Few eligible patients undergo radical cholecystectomy

HOLLYWOOD, FLA. – Patients with stage T1b gallbladder cancer who can tolerate surgery should undergo radical cholecystectomy, Dr. Chandrakanth Are said at the annual conference of the National Comprehensive Cancer Network.

Although there is little controversy about the need for simple cholecystectomy in patients with carcinoma in situ and those with T1a disease, or about the need for radical cholecystectomy in those with T2 disease or in those with T3 disease in whom the procedure will be curative, there has been less certainty about the treatment for T1b disease, said Dr. Are.

"Ten to 15 years ago we weren’t doing [radical cholecystectomy] in these patients, but we found out that is probably what we should be doing," he said. Multiple studies suggest that about 15% of patients with T1b disease have positive lymph nodes, compared with less than 3% of those with T1a disease, and that more than 10% of T1a and T1b patients have residual disease after simple cholecystectomy, with most of those cases attributable to T1b disease, he noted.

The problem is that patients with T1b disease, as well as patients with T2 disease, remain undertreated, said Dr. Are of the Fred & Pamela Buffett Cancer Center at the Nebraska Medical Center, Omaha.

At least two studies have demonstrated that few eligible patients undergo radical cholecystectomy. Both studies used data from the Surveillance, Epidemiology, and End Results (SEER) registry.

One showed that of 2,385 resected patients with T1-T3 M0 gallbladder cancer, only 8.6% underwent en bloc resection, and 5.3% had a lymphadenectomy (J. Am. Coll Surg. 2008;207:371-82).

Another showed that of 382 patients with T2 disease, only 14 underwent radical cholecystectomy (Am. J. Surg. 2007;194:820-5).

"If this is the fate of patients with T2, imagine where patients with T1b stand," he said, adding that more education is needed about the appropriate management of patients with Stage T1b disease, and more emphasis should be placed on referring these patients to centers of excellence.

Dr. Are cited other controversies in the treatment of gallbladder cancer as follows:

• Bile duct resection. Historically, bile duct resection has been performed at the time of cholecystectomy, but this practice has been found to increase morbidity without providing any survival benefit, Dr. Are said.

Current thinking is that bile duct resection should be performed only in patients with a positive cystic duct margin (because studies suggest that more than 40% of such cases will have common bile duct involvement), and in cases in which extensive lymph node dissection is necessary and might cause ischemia of the duct, he said.

• Extent of lymph node excision. There has been uncertainty regarding the appropriate number of lymph nodes to excise, but data suggest that survival improves with excision of five or more. In one study in which lymph node data were available for more than 2,500 patients, 68% had no lymph nodes excised, 28% had one to four excised, and 4% had more than five excised. The hazard ratios for survival were 0.55 (P less than .001) for one to four vs. no nodes, and 0.63 (P = .03) for more than five nodes vs. one to four nodes (Arch. Surg. 2011;146:734-8).

Another study of 122 patients showed improved survival among those with greater than six vs. less than six nodes excised, although the median total lymph node count was three (Ann. Surg. 2011;254:320-5).

The matter of setting a standard for the number of lymph nodes to dissect was discussed at a consensus conference in January, and guidelines are forthcoming.

Dr. Are predicted the consensus will be that three to six lymph nodes should be excised.

• Port sites metastases. Studies suggest that up to 19% of patients who undergo laparoscopic cholecystectomy will develop port site metastases, and it was thought that these sites should be resected. However, recent findings from a series of 113 patients, of whom 19% developed port site metastases, showed that while survival was significantly worse in those patients (42 months vs. 17 months in those without port site metastases), resection did not change the outcome (Ann. Surg. Oncol. 2012;19:409-17).

The current thinking is that port site metastases is a marker of underlying aggressive disease, and that resection is not warranted, Dr. Are said.

