Distinct gene expression pathways in islets from individuals with short- and long-duration type 1 diabetes.

AIMS: Our current understanding of the pathogenesis of type 1 diabetes (T1D) arose, in large part, from studies using the non-obese diabetic (NOD) mouse model. In the present study, we chose a human-focused method to investigate T1D disease mechanisms and potential targets for therapeutic intervention by directly analysing human donor pancreatic islets from individuals with T1D. MATERIALS AND METHODS: We obtained islets from a young individual with T1D for 3 years and from an older individual with T1D for 27 years and performed unbiased functional genomic analysis by high-depth RNA sequencing; the T1D islets were compared with islets isolated from 3 non-diabetic donors. RESULTS: The islets procured from these T1D donors represent a unique opportunity to identify gene expression changes in islets after significantly different disease duration. Data analysis identified several inflammatory pathways up-regulated in short-duration disease, which notably included many components of innate immunity. As proof of concept for translation, one of the pathways, governed by IL-23(p19), was selected for further study in NOD mice because of ongoing human trials of biologics against this target for different indications. A mouse monoclonal antibody directed against IL-23(p19) when administered to NOD mice resulted in a significant reduction in incidence of diabetes. CONCLUSION: While the sample size for this study is small, our data demonstrate that the direct analysis of human islets provides a greater understanding of human disease. These data, together with the analysis of an expanded cohort to be obtained by future collaborative efforts, might result in the identification of promising novel targets for translation into effective therapeutic interventions for human T1D, with the added benefit of repurposing known biologicals for use in different indications.

Risk-reducing appendectomy and the elimination of BRCA1-associated intraperitoneal cancer.

Risk-reducing bilateral salpingo-oophorectomy (RRBSO) and risk-reducing mastectomy are widely used for BRCA1 and BRCA2 mutation carriers to reduce the risk of ovarian and breast cancer. To our knowledge, no risk-reduction therapy has addressed the BCRA1/2 carrier lifetime risk of intra-abdominal peritoneal carcinoma from an appendix source. We identified a BRCA1 carrier in a hereditary breast and ovarian cancer kindred who developed a low-grade malignant appendiceal mucocele 2 years after risk-reducing salpingo-oophorectomy. Our retrospective meta-analysis assessed the risk of intraperitoneal appendiceal cancer in BRCA1/2 carriers after RRBSO to determine whether elective risk-reduction appendectomy could reduce the incidence of intraperitoneal cancer. Data sources included the case report and 12 reports of BRCA1 and BRCA2 carriers after RRBSO with ovarian, fallopian tube, breast, and peritoneal cancer published from January 1, 1985, through April 30, 2012. Main outcome measures were nonovarian, non-fallopian tube, nonbreast, positive intra-abdominal peritoneal carcinoma in previously cancer-free BRCA1/2 carriers after RRBSO. The source of intraperitoneal cancer in BRCA1/2 carriers after risk-reducing salpingo-oophorectomy is highly likely the appendix. Use of risk-reduction appendectomy with RRBSO in younger BRCA1/2 carriers may reduce lifetime risk of malignant tumor and eliminate intraperitoneal cancer.

Cardiac recurrence in a patient with long-term survival from metastatic colon cancer.

Metastatic colorectal cancer represents a major health problem in the US and worldwide. Forty percent of patients undergoing resection of the primary tumor will experience relapse. In this brief review, we describe a case of a woman with metastatic disease and long-term survival culminating with an unusual myocardial recurrence. Over three decades, a multimodality approach has evolved to allow for long-term survival in selected patients with metastatic colorectal cancer. In this case report, the role of multiple aggressive surgical resections is emphasized.

Optimizing perioperative decision making: improved information for clinical workflow planning.

Perioperative care is complex and involves multiple interconnected subsystems. Delayed starts, prolonged cases and overtime are common. Surgical procedures account for 40-70% of hospital revenues and 30-40% of total costs. Most planning and scheduling in healthcare is done without modern planning tools, which have potential for improving access by assisting in operations planning support. We identified key planning scenarios of interest to perioperative leaders, in order to examine the feasibility of applying combinatorial optimization software solving some of those planning issues in the operative setting. Perioperative leaders desire a broad range of tools for planning and assessing alternate solutions. Our modeled solutions generated feasible solutions that varied as expected, based on resource and policy assumptions and found better utilization of scarce resources. Combinatorial optimization modeling can effectively evaluate alternatives to support key decisions for planning clinical workflow and improving care efficiency and satisfaction.

