Cases Of Chronic Pancreatitis Research Articles

Abstract LB-134: Sequential validation of blood-based protein biomarker candidates for early-stage pancreatic cancer

Abstract Purpose: CA19-9, which is currently in clinical use as a pancreatic ductal adenocarcinoma (PDAC) biomarker, has limited performance in detecting early stage disease. We and others have identified protein biomarker candidates that have the potential to complement CA19.9. We have carried out sequential validations starting with 32 protein biomarker candidates to develop a marker panel to improve detection of early stage disease compared with CA19.9 alone. Patients and Methods: Multiple independent sample sets consisting of PDAC cases, benign pancreatic disease and healthy controls were utilized for immunoassays of candidate markers which after sequential validations yielded a panel of three markers that was further tested in a blinded setting. Results: The 32 biomarker candidates were initially tested in a sample set consisting of 75 PDAC cases, 29 healthy controls, and 19 chronic pancreatitis cases which narrowed the list to seven biomarker candidates. A second independent set of 73 early-stage PDAC cases, 60 healthy controls, and 74 benign pancreatic disease cases (60 chronic pancreatitis cases and 14 benign pancreatic cyst cases) yielded a panel of three markers, including CA19-9, with an AUC (95%CI) of 0.949 (0.917-0.981) and sensitivity of 0.849 at 95% specificity. Additional blinded testing of the model was done using an independent set of plasma samples from 39 resectable PDAC patients and 82 matched healthy controls, yielding an AUC of 0.887. The performance of the biomarker panel was significantly improved compared to CA19-9 alone (P < 0.001) in both plasma sample sets. Conclusion: We validated a protein-based three marker panel with significantly improved performance compared to CA19-9 with the potential to contribute to strategies for detecting early-stage PDAC. Citation Format: Michela Capello, Leonidas E. Bantis, Ghislaine Scelo, Yang Zhao, Dilsher S. Dhillon, Hong Wang, James L. Abbruzzese, Anirban Maitra, Margaret A. Tempero, Randall Brand, Matthew A. Firpo, Sean Mulvihill, Matthew H. Katz, Paul Brennan, Ziding Feng, Samir M. Hanash, Ayumu Taguchi. Sequential validation of blood-based protein biomarker candidates for early-stage pancreatic cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-134.

Estudo clínico-epidemiológico das pancreatites em um hospital de referência terciária entre 2013 e 2014

Introduction: Clinical manifestations of pancreatitis are so varied that if the physician only bear the classic symptoms, he will diagnose just part of the cases. Method: This is a descriptive study of patients diagnosed with acute or chronic pancreatitis in the Conjunto Hospitalar de Sorocaba, Sao Paulo, Brazil. We reviewed 39 medical records, which covered all cases of pancreatitis from June 2013 to June 2014. Results: We found 26 cases of acute pancreatitis and 4 of chronic pancreatatis. Biliary etiology accounted for 50,0% of cases, followed by alcoholic (26.7%) and idiopathic (13.3%). The classic upper abdominal pain was found in 11 patients, and in 3 of them it irradiates to the back. Several other painful manifestations have been reported. The duration of the pain ranged from 6 hours to 5 months. The etiologies found showed different distribution between genders. The duration of pain was higher among cases of chronic pancreatitis (median 70.5 versus 2 days; p=0.02), and the values of amylase were higher in acute pancreatitis (median 929 versus 52.5 U/L; p=0.00). Conclusions: Acute pancreatitis and chronic acutized pancreatitis, when properly diagnosed, have a benign curse, solving in a few days. The characterization of pain and other clinical manifestations are little scrutinized in medical records, perhaps because of the relative ease of classic cases diagnosis and the availability of laboratory tests. de avaliacao laboratorial.

Clinical case of chronic calcific pancreatitis in a patient with parathyroid carcinoma caused primary hyperparathyroidism

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

EUS Guided Coiling for Bleeding Duodenal Collateral Vessel

65 year old male, a chronic smoker and alcoholic and a diagnosed case of chronic calcific pancreatitis since 2014, presented with recurrent abdominal pain, loss of weight and loss of appetite. CT SCAN of abdomen showed 3.4 x 3.6 cm mass in the head of pancreaas with biliary and pancreatic ductal dilation. It also showed calcification of pancreatic parenchyma. EUS guided FNA was suggestive of neuroendocrine tumor of pancreas. Prominant collaterals were seen adjacent to the mass. He presented a week later with massive upper GI bleed from the 2nd part of duodenum. Initial endoscopic hemostasis was achieved with hemoclips. However, as he rebled within 48hrs, EUS was done which showed active bleeding from the collateral seen near the mass. EUS guided coil (4 mm size, Three in number) were placed into the collateral. Complete thrombosis of the collateral was noted. Hemostasis was achieved. Patient remained stable and was discharged after 3 days.

