Hepatectomy for liver metastasis from ampullary cancer after pancreatoduodenectomy

A 51-year-old Japanese woman with a solitary liver metastasis originating from a carcinoma of the ampulla of Vater was successfully treated by partial hepatectomy 19 months after curative pancreatoduodenectomy with lymphadenectomy. Histologic examination revealed a stage III well-differentiated tubular adenocarcinoma (pT2, pN1, and pM0). Postoperative serum concentrations of carcinoembryonic antigen increased exponentially to 133 ng/mL. The carcinoembryonic antigen doubling time was 63 days. Computed tomography and ultrasonography of the abdomen showed a solitary metastasis in segment VI of the liver. Since neither local recurrences nor other distant metastases were detected, the patient underwent partial hepatectomy. Histologic study confirmed the presence of a metastatic liver tumor from the ampullary carcinoma. The carcinoembryonic antigen levels returned to normal immediately after the partial hepatectomy. She was well without signs of recurrence 18 months after partial hepatectomy.     

Twelve years survival with repeated hepatectomy and lung resection for metastasis from carcinoma of the papilla of Vater after pancreaticoduodenectomy

We present a 60-year-old woman who underwent three times hepatectomy and lung resection for metastasis originating from a carcinoma of the papilla of Vater after pancreaticoduodenectomy with lymphadenectomy during 12 years. Pancreaticoduodenectomy was performed in 1980 and histological examination of original tumor revealed a stage IIA papillary adenocarcinoma (pT3, pN0, pM0). Repetitive hepatectomy underwent in 1986 (S7,8), 1988 (S2), 1991 (S4) and bilateral partial resection of lung (right S1, left S2.3) in 1990. She died from multiple skin, bone and lung metastases 12 years after pancreaticoduodenectomy. The current case is very rare, however, if patients with carcinoma of the papilla of Vater have localized liver metastases and no local recurrence, liver metastases should be resected to improve the chances for long-term survival.     

Peritoneal recurrence of ampullary carcinoma following curative pancreatoduodenectomy

A 72 year-old Japanese man with peritoneal recurrence of carcinoma of the ampulla of Vater after curative pancreatoduodenectomy is presented. He was treated by percutaneous transhepatic biliary drainage (PTBD) for obstructive jaundice. The PTBD catheter dislodged 14 days later. He underwent emergency open peritoneal lavage and external choledochal drainage for diffuse bile peritonitis. Cytologic examination of bile obtained from the T-tube revealed malignant cells. He underwent pancreatoduodenectomy with regional lymph node dissection 2 months later for ampullary carcinoma. Pathologic examination showed a macroscopic protruding, 8 x 7 x 10 mm, papillary adenocarcinoma of the ampulla of Vater. The tumor was classified as stage II with pT2, pN0, and pM0. Eight months later, cytologic examination of ascites demonstrated adenocarcinoma cells. The patient died with peritoneal recurrence 10 months after curative pancreatoduodenectomy.     

Small-cell neuroendocrine carcinoma of the ampulla of Vater

We report a patient (an 80-year-old woman) with anemia and fecal occult blood, who had an emergency operation for carcinoma of the cecum (well-differentiated adenocarcinoma without local lymph node metastasis). Postoperative magnetic resonance cholangiopancreatography, cholangiography, and upper gastroduodenal endoscopy showed a tumor of the ampulla of Vater, and pylorus-preserving pancreatoduodenectomy was performed. Histology of the resected tumor was that of small-cell carcinoma, and immunohistochemistry showed positive staining for neuron-specific enolase, chromogranin A, and synaptophysin, confirming the neuroendocrine nature of the tumor. As the histology of the tumor was distinct from cecal carcinoma, and no tumors were found in other organs, the tumor was diagnosed as primary small-cell neuroendocrine carcinoma of the ampulla of Vater. The patient died due to multiple liver metastases of the carcinoma of the ampulla of Vater 7 months after the pancreatoduodenectomy. The clinical and morphological features of this disease have been reported in nine individuals previously.     

