Ask the Experts - Liver Transplantation in Patient With Adenocarcinoma...
Ask the Experts - Liver Transplantation in Patient With Adenocarcinoma...
A 28-year-old man with a 19-year history of ulcerative colitis underwent a laparoscopic cholecystectomy for biliary colic in December of 1999. The specimen contained high-grade adenocarcinoma in situ. The cystic duct margins were positive. Subsequent endoscopic retrograde cholangiopancreatogram revealed multiple strictures of the hilar and distal common bile ducts. Brushings of the strictures were negative for malignancy. Serum alfa-fetoprotein and carcinoembryonic antigens were normal. Computerized tomography of the abdomen and pelvis was normal. In December of 2000, we took the patient to the operating room for orthotopic liver transplantation. On abdominal exploration we noted a mass at the head of the pancreas and several enlarged portal nodes. Frozen section of the portal nodes was negative for malignancy. On-table esophagogastroduodenoscopy revealed a normal duodenum and ampulla. How would you proceed at this time?
Liise Kayler, MD
We at the Fred Hutchinson Cancer Research Center have looked at this issue and recently published a study. The abstract follows:
Although not specifically provided in the history, the case presented is consistent with a liver diagnosis of primary sclerosing cholangitis (PSC). PSC is a chronic, cholestatic liver disease of unknown etiology that leads to biliary strictures, cholangitis, and often cirrhosis. Liver transplantation is the only therapeutic option for patients with PSC-induced end-stage liver disease. The results of transplantation for PSC are excellent, with 1-year survival rates of approximately 90% and 5-year survival rates of 75% to 85%.
Cholangiocarcinoma is a devastating complication of PSC and develops in 10% to 20% of patients with long-standing PSC. Risk factors include biliary dysplasia, coexistence of inflammatory bowel disease, colon cancer, and smoking. Unfortunately, no reliable screening methods exist to detect cholangiocarcinoma in the setting of PSC. The most commonly used tests are ERCP brushings, serum CA19-9 levels, and radiologic imaging with CT scan, MRI, or both. The simple truth remains: Cholangiocarcinoma is hard to diagnose preoperatively and is even harder to treat.
The results of liver transplantation for patients with clinically proven cholangiocarcinoma are very poor. In the series from Pittsburgh, 27 patients underwent liver transplantation for PSC with clinically identified hilar cholangiocarcinoma. Survival rates at 1, 3, and 5 years were 60%, 32%, and 25%, respectively. Similar results were seen for those undergoing liver transplantation for peripheral cholangiocarcinoma. This survival rate is significantly worse than that of those transplanted without cholangiocarcinoma. Positive lymph nodes and positive resection margins were associated with a worse prognosis. Similar findings were reported from the Cincinnati Transplant Tumor Registry database. In this analysis, 207 patients underwent liver transplantation for unresectable cholangiocarcinoma or cholangiohepatoma. Survival rates at 1, 2, and 5 years were 72%, 48%, and 23%, respectively.
Given that liver transplantation for unresectable cholangiocarcinoma is usually associated with early disease relapse and limited survival, most programs have abandoned transplantation for clinically recognized cholangiocarcinoma. This is especially important given the gross organ donor shortage. However, it should be mentioned that an aggressive approach has been reported when liver transplantation along with pancreaticoduodenectomy (Whipple procedure) has been performed in the setting of cholangiocarcinoma. Although the rate of curative resection margins increased with this procedure, a survival benefit was not seen, and this approach is not practiced at most transplant centers. Recently, the Mayo Clinic group has shown prolonged, disease-free survival in highly selected patients with early-stage cholangiocarcinoma after liver transplantation when preoperative irradiation is combined with adjuvant chemotherapy.
Incidental microscopic, node-negative cholangiocarcinoma is detected in 10% to 15% of explanted livers of patients transplanted for PSC. Survival in this subset is much better than that of those transplanted with clinically documented cholangiocarcinoma. In the UCLA series of 127 patients transplanted for PSC, 8% were found to have incidental microscopic cholangiocarcinoma. Survival rates at 1, 2, and 5 years were 100%, 83%, and 83%, respectively.
Management of the specific case presented is controversial and illustrates the difficulties in diagnosing cholangiocarcinoma. A 28-year-old man with biliary strictures (and presumed PSC) was taken to the operating room for liver transplantation 1 year after diagnosis of adenocarcinoma in situ during cholecystectomy. Despite a negative preoperative evaluation, a mass was encountered in the head of the pancreas at exploration. Although frozen section of the lymph nodes was negative, frozen section diagnosis can be difficult. It is a good practice to ensure that the biopsies are interpreted by an experienced liver transplant pathologist. If the diagnosis is uncertain, additional opinions should be obtained. Furthermore, no mention of biopsy of the pancreatic mass itself was given. In the absence of a history of pancreatitis, it is very worrisome that this mass represents a malignancy rather than an inflammatory process. Multiple biopsies of this mass should be done, including a transduodenal approach if necessary. If the mass is malignant, then the consensus is to close the patient and not proceed with the liver transplantation. If all biopsies are negative after thorough pathologic evaluation, then it is reasonable to proceed with the liver transplant, recognizing the risk exists that the permanent section may reveal malignancy. Although combined liver transplantation and Whipple procedure has been reported, it does not appear to prolong survival in the setting of malignancy.