• Jaundice. A number of patients with gallbladder cancer present with jaundice, and data from countries in the West where the disease incidence is relatively low have suggested that jaundice is associated with poor prognosis and is thus a contraindication to resection. One U.S. study showed a 6-month survival among resected patients with jaundice, compared with 16 months for those with no jaundice. None of the patients with jaundice survived 2 years, compared with 21% of those without jaundice (Ann. Surg. Oncol. 2004;11:310-15).

Subsequent studies, including studies from India where the incidence is much higher, showed better survival. One, for example, demonstrated 50% survival among resected patients with jaundice; another demonstrated 23% 5-year survival.

"So the current recommendation is that the presence of jaundice is still a contraindication [to resection], but not an absolute contraindication," Dr. Are said.

It is a relative contraindication in selected patients; those with appropriate T stage who are fit enough for surgery and anesthesia should proceed to surgery, he added, noting that in those who are unresectable, it is important to think of biliary drainage.

"Unless you do that, it will be hard for them to get chemotherapy," he said.

• Extent of hepatic resection. The standard of care with respect to hepatic resection at the time of radical cholecystectomy is to resect only segments 4b and 5 of the liver. The controversy is whether more should be resected.

Data as to whether more extensive resection confers a survival benefit have been conflicting, with some studies showing a benefit with right lobectomy or extended right lobectomy, and others showing no such benefit, Dr. Are said.

The current standard of resecting 4b and 5 is adequate, except in selected cases where the intent of resecting more is to obtain negative margins, he said.

Dr. Are reported having no relevant disclosures.

HOLLYWOOD, FLA. – Patients with stage T1b gallbladder cancer who can tolerate surgery should undergo radical cholecystectomy, Dr. Chandrakanth Are said at the annual conference of the National Comprehensive Cancer Network.

Although there is little controversy about the need for simple cholecystectomy in patients with carcinoma in situ and those with T1a disease, or about the need for radical cholecystectomy in those with T2 disease or in those with T3 disease in whom the procedure will be curative, there has been less certainty about the treatment for T1b disease, said Dr. Are.

"Ten to 15 years ago we weren’t doing [radical cholecystectomy] in these patients, but we found out that is probably what we should be doing," he said. Multiple studies suggest that about 15% of patients with T1b disease have positive lymph nodes, compared with less than 3% of those with T1a disease, and that more than 10% of T1a and T1b patients have residual disease after simple cholecystectomy, with most of those cases attributable to T1b disease, he noted.

The problem is that patients with T1b disease, as well as patients with T2 disease, remain undertreated, said Dr. Are of the Fred & Pamela Buffett Cancer Center at the Nebraska Medical Center, Omaha.

At least two studies have demonstrated that few eligible patients undergo radical cholecystectomy. Both studies used data from the Surveillance, Epidemiology, and End Results (SEER) registry.

One showed that of 2,385 resected patients with T1-T3 M0 gallbladder cancer, only 8.6% underwent en bloc resection, and 5.3% had a lymphadenectomy (J. Am. Coll Surg. 2008;207:371-82).

Another showed that of 382 patients with T2 disease, only 14 underwent radical cholecystectomy (Am. J. Surg. 2007;194:820-5).

"If this is the fate of patients with T2, imagine where patients with T1b stand," he said, adding that more education is needed about the appropriate management of patients with Stage T1b disease, and more emphasis should be placed on referring these patients to centers of excellence.

Dr. Are cited other controversies in the treatment of gallbladder cancer as follows:

• Bile duct resection. Historically, bile duct resection has been performed at the time of cholecystectomy, but this practice has been found to increase morbidity without providing any survival benefit, Dr. Are said.

Current thinking is that bile duct resection should be performed only in patients with a positive cystic duct margin (because studies suggest that more than 40% of such cases will have common bile duct involvement), and in cases in which extensive lymph node dissection is necessary and might cause ischemia of the duct, he said.

• Extent of lymph node excision. There has been uncertainty regarding the appropriate number of lymph nodes to excise, but data suggest that survival improves with excision of five or more. In one study in which lymph node data were available for more than 2,500 patients, 68% had no lymph nodes excised, 28% had one to four excised, and 4% had more than five excised. The hazard ratios for survival were 0.55 (P less than .001) for one to four vs. no nodes, and 0.63 (P = .03) for more than five nodes vs. one to four nodes (Arch. Surg. 2011;146:734-8).