Long-term survival after hepatectomy for hepatic recurrence of carcinoma of the papilla of Vater

We present herein a rare case of a long‐term survivor after major hepatectomy performed for a metastatic liver tumor from carcinoma of the papilla of Vater. A 74‐year‐old man had undergone a pancreaticoduodenectomy for carcinoma of the papilla of Vater with obstructive jaundice, in April 1995. Histologically, an exposed mass‐forming type of tumor, measuring 40 × 30 mm, was composed of mucinous and papillary adenocarcinoma, invading into the muscularis propria of the duodenum, without lymph node metastases. The patient did not receive any type of chemotherapy. In September 1999, a solitary hepatic tumor, 3.5 cm in diameter, was detected in segment VIII of the liver by computed tomography. In November 1999, right hepatic lobectomy was carried out. The anterior and posterior portal pedicles were ligated and dissected in the hepatic parenchyma so as not to compromise the hepaticojejunostomy. After the hepatectomy, the patient was treated with low‐dose tegafur/uracil/cisplatin therapy for approximately 2 years. He has been doing well, without recurrence, for 5 years after the hepatectomy. Hepatectomy for hepatic metastases from carcinoma of the papilla of Vater is thought to be a useful surgical treatment in selected patients.     

Successfully treated metachronous liver metastasis of alpha-fetoprotein-producing early gastric cancer: case report

We treated a 57-year-old male with liver metastasis derived from an alpha-fetoprotein-producing early gastric cancer. Eleven months after distal gastrectomy with D2 lymph node dissection, the patient underwent hepatectomy of segment 4 to resect a liver tumor 3 cm in diameter found by abdominal computed tomography. Immunohistochemical examination of the stomach and liver specimens, using anti-alpha-fetoprotein antibody, showed partial alpha-fetoprotein expression in both the primary gastric and metastatic hepatic tumors. The patient's serum alpha-fetoprotein level had been elevated at 302 ng/mL before hepatectomy, but the level remained below 5 ng/mL postoperatively. The patient remains alive without tumor recurrence 3 years after hepatectomy. There have been few previous reports of good outcome after curative resection of a metachronous liver metastasis derived from alpha-fetoprotein-producing gastric cancer. The assessment of serum alpha-fetoprotein level may be useful for detecting and monitoring liver metastasis in gastric cancer, especially for alpha-fetoprotein-producing tumors.     

Resection of localized recurrences after hepatectomy of colorectal cancer metastases

BACKGROUND/AIMS: Hepatectomy is generally considered the only mode of curative treatment available for patients with colorectal liver metastases, even though recurrence occurs in more than 60% of the patients. METHODOLOGY: This is a retrospective study examining the survival of 11 patients undergoing surgical excision of recurrences gained from 46 patients undergoing initial hepatectomy for metastatic colorectal cancer. These 46 patients had curative hepatectomy and no extrahepatic metastasis. RESULTS: Cancer recurred in 29 of the 46 patients after a median follow-up time of 29.5 months (range 2-183 months), and 11 had curative resection of localized recurrences. In 6 patients, the liver was the only site of recurrence and 4 patients had isolated lung metastases. One patient had liver and lung metastases. There was no perioperative mortality. The median survival time and cumulative 5-year survival rate for 11 patients after the repeated resection were 28 months and 43.8%, respectively. These results were comparable to the survival for 46 patients after the initial hepatectomy, in which the median survival was 29.5 months and the 5-year survival rate was 49.0%. CONCLUSIONS: In appropriately selected patients with colorectal cancer, surgical excision of localized recurrences after hepatectomy may be effective in prolonging survival.     

