stage II or III cases.^21,22 It can be successfully employed after laser treatment and in surgical defects of all sizes with little to no contractures or reduced range of motion.⁶ Ultimately, the choice to heal via secondary intention should be made after thorough assessment of patient needs and with ample education to ensure compliance.

Primary Closure
Primary closure is the suture-mediated closing technique that is most often used in wound closure for lower-grade HS cases, especially smaller excisions. However, it is associated with potential complications. If HS lesions are not effectively excised, disease can then recur at the periphery of the excision and wound dehiscence can manifest more readily, especially as wound size increases.²³ Consequently, primary closure is associated with the highest recurrence rates among closure techniques.¹⁷ Avoiding primary closure in active disease also is recommended due to the potential of burying residual foci of inflammation.⁶ Finally, primary closures lack skin coverage and thus often are not viable options in most perianal and genital lesions that require more extensive reconstruction. Retrospective case series and case reports exist on primary excision, but further study is needed.

Skin Grafts
Skin grafting is a technique of surgically transplanting a piece of healthy skin from one body site to another. Skin grafts typically are used when primary closure or skin flaps are not feasible (eg, in large wounds) and also when shorter time to wound closure is a greater concern in patient recovery.^2,24 Additionally, skin grafts can be employed on large flat surfaces of the body, such as the buttocks or thighs, for timely wound closure when wound contraction is less effective or wound healing is slow via epithelization. Types of skin graft techniques include split-thickness skin graft (STSG), full-thickness skin graft, and recycled skin graft. All 3 types have demonstrated acceptable functional and aesthetic results in observational studies and case reports, and thus deciding which technique to use should include individualized assessment.^2,25 The STSG has several advantages over the full-thickness skin graft, including hairlessness (ie, without hair follicles), ease of harvest, and a less complicated transfer to contaminated lesional areas such as those in HS.²⁶ Additionally, STSGs allow for closure of even the largest wounds with minimal risk of serious infection. Split-thickness skin grafts are considered one of the most efficacious tools for axilla reconstruction; however, they require prolonged immobilization of the arm, result in sequelae in donor sites, and do not always prevent retractile scars.²⁶ The recycled skin graft technique can be used to treat chronic gluteal HS, but reliability and outcomes have not been reported. Skin grafting after excision is associated with increased pain, immobilization, prolonged hospitalization, and longer healing times compared to skin flaps.¹⁹ In a systematic review of wound healing techniques following wide excision, grafting was shown to have the lowest recurrence rate (6%) compared to skin flaps (8%) and primary closure (15%).¹⁷ The absence of hair follicles and sweat glands in STSGs may be advantageous in HS because both hair follicles and sweat glands are thought to play more roles in the pathogenesis of HS.^18,24 Most studies on skin grafts are limited to case reports.

Skin Flaps
Skin flaps are similar to skin grafts in that healthy skin is transplanted from one site to another; the difference is that flaps maintain an intact blood supply, whereas skin grafts depend on growth of new blood vessels.^12,13 The primary advantage of skin flaps is that they provide the best quality of skin due to the thick tissue coverage, which is an important concern, especially in aesthetic scenarios. Additionally, they have been shown to provide shorter healing times than grafts, primary closure, and secondary healing, which can be especially important when functional disability is a concern in the postoperative period.²⁶ However, their use should be limited due to several complications owing to their blood supply, as there is a high risk of ischemia to distant portions of flaps, which often can progress to necrosis and hemorrhage during the harvesting process.² Thus, skin flaps are incredibly difficult to use in larger wounds and often require debulking due to their thickness. Additionally, skin flaps are definitive by nature, which can pose an issue if HS recurs locally. Skin flaps are recommended only when their use is mandatory, such as in the coverage of important anatomic structures (eg, exposed neurovascular bundles and large vessels).² Advances have been made in flap construction, and now several types of flaps are employed in several body areas with differing indications and recommendations.^2,21 As with skin grafts, most studies in the literature are case reports; therefore, further investigation is needed.

Combination Reconstructions
Combination reconstructions refer to the simultaneous use of multiple closure or healing techniques. By combining 2 or more methods, surgeons can utilize the advantages of each technique to provide an individualized approach that can substantially diminish wound surface area and accelerate wound healing.² For example, with the starlike technique, 5 equilateral triangles bordering a foci of axillary disease are excised in addition to the central foci, and the edges of each triangle are then sutured together to create a final scar of considerably smaller size. The starlike technique allows the wound to be partially sutured while leaving the remaining area to heal by secondary intention.² There are a small number of case series and prospective studies on combined reconstructions in HS but no RCTs.

Conclusion

Many procedures exist as options for treatment of patients with HS. Deroofing and cryoinsufflation are options for localized Hurley stage I or II disease. For more severe Hurley stage II or III disease, skin tissue–saving excision with electrosurgical peeling or wide surgical excisions are preferred. Following excision, there are many options for wound closure, but our preference is to allow the wound to heal by secondary intention. It is imperative that dermatologists are informed on the different techniques for treating this disease to determine the best route of care for their patients.

SAN FRANCISCO – What can women with migraine expect during the menopausal transition?

About 60% will experience a change in their headache pattern. And for 60% of that group, it’s a change for the worse, Yu-Chen Cheng, MD, reported at the annual meeting of the American Headache Society.

She presented a retrospective longitudinal study of 60 women with a preexisting history of migraine who were followed through the menopausal transition. All had long-term medical records available, including brain imaging results and hormonal laboratory data.

The impetus for the study was the fact that even though three-quarters of America’s estimated 38 million migraineurs are women, all of whom will eventually undergo menopause, the question of what happens to them headache-wise as they go through this process of permanent cessation of ovarian function has received little research attention.

©Eraxion/thinkstockphotos.com

[email protected]

SOURCE: Cheng Y-C and Maleki N. Headache. 2018;58:71. Abstract OR16.

SAN FRANCISCO – What can women with migraine expect during the menopausal transition?

About 60% will experience a change in their headache pattern. And for 60% of that group, it’s a change for the worse, Yu-Chen Cheng, MD, reported at the annual meeting of the American Headache Society.

She presented a retrospective longitudinal study of 60 women with a preexisting history of migraine who were followed through the menopausal transition. All had long-term medical records available, including brain imaging results and hormonal laboratory data.

The impetus for the study was the fact that even though three-quarters of America’s estimated 38 million migraineurs are women, all of whom will eventually undergo menopause, the question of what happens to them headache-wise as they go through this process of permanent cessation of ovarian function has received little research attention.

©Eraxion/thinkstockphotos.com

[email protected]

SOURCE: Cheng Y-C and Maleki N. Headache. 2018;58:71. Abstract OR16.

SAN FRANCISCO – What can women with migraine expect during the menopausal transition?

About 60% will experience a change in their headache pattern. And for 60% of that group, it’s a change for the worse, Yu-Chen Cheng, MD, reported at the annual meeting of the American Headache Society.

She presented a retrospective longitudinal study of 60 women with a preexisting history of migraine who were followed through the menopausal transition. All had long-term medical records available, including brain imaging results and hormonal laboratory data.

The impetus for the study was the fact that even though three-quarters of America’s estimated 38 million migraineurs are women, all of whom will eventually undergo menopause, the question of what happens to them headache-wise as they go through this process of permanent cessation of ovarian function has received little research attention.

©Eraxion/thinkstockphotos.com

[email protected]

SOURCE: Cheng Y-C and Maleki N. Headache. 2018;58:71. Abstract OR16.

We are fortunate to have plentiful acne treatment options available that cater to each patient’s clinical examination, predispositions, and triggers, but the choices are daunting amidst the vast prescription and over-the-counter (OTC) topicals available along with disparate insurance and cost nuances. In addition, when prescribing generic oral therapies, it is complicated to parse out regional differences in price, supply, and insurance coverage to advocate best for each patient and land upon the delicate balance between efficacy, safety, and financial stewardship, both at an individual and community level. I will outline some challenges and solutions to the management of acne amidst these complicated factors.

Oral Therapies

For isotretinoin, generic choices, cost, and tiering within insurance plans are perpetual moving targets despite the drug being the only member of its class.¹ Prescriber resources include tandem searches of electronic medical record price estimates within each insurance formulary, individual pharmacy search engines, and compilation mobile applications such as GoodRx to select the most affordable version for each patient. As an example of a regional trend, isotretinoin generic coverage by one provider in Pennsylvania shifted earlier this year so that every patient, whether new to isotretinoin or midcourse, required a new prior authorization with more stringent coverage requirements including failure of 2 oral antibiotics. Swiftly thereafter, efforts across the state driven by the Pennsylvania Academy of Dermatology and Dermatologic Surgery and its members and fueled by poignant patient vignettes about fragmented and substandard patient care helped to reverse this policy and remove the prior authorization mandate.²

Tetracyclines have experienced broad cost swings, mostly based on disruption of manufacturing at the limited number of distribution sites in the United States. In 2011, a tetracycline shortage arose due to a major manufacturer’s recall³ and persisted with subsequent material shortages, as doxycycline became the preferred and cheaper member of the class. Doxycycline price tag hikes then occurred following Hurricane Sandy when an East Coast manufacturing site was damaged.³ Spironolactone backorder also has been frequent due to recent raw material shortages and delays in production,³ forcing pharmacies to refill small amounts of medication in various dosage forms despite patients owing the same copayment per prescription.

