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Pathology and genetics of tumours of the digestive system

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Objective The study was conducted to determine whether the performance of an extended lymphadenectomy and retroperitoneal soft-tissue clearance in association with a pancreatoduodenal resection improves the long-term survival of patients with a potentially curable adenocarcinoma of the head of the pancreas. Background Data The usefulness of performing an extended lymphadenectomy and retroperitoneal soft-tissue clearance in conjunction with a pancreatoduodenal resection in the treatment of ductal adenocarcinoma of the head of the pancreas is still unknown. Published studies suggest a benefit for the procedure in terms of better long-term survival rates; however, these studies were retrospective or did not prospectively evaluate large series of patients. Materials and Methods Eighty-one patients undergoing a pancreatoduodenal resection for a potentially curable ductal adenocarcinoma of the head of the pancreas were randomized to a standard (n = 40) or extended (n = 41) lymphadenectomy and retroperitoneal soft-tissue clearance in a prospective, multicentric study. The standard lymphadenectomy included removal of the anterior and posterior pancreatoduodenal, pyloric, and biliary duct, superior and inferior pancreatic head, and body lymph node stations. In addition to the above, the extended lymphadenectomy included removal of lymph nodes from the hepatic hilum and along the aorta from the diaphragmatic hiatus to the inferior mesenteric artery and laterally to both renal hila, with circumferential clearance of the origin of the celiac trunk 508 and superior mesenteric artery. Patients did not receive any postoperative adjuvant therapy. Results Demographic (age, gender) and histopathologic (tumor size, stage, differentiation, oncologic clearance) characteristics were similar in the two patient groups. Performance of the extended lymphadenectomy added time to the procedure, although the difference did not reach statistical significance (397 ± 50 minutes vs. 372 ± 50 minutes, p > 0.05). Transfusion requirements, postoperative morbidity and mortality rates, and overall survival did not differ between the two groups. When subgroups of patients were analyzed, using an a posteriori analysis that was not planned at the time of study design, there was a significantly (p 0.001), diameter ( 2.0 cm., p < 0.01), lymph node metastasis (absent vs. present, p < 0.01) and need for 4 or more units of transfused blood (< 4 vs. ≥ 4, p <0.01). Conclusions The addition of an extended lymphadenectomy and retroperitoneal soft-tissue clearance to a pancreatoduodenal resection does not significantly increase morbidity and mortality rates. Although the overall survival rate does not differ in the two groups, there appears to be a trend toward longer survival in node positive patients treated with an extended rather than a standard lymphadenectomy.

Standard versus extended lymphadenectomy associated with pancreatoduodenectomy in the surgical treatment of adenocarcinoma of the head of the pancreas: a multicenter, prospective, randomized study. Lymphadenectomy Study Group.

Chemoradiation prior to pancreaticoduodenectomy ensures that all patients who undergo resection complete multimodality therapy, avoids resection in patients with rapidly progressive disease, and allows radiation therapy to be delivered to well-oxygenated cells before surgical devascularization. Twenty-eight patients with cytologic or histologic proof of localized adenocarcinoma of the pancreatic head received preoperative chemoradiation (fluorouracil, 300 mg/m2 per day, and 50.4 Gy) with the intent of proceeding to resection; all 28 completed this preoperative therapy. Hospital admission because of gastrointestinal toxic effects was required in nine patients, yet no patient experienced a delay in operation. Restaging was performed 4 to 5 weeks after completion of chemoradiation, and five patients were found to have metastatic disease; the 23 patients without evidence of progressive disease underwent laparotomy. At laparotomy, three patients were found to have unsuspected metastatic disease, three patients had unresectable locally advanced disease, and 17 patients were able to undergo pancreaticoduodenectomy. One perioperative death resulted from myocardial infarction, and perioperative complications occurred in three patients. Histologic evidence of tumor cell injury was present in all resected specimens. Our results suggest that pancreaticoduodenectomy can be performed with a low incidence of complications after chemoradiation for localized adenocarcinoma of the pancreas.

Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas.