Large cell neuroendocrine carcinoma of the ampulla of Vater

BACKGROUND: Neuroendocrine tumors of the ampulla of Vater are extremely rare, and few cases of large cell neuroendocrine carcinoma (LCNEC) of the ampulla have been reported. METHODS: A 48-year-old male with obstructive jaundice was admitted to our hospital. On examination the patient was found to have a periampullary growth and subsequently underwent the Whipple's procedure. RESULTS: Histopathological examination and immunohistochemistry revealed features of LCNEC of the ampulla of Vater. The patient developed multiple liver metastases 6 months after Whipple's procedure. CONCLUSION: LCNEC of the ampulla of Vater is rare and highly aggressive, with a dismal prognosis.     

Repeat hepatectomy for recurrent hepatic metastases from colorectal cancer.

BACKGROUND/AIMS: Resection of liver metastases from colorectal cancer is accepted as a safe, and curative treatment. Furthermore, repeat hepatectomy has been indicated for hepatic recurrence after initial hepatectomy to achieve long-term survival or cure. The present study is a retrospective review of our results using repeat hepatectomy for colorectal liver metastases to identify outcomes and prognostic factors associated with long-term survival. METHODOLOGY: Ninety-four patients underwent an initial hepatectomy for colorectal metastases between 1990 and 1995. Thirty patients had hepatic recurrence after the initial hepatectomy. Eleven patients underwent repeat hepatectomy for isolated hepatic recurrence. RESULTS: The operative mortality was 0%. The overall 5-year survival rate after detection of second liver metastases of 11 patients was 45.5%. The distribution of first liver metastases and disease-free interval between the first and second hepatectomy demonstrated significance in relation to survival after repeat hepatectomy (P = 0.0303 and 0.0338). CONCLUSIONS: Repeat hepatectomy for recurrent liver metastases from colorectal cancer was the most effective treatment to improve survival time for selected patients. In patients with isolated second liver metastasis, unilateral spread of first liver metastases, and a disease-free interval between the first and second hepatectomies of more than 12 months, long-term survival or cure can be expected after repeat hepatectomy.     

Prognostic factors in patients with carcinoma of the papilla of Vater

BACKGROUND/AIMS: The prognosis after curative resection for patients with carcinoma of the papilla of Vater is relatively better than that for other peripancreatic cancer. However, prognostic factors after resection of the carcinoma have not been identified. METHODOLOGY: From 1983 to 1999, 16 patients with carcinoma of the papilla of Vater underwent standard pancreatoduodenectomy and dissection of regional lymph nodes. We followed the patients for 63 days to 17 years (median, 27 months) and analyzed clinicopathologic variables in relation to prognosis. RESULTS: The survival rate at 5 years was 50.5%. The morphologic factors predicting poor outcome were macroscopic ulcer formation and microscopic pancreatic, venous, or perineural invasion. Tumors with ulcer formation tended to infiltrate into the duodenum and pancreas, but not into veins or the perineural space. Eight of 16 patients died due to recurrence of the cancer; liver metastasis (n = 6) or peritoneal dissemination (n = 2). CONCLUSIONS: Patients with carcinoma of the papilla of Vater demonstrating ulcer formation or invasion into the pancreas, vein, or perineural space may benefit from adjuvant therapy to reduce the risk of liver metastasis. Careful observation is essential for liver metastasis or peritoneal dissemination after surgery; especially in patients with ulcer formation or venous invasion.     

Analysis of the prognostic factors for liver metastasis of gastric cancer after hepatic resection: a multi-institutional study of the indications for resection