Test–retest reliability of 3D EPI MR elastography of the pancreas

To determine the repeatability of three-dimensional echo planar imaging magnetic resonance (MR) elastography (3D EPI MRE) for assessing pancreatic stiffness in healthy volunteers, patients with chronic pancreatitis, and patients with pancreatic ductal adenocarcinoma (PDAC). 3D EPI MRE was used to assess pancreatic stiffness in five healthy volunteers, and five and three patients with histopathologically confirmed chronic pancreatitis and PDAC, respectively. The study participants underwent two scans, separated by a 1-day interval (referred to as time point 1 and time point 2). Scanning was performed using a 3 T MR machine using a multi-section EPI pulse sequence to assess the mean stiffness of the tumours in PDAC cases, and pancreatic parenchyma in chronic pancreatitis cases and healthy volunteers. A direct-inversion algorithm with 3D post-processing was used to estimate shear stiffness and generate elastograms. Stiffness was measured independently by two analysts. Between the two analysts, the mean stiffness of all 13 pancreases was highly reproducible, with an intraclass correlation coefficient (ICC) of 0.975 (95% confidence interval [CI]: 0.945-0.989) across the two time points (r=0.973, p<0.001). Bland-Altman analysis found a difference in mean stiffness of 0.01kPa (95% agreement limits: -0.53-0.55kPa). Between the two time points, the ICC was 0.973 (95% CI: 0.941-0.988) across the two analysts (r=0.975, p<0.001), and the difference in stiffness by Bland-Altman analysis was 0.05kPa (95% agreement limits: -0.51-0.60kPa). The mean stiffness value of pancreases with PDAC was 2.89±1.20kPa, which was significantly higher than that of normal pancreases (1.11±0.08kPa, p<0.001) and of pancreases with chronic pancreatitis (1.53±0.04kPa, p<0.001). 3D-MRE is a highly reproducible method for assessing pancreatic stiffness.

Clinical Profile, Etiology, and Treatment of Chronic Pancreatitis in North American Women: Analysis of a Large Multicenter Cohort.

Historically, chronic pancreatitis (CP) was considered a disease of alcoholic males, but recent data suggest its etiology to be complex. To better understand CP in women, we compared data on women and men with CP in a large, prospectively ascertained multicenter US cohort. Patients with CP enrolled in the NAPS2 Continuation and Validation study were studied. Information on demographics, etiology, risk factors, phenotype, and treatment(s) used was obtained from detailed questionnaires completed by the patients and physicians. Of 521 cases, 45% were women. Women were significantly (P < 0.05) less likely to have alcohol etiology (30% vs 58.5%) and more likely to have nonalcoholic etiologies (idiopathic, 32% vs 18%; obstructive, 12% vs 2.4%; genetic, 12.8% vs 7.3%). Demographics, pain experience, morphologic findings, exocrine and endocrine insufficiency, CP-related disability, and use of medical therapies were mostly similar in both sexes. Sphincterotomy (biliary, 33% vs 24%; pancreatic, 38% vs 28%; P < 0.05) was performed more frequently in women, whereas cyst/pseudocyst operations were more common in men (6.6 vs 2.6%, P = 0.02). Most CP cases in women are from nonalcoholic etiologies. In contrast to many other chronic diseases, clinical phenotype of CP is determined by the disease and is independent of sex.

Common Variants in CLDN2 and MORC4 Genes Confer Disease Susceptibility in Patients with Chronic Pancreatitis.

