Antioxidants for Pancreatic Functions in Chronic Pancreatitis: A Double-blind Randomized Placebo-controlled Pilot Study.

BACKGROUND: Antioxidants (AO) supplementation in chronic pancreatitis (CP) has been evaluated for pain. But it is not clear whether AO in CP have an effect on pancreatic functions and other clinical outcomes. We evaluated effect of AO on endocrine function in CP. MATERIALS AND METHODS: Double-blind placebo (PL)-controlled randomized pilot study on 107 patients with CP assigned to receive daily combined AO or PL for 6 months. Primary outcome was: improvement in endocrine function (Homeostasis Model Assessment-Insulin Resistance). Secondary outcome measures were: improvement in C-peptide, Qualitative Insulin Sensitivity Check Index, exocrine pancreatic function (fecal elastase), surrogate markers of fibrosis (platelet-derived growth factor BB, transforming growth factor-ß1, α-smooth muscle actin), quality of life (QOL), pain, nutritional status, markers of oxidative stress (OS), AO status, and inflammation. RESULTS: There was an increase in levels of serum selenium (107.2±26.9 to 109.7±26.9 vs. 104.1±28.6 to 124.0±33.6 µg/L, P=0.022) and serum vitamin E [0.58 (range, 0.27-3.22) to 0.66 (range, 0.34-1.98) vs. 0.63 (range, 0.28-1.73) to 1.09 (range, 0.25-2.91) mg/dL, P=0.001] in the AO than the PL group. However, no significant differences were observed between groups in any of the primary or secondary outcome measures. CONCLUSIONS: Supplementation with AO to patients with CP causes a sustained increase in blood levels of AO; however, it has no addition benefit over PL on endocrine and exocrine functions, markers of fibrosis, OS and inflammation, nutritional status, pain and QOL. Further larger studies with adequate sample size are required.

Association of endotoxaemia & gut permeability with complications of acute pancreatitis: Secondary analysis of data.

Background & objectives: In acute pancreatitis (AP) gut barrier dysfunction is considered as an important predisposing factor leading to increased intestinal permeability (IP). In this study a pooled analysis of data published in our previous four studies on various aspects of gut permeability and endotoxaemia in patients with AP was attempted to find an association between increased IP and severity of disease and associated complications. Methods: This study was a pooled analysis of data of four previously published prospective studies on AP. Gut permeability, assessed by lactulose/mannitol excretion in urine and endotoxin core antibodies type IgG and IgM (EndoCab IgG and IgM) were measured on days zero and seven (D0 and D7) of admission. All patients received standard treatment of AP. We studied whether IgG and IgM anti-endotoxin titres and lactulose-mannitol ratio (LMR) at admission and D7 were associated with organ failure, infection and mortality. Results: The titres of anti-endotoxin IgG and IgM were lower in all patients of AP (n=204), both in mild AP (n=24) and severe AP (n=180) in the first week, compared to controls (n=15). There was no significant difference in serum IgG and IgM anti-endotoxin levels and LMR at baseline and at D7 among patients with organ failure, infection and mortality. Interpretation & conclusions: Our findings showed that serum IgG and IgM anti-endotoxin titres and LMR at admission and at day 7 were not associated with organ failure, infection, and death of patients with AP.

Potential of Fecal Calprotectin as an Objective Marker to Discriminate Hospitalized Patients with Acute Severe Colitis from Outpatients with Less Severe Disease.

