Search

Gene products downregulated greater than or equal to 2.4-fold by JQ1 in CCA1 tumors.

Immunoblot analysis showing that JQ1 downregulates TEK, Chk1, MSH2 and LCK expression in CCA2 tumors, but not in CCA1 tumors.

Cholangiocarcinoma (CCA) is a fatal disease with a 5-year survival of Mol Cancer Ther; 17(1); 107–18. ©2017 AACR.

Expression Indices

Patient-derived xenograft (PDX) models of cholangiocarcinoma (CCA): tumor growth and histology.

Pathways to which the identified 24 genes downregulated by JQ1 treatment in CCA2 (Figure 5) contribute.

Time course of increase in tumor volume in mice treated with vehicle (VC) or JQ1.

Immunohistochemistry analysis and nuclear expression indices of BRD4 in first generation (F1) CCA3, CCA4 and CCA5.

EGFR and c-Myc proteins are overexpressed to similar levels in F0 and corresponding F1 tumors.

CCR Translation for This Article from Serum Biomarker Panels for the Detection of Pancreatic Cancer

Purpose: Serum–biomarker based screening for pancreatic cancer could greatly improve survival in appropriately targeted high-risk populations.Experimental Design: Eighty-three circulating proteins were analyzed in sera of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC, n = 333), benign pancreatic conditions (n = 144), and healthy control individuals (n = 227). Samples from each group were split randomly into training and blinded validation sets prior to analysis. A Metropolis algorithm with Monte Carlo simulation (MMC) was used to identify discriminatory biomarker panels in the training set. Identified panels were evaluated in the validation set and in patients diagnosed with colon (n = 33), lung (n = 62), and breast (n = 108) cancers.Results: Several robust profiles of protein alterations were present in sera of PDAC patients compared to the Healthy and Benign groups. In the training set (n = 160 PDAC, 74 Benign, 107 Healthy), the panel of CA 19–9, ICAM-1, and OPG discriminated PDAC patients from Healthy controls with a sensitivity/specificity (SN/SP) of 88/90%, while the panel of CA 19–9, CEA, and TIMP-1 discriminated PDAC patients from Benign subjects with an SN/SP of 76/90%. In an independent validation set (n = 173 PDAC, 70 Benign, 120 Healthy), the panel of CA 19–9, ICAM-1 and OPG demonstrated an SN/SP of 78/94% while the panel of CA19–9, CEA, and TIMP-1 demonstrated an SN/SP of 71/89%. The CA19–9, ICAM-1, OPG panel is selective for PDAC and does not recognize breast (SP = 100%), lung (SP = 97%), or colon (SP = 97%) cancer.Conclusions: The PDAC-specific biomarker panels identified in this investigation warrant additional clinical validation to determine their role in screening targeted high-risk populations. Clin Cancer Res; 17(4); 805–16. ©2010 AACR.

Supplementary Figures S1-S2; Supplementary Tables S1-S2.

Intraperitoneal drain placement decreases morbidity and mortality in patients who develop a clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). It is unknown whether multiple drains mitigate CR-POPF better than a single drain. We hypothesized that multiple drains decrease the complication burden more than a single drain in cases at greater risk for CR-POPF.The Fistula Risk Score (FRS), mitigation strategies (including number of drains placed), and clinical outcomes were obtained from a multi-institutional database of PDs performed from 2003 to 2020. Outcomes were compared between cases utilizing 0, 1, or 2 intraperitoneal drains. Multivariable regression analysis was used to evaluate the optimal drainage approach.A total of 4,292 PDs used 0 (7.3%), 1 (45.2%), or 2 (47.5%) drains with an observed CR-POPF rate of 9.6%, which was higher in intermediate/high FRS zone cases compared with negligible/low FRS zone cases (13% vs 2.4%, P.001). The number of drains placed also correlated with FRS zone (median of 2 in intermediate/high vs 1 in negligible/low risk cases). In intermediate/high risk cases, the use of 2 drains instead of 1 was not associated with a reduced rate of CR-POPF, average complication burden attributed to a CR-POPF, reoperations, or mortality. Obviation of drains was associated with significant increases in complication burden and mortality - regardless of the FRS zone.In intermediate/high risk zone cases, placement of a single drain or multiple drains appears to mitigate the complication burden while use of no drains is associated with inferior outcomes.

Background: The association between intraoperative estimated blood loss and outcomes after pancreatoduodenectomy has, thus far, been rarely explored. Methods: In total, 7,706 pancreatoduodenectomies performed at 18 international institutions composing the Pancreas Fistula Study Group were examined (2003-2020). High estimated blood loss (>700 mL) was defined as twice the median. Propensity score matching (1:1 exact-match) was employed to adjust for variables associated with high estimated blood loss and clinically relevant pancreatic fistula occurrence. The study was powered to detect a 33% clinically relevant pancreatic fistula increase in the high estimated blood loss group, with a = 0.05 and b = 0.2. Results: The propensity score model included 966 patients with high estimated blood loss and 966 patients with lower estimated blood loss; all covariate imbalantces were solved. Patients with high estimated blood loss patients experienced higher clinically relevant pancreatic fistula rates (19.4 vs 12.6%, odds ratio 1.66; P < .001), as well as higher severe complication rates (27.8 vs 15.6%), transfusions (50.1 vs 14.3%), reoperations (9.2 vs 4.0%), intensive care unit transfers (9.9 vs 4.8%) and 90-day mortality (4.7 vs 2.0%, all P < .001). High estimated blood loss was an independent predictor for clinically relevant pancreatic fistula (odds ratio 1.78, 95% confidence interval 1.37-2.32), as were prophylactic Octreotide administration (odds ratio 1.95, 95% confidence interval 1.46-2.61) and soft pancreatic texture (odds ratio 5.32, 95% confidence interval 3.74-5.57; all P < .001). Moreover, a second model including 1,126 pancreatoduodenectomies was derived including vascular resections as additional confounder (14.0% vascular resections performed in each group). On multivariable regression, high estimated blood loss was confirmed an independent predictor for clinically relevant pancreatic fistula reduction (odds ratio 1.80, 95% confidence interval 1.32-2.4 4; P < .001), whereas vascular resection was not (odds ratio 0.64, 95% confidence interval 0.34-1.88; P 1/4 .156). Conclusion: This study better establishes the relationship between estimated blood loss and outcomes after pancreatoduodenectomy. Despite inherent contributions to blood loss, its minimization is an actionable opportunity for clinically relevant pancreatic fistula reduction and performance optimization in pancreatoduodenectomy. Accordingly, practical insights are offered to achieve this goal. (c) 2021 Elsevier Inc. All rights reserved.