A recent genome-wide association study (GWAS) identified association with variants in X-linked CLDN2 and MORC4, and PRSS1-PRSS2 loci with chronic pancreatitis (CP) in North American patients of European ancestry. We selected 9 variants from the reported GWAS and replicated the association with CP in Indian patients by genotyping 1807 unrelated Indians of Indo-European ethnicity, including 519 patients with CP and 1288 controls. The etiology of CP was idiopathic in 83.62% and alcoholic in 16.38% of 519 patients. Our study confirmed a significant association of 2 variants in CLDN2 gene (rs4409525—OR 1.71, P = 1.38 x 10-09; rs12008279—OR 1.56, P = 1.53 x 10-04) and 2 variants in MORC4 gene (rs12688220—OR 1.72, P = 9.20 x 10-09; rs6622126—OR 1.75, P = 4.04x10-05) in Indian patients with CP. We also found significant association at PRSS1-PRSS2 locus (OR 0.60; P = 9.92 x 10-06) and SAMD12-TNFRSF11B (OR 0.49, 95% CI [0.31–0.78], P = 0.0027). A variant in the gene MORC4 (rs12688220) showed significant interaction with alcohol (OR for homozygous and heterozygous risk allele -14.62 and 1.51 respectively, P = 0.0068) suggesting gene-environment interaction. A combined analysis of the genes CLDN2 and MORC4 based on an effective risk allele score revealed a higher percentage of individuals homozygous for the risk allele in CP cases with 5.09 fold enhanced risk in individuals with 7 or more effective risk alleles compared with individuals with 3 or less risk alleles (P = 1.88 x 10-14). Genetic variants in CLDN2 and MORC4 genes were associated with CP in Indian patients.

Spanish multicenter study to estimate the incidence of chronic pancreatitis.

To estimate the incidence of chronic pancreatitis in Spain as diagnosed with endoscopic ultrasound (EUS), and to assess the risk factors and complications detected. A descriptive, observational study of chronic pancreatitis cases diagnosed in Spanish health care centers with an EUS unit. A structured questionnaire was used to evaluate the incidence of the disease (cases identified over 18 months: from January 2011 to June 2012), risk factors, EUS criteria, Rosemont classification, and frequency of local complications. Twenty-three centers were selected serving a total reference area of 14,752,704 population. During the study period 1,031 chronic pancreatitis cases were diagnosed, with an incidence of 4.66 cases per 105 inhabitants/year (95% CI: 4.65-4.67). Tobacco and alcohol use appear as risk factors in 63.8% and 66.7% of cases, respectively. Of these, 53.3% met > 5 EUS criteria for chronic pancreatitis, and 69% had findings suggestive of or consistent with chronic pancreatitis according to the Rosemont classification. Most prevalent complications included calcifications (34.7%), pseudocysts (16%), and presence of an inflammatory pancreatic tumor (10.4%). The incidence of chronic pancreatitis in Spain is similar to that of other European countries. Given the widespread use of the technique, EUS units are key in detecting the disease, and their activity and results allow to estimate the incidence of chronic pancreatitis over wide, representative population areas.

A Case of Chronic Calcific Nonalcoholic Pancreatitis.

Tropical Calcific Pancreatitis (TCP) is a type of chronic calcific nonalcoholic pancreatitis. Similar to nonalcoholic chronic pancreatitis, it presents in the second and third decades of life; however this type is reported mostly in the developing tropical and subtropical countries. It is associated with the formation of pancreatic calculi and a high probability of developing insulin-dependent diabetes mellitus. Epidemiologic studies have shown that these patients have an increased risk of developing pancreatic carcinoma. The etiology of TCP remains uncertain, with the current consensus suggesting genetics as well as possible toxicity from consuming large amounts of cassava, a tuber. Definite diagnosis of TCP requires younger age of onset, history of malnutrition, and presence of diabetes mellitus along with extensive pancreatic calcification and ductal calculi. When patients meet most but not all of these conditions the term Idiopathic Chronic Pancreatitis (ICP) is used. This is a case of a 44-year-old man who presented with most features seen in TCP, and however, was diagnosed with ICP.

Inferoposterior duodenal approach for laparoscopic pancreaticoduodenectomy.

