Heterotopic pancreas in the ampulla of Vater and papilla]

From 1977 to 1987, six cases of heterotopic pancreas at the ampulla of Vater and the papilla were encountered. All patients were suffering from obstructive jaundice and misdiagnosed as having periampullary cancer and pancreaticoduodenectomy was done. The entity was rare and extremely difficult to diagnose even during exploration. The pathology, diagnosis and surgical treatment of this disease were discussed.     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7–, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20–, MUC2–). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Tamoxifen therapy in unresectable adenocarcinoma of the pancreas and the papilla of Vater

Between 1984 and 1987, 176 Norwegian patients with histologically verified unresectable pancreatic adenocarcinoma were randomized to double-blind treatment with oral tamoxifen (30 mg daily; 48 men and 44 women) or placebo (47 men and 37 women). Analysis of oestrogen receptor activity in the carcinomas was not performed. There were no statistically significant differences between the two groups according to age, Karnofsky performance index, tumour node metastasis (TNM) stage, operative treatment or other patient characteristics. The tamoxifen or placebo treatment continued to death or to 10 months after accrual into the trial was stopped. In the tamoxifen group, the mean and median survivals were 205 and 115 days, respectively. These values did not differ statistically from the 192 and 122 days, respectively, observed in the placebo group. Additional retrospective analyses of sex and stage revealed no beneficial effect of tamoxifen upon survival. For women in stage III (any T N1 M0), mean and median survivals were 255 and 191 days, respectively, compared with values of 84 and 45 days, respectively, in the placebo group (P = 0.011). After 2.5 years, three (7 per cent) women in the tamoxifen group were still alive compared with no survivors in the placebo group. No male patients survived beyond 2.5 years. This therapeutic result in a small subgroup of women is probably incidental and not an effect of tamoxifen.     

An annular pancreas associated with carcinoma of the papilla of Vater: report of a case

An annular pancreas is an uncommon congenital anomaly that usually presents early in childhood. Malignancy in the setting of an annular pancreas is unusual. We herein report a case of annular pancreas with carcinoma of the papilla of Vater. A 59-year-old man presented with epigastric discomfort and was referred to us after gastroduodenal endoscopy showed a tumor of the papilla of Vater. Preoperative imaging showed the pancreatic parenchyma encircling the descending duodenum and a tumor at the papilla of Vater. A pancreaticoduodenectomy was performed for the annular pancreas and the ampullary tumor. Histological examination confirmed a complete annular pancreas and carcinoma in situ of the papilla of Vater. We also provide a review of the reported cases of an annular pancreas with periampullary neoplasms and discuss the clinical characteristics of this anomaly.     

Clinicopathological and immunohistochemical studies on carcinoma of the papilla of Vater]

The non-invasive adenomatous component (nac) was observed in 44% of 32 resected specimens of carcinoma of the papilla of Vater. Incidence of the "nac" positive carcinoma declined with cancer staging, but there was no significant relationship between the "nac" and tumor size. The "nac" positive rates in "tumor forming", "ulcerating" and "mixed" types were 65, 0 and 38%, respectively. The "nac" negative carcinoma metastasized more frequently to the lymph nodes, duodenum, pancreas and veins. The five year survival rates of the patients with the "nac" positive and negative carcinoma were 78 and 22%, respectively. Immunohistochemically, the "nac" positive carcinoma mostly showed partial distribution of CA19-9, while the "nac" negative carcinoma, carcinoma of the pancreas and bile duct mostly showed diffuse distribution. The intact mucosa of the common channel and orifice of the papilla almost showed partial distribution, and duodenal mucosa showed negative distribution. The pancreatic and bile duct almost indicated diffuse distribution. The "nac" may be precancerous condition and the "nac" positive carcinoma may arise from the common channel or the orifice of the papilla or the duodenum. But the "nac" negative carcinoma may belong primarily to carcinoma of the pancreas and bile duct as de-novo carcinoma.     

Reimplantation of the papilla of Vater

Detachment of the papilla of Vater from the duodenum may happen (a) deliberately, during duodenal resection for tumour without concomitant resection of the pancreatic head, and (b) accidentally in the course of gastrectomy for duodenal ulcer, when attempts to exteriorize the ulcer are made. In this report two case histories are cited encompassing both of these circumstances, in which the ampulla was successfully reimplanted into a Roux loop.     