OBJECTIVES Although lumen-apposing metal stents (LAMS) are being increasingly used in lieu of plastic stents, the clinical approach to endoscopic management of pancreatic fluid collections (PFCs) is poorly standardized. We compared outcomes of approaches over two time intervals, initially using plastic stents and later integrating LAMS. METHODS This was a retrospective, observational, before-after study of prospectively collected data on consecutive patients with symptomatic PFCs managed over two time periods. In the initial period (January 2010-January 2015) endoscopic treatment was undertaken with plastic stents and in the later period (February 2015-August 2020) by integration of LAMS with selective use of plastic stents. The treatment strategy in both periods were tailored to size, extent, type of PFC and stepwise response to intervention. The main outcome was treatment success, defined as resolution of PFC and presenting symptoms at 6-month follow-up. RESULTS A total of 160 patients were treated with plastic stents and 227 patients were treated using an integrated LAMS approach. Treatment success was significantly higher for the integrated approach compared to using only plastic stents (95.6 vs. 89.4%; P = 0.018), which was confirmed to be predictive of treatment success on multivariable logistic regression analysis (odds ratio 2.7, 95% confidence interval 1.1-6.4; P = 0.028). CONCLUSIONS A structured approach integrating LAMS with selective use of plastic stents improved treatment success in patients with PFCs compared to an approach using only plastic stents.

To investigate the role of intraoperative estimated blood loss (EBL) on development of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatoduodenectomy (PD).Minimizing EBL has been shown to decrease transfusions and provide better perioperative outcomes in PD. EBL is also felt to be influential on CR-POPF development.This study consists of 5534 PDs from a 17-institution collaborative (2003-2018). EBL was progressively categorized (≤150mL; 151-400mL; 401-1,000 mL;1,000 mL). Impact of additive EBL was assessed using 20 3- factor fistula risk score (FRS) scenarios reflective of endogenous CR-POPF risk.CR-POPF developed in 13.6% of patients (N = 753) and median EBL was 400 mL (interquartile range 250-600 mL). CR-POPF and Grade C POPF were associated with elevated EBL (median 350 vs 400 mL, P = 0.002; 372 vs 500 mL, P0.001, respectively). Progressive EBL cohorts displayed incremental CR-POPF rates (8.5%, 13.4%, 15.2%, 16.9%; P0.001). EBL400mL was associated with increased CR-POPF occurrence in 13/20 endogenous risk scenarios. Moreover, 8 of 10 scenarios predicated on a soft gland demonstrated increased CR-POPF incidence. Hypothetical projections demonstrate significant reductions in CR-POPF can be obtained with 1-, 2-, and 3-point decreases in FRS points attributed to EBL risk (12.2%, 17.4%, and 20.0%; P0.001). This is especially pronounced in high-risk (FRS7-10) patients, who demonstrate up to a 31% reduction (P0.001). Surgeons in the lowest-quartile of median EBL demonstrated CR-POPF rates less than half those in the upper-quartile (7.9% vs 18.8%; P0.001).EBL independently contributes significant biological risk to CR-POPF. Substantial reductions in CR-POPF occurrence are projected and obtainable by minimizing EBL. Decreased individual surgeon EBL is associated with improvements in CR-POPF.

Cirrhotic liver disease is an important cause of peri-operative morbidity and mortality in general surgical patients. Early recognition and optimization of liver dysfunction is imperative before any elective surgery. Patients with MELD 20 or classified as Child C should undergo transplantation before any elective procedure given mortality exceeds 40%. Laparoscopic procedures are feasible and safe in cirrhotic patients.

Cholangiocarcinoma (CCA) is a fatal disease with a 5-year survival of

Evidence suggests externalized trans-anastomotic stents may be beneficial as a fistula mitigation strategy for pancreatoduodenectomy (PD); however, previous studies have not been rigorously risk-adjusted. From 2001 to 2015, PDs were performed at three institutions, with externalized stents placed at the surgeon’s discretion. The Fistula Risk Score (FRS) and the Modified Accordion Severity Grading System were used to analyze occurrence and severity of clinically relevant postoperative pancreatic fistula (CR-POPF) across various risk scenarios. Of 729 PDs, externalized stents were placed during 129 (17.7 %). Overall, CR-POPFs occurred in 77 (10.6 %) patients. The median FRS of patients who received externalized stents was significantly higher compared with patients who did not (6 vs. 3, p

We present a cancer nanomedicine based on acidic pH targeted gold nanorods designed for multispectral optoacoustic tomography (MSOT). We have designed gold nanorods coated with mesoporous silica and subsequently capped with chitosan (CMGs). We have conjugated pH-sensitive variant 7 pHLIP peptide to the CMGs (V7-CMG) to provide targeting specificity to the acidic tumor microenvironment. In vitro, treatment of S2VP10 and MiaPaca2 cells with V7-CMG containing gemcitabine resulted in significantly greater cytotoxicity with 97% and 96.5% cell death, respectively than gemcitabine alone 60% and 76% death at pH 6.5 (S2VP10 pH 6.5 p=0.009; MiaPaca2 pH 6.5 p=0.0197). In vivo, the V7-CMGs provided the contrast and targeting specificity necessary for MSOT of retroperitoneal orthotopic pancreatic tumors. In the in vivo S2VP10 model, the V7-CMG particle preferentially accumulated within the tumor at 17.1 MSOT a.u. signal compared with 0.7 MSOT a.u. in untargeted CMG control in tumor (P = 0.0002). Similarly, V7-CMG signal was 9.34 MSOT a.u. in the S2013 model compared with untargeted CMG signal at 0.15 MSOT a.u. (P = 0.0004). The pH-sensitivity of the targeting pHLIP peptide and chitosan coating makes the particles suitable for simultaneous in vivo tumor imaging and drug delivery.