To investigate the advantages of inferoposterior duodenal approach (IPDA) for laparoscopic pancreaticoduodenectomy (LPD). A total of 36 patients subjected to LPD were admitted to the Affiliated Yijishan Hospital of Wannan Medical College from December 2009 to February 2015. These patients were diagnosed with an ampullary tumour or a pancreatic head tumour through computed tomography, magnetic resonance imaging or endoscopic retrograde cholangiopancreatography preoperatively. The cases were selected on the basis of the following criteria: tumour diameter < 4 cm; no signs of peripheral vascular invasion; evident lymph node swelling; and distant metastasis. Of the 36 cases, 20 were subjected to anterior approach (AA; AA group) and 16 were subjected to IPDA (IPDA group). Specimen removal time, intraoperative blood loss and postoperative complications in the two groups were observed, and their differences were compared. During the operation, 2 cases in the AA group and 2 cases in the IPDA group were converted to laparotomy; these cases were excluded from statistical analysis. The remaining 32 cases successfully completed the surgery. The AA group and IPDA group exhibited the specimen removal time of 205 ± 52 and 160 ± 35 min, respectively, and the difference was significant (P < 0.01). The AA group and IPDA group revealed the intraoperative blood loss of 360 ± 210 mL and 310 ± 180 mL, respectively, but these values were not significantly different. Postoperative pathological results revealed 4 cases of inferior common bile duct cancer, 8 cases of duodenal papillary cancer, 6 cases of ampullary cancer, 13 cases of pancreatic cancer, 3 cases of chronic pancreatitis accompanied with cyst formation or duct expansion, and 2 cases of mucinous cystic tumour in the pancreatic head. The postoperative complications were pulmonary Staphylococcus aureus infection, incision faulty union, ascites induced poor drainage accompanied with infection, bile leakage, pancreatic leakage and delayed abdominal bleeding. In IPDA, probing for important steps can be performed in early stages, surgical procedures can be optimised and operation time can be shortened.

Alcohol and hypertriglyceridemia lead to different outcomes through different expression and activation of hypoxia inducible factor and nuclear factor kappaB during acute pancreatitis

Chronic pancreatitis (CP) patients are at risk for fat-soluble vitamins (A, D, E, K) deficiency, but available studies are small and heterogeneous. We conducted a systematic review and meta-analysis to determine the prevalence of fat–soluble vitamins deficiency in CP patients.Medline was searched up to January 2016 for case series and case-control studies reporting prevalence of fat-soluble vitamin deficiency in CP patients. The prevalent deficiency rate was pooled for included studies, and deficiency rate between CP and controls, with relative odds ratio (OR) and 95% confidence interval (CI) calculated for case-control studies.Twelve studies including 548 patients included. With a random-effect model, the pooled prevalence rate of vitamin A, D and E deficiency were 16.8% (95%CI 6.9–35.7), 57.6% (95%CI 43.9–70.4) and 29.2% (95%CI 8.6–64.5) respectively, with considerable heterogeneity (I2 = 75%, 87.1% and 92%). Only one study evaluated vitamin K deficiency. The pooled OR for vitamin D deficiency in CP cases compared with controls was 1.17 (95% CI 0.77–1.78). Sensitivity analyses showed lower prevalence of vitamin A and E, and higher prevalence of vitamin D deficiency in high-quality studies. The rate of pancreatic exocrine insufficiency did not seem affect the deficiency rates, while the use of different cut-offs influences results and heterogeneity for vitamin E, but not A.Fat-soluble vitamins deficiency is frequent in CP patients, with considerable heterogeneity. There is, however, no apparent increased risk of vitamin D deficiency in CP compared to controls. Larger, high-quality studies are necessary to better estimate the prevalence of fat-soluble vitamins deficiency, including vitamin K.

Clinical profile of PanIN lesions in tropical chronic pancreatitis.

Chronic pancreatitis (CP) found in the tropical countries is known to have a higher risk for carcinoma of the pancreas. This study aimed to explore the clinical profile of pancreatic intraepithelial neoplasia (PanIN), one of the precursors of carcinoma of the pancreas, in tropical CP and to identify the possible clinical predictors of the same. A retrospective study was done enrolling patients who underwent either Frey's procedure or pancreatic resection for symptomatic CP, between January 2008 and December 2012. They were grouped into PanIN positive and PanIN negative based on histopathology. Their clinical and laboratory parameters were compared statistically to identify the predictors of the PanIN status. Sixty-two tropical CP patients who had Frey's procedure or pancreatic resection were enrolled into this study; 38.7 % cases showed PanIN changes and 61.29 % had no PanIN changes. Majority of the clinical and laboratory parameters were found comparable between the two groups except obstructive jaundice and CA 19-9 value >137.5 which were there in 54.2 % of PanIN-positive cases. On histopathology, 54.83 % cases were benign CP and 45.16 % were malignant CP. Among the benign CP, 33.3 % were PanIN positive and among those with malignancy 66.7 % were PanIN positive. Low-grade PanINs were seen in 73 % cases of benign CP and in 26.1 % of malignancy whereas high-grade PanIN-3 lesions were seen exclusively in patients with malignancy. High-grade PanIN-3 lesions showed significant association with pancreatic malignancy. Obstructive jaundice and CA 19-9 ≥ 137.5 could predict PanIN positivity.