Topical Therapies

Topical retinoid prescription affordability has always been fraught with difficulty owing to age cutoffs because it is often restricted to patients younger than 25 or 40 years, depending on the plan,^4,5 but the availability of adapalene gel 0.1% as an OTC preparation in 2016 has broadened retinoid access and use.⁶ Prescription benzoyl peroxide (BPO) products alone or in combination with retinoids or topical antibiotics (or other combination topical therapies) comprise a large number of branded prescriptions often not covered by insurance or are only affordable using proprietary and intermittently available coupon cards (eg, BPO-clindamycin, clindamycin-tretinoin, BPO-adapalene); therefore, prescribers tend to dispense the individual ingredients and instruct the patient to compound them at home. Furthermore, BPO products can be purchased in effective concentrations as OTC products, and patients looking to procure more affordable, albeit less effective, topical retinoids that also have less irritation potential reach for OTC nightly retinol creams nestled in the antiaging section of the pharmacy.⁷

Opportunities to be involved in the larger scaffold of patient advocacy also are plentiful at the state and national levels. For example, with the support of dermatology state societies and the American Academy of Dermatology Association, Pennsylvania House Bill 2211⁸ and similar bills in other states call for reversal of the gag clause that prevents pharmacists from disclosing the best medication price to patients. Also guided by the American Academy of Dermatology Association, prior authorization model legislation to promote transparency across insurers in this haphazard process is emerging across the country.^9,10

Final Thoughts

These examples of acne medication access and cost quandaries serve to embody the daily problem-solving that dermatologists execute as part of their growing administrative and economic duties. They also represent worthy efforts to consider on behalf of patients, their pocketbooks, and the prudent use of their dermatologists’ time.

We are fortunate to have plentiful acne treatment options available that cater to each patient’s clinical examination, predispositions, and triggers, but the choices are daunting amidst the vast prescription and over-the-counter (OTC) topicals available along with disparate insurance and cost nuances. In addition, when prescribing generic oral therapies, it is complicated to parse out regional differences in price, supply, and insurance coverage to advocate best for each patient and land upon the delicate balance between efficacy, safety, and financial stewardship, both at an individual and community level. I will outline some challenges and solutions to the management of acne amidst these complicated factors.

Oral Therapies

For isotretinoin, generic choices, cost, and tiering within insurance plans are perpetual moving targets despite the drug being the only member of its class.¹ Prescriber resources include tandem searches of electronic medical record price estimates within each insurance formulary, individual pharmacy search engines, and compilation mobile applications such as GoodRx to select the most affordable version for each patient. As an example of a regional trend, isotretinoin generic coverage by one provider in Pennsylvania shifted earlier this year so that every patient, whether new to isotretinoin or midcourse, required a new prior authorization with more stringent coverage requirements including failure of 2 oral antibiotics. Swiftly thereafter, efforts across the state driven by the Pennsylvania Academy of Dermatology and Dermatologic Surgery and its members and fueled by poignant patient vignettes about fragmented and substandard patient care helped to reverse this policy and remove the prior authorization mandate.²

Tetracyclines have experienced broad cost swings, mostly based on disruption of manufacturing at the limited number of distribution sites in the United States. In 2011, a tetracycline shortage arose due to a major manufacturer’s recall³ and persisted with subsequent material shortages, as doxycycline became the preferred and cheaper member of the class. Doxycycline price tag hikes then occurred following Hurricane Sandy when an East Coast manufacturing site was damaged.³ Spironolactone backorder also has been frequent due to recent raw material shortages and delays in production,³ forcing pharmacies to refill small amounts of medication in various dosage forms despite patients owing the same copayment per prescription.

Topical Therapies

Topical retinoid prescription affordability has always been fraught with difficulty owing to age cutoffs because it is often restricted to patients younger than 25 or 40 years, depending on the plan,^4,5 but the availability of adapalene gel 0.1% as an OTC preparation in 2016 has broadened retinoid access and use.⁶ Prescription benzoyl peroxide (BPO) products alone or in combination with retinoids or topical antibiotics (or other combination topical therapies) comprise a large number of branded prescriptions often not covered by insurance or are only affordable using proprietary and intermittently available coupon cards (eg, BPO-clindamycin, clindamycin-tretinoin, BPO-adapalene); therefore, prescribers tend to dispense the individual ingredients and instruct the patient to compound them at home. Furthermore, BPO products can be purchased in effective concentrations as OTC products, and patients looking to procure more affordable, albeit less effective, topical retinoids that also have less irritation potential reach for OTC nightly retinol creams nestled in the antiaging section of the pharmacy.⁷

Opportunities to be involved in the larger scaffold of patient advocacy also are plentiful at the state and national levels. For example, with the support of dermatology state societies and the American Academy of Dermatology Association, Pennsylvania House Bill 2211⁸ and similar bills in other states call for reversal of the gag clause that prevents pharmacists from disclosing the best medication price to patients. Also guided by the American Academy of Dermatology Association, prior authorization model legislation to promote transparency across insurers in this haphazard process is emerging across the country.^9,10

Final Thoughts

These examples of acne medication access and cost quandaries serve to embody the daily problem-solving that dermatologists execute as part of their growing administrative and economic duties. They also represent worthy efforts to consider on behalf of patients, their pocketbooks, and the prudent use of their dermatologists’ time.

We are fortunate to have plentiful acne treatment options available that cater to each patient’s clinical examination, predispositions, and triggers, but the choices are daunting amidst the vast prescription and over-the-counter (OTC) topicals available along with disparate insurance and cost nuances. In addition, when prescribing generic oral therapies, it is complicated to parse out regional differences in price, supply, and insurance coverage to advocate best for each patient and land upon the delicate balance between efficacy, safety, and financial stewardship, both at an individual and community level. I will outline some challenges and solutions to the management of acne amidst these complicated factors.

Oral Therapies

For isotretinoin, generic choices, cost, and tiering within insurance plans are perpetual moving targets despite the drug being the only member of its class.¹ Prescriber resources include tandem searches of electronic medical record price estimates within each insurance formulary, individual pharmacy search engines, and compilation mobile applications such as GoodRx to select the most affordable version for each patient. As an example of a regional trend, isotretinoin generic coverage by one provider in Pennsylvania shifted earlier this year so that every patient, whether new to isotretinoin or midcourse, required a new prior authorization with more stringent coverage requirements including failure of 2 oral antibiotics. Swiftly thereafter, efforts across the state driven by the Pennsylvania Academy of Dermatology and Dermatologic Surgery and its members and fueled by poignant patient vignettes about fragmented and substandard patient care helped to reverse this policy and remove the prior authorization mandate.²

Tetracyclines have experienced broad cost swings, mostly based on disruption of manufacturing at the limited number of distribution sites in the United States. In 2011, a tetracycline shortage arose due to a major manufacturer’s recall³ and persisted with subsequent material shortages, as doxycycline became the preferred and cheaper member of the class. Doxycycline price tag hikes then occurred following Hurricane Sandy when an East Coast manufacturing site was damaged.³ Spironolactone backorder also has been frequent due to recent raw material shortages and delays in production,³ forcing pharmacies to refill small amounts of medication in various dosage forms despite patients owing the same copayment per prescription.

Topical Therapies

Topical retinoid prescription affordability has always been fraught with difficulty owing to age cutoffs because it is often restricted to patients younger than 25 or 40 years, depending on the plan,^4,5 but the availability of adapalene gel 0.1% as an OTC preparation in 2016 has broadened retinoid access and use.⁶ Prescription benzoyl peroxide (BPO) products alone or in combination with retinoids or topical antibiotics (or other combination topical therapies) comprise a large number of branded prescriptions often not covered by insurance or are only affordable using proprietary and intermittently available coupon cards (eg, BPO-clindamycin, clindamycin-tretinoin, BPO-adapalene); therefore, prescribers tend to dispense the individual ingredients and instruct the patient to compound them at home. Furthermore, BPO products can be purchased in effective concentrations as OTC products, and patients looking to procure more affordable, albeit less effective, topical retinoids that also have less irritation potential reach for OTC nightly retinol creams nestled in the antiaging section of the pharmacy.⁷

Opportunities to be involved in the larger scaffold of patient advocacy also are plentiful at the state and national levels. For example, with the support of dermatology state societies and the American Academy of Dermatology Association, Pennsylvania House Bill 2211⁸ and similar bills in other states call for reversal of the gag clause that prevents pharmacists from disclosing the best medication price to patients. Also guided by the American Academy of Dermatology Association, prior authorization model legislation to promote transparency across insurers in this haphazard process is emerging across the country.^9,10

Final Thoughts

These examples of acne medication access and cost quandaries serve to embody the daily problem-solving that dermatologists execute as part of their growing administrative and economic duties. They also represent worthy efforts to consider on behalf of patients, their pocketbooks, and the prudent use of their dermatologists’ time.

A 2005 update in Medicare reimbursement policy had a modest effect on the use of implantable cardioverter defibrillators for primary prevention, but it took a whistle-blower and a federal lawsuit to bring the numbers down substantially.

Usage dropped just slightly from 2007 to 2009, after Medicare updated its appropriate use criteria, Nihar R. Desai, MD, MPH, and his colleagues reported in JAMA. From 2010 to 2011, after the Department of Justice suit became public knowledge, the declines were significantly greater: 7.4% in hospitals that eventually settled for a total of $280 million, and 4.7% in hospitals that weren’t named in the suit.

The government launched the suit in 2010, after a whistle-blower used Medicare data to allege that many hospitals weren’t waiting the appropriate amount of time to implant an implantable cardioverter defibrillator (ICD) after a heart attack or coronary revascularization, wrote Dr. Desai of Yale University, New Haven, Conn., and his team. These procedures would have been against the 2005 Centers for Medicare & Medicaid Services National Coverage Determination (NCD), which required delaying implantation for 40 days after a heart attack and 90 days after a revascularization.

Just a year after the suit was filed, an independent investigator concluded that 22.5% of the ICDs implanted from 2006 to 2009 for primary prevention were not evidence based.

Dr. Desai and his coauthors used CMS data to examine changes in the proportion of primary-prevention ICD implantations at hospitals that eventually settled the suit, and those that did not. The study spanned 2007-2015 and comprised 1,809 U.S. hospitals in the National Cardiovascular Data Registry ICD Registry; of these, 452 hospitals that had done 99,591 procedures reached settlements.