BACKGROUND: Acute severe colitis (ASC) is conventionally diagnosed by Truelove and Witts' criteria which are non-specific and can be affected by other pathologic conditions. Fecal calprotectin (FCP) is a gut-specific marker of inflammation which can predict short-term outcomes in patients with ASC. We aimed to define the role of FCP in the diagnosis of ASC. METHODS: This prospective observational cohort study included adult patients (> 18 years) with ulcerative colitis (UC) for whom FCP was measured and was under follow-up from April 2015 to December 2016. Patients were divided into two cohorts: (1) all consecutive hospitalized patients with ASC as defined by Truelove and Witts' criteria; (2) outpatients with active UC (defined by Mayo score) who did not fulfill Truelove and Witts' criteria. FCP levels were compared between the two cohorts, and a cutoff for FCP to diagnose ASC was determined. RESULTS: Of 97 patients, 49 were diagnosed with ASC (mean age: 36.1 ± 11.9 years, 36 males) and 48 with active UC (mean age: 37.9 ± 12.4 years, 25 males). Median FCP levels were significantly higher in patients with ASC [1776(952-3123) vs 282(43-568) µg/g, p < 0.001] than mild to moderately active UC (n = 48) or moderately active UC [n = 35, 1776(952-3123) vs 332(106-700) µg/g, p < 0.001]. A FCP cutoff of 782 µg/g of stool had excellent diagnostic accuracy, with an area under the curve of 0.92(95% CI 0.87-0.97), sensitivity of 84% and specificity of 88% to differentiate ASC from active UC. CONCLUSION: FCP could differentiate ASC from mild to moderate patients with UC, but requires validation before clinical use.

Kitchen-based diet versus commercial polymeric formulation in acute pancreatitis: a pilot randomized comparative study.

INTRODUCTION: Nutrition plays an important role in management of acute pancreatitis (AP) and decreases its severity and infectious complications. Various formulations of enteral nutrition (EN) are available and are costly. For developing countries, cost and availability is a major issue and kitchen-based diet should be explored in patients with AP. AIM: Comparison of kitchen-based diet with a commercially available polymeric formulation in terms of various outcomes in patients with AP within 14 days after the onset of pain. METHODS: Sixty patients (39 male, mean age 36.1 ± 12.7 years) of moderately severe and severe AP of any etiology were randomized (30 in each group) to either kitchen-based diet or commercial polymeric formulation group. Outcome measures were refeeding pain, tolerability, infectious complications, mortality, total hospital/intensive care unit stay; and change in serum C-reactive protein (CRP), transferrin and pre albumin. RESULTS: There was no significant difference in baseline demographic and biochemical parameters in both groups. No difference was observed in refeeding pain (7.1% vs 8%, p = 0.99), tolerability (28.6% vs 12%, p = 0.17), infectious complications (57.14% vs 36%, p = 0.12), mortality (31.7% vs 20%, p = 0.69), hospital stay (19.5 vs 23.5 days, p = 0.86), CRP (74.4 vs 59 mg/L, p = 0.97), transferrin levels (23.6 vs 25.6 mg/dL, p = 0.75) and pre albumin (9.45 vs 13.09 mg/dL, p = 0.68) in both groups. CONCLUSION: Kitchen-based diet is comparable to commercial polymeric formulation for the early initiation of enteral nutrition in patients with severe or moderately severe acute pancreatitis. CLINICAL TRIAL REGISTRATION: Trial registered with the Clinical Trials registry-India (CTRI/2018/01/011188).

Alterations in intestinal permeability and endotoxemia in severe acute pancreatitis.

BACKGROUND: Intestinal permeability increases early in the course of acute pancreatitis and is associated with sepsis and organ failure. AIM: To evaluate the intestinal permeability (IP) and anti-endotoxin antibodies immunoglobulin G and A (AEA IgG and A) in severe acute pancreatitis (SAP) as compared to healthy controls and determine their significance in relation to various complications of SAP. METHODS: IP was measured by urinary lactulose/mannitol (LM) excretion ratio and anti-endotoxin antibodies by Endocab ELISA kit at days one and seven of admission (D1 and D7). RESULTS: Thirty one patients of SAP [mean age (42.0 +/- 15.8) years, APACHE II scores (8.8 +/- 5.4) and CT severity index (6.4 +/- 2.0)] were included in this study. Infected pancreatic necrosis was detected in 13 (42%) patients of whom three died. Six died of persistent organ failure. Median values of LM ratio at D1 and D7 were similar to those in healthy controls. Patients experiencing complications [organ failure (4/9, 44%), infected pancreatic necrosis (5/10, 50%) and death (1/2, 50%)] manifested a substantial increase in their intestinal permeability at D7. Anti-endotoxin antibodies IgG were lower (p = 0.003) in patients than the controls at admission. AEA IgG were lower (p = 0.03) in non-survivors as compared to survivors at D7. CONCLUSION: Patients experiencing complications of severe acute pancreatitis showed an increase in intestinal permeability. Higher endotoxemia predicted poor outcome in severe acute pancreatitis.

