John M. Howard

Papillary cystic and solid tumors of the pancreas: A pancreatic embryonic tumor? Studies of three cases and cumulative review of the world's literature

BACKGROUNDnThe papillary cystic and solid tumor of the pancreas is rare. It occurs predominantly in young women, and most present a benign behavior. The pathogenesis of this tumor has attracted a number of investigations but remains unclear.nnnMETHODSnWe present three patients with this tumor and a review of 289 others from the worlds literature, a total of 292 cases. On the basis of the analyses of the clinical and pathologic features from the reported cases, the pathogenesis of this unusual tumor has been further explored.nnnRESULTSnNinety percent of the patients were female, with a mean age of 23.9 years. The tumors were usually quite large with a mean diameter of 10.3 cm. Ninety-two percent of these tumors were totally or partially cystic. Rupture of the capsule resulted in hemoperitoneum in eight cases, five of which were without any identifiable cause. Forty-three tumors (14.7%) have been recognized as malignant. The overall prognosis has been excellent and an aggressive approach to resection is indicated.nnnCONCLUSIONSnThe results of immunohistochemical staining and electromicroscopy were rather diverse, but most, including the current cases, support the hypothesis that the tumor originates from pleuripotential embryonic stem cells. Thus the term pancreatic embryonic tumors seems preferable to papillary cystic and solid tumor of the pancreas to delineate the origin of the tumor and to reflect some of its biologic characteristics.

Overexpression of HER2/neu oncogene in pancreatic cancer correlates with shortened survival

SummaryFor the purpose of determining the prognostic significance of HER2/neu oncogene in pancreatic and ampullary cancers, 21 pancreatic cancers of ductal origin and six cancers of the ampulla of Vater were studied immunohistochemically using the monoclonal antibody (MAb) CB11, specifically reactive with HER2/neu product. Staining of the epithelium of the normal duct and acini was negative or weakly positive. Moderately and strongly positive reactions indicated the overexpression of this gene, and were found in 10 of 21 (47.6%) pancreatic cancers of ductal origin and in 2 of 6 (33.3%) ampullary adenocarcinomas. Overexpression of HER2/neu was closely and inversely related to the survival of the patients with pancreatic cancer of ductal origin: 19.1±11.7 mo for those not overexpressing vs 7.3±3.8 mo for the overexpressors (p<0.01). Among the pancreatic cancer group, 11 patients underwent cancer resection. The average survival for the 7 with nonoverexpressing cancer was 21.4±14.3 mo vs 10.5±3.6 mo for those with the overexpressing tumor. Among those not undergoing resection, the average survival for the 4 with nonoverexpressing cancer was 15.0 ±3.8 mo as contrasted to 5.2±2.1 mo for the overexpressors (p<0.01). Although the number of patients is small, these findings duggest that the overexpression of HER2/neu gene product may be frequently found in pancreatic cancer of ductal origin and may be one of the useful prognostic biomarkers for this cancer.

Cystic neoplasms and true cysts of the pancreas.

As the spectrum of pancreatic cysts evolves, sped by the increasing utilization of CT scanning, it becomes apparent that the surgeon must gain information preoperatively about the family history, as well as the personal history of the patient. The presence of cysts in the liver or kidney should be sought. The relation of the lesion to the duodenum and biliary tract needs to be defined. The possibility that the cyst represents necrosis of a primary adenocarcinoma of the pancreatic duct should be considered prior to laparotomy. At the time of operation, biopsy of the cyst wall and frozen-section study are fundamental to a decision whether resection or drainage is the treatment of choice. Resection is generally the treatment of the cystic neoplasms, drainage the treatment of pseudocysts. The failure of the surgeon to distinguish between the two groups may be catastrophic. The true cysts and cystic neoplasms of the pancreas are rare lesions. The clinical and radiologic characteristics, the pathologic features, and the natural history of these lesions are not fully documented. Therefore, when they are encountered, the clinician who will carefully document their characteristics can make a contribution to our knowledge.

Pancreaticoduodenectomy (Whipple resection) in the treatment of chronic pancreatitis