After the steeper drops in 2010 and 2011, the number of procedures leveled off. From July 2011 to 2015, the proportions of ICDs not meeting the NCD criteria were similar and stable in both hospital settlement groups, with an annual change of −0.5% for settlement hospitals and −0.4% for nonsettlement hospitals, the team wrote.

Despite the changes, there was “persistent variation” among hospitals, with more than 14% of the primary-prevention ICDs not meeting NCD criteria at some of the worst-performing hospitals.

The decreases weren’t just in Medicare beneficiaries, though. Hospitals were rethinking this indication for ICD use in everyone, although the investigators found no evidence that the changing clinical landscape endangered the health of patients.

“The analyses of secondary prevention ICDs do not suggest that access to necessary procedures was negatively affected by the investigation. … These analyses offer some reassurance, but further research into hospital responses to the investigation could offer additional insights about possible unintended consequences,” the investigators wrote.

The study was sponsored by the Agency for Healthcare Research and Quality. Dr. Desai had no financial disclosures.

[email protected]

SOURCE: Desai NR et al. JAMA. 2018; 320: 63-71.

A 2005 update in Medicare reimbursement policy had a modest effect on the use of implantable cardioverter defibrillators for primary prevention, but it took a whistle-blower and a federal lawsuit to bring the numbers down substantially.

Usage dropped just slightly from 2007 to 2009, after Medicare updated its appropriate use criteria, Nihar R. Desai, MD, MPH, and his colleagues reported in JAMA. From 2010 to 2011, after the Department of Justice suit became public knowledge, the declines were significantly greater: 7.4% in hospitals that eventually settled for a total of $280 million, and 4.7% in hospitals that weren’t named in the suit.

The government launched the suit in 2010, after a whistle-blower used Medicare data to allege that many hospitals weren’t waiting the appropriate amount of time to implant an implantable cardioverter defibrillator (ICD) after a heart attack or coronary revascularization, wrote Dr. Desai of Yale University, New Haven, Conn., and his team. These procedures would have been against the 2005 Centers for Medicare & Medicaid Services National Coverage Determination (NCD), which required delaying implantation for 40 days after a heart attack and 90 days after a revascularization.

Just a year after the suit was filed, an independent investigator concluded that 22.5% of the ICDs implanted from 2006 to 2009 for primary prevention were not evidence based.

Dr. Desai and his coauthors used CMS data to examine changes in the proportion of primary-prevention ICD implantations at hospitals that eventually settled the suit, and those that did not. The study spanned 2007-2015 and comprised 1,809 U.S. hospitals in the National Cardiovascular Data Registry ICD Registry; of these, 452 hospitals that had done 99,591 procedures reached settlements.

After the steeper drops in 2010 and 2011, the number of procedures leveled off. From July 2011 to 2015, the proportions of ICDs not meeting the NCD criteria were similar and stable in both hospital settlement groups, with an annual change of −0.5% for settlement hospitals and −0.4% for nonsettlement hospitals, the team wrote.

Despite the changes, there was “persistent variation” among hospitals, with more than 14% of the primary-prevention ICDs not meeting NCD criteria at some of the worst-performing hospitals.

The decreases weren’t just in Medicare beneficiaries, though. Hospitals were rethinking this indication for ICD use in everyone, although the investigators found no evidence that the changing clinical landscape endangered the health of patients.

“The analyses of secondary prevention ICDs do not suggest that access to necessary procedures was negatively affected by the investigation. … These analyses offer some reassurance, but further research into hospital responses to the investigation could offer additional insights about possible unintended consequences,” the investigators wrote.

The study was sponsored by the Agency for Healthcare Research and Quality. Dr. Desai had no financial disclosures.

[email protected]

SOURCE: Desai NR et al. JAMA. 2018; 320: 63-71.

A 2005 update in Medicare reimbursement policy had a modest effect on the use of implantable cardioverter defibrillators for primary prevention, but it took a whistle-blower and a federal lawsuit to bring the numbers down substantially.

Usage dropped just slightly from 2007 to 2009, after Medicare updated its appropriate use criteria, Nihar R. Desai, MD, MPH, and his colleagues reported in JAMA. From 2010 to 2011, after the Department of Justice suit became public knowledge, the declines were significantly greater: 7.4% in hospitals that eventually settled for a total of $280 million, and 4.7% in hospitals that weren’t named in the suit.

The government launched the suit in 2010, after a whistle-blower used Medicare data to allege that many hospitals weren’t waiting the appropriate amount of time to implant an implantable cardioverter defibrillator (ICD) after a heart attack or coronary revascularization, wrote Dr. Desai of Yale University, New Haven, Conn., and his team. These procedures would have been against the 2005 Centers for Medicare & Medicaid Services National Coverage Determination (NCD), which required delaying implantation for 40 days after a heart attack and 90 days after a revascularization.

Just a year after the suit was filed, an independent investigator concluded that 22.5% of the ICDs implanted from 2006 to 2009 for primary prevention were not evidence based.

Dr. Desai and his coauthors used CMS data to examine changes in the proportion of primary-prevention ICD implantations at hospitals that eventually settled the suit, and those that did not. The study spanned 2007-2015 and comprised 1,809 U.S. hospitals in the National Cardiovascular Data Registry ICD Registry; of these, 452 hospitals that had done 99,591 procedures reached settlements.

After the steeper drops in 2010 and 2011, the number of procedures leveled off. From July 2011 to 2015, the proportions of ICDs not meeting the NCD criteria were similar and stable in both hospital settlement groups, with an annual change of −0.5% for settlement hospitals and −0.4% for nonsettlement hospitals, the team wrote.

Despite the changes, there was “persistent variation” among hospitals, with more than 14% of the primary-prevention ICDs not meeting NCD criteria at some of the worst-performing hospitals.

The decreases weren’t just in Medicare beneficiaries, though. Hospitals were rethinking this indication for ICD use in everyone, although the investigators found no evidence that the changing clinical landscape endangered the health of patients.

“The analyses of secondary prevention ICDs do not suggest that access to necessary procedures was negatively affected by the investigation. … These analyses offer some reassurance, but further research into hospital responses to the investigation could offer additional insights about possible unintended consequences,” the investigators wrote.

The study was sponsored by the Agency for Healthcare Research and Quality. Dr. Desai had no financial disclosures.

[email protected]

SOURCE: Desai NR et al. JAMA. 2018; 320: 63-71.

STOCKHOLM – Patients with chronic lymphocytic leukemia (CLL) who experience relapse after therapy with a B-cell receptor signaling inhibitor tend to have a swiftly progressive disease course that requires immediate intervention. For these patients, a rapid venetoclax dose-escalation protocol may be a safe way to quickly regain disease control, and possibly bridge to salvage therapies, investigators reported.

Of 15 patients with CLL who relapsed after treatment with a B-cell receptor inhibitor (BCRi), all were able to get to their target dose of venetoclax under close inpatient monitoring at a median of 12 days, compared with the 35 days usually required for venetoclax dose escalation, reported Farrukh T. Awan, MD, of Ohio State University Comprehensive Cancer Center in Columbus, and his colleagues.

Only two patients developed clinical tumor lysis syndrome (TLS), a common occurrence with venetoclax therapy, and this adverse event was manageable, Dr. Awan said at the annual congress of the European Hematology Association.

“The reason why we have been doing a slow ramp up on venetoclax is the original toxicity issues that we saw early on,” he said in an interview. “But unfortunately, a lot of patients are progressing on these new agents and have very rapid disease progression, and what we have seen is that if you stop the ibrutinib, the disease progresses very quickly, and by the time they can get up to the effective dose of venetoclax, they’re too sick to continue, or they might even die from disease progression.”

Neil Osterweil/MDedge News

The incidence of clinical TLS was 13.2%, occurring in two patients, one at the initial 20-mg dose, and one at the 200-mg dose level. Another five patients had asymptomatic TLS. Other treatment-related adverse events were anemia in seven patients, neutropenia in six patients, thrombocytopenia in five patients, and lung infection in one patient.

Twelve patients had a partial response, one had stable disease, and two had progressive disease. The mean time to best response was 71 days.

One-year progression-free survival was 49%, and 1-year overall survival was 68%.

The investigators found that for patients who still have some disease control with a BCRi, it may be possible to keep them on that drug while transitioning to venetoclax. The rapid dose escalation protocol should only be attempted in highly experience comprehensive cancer centers, Dr. Awan said.

“Under very close monitoring in an experienced inpatient setting, where the nurses are very used to doing this on a weekly basis in a very high volume center, I think that our data show that we could do this without affecting toxicity significantly or mortality,” he said.

Venetoclax therapy could buy enough time for patients to bridge to other options, such as chimeric antigen receptor (CAR) T-cell therapy or allogeneic stem cell transplant, he noted.

“But if we had waited 4 weeks, most of these patients would not have made it,” he said.

The study was internally funded. Dr. Awan reported research funding from Gilead, Pharmacyclics, AbbVie, and Janssen.

SOURCE: Koenig K et al. EHA Congress, Abstract PF357.

STOCKHOLM – Patients with chronic lymphocytic leukemia (CLL) who experience relapse after therapy with a B-cell receptor signaling inhibitor tend to have a swiftly progressive disease course that requires immediate intervention. For these patients, a rapid venetoclax dose-escalation protocol may be a safe way to quickly regain disease control, and possibly bridge to salvage therapies, investigators reported.

Of 15 patients with CLL who relapsed after treatment with a B-cell receptor inhibitor (BCRi), all were able to get to their target dose of venetoclax under close inpatient monitoring at a median of 12 days, compared with the 35 days usually required for venetoclax dose escalation, reported Farrukh T. Awan, MD, of Ohio State University Comprehensive Cancer Center in Columbus, and his colleagues.

Only two patients developed clinical tumor lysis syndrome (TLS), a common occurrence with venetoclax therapy, and this adverse event was manageable, Dr. Awan said at the annual congress of the European Hematology Association.