Serum Bile Acids in Intrahepatic Cholestasis of Pregnancy (ICP), Versus Pregnant and Nonpregnant Controls in Asian Indian Women and a Proposed Scoring to Optimize Management in ICP.

Objectives: This prospective clinical trial was conducted to assess serum bile acids (BA) levels in women with intrahepatic cholestasis of pregnancy (ICP) compared to both pregnant and non-pregnant controls; and evaluate perinatal outcome in relation to bile acid levels. A scoring is proposed based on biochemical markers to optimize management in ICP cases. Materials and Methods: Serum bile-acids(BA) were assessed in 71 intrahepatic-cholestasis of pregnancy(ICP) cases (group-I), versus 50 pregnant (group-II) and 35 non-pregnant (group-III) controls. Ursodeoxycholic acid (UDCA) was administered in ICP group. Baseline bilirubin (SB), aminotransferases (AT), alkaline-phosphatase were sent in groups I & II. Investigations were repeated in group-I after 4 weeks. Perinatal complications were noted. Results: Mean BA in group-I was 75.92 ± 39.9 µmol/L which reduced to 41.3 ± 15.4 µmol/L(45.6%, p < 0.001) with UDCA. Mean BA was 29.2 ± 5.7 and 5.9 ± 1.8 µmol/L in group-II and group-III. UDCA significantly reduced itching-score. Rate of fetal distress linearly increased with the increasing baseline levels of serum BA, AT and SB: from 2.5 to 100% at BA < 40 and ≥ 200 µmol/L, (p = 0.008); from 16.1 to 100% at AT < 100 and ≥ 500 IU/mL(p = 0.016); and from 6.8 to 100% at SB < 0.8 and > 5 mg/dL (p = 0.001); respectively. Their baseline levels were divided into 5 groups in correlation to fetal distress. Serum BA < 40, 40-80, 80-120, 120-200, ≥ 200 µmol/L; AT < 100,100-200,200-500, ≥ 500 IU/mL; and SB < 0.8, 0.8-1.0, 1.1-2, 2.1-5 and > 5 mg/dL. Nutan ICP scoring was proposed with a score 0 to 4 given to each parameter and score-based management protocol was suggested for fetal surveillance and delivery. Conclusions: SBA are higher in Asian Indian pregnant women. Levels > 30 µmol/L can be taken as a cut off for diagnosing ICP in Asian-Indian women. Adopting higher cut-offs for this geographic part will avoid over-diagnosing ICP and iatrogenic early termination of pregnancy. Suggested scoring will help clinicians in optimizing the time of delivery on an individualized basis.

Demonstration of Gut-Barrier Dysfunction in Early Stages of Non-alcoholic Fatty Liver Disease: A Proof-Of-Concept Study.

Background/Aims: Gut-barrier dysfunction is well recognized in pathogenesis of both non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). However, comparison of components of this dysfunction between the two etiologies remains unexplored especially in early stages of NAFLD. Methods: Components of gut-barrier dysfunction like alterations in intestinal permeability (IP) by lactulose mannitol ratio (LMR) in urine, systemic endotoxemia (IgG and IgM anti-endotoxin antibodies), systemic inflammation (serum tumor necrosis factor alpha [TNF-α] and interleukin-1 [IL-1] levels), tight junction (TJ) proteins expression in duodenal biopsy and stool microbiota composition using Oxford Nanopore MinION device were prospectively evaluated in patients with NAFLD (n = 34) with no cirrhosis, ALD (n = 28) and were compared with disease free controls (n = 20). Results: Patients with ALD had more advanced disease than those with NAFLD (median liver stiffness -NAFLD:7.1 kPa [5.9-8.9] vs. ALD:14.3 kPa [9.6-24], P < 0.001]. Median LMR was significantly higher in NAFLD and ALD group when compared to controls (NAFLD 0.054 [0.037-0.17] vs. controls 0.027 [0.021-0.045] (P = 0.001)) and ALD 0.043 [0.03-0.068] vs. controls 0.027 [0.021-0.045] (P = 0.019)]. Anti-endotoxin antibody titer (IgM) (MMU/mL) was lowest in NAFLD 72.9 [3.2-1089.5] compared to ALD 120.6 [20.1-728]) (P = 0.042) and controls 155.3 [23.8-442.9]) (P = 0.021). Median TNF-α (pg/mL) levels were elevated in patients with NAFLD (53.3 [24.5-115]) compared to controls (16.1 [10.8-33.3]) (P < 0.001) and ALD (12.3 [10.1-42.7]) (P < 0.001). Expression of zonulin-1 and claudin-3 in duodenal mucosa was lowest in NAFLD. On principal co-ordinate analysis (PCoA), the global bacterial composition was significantly different across the three groups (PERMANOVA test, P < 0.001). Conclusion: While remaining activated in both etiologies, gut-barrier dysfunction abnormalities were more pronounced in NAFLD at early stages compared to ALD despite more advanced disease in the latter.