Background Pancreatic adenocarcinoma patients have low survival rates due to late-stage diagnosis and high rates of cancer recurrence even after surgical resection. It is important to understand the molecular characteristics associated with survival differences in pancreatic adenocarcinoma tumors that may inform patient care. Results RNA sequencing was performed for 51 patient tumor tissues extracted from patients undergoing surgical resection, and expression was associated with overall survival time from diagnosis. Our analysis uncovered 323 transcripts whose expression correlates with survival time in our pancreatic patient cohort. This genomic signature was validated in an independent RNA-seq dataset of 68 additional patients from the International Cancer Genome Consortium. We demonstrate that this transcriptional profile is largely independent of markers of cellular division and present a 19-transcript predictive model built from a subset of the 323 transcripts that can distinguish patients with differing survival times across both the training and validation patient cohorts. We present evidence that a subset of the survival-associated transcripts is associated with resistance to gemcitabine treatment in vitro, and reveal that reduced expression of one of the survival-associated transcripts, Angiopoietin-like 4, impairs growth of a gemcitabine-resistant pancreatic cancer cell line. Conclusions Gene expression patterns in pancreatic adenocarcinoma tumors can distinguish patients with differing survival outcomes after undergoing surgical resection, and the survival difference could be associated with the intrinsic gemcitabine sensitivity of primary patient tumors. Thus, these transcriptional differences may impact patient care by distinguishing patients who would benefit from a non-gemcitabine based therapy.

Background The optimal treatment and management of locally advanced pancreatic cancer (LAPC) remains unclear and controversial. This study aimed to report the initial outcomes of the AHPBA Registry and evaluate the reproducibility of existing evidence that the addition of Irreversible Electroporation (IRE), a nonthermal ablative treatment, confers survival benefits beyond standard therapeutic options for patients with LAPC. Methods From December 2015 to October 2017, patients with LAPC were treated with open-technique IRE following the AHPBA Registry Protocols. Patient demographics, long-term outcomes, and adverse events were recorded. Survival analyses were performed using Kaplan-Meier (KM) curves for overall survival (OS), progression free survival (PFS) and time to progression (TTP). Results A total of 152 patients underwent successful IRE. Morbidity and mortality were 18% and 2% respectively, with 19 (13%) patients experiencing severe adverse events. Nine (6%) patients presented with local recurrence. Median TTP, PFS, and OS from diagnosis were 27.3 months, 22.8 months, and 30.7 months respectively. Conclusion The combination of IRE with established multiagent therapy is safe and demonstrates encouraging survival among patients with LAPC. IRE is associated with a low rate of serious adverse events and has been optimized for more widespread adoption through the standardized protocols available through the AHPBA registry.

The purpose of this study was to investigate the effect of radiotherapy on local control and mordibity for patients with resected lymph node-positive pancreatic cancer as compared to gemcitabine-based chemotherapy alone. Sixty-nine patients received adjuvant therapy for pancreatic adenocarcinoma with lymph node involvement after surgical resection and met the inclusion criteria for this analysis. Forty (58 %) patients received postoperative radiotherapy (PORT) to a median dose of 50.4 Gy with capecitabine or 5-fluorouracil concurrently in all but one case; 15 patients also received gemcitabine prior to PORT. Twenty-nine (42 %) patients received gemcitabine-based chemotherapy without PORT for a median of 6 cycles. The median overall survival for patients receiving PORT was 24.4 months compared to 25.6 months for patients not receiving PORT (p = 0.943). At 2 years, the rate of local control was 57 % for patients receiving PORT compared to 37 % for those who did not (p = 0.034). At 2 years, the rate of palliative local interventions was 16 % for patients receiving PORT compared to 18 % for patients who did not (p = 0.821). The use of PORT was associated with improved local control in the gemcitabine era for patients with resected, node-positive, pancreatic adenocarcinoma. The rates of overall survival and palliative interventions did not differ between the two groups.

Objective: The study aim was to quantify the burden of complications of pancreatoduodenectomy (PD). Background: The Postoperative Morbidity Index (PMI) is a quantitative measure of the average burden of complications of a procedure. It is based on highly validated systems—ACS-NSQIP and the Modified Accordion Severity Grading System. Methods: Nine centers contributed ACS-NSQIP complication data for 1589 patients undergoing PD from 2005 to 2011. Each complication was assigned a severity weight ranging from 0.11 for the least severe complication to 1.00 for postoperative death, and PMI was derived. Contribution to total burden by each complication grade was used to generate a severity profile (“spectrogram”) for PD. Associations with PMI were determined by regression analysis. Results: ACS-NSQIP complications occurred in 528 cases (33.2%). The non–risk-adjusted PMI was 0.115 (SD = 0.023) for all centers and 0.113 (SD = 0.005) for the 7 centers that contributed at least 100 cases. Grade 2 complications were predominant in frequency, and the most common complication was postoperative bleeding/transfusion. Frequency and burden of complications differed markedly. For instance, severe complications (grades 4/5/6) accounted for only about 20% of complications but for more than 40% of the burden of complications. Organ space infection had the highest burden of any complication. The average burden in cases in which a complication actually occurred was 0.346. Conclusions: This study develops a quantitative non–risk-adjusted benchmark for postoperative morbidity of PD. The method quantifies the burden of types and grades of postoperative complications and should prove useful in identifying areas that require quality improvement.

While contemporary studies demonstrate decreasing complication rates following total pancreatectomy (TP), none have quantified the impact of post-TP complications. The Postoperative Morbidity Index (PMI)—a quantitative measure of postoperative morbidity—combines ACS-NSQIP complication data with severity weighting derived from Modified Accordion Grading System. We establish the PMI for TP in a multi-institutional cohort. Nine institutions contributed ACS-NSQIP data for 64 TPs (2005–2011). Each complication was assigned an Accordion severity weight ranging from 0.110 (grade 1/mild) to 1.00 (grade 6/death). PMI equals the sum of complication severity weights (“Total Burden”) divided by total number of patients. Overall, 29 patients (45.3 %) suffered 55 ACS-NSQIP complications; 15 (23.4 %) had >1 complication. Thirteen patients (20.3 %) were readmitted and one death (1.6 %) occurred within 30 days. Non-risk adjusted PMI was 0.151, while PMI for complication-bearing cases rose to 0.333. Bleeding/Transfusion and Sepsis were the most common complications. Discordance between frequency and burden of complications was observed. While grades 4–6 comprised only 18.5 % of complications, they contributed 37.1 % to the series’ total burden. This multi-institutional series is the first to quantify the complication burden following TP using the rigor of ACS-NSQIP. A PMI of 0.151 indicates that, collectively, patients undergoing TP have an average burden of complications in the mild to moderate severity range, although complication-bearing patients have a considerable reduction in health utility.