“The reason why we have been doing a slow ramp up on venetoclax is the original toxicity issues that we saw early on,” he said in an interview. “But unfortunately, a lot of patients are progressing on these new agents and have very rapid disease progression, and what we have seen is that if you stop the ibrutinib, the disease progresses very quickly, and by the time they can get up to the effective dose of venetoclax, they’re too sick to continue, or they might even die from disease progression.”

Neil Osterweil/MDedge News

The incidence of clinical TLS was 13.2%, occurring in two patients, one at the initial 20-mg dose, and one at the 200-mg dose level. Another five patients had asymptomatic TLS. Other treatment-related adverse events were anemia in seven patients, neutropenia in six patients, thrombocytopenia in five patients, and lung infection in one patient.

Twelve patients had a partial response, one had stable disease, and two had progressive disease. The mean time to best response was 71 days.

One-year progression-free survival was 49%, and 1-year overall survival was 68%.

The investigators found that for patients who still have some disease control with a BCRi, it may be possible to keep them on that drug while transitioning to venetoclax. The rapid dose escalation protocol should only be attempted in highly experience comprehensive cancer centers, Dr. Awan said.

“Under very close monitoring in an experienced inpatient setting, where the nurses are very used to doing this on a weekly basis in a very high volume center, I think that our data show that we could do this without affecting toxicity significantly or mortality,” he said.

Venetoclax therapy could buy enough time for patients to bridge to other options, such as chimeric antigen receptor (CAR) T-cell therapy or allogeneic stem cell transplant, he noted.

“But if we had waited 4 weeks, most of these patients would not have made it,” he said.

The study was internally funded. Dr. Awan reported research funding from Gilead, Pharmacyclics, AbbVie, and Janssen.

SOURCE: Koenig K et al. EHA Congress, Abstract PF357.

STOCKHOLM – Patients with chronic lymphocytic leukemia (CLL) who experience relapse after therapy with a B-cell receptor signaling inhibitor tend to have a swiftly progressive disease course that requires immediate intervention. For these patients, a rapid venetoclax dose-escalation protocol may be a safe way to quickly regain disease control, and possibly bridge to salvage therapies, investigators reported.

Of 15 patients with CLL who relapsed after treatment with a B-cell receptor inhibitor (BCRi), all were able to get to their target dose of venetoclax under close inpatient monitoring at a median of 12 days, compared with the 35 days usually required for venetoclax dose escalation, reported Farrukh T. Awan, MD, of Ohio State University Comprehensive Cancer Center in Columbus, and his colleagues.

Only two patients developed clinical tumor lysis syndrome (TLS), a common occurrence with venetoclax therapy, and this adverse event was manageable, Dr. Awan said at the annual congress of the European Hematology Association.

“The reason why we have been doing a slow ramp up on venetoclax is the original toxicity issues that we saw early on,” he said in an interview. “But unfortunately, a lot of patients are progressing on these new agents and have very rapid disease progression, and what we have seen is that if you stop the ibrutinib, the disease progresses very quickly, and by the time they can get up to the effective dose of venetoclax, they’re too sick to continue, or they might even die from disease progression.”

Neil Osterweil/MDedge News

The incidence of clinical TLS was 13.2%, occurring in two patients, one at the initial 20-mg dose, and one at the 200-mg dose level. Another five patients had asymptomatic TLS. Other treatment-related adverse events were anemia in seven patients, neutropenia in six patients, thrombocytopenia in five patients, and lung infection in one patient.

Twelve patients had a partial response, one had stable disease, and two had progressive disease. The mean time to best response was 71 days.

One-year progression-free survival was 49%, and 1-year overall survival was 68%.

The investigators found that for patients who still have some disease control with a BCRi, it may be possible to keep them on that drug while transitioning to venetoclax. The rapid dose escalation protocol should only be attempted in highly experience comprehensive cancer centers, Dr. Awan said.

“Under very close monitoring in an experienced inpatient setting, where the nurses are very used to doing this on a weekly basis in a very high volume center, I think that our data show that we could do this without affecting toxicity significantly or mortality,” he said.

Venetoclax therapy could buy enough time for patients to bridge to other options, such as chimeric antigen receptor (CAR) T-cell therapy or allogeneic stem cell transplant, he noted.

“But if we had waited 4 weeks, most of these patients would not have made it,” he said.

The study was internally funded. Dr. Awan reported research funding from Gilead, Pharmacyclics, AbbVie, and Janssen.

SOURCE: Koenig K et al. EHA Congress, Abstract PF357.

When he was about 12, a now 41-year-old man noticed that the skin on his left chest was darkening. For several years afterward, the darkness spread and deepened, and the area became hairy. In young adulthood, he experienced occasional outbreaks of what looked like acne on the lesion; this eventually cleared.

He now finds the hairiness increasingly bothersome, so he shaves the worst parts of it. Upon consulting his primary care provider, he was assured that the lesion is “a birthmark.” Unsatisfied with this answer, the patient took the advice of a friend and decided to consult dermatology.

EXAMINATION
A polygonal, hyperpigmented, hypertrichotic patch covers most of the patient’s left pectoral area. The lateral margin is irregular but well-defined. There is obvious partial regrowth of the shaved hair on the lateral margin, but it stops abruptly at that point.

The breast and surrounding tissue appear normal. No areas of hyperpigmentation or hypertrichosis are seen elsewhere.

What is the diagnosis?

The researchers were also surprised to find that only 30% of the reported lesions occurred above the nipple, because the first descriptions of BN gave the impression that the shoulder and chest were most commonly affected. We now know that BN can also be found on arms and legs.

Usually a benign condition, BN can be associated with skeletal or soft-tissue deformities in the affected area (eg, ipsilateral breast hypoplasia). Malignancies—most notably melanoma—have also been reported with BN but are especially uncommon.

The differential includes the café-au-lait macules of neurofibromatosis, Albright disease, and congenital melanocytic nevus. The history of BN (ie, presentation, hypertrichosis, gender of patient, and distribution) usually allow a clinical diagnosis.

Treatment is limited to laser hair removal or laser removal or reduction of pigment.

TAKE-HOME LEARNING POINTS

• Becker nevus (BN) is far more common in males than females.
• BN typically manifests during puberty, which aligns with the suspected androgenic etiology.
• Though the shoulders and chest are the most commonly affected areas, BNs can also appear on the flank, arms, or legs.
• The lesions are rarely associated with serious pathology; hypoplasia of the ipsilateral breast is the most common of these complications.

When he was about 12, a now 41-year-old man noticed that the skin on his left chest was darkening. For several years afterward, the darkness spread and deepened, and the area became hairy. In young adulthood, he experienced occasional outbreaks of what looked like acne on the lesion; this eventually cleared.

He now finds the hairiness increasingly bothersome, so he shaves the worst parts of it. Upon consulting his primary care provider, he was assured that the lesion is “a birthmark.” Unsatisfied with this answer, the patient took the advice of a friend and decided to consult dermatology.

EXAMINATION
A polygonal, hyperpigmented, hypertrichotic patch covers most of the patient’s left pectoral area. The lateral margin is irregular but well-defined. There is obvious partial regrowth of the shaved hair on the lateral margin, but it stops abruptly at that point.

The breast and surrounding tissue appear normal. No areas of hyperpigmentation or hypertrichosis are seen elsewhere.

What is the diagnosis?

The researchers were also surprised to find that only 30% of the reported lesions occurred above the nipple, because the first descriptions of BN gave the impression that the shoulder and chest were most commonly affected. We now know that BN can also be found on arms and legs.

Usually a benign condition, BN can be associated with skeletal or soft-tissue deformities in the affected area (eg, ipsilateral breast hypoplasia). Malignancies—most notably melanoma—have also been reported with BN but are especially uncommon.

The differential includes the café-au-lait macules of neurofibromatosis, Albright disease, and congenital melanocytic nevus. The history of BN (ie, presentation, hypertrichosis, gender of patient, and distribution) usually allow a clinical diagnosis.

Treatment is limited to laser hair removal or laser removal or reduction of pigment.

TAKE-HOME LEARNING POINTS

• Becker nevus (BN) is far more common in males than females.
• BN typically manifests during puberty, which aligns with the suspected androgenic etiology.
• Though the shoulders and chest are the most commonly affected areas, BNs can also appear on the flank, arms, or legs.
• The lesions are rarely associated with serious pathology; hypoplasia of the ipsilateral breast is the most common of these complications.

When he was about 12, a now 41-year-old man noticed that the skin on his left chest was darkening. For several years afterward, the darkness spread and deepened, and the area became hairy. In young adulthood, he experienced occasional outbreaks of what looked like acne on the lesion; this eventually cleared.

He now finds the hairiness increasingly bothersome, so he shaves the worst parts of it. Upon consulting his primary care provider, he was assured that the lesion is “a birthmark.” Unsatisfied with this answer, the patient took the advice of a friend and decided to consult dermatology.

EXAMINATION
A polygonal, hyperpigmented, hypertrichotic patch covers most of the patient’s left pectoral area. The lateral margin is irregular but well-defined. There is obvious partial regrowth of the shaved hair on the lateral margin, but it stops abruptly at that point.

The breast and surrounding tissue appear normal. No areas of hyperpigmentation or hypertrichosis are seen elsewhere.

What is the diagnosis?

The researchers were also surprised to find that only 30% of the reported lesions occurred above the nipple, because the first descriptions of BN gave the impression that the shoulder and chest were most commonly affected. We now know that BN can also be found on arms and legs.

Usually a benign condition, BN can be associated with skeletal or soft-tissue deformities in the affected area (eg, ipsilateral breast hypoplasia). Malignancies—most notably melanoma—have also been reported with BN but are especially uncommon.

The differential includes the café-au-lait macules of neurofibromatosis, Albright disease, and congenital melanocytic nevus. The history of BN (ie, presentation, hypertrichosis, gender of patient, and distribution) usually allow a clinical diagnosis.

Treatment is limited to laser hair removal or laser removal or reduction of pigment.