Acute Recurrent Pancreatitis; Relative Risk Factors, Etiology ,Diagnosis Procedure And Treatment In the Pancreatic disease Institute of Wuhan Union Hospital Of China

This study describes the relative risk factors, etiology and treatment option of recurrent acute pancreatitis. The data of 71 patients with acute recurrent pancreatitis were retrospectively studied from January 2010 to December 2014. Of 71 patients, 41 were male and 30 were female with a sex ratio of 1.4:1 with a mean age of 49 years. Their age ranged from 14 to 85 years. After reviewing the clinical data, the risk factors were analyzed using univariate and multivariate analysis. The etiology was investigated in each case using specialized laboratory analysis, ERCP, EUS and MRCP. Their pain was labeled severe, moderate and mild by using the Analgesic Ladder by World Health Organization. Subsequent to the investigation reports, therapeutic ERCP and endoscopic sphincterotomy were performed. Of the 71 patients, 52 cases were biliary pancreatitis, 13 were idiopathic pancreatitis, 3 were alcohol induced pancreatitis and 3 were hyperlipidemia pancreatitis. The univariate analysis showed easy recurrence with obstructive jaundice, hepatic function injury and local complication of pancreas (P=0.016< 0.05 P= 0.003<0.05 and P= 0.024< 0.05 correspondingly). Multivariate analysis showed no single factor related to recurrence. Upon definition of etiology, there were 33 cases of common bile duct stones, 14 cases of pancreatic duct stones, 5 cases of gallbladder stones, 3 cases of pancreas divisum, 2 cases of ampullary tumor, 4 cases of sphincter of Oddi dysfunction, 6 cases of chronic pancreatitis, 1 cases of post liver transplant complication and 3 cases of duodenal diverticulum. The 71 patients performed ERCP followed by either endoscopic sphincterotomy in 69 cases or endoscopic resection in 2 cases. The procedure was curative and successfully performed. A complication rate of 2.8% with no mortality was observed. Post-therapy, a decline in pain intensity was observed in 56 cases of the patients. ERCP and endoscopic sphincterotomy has a curative effect in diverse etiology of acute recurrent pancreatitis.

Is It Really a Malignancy? A Case of Chronic Pancreatitis With Vitamin D Deficiency Masquerading as Malignancy

Chronic pancreatitis is longstanding inflammation of the pancreas that causes scarring and damage to the organ which eventually leads to alteration in its structure and function. Chronic pancreatitis can cause severe vitamin D deficiency, which could be significant, causing secondary hyperparathyroidism and bone lesions. Clinicians should be aware of the causes of bone lesion found incidentally. Most common differential for a patient with Bone lesion is malignancy. Other causes not uncommon but to be considered as seen in our patient are vitamin D deficiency secondary to causes such as chronic pancreatitis. 49 year-old African American inmate presented to our hospital, as a transfer from outside facility with a concern of metastatic cancer after bone scan showed evidence of osteoplastic lesions in the humeri and ribs. Patient has history of significant weight loss, night sweats, generalized weakness and bone pain over a course of one year. He also has a history of rib fracture secondary to simple fall. He reported a history of heavy alcohol abuse before he was incarcerated in prison in 1995. On Physical exam he looked cachectic, clinically anemic. Chest was clear to auscultation with chest wall tenderness. Abdomen is soft with no organomegally. Rectal exam was negative. His admission labs were remarkable for Calcium 5.9 mg/dl, Vitamin D level was undetectable. His HIV serology was negative. Repeated bone scan shows pathologic radio tracer uptake in the ribs and pubic bones. Malignancy work up including CT scan chest, abdomen and pelvis was unremarkable. Tumor markers including PSA were negative. Pancreas was noted to be atrophic with calcification in the abdominal CT scan. On further questioning, patient gave history of chronic abdominal pain and diarrheal episodes. We ordered PTH. It was 1590 pg/ml. It was concluded that his clinical manifestation is related to severe pancreatitis with subsequent malabsorption syndrome and severe vitamin D deficiency which have led to what's called brown tumors of the bone with pathological fracture. Patient then was started on pancreatic enzymes replacement, Vitamin D and calcium.Figure 1Figure 2We are reporting a rare presentation of chronic pancreatitis. Clinical manifestation such bone pain, fractures, and weight loss with bone lesions in bone scan could be misleading of cancer diagnosis and could lead to ordering complex and expensive tests. Clinician should be alert to the late and severe presentation of chronic pancreatitis causing vitamin D deficiency with subsequent secondary hyperparathyroidism leading to Brown tumors particularly in patient who have dark skin, prisoners with limited sun exposure such as in our patient. These patients will benefit with simple lab tests such as vitamin D levels and if low, then PTH levels. We can cut back on malignancy workup and save lot on financial burden in Health Care.