Pathology and genetics: Tumours of the digestive system

We performed a retrospective review of 59 pancreatic resections for ductal carcinoma of the pancreas head performed between 1971 and 1983. In addition to pancreaticoduodenectomy, 37 consecutive patients (from 1971 to 1981) received lymphatic dissection adjacent to the pancreatic head (Group R1), whereas another 22 patients (from 1981 to 1983) received a wider range of lymphatic and soft tissue dissection, including the para-aortic region (Group R2). These groups did not differ with regard to operative mortality rate or background factors in the patients who tolerated operation. The 3-year cumulative survival rate was 13% in the R1 group vs. 38% in the R2 group (p less than 0.05). Almost all of the deaths from cancer recurrence occurred within 3 years after operation; the cumulative rate of death from local recurrence decreased from 67 to 16% (p less than 0.05) at 3 years. Among the patients with nodal involvement, there was no 3-year survivor in the R1 group, but four (27%) in the R2 group (p less than 0.05) survived. Among the patients whose tumor size exceeded 4 cm with retroperitoneal invasion, there was no 3-year survivor in either group and most patients died of distant metastasis. Extended clearance of regional lymph nodes and soft tissue appears to benefit patients with ductal carcinoma of the pancreatic head whose tumor size is less than 4 cm without severe invasion to the retroperitoneal space.

Practical usefulness of lymphatic and connective tissue clearance for the carcinoma of the pancreas head.

This retrospective study attempted to determine the indications for extended pancreatectomy for locally advanced carcinoma of the pancreas, in terms of postoperative prognosis. An extended pancreatectomy with portal vein or superior mesenteric vein (PV/SMV) resection and regional lymphadenectomy was performed in 35 of 50 consecutive cancers that extended into the retroperitoneal spaces and involved the PV or SMV. Among the many background factors in the 35 resected specimens, the degree of PV/SMV invasion by the cancer was most closely associated with prognosis, despite resection of all involved PV/SMV. This factor generally correlated with the preoperative findings on the portal phase of superior mesenteric arteriograph. In 17 selected patients in whom PV/SMV invasion had been angiographically both semicircular or less and 1.2 cm (1.4 cm on the film) or less in length, the 3-year survival rate was 59%. This survival rate was significantly higher than the 29% 3-year survival rate in all 35 patients (p less than 0.05). Conversely, among the 18 patients in whom invasion was angiographically either beyond semicircular or more than 1.2 cm (1.4 cm on the film) in length, there were no 1.5-year survivors, and this result was even worse than that of 15 nonresectable cases. Based on postoperative survival, the degrees of PV/SMV invasion on preoperative angiography (narrowing pattern and length) are good indicators for aggressive pancreatectomy for locally advanced pancreatic cancer.

Preoperative indications for extended pancreatectomy for locally advanced pancreas cancer involving the portal vein.

Acinar cell carcinoma (ACC) is an uncommon malignant tumor of the pancreas and it remains unclear how best to treat such tumors, especially at an advanced stage or after disease relapse. We report a 15-year survivor after successful resection of locally advanced ACC of the pancreatic head with en bloc resection of the common hepatic artery. Nine years after surgery, she developed massive bloody ascites containing many cancer cells of acinar cell origin. A volume of 2,000 mL of ascites was aspirated and 20 mg of cisplatin was injected into the peritoneal cavity biweekly. After this treatment had been repeated four times at our outpatient clinic, the ascites disappeared without the appearance of any adverse side effects. The patient was alive 6 years after chemotherapy and had shown no signs of disease relapse. These observations suggested that pancreatic ACC may be very sensitive to cisplatin, if it can efficiently reach the cancer cells. Intraperitoneal cisplatin administration is, therefore, worth performing for treatment of the peritoneal seeding ACC. Acinar cell carcinomas of the pancreas are uncommon neoplasms, accounting for 1–2% of all cases of exocrine pancreatic tumors (1). The overall 5-year survival rate was reported to be as low as 6% by Klimstra and 0% by Cubilla (2,3), and no optimal treatment strategy for ACC has yet been determined. The liver is the most common site of distant metastasis from pancreatic ACC. Some recent reports suggested a good response rate of liver metastases of ACC to intra-arterial chemotherapy with a combination of 5-fluorouracil (5-FU) and cisplatin (CDDP) (4,5). Peritoneal spreading is less common than liver metastasis in pancreatic ACC, and there have been no previous reports of active or successful treatment for this condition. However, we report a case in which peritoneal carcinomatosis had once developed after resection of primary pancreatic ACC but it was successfully cured by an intraperitoneal administration of CDDP. These findings have important implications for the future of ACC treatment, especially at advanced stages or after cancer recurrence.

Acinar cell carcinoma of the pancreas successfully treated by en bloc resection and intraperitoneal chemotherapy for peritoneal relapse: a case report of a 15-year survivor.

Y O Sasaki

Papers

Practical usefulness of lymphatic and connective tissue clearance for the carcinoma of the pancreas head.

Preoperative indications for extended pancreatectomy for locally advanced pancreas cancer involving the portal vein.

Acinar cell carcinoma of the pancreas successfully treated by en bloc resection and intraperitoneal chemotherapy for peritoneal relapse: a case report of a 15-year survivor.