Stanley R. Friesen

Importance of pathologic staging in the surgical management of adenocarcinoma of the exocrine pancreas

Abstract A retrospective analysis of 348 patients with adenocarcinoma of the exocrine pancreas was carried out to determine the effects of stage of the disease on survival time with and without definitive surgical treatment. The extent of the disease as judged by operative and histologic findings at the time of operation was staged as follows: stage I, local disease only; stage II, invasion of surrounding tissues; stage III, regional node metastases; stage IV, generalized carcinoma. The mean time of survival in 125 patients who underwent laparotomy and biopsy only for diagnosis was 0.15 year with no significant difference in survival time for the four different stages of disease. One hundred seventy-two patients underwent palliative procedures with a mean survival time of 0.42 year. Survival time was significantly better for patients with stage I, stage II, and stage III disease after palliative procedures, whereas with stage IV disease survival was similar to that seen with laparotomy only. Fifty-one patients underwent excisional procedures with a mean survival time of 0.95 year. Resections for stage I and stage II disease resulted in survival times of 1.4 and 1.2 years, respectively. However, for stage III and stage IV disease the survival time after resection was almost identical to that observed with palliative procedures only. This study reveals that survival time for stage I and stage II disease is significantly longer after excisional procedures, whereas for stage III disease palliative procedures yield survival expectations similar to those for resections.

Pancreatic polypeptide as screening marker for pancreatic polypeptide apudomas in multiple endocrinopathies

Prospective screening was carried out in 12 members of three families with multiple endocrine adenopathies, type I (MEA,I) and in 14 patients with no multiple endocrine adenopathies with and without other endorcinopathies. Elevated basal and responsive (after a meal) plasma concentrations of a relatively new candidate-hormone, human pancreatic polypeptide (hPP), were associated with pancreatic apudoma tumors in three asymptomatic patients with multiple endocrine adenopathies, type I. Two of these patients had excision of the tumors that resulted in normal plasma hPP concentrations postoperatively. Both tumors contained hPP predominantly by immunocytochemistry; one, a pure pancreatic polypeptide apudoma, was studied extensively demonstrating also by radioimmunoassay a high content of hPP and negligible amounts of insulin, glucagon, somatostatin, vasoactive intestinal polypeptide and gastrin. In this patient plasma concentrations of other polypeptides including insulin, glucagon, somatostatin, vasoactive intestinal polypeptide, gastrin, parathyrin, thyrocalcitonin, prolactin, corticotropin, growth hormone, thyrtropin and amine, serotonin, were within normal limits. The other patient, after excision of an hPP-detected pancreatic mixed hPP-gastrinoma, also became eugastrinemic postoperatively. Normal basal plasma hPP concentrations, but with exaggerated hPP responses to a meal in 11 patients, were associated with various combinations of islet cell hyperplasia, antral G cell hyperplasia with moderate hypergastrinemia and parathyroid hyperplasia. The patients with multiple endocrine adenopathies who have demonstrated this type of increased hPP response to a meal have not been operated on but are at risk for islet hyperplasia. Four of the 12 patients with multiple endocrine adenopathies, type I, with both normal basal and normally responsive hPP concentrations have no evidence as yet of pancreatic involvement.

Outcome of lymph node involvement in patients with the Zollinger-Ellison syndrome.

Prognosis of gastrinoma patients with metastases to lymph nodes only is uncertain, and the true nature of isolated nodal gastrinomas remains controversial. The purpose of this study was to determine the outcome of such patients and whether nodal gastrinomas may occur as primary lesions. Eleven patients with nodal involvement but without hepatic metastases are reported (mean follow-up of 129 months). Primary gastrinomas were located in the duodenum in seven (Group 1) and not identified in four (Group 2). In Group 1, five patients remained eugastrinemic after excision of all gross tumors and gastrectomy (n = 4) or pancreaticoduodenectomy (n = 1), one patient had residual disease and died of other causes (survival of 88 months), and one patient had MEA-I syndrome with multiple gastrinomas (follow-up of 126 months). In Group 2, three patients became eugastrinemic after nodal excision and total gastrectomy (mean follow-up of 212 months) and may represent primary nodal gastrinomas, and in one patient, liver metastases developed and the patient died. Four deaths occurred in a 27-year period, but only one was tumor-related. There was no significant difference in 20-year survival rates between the two groups (85% vs. 75%). It is concluded that 1) lymph node gastrinomas are usually metastatic from primary duodenal lesions, 2) although rare, nodal gastrinomas may occur as primary lesions, and 3) in the absence of hepatic metastases, lymph node gastrinomas, whether primary or metastatic, have a good prognosis and should not deter aggressive surgical treatment.

Glucagon, gastrin, and carcinoid tumors of the duodenum, pancreas, and stomach: Polypeptide “apudomas” of the foregut

Endocrine tumors of the foregut appear to have an embryologic “raison d’etre” in that the cells of most of these tumors have developed in common from precursor neuroectodermal cells which have migrated from the neural crest. Pearse and Polak [I] and Carvalheira, Welsch, and Pearse [2] have shown that a majority of the cells in the foregut endocrine system share common cytochemical properties, including their ability to take up and decarboxylate certain amino acids which are the precursors of fluorogenic amines (amine precursor uptake and decarboxylation [APUD] cells). The precursor cells in mouse embryos can be made to fluoresce, after injection of the exogenous precursor L-dopa into the pregnant mouse, by a process of formaldehyde-induced fluorescence (FIF) [3]; using this method, Polak and Pearse [1,4] have demonstrated the migration of the fluorescent neuroectodermal cells from the neural crest to the epithelium of the endoderm of the pharyngeal pouches, stomach, duodenum, and pancreas. These endocrine cells, once toti-potential, are located in the human foregut from the anterior pituitary to the mid-duodenum and pancreas, and also in the loci of the neuroendocrine system of the adrenal medulla, paraganglionic tissues, and other mesodermal areas [5,6].