TAKE-HOME LEARNING POINTS

• Becker nevus (BN) is far more common in males than females.
• BN typically manifests during puberty, which aligns with the suspected androgenic etiology.
• Though the shoulders and chest are the most commonly affected areas, BNs can also appear on the flank, arms, or legs.
• The lesions are rarely associated with serious pathology; hypoplasia of the ipsilateral breast is the most common of these complications.

New clinical guidelines for pediatric hypertension resulted in increased prevalence of hypertension and improved sensitivity in detecting target organ damage among at-risk youth, according to findings published in Pediatrics.

In a clinical practice guideline (CPG) published in 2017, the American Academy of Pediatrics updated its 2004 guideline to include new reference tables for BP values in addition to new definitions of elevated BP and hypertension, including absolute BP cutoff values for adolescents aged 13 years and older (Pediatrics. 2017 Sep;140[6]:e20173035). This was intended to “emulate the recently updated adult hypertension guidelines and to simplify the process of identifying and classifying hypertension in adolescents,” wrote Michael Khoury, MD, of the Heart Institute at Cincinnati Children’s Hospital Medical Center, and his coauthors.

To evaluate the impact of the new guidelines on the prevalence of hypertension and associations with target organ damage, the investigators used data from a study on obesity and type 2 diabetes in 364 patients aged 10-17 years; 59% were obese, and 30% had type 2 diabetes. Three groups were identified: patients with obesity and type 2 diabetes, patients with obesity but no type 2 diabetes, and healthy (“lean”) controls.

Patients fasted overnight for a minimum of 10 hours, after which body mass index was calculated, blood pressure was taken, and anthropometric, laboratory, echocardiography, and carotid assessments were performed. Average BP measurements were categorized according to the 2004 guideline and to the new CPG.

In carotid ultrasonography assessments, a composite of carotid intima-media thickness was formed from the average of three sites, and a composite carotid intima-media thickness greater than or equal to the 90th percentile of that measured in the lean patients, who were the controls, was considered abnormal. In echocardiography assessments, left ventricular mass (LVM) and LVM index were calculated. Elevated LVM was defined by the pediatric cutoff of LVM index greater than or equal to 38.6 g/m.

For diastolic function, tissue Doppler velocities under the 10th percentile and an average early left ventricular filling/peak early myocardial velocity ratio greater than or equal to the 90th percentile in controls were considered abnormal. Lastly, pulse wave velocity (PWV) was measured to determine arterial stiffness, and a PWV greater than or equal to the 90th percentile for the controls was considered abnormal.

BP classification under the new guideline resulted in an increased prevalence of hypertension at 13% (10% stage 1, 3% stage 2), compared with the 2004 guideline at 8% (6% stage 1, 2% stage 2), with a P value of .007.

Of the 75 patients classified as having elevated BP in the 2004 guideline, 19 (25%) were reclassified as having stage 1 hypertension under the CPG. These 19 patients were older, compared with patients who remained in the elevated blood pressure category (16.5 ± 0.9 vs. 15.5 ± 1.7 years; P = .02). The patients who were reclassified also had higher body mass indexes (38.8 ± 8.2 vs. 33.6 ± 7.4; P = .01) and diastolic blood pressures (76.5 mm Hg ± 8.7 vs. 62.1 ± 12.2 mm Hg; P less than .001), Dr. Khoury and his colleagues reported.

Reclassification to a higher BP category was associated with increased odds of an abnormal target organ damage (TOD) values, and both guidelines produced similar odds, “suggesting that the two guidelines produce similar associations with TOD,” the authors wrote. Reclassification based on the CPG definition accounted for 31% of patients with increased LVM, compared with 20% as defined in the 2004 guideline (P less than .001), and for 33% of patients with abnormal PWV, compared with 23% in the 2004 guideline, suggesting improved sensitivity of hypertension categorization in detecting LVM. A similar effect was seen in other measures of TOD, the authors noted.

The findings suggest that, combined with the increased prevalence of hypertension under the new guidelines, “the CPG may contribute to an increased detection of abnormal LVM and other measures of TOD,” the authors wrote. “This, in turn, may contribute to risk stratification in clinical decision making for youth presenting with BP concerns,” they concluded.

The study was supported by a National Institutes of Health grant. The authors had no relevant disclosures.

SOURCE: Khoury M et al. Pediatrics. 2018 Jul 5. doi: 10.1542/peds.2018-0245.

New clinical guidelines for pediatric hypertension resulted in increased prevalence of hypertension and improved sensitivity in detecting target organ damage among at-risk youth, according to findings published in Pediatrics.

In a clinical practice guideline (CPG) published in 2017, the American Academy of Pediatrics updated its 2004 guideline to include new reference tables for BP values in addition to new definitions of elevated BP and hypertension, including absolute BP cutoff values for adolescents aged 13 years and older (Pediatrics. 2017 Sep;140[6]:e20173035). This was intended to “emulate the recently updated adult hypertension guidelines and to simplify the process of identifying and classifying hypertension in adolescents,” wrote Michael Khoury, MD, of the Heart Institute at Cincinnati Children’s Hospital Medical Center, and his coauthors.

To evaluate the impact of the new guidelines on the prevalence of hypertension and associations with target organ damage, the investigators used data from a study on obesity and type 2 diabetes in 364 patients aged 10-17 years; 59% were obese, and 30% had type 2 diabetes. Three groups were identified: patients with obesity and type 2 diabetes, patients with obesity but no type 2 diabetes, and healthy (“lean”) controls.

Patients fasted overnight for a minimum of 10 hours, after which body mass index was calculated, blood pressure was taken, and anthropometric, laboratory, echocardiography, and carotid assessments were performed. Average BP measurements were categorized according to the 2004 guideline and to the new CPG.

In carotid ultrasonography assessments, a composite of carotid intima-media thickness was formed from the average of three sites, and a composite carotid intima-media thickness greater than or equal to the 90th percentile of that measured in the lean patients, who were the controls, was considered abnormal. In echocardiography assessments, left ventricular mass (LVM) and LVM index were calculated. Elevated LVM was defined by the pediatric cutoff of LVM index greater than or equal to 38.6 g/m.

For diastolic function, tissue Doppler velocities under the 10th percentile and an average early left ventricular filling/peak early myocardial velocity ratio greater than or equal to the 90th percentile in controls were considered abnormal. Lastly, pulse wave velocity (PWV) was measured to determine arterial stiffness, and a PWV greater than or equal to the 90th percentile for the controls was considered abnormal.

BP classification under the new guideline resulted in an increased prevalence of hypertension at 13% (10% stage 1, 3% stage 2), compared with the 2004 guideline at 8% (6% stage 1, 2% stage 2), with a P value of .007.

Of the 75 patients classified as having elevated BP in the 2004 guideline, 19 (25%) were reclassified as having stage 1 hypertension under the CPG. These 19 patients were older, compared with patients who remained in the elevated blood pressure category (16.5 ± 0.9 vs. 15.5 ± 1.7 years; P = .02). The patients who were reclassified also had higher body mass indexes (38.8 ± 8.2 vs. 33.6 ± 7.4; P = .01) and diastolic blood pressures (76.5 mm Hg ± 8.7 vs. 62.1 ± 12.2 mm Hg; P less than .001), Dr. Khoury and his colleagues reported.

Reclassification to a higher BP category was associated with increased odds of an abnormal target organ damage (TOD) values, and both guidelines produced similar odds, “suggesting that the two guidelines produce similar associations with TOD,” the authors wrote. Reclassification based on the CPG definition accounted for 31% of patients with increased LVM, compared with 20% as defined in the 2004 guideline (P less than .001), and for 33% of patients with abnormal PWV, compared with 23% in the 2004 guideline, suggesting improved sensitivity of hypertension categorization in detecting LVM. A similar effect was seen in other measures of TOD, the authors noted.

The findings suggest that, combined with the increased prevalence of hypertension under the new guidelines, “the CPG may contribute to an increased detection of abnormal LVM and other measures of TOD,” the authors wrote. “This, in turn, may contribute to risk stratification in clinical decision making for youth presenting with BP concerns,” they concluded.

The study was supported by a National Institutes of Health grant. The authors had no relevant disclosures.

SOURCE: Khoury M et al. Pediatrics. 2018 Jul 5. doi: 10.1542/peds.2018-0245.

New clinical guidelines for pediatric hypertension resulted in increased prevalence of hypertension and improved sensitivity in detecting target organ damage among at-risk youth, according to findings published in Pediatrics.

In a clinical practice guideline (CPG) published in 2017, the American Academy of Pediatrics updated its 2004 guideline to include new reference tables for BP values in addition to new definitions of elevated BP and hypertension, including absolute BP cutoff values for adolescents aged 13 years and older (Pediatrics. 2017 Sep;140[6]:e20173035). This was intended to “emulate the recently updated adult hypertension guidelines and to simplify the process of identifying and classifying hypertension in adolescents,” wrote Michael Khoury, MD, of the Heart Institute at Cincinnati Children’s Hospital Medical Center, and his coauthors.

To evaluate the impact of the new guidelines on the prevalence of hypertension and associations with target organ damage, the investigators used data from a study on obesity and type 2 diabetes in 364 patients aged 10-17 years; 59% were obese, and 30% had type 2 diabetes. Three groups were identified: patients with obesity and type 2 diabetes, patients with obesity but no type 2 diabetes, and healthy (“lean”) controls.

Patients fasted overnight for a minimum of 10 hours, after which body mass index was calculated, blood pressure was taken, and anthropometric, laboratory, echocardiography, and carotid assessments were performed. Average BP measurements were categorized according to the 2004 guideline and to the new CPG.

In carotid ultrasonography assessments, a composite of carotid intima-media thickness was formed from the average of three sites, and a composite carotid intima-media thickness greater than or equal to the 90th percentile of that measured in the lean patients, who were the controls, was considered abnormal. In echocardiography assessments, left ventricular mass (LVM) and LVM index were calculated. Elevated LVM was defined by the pediatric cutoff of LVM index greater than or equal to 38.6 g/m.