AbstractThe armamentarium of the pancreatic surgeon must include multiple operative techniques, to be adapted to the clinical and anatomical findings in the patient with chronic pancreatitis. Pancreaticoduodenectomy is an essential component of this armamentarium. Its indications and limitations require continued refinement.nPancreaticoduodenectomy (Whipple operation) provides excellent results in the relief of the pain of chronic pancreatitis. The incidence of reoperation for control of pain after this procedure is less than after drainage procedures. The postoperative mortality rate in recent reports is less than 2%. Whereas resection of pancreatic tissue diminishes pancreatic function, the metabolic deficits are partially compensated by the better nutritional status resulting from pain relief and discontinuation of narcotics.nIn experienced hands, pancreaticoduodenectomy would appear to be the procedure of choice in patients with small pancreatic ducts. In selected patients, it appears to be a good procedure and, possibly, the operation of choice when the disease is predominantly present in the head of the pancreas and/or the uncinate process, especially when strictures involve the common bile duct and duodenum. The authors prefer the procedure when a hard, chronically-inflamed mass is present in the head of the pancreas.nIn our experience, if the suspicion of malignancy of the head of the pancreas persists at operation, pancreaticoduodenectomy is the procedure of choice. Before undertaking resection, the individual surgeon must assess his/her own experience; a low risk is essential.nThe continuing alcoholic is not a candidate for pancreaticoduodenectomy. Those who will not stop drinking should seldom be accepted for resection. The same limitation exists for the narcotic addict, but few such patients are encountered today.nIn the authors experience, the operation is excellent for the relief of pain. It is the lifestyle of the continuing alcoholic that poses the more significant problem.RésuméLe chirurgien du pancréas doit disposer de plusieurs interventions adaptées aux données cliniques et anatomiques du patient qui a une pancréatite chronique. La duodénopancréatectomie céphalique est lélément essentiel de cette panoplie. On doit en préciser les indications et les limites.La duodénopancréatectomie céphalique (opération de Wipple) donne dexcellents résultats pour soulager la douleur de la pancréatite chronique. Lincidence des réopérations nécessaires après cette intervention pour soulager la douleur est bien moindre quaprès les anastomoses pancréaticojéjunales. Dans la littérature récente, la mortalité est de moins de 2%. La résection du parenchyme diminue la fonction pancréatique, les déficits métaboliques sont en partie compensés lamélioration de létat nutritionnel, conséquence du soulagement de la douleur et de larrêt de la prise dantalgiques.En mains expérimentées, la duodénopancréatectomie paraît le procédé de choix chez les patients dont le canal a un petit calibre. Chez certains patients sélectionnés, elle est indiquée quand la maladie prédomine dans la tête et/ou dans le procédé unciné, surtout sil existe aussi une sténose du cholédoque et du duodénum. Les auteurs préfèrent pratiquer ce procédé en cas de masse inflammatoire chronique dans la tête du pancréas.Dans notre expérience, la duodénopancréatectomie est aussi indiquée sil y suspicion de cancer. Avant dentreprendre ce type de résection, le chirurgien doit interroger ses capacités car il est essentiel de ne pas augmenter le risque couru par le patient. Lalcoolique qui continue à boire ne doit pas être candidat à la duodénopancréatectomie. On devrait de même refuser les malades accoutumés aux antalgiques mais on rencontre peu de nos jours ce type de patients.Dans lexpérience des auteurs, cette intervention soulage la douleur: ce qui compte le plus, cest la qualité de la vie de lopéré.ResumenEl armamentario del cirujano de pancreas debe incluír múltiples técnicas operatorias capaces de ser adaptadas a los diferentes cuadros chínicos y anatómicos que se presentan en el paciente con pancreatitis crónica. La pancreaticoduodenectomía es un componente esencial de tal armamentario; sus indicaciones y limitaciones requieren un continuado refinamiento.La pancreaticoduodenectomía (operación de Whipple) da excelentes resultados en cuanto al control del dolor en la pancreatitis crónica. La tasa de reoperación para control del dolor con este procedimiento es menor que con los procedimientos de drenaje. La tasa de mortalidad postoperatoria en reportes recientes es de menos del 2%. A pesar de que la resección del tejido pancreático disminuye la función pancreática, los déficits metabólicos son parcialmente compensados por un mejor estado nutritional consecuente al control del dolor y a descontinuar los narcóticos.En manos expertas la pancreaticoduodenectomía parece ser el procedimiento de elección en pacientes con canales pancreáticos pequeños. En casos seleccionados aparece como un buen procedimiento, y tal vez como la operatión de escogencia, cuando la enfermedad esta primordialmente localizada sobre la cabeza y/o el proceso uncinado del páncreas y especialmente cuando hay estrecheces del colédoco y el duodeno. Los autores prefieren este procedimiento cuando se presenta una masa firme de inflamación crónica en la cabeza del páncreas.En nuestra experiencia, si durante la operación persiste la sospecha de neoplasia maligna, la pancreaticoduodenectomía es el procedimiento de elección. Antes de emprender el procedimiento, el cirujano debe valorar su propia experiencia individual; un bajo riesgo es prerrequisito esencial.El alcohólico persistente no es candidato para pancreaticoduodenectomía, y aquellas personas que no dejen de tomar muy rara vez deben ser aceptadas para operación. Las mismas limitaciones existen para el adicto a los narcóticos, pero pocos de estos pacientes se presentan en la actualidad.En la experiencia del autor la operación es excelente en cuanto al control del dolor. Realmente es el estilo de vida del alcohólico consuetudinario el problema de mayor significacion en el manejo del paciente con pancreatitis crónica.