Role of probiotics on gut permeability and endotoxemia in patients with acute pancreatitis: a double-blind randomized controlled trial.

GOALS: To study the role of probiotics on gut permeability and endotoxemia in patients with acute pancreatitis (AP). BACKGROUND: Bacterial translocation has been implicated in infective complications in AP, which has been shown to be prevented by probiotics. STUDY: A double-blind, randomized placebo-controlled trial was conducted. Consecutive patients with AP presenting within 72 hours after the onset of abdominal pain or who had been nil orally at the time of presentation for up to 5 days were included in the study. The probiotic group received 4 sachets of Probiotics (2.5 billion bacteria per sachet) whereas the placebo group received 4 sachets of placebo for 7 days. Primary outcome measures were effect on gut permeability [assessed by lactulose/mannitol (L/M) excretion in urine] and endotoxemia assessed by endotoxin-core antibody types IgG and IgM (EndoCab IgG and IgM). Secondary outcome measures were mortality, total hospital/intensive care unit stay, abdominal discomfort, organ failure, C-reactive protein, and prealbumin levels. The study was prematurely stopped after the publication of probiotic prophylaxis in patients with predicted severe acute pancreatitis trial. RESULTS: From March 2007 to May 2008, 50 patients with AP were included in the study (26 in placebo group and 24 in probiotic group). There was no difference after intervention in gut permeability, whereas values of C-reactive protein and immunoglobulins decreased significantly [IgG: 140 (20-920) to 90 (20-600) GGU/mL and IgM: 65 (13-230) to 51 (9-240) GMU/mL] in the probiotic group. No difference was observed in prealbumin values, duration of hospital/intensive care unit stay, and mortality in both the groups. CONCLUSIONS: No significant trend was identified for an effect of probiotics on gut permeability or endotoxemia in AP. However, the study was underpowered owing to premature study termination.

Gluten content in labeled and unlabeled gluten-free food products used by patients with celiac disease.

OBJECTIVE: Gluten-free (GF) diet is the only reliable treatment for patients with celiac disease (CeD), but data on the extent of gluten contamination in GF food available in India is scanty. We evaluated gluten content in labeled, imported, and non-labeled GF food products currently available in the Indian market. METHODS: Overall, 794 processed and commercially available packaged GF products (labeled GF (n = 360), imported GF (n = 80), and non-labeled/naturally GF (n = 354)) were collected from supermarkets of National Capital Region of India. Those unavailable in stores were purchased from e-commerce sites or directly from the manufacturers. Gluten level in them was determined by Ridascreen Gliadin sandwich R5 enzyme-linked immunosorbent assay (R-Biopharm AG, Germany). As per Codex Alimentarius and Food Safety and Standard Authority of India, "gluten free" labeled products must not contain > 20 mg/kg of gluten. RESULTS: Overall, 10.1% of 794 GF products including 38 (10.8%) of 360 labeled and 42 (11.8%) of 354 non-labeled/naturally GF food products had gluten content > 20 mg/kg (range: 24.43-355 and 23.2-463.8 mg/kg, respectively). None of the imported GF products had gluten more than the recommended limits. Contaminated products most commonly belonged to cereal and their products (flours, coarse grains, pasta/macaroni, snack foods) pulse flours, spices, and bakery items. CONCLUSIONS: A substantial proportion (10.1%) of GF food products (both labeled and non-labeled) available in India have gluten content greater than the prescribed limits of <20 mg/kg. Physicians, dietitians, support group, and patients with CeD should be made aware of this fact and regulatory bodies should ensure quality assurance.