For diastolic function, tissue Doppler velocities under the 10th percentile and an average early left ventricular filling/peak early myocardial velocity ratio greater than or equal to the 90th percentile in controls were considered abnormal. Lastly, pulse wave velocity (PWV) was measured to determine arterial stiffness, and a PWV greater than or equal to the 90th percentile for the controls was considered abnormal.

BP classification under the new guideline resulted in an increased prevalence of hypertension at 13% (10% stage 1, 3% stage 2), compared with the 2004 guideline at 8% (6% stage 1, 2% stage 2), with a P value of .007.

Of the 75 patients classified as having elevated BP in the 2004 guideline, 19 (25%) were reclassified as having stage 1 hypertension under the CPG. These 19 patients were older, compared with patients who remained in the elevated blood pressure category (16.5 ± 0.9 vs. 15.5 ± 1.7 years; P = .02). The patients who were reclassified also had higher body mass indexes (38.8 ± 8.2 vs. 33.6 ± 7.4; P = .01) and diastolic blood pressures (76.5 mm Hg ± 8.7 vs. 62.1 ± 12.2 mm Hg; P less than .001), Dr. Khoury and his colleagues reported.

Reclassification to a higher BP category was associated with increased odds of an abnormal target organ damage (TOD) values, and both guidelines produced similar odds, “suggesting that the two guidelines produce similar associations with TOD,” the authors wrote. Reclassification based on the CPG definition accounted for 31% of patients with increased LVM, compared with 20% as defined in the 2004 guideline (P less than .001), and for 33% of patients with abnormal PWV, compared with 23% in the 2004 guideline, suggesting improved sensitivity of hypertension categorization in detecting LVM. A similar effect was seen in other measures of TOD, the authors noted.

The findings suggest that, combined with the increased prevalence of hypertension under the new guidelines, “the CPG may contribute to an increased detection of abnormal LVM and other measures of TOD,” the authors wrote. “This, in turn, may contribute to risk stratification in clinical decision making for youth presenting with BP concerns,” they concluded.

The study was supported by a National Institutes of Health grant. The authors had no relevant disclosures.

SOURCE: Khoury M et al. Pediatrics. 2018 Jul 5. doi: 10.1542/peds.2018-0245.

When patients lack typical symptoms of gastroesophageal reflux disease (GERD) and have extraesophageal symptoms, ENT, allergy, and pulmonary work-ups are “essential and often should be performed initially,” experts note in an American Gastroenterological Association clinical practice update.

Extraesophageal symptoms often are unrelated to GERD or are multifactorial, wrote Michael F. Vaezi, MD, PhD, of Vanderbilt University Medical Center in Nashville, Tenn., and his associates in Clinical Gastroenterology and Hepatology. Gastroenterologists often are asked to look for reflux as the cause of extraesophageal symptoms before other etiologies have been ruled out.

Proposed extraesophageal manifestations of GERD range from chronic throat clearing and dysphonia to otitis, pulmonary fibrosis, laryngeal cancer, and even lung transplant rejection. Stronger evidence links GERD with symptoms of asthma, cough, and hoarseness, the experts note. “When less stringent criteria are used, the attributions are broader and could include sore throat, sinusitis, ear pain, and pulmonary fibrosis.”

When asked to assess whether GERD is causing extraesophageal symptoms, consider the “constellation” of patient presentation, test results, and treatment response, according to the clinical practice update. No diagnostic tests “unequivocally link any suspected extraesophageal symptom to GERD.” For patients who have both extraesophageal symptoms and typical symptoms of GERD, the authors suggest an evaluator regimen of 6-8 weeks of empiric, aggressive (twice-daily) proton pump inhibitor (PPI) therapy. If aggressive acid suppression therapy appears to improve extra­esophageal symptoms, patients should be titrated to the lowest effective treatment dose.If symptoms persist despite an aggressive trial of a PPI, and patients have a body mass index under 25, and a seemingly low probability of GERD, then the experts recommend pH testing “off” therapy and seeking other etiologies for extraesophageal symptoms. If symptoms persist and a patients’ BMI exceeds 25 with a high suspicion of GERD, they recommend evaluations for concomitant asthma or lung disease. If these work-ups are positive, they recommend multichannel intraluminal impedance testing or pH monitoring on treatment.

The clinical practice update strongly discourages surgical treatment of extraesophageal GERD symptoms except in specific populations, such as when patients have objective signs of treatment-refractory GERD and have not responded to comprehensive therapy for other possible causes of extraesophageal symptoms. Recent data suggest that surgery can benefit patients with confirmed structural defects, such as hiatal hernia, which are causing symptomatic, volume-based regurgitation, the experts note. Ideally, these patients should first undergo pH and impedance monitoring to objectively measure the effects of reflux. Additionally, surgical fundoplication “might be beneficial” for patients whose extraesophageal symptoms clearly have responded to PPI therapy but who refuse long-term PPI therapy or who develop unacceptable side effects.

The practice update also extensively discusses the role of testing to evaluate the role of GERD in extraesophageal symptoms. Barium esophagography is insensitive for GERD and is useful only for evaluating dysphagia and the size and type of a hiatal hernia, the experts note. Abnormal laryngoscopy or pharyngoscopic findings are more useful but should not be the “initial driving force” behind a GERD diagnosis and do not necessarily link GERD to extraesophageal symptoms. Likewise, esophagogastroduodenoscopy can identify esophagitis, which signifies GERD but does not establish it as etiologic.

Positive ambulatory pH or impedance monitoring or pharyngeal pH tests also do not definitively link reflux to suspected extraesophageal symptoms, the experts note. They suggest considering “on” therapy monitoring to evaluate treatment efficacy and to time reflux events relative to symptoms in patients with esophagitis, Barrett’s esophagus, or a large hiatal hernia. Conversely, they recommend considering “off” treatment testing to rule out GERD in patients who have no history of confirmed or suspected reflux and who have not responded to PPI therapy.

Novel tests, such as salivary pepsin and mucosal impedance, have “no clear role in establishing GERD as the cause of extraesophageal symptoms,” the experts emphasize. Clinician scientists also debate the exact pathophysiology of extraesophageal GERD sequelae. While chronic exposure to gastric refluxate clearly can harm proximal structures such as the pharynx, larynx, and bronchial tree, it remains unclear how much acid is necessary to cause injury and whether bile, pepsin, or neurogenic stimulation play a role.

Dr. Vaezi reported having no conflicts of interest. Senior author Frank Zerbib, MD, PhD, reported receiving devices for research purposes from Medtronic and Sandhill Scientific.
 

SOURCE: Vaezi MF et al. Clin Gastroenterol Hepatol. 2018 Feb 7. doi: 10.1016/j.cgh.2018.02.001.

When patients lack typical symptoms of gastroesophageal reflux disease (GERD) and have extraesophageal symptoms, ENT, allergy, and pulmonary work-ups are “essential and often should be performed initially,” experts note in an American Gastroenterological Association clinical practice update.

Extraesophageal symptoms often are unrelated to GERD or are multifactorial, wrote Michael F. Vaezi, MD, PhD, of Vanderbilt University Medical Center in Nashville, Tenn., and his associates in Clinical Gastroenterology and Hepatology. Gastroenterologists often are asked to look for reflux as the cause of extraesophageal symptoms before other etiologies have been ruled out.

Proposed extraesophageal manifestations of GERD range from chronic throat clearing and dysphonia to otitis, pulmonary fibrosis, laryngeal cancer, and even lung transplant rejection. Stronger evidence links GERD with symptoms of asthma, cough, and hoarseness, the experts note. “When less stringent criteria are used, the attributions are broader and could include sore throat, sinusitis, ear pain, and pulmonary fibrosis.”

When asked to assess whether GERD is causing extraesophageal symptoms, consider the “constellation” of patient presentation, test results, and treatment response, according to the clinical practice update. No diagnostic tests “unequivocally link any suspected extraesophageal symptom to GERD.” For patients who have both extraesophageal symptoms and typical symptoms of GERD, the authors suggest an evaluator regimen of 6-8 weeks of empiric, aggressive (twice-daily) proton pump inhibitor (PPI) therapy. If aggressive acid suppression therapy appears to improve extra­esophageal symptoms, patients should be titrated to the lowest effective treatment dose.If symptoms persist despite an aggressive trial of a PPI, and patients have a body mass index under 25, and a seemingly low probability of GERD, then the experts recommend pH testing “off” therapy and seeking other etiologies for extraesophageal symptoms. If symptoms persist and a patients’ BMI exceeds 25 with a high suspicion of GERD, they recommend evaluations for concomitant asthma or lung disease. If these work-ups are positive, they recommend multichannel intraluminal impedance testing or pH monitoring on treatment.

The clinical practice update strongly discourages surgical treatment of extraesophageal GERD symptoms except in specific populations, such as when patients have objective signs of treatment-refractory GERD and have not responded to comprehensive therapy for other possible causes of extraesophageal symptoms. Recent data suggest that surgery can benefit patients with confirmed structural defects, such as hiatal hernia, which are causing symptomatic, volume-based regurgitation, the experts note. Ideally, these patients should first undergo pH and impedance monitoring to objectively measure the effects of reflux. Additionally, surgical fundoplication “might be beneficial” for patients whose extraesophageal symptoms clearly have responded to PPI therapy but who refuse long-term PPI therapy or who develop unacceptable side effects.

The practice update also extensively discusses the role of testing to evaluate the role of GERD in extraesophageal symptoms. Barium esophagography is insensitive for GERD and is useful only for evaluating dysphagia and the size and type of a hiatal hernia, the experts note. Abnormal laryngoscopy or pharyngoscopic findings are more useful but should not be the “initial driving force” behind a GERD diagnosis and do not necessarily link GERD to extraesophageal symptoms. Likewise, esophagogastroduodenoscopy can identify esophagitis, which signifies GERD but does not establish it as etiologic.