To identify a clinical fistula risk score following distal pancreatectomy.Clinically relevant pancreatic fistula (CR-POPF) following distal pancreatectomy (DP) is a dominant contributor to procedural morbidity, yet risk factors attributable to CR-POPF and effective practices to reduce its occurrence remain elusive.This multinational, retrospective study of 2026 DPs involved 52 surgeons at 10 institutions (2001-2016). CR-POPFs were defined by 2016 International Study Group criteria, and risk models generated using stepwise logistic regression analysis were evaluated by c-statistic. Mitigation strategies were assessed by regression modeling while controlling for identified risk factors and treating institution.CR-POPF occurred following 306 (15.1%) DPs. Risk factors independently associated with CR-POPF included: age (60 yrs: OR 1.42, 95% CI 1.05-1.82), obesity (OR 1.54, 95% CI 1.19-2.12), hypoalbuminenia (OR 1.63, 95% CI 1.06-2.51), the absence of epidural anesthesia (OR 1.59, 95% CI 1.17-2.16), neuroendocrine or nonmalignant pathology (OR 1.56, 95% CI 1.18-2.06), concomitant splenectomy (OR 1.99, 95% CI 1.25-3.17), and vascular resection (OR 2.29, 95% CI 1.25-3.17). After adjusting for inherent risk between cases by multivariable regression, the following were not independently associated with CR-POPF: method of transection, suture ligation of the pancreatic duct, staple size, the use of staple line reinforcement, tissue patches, biologic sealants, or prophylactic octreotide. Intraoperative drainage was associated with a greater fistula rate (OR 2.09, 95% CI 1.51-3.78) but reduced fistula severity (P0.001).From this large analysis of pancreatic fistula following DP, CR-POPF occurrence cannot be reliably predicted. Opportunities for developing a risk score model are limited for performing risk-adjusted analyses of mitigation strategies and surgeon performance.

Chronic pancreatitis is a multifactorial disease process associated with high morbidity. The workup and perioperative management of this disease can be challenging given its complex pathophysiology. Multidisciplinary lifestyle and medical management strategies should be utilized when feasible prior to invasive interventions, either endoscopic or surgical. Using a case presentation format, key perioperative assessment and management strategies for chronic pancreatitis are highlighted, in addition to technical pearls to guide intraoperative management using the Frey procedure (duodenal-preserving partial pancreatic head resection with lateral pancreaticojejunostomy). Patients with pancreatic ductal dilation greater than or equal to 7 mm, or dilated with multiple ductal strictures causing disabling or severe pain, should undergo a Frey procedure. Asymptomatic patients or those with an inflammatory mass/calcification in the pancreatic head associated with ductal dilation are also candidates.

There is an author's name misspelled in the published paper, Shyam Varadarajula should be Shyam Varadarajulu.

Importance Ampullary adenocarcinoma is a rare malignant neoplasm that arises within the duodenal ampullary complex. The role of adjuvant therapy (AT) in the treatment of ampullary adenocarcinoma has not been clearly defined. Objective To determine if long-term survival after curative-intent resection of ampullary adenocarcinoma may be improved by selection of patients for AT directed by histologic subtype. Design, setting, and participants This multinational, retrospective cohort study was conducted at 12 institutions from April 1, 2000, to July 31, 2017, among 357 patients with resected, nonmetastatic ampullary adenocarcinoma receiving surgery alone or AT. Cox proportional hazards regression was used to identify covariates associated with overall survival. The surgery alone and AT cohorts were matched 1:1 by propensity scores based on the likelihood of receiving AT or by survival hazard from Cox modeling. Overall survival was compared with Kaplan-Meier estimates. Exposures Adjuvant chemotherapy (fluorouracil- or gemcitabine-based) with or without radiotherapy. Main outcomes and measures Overall survival. Results A total of 357 patients (156 women and 201 men; median age, 65.8 years [interquartile range, 58-74 years]) underwent curative-intent resection of ampullary adenocarcinoma. Patients with intestinal subtype had a longer median overall survival compared with those with pancreatobiliary subtype (77 vs 54 months; P = .05). Histologic subtype was not associated with AT administration (intestinal, 52.9% [101 of 191]; and pancreatobiliary, 59.5% [78 of 131]; P = .24). Patients with pancreatobiliary histologic subtype most commonly received gemcitabine-based regimens (71.0% [22 of 31]) or combinations of gemcitabine and fluorouracil (12.9% [4 of 31]), whereas treatment of those with intestinal histologic subtype was more varied (fluorouracil, 50.0% [17 of 34]; gemcitabine, 44.1% [15 of 34]; P = .01). In the propensity score-matched cohort, AT was not associated with a survival benefit for either histologic subtype (intestinal: hazard ratio, 1.21; 95% CI, 0.67-2.16; P = .53; pancreatobiliary: hazard ratio, 1.35; 95% CI, 0.66-2.76; P = .41). Conclusions and relevance Adjuvant therapy was more frequently used in patients with poor prognostic factors but was not associated with demonstrable improvements in survival, regardless of tumor histologic subtype. The value of a multimodality regimen remains poorly defined.

BackgroundThe Post‐operative Morbidity Index (PMI) is a quantitative utility measure of a complication burden created by severity weighting. The Fistula Risk Score (FRS) is a validated model that predicts whether a patient will develop a post‐operative pancreatic fistula (POPF). These novel tools might provide further discrimination of the ISGPF grading system.MethodsFrom 2001 to 2012, 1021 pancreaticoduodenectomies were performed at four institutions. POPFs were categorized by ISGPF standards. PMI scores were calculated based on the Modified Accordion Severity Grading System. FRS scores were assigned according to the relative influence of four recognized factors for developing a clinically relevant POPF (CR‐POPF).ResultsIn total, 231 patients (22.6%) developed a POPF, of which 54.1% were CR‐POPFs. The PMI differed significantly between the ISGPF grades and patients with no or non‐fistulous complications (P < 0.001). 64.9% of POPFs and 84.0% of CR‐POPFs contributed the highest Accordion grade to the PMI. Overall, the FRS correlated well with PMI (R2 = 0.81, P < 0.001).ConclusionThese data quantitatively reinforce the ISGPF grades that were developed qualitatively around the concept of clinical severity. CR‐POPFs usually reflect the patient's highest Accordion score whereas biochemical POPFs are often superseded. The correlation between FRS and PMI indicates that risk factors for a fistula contribute to overall pancreaticoduodenectomy morbidity.

