Primary Pancreatic Secretinoma: Further Evidence Supporting Secretin as a Diarrheogenic Hormone.

OBJECTIVES: To document the existence of primary pancreatic secretinoma in patients with watery diarrhea syndrome (WDS) and achlorhydria and establish secretin as a diarrheogenic hormone. BACKGROUND: Vasoactive intestinal peptide (VIP) has been widely accepted as the main mediator of WDS. However, in 1968, Zollinger et al reported 2 female patients with pancreatic neuroendocrine tumors, WDS, and achlorhydria. During surgery on the first, a 24-year-old patient, they noticed distended duodenum filled with fluid and a dilated gallbladder containing dilute bile with high bicarbonate concentration. After excision of the tumor, WDS ceased and gastric acid secretion returned. The second, a 47-year-old, patient's metastatic tumor extract given intravenously in dogs, produced significantly increased pancreatic and biliary fluid rich in bicarbonate. They suggested a secretin-like hormone of islet cell origin explains WDS and achlorhydria. These observations, however, predated radioimmunoassay, immunohistochemical staining, and other molecular studies. METHODS: The first patient's tumor tissue was investigated for secretin and VIP. Using both immunohistochemistry and laser microdissection and pressure catapulting technique for RNA isolation and subsequent reverse transcription polymerase chain reaction, the expression levels of secretin, and VIP were measured. RESULTS: Immunoreactive secretin and its mRNA were predominantly found in the tumor tissue whereas VIP and its mRNA were scarce. CONCLUSIONS: The findings strongly support that the WDS and achlorhydria in this patient may have been caused by secretin as originally proposed in 1968 and that secretin may act as a diarrheogenic hormone.

The surgical clerkship: a contemporary paradigm.

BACKGROUND: Traditional surgical clerkships have been composed of hospitalized patients, usually in academic centers, daily resident interaction, periodic attending rounds, assigned texts, and a lecture format. However, traditional clerkships do not reflect the current changes in learning theory nor the economic realities of today's surgical practice. Initiated in 2001, the allopathic Florida State University College of Medicine provided an opportunity to create a contemporary surgical clerkship. METHODS: At each of 6 regional campuses, clerkship students served as apprentices to a board-certified community surgeon. In addition, during weekly meetings with the student, a campus-specific Clerkship Director administered a centralized curriculum with defined objectives and competencies. Contact with residents was minimal, and lectures were not used. Students were free to choose from suggested texts or to use alternative learning sources. An electronic data system monitored patient contacts. Evaluations of the students' clinical performance are 360 degrees. RESULTS: To date, 450 students have graduated. No significant differences were found between campuses for the following: types of patients encountered, U.S. Medical Liscensure Examination Step 2 Clinical Knowledge and Clinical Skills scores, internal Objective Structured Clinical Examination results, or National Board of Medical Examiners scores (P > 0.05). The national examination metrics have been met or exceeded. On the recent anonymous Association of American Medical Colleges Graduation Questionnaire survey, the students rated the surgery clerkship as the best course in the school. Overall, 23.3% of graduates have chosen some aspect of surgery as a career. CONCLUSIONS: A quality clerkship in surgery can be provided using a nontraditional community-based system, with as many as 6 distributed campuses. Also, the distributed campus model does not lead to inequality in learning opportunities, surgical experiences, or basic surgical knowledge. Third, documentation of campus comparability is markedly assisted by electronic monitoring. Fourth, the tutorial model offers, at the very least, a comparable learning experience and is strongly supported by both students and the community surgical faculty. Finally, student learning and acquisition of a fund of surgical knowledge in this system has been confirmed by national metrics.

Management of severe acute pancreatitis: a surgical odyssey.