Positive ambulatory pH or impedance monitoring or pharyngeal pH tests also do not definitively link reflux to suspected extraesophageal symptoms, the experts note. They suggest considering “on” therapy monitoring to evaluate treatment efficacy and to time reflux events relative to symptoms in patients with esophagitis, Barrett’s esophagus, or a large hiatal hernia. Conversely, they recommend considering “off” treatment testing to rule out GERD in patients who have no history of confirmed or suspected reflux and who have not responded to PPI therapy.

Novel tests, such as salivary pepsin and mucosal impedance, have “no clear role in establishing GERD as the cause of extraesophageal symptoms,” the experts emphasize. Clinician scientists also debate the exact pathophysiology of extraesophageal GERD sequelae. While chronic exposure to gastric refluxate clearly can harm proximal structures such as the pharynx, larynx, and bronchial tree, it remains unclear how much acid is necessary to cause injury and whether bile, pepsin, or neurogenic stimulation play a role.

Dr. Vaezi reported having no conflicts of interest. Senior author Frank Zerbib, MD, PhD, reported receiving devices for research purposes from Medtronic and Sandhill Scientific.
 

SOURCE: Vaezi MF et al. Clin Gastroenterol Hepatol. 2018 Feb 7. doi: 10.1016/j.cgh.2018.02.001.

When patients lack typical symptoms of gastroesophageal reflux disease (GERD) and have extraesophageal symptoms, ENT, allergy, and pulmonary work-ups are “essential and often should be performed initially,” experts note in an American Gastroenterological Association clinical practice update.

Extraesophageal symptoms often are unrelated to GERD or are multifactorial, wrote Michael F. Vaezi, MD, PhD, of Vanderbilt University Medical Center in Nashville, Tenn., and his associates in Clinical Gastroenterology and Hepatology. Gastroenterologists often are asked to look for reflux as the cause of extraesophageal symptoms before other etiologies have been ruled out.

Proposed extraesophageal manifestations of GERD range from chronic throat clearing and dysphonia to otitis, pulmonary fibrosis, laryngeal cancer, and even lung transplant rejection. Stronger evidence links GERD with symptoms of asthma, cough, and hoarseness, the experts note. “When less stringent criteria are used, the attributions are broader and could include sore throat, sinusitis, ear pain, and pulmonary fibrosis.”

When asked to assess whether GERD is causing extraesophageal symptoms, consider the “constellation” of patient presentation, test results, and treatment response, according to the clinical practice update. No diagnostic tests “unequivocally link any suspected extraesophageal symptom to GERD.” For patients who have both extraesophageal symptoms and typical symptoms of GERD, the authors suggest an evaluator regimen of 6-8 weeks of empiric, aggressive (twice-daily) proton pump inhibitor (PPI) therapy. If aggressive acid suppression therapy appears to improve extra­esophageal symptoms, patients should be titrated to the lowest effective treatment dose.If symptoms persist despite an aggressive trial of a PPI, and patients have a body mass index under 25, and a seemingly low probability of GERD, then the experts recommend pH testing “off” therapy and seeking other etiologies for extraesophageal symptoms. If symptoms persist and a patients’ BMI exceeds 25 with a high suspicion of GERD, they recommend evaluations for concomitant asthma or lung disease. If these work-ups are positive, they recommend multichannel intraluminal impedance testing or pH monitoring on treatment.

The clinical practice update strongly discourages surgical treatment of extraesophageal GERD symptoms except in specific populations, such as when patients have objective signs of treatment-refractory GERD and have not responded to comprehensive therapy for other possible causes of extraesophageal symptoms. Recent data suggest that surgery can benefit patients with confirmed structural defects, such as hiatal hernia, which are causing symptomatic, volume-based regurgitation, the experts note. Ideally, these patients should first undergo pH and impedance monitoring to objectively measure the effects of reflux. Additionally, surgical fundoplication “might be beneficial” for patients whose extraesophageal symptoms clearly have responded to PPI therapy but who refuse long-term PPI therapy or who develop unacceptable side effects.

The practice update also extensively discusses the role of testing to evaluate the role of GERD in extraesophageal symptoms. Barium esophagography is insensitive for GERD and is useful only for evaluating dysphagia and the size and type of a hiatal hernia, the experts note. Abnormal laryngoscopy or pharyngoscopic findings are more useful but should not be the “initial driving force” behind a GERD diagnosis and do not necessarily link GERD to extraesophageal symptoms. Likewise, esophagogastroduodenoscopy can identify esophagitis, which signifies GERD but does not establish it as etiologic.

Positive ambulatory pH or impedance monitoring or pharyngeal pH tests also do not definitively link reflux to suspected extraesophageal symptoms, the experts note. They suggest considering “on” therapy monitoring to evaluate treatment efficacy and to time reflux events relative to symptoms in patients with esophagitis, Barrett’s esophagus, or a large hiatal hernia. Conversely, they recommend considering “off” treatment testing to rule out GERD in patients who have no history of confirmed or suspected reflux and who have not responded to PPI therapy.

Novel tests, such as salivary pepsin and mucosal impedance, have “no clear role in establishing GERD as the cause of extraesophageal symptoms,” the experts emphasize. Clinician scientists also debate the exact pathophysiology of extraesophageal GERD sequelae. While chronic exposure to gastric refluxate clearly can harm proximal structures such as the pharynx, larynx, and bronchial tree, it remains unclear how much acid is necessary to cause injury and whether bile, pepsin, or neurogenic stimulation play a role.

Dr. Vaezi reported having no conflicts of interest. Senior author Frank Zerbib, MD, PhD, reported receiving devices for research purposes from Medtronic and Sandhill Scientific.
 

SOURCE: Vaezi MF et al. Clin Gastroenterol Hepatol. 2018 Feb 7. doi: 10.1016/j.cgh.2018.02.001.

I write this editorial at the end of June as summer officially begins. Much of the country—my New Mexico home included—is suffering under an unbearable heat wave in which even those without belief pray for rain. Summer for many is associated with vacations, family trips, and happy hours in the swimming pool among other enjoyable activities that provide a welcome and much deserved break from routine and relief from the grind of work and school. In the words of the George Gershwin tune, “Summertime, and the livin’ is easy.”

In stark contrast to this season, where there is more lightness in being, is the heaviness of the news reports about the Department of Veteran Affairs (VA) that have been featured in the media and the federal press. I suspect I am not alone in having a hard time opening those e-mails; feeling once more the weight of failure on the VA and the employees who have dedicated a good part of their careers to its mission. Even for the VA, June has seen an exceptional string of bad press. I ask as you read this column to think about what the adjective bad means in this context. In the conclusion to this column, I will suggest that the meaning is multivalent.

Among the most distressing stories was the USA Today and Boston Globe headline, “Secret VA nursing home ratings hide poor quality of care from the public.”² In an all too predictable sequence, this led justifiably to a cascade of demands from the fifth estate, congressional representatives, the administration, veterans and their families, and watchdog organizations for release of the data, investigation of the allegedly deplorable conditions, and rapid fixes to the problems along with the punishment of the guilty.

As an ethicist I am committed to the principles of transparency and accountability that these entities rightly adjure in the wake of any disclosure of a breach of duty to treat each veteran with the best we have—especially the disabled, elderly, and vulnerable. But I have come to believe that the way in which this cycle of scandal and reaction plays out over and over again in VA facilities across the country, what I call “caring under the microscope,” is actually undermining the righteous goals it seeks to achieve.

I encourage you to try this online. Search for the phrase, “VA under microscope” and see what you get. Briefly read the summary, or the entire story if you have the inclination, and then take a few minutes to reflect on the emotional impact of what you read. Under a microscope is an idiom coined to capture the experience of being the object of close inspection and intense scrutiny. As most everyone knows from their own science education, microscopes magnify images that cannot normally be seen with the human eye, allowing us to observe a more detailed and focused image. The microscope surely helped revolutionize medicine and science. But what effect does such amplified and constant observation have on VA employees?³

For the thousands of staff members who do their job every day with all the empathy and skill, integrity, and dedication they can muster, there is demoralization. Researchers in the health professions describe it as “a feeling state of dejection, hopelessness, and a sense of personal ‘incompetence’ that may be tied to a loss of or threat to one’s own goals or values. It has an existential dimension when beliefs and values about oneself are disconfirmed.”⁴ If you are a nurse assigned to one of VA’s nursing homes, daily striving to ensure patients are clean and comfortable, or a therapist in a continuing living center using all your training to maximize an elder’s mobility and participation in activities, you might well begin to doubt your ability as a professional and question the worth of your work. This is exactly the opposite outcome that the microscopic oversight is intended to attain.

The impact of demoralization on health professionals directly contributes to unprecedented burnout and turnover. Were this not damaging enough, it also has an insidious rippling effect—like contaminated groundwater that poisons where it should be reviving. The humanistic, even spiritual, heart of all the health professions is the relationship between the practitioner and the patient, ideally a relationship of mutual respect and trust. Waves of negative news triggering harsh and unyielding criticism distort even the strongest, purest therapeutic alliances with fear and distrust, just as a microscope not properly focused changes a beautiful image into a blurred muddle.

Worried families of veterans staring at this picture invariably are drawn into the hyper media focus, feeling alarmed and betrayed, even when their loved one may be receiving excellent VA care. In 20 years as a physician and ethicist in VA hospitals, clinics, and community living centers, I know well that bad things happen to good people (both patients and staff). Yet VA patients, families, and staff are seldom offered the wider corrective vision that would note that bad things also happen in other health care institutions and good care is delivered in the VA. Acting Secretary of Veterans Affairs Peter O’Rourke crisply summarized in his response to the nursing home story.⁵

No veteran or any other human being in a VA or any other nursing home should ever be medicated into a zombie state or left alone in pain like those patients reported in the news story. And if the USA Today story improves the care of a single VA patient, then good has been done at least in the short run. Yet we must also take the long view and consider the moral and psychological outcome of prolonged demoralization on the very staff who must carry out the congressional mandates.