BACKGROUND/AIMS: The number of reports of hepatic resection for metastatic gastric cancer is very small. The outcome and indications of hepatic resection for metastatic gastric cancer remains unknown. METHODOLOGY: A multi-institutional study was made. Thirty-six patients who underwent a hepatic resection for liver metastasis of gastric cancer with no residual tumor were included in this study. The clinicopathological factors were examined as prognostic factors by multivariate analyses. Thirty patients had recurrence and the recurrence pattern and risk factors for extrahepatic recurrence was examined. RESULTS: The overall survival rate was 64% at 1 year, 43% at 2 years, 26% at 3 years 26% at 5 years, and 26% at 10 years after hepatectomy. Multivariate analysis showed that lymphatic invasion, venous invasion of cancer cells of primary gastric cancer and the number of the liver metastasis (> 3) were independent poor prognostic factors after hepatic resection. The most common recurrence pattern was intrahepatic recurrence in 22 patients (73%). The risk factors for extrahepatic recurrence was serosal invasion, lymph node metastasis of primary gastric cancer, stage, and curability of operation. CONCLUSIONS: Hepatic resection for liver metastasis should be attempted in case primary gastric cancer has neither lymphatic invasion nor venous invasion. The most common recurrent site was the liver. In patients with advanced gastric cancer, having neither serosal invasion nor lymph node metastasis, who underwent a less curative operation, the intra-hepatic recurrence would be expected. Thus, aggressive adjuvant chemotherapy through the hepatic artery may improve the survival after hepatectomy in these patients.     

Resection of liver metastasis from extrahepatic bile duct carcinoma previously treated by pancreatoduodenectomy

No English report of a 5-year survivor with liver metastasis from periampullary carcinoma has been published to date. Here, we report a 52-year-old woman with liver metastasis previously treated with pylorus-preserving pancreatoduodenectomy for extrahepatic bile duct carcinoma, who underwent hepatectomy and has survived for more than 5 years without recurrence after the procedure. This outcome suggests that hepatic resection is effective for selected patients with liver metastasis from extrahepatic bile duct carcinoma previously treated by pancreatoduodenectomy. When a patient has a solitary metastasis of the liver with no other evidence of recurrence, surgical resection of the liver metastasis should be considered a valid option.     

Guidelines for the management of biliary tract and ampullary carcinomas: surgical treatment

The only curative treatment in biliary tract cancer is surgical treatment. Therefore, the suitability of curative resection should be investigated in the first place. In the presence of metastasis to the liver, lung, peritoneum, or distant lymph nodes, curative resection is not suitable. No definite consensus has been reached on local extension factors and curability. Measures of hepatic functional reserve in the jaundiced liver include future liver remnant volume and the indocyanine green (ICG) clearance test. Preoperative portal vein embolization may be considered in patients in whom right hepatectomy or more, or hepatectomy with a resection rate exceeding 50%–60% is planned. Postoperative complications and surgery-related mortality may be reduced with the use of portal vein embolization. Although hepatectomy and/or pancreaticoduodenectomy are preferable for the curative resection of bile duct cancer, extrahepatic bile duct resection alone is also considered in patients for whom it is judged that curative resection would be achieved after a strict diagnosis of its local extension. Also, combined caudate lobe resection is recommended for hilar cholangiocarcinoma. Because the prognosis of patients treated with combined portal vein resection is significantly better than that of unresected patients, combined portal vein resection may be carried out. Prognostic factors after resection for bile duct cancer include positive surgical margins, especially in the ductal stump; lymph node metastasis; perineural invasion; and combined vascular resection due to portal vein and/or hepatic artery invasion. For patients with suspected gallbladder cancer, laparoscopic cholecystectomy is not recommended, and open cholecystectomy should be performed as a rule. When gallbladder cancer invading the subserosal layer or deeper has been detected after simple cholecystectomy, additional resection should be considered. Prognostic factors after resection for gallbladder cancer include the depth of mural invasion; lymph node metastasis; extramural extension, especially into the hepatoduodenal ligament; perineural invasion; and the degree of curability. Pancreaticoduodenectomy is indicated for ampullary carcinoma, and limited operation is also indicated for carcinoma in adenoma. The prognostic factors after resection for ampullary carcinoma include lymph node metastasis, pancreatic invasion, and perineural invasion.     