Throughout much of history, surgery of the pancreas was restricted to drainage of abscesses and treatment of traumatic wounds. At the turn of the 20th century under the impetus of anesthesia, such surgical stalwarts as Mayo Robson, Mickulicz, and Moynihan began to deploy laparotomy and gauze drainage in an effort to salvage patients afflicted with severe acute pancreatitis (SAP). Over the next thirty years, surgical intervention in SAP became the therapy for choice, despite surgical mortality rates that often exceeded 50%.When the discovery of the serum test for amylase revealed that clinically milder forms of acute pancreatitis existed that could respond to nonoperative therapy, a wave of conservatism emerged, and, for the next quarter century, surgical intervention for SAP was rarely practiced. However, by the 1960s, conservative mortality rates for SAP were reported to be as high as 60% to 80%, leading surgeons to not only refine the indications for surgery in SAP, but also to consider new approaches. Extensive pancreatic resections for SAP became the vogue in continental surgical centers in the 1960s and 1970s, but often resulted in high mortality rates and inadvertent removal of viable tissue.Accurate diagnosis of pancreatic necrosis by dynamic CT led to new approaches for management. Some surgeons recommended restricting intervention to those with documented infected necrosis, and proposed delayed exploration employing sequestrectomy and open-packing. Others advocated debridement early in the course of the disease for all patients with necrotizing pancreatitis, regardless of the status of infection. In the 1990s, however, a series of prospective studies emerged proving that nonoperative management of patients with sterile pancreatic necrosis was superior to surgical intervention, and that delayed intervention provided improved surgical mortality rates.The surgical odyssey in managing the necrotizing form of SAP, from simple drainage, to resection, to debridement, to sequestrectomy, although somewhat tortuous, is nevertheless an notable example of how evidence-based knowledge leads to improvement in patient care. Today's 10% to 20% surgical mortality rates reflect not only considerable advances in surgical management, but also highlight concomitant improvements in fluid therapy, antibiotics, and intensive care. Although history documents the important contributions that surgical practitioners have made to acute pancreatitis and its complications, surgeons are rarely complacent, and the recent emergence of minimally invasive techniques holds future promise for patients afflicted with this "... most formidable of catastrophes."

Intervention in necrotizing pancreatitis: an evidence-based review of surgical and percutaneous alternatives.

Interventional therapy in necrotizing pancreatitis is evolving. Efforts to modify or prevent pancreatic necrosis by intra-arterial infusion of antibiotics and antiproteases have been described. Moreover, traditional approaches to the surgical management of infected pancreatic necrosis are being challenged by a host of endoscopic and percutaneous techniques. While these approaches are potentially valuable additions to interventional therapy in necrotizing pancreatitis, few evidence-based studies are available to support their supplanting more traditional approaches at this time. Cooperative evidence-based multiinstitutional studies will be required to address the validity of these proposals.

Is there a role for chemoradiation in the management of cystadenocarcinoma of the pancreas?

Despite a paucity of data, cystadenocarcinoma of the pancreas has been considered to be resistant to chemoradiation, with a limited effect similar to that of the more common pancreatic adenocarcinoma. We describe a case of a partially excised cystadenocarcinoma with a positive surgical margin that was treated by neoadjuvant chemoradiation. No epithelial elements were found on histologic examination after reresection. Three previous cases of dramatic response of pancreatic cystadenocarcinoma to chemoradiation have been described in the literature. The current dogma alleging poor response of pancreatic cystadenocarcinoma to chemoradiation may be in error.

Nerve blocks and neuroablative surgery for chronic pancreatitis.

Surgical decompressive procedures for "large-duct" chronic pancreatitis have been notably successful in relieving pain. However, management of patients with intractable pain from "small-duct" chronic pancreatitis has been difficult, often resulting in narcotic addiction and/or malnutrition from major pancreatic resection. In view of the disappointing results from extensive pancreatic resections in these cases, denervation of pancreatic sympathetic pain afferents has been suggested as an alternative. Although denervation procedures have been attempted at multiple anatomical levels, results have unfortunately been mixed. The observed variability in results has been attributed to poor patient selection, incomplete understanding of neurophysiology of pancreatic pain, and perhaps inadequate knowledge of pancreatic neuroanatomy. At present, the preferred form of neural ablation is splanchnicectomy. However, a consistent and reliable method for identifying candidates for splanchnicectomy is critical, as it is clinically difficult to distinguish true pancreatic pain from other nociceptive conditions masquerading as pancreatic pain. Differential epidural anesthesia (DEA) is a promising, safe test for initial evaluation and patient selection, although it is not as precise as sometimes claimed. Patients responding to sympathetic block during DEA seem to be the best candidates for operative sympathetic ablation. At the moment, the optimal surgical approach to splanchnic ablation, which offers the least morbid technique, most favorable results, and an attractive risk-benefit ratio, is bilateral thoracoscopic splanchnicectomy. More experience and longer follow-up will be necessary to evaluate this approach.

Guiding the reluctant. A primer on guidelines in general and pancreatitis in particular.

Within the past 5 years, no fewer than 6 guidelines for the management of acute pancreatitis have appeared in the literature, including the current submission from the International Association of Pancreatology. When these collected guidelines are subjected to comparison, however, marked similarities emerge between the proposals, and significant differences are rare. Surprisingly, neither the passage of time nor the application of evidence-based medicine techniques to the creation of guidelines for acute pancreatitis has resulted in substantive changes to the original guidelines offered by the Atlanta Symposium. Moreover, it is important to realize that, despite claims of objectivity, opinion may enter into the process of guideline creation whenever proposals are based upon lesser levels of evidence. Until the guidelines common to these collected proposals have been supported by randomized controlled trials, it is unlikely that we need any more guidelines for acute pancreatitis.