While laparoscopy-assisted endoscopic retrograde cholangiopancreatography can be performed for the diagnosis and management of pancreaticobiliary diseases in patients with Roux-en-Y (RY) anatomy; the technical feasibility of performing laparoscopy-assisted endoscopic ultrasound (EUS) is unknown.In this report, we describe the technique for performing laparoscopy-assisted EUS in two patients with RY gastric bypass anatomy who presented with obstructive jaundice, abnormal liver function tests, and dilated biliary tree.While the examination was normal in one patient, EUS-guided fine needle aspiration of pancreatic head mass revealed adenocarcinoma in the other.Laparoscopic assisted EUS examination including FNA is feasible in Roux-en-Y surgical anatomy.

To study the effect of disconnected pancreatic duct syndrome (DPDS) on endoscopic management of pancreatic fluid collections (PFCs).Data on the impact of DPDS in patients undergoing endoscopic treatment of PFCs are limited.Retrospective study of patients undergoing endoscopic drainage of PFCs from 2003 to 2015. If treatment response was suboptimal following initial endoscopic or endoscopic ultrasound-guided transmural drainage, hybrid interventions (endoscopic ultrasound-guided multigate/dual modality technique, endoscopic/percutaneous sinus tract necrosectomy) were performed. Transmural stents were left permanently in situ in DPDS patients from 2008 onwards. Main outcome measures were to evaluate the effect of DPDS on need for hybrid treatment, reinterventions, rescue surgery, length of stay, and overall treatment success.Of 361 patients, 34 (9.4%) were acute collections, 178 (49.3%) pseudocysts, and 149 (41.3%) walled-off necrosis (WON). DPDS was present in 167 (46.3%) patients, absent in 124 (34.3%), unknown in 70 (19.4%), and occurred more frequently in WON compared to other PFCs (68.3% vs 31.7%; P0.001). Although there was no difference in treatment success, more patients with DPDS required hybrid treatment (31.1% vs 4.8%, P0.001), reinterventions (30% vs 18.5%, P = 0.03), rescue-surgery (13.2% vs 4.8%, P = 0.02), and longer length of stay [median (interquartile range) days, 3 (2-10) vs 2 (1-4), P = 0.003]. PFC recurrence was lower in patients with DPDS with permanent transmural stents (17.4% vs 1.7%, P0.001). On multivariate logistic regression, DPDS [odds ratio (OR) 2.99], WON (OR 3.37), PFC size of 100 mm or more (OR 2.66), and multiple PFCs (OR 10.6) were associated with need for hybrid treatment.DPDS has a significant effect on endoscopic management of PFCs as more patients required hybrid treatment, reinterventions, and rescue surgery for achieving optimal clinical outcomes.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis which has not appreciably changed over the past decades despite advances in surgical and medical therapies. Most patients present with advanced disease and are not amenable to surgical extirpation. Even with intended curative resection, long-term survival is rare as PDAC is likely systemic very early in the disease process. There are currently no valid screening tools for PDAC but an increasing number of pancreatic lesions are detected due to the ubiquitous use of abdominal imaging in the workup for other diseases. A pancreatic incidental finding may be an opportunity for early diagnosis of a pancreatic malignancy. Conversely, however, many incidentally discovered pancreatic lesions are of little clinical consequence and pancreatic surgery has a high associated morbidity. Thus the management of a pancreatic incidentaloma is a medical quandary. In this article, we discuss the various incidentally discovered pancreatic lesions, with particular attention to the risk of pancreatic malignancy and potential management strategies.

The aim of this study was to assess for any trend in management of pancreatic fluid collections (PFCs) and identify impacting factors. The endoscopy and surgical databases were queried for PFC patients. PFCs were categorized as pseudocysts (PP) or complex collections (CC) that included abscess/necrosis. The outcome measures were to compare the utilization of surgery and endoscopy from 2004 to 2007 (group I) and from 2008 to 2010 (group II) and identify factors impacting practice patterns. A total of 285 patients were treated: group I included 119 and group II 166. Of 119 group I patients, 29 per cent were treated by surgery and 71 per cent by endoscopy. Of 85 endoscopy patients, 42 per cent were drained by conventional transmural drainage and 58 per cent by endoscopic ultrasound (EUS). Of 166 group II patients, 31 per cent were treated surgically and 69 per cent endoscopically. Of the 115 endoscopy patients, 17 per cent were drained by conventional transmural drainage and 83 per cent by EUS. Compared with group I, all pseudocysts in group II were treated by endoscopy (84% vs 100%, P = 0.001). There was no difference in the rate of CC treated by endoscopy between both groups (57.7% vs 56.8%, P = 0.9). PFCs not causing luminal compression ( P < 0.0001) or measuring

Background and Aim: The aim of the present study was to evaluate the frequency of complications during endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFC), identify contributing factors, and report on management outcomes. Methods: All patients who underwent EUS-guided PFC drainage over 7 years were enrolled. Indications, demographics, technical details, complications, surgical interventions, and final outcomes were prospectively recorded. Results: Of 148 patients who underwent EUS, PFC was located in the pancreatic body in 84 (56.8%), in the tail in 45 (30.4%), in the head in 15 (10.1%), and in the uncinate region in four patients (2.7%). Perforation was encountered at the site of transmural stenting in two patients (1.3%, 95% confidence interval [CI]: 0.41–4.76) with a pseudocyst in the uncinate region that was drained transgastrically. When compared to other locations, perforation was more common with PFC involving the uncinate region (0% vs 50%, P = 0.0005). Other complications included bleeding in one (0.67%, 95% CI: 0.16, 3.68), stent migration in 1 (0.67%, 95% CI: 0.16, 3.68), and infection in four patients (2.7%, 95% CI: 1.09, 6.73). Bleeding occurred in a patient with underlying acquired factor VIII inhibitors, stent migration in a patient who underwent drainage via the gastric cardia, and infection in two patients with pseudocysts and two with necrosis. While two patients who developed post-procedural infection and one with stent migration were managed endoscopically, both perforations required surgery. Surgical debridement was performed in two patients who developed infection with successful outcomes in one, and death from underlying comorbidity in the other. Conclusions: Complications are rare during EUS-guided drainage of PFC and can be managed successfully in most patients.