Carcinoid Tumors of the Pancreas: Status Report Based on Two Cases and Review of the World's Literature

SummaryConclusion. The diagnosis of a pancreatic carcinoid should be based on the measurement of serotonin in serum or its demonstration in the tumor and/or by the measurement of its derivative (5-HIAA) in urine. Carcinoid of the pancreas is a rare but definite entity; usually having metastasized by the time of diagnosis. The term “serotonin-producing tumor of the pancreas” has been suggested as an alternative designation for “pancreatic carcinoid.”Background. The literature on carcinoid tumors of the pancreas is confusing because much of it preceded the development of the more specific immunological, chemical and staining techniques currently available.Methods. 43 case reports were collected from the world’s literature, based on a demonstrable pancreatic neuroendocrine tumor plus a positive finding of at least one of the following without another dominant hormone being demonstrated: elevation of 5-Hydroxytryptamine (5-HT) (serotonin) in the serum or detected in tumor tissue, and/or elevation of 5-Hydroxyindole acetic acid (5-HIAA) in the urine. In addition to these two hormone-specific assays, information was collected on the silver-staining properties of the tumor; properties which have traditionally been associated with carcinoid tumors. Positive silver staining in tumor cells (argyrophilic and/or argentaffin reaction) is strongly indicative of the carcinoid tumor but the findings are less specific than the hormone assays and immunohistologic stains.Results. In this review of 43 cases, including two current ones, the pancreatic carcinoid tumor has the following important features:1.It is a rare tumor that is usually diagnosed late when the tumor is large and has metastasized. Thirty-eight (88.4%) have been malignant. They are, therefore, associated with a high incidence of the “carcinoid syndrome.”2.To date, prognosis in therapy is poor, based on delayed diagnosis, a resultant low incidence of resectability, and an uncertain duration of survival after resection.3.Pancreatic carcinoid tumors remain difficult to differentiate from other endocrine tumors. The measurement of urinary 5-HIAA excretion or the demonstration of elevated serotonin level in the tumor or in serum is essential to its distinction. Silver staining of the tumor, although of historic importance, has been superceded by the hormone-specific studies.4.To distinguish it from other endocrine tumors of the pancreas, the terms “pancreatic serotoninoma” or “serotonin-producing tumor of the pancreas” have been suggested as possible alternatives.Its growth characteristics may be related more to its cell of origin than to its extent of hormone secretion. Not all of the tumors result in recognizable hyperserotoninemia.

Development and progress in resective surgery for pancreatic cancer.

Abstract. Pancreatoduodenectomy was developed from experience gained with transduodenal ampullectomy, preceded by a relatively bloodless cholecystoenterostomy. Although Codivilla (1898) and Kausch (1909) each achieved a single survivor following pancreatoduodenectomy, further development of the operation had to await discovery of vitamin K and a description of human blood types, the latter leading to the development of blood banks. After vitamin K and blood banks became available, Allen O. Whipple and his resident C.R. Mullins developed the two-stage pancreatoduodenectomy (1934–1935) and Whipple the one-stage procedure (1940). Although the mortality rate from pancreatoduodenectomy remained approximately 33% for more than 25 after Whipples reports, concentration of resection in “centers of specialization” has now reduced mortality rates below 5%. Thus operative survival has been achieved, but long-term survival has not kept pace. Long-term data remain inadequate because they are usually expressed as Kaplan-Meier estimates and because of the nonuniformity of reporting (e.g., exclusion of postoperative deaths and palliative resections, intraoperative adjuvant therapies, and variations of operative techniques). Widely based Kaplan-Meier estimates of 5-year survival range from 12% to 15% after resection and more than 20% in selected categories. Total pancreatectomy has not improved short- or long-term survival rates. Extended lymphadenectomy and resection of peripancreatic soft tissues, as currently developed in several surgical clinics in Japan, suggest a higher incidence of complications but perhaps more long-term survivors. Interpretation of their data is currently subject to the same limitations noted above. As our surgical forebears needed vitamin K and blood banks to achieve postresection survival, we and our students need effective adjuvant therapy of micrometastases and better modalities for early diagnosis to improve long-term survival.