Recurrent pneumonia and colobronchial fistula from Crohn's disease: Infliximab alters and simplifies surgical management.

We report a rare case of right-sided colobronchial fistula in a 47-year-old, severely malnourished male with a history of regional enteritis and recurrent right lower and middle lobe pneumonias medically managed with the addition of the immunomodulator infliximab prior to surgery. On admission, evaluation of sputum cultures and chest radiograph pattern of pneumonia led to the suspicion of colobronchial fistula. This diagnosis was confirmed by abdominal CT enteroclysis. This patient's pneumonia was initially treated with empiric antibiotics, then focused antibiotics based on culture results. The treatment for the regional enteritis and the secondary colobronchial fistula consisted of immunosuppression with infliximab, bowel rest, and total parenteral nutrition. The patient was discharged on a limited course of prednisone and received maintenance therapy with 3mg/kg IV infliximab infusions for four additional treatments with dramatic improvement in his clinical condition. Surgical therapy consisted of only bowel resection; no thoracic surgery or lung resection was necessary. The patient has had a dramatic improvement in his clinical condition and is currently disease-free on no maintenance therapy. The use of TNF-blocking agents such as infliximab may simplify the surgical approach in patients with complicated fistulous Crohn's disease.

Single-port laparoscopic right hemicolectomy: a safe alternative to conventional laparoscopy.

PURPOSE: Single-port laparoscopic surgery has evolved from an effort to minimize tissue trauma, limit morbidity, and maximize cosmesis. Limited data exist comparing single-port with conventional laparoscopy for right colectomy. Our aim is to compare single-port with laparoscopic colectomy with regard to safety and feasibility. We assert that this approach can be adopted in a safe and efficacious manner while using standard laparoscopic instrumentation. METHODS: This is a retrospective analysis of prospectively gathered data regarding 16 single-port and 27 conventional laparoscopic right hemicolectomies performed by a single surgeon between January 2008 and February 2009. Demographics, operative outcomes, and morbidity were included and analyzed using either Student t test or Fisher exact probability test. RESULTS: Single-port and conventional laparoscopic groups were similar with regard to age, gender, body mass index, prior abdominal surgery, and co-morbidity. Seventy-five percent and 70% of the operations were performed for malignancy in the single-port and the conventional laparoscopy group, respectively (P = .69). Operative duration was 106 minutes in the single-port group vs 100 minutes in the conventional group (P = .64). Blood loss was 54 mL and 90 mL, respectively (P = .07). No conversions or additions of ports occurred. Hospital stay was 5.3 days in the single-port group vs 6 days in the conventional group (P = .53). Margins were negative in both groups. Mean lymph node number was 18 and 16 nodes (P = .92). There was one death in the conventional group (P = .44). Morbidity including wound infection was 18.8% and 14.9%, respectively (P = .73). CONCLUSIONS: These findings support single-port right colectomy as a safe and efficacious approach to right colon resections in patients eligible for laparoscopy with minimal additional equipment or learning curve for experienced laparoscopic colorectal surgeons. The single port was undertaken without an increase in morbidity or mortality. There was no increase in operative time with use of the single-port approach. Finally, adequate lymph node harvest and margin clearance was maintained.

Robotic distal pancreatectomy: cost effective?