Endoscopy is a minimally invasive technique for the drainage of peripancreatic fluid collections. This study evaluated the clinical outcomes and predictors of treatment success in consecutive patients undergoing endoscopic transmural drainage of peripancreatic fluid collections. This is a retrospective study of patients who underwent endoscopic drainage of peripancreatic fluid collections over 7 years. Prior to drainage, an ERCP was attempted for stent placement in all patients with a pancreatic duct leak. Drainages were performed using conventional endoscopy or endoscopic ultrasound. Transmural stents and/or drainage catheters were deployed and endoscopic necrosectomy was undertaken when required. Data on clinical outcomes and complications were collected prospectively. A total of 211 patients underwent drainage of peripancreatic fluid collections that was classified as pseudocyst in 45%, abscess in 28%, and necrosis in 27%. Mean diameter of the fluid collection was 100.6 mm, and 34.5% of patients had pancreatic duct stent placement. Median duration of follow-up was 356 days. Treatment success was 85.3% and was higher for pseudocyst and abscess compared to necrosis (93.5% vs. 63.2%, p

Background Walled-off pancreatic necrosis often leads to severe clinical deterioration necessitating open debridement or endoscopic necrosectomy. A new EUS-based approach was devised to manage this condition by creating multiple transluminal gateways to facilitate effective drainage of the necrotic contents. Objective To compare treatment outcomes between patients with walled-off pancreatic necrosis managed endoscopically by a multiple transluminal gateway technique (MTGT) or a conventional drainage technique (CDT). Design Retrospective study. Setting Tertiary-care referral center. Patients This study involved patients with severe acute pancreatitis complicated by walled-off pancreatic necrosis managed endoscopically. Intervention In MTGT, 2 or 3 transmural tracts were created by using EUS guidance between the necrotic cavity and the GI lumen. While one tract was used to flush normal saline solution via a nasocystic catheter, multiple stents were deployed in others to facilitate drainage of necrotic contents. In the CDT, two stents with a nasocystic catheter were deployed via 1 transmural tract. Main Outcome Measurements Resolution of symptoms, radiological findings on follow-up CT, and the need for subsequent surgery or endoscopic necrosectomy. Results Of 60 patients with symptomatic walled-off pancreatic necrosis, 12 (3 women, mean age 55.1 years) were managed by MTGT and 48 (12 women, mean age 55.2 years) by CDT. Treatment was successful in 11 of 12 (91.7%) patients managed by MTGT versus 25 of 48 (52.1%) managed by CDT ( P = .01). Although 1 patient in the MTGT cohort required endoscopic necrosectomy, in the CDT cohort, 17 required surgery, 3 underwent endoscopic necrosectomy, and 3 died of multiple-organ failure. Treatment success was more likely for patients treated by MTGT than by CDT (adjusted odds ratio=9.24; 95% confidence interval, 1.08-79.02; P = .04) when we adjusted for the size of the walled-off pancreatic necrosis and pancreatic duct stent placement. Limitations Selective patient population. Conclusion The EUS-guided MTGT is an effective treatment option for the management of symptomatic walled-off pancreatic necrosis because it obviates the need for surgery and endoscopic necrosectomy and its attendant procedure-related morbidity. Prospective studies are required to confirm these preliminary but promising data.

Background It is unclear whether plastic or metal stents are more suitable for preoperative biliary decompression in pancreatic cancer. The objective of this study was to compare the rate of endoscopic reinterventions in patients with pancreatic cancer undergoing plastic or self-expandable metal stent (SEMS) placements for preoperative biliary decompression. Methods This was a retrospective study of all patients with obstructive jaundice secondary to pancreatic head cancer who underwent their index endoscopic retrograde cholangiopancreatography (ERCP) and all follow-up biliary stent placements at our center before undergoing pancreaticoduodenectomy. Plastic or SEMS were placed at ERCP for biliary decompression. The main outcome measure was to compare the rate of endoscopic reinterventions between the plastic and SEMS cohorts. Results 29 patients who underwent pancreaticoduodenectomy had preoperative biliary stent placement (18 plastic, 11 SEMS) at our center. Whereas none of the 11 patients who underwent SEMS placement had stent dysfunction, 7 of 18 (39%) patients with plastic stents required endoscopic reintervention before surgery (P = 0.02). Reinterventions were due to cholangitis (n = 1) or persistent elevation in serum bilirubin levels (n = 6). Two patients with SEMS underwent EUS-guided fine-needle aspiration after ERCP, which yielded a positive diagnosis of cancer in all cases; SEMS did not impair visualization of the tumor mass at EUS. Pancreaticoduodenectomy was undertaken successfully in all 29 patients and the presence of a SEMS did not interfere with biliary anastomosis. On univariate logistic regression, only SEMS placement was associated with less need for endoscopic reintervention (P = 0.02). Conclusions SEMS are superior to plastic stents for preoperative biliary decompression in pancreatic cancer. Electronic supplementary material The online version of this article (doi:10.1007/s00464-010-1552-6) contains supplementary material, which is available to authorized users.

Pancreatic necrosis, a complication of severe pancreatitis, may become infected, resulting in significant morbidity and potential mortality. Infected necrosis was heretofore considered a surgical condition, and despite aggressive operative management, the mortality remained high. With a better understanding of the natural history of necrosis, established methods to diagnose infection and the increasing use of minimally invasive techniques, less aggressive therapies have been utilized with some success. The present study evaluated a step-up approach for the treatment of infected pancreatic necrosis, utilizing endoscopic and percutaneous techniques, and if ineffective, necrosectomy with a minimally invasive retroperitoneal approach. They compared this step-up approach to the standard open necrosectomy. They demonstrated that when using such an approach compared with open necrosectomy, the frequency of major complications such as organ failure, perforation, fistula or even death was significantly less than in those who received conventional open necrosectomy. Indeed, for those randomized to the step-up approach, roughly a third of the patients were successfully treated with percutaneous drainage alone. In the long-term, development of diabetes was also less frequent in those receiving less aggressive therapy. These findings, in combination with other reports, suggest that the dogma that open necrosectomy is mandatory for all patients with infected necrosis should be re-evaluated, and that less aggressive treatments as part of a multidisciplinary approach can reduce morbidity and mortality.