A 28-year-old man with a 19-year history of ulcerative colitis underwent a laparoscopic cholecystectomy for biliary colic in December of 1999. The specimen contained high-grade adenocarcinoma in situ. The cystic duct margins were positive. Subsequent endoscopic retrograde cholangiopancreatogram revealed multiple strictures of the hilar and distal common bile ducts. Brushings of the strictures were negative for malignancy. Serum alfa-fetoprotein and carcinoembryonic antigens were normal. Computerized tomography of the abdomen and pelvis was normal. In December of 2000, we took the patient to the operating room for orthotopic liver transplantation. On abdominal exploration we noted a mass at the head of the pancreas and several enlarged portal nodes. Frozen section of the portal nodes was negative for malignancy. On-table esophagogastroduodenoscopy revealed a normal duodenum and ampulla. How would you proceed at this time?
Liise Kayler, MD
We at the Fred Hutchinson Cancer Research Center have looked at this issue and recently published a study. The abstract follows:
Although not specifically provided in the history, the case presented is consistent with a liver diagnosis of primary sclerosing cholangitis (PSC). PSC is a chronic, cholestatic liver disease of unknown etiology that leads to biliary strictures, cholangitis, and often cirrhosis. Liver transplantation is the only therapeutic option for patients with PSC-induced end-stage liver disease. The results of transplantation for PSC are excellent, with 1-year survival rates of approximately 90% and 5-year survival rates of 75% to 85%.
Cholangiocarcinoma is a devastating complication of PSC and develops in 10% to 20% of patients with long-standing PSC. Risk factors include biliary dysplasia, coexistence of inflammatory bowel disease, colon cancer, and smoking. Unfortunately, no reliable screening methods exist to detect cholangiocarcinoma in the setting of PSC. The most commonly used tests are ERCP brushings, serum CA19-9 levels, and radiologic imaging with CT scan, MRI, or both. The simple truth remains: Cholangiocarcinoma is hard to diagnose preoperatively and is even harder to treat.
The results of liver transplantation for patients with clinically proven cholangiocarcinoma are very poor. In the series from Pittsburgh, 27 patients underwent liver transplantation for PSC with clinically identified hilar cholangiocarcinoma. Survival rates at 1, 3, and 5 years were 60%, 32%, and 25%, respectively. Similar results were seen for those undergoing liver transplantation for peripheral cholangiocarcinoma. This survival rate is significantly worse than that of those transplanted without cholangiocarcinoma. Positive lymph nodes and positive resection margins were associated with a worse prognosis. Similar findings were reported from the Cincinnati Transplant Tumor Registry database. In this analysis, 207 patients underwent liver transplantation for unresectable cholangiocarcinoma or cholangiohepatoma. Survival rates at 1, 2, and 5 years were 72%, 48%, and 23%, respectively.
Given that liver transplantation for unresectable cholangiocarcinoma is usually associated with early disease relapse and limited survival, most programs have abandoned transplantation for clinically recognized cholangiocarcinoma. This is especially important given the gross organ donor shortage. However, it should be mentioned that an aggressive approach has been reported when liver transplantation along with pancreaticoduodenectomy (Whipple procedure) has been performed in the setting of cholangiocarcinoma. Although the rate of curative resection margins increased with this procedure, a survival benefit was not seen, and this approach is not practiced at most transplant centers. Recently, the Mayo Clinic group has shown prolonged, disease-free survival in highly selected patients with early-stage cholangiocarcinoma after liver transplantation when preoperative irradiation is combined with adjuvant chemotherapy.
Incidental microscopic, node-negative cholangiocarcinoma is detected in 10% to 15% of explanted livers of patients transplanted for PSC. Survival in this subset is much better than that of those transplanted with clinically documented cholangiocarcinoma. In the UCLA series of 127 patients transplanted for PSC, 8% were found to have incidental microscopic cholangiocarcinoma. Survival rates at 1, 2, and 5 years were 100%, 83%, and 83%, respectively.
Management of the specific case presented is controversial and illustrates the difficulties in diagnosing cholangiocarcinoma. A 28-year-old man with biliary strictures (and presumed PSC) was taken to the operating room for liver transplantation 1 year after diagnosis of adenocarcinoma in situ during cholecystectomy. Despite a negative preoperative evaluation, a mass was encountered in the head of the pancreas at exploration. Although frozen section of the lymph nodes was negative, frozen section diagnosis can be difficult. It is a good practice to ensure that the biopsies are interpreted by an experienced liver transplant pathologist. If the diagnosis is uncertain, additional opinions should be obtained. Furthermore, no mention of biopsy of the pancreatic mass itself was given. In the absence of a history of pancreatitis, it is very worrisome that this mass represents a malignancy rather than an inflammatory process. Multiple biopsies of this mass should be done, including a transduodenal approach if necessary. If the mass is malignant, then the consensus is to close the patient and not proceed with the liver transplantation. If all biopsies are negative after thorough pathologic evaluation, then it is reasonable to proceed with the liver transplant, recognizing the risk exists that the permanent section may reveal malignancy. Although combined liver transplantation and Whipple procedure has been reported, it does not appear to prolong survival in the setting of malignancy.
Source...