Cause and effect relationship of malnutrition with idiopathic chronic pancreatitis: prospective case-control study.

BACKGROUND AND AIM: Patients with chronic pancreatitis are often malnourished. The role of malnutrition in the pathogenesis of chronic pancreatitis is unclear. The aim of the present article was to study prospectively the cause and effect relationship of malnutrition with idiopathic chronic pancreatitis in a case-control study. METHODS: Consecutive patients with chronic pancreatitis underwent anthropometry, nutritional and dietary assessments. For dietary assessment, food frequency questionnaire and 24-hour dietary recall methods were used. Primary outcome measure was cause and effect relationship of malnutrition with idiopathic chronic pancreatitis. RESULTS: Of 201 patients with chronic pancreatitis, 120 had idiopathic chronic pancreatitis (mean age 29.60 years, 74 males) who formed the study group. None of the patients consumed cassava. The nutritional status and dietary intake of the patients before the onset of chronic pancreatitis were comparable with those of controls with 20.6% of patients and 22.5% of controls being malnourished (body mass index [BMI] < 18.5). After the onset of chronic pancreatitis, 56.5% of patients lost weight and significantly more patients became malnourished compared with controls (45.8% vs 22.5%; P < 0.001). The causes of weight loss were diabetes, higher calories from proteins, and pseudocyst. CONCLUSION: Malnutrition was not a cause of idiopathic chronic pancreatitis and weight loss occurred as an effect of chronic pancreatitis. Cassava was not found to be a cause of idiopathic chronic pancreatitis.

Progression of Chronic Pancreatitis to Pancreatic Cancer: Is There a Role of Gene Mutations as a Screening Tool?

OBJECTIVES: Early detection of pancreatic ductal adenocarcinoma still remains a challenge. Patients with chronic pancreatitis (CP) have a markedly increased risk of pancreatic cancer. Mutations in oncogenes and/or tumor suppressor genes play a role in development of pancreatic ductal adenocarcinoma. This study assessed mutations in KRAS and p53 gene in blood as a screening tool for malignant transformation in CP patients. METHODS: This was a cohort, single-center study including 294 CP patients. DNA was isolated from plasma of CP patients, and KRAS mutations were identified using polymerase chain reaction-restriction fragment length polymorphism. Patients with positive KRAS mutation were screened for malignancy using positron emission tomography or endoscopic ultrasound. Mutations in p53 gene were analyzed by sequencing. Tissue samples from CP and pancreatic cancer patients were also tested for mutations in KRAS and p53 genes. RESULTS: The plasma samples of 64 CP patients were positive for KRAS mutation, and 4 had mutation in p53 gene also. No patient positive for KRAS mutation and/or p53 mutation was found to have malignant transformation. CONCLUSION: Detection of KRAS or p53 mutation in plasma is not an effective screening tool for pancreatic cancer because accumulation of multiple mutations is required for malignant transformation in the pancreas.

Faecal Calprotectin and UCEIS Predict Short-term Outcomes in Acute Severe Colitis: Prospective Cohort Study.