(1) To determine the safety of the epidermal growth factor receptor (EGFR) antibody cetuximab with concurrent gemcitabine and abdominal radiation in the treatment of patients with locally advanced adenocarcinoma of the pancreas. (2) To evaluate the feasibility of pancreatic cancer cell epithelial-mesenchymal transition (EMT) molecular profiling as a potential predictor of response to anti-EGFR treatment.Patients with non-metastatic, locally advanced pancreatic cancer were treated in this dose escalation study with gemcitabine (0-300 mg/m(2)/week) given concurrently with cetuximab (400 mg/m(2) loading dose, 250 mg/m(2) weekly maintenance dose) and abdominal irradiation (50.4 Gy). Expression of E-cadherin and vimentin was assessed by immunohistochemistry in diagnostic endoscopic ultrasound fine-needle aspiration (EUS-FNA) specimens.Sixteen patients were enrolled in 4 treatment cohorts with escalating doses of gemcitabine. Incidence of grade 1-2 adverse events was 96%, and incidence of 3-4 adverse events was 9%. There were no treatment-related mortalities. Two patients who exhibited favorable treatment response underwent surgical exploration and were intraoperatively confirmed to have unresectable tumors. Median overall survival was 10.5 months. Pancreatic cancer cell expression of E-cadherin and vimentin was successfully determined in EUS-FNA specimens from 4 patients.Cetuximab can be safely administered with abdominal radiation and concurrent gemcitabine (up to 300 mg/m(2)/week) in patients with locally advanced adenocarcinoma of the pancreas. This combined therapy modality exhibited limited activity. Diagnostic EUS-FNA specimens could be analyzed for molecular markers of EMT in a minority of patients with pancreatic cancer.

Background Peripancreatic fluid collections (PFCs) are a common complication after distal pancreatectomy and are usually managed by percutaneous drainage. The role of EUS in the management of postoperative PFCs has not been previously reported. Objective To evaluate the role of EUS in the management of PFCs after distal pancreatectomy. Study Design Case series. Setting Academic tertiary referral center. Patients Symptomatic patients with PFCs after a distal pancreatectomy. Interventions At EUS, the PFCs were accessed transgastrically by using a 19-gauge FNA needle and after passage of a 0.035-inch guidewire; sequential dilation of the transgastric tract was performed up to 8 mm and multiple 7F or 10F double-pigtail stents were deployed. Nasocystic drainage catheters were deployed in those with poor drainage at the time of endoscopy. Main Outcome Measurements To evaluate the technical and treatment success and safety profile of the EUS-based approach for management of PFCs after distal pancreatectomy. Results Ten patients (6 men, 4 women; mean age, 56.8 years [range 20-76 years]) underwent EUS-guided drainage of PFCs after distal pancreatectomy over a 30-month period. Indications for distal pancreatectomy were neuroendocrine tumor in 5 patients, focal chronic pancreatitis in 2, cyst neoplasm in 1, adenocarcinoma in 1, and trauma in 1. The mean size of the PFCs (largest dimension) was 91.4 mm (range 45-140 mm). EUS-guided drainage was technically successful in all 10 patients; 1 patient underwent EUS-guided drainage of 2 large noncommunicating PFCs in the same endoscopy session. Treatment was successful in 9 (90%) of 10 patients; 1 patient had persistent symptoms requiring reoperation. No procedural complications were encountered. At a mean follow-up of 151 days (range 96-280 days), all 9 patients were doing well without any evidence of symptom recurrence. Limitations Small number of patients and lack of a comparative treatment group. Conclusions EUS-guided drainage is a minimally invasive, safe, and highly effective technique for the management of symptomatic PFC after distal pancreatectomy.

Pancreatic necrosis is associated with high morbidity and mortality. The Atlanta Classification underwent proposed revisions in 2007 to better categorize acute pancreatitis.From 1999 to 2008, patients with pancreatic necrosis treated with surgical debridement were analyzed. Computed tomography (CT) images were independently reviewed to classify of pancreatic collections according to the revised Atlanta classification.Seventy-three patients were categorized as infected extrapancreatic necrosis (40%), sterile extrapancreatic necrosis (29%), infected pancreatic necrosis (15%), sterile pancreatic necrosis (11%), or post-necrotic collection (5%). Mortality was 14%, and morbidity was 55%. Debridement with external drainage or open packing was associated with higher mortality than cystgastrostomy (p = 0.03). Atlanta Classification was not associated with operative procedure or mortality. Degree of chronic disease, demonstrated by albumin level, and infection were associated with longer stay (p0.05).Type of necrosis by the revised Atlanta Classification was not associated with outcomes or type of operation. Debridement by cystgastrostomy was associated with lower mortality rates than external drainage or open packing. Length of stay was increased in patients with evidence of chronic disease, infection, and postoperative complications. Necrotizing pancreatitis continues to be associated with significant morbidity and mortality and should undergo aggressive treatment at tertiary care centers.

Laparoscopic (lap) pancreatic surgery has been increasingly reported since its introduction in 1992. A retrospective analysis of consecutive patients undergoing elective lap and open distal pancreatectomy from 2002 to 2007 was performed. Univariate analysis was completed to evaluate perioperative variables. Logistic regression analysis was used to model predictors of postoperative pancreatic fistula. One hundred forty-eight subjects underwent distal pancreatectomy; 98 completed open, 44 lap, and six converted to open. There was no significant difference in the incidence of postoperative morbidity or mortality between the surgical approaches. Decreased operative time (156 vs 200 minutes, P < 0.01), blood loss (157 vs 719 mL, P < 0.01), and length of stay (5.9 vs 8.6 days, P < 0.01) were seen in the lap group. There was no significant difference in the rate of all pancreatic fistula formation (50 vs 46%, P = 0.94) or clinically significant leaks (18 vs 19%, P = 0.97) between techniques. A preoperative biopsy-proven cancer, increasing body mass index, history of pancreatitis, and male gender were significant predictors of having a pancreatic fistula. Lap and open distal pancreatectomy are performed safely at high-volume pancreatic surgery centers. This report provides ongoing support of the feasibility and safety of the lap approach with improved perioperative outcomes and equivalent pancreatic fistula rate.