BACKGROUND: Minimally invasive techniques and even robotics in pancreaticobiliary surgery are being used increasingly. Cost-effectiveness is a practical burden associated with the introduction of surgical innovation. This study compares the costs and the outcomes of open, laparoscopic, and robotic distal pancreatectomies. We hypothesized that robotic distal pancreatectomy is cost-effective. METHODS: Between August 2008 and August 2009, 77 distal pancreatectomies were performed at a single academic medical center. A retrospective analysis of prospectively collected data on demographics, short-term outcomes, and direct cost was performed. RESULTS: Thirty-two open distal pancreatectomies, 28 laparoscopic distal pancreatectomies, and 17 robotic distal pancreatectomies were performed. Age, American Society of Anesthesia preoperative risk score, and specimen length were similar. Indications for laparoscopic distal pancreatectomies and robotic distal pancreatectomies included more cystic neoplasms (49%) and fewer malignancies (29%) versus open distal pancreatectomies (16% and 47%). Spleen preservation occurred in 65% robotic distal pancreatectomies versus 12% and 29% in open distal pancreatectomies and laparoscopic distal pancreatectomies (P < .05). The operative time averaged 298 minutes in robotic distal pancreatectomies versus 245 and 222 minutes in open distal pancreatectomies and laparoscopic distal pancreatectomies (P < .05). Blood loss and morbidity were similar with no mortality. The length of stay was 4 days in robotic distal pancreatectomies versus 8 and 6 in open distal pancreatectomies and laparoscopic distal pancreatectomies (P < .05). The total cost was $10,588 in robotic distal pancreatectomies versus $16,059 and $12,986 in open distal pancreatectomies and laparoscopic distal pancreatectomies. CONCLUSION: These data suggest direct hospital costs are comparable among all groups. They suggest a shorter length of stay in robotic versus laparoscopic or open approaches. Finally, spleen and vessel preservation rates may improve with a robotic approach at the expense of increased operative time. In summary, robotic distal pancreatectomy is safe and cost effective in selected cases.

Preservation of replaced or accessory right hepatic artery during pancreaticoduodenectomy for adenocarcinoma: impact on margin status and survival.

AIM: The aim of the study was to determine the impact of replaced or accessory right hepatic artery (RARHA) during pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PA). METHODS: Four hundred seventy-one consecutive patients underwent PD for PA at the two institutions; 47 patients (10%) had RARHA: 16 patients (neoRARHA group) received neoadjuvant chemoradiation, and 31 patients did not receive preoperative treatment (RARHA group). Thirty-one matched patients without RARHA comprised our control group. RESULTS: RARHA was preserved in 44 patients; three patients with involved RARHA had reconstruction (n = 2) or ligation (n = 1). Patients with R1 resection (n = 8) had tumor size ≥3 cm. Patients in the neoRARHA group had identical positive margin rate when compared with patients in RARHA group (p = 0.6). No difference was noted in median or 3-year overall survival times between RARHA group and control group. Two patients in RARHA group with involved RARHA died of disease progression after 6 and 12 months of follow-up. One patient in neoRARHA group with involved RARHA was still alive without recurrence after 28 months' follow-up. CONCLUSIONS: Pathologic findings did not show increased positive margins despite preservation of RARHA. In contrast, patients with frank RARHA involvement seemed to have poor survival. Thus, patients with suspicion of involved RARHA should be considered for neoadjuvant chemoradiation.

Laparoscopic colectomy: does the learning curve extend beyond colorectal surgery fellowship?

BACKGROUND AND OBJECTIVES: As minimally invasive colon and rectal resection has become increasingly prevalent over the past decade, the role that fellowship training plays has become an important question. This analysis examines the learning curve of one fellowship-trained colorectal surgeon in his first 100 cases. METHODS: This was a prospectively collected retrospective analysis of the first 100 laparoscopic colon and rectal resections performed between July 2007 and July 2008 by a colorectal (CRS) fellowship trained surgeon at a Veteran's Administration (VA) and county hospital. Included were all emergent and nonemergent laparoscopic cases. RESULTS: Mean age was 63(range, 36 to 91). The 100 resections included 42 right, 6 left, 32 sigmoid, 13 rectal, and 7 total abdominal colectomies. Indications were 55% cancer, 20% unresectable polyp, 18% diverticular, 4% inflammatory, and 3% other. Overall mortality was 3%. Overall morbidity including wound infection was 24%. Early and late groups were similar in age, ASA score, and indication. Conversion rate was 4%. No statistical difference was seen in mortality, morbidity, EBL, LOS, margin, lymph nodes, or conversions between the first and second 50 cases (P<0.05). Right and sigmoid colectomy operative time decreased by 40.0% and 19.6%, respectively. CONCLUSION: Prior investigators have demonstrated a significant learning curve for laparoscopic colorectal surgery. In the first 100 cases, there is no difference in mortality or morbidity between early and late cases. Alternatively, operative times decreased with experience. Laparoscopic training during CRS fellowship surpasses the learning curve in regard to safety and outcome, whereas operative efficiency improves over the first year of practice.

Pancreatic fistula following pancreaticoduodenectomy: clinical predictors and patient outcomes.