Carcinoma in adenoma of the papilla of Vater

Carcinoma in adenoma of the papilla of Vater is extremely rare. We now report a case of adenocarcinoma in adenoma of the papilla of Vater and the clinicopathological findings are discussed. A 73-year-old Japanese woman was endoscopically diagnosed as a case of carcinoma combined with adenoma of the papilla of Vater. She underwent pancreatoduodenectomy and the postoperative course was statisfactory. Histological examination of the resected tissues revealed a superficial adenocarcinoma in the adenoma of the papilla of Vater. In certain cases, carcinoma of the papilla of Vater may develop from a pre-existing adenoma in the region. Therefore, we recommend that pancreatoduodenectomy should be done when an adenoma presents in this region.     

Neoplastic diseases of the papilla of Vater

Although it is quite small, the papilla of Vater is an important part of the body. Carcinoma of the papilla may be one of the smallest cancers that can cause death. The 5-year survival rate after resection was 51%, which is not satisfactory. In this article, the topics discussed are (1) pathogenesis, (2) histological characteristics, and (3) the molecular biological characteristics of carcinoma of the papilla of Vater. From results obtained by the investigation of 576 autopsied and 51 resected cases, atypical epithelium was found most frequently in the common channel, where pancreatic juice and bile mix physiologically. Atypical epithelia may be a precursor of carcinoma of the papilla of Vater. Carcinoma of the papilla of Vater could be classified into two types histologically, an intestinal type and a pancreaticobiliary type. The prognosis of patients with the intestinal type was much better than that of patients with the pancreaticobiliary type. These two types of carcinoma should be treated by different operative procedures or adjuvant therapies. Regarding the molecular biological characteristics of carcinoma of the papilla of Vater; (1) K-ras mutation is mainly associated with the intestinal type, and carcinomas of the intestinal and pancreaticobiliary types may develop via different mechanisms; (2) p53 overexpression may play a role in tumor ulceration; and (3) p21/Waf1 overexpression was significantly correlated with a poor prognosis.     

Carcinoma in adenoma of the papilla of Vater

Carcinoma in adenoma of the papilla of Vater is extremely rare. We now report a case of adenocarcinoma in adenoma of the papilla of Vater and the clinicopathological findings are discussed. A 73-year-old Japanese woman was endoscopically diagnosed as a case of carcinoma combined with adenoma of the papilla of Vater. She underwent pancreatoduodenectomy and the postoperative course was satisfactory. Histological examination of the resected tissues revealed a superficial adenocarcinoma in the adenoma of the papilla of Vater. In certain cases, carcinoma of the papilla of Vater may develop from a pre-existing adenoma in the region. Therefore, we recommend that pancreatoduodenectomy should be done when an adenoma presents in this region.     

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.     

Anomalous location of the papilla of Vater.

The location of the papilla of Vater in the third (horizontal portion) of the duodenum is a rare finding. In this report the thirty-eighth case is described and the available world literature is reviewed.     

Nodal involvement as an indicator of postoperative liver metastasis in carcinoma of the papilla of Vater

BACKGROUND/PURPOSE: Although lymph node metastatic involvement is one of the most important prognostic factors for carcinoma of the papilla of Vater, a detailed analysis of this factor in relation to prognosis has not been conducted. METHODS: From 1985 to 2003, 29 patients with carcinoma of the papilla of Vater underwent pancreaticoduodenectomy and dissection of regional lymph nodes at Yamagata University Hospital. We analyzed clinicopathologic variables in relation to prognosis and precisely evaluated nodal involvement in each patient to determine lymphatic flow. Furthermore, the relationship between recurrent site and nodal involvement was investigated. RESULTS: The overall survival rate was 55% at 5 years. The significant prognostic factors were morphological ulcer formation (P = 0.04), histological type (P = 0.03), nodal involvement (P = 0.002), and lymphatic invasion (P = 0.03). Multivariate analysis indicated no independent factor, but nodal involvement may be the strongest prognostic factor. The overall rate of nodal involvement was 41.4% (12 of 29 patients). The metastatic rates in the superior posterior pancreaticoduodenal lymph nodes, the inferior posterior pancreaticoduodenal lymph nodes, the superior mesenteric lymph nodes, and paraaortic lymph nodes were high (31.0%, 20.7%, 17.2%, and 13.8%, respectively). Patients with nodal involvement had a significantly higher rate of liver metastasis after surgery than those without it (P = 0.02). Ulcer formation and histological type were significantly correlated with nodal involvement (P = 0.05 and P = 0.002, respectively). CONCLUSIONS: Nodal involvement is the most important prognostic factor in patients with carcinoma of the papilla of Vater. Patients with nodal involvement are at high risk of liver metastasis; therefore, adjuvant therapy may be necessary for the control of liver metastasis. Preoperative ulcer formation and histological type in the biopsy specimen are good indicators for extended lymph node dissection and adjuvant therapy, because these variables are correlated with nodal involvement. However, our data revealed only the sites of the positive nodes, without addressing the effect of extended lymph node dissection and adjuvant chemotherapy. To date, there has been reporting of extended lymph node dissection and adjuvant chemotherapy in patients with carcinoma of the papilla of Vater. Further studies will be necessary to resolve these problems.     