Adenocarcinoma of duodenum and ampulla of Vater: Clinicopathology study and expression of p53, c-neu, TGF-α, CEA, and EMA

Oncogenes, tumor suppressor genes, and growth factors are being explored as to their role in the initiation and progression of most neoplasms, but little information exists on the expression of oncoproteins or growth factors in adenocarcinoma of the duodenum or ampulla of Vater. This report covers expressions of p53, c‐neu, TGF‐α, CEA, and EMA in duodenal adenocarcinoma and ampullary adenocarcinoma, as well as correlations between expressions and tumor stage, histological grade and patient survival. The expression of p53, c‐neu, TGF‐α, CEA, and EMA has been studied in 15 duodenal adenocarcinomas and in eight ampullary adenocarcinomas by avidin‐biotin‐peroxidase complex indirect immunoperoxidase technique. The positive reaction for p53, c‐neu, TGF‐α, CEA, and EMA in duodenal adenocarcinoma was 20%, 60%, 60%, 73%, and 100%, respectively, and in ampullary adenocarcinoma, 13%, 100%, 50%, 63%, and 100%. Among the duodenal tumors, C‐neu and p53 expression was noted more frequently in groups with high histological grades. Patients with c‐neu positive duodenal adenocarcinoma had a shorter survival than the patients with c‐neu negative duodenal adenocarcinoma (P < 0.01). C‐neu product may serve as an unfavorable prognostic indicator in duodenal adenocarcinoma. No statistically significant correlation was found between the expressions of CEA, EMA, p53, and TGF‐α and patient survival, tumor stage, or histological grade in either duodenal or ampullary adenocarcinomas.

Pancreatitis associated with neuroendocrine (islet cell) tumors of the pancreas

BACKGROUNDnThe association of pancreatitis with neuroendocrine tumors of the pancreas is uncommon, whereas its association with exocrine pancreatic cancer is well recognized. Since the latter, but not the islet cell tumor, is thought to originate within the ductal system, it is not surprising that pancreatitis is less likely to result from the islet cell tumor. The senior author has recently noted that the first recognizable indication of an islet cell carcinoma may be one or more discrete attacks of acute pancreatitis.nnnMETHODS AND RESULTSnAcute pancreatitis, resulting from an islet cell tumor, has been observed in five patients, in one of whom it had become chronic. In four of the patients, the tumor was malignant. A review of the English language literature reveals 14 such patients with pancreatitis, and 2 others have been noted in other languages (a total of 21 patients). The tumor was malignant in 15 of the 21 patients (71%). Although the development of pancreatitis was found to result from the obstruction of the duct in most patients, at least three seemed unrelated. In 12 of 21 cases (57%), an acute attack of pancreatitis, usually recurrent, was the initial syndrome, in contradistinction to pancreatitis resulting from exocrine tumors, which has usually been chronic in nature.nnnCONCLUSIONnPancreatitis, particularly acute pancreatitis, may result from an islet cell tumor. Although unusual, its occurrence may be the first signal of the presence of the tumor. In our experience, obstruction of the pancreatic duct by the islet cell carcinoma appears to be the important etiologic factor.

Treatment of cancer of the pancreas by precision high dose (PHD) external photon beam and intraoperative electron beam therapy (IOEBT)

Twenty-five patients with a diagnosis of unresectable adenocarcinoma of the pancreas were explored in the Clement O. Miniger (COMROC) IOEBT operating amphitheater at the Medical College of Ohio. Seventeen were treated with IOEBT (20-30 Gy, 15 or 18 meV electrons) PHD external beam radiation therapy (40-60 Gy, 1.8 Gy per fraction) plus appropriate operative biliary and gastrointestinal bypass procedures. No intraoperative complications were observed. Two patients died of causes that may have been treatment-related. Two patients developed abdominocutaneous fistulae. Pain was ameliorated in eleven of twelve patients. Jaundice was relieved in all patients. Four of ten patients with weight loss showed a reversal of that trend. Patient survival was not significantly different from that of patients treated with high-dose precision therapy alone.

Johann Georg Wirsüng (1589-1643) and the pancreatic duct: the prosector of Padua, Italy

Although his primacy was subsequently challenged by a student, it is now known that Johann Georg Wirsüng, the prosector of Padua, Italy, discovered the human pancreatic duct in 1642 during the dissection of an executed murderer. Instead of publishing his discovery, he engraved a drawing of the duct on a copper plate, from which he made seven or more imprints. The copies were sent to leading anatomists of Europe with the question, Should I call it an artery or a vein? I never found blood in it .... Three and a half centuries later, the copper plate remains well preserved and the authors, to the surprise of European surgeons and librarians, but with their aid, have traced six copies of the ductus Wirsüngianus imprints still in existence. This is the story of Wirsüng the man, his subsequent assassination, and finally the recognition that his finding had opened a new field of science.