Genetic analysis of the bicarbonate secreting anion exchanger SLC26A6 in chronic pancreatitis.

Pancreatic ductal HCO3(-) secretion is critically dependent on the cystic fibrosis transmembrane conductance regulator chloride channel (CFTR) and the solute-linked carrier 26 member 6 anion transporter (SLC26A6). Deterioration of HCO3(-) secretion is observed in chronic pancreatitis (CP), and CFTR mutations increase CP risk. Therefore, SLC26A6 is a reasonable candidate for a CP susceptibility gene, which has not been investigated in CP patients so far. As a first screening cohort, 106 subjects with CP and 99 control subjects with no pancreatic disease were recruited from the Hungarian National Pancreas Registry. In 60 non-alcoholic CP cases the entire SLC26A6 coding region was sequenced. In the Hungarian cohort variants c.616G>A (p.V206M) and c.1191C>A (p.P397=) were further genotyped by restriction fragment length polymorphism analysis. In a German replication cohort all exons were sequenced in 40 non-alcoholic CP cases and variant c.616G>A (p.V206M) was further analyzed by sequencing in 321 CP cases and 171 controls. Sequencing of the entire coding region revealed four common variants: intronic variants c.23+78_110del, c.183-4C>A, c.1134+32C>A, and missense variant c.616G>A (p.V206M) which were found in linkage disequilibrium indicating a conserved haplotype. The distribution of the haplotype did not show a significant difference between patients and controls in the two cohorts. A synonymous variant c.1191C>A (p.P397=) and two intronic variants c.1248+9_20del and c.-10C>T were detected in single cases. Our data show that SLC26A6 variants do not alter the risk for the development of CP.

Abstract B23: Plasma basigin as an early detection biomarker for pancreatic adenocarcinoma

Abstract Poor survival rates for pancreatic adenocarcinoma (PDAC) are in part due to late presentation. Earlier diagnosis is recognized as a means to improve outcomes by increasing the possibility for potentially curative treatment. Identification of early detection biomarkers is a research priority. The stromal compartment is a potential source for biomarkers as a strong desmoplastic response is a hallmark of PDAC. The interaction of mesenchymal, cancer, and inflammatory cells in the tumor induce secretion of autocrine and paracrine effectors and extracellular matrix remodeling enzymes that contribute to tumor growth, invasion, angiogenesis, and metastasis. Basigin (BSG), a cell surface glycoprotein, plays a role in the interaction of cancer and mesenchymal cells through the stimulation of extracellular matrix remodeling enzymes. Circulating BSG has also been demonstrated as a diagnostic/prognostic biomarker for other cancers. We evaluated the potential utility of plasma BSG as a PDAC diagnostic and prognostic biomarker. BSG levels were measured by ELISA in plasma from 106 healthy control subjects (mean = 3.29 ng/ml, 95% CI =3.0 – 3.6), 77 patients with chronic pancreatitis (3.72 ng/ml, 3.3 – 4.1 CI), and 112 pre-treatment samples from patients with PDAC (4.19 ng/ml, 3.9 – 4.5 CI). Nonparametric analysis revealed a significant difference for the model (P = 0.02, Wilcoxon). By ANOVA and Tukey-Kramer post-hoc tests, the distributions of BSG levels in PDAC and healthy control subjects were significantly different (P = 0.0003), but the comparison of PDAC to chronic pancreatitis cases was not significant (P = 0.147). A striking difference was noted after separating the PDAC cases into early stage (I-II) and late stage (III-IV) groups. ANOVA indicated that early stage disease (N = 70, 4.61 ng/ml, 4.2 – 5.0 CI) had significantly elevated BSG levels compared to healthy controls (P &amp;lt; 0.0001), chronic pancreatitis cases (P = 0.006), and late stage PDAC cases (P = 0.003, N = 42, 3.48 ng/ml, 2.9 – 3.9 CI). Increased plasma BSG levels were also significantly related to decreased survival in univariate Cox proportional hazards models (P = 0.01) indicating a 14% increase in risk per 1 ng/ml. This relationship remained significant in multivariate models adjusting for stage and post-diagnosis treatments. The results suggest that circulating BSG is an early stage phenomenon during PDAC development and would apparently be unique in its ability to specifically identify early stage PDAC cases. If validated, this biomarker should substantially contribute to the accuracy of an early detection biomarker panel. Further investigations are warranted into the usefulness of circulating BSG for early detection, selection of patients for surgical resection, identification of recurrence, screening high-risks groups and/or inclusion in panel screens. Citation Format: Samaa Kamal, Matthew A. Firpo, Courtney L. Scaife, Adler G. Douglas, Kenneth M. Boucher, Sean J. Mulvihill. Plasma basigin as an early detection biomarker for pancreatic adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B23.