Pseudo-Zollinger-Ellison syndrome: hypergastrinemia, hyperchlorhydria without tumor.

The purpose of the investigation was to detect ulcer patients having nontumorous hypergastrinemic hyperchlorhydria and to diagnostically differentiate this pseudo-Zollinger-Ellison syndrome from neurogenic duodenal ulcer disease and pancreatic gastrinomas. Nine patients having clinical, radiologic and humoral findings simulating the Zollinger-Ellison syndrome or severe duodenal ulcer disease were studied by physiologic provocative testing. The patients, not having pancreaticoduodenal gastrinomas, had an antral mucosal source of their moderate hypergastrinemia even after vagotomy with drainage, which was eliminated in eight patients treated by surgical antrectomy, resulting in normal serum gastrin concentrations. The pseudo-Zollinger-Ellison syndrome is, thus, characterized physiologically by an exaggerated gastrin response to meals, no response to secretin stimulation and pathologically by hyperfunctioning hyperplastic G cells of the antrum. The clinical, physiologic, pathologic and surgical features were integrated for accurate diagnosis and treatment

Treatment of the Zollinger-Ellison syndrome: A 25 year assessment

An assessment of treatment methods for the Zollinger-Ellison syndrome over 25 years suggests that the dual surgical approach of excision of resectable tumor and total gastrectomy provides the greatest possibility of attaining tumor and serum gastrin control. Normal serum gastrin levels and reduction of tumor status, not observed with nonoperative management, were attained by surgical treatment, particularly when the tumor (or hyperplasia) was limited to the pancreas, stomach, duodenum and regional lymph nodes. Eleven of 16 such operations resulted in tumor control, and 10 of these patients developed normal serum gastrin concentrations. In elective clinical situations combined medical and surgical therapy is a rational approach allowing confirmation of diagnosis and safe, definitive surgical control of the syndrome before metastases occur.

Significance of tumor spread in adenocarcinoma of the ampulla of vater

Twenty-eight patients with ampullary carcinoma were treated between 1965 and 1988: 22 underwent pancreaticoduodenectomy with 1 operative death (5 percent), 1 had local excision, 3 had bypass, and 2 were not explored. Of the 21 patients who survived pancreaticoduodenectomy, 4 had tumor confined to the ampulla, 7 had tumor extending into the duodenum, and 10 had tumor invasion beyond the duodenum. Nine of these patients had positive lymph nodes and 12 had negative lymph nodes. The patient who had local excision was disease-free at last follow-up 104 months postoperatively. Each of the three bypassed patients died of tumor progression within 15 months. The estimated 5-year survival rate for resected patients was 60 percent and was independently related to lymph node metastases (p = 0.031) and to tumor size (p = 0.039). This experience suggests that long-term survival is possible in patients with lymph node metastases or invasive tumors extending beyond the duodenal wall and that curative pancreaticoduodenectomy can be performed with a low operative mortality; therefore, aggressive surgical resection is recommended for all patients with ampullary carcinoma.

Characteristics of duodenal wall gastrinomas

Fifteen patients with duodenal wall gastrinomas (DWGs) and the Zollinger-Ellison syndrome have been treated since 1960. In 6 of 11 patients, DWGs were recognized at operation and totally excised. In four patients, the tumor was subsequently found in the proximal duodenum of the surgical specimens. In 12 patients, DWGs were single and lymph node metastases were present in 8. In three patients, DWGs were multiple and lymph node metastases were present in two. All DWGs were submucosal and all were located in the first or second portions of the duodenum except one found in the fourth portion. Tumor size ranged from 1 to 15 mm, and nine were less than 5 mm. Of 12 patients with single DWGs, 9 have remained eugastrinemic after resection (mean follow-up: 5.5 years). None of the patients with multiple DWGs became eugastrinemic after surgery. DWGs are characteristically single, small or microscopic, submucosal, located in the proximal duodenum, rarely metastasize to the liver, and are usually curable by surgical resection.

Role of Hemoconcentration in Production of Gastric and Duodenal Ulcer Following Experimental Burns.

Conclusions Evidence is presented to show that increased concentration of the blood following burns is an important factor in the occurrence of gastro-duodenal ulcer after experimental burns. (The occurrence of gastro-intestinal congestion, erosion and/or ulcer in burns is directly related to the occurrence of hemoconcentration). Moreover, gastro-intestinal abnormality following burns, even when accompanied by histamine administration, may be prevented by avoidance of the hemoconcentration of burns by proper therapy. The incidence of gastric and/or duodenal ulceration provoked by hemoconcentration in burns is markedly increased when histamine-in-beeswax administration accompanies the burn.

Vagotomy Fails to Protect Against Histamine-Provoked Ulcer.

Conclusions 1. Bilateral vagotomy (infra- and supradiaphragmatic) failed to protect against ulcer or erosion (gastric and/or duodenal) produced by chronic histamine action in the dog, cat and rabbit.