Pancreatic fistula continues to be a common complication following PD. This study seeks to identify clinical factors which may predict pancreatic fistula (PF) and evaluate the effect of PF on outcomes following pancreaticoduodenectomy (PD). We performed a retrospective analysis of a clinical database at an academic tertiary care hospital with a high volume of pancreatic surgery. Five hundred ten consecutive patients underwent PD, and PF occurred in 46 patients (9%). Perioperative mortality of patients with PF was 0%. Forty-five of 46 PF (98%) closed without reoperation with a mean time to closure of 34 days. Patients who developed PF showed a higher incidence of wound infection, intra-abdominal abscess, need for reoperation, and hospital length of stay. Multivariate analysis demonstrated an invaginated pancreatic anastomosis and closed suction intraperitoneal drainage were associated with PF whereas a diagnosis of chronic pancreatitis and endoscopic stenting conferred protection. Development of PF following PD in this series was predicted by gender, preoperative stenting, pancreatic anastomotic technique, and pancreas pathology. Outcomes in patients with PF are remarkable for a higher rate of septic complications, longer hospital stays, but in this study, no increased mortality.

A pilot study of perillyl alcohol in pancreatic cancer.

BACKGROUND: Chemotherapy has been largely unsuccessful in pancreatic cancer. Measurement of cell-specific biological endpoints may clarify the evaluation of a newer generation of compounds. Perillyl alcohol has shown chemotherapeutic activity in preclinical systems through enhancing apoptosis. AIMS: To pilot a new trial template for testing novel agents in pancreatic cancer and to assess the biological activity of perillyl alcohol in patients with resectable pancreatic cancer. METHODS: Apoptosis was quantified with ApopTag in situ, Bak staining, and light microscopy. Tumor size, serum CA 19-9 level, and survival were also measured. RESULTS: Eight patients enrolled. Toxicity was mild and perillyl alcohol was generally well tolerated. Tumor size and CA 19-9 level were unchanged with perillyl alcohol treatment. Survival time was longer in patients who received full perillyl alcohol treatment (288 +/- 32 days) compared to those who did not (204 +/- 96 days), but this result did not achieve statistical significance (P = 0.2). There was a trend toward greater apoptosis in patients receiving perillyl alcohol compared to fresh operative controls; there was also a suggestion of greater apoptosis in tumor compared to normal pancreatic tissue in the same patient. CONCLUSIONS: Incorporation of cell-specific biological endpoints is challenging but feasible and should be used in clinical studies of pancreatic cancer treatment. Our pilot study suggests that perillyl alcohol may indeed have effects on biological endpoints. This study will serve as a useful template for examining cell-specific biological endpoints in the testing of future agents that are thought to induce apoptosis in pancreatic cancer.

A margin-negative R0 resection accomplished with minimal postoperative complications is the surgeon's contribution to long-term survival in pancreatic cancer.

Pancreatic cancer has a poor prognosis with complete surgical resection being the only therapy to offer a realistic chance for long-term survival. The aim of this study is to identify surgery-related variables that influence long-term survival. Between 1990 and 2002, 226 consecutive patients (mean age of 64+/-11 years) had resection for pancreatic adenocarcinoma. Prognostic variables in these patients were analyzed using univariate and multivariate analysis. Two hundred four patients (90%) had pancreaticoduodenectomy, 13 patients (6%) had distal pancreatectomy, and 9 patients (4%) had a TP. Stage I disease was present in 50 (22%), stage II disease in 170 (75%), and stage III disease in 6 (3%). R0 resections were achieved in 70%. Operative morbidity was 36% and 30-day mortality was 6%. Actual 1-year, 3-year, and 5-year survival rates were 49% (n=111), 14% (n=31), and 4% (n=9). Using multivariate analysis: tumor size, tumor differentiation, obtaining an R0 resection, and lack of postoperative complications were variables associated with long-term survival. Long-term survival in patients with pancreatic cancer after resection remains poor. Achieving a margin negative resection (R0) with no postoperative complications are prognostic variables that can be affected by the surgeon.

Parthenolide cooperates with NS398 to inhibit growth of human hepatocellular carcinoma cells through effects on apoptosis and G0-G1 cell cycle arrest.