Abstract A83: Nuclear morphometry differentiates chronic pancreatitis, IPMN, and pancreatic carcinoma

Abstract Background: It can be difficult to distinguish between chronic pancreatitis (CP), IPMN, and pancreatic carcinoma (PC) on tissue biopsy. Nuclear morphometry can measure up to 93 unique nuclear features based on standard histopathology. The goal of this work is to build novel, objective, and accurate prediction tools, based on nuclear morphometric signatures in high resolution images of nuclei of histologic sections, for classifying pancreatic tissues into three distinct groups. Materials &amp; Methods: 44 patients who underwent pancreatic resections were identified. 12 cases of CP, 16 cases of IPMN, and 16 cases of PC were utilized in this pilot study. 180 ± 22 nuclei from each lesion were imaged with high resolution microscopy. Clincodemographic data was obtained retrospectively from the medical record. Statistically significant nuclear features were determined by a fully automated penalized multinomial regression algorithm in order to determine a multi-class classifier and simultaneously identify important nuclear features. The LASSO penalty function, and associated regularization parameter, is adaptively chosen by cross validation to prevent over-fitting. In order to test the veracity of the automated algorithm, we randomly removed 25% of the cases as a training set and utilized the remaining cases as a test set; this was repeated 10 times. Results: The average age was 64 ± 15 years, with patients in the CP being slightly younger; 63% were male. Median follow-up time was 3 years in the CP group, 3 years in the IPMN group, and 5 years in PC group. The method described automatically identified 6 unique and statistically significant nuclear features (corrected overall P &amp;lt; 0.005); these features related to nuclear heterogeneity and chromatin shapes. Cases assigned to 1 of the 3 groups were correctly assigned with an overall accuracy of 84.5%. Interestingly, cases of incorrect classification had larger proportion of nuclei from all three groups suggesting a mixed morphologic lesion. Conclusions: Nuclear morphometry classifies pancreatic lesions into CP, IPMN, and PC with 84.5% accuracy using a fully automated algorithm to determine statistically significant and unique nuclear features. Since the incorrectly classified lesions had a larger proportion of mixed nuclei, diagnostic uncertainty may be determined in a quantitative manner allowing for a confidence probability estimation of whether a given lesions should be classified as a CP, IPMN, or PC. Further studies will validate these results in a resected cohort as well as a cohort based on biopsied specimens alone. Citation Format: Evan S. Glazer, Hao Zhang, Kimberly A. Hill, Charmi Patel, Stephanie T. Kha, Peter H. Bartels, Michael L. Yozwiak, Hubert G. Bartels, Joseph C. Watkins, David S. Alberts, Robert S. Krouse. Nuclear morphometry differentiates chronic pancreatitis, IPMN, and pancreatic carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A83.

The Posterior Approach for Laparoscopic Distal Pancreatectomy: A Valid Choice for Resection of Complex Lesions of the Distal Pancreas.