KL-6 mucin expression in carcinoma of the ampulla of Vater： Association with cancer progression

AIM: To assess histochemical expression of KL-6 and its clinicopathological significance in carcinoma of the ampulla of Vater. METHODS: Ampullary carcinoma tissues were collected from 38 patients who underwent pancreatoduodenectomy or local resection. Tissues were subjected to immunohistochemical analysis using KL-6 antibody. RESULTS: Positive staining of ampullary carcinoma cells was observed in 26 (68.4%) cases. Staining was not found in the surrounding non-cancer regions of the ampullary tissues. Remarkable KL-6 expression was observed in invasive carcinoma cells in pancreatic and duodenal tissues and in metastatic carcinoma cells in lymph nodes. Positive KL-6 expression was related to lymph node metastasis (P=0.020), pancreatic invasion (P=0.016), duodenal invasion (P= 0.034), and advanced stage of TNM clinical classification (P=0.010). Survival analysis showed that positive expression of KL-6 was related to a poorer prognosis (P=0.029). CONCLUSION: The aberrant expression of KL-6 mucin is significantly related to unfavorable behaviors of carcinoma of the ampulla of Vater.     

Management of liver metastases from colorectal cancer

About 50% of colorectal cancer patients develop liver metastasis, and liver resection is considered the only curative therapy. However, the rate of recurrence is high, which contributes to poor prognosis. Since surgical resection coverage has increased because of improved hepatectomy including portal vein embolization, tumors shrink because of the effectiveness of recent chemotherapy, such as FOLFOX and FOLFIRI, and it has become possible for many patients whose cancer was judged unresectable before to undergo resection. Improvement of new anticancer drugs such as molecularly targeted biologics is greatly changing therapeutic systems of metastatic colorectal cancer, and it is time for us to innovate stage IV therapy. In this report, we will review new treatment strategies for metastatic liver cancer from colorectal cancer, clinical trials of new anticancer drugs for liver metastasis, surgery and ablation as local therapy, and further clarify complex therapeutic systems for metastatic liver tumors from colorectal cancer.     

Appraisal of transarterial immunoembolization for hepatocellular carcinoma: a clinicopathologic study

Recurrence of hepatocellular carcinoma (HCC) is frequent, even after apparently curative resection. Preoperative transcatheter arterial chemoembolization (TAE) does not improve disease-free survival after hepatic resection. We previously reported the potential usefulness of transarterial immunoembolization (TIE), a newly developed arterial embolization technique using OK-432 and fibrinogen, as preoperative treatment. In this study, we further investigated the effect of TIE by histologic examination of the resected specimens and compared it with conventional TAE in a prospective nonrandomized manner. Thirty-nine patients underwent TIE (n = 17) or TAE (n = 22) before curative hepatectomy for HCC. Transarterial immunoembolization was performed according to the standard protocol using OK-432, fibrinogen, and thrombin. Histologic changes in cancerous and noncancerous liver tissues were examined at different stages after TIE. Histologic grading of cancer cell injury according to the modified Shimosato criteria (Grades 0-IV, in increasing order of severity of cell injury) and postoperative disease-free survival were compared between the two groups. Based on the results of histopathology, TAE was more effective than TIE against the main tumor. In contrast, TIE was significantly more effective than TAE against extracapsular invasion and intrahepatic metastasis. Disease-free survival after hepatectomy tended to be better in patients pretreated with TIE than TAE. Postoperative tumor recurrences in the TIE group (n = 4) occurred in the nontreatment regions, whereas tumor recurrences in TAE group developed mostly (8 of 11 patients) in treated liver regions. Based on results of histologic examination, TIE seems to be more effective than conventional TAE against extracapsular invasion and intrahepatic metastasis. Data for disease-free survival and recurrence site suggest TIE may be a useful preoperative treatment.     