Although prior studies evaluated the role of EUS and EGD for drainage of pancreatic pseudocysts, there are no randomized trials that compared the technical outcomes between both modalities.To compare the rate of technical success between EUS and EGD for transmural drainage of pancreatic pseudocysts.A prospective randomized trial.A tertiary-referral center.Those with a history of pancreatitis and symptomatic pancreatic pseudocysts that measured greater than 4 cm in size who were referred for endoscopic transmural drainage. Patients with pancreatic abscess or necrosis were excluded.Technical success was defined as the ability to access and drain a pseudocyst by placement of transmural stents. Complications were assessed at 24 hours and at day 30. Treatment success was defined as the complete resolution or decrease in size of the pseudocyst toor=2 cm on CT in association with clinical resolution of symptoms at 6 weeks of follow-up.Thirty patients were randomized to undergo pseudocyst drainage by EUS (n = 15) or EGD (n = 15) over a 6-month period. Of the 15 patients randomized to EUS, drainage was not undertaken in one, because an alternative diagnosis of biliary cystadenoma was established at EUS and was excluded (after randomization) from analysis. The mean age of the patients was 47 years; 62% were men (18/29). Except for their sex, there was no difference in patient or clinical characteristics between the 2 cohorts. Although all the patients (n = 14) randomized to an EUS underwent successful drainage (100%), the procedure was technically successful in only 5 of 15 patients (33%) randomized to an EGD (P.001). All 10 patients who failed drainage by EGD underwent successful drainage of the pseudocyst on a crossover to EUS. There was no significant difference in the rates of treatment success between EUS and EGD after stenting, either by intention-to-treat (ITT) analysis (100% vs 87%; P = .48) or as-treated analysis (95.8% vs 80%; P = .32). Major procedure-related bleeding was encountered in 2 patients in whom drainage by EGD was attempted; one resulted in death and the other necessitated a blood transfusion. No significant difference was observed between EUS and EGD with regard to complications either by ITT (0% vs 13%; P = .48) or as-treated analyses (4% vs 20%; P = .32). Technical success was significantly greater for EUS than EGD, even after adjusting for luminal compression and sex (adjusted exact odds ratio 39.4; P = .001).Short duration of follow-up.When available, EUS should be considered as the first-line treatment modality for endoscopic drainage of pancreatic pseudocysts given its high technical success rate.

The proteome varies with physiologic and disease states. Few studies have been reported that differentiate the proteome of those with pancreatic cancer. To apply proteomic-based technologies to body fluids. To differentiate pancreatic neoplasia from nonneoplastic pancreatic disease. Samples from 50 patients (15 healthy (H), 24 cancer (Ca), 11 chronic pancreatitis (CP)) were prospectively collected and underwent analysis. A high-throughput method, using high-affinity solid lipophilic extraction resins, enriched low molecular weight proteins for extraction with a high-speed 200-Hz matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-MS; Bruker Ultraflex III). Samples underwent software processing with FlexAnalysis, Clinprot, MatLab, and Statistica (baseline, align, and normalize spectra). Nonparametric pairwise statistics, multidimensional scaling, hierarchical analysis, and leave-one-out cross validation completed the analysis. Sensitivity (sn) and specificity (sp) of group comparisons were determined. Two top-down-directed protein identification approaches were combined with MALDI-MS and tandem mass spectrometry to fully characterize the most significant protein biomarker. Using eight serum features, we differentiated Ca from H (sn 88%, sp 93%), Ca from CP (sn 88%, sp 30%), and Ca from both H and CP combined (sn 88%, sp 66%). In addition, nine features obtained from urine differentiated Ca from both H and CP combined with high efficiency (sn 90%, sp 90%). Interestingly, the plasma samples (considered by the Human Proteome Organization to be the preferred biological fluid) did not show significant differences. Multidimensional scaling indicated that markers from both serum and urine led to a highly effective clinical indicator of each specific disease state. The proteomic analysis of noninvasively acquired biological fluids provided a high level of predictability for diagnosing pancreatic cancer. While the proteomic analysis of serum was capable of screening individuals for pancreatic disease (i.e., CP and Ca vs. H), specific urine biomarkers further distinguished malignancy (Ca) from chronic inflammation (CP).

Early diagnosis and curative resection are significant predictors of survival in patients with pancreatic cancer. We hypothesize that cholecystectomy within 12 months of pancreatic cancer affects 1-year survival. The Surveillance Epidemiology and End Result (SEER) database linked to Medicare data was used to identify patients diagnosed with pancreatic cancer who underwent cholecystectomy 1 to 12 months prior to cancer diagnosis. The SEER database identified 32,569 patients from 1995 to 2002; 415 (1.3%) underwent cholecystectomy prior to cancer diagnosis. Patients who underwent cholecystectomy had a higher proportion of diabetes (40.2% vs 20.5%; P < 0.01), obesity (8.9% vs 3.1%; P < 0.01), jaundice (17.3% vs 0.7%; P < 0.01), cholelithiasis (70.4% vs 4.2%; P < 0.01), choledocholithiasis (0.7% vs 0.0%; P < 0.01), weight loss (17.3% vs 4.7%; P < 0.01), abdominal pain (79.5% vs 22.5%), steatorrhea (0.7% vs 0.0%; P < 0.01), and cholecystitis (32.3% vs 1.7%; P < 0.0001). After controlling for tumor stage, patient demographics, and symptoms, survival at 1 year was significantly lower in patients undergoing cholecystectomy (OR, 0.75; 95% CI, 0.58–0.97). Recent cholecystectomy is associated with decreased 1-year survival among patients with pancreatic cancer. For patients older than 65 years of age, further evaluation prior to cholecystectomy may be necessary to exclude pancreatic cancer, especially patients with jaundice, weight loss, and steatorrhea.

Pancreatic resection can alleviate pain in properly selected patients with severe chronic pancreatitis (CP), although the apancreatic state causes “brittle” diabetes. Islet auto-transplantation (IAT) after resection can decrease diabetes-related morbidity. Twenty-six consecutive patients with CP who underwent 27 pancreatic resections with IAT from April 2005 to December 2007 were evaluated in this retrospective case control study. Data were collected by chart and operative note reviews and query of hospital databases. Subgroup analysis was performed on 21 cases of total pancreatectomy and six cases of pancreaticoduodenectomy (PD). Mean age was 43.8 years and 46.2 per cent of patients were female. The most common etiology of CP was alcoholism (34.6%), followed by idiopathic causes (30.8%) and pancreatic divisum (23.1%). There was no mortality and the complication rate was 56 per cent. Islet equivalents infused and islet equivalents/gram of pancreas were 82,094 and 2,739 respectively. Mean discharge insulin dose was 10.7 units/day. Mean follow-up was 6.5 months. At 6 months, 80 per cent of patients reporting had decreased or eliminated their use of narcotic medication and all total pancreatectomy patients required insulin (mean 23 units/day). In appropriately selected patients, pancreatic resection with IAT is safe and effective for the treatment of intractable pain associated with CP.