Laparoscopic distal pancreatectomy (LDP) is replacing open surgery as the technique of choice for benign and premalignant lesions of the left pancreas. In most laparoscopic series, the supine decubitus or semilateral position is preferred. A posterior approach with the patient in full right lateral decubitus (PA-FRLD) has been proposed as an alternative. From July 2012 to November 2014 we performed 14 LDPs. PA-FRLD was chosen in 8 patients; in 6 patients splenectomy was also performed. Definitive diagnoses were 3 cases of pancreatic ductal adenocarcinoma, 2 cases of nonfunctioning neuroendocrine tumors, 1 case of bulky serous cystic neoplasm, 1 case of inflammatory chronic pancreatitis, and 1 case of pancreatic trauma (duct disruption). No conversions were required. No postoperative pancreatic fistula was detected. No patient required transfusion. Two patients had Clavien II and IIIb postoperative complications. In both cases in which preservation of the splenic vessels was attempted, it was successfully achieved. The PA-FRLD position is a valid alternative to the supine or semilateral position for LDP. This approach is especially beneficial for resection of complex and bulky lesions of the tail of the pancreas and those in close contact with retroperitoneal organs and can also facilitate spleen-preserving LDP.

Etiology, pathology, management and prognosis of chronic pancreatitis in Chinese population: A retrospective study

The purpose of this study was to investigate the etiology, pathological characteristics, management and prognosis of chronic pancreatitis in the Chinese population. The clinical data of 142 patients with chronic pancreatitis were retrospectively studied. All patients were of Chinese nationality and hospitalized from January 2008 to December 2011. Their ages ranged from 14 to 76 years, with a mean of 43 years. Of 142 patients, there were 72 cases of obstructive chronic pancreatitis (50.70%), 19 cases of alcoholic chronic pancreatitis (13.38%), 14 cases of autoimmune pancreatitis (9.86%) and 37 cases of undetermined etiology (26.06%). Pathologically, the average inflammatory mass diameter was 3.8 ± 3.3 cm, biliary obstruction occurred in 36 cases, gall stones in 70 cases, calcification in 88 cases, ductal dilatation in 61 cases, side branch dilatation in 32 cases, ductal irregularity in 10 cases, lymphocytic inflammation in 23 cases, obliterative phlebitis in 14 cases, extra pancreatic lesion in 19 cases and fibrosis in 142 cases. Location of pancreatic lesion in the region of head (n=97), neck (n=16), body (n=12), tail (n=15) and whole pancreas (n=2) influenced the choice of surgical procedures. Ninety-four patients (66.20%) received surgical treatment and 33.80% received other treatments. After operation, 80.85% of 94 patients experienced decreased pain, and 8.51% of 94 showed recovery of endocrine function but with a complication rate of 12.77%. All the operations were performed successfully. According to the pain scale of European Organization for Research and Treatment of Cancer (QLQ-C30) a decrease from 76 ± 22 to 14 ± 18 was observed. Etiology, pathological characteristics, management and prognosis of chronic pancreatitis in the Chinese population vary from others.

Small intestinal bacterial overgrowth in chronic pancreatitis: Systematic review and meta-analysis

Background & aim: Small intestinal bacterial overgrowth (SIBO) has been proposed as a factor causing symptoms and potentially impairing the nutritional status of patients with chronic pancreatitis (CP), but evidence is conflicting. A systematic review and meta-analysis were conducted on the prevalence of SIBO in CP. Methods: Medline was searched up to November 2014. Case series and case-control studies investigating SIBO in adult patients with CP were considered eligible. The prevalence of positive tests was pooled for included studies, and the rate of positivity between CP cases and controls, and the relative OR and 95% confidence interval (CI) calculated. Results: Six studies were identified from an initial list of 1579, containing 186 CP patients. The pooled prevalence of positive tests (either glucose or lactulose H2 Breath Test) was 30% (95% CI 15%-51%), with significant heterogeneity (I2=77%). A sensitivity analysis excluding the only study employing lactulose BT gave a pooled prevalence of 23% (95% CI 14%-36%), with reduced heterogeneity (I2=58%). The pooled odds ratio for positive tests in CP cases compared with controls was 5.7 (95% CI 1.6-20.7; p=0.007; I2=67%), being reduced to 2.8 (95% CI 1.2-6.8; p=0.017; I2=32%) when the study employing lactulose was excluded. Conclusions: One of four patients with CP is affected by SIBO, with a significantly increased risk over controls, although results are heterogeneous, and studies carry several limitations. The use of lactulose H2 BT seem to overestimate SIBO. The impact of SIBO and its treatment on the nutritional status of CP patients deserve further investigation.