Another study of 122 patients showed improved survival among those with greater than six vs. less than six nodes excised, although the median total lymph node count was three (Ann. Surg. 2011;254:320-5).

The matter of setting a standard for the number of lymph nodes to dissect was discussed at a consensus conference in January, and guidelines are forthcoming.

Dr. Are predicted the consensus will be that three to six lymph nodes should be excised.

• Port sites metastases. Studies suggest that up to 19% of patients who undergo laparoscopic cholecystectomy will develop port site metastases, and it was thought that these sites should be resected. However, recent findings from a series of 113 patients, of whom 19% developed port site metastases, showed that while survival was significantly worse in those patients (42 months vs. 17 months in those without port site metastases), resection did not change the outcome (Ann. Surg. Oncol. 2012;19:409-17).

The current thinking is that port site metastases is a marker of underlying aggressive disease, and that resection is not warranted, Dr. Are said.

• Jaundice. A number of patients with gallbladder cancer present with jaundice, and data from countries in the West where the disease incidence is relatively low have suggested that jaundice is associated with poor prognosis and is thus a contraindication to resection. One U.S. study showed a 6-month survival among resected patients with jaundice, compared with 16 months for those with no jaundice. None of the patients with jaundice survived 2 years, compared with 21% of those without jaundice (Ann. Surg. Oncol. 2004;11:310-15).

Subsequent studies, including studies from India where the incidence is much higher, showed better survival. One, for example, demonstrated 50% survival among resected patients with jaundice; another demonstrated 23% 5-year survival.

"So the current recommendation is that the presence of jaundice is still a contraindication [to resection], but not an absolute contraindication," Dr. Are said.

It is a relative contraindication in selected patients; those with appropriate T stage who are fit enough for surgery and anesthesia should proceed to surgery, he added, noting that in those who are unresectable, it is important to think of biliary drainage.

"Unless you do that, it will be hard for them to get chemotherapy," he said.

• Extent of hepatic resection. The standard of care with respect to hepatic resection at the time of radical cholecystectomy is to resect only segments 4b and 5 of the liver. The controversy is whether more should be resected.

Data as to whether more extensive resection confers a survival benefit have been conflicting, with some studies showing a benefit with right lobectomy or extended right lobectomy, and others showing no such benefit, Dr. Are said.

The current standard of resecting 4b and 5 is adequate, except in selected cases where the intent of resecting more is to obtain negative margins, he said.

Dr. Are reported having no relevant disclosures.

HOLLYWOOD, FLA. – Patients with stage T1b gallbladder cancer who can tolerate surgery should undergo radical cholecystectomy, Dr. Chandrakanth Are said at the annual conference of the National Comprehensive Cancer Network.

Although there is little controversy about the need for simple cholecystectomy in patients with carcinoma in situ and those with T1a disease, or about the need for radical cholecystectomy in those with T2 disease or in those with T3 disease in whom the procedure will be curative, there has been less certainty about the treatment for T1b disease, said Dr. Are.

"Ten to 15 years ago we weren’t doing [radical cholecystectomy] in these patients, but we found out that is probably what we should be doing," he said. Multiple studies suggest that about 15% of patients with T1b disease have positive lymph nodes, compared with less than 3% of those with T1a disease, and that more than 10% of T1a and T1b patients have residual disease after simple cholecystectomy, with most of those cases attributable to T1b disease, he noted.

The problem is that patients with T1b disease, as well as patients with T2 disease, remain undertreated, said Dr. Are of the Fred & Pamela Buffett Cancer Center at the Nebraska Medical Center, Omaha.

At least two studies have demonstrated that few eligible patients undergo radical cholecystectomy. Both studies used data from the Surveillance, Epidemiology, and End Results (SEER) registry.