Chemotherapy to date has not been effective in the treatment of human hepatocellular carcinoma. More effective treatment strategies may involve combinations of agents with activity against hepatocellular carcinoma. Parthenolide, a nuclear factor-kappaB (NF-kappaB) inhibitor, and NS398, a cyclooxygenase (COX)-2 inhibitor, have been shown to individually suppress the growth of hepatocellular carcinoma cells in vitro. To investigate their effects in combination, three human hepatocellular carcinoma lines (Hep3B, HepG2, and PLC) were treated with parthenolide and/or NS398. Parthenolide (0.1-10 micromol/L) and NS398 (1-100 micromol/L) each caused concentration-dependent growth inhibition in all cell lines. The addition of parthenolide to NS398 reduced the concentration of NS398 required to inhibit hepatocellular carcinoma growth. Because parthenolide and COX-2 inhibitors have been reported to influence NF-kappaB activity, the effects on this pathway were investigated. The combination of parthenolide/NS398 inhibited phosphorylation of the NF-kappaB-inhibitory protein IkappaBalpha and increased total IkappaBalpha levels. NF-kappaB DNA-binding and transcriptional activities were inhibited more by the combination than the single agents in Hep3B and HepG2 cells but not in PLC cells. The response of PLC cells to NS398 was augmented by p65 small interfering RNA to inhibit NF-kappaB p65 protein expression. The combination of parthenolide/NS398 increased apoptosis only in PLC cells, suggesting that the combination may decrease the apoptotic threshold in these cells. In Hep3B and HepG2 cells, combination treatment with NS398/parthenolide altered the cell cycle distribution resulting in more G0-G1 accumulation. Cyclin D1 levels were further decreased by combination treatment in all cell lines, correlating with the cell cycle alterations. Our results suggest that parthenolide may be effective in combination with COX-2 inhibitors for the treatment of hepatocellular carcinoma.

The effects of a novel MEK inhibitor PD184161 on MEK-ERK signaling and growth in human liver cancer.

The MEK-ERK growth signaling pathway is important in human hepatocellular carcinoma (HCC). To evaluate the targeting of this pathway in HCC, we characterized a novel, orally-active MEK inhibitor, PD184161, using human HCC cells (HepG2, Hep3B, PLC, and SKHep) and in vivo human tumor xenografts. PD184161 inhibited MEK activity (IC50 = 10-100 nM) in a time- and concentration-dependent manner more effectively than PD098059 or U0126. PD184161 inhibited cell proliferation and induced apoptosis at concentrations of > or = 1.0 microM in a time- and concentration-dependent manner. In vivo, tumor xenograft P-ERK levels were significantly reduced 3 to 12 hours after an oral dose of PD184161 (P < .05). Contrarily, tumor xenograft P-ERK levels following long-term (24 days) daily dosing of PD184161 were refractory to this signaling effect. PD184161 significantly suppressed tumor engraftment and initial growth (P < .0001); however, established tumors were not significantly affected. In conclusion, PD184161 has antitumor effects in HCC in vitro and in vivo that appear to correlate with suppression of MEK activity. These studies demonstrate that PD184161 is unable to suppress MEK activity in HCC xenografts in the long term. Thus, we speculate that the degree of success of MEK targeted treatment in HCC and other cancers may, in part, depend on the discovery of mechanisms governing MEK inhibitor signaling resistance.

Parthenolide and sulindac cooperate to mediate growth suppression and inhibit the nuclear factor-kappa B pathway in pancreatic carcinoma cells.

Activation of the transcription factor nuclear factor-kappa B (NF-kappa B) has been implicated in pancreatic tumorigenesis. We evaluated the effect of a novel NF-kappa B inhibitor, parthenolide, a sesquiterpene lactone isolated from the herb feverfew, in three human pancreatic tumor cell lines (BxPC-3, PANC-1, and MIA PaCa-2). Parthenolide inhibited pancreatic cancer cell growth in a dose-dependent manner with substantial growth inhibition observed between 5 and 10 micromol/L parthenolide in all three cell lines. Parthenolide treatment also dose-dependently increased the amount of the NF-kappa B inhibitory protein, I kappa B-alpha, and decreased NF-kappa B DNA binding activity. We have previously shown that nonsteroidal anti-inflammatory drugs (NSAID) suppress the growth of pancreatic cancer cells. To determine whether inhibition of the NF-kappa B pathway by parthenolide could sensitize pancreatic cancer cells to NSAID inhibition, BxPC-3, PANC-1, and MIA PaCa-2 cells were treated with parthenolide and the NSAID sulindac, either alone or in combination. Treatment with the combination of parthenolide and sulindac inhibited cell growth synergistically in MIA PaCa-2 and BxPC-3 cells and additively in PANC-1 cells. In addition, treatment with the parthenolide/sulindac combination lowered the threshold for apoptosis. Increased levels of I kappa B-alpha protein were detected, especially in MIA PaCa-2 cells, after treatment with parthenolide and sulindac compared with each agent alone. Similarly, decreased NF-kappa B DNA binding and transcriptional activities were detected in cells treated with the combination compared with the single agents, demonstrating cooperative targeting of the NF-kappa B pathway. These data provide preclinical support for a combined chemotherapeutic approach with NF-kappa B inhibitors and NSAIDs for the treatment of pancreatic adenocarcinoma.