Heterotopic pancreas in the ampulla of Vater

We report a patient in whom heterotopic pancreatic tissue was found within the ampulla and treated by ampullectomy. Only 16 cases of pancreatic tissue located at the ampulla of Vater have been reported in the literature and pancreaticoduodenectomy has been performed in more than half the cases because malignancy was suspected preoperatively, reflecting a rather aggressive surgical attitude. An accurate preoperative evaluation thus appears decisive to avoid unnecessary radical surgery. Endoscopic treatment of ampullary tumors is emerging as a viable alternative to surgical treatment. Local surgical excision is a reasonable option to endoscopic treatment. The possibility of heterotopic pancreatic tissue, though rare, should be included in the differential diagnosis of papillary tumors. Histologic confirmation (frozen or delayed) is mandatory before attempting such major surgery.     

Pathogenesis and treatment of neoplastic diseases of the papilla of Vater: Kausch-Whipple procedure with lymph node dissection in cancer of the papilla of Vater

Cancer of the papilla or the ampulla of Vater appears, from a clinical point of view, to be an intraduodenal or ampullary cancer. An adenoma-dysplasia-carcinoma sequence has been established. In 20%–40% of the patients with an adenoma of the papilla, a cancerous lesion in the adenoma is additionally observed. Oncological resection using a Kausch-Whipple technique or a pylorus-preserving partial pancreatico-duodenectomy (PPPD) offers a 5-year survival probability of between 45% and 65%. The hospital mortality after oncological resection at experienced centers is below 5%. The most frequent treatment-related complication is pancreatic fistula, which occurs in around 20% of the patients. In about 10% of the patients with a pT₁ cancer and in 25% to 67% with pT₂ and pT₃ cancer, lymph node involvement has been observed. Lymph nodes in front of and behind the head of the pancreas are the primary targets for cancer cell disseminations. In more than one-third of the patients, lymph nodes in the inter-aortocaval space and the lymph nodes around the superior mesenteric artery and the nodes in the pancreatic segment of the hepatoduodenal ligament are involved. Therefore, tissue dissection, including, selectively, the N₂ lymph nodes, is an essential component of radical surgery for cancer of the papilla. A standard Kausch-Whipple resection or PPPD without a selective extended lymph node dissection, including the interaortocaval and superior mesenteric artery nodes, results in about 30% of the patients having an R₂-resection, i.e., with cancer left behind. The long-term survival is determined by the tumor biological factors: (1) absence of lymph node involvement and (2) absence of infiltration into the pancreas. The surgeons contribution to the cure of cancer of the papilla is to perform an R₀-resection with low hospital mortality and low postoperative morbidity. Patients without lymph node involvement, and with absence of infiltration into the pancreas, no lymph vessel invasion, and tumor-negative margins have major benefits from oncological resection in regard to curability of the cancer.     

Ampullectomy for adenoma of the papilla and ampulla of Vater

Introduction: The frequency of malignant adenomas of the papilla figures between 15 and 30%. Villous adenoma is considered to be a premalignant lesion. Treatment: Resection of the papilla is indicated in large tubular and small tubulovillous adenoma. Ampullectomy, however, is mandatory in villous adenoma with severe dysplasia and large villous or tubulovillous adenoma. If villous adenoma with a low-risk pT1 N0 M0 G1/2-cancer is treated by ampullectomy, local lymph dissection should also be performed. Ampullectomy includes extirpation of the ampulla of Vater and reinsertion of the common bile duct and the pancreatic main duct into the duodenal wall. Results: Hospital mortality after ampullectomy is less than 0.4%, and surgical morbidity, e.g., cholangitis, below 10%. Received: 2 March 1998