One showed that of 2,385 resected patients with T1-T3 M0 gallbladder cancer, only 8.6% underwent en bloc resection, and 5.3% had a lymphadenectomy (J. Am. Coll Surg. 2008;207:371-82).

Another showed that of 382 patients with T2 disease, only 14 underwent radical cholecystectomy (Am. J. Surg. 2007;194:820-5).

"If this is the fate of patients with T2, imagine where patients with T1b stand," he said, adding that more education is needed about the appropriate management of patients with Stage T1b disease, and more emphasis should be placed on referring these patients to centers of excellence.

Dr. Are cited other controversies in the treatment of gallbladder cancer as follows:

• Bile duct resection. Historically, bile duct resection has been performed at the time of cholecystectomy, but this practice has been found to increase morbidity without providing any survival benefit, Dr. Are said.

Current thinking is that bile duct resection should be performed only in patients with a positive cystic duct margin (because studies suggest that more than 40% of such cases will have common bile duct involvement), and in cases in which extensive lymph node dissection is necessary and might cause ischemia of the duct, he said.

• Extent of lymph node excision. There has been uncertainty regarding the appropriate number of lymph nodes to excise, but data suggest that survival improves with excision of five or more. In one study in which lymph node data were available for more than 2,500 patients, 68% had no lymph nodes excised, 28% had one to four excised, and 4% had more than five excised. The hazard ratios for survival were 0.55 (P less than .001) for one to four vs. no nodes, and 0.63 (P = .03) for more than five nodes vs. one to four nodes (Arch. Surg. 2011;146:734-8).

Another study of 122 patients showed improved survival among those with greater than six vs. less than six nodes excised, although the median total lymph node count was three (Ann. Surg. 2011;254:320-5).

The matter of setting a standard for the number of lymph nodes to dissect was discussed at a consensus conference in January, and guidelines are forthcoming.

Dr. Are predicted the consensus will be that three to six lymph nodes should be excised.

• Port sites metastases. Studies suggest that up to 19% of patients who undergo laparoscopic cholecystectomy will develop port site metastases, and it was thought that these sites should be resected. However, recent findings from a series of 113 patients, of whom 19% developed port site metastases, showed that while survival was significantly worse in those patients (42 months vs. 17 months in those without port site metastases), resection did not change the outcome (Ann. Surg. Oncol. 2012;19:409-17).

The current thinking is that port site metastases is a marker of underlying aggressive disease, and that resection is not warranted, Dr. Are said.

• Jaundice. A number of patients with gallbladder cancer present with jaundice, and data from countries in the West where the disease incidence is relatively low have suggested that jaundice is associated with poor prognosis and is thus a contraindication to resection. One U.S. study showed a 6-month survival among resected patients with jaundice, compared with 16 months for those with no jaundice. None of the patients with jaundice survived 2 years, compared with 21% of those without jaundice (Ann. Surg. Oncol. 2004;11:310-15).

Subsequent studies, including studies from India where the incidence is much higher, showed better survival. One, for example, demonstrated 50% survival among resected patients with jaundice; another demonstrated 23% 5-year survival.

"So the current recommendation is that the presence of jaundice is still a contraindication [to resection], but not an absolute contraindication," Dr. Are said.

It is a relative contraindication in selected patients; those with appropriate T stage who are fit enough for surgery and anesthesia should proceed to surgery, he added, noting that in those who are unresectable, it is important to think of biliary drainage.

"Unless you do that, it will be hard for them to get chemotherapy," he said.

• Extent of hepatic resection. The standard of care with respect to hepatic resection at the time of radical cholecystectomy is to resect only segments 4b and 5 of the liver. The controversy is whether more should be resected.

Data as to whether more extensive resection confers a survival benefit have been conflicting, with some studies showing a benefit with right lobectomy or extended right lobectomy, and others showing no such benefit, Dr. Are said.

The current standard of resecting 4b and 5 is adequate, except in selected cases where the intent of resecting more is to obtain negative margins, he said.

Dr. Are reported having no relevant disclosures.