Lack of prognostic importance of reverse-transcriptase polymerase chain reaction detection of circulating messenger RNA in patients with melanoma.

BACKGROUND: Molecular serologic markers for detecting early melanoma metastases have been described. The objective of this study was to determine whether reverse-transcriptase polymerase chain reaction detection of circulating tyrosinase messenger RNA (mRNA) can identify the presence of subclinical metastases and predict subsequent clinical recurrence in surgically treated melanoma patients who are at significant risk for relapse. METHODS: Preoperative peripheral blood samples of disease-free melanoma patients, disease stage ranging from I to IV, were analyzed for the presence of tyrosinase mRNA by semiquantitative reverse-transcriptase polymerase chain reaction as a putative marker for circulating melanoma cells. Multivariate analysis was performed to evaluate the prognostic value of tyrosinase mRNA in the blood and in the correlating pathologic stage of disease with recurrence and survival. RESULTS: The study group consisted of 96 patients. The mean age was 54 years (range, 24 to 83 years). The mean Breslow thickness was 3 mm (range, 0.9 to 21 mm). Circulating melanoma cells were detected in 66 patients (69 percent). Blood polymerase chain reaction positivity by American Joint Committee on Cancer stage was as follows: stage I, 19 of 28 patients (68 percent); stage II, 17 of 25 patients (68 percent); stage III, 28 of 41 patients (68 percent); and stage IV, two of two patients (100 percent). Tyrosinase detection was not associated with stage of disease (p = 0.77). At a median follow-up of 30 months, disease recurred in 21 patients (22 percent), and 15 patients (16 percent) died. Disease stage of the patients correlated with recurrence (p < 0.0001) and death (p < 0.0001). The finding of mRNA tyrosinase in peripheral blood samples was not associated with recurrence (p = 0.1) or death (p = 0.77). CONCLUSIONS: The use of polymerase chain reaction to detect circulating tyrosinase mRNA in peripheral blood does not correlate with traditional prognostic indicators in patients with cutaneous melanoma and does not appear to be an effective prognostic tool.

Pancreatic duct strictures are a common cause of recurrent pancreatitis after successful management of pancreatic necrosis.

BACKGROUND: Successful surgical management of pancreatic necrosis can result in structural changes that cause recurrent pancreatitis. The purpose of this study is to review our clinical experience managing recurrent pancreatitis in patients after successful pancreatic debridement. METHODS: We retrospectively reviewed 98 patients with pancreatic necrosis treated by debridement who made a complete recovery at our institution over an 8-year period (January 1995 to January 2003). RESULTS: Fourteen patients (14%) developed recurrent pancreatitis 5 to 39 months (median, 15 months) after recovery. Five patients (36%) had pancreatic pseudocysts and 9 (64%) had radiologic evidence of obstructive pancreatitis. All patients had either a high-grade pancreatic duct stricture (N=7) or complete duct cutoff (N=7), localized to the pancreatic neck (N=10) or proximal pancreatic body (N=4) identified by either endoscopic retrograde cholangiopancreatography or magnetic resonance cholangiopancreatography. Two patients failed endoscopic stent therapy. All patients required re-operative treatment: 6 distal pancreatectomy, 6 pancreatico-jejunostomy Roux-en-Y, and 2 cystojejunostomy Roux-en-Y with no recurrence of pancreatitis after a median follow-up of 22 months. CONCLUSIONS: Recurrent pancreatitis occurs in 14% of patients after successful pancreatic debridement. Pancreatic duct obstruction in the neck or proximal body is the primary etiologic factor. Re-operation directed at alleviating this ductal obstruction by resection or drainage is effective.