Intraoperative thermal ablation therapy for small colorectal metastases to the liver

BACKGROUND/AIMS: Thermal ablation (TA) therapies such as microwave coagulation therapy (MCT) and radiofrequency interstitial thermal ablation (RFA) for colorectal metastasis to the liver cannot always achieve a complete tumor cell death, and the multiple insertions of the TA probe may lead to intrahepatic dissemination and/or distant metastasis. METHODOLOGY: The achieved local control rate, any recurrence in the residual liver, and any extrahepatic recurrence has been evaluated in 105 patients who underwent hepatectomy and/or intraoperative TA between 1994 and 2004. RESULTS: A total of 102 unresectable liver metastatic lesions (mean size 21mm) were selectively treated with TA either as initial treatment (32 patients) and/or as re-treatment (18 patients) for recurrence in the residual liver, in combination with hepatectomy. Overall, TA achieved a high local tumor control rate of 95%. Multivariate analysis revealed that initial-TA therapy was not a significant predictive factor of hepatic recurrence or any recurrence. CONCLUSION: TA therapies in combination with hepatectomy may offer increased resectability without increased risk of intrahepatic dissemination or extrahepatic recurrence for certain patients who would otherwise be deemed inoperable, when relatively small tumors are indicated for TA.     

Primary acinar cell carcinoma of the ampulla of Vater

Acinar cell carcinoma of the pancreatobiliary system is a relatively rare malignant neoplasm arising usually in the pancreatic parenchyma. We experienced a 68-year-old woman who presented with obstructive jaundice due to an ampullary mass 1.0 cm in diameter, detected by abdominal computed tomography and endoscopic examination. The patient underwent a curative surgical operation, and histopathological examination revealed that the tumor was confined to the ampulla of Vater with no continuity to the pancreatic parenchyma. The tumor cells showed acinar or tubular arrangement with eosinophilic to basophilic granular cytoplasm, findings identical to those of acinar cell carcinoma of the pancreas. Immunohistochemically, the tumor cells were positive for lipase. From these findings, we concluded that the tumor was primary acinar cell carcinoma arising in the ampulla of Vater, probably originating from heterotopic pancreatic tissue. This is the first reported case of primary acinar cell carcinoma in the ampulla of Vater.     

A case of duodenal carcinoid tumor accompanied by liver metastasis and lymph node metastases in a patient with von Recklinghausen disease

We report a case of duodenal carcinoid tumor accompanied by liver metastasis and lymph node metastases in a patient with von Recklinghausen disease. A 48-year-old woman with von Recklinghausen disease was referred to our hospital because of a submucosal tumor at the ampulla of Vater detected by upper gastrointestinal endoscopy. The lesion was diagnosed as a carcinoid tumor based on the pathology of the biopsy specimen. At operation, although there were liver metastasis on the surface of S3 the liver and regional lymph node metastases, we selected pancreatoduodenectomy with lymph node dissection and enucleation of the liver metastasis. The postoperative course was good and the woman was discharged on postoperative day 33. No recurrence has been seen at 24 months since surgery.     

Usefulness of follow-up after pancreatoduodenectomy for carcinoma of the ampulla of Vater

Background: The prognosis for carcinoma of the ampulla of Vater (CAV) is better than for pancreatic cancer. The 5-year survival median rate after resection of CAV is 45%, but late recurrences remain possible. Several survival factors have been identified (lymph nodes, perineural invasion), but few data are available on the type of recurrences, their impact and their management. Patients and methods: A total of 41 patients treated by pancreatoduodenectomy (PD) for CAV from 1980 to 2003 were studied retrospectively. Patient selection, long-term survival recurrence rate and recurrence treatment were reviewed. Univariate and multivariate proportional hazards analysis were conducted on this series. Results: The mean follow-up was 48 months. Five-year survival was 62.8%. Eleven patients had recurrences (6–67 months). Recurrence was associated with time to all-causes death (hazard ratio [HR] 4.3, p=0.003). Factors predictive of recurrence were perineural invasion (HR 5.3, p=0.02), lymph node invasion (HR 5.3, p=0.02) and differentiation (HR 0.2, p=0.05). Three patients underwent surgical R0 treatment of their recurrences. Two who presented with solitary liver metastasis are alive and disease-free. Conclusions: Recurrence represents a serious threat in the prognosis of CAV after surgery. Some of these recurrences, in particular liver metastases, are accessible for a curative treatment. This finding supports the usefulness of a close and long-term follow-up after surgery to improve survival of patients with CAV, especially in the group of patients with a good prognosis.