In the same time frame as the nursing home scandal, the VA Office of Inspector General also issued a report on the continued understaffing in the VA.⁶ This may be the most concerning aftermath of demoralization. One of my best residents had thought about the VA but in the end made a different choice when he completed his training. When I asked him why he told me, “I am afraid to end up in the newspaper.”

Summer will go by far too quickly. Enjoy it while you can so that with renewed strength we may all search for a better way that the light of truth and heat of power can do what they must while also not withering the spirit of caring that animates the people of the VA.

I write this editorial at the end of June as summer officially begins. Much of the country—my New Mexico home included—is suffering under an unbearable heat wave in which even those without belief pray for rain. Summer for many is associated with vacations, family trips, and happy hours in the swimming pool among other enjoyable activities that provide a welcome and much deserved break from routine and relief from the grind of work and school. In the words of the George Gershwin tune, “Summertime, and the livin’ is easy.”

In stark contrast to this season, where there is more lightness in being, is the heaviness of the news reports about the Department of Veteran Affairs (VA) that have been featured in the media and the federal press. I suspect I am not alone in having a hard time opening those e-mails; feeling once more the weight of failure on the VA and the employees who have dedicated a good part of their careers to its mission. Even for the VA, June has seen an exceptional string of bad press. I ask as you read this column to think about what the adjective bad means in this context. In the conclusion to this column, I will suggest that the meaning is multivalent.

Among the most distressing stories was the USA Today and Boston Globe headline, “Secret VA nursing home ratings hide poor quality of care from the public.”² In an all too predictable sequence, this led justifiably to a cascade of demands from the fifth estate, congressional representatives, the administration, veterans and their families, and watchdog organizations for release of the data, investigation of the allegedly deplorable conditions, and rapid fixes to the problems along with the punishment of the guilty.

As an ethicist I am committed to the principles of transparency and accountability that these entities rightly adjure in the wake of any disclosure of a breach of duty to treat each veteran with the best we have—especially the disabled, elderly, and vulnerable. But I have come to believe that the way in which this cycle of scandal and reaction plays out over and over again in VA facilities across the country, what I call “caring under the microscope,” is actually undermining the righteous goals it seeks to achieve.

I encourage you to try this online. Search for the phrase, “VA under microscope” and see what you get. Briefly read the summary, or the entire story if you have the inclination, and then take a few minutes to reflect on the emotional impact of what you read. Under a microscope is an idiom coined to capture the experience of being the object of close inspection and intense scrutiny. As most everyone knows from their own science education, microscopes magnify images that cannot normally be seen with the human eye, allowing us to observe a more detailed and focused image. The microscope surely helped revolutionize medicine and science. But what effect does such amplified and constant observation have on VA employees?³

For the thousands of staff members who do their job every day with all the empathy and skill, integrity, and dedication they can muster, there is demoralization. Researchers in the health professions describe it as “a feeling state of dejection, hopelessness, and a sense of personal ‘incompetence’ that may be tied to a loss of or threat to one’s own goals or values. It has an existential dimension when beliefs and values about oneself are disconfirmed.”⁴ If you are a nurse assigned to one of VA’s nursing homes, daily striving to ensure patients are clean and comfortable, or a therapist in a continuing living center using all your training to maximize an elder’s mobility and participation in activities, you might well begin to doubt your ability as a professional and question the worth of your work. This is exactly the opposite outcome that the microscopic oversight is intended to attain.

The impact of demoralization on health professionals directly contributes to unprecedented burnout and turnover. Were this not damaging enough, it also has an insidious rippling effect—like contaminated groundwater that poisons where it should be reviving. The humanistic, even spiritual, heart of all the health professions is the relationship between the practitioner and the patient, ideally a relationship of mutual respect and trust. Waves of negative news triggering harsh and unyielding criticism distort even the strongest, purest therapeutic alliances with fear and distrust, just as a microscope not properly focused changes a beautiful image into a blurred muddle.

Worried families of veterans staring at this picture invariably are drawn into the hyper media focus, feeling alarmed and betrayed, even when their loved one may be receiving excellent VA care. In 20 years as a physician and ethicist in VA hospitals, clinics, and community living centers, I know well that bad things happen to good people (both patients and staff). Yet VA patients, families, and staff are seldom offered the wider corrective vision that would note that bad things also happen in other health care institutions and good care is delivered in the VA. Acting Secretary of Veterans Affairs Peter O’Rourke crisply summarized in his response to the nursing home story.⁵

No veteran or any other human being in a VA or any other nursing home should ever be medicated into a zombie state or left alone in pain like those patients reported in the news story. And if the USA Today story improves the care of a single VA patient, then good has been done at least in the short run. Yet we must also take the long view and consider the moral and psychological outcome of prolonged demoralization on the very staff who must carry out the congressional mandates.

In the same time frame as the nursing home scandal, the VA Office of Inspector General also issued a report on the continued understaffing in the VA.⁶ This may be the most concerning aftermath of demoralization. One of my best residents had thought about the VA but in the end made a different choice when he completed his training. When I asked him why he told me, “I am afraid to end up in the newspaper.”

Summer will go by far too quickly. Enjoy it while you can so that with renewed strength we may all search for a better way that the light of truth and heat of power can do what they must while also not withering the spirit of caring that animates the people of the VA.

I write this editorial at the end of June as summer officially begins. Much of the country—my New Mexico home included—is suffering under an unbearable heat wave in which even those without belief pray for rain. Summer for many is associated with vacations, family trips, and happy hours in the swimming pool among other enjoyable activities that provide a welcome and much deserved break from routine and relief from the grind of work and school. In the words of the George Gershwin tune, “Summertime, and the livin’ is easy.”

In stark contrast to this season, where there is more lightness in being, is the heaviness of the news reports about the Department of Veteran Affairs (VA) that have been featured in the media and the federal press. I suspect I am not alone in having a hard time opening those e-mails; feeling once more the weight of failure on the VA and the employees who have dedicated a good part of their careers to its mission. Even for the VA, June has seen an exceptional string of bad press. I ask as you read this column to think about what the adjective bad means in this context. In the conclusion to this column, I will suggest that the meaning is multivalent.

Among the most distressing stories was the USA Today and Boston Globe headline, “Secret VA nursing home ratings hide poor quality of care from the public.”² In an all too predictable sequence, this led justifiably to a cascade of demands from the fifth estate, congressional representatives, the administration, veterans and their families, and watchdog organizations for release of the data, investigation of the allegedly deplorable conditions, and rapid fixes to the problems along with the punishment of the guilty.

As an ethicist I am committed to the principles of transparency and accountability that these entities rightly adjure in the wake of any disclosure of a breach of duty to treat each veteran with the best we have—especially the disabled, elderly, and vulnerable. But I have come to believe that the way in which this cycle of scandal and reaction plays out over and over again in VA facilities across the country, what I call “caring under the microscope,” is actually undermining the righteous goals it seeks to achieve.

I encourage you to try this online. Search for the phrase, “VA under microscope” and see what you get. Briefly read the summary, or the entire story if you have the inclination, and then take a few minutes to reflect on the emotional impact of what you read. Under a microscope is an idiom coined to capture the experience of being the object of close inspection and intense scrutiny. As most everyone knows from their own science education, microscopes magnify images that cannot normally be seen with the human eye, allowing us to observe a more detailed and focused image. The microscope surely helped revolutionize medicine and science. But what effect does such amplified and constant observation have on VA employees?³

For the thousands of staff members who do their job every day with all the empathy and skill, integrity, and dedication they can muster, there is demoralization. Researchers in the health professions describe it as “a feeling state of dejection, hopelessness, and a sense of personal ‘incompetence’ that may be tied to a loss of or threat to one’s own goals or values. It has an existential dimension when beliefs and values about oneself are disconfirmed.”⁴ If you are a nurse assigned to one of VA’s nursing homes, daily striving to ensure patients are clean and comfortable, or a therapist in a continuing living center using all your training to maximize an elder’s mobility and participation in activities, you might well begin to doubt your ability as a professional and question the worth of your work. This is exactly the opposite outcome that the microscopic oversight is intended to attain.

The impact of demoralization on health professionals directly contributes to unprecedented burnout and turnover. Were this not damaging enough, it also has an insidious rippling effect—like contaminated groundwater that poisons where it should be reviving. The humanistic, even spiritual, heart of all the health professions is the relationship between the practitioner and the patient, ideally a relationship of mutual respect and trust. Waves of negative news triggering harsh and unyielding criticism distort even the strongest, purest therapeutic alliances with fear and distrust, just as a microscope not properly focused changes a beautiful image into a blurred muddle.

Worried families of veterans staring at this picture invariably are drawn into the hyper media focus, feeling alarmed and betrayed, even when their loved one may be receiving excellent VA care. In 20 years as a physician and ethicist in VA hospitals, clinics, and community living centers, I know well that bad things happen to good people (both patients and staff). Yet VA patients, families, and staff are seldom offered the wider corrective vision that would note that bad things also happen in other health care institutions and good care is delivered in the VA. Acting Secretary of Veterans Affairs Peter O’Rourke crisply summarized in his response to the nursing home story.⁵

No veteran or any other human being in a VA or any other nursing home should ever be medicated into a zombie state or left alone in pain like those patients reported in the news story. And if the USA Today story improves the care of a single VA patient, then good has been done at least in the short run. Yet we must also take the long view and consider the moral and psychological outcome of prolonged demoralization on the very staff who must carry out the congressional mandates.

In the same time frame as the nursing home scandal, the VA Office of Inspector General also issued a report on the continued understaffing in the VA.⁶ This may be the most concerning aftermath of demoralization. One of my best residents had thought about the VA but in the end made a different choice when he completed his training. When I asked him why he told me, “I am afraid to end up in the newspaper.”

Summer will go by far too quickly. Enjoy it while you can so that with renewed strength we may all search for a better way that the light of truth and heat of power can do what they must while also not withering the spirit of caring that animates the people of the VA.