BACKGROUND AND AIMS: Early objective markers for failure of intravenous[iv] corticosteroid for acute severe colitis [ASC] can avoid delay in rescue therapy or colectomy. We investigated faecal calprotectin [FC], C-reactive protein [CRP], and endoscopy using the ulcerative colitis endoscopic index of severity [UCEIS] as predictors of steroid failure following intensive therapy of ASC. METHODS: Consecutive patients with ASC satisfying Truelove and Witts' criteria, hospitalised at a single centre from May 2015 to November 2016, were included; all received iv corticosteroids. The primary outcome measure was steroid failure defined as colectomy and/or rescue therapy with ciclosporin or infliximab during admission. FC levels were measured at admission and on Day 3 of intensive therapy. UCEIS was scored at admission, and CRP on Day 3 of intensive therapy. RESULTS: Of 49 patients, 21 [43%] failed iv corticosteroids and 15 [31%] underwent surgery. FC levels were significantly higher in steroid failures (2522 [590-9654] µg/g) compared with steroid responders (1530 [352-10278] µg/g) at admission [p = 0.04], as well as on Day 3 of iv corticosteroid therapy (2718 [222-9175] µg/g vs 727 [218-4062] µg/g, p = 0.001). Steroid failures had a higher median [range] UCEIS score than responders (6 [4-8] vs 5 [4-7] [p = 0.001]). CRP level did not differ significantly between steroid failures and responders. A UCEIS > 6 at admission and FC > 1000 µg/g on Day 3 were independent predictors of steroid failure and need for rescue therapy/colectomy. CONCLUSIONS: All patients with UCEIS > 6 and Day 3 FC > 1000 µg/g failed iv corticosteroids. The UCEIS score on admission and Day 3 FC are early predictors of failure of ivcorticosteroid therapy.

Serum human trefoil factor 3 is a biomarker for mucosal healing in ulcerative colitis patients with minimal disease activity.

BACKGROUND: The goals of treating ulcerative colitis (UC) have shifted from clinical remission to mucosal healing. Non-invasive biomarkers are required to assess mucosal healing as endoscopic assessment is inconvenient for patients. Enhanced expression of trefoil factor 3 (TFF3, a mucin-associated peptide) is observed after injury of the gastrointestinal tract. The present study was designed to evaluate TFF3 as a biomarker of mucosal healing in patients with UC. METHODS: This cross-sectional study included consecutive patients with UC (18-65 years old, disease duration >3 months, either left-sided colitis or pancolitis) who had a Simple Clinical Colitis Activity Index (SCCAI) <6. Colonoscopy was done to assess the presence or absence of mucosal healing (defined using the Baron score) in all patients. Serum level of TFF3 was assessed in all patients and 20 healthy controls. RESULTS: Seventy-four patients were included [mean age 37.2±10.9 years, 47 males, median disease duration 4.8 years (IQR 3-8.3), median SCCAI = 0] in the study. Forty-three patients had mucosal healing (Baron score 0 or 1) and 31 did not (Baron score 2 or 3). Median TFF3 level in patients without mucosal healing was significantly higher than that in patients with mucosal healing [1.5 (IQR 1.2-1.9) vs 1.1 (IQR 0.8-1.3) ng/ml, p = 0.01] and healthy controls [0.85 (IQR 0.7-1.2) ng/ml, p < 0.001]. A serum TFF3 level of <1.27 ng/ml (as determined by the receiver operating characteristic curve; area under the curve 0.73) had sensitivity, specificity, positive predictive value and negative predictive value of 70, 68, 75 and 62%, respectively, for identifying patients with mucosal healing. CONCLUSION: Serum TFF3 can potentially be used as a biomarker to assess mucosal healing in UC patients.

Effect of oral glutamine supplementation on gut permeability and endotoxemia in patients with severe acute pancreatitis: a randomized controlled trial.

OBJECTIVE: The aim of this study is to evaluate the effect of oral glutamine (GL) supplementation on gut permeability and endotoxemia (surrogate end point) in patients with severe acute pancreatitis. METHODS: In a randomized controlled trial, patients were randomized to be given placebo or GL for 7 days. The primary outcome measures include the effect on gut permeability (assessed by lactulose/mannitol excretion in urine and endotoxemia assessed by endotoxin core antibodies type IgG and IgM (EndoCab IgG and IgM). The secondary outcome measures include infectious complications, mortality, total hospital/intensive care unit stay, C-reactive protein, and prealbumin levels. RESULTS: Patients were assigned to GL (n = 41) and placebo (n = 39) groups. There was no change in gut permeability after the intervention. However, the EndoCab IgM levels increased significantly (33 [4, 175] to 40 [8, 350] GMU/mL; P = 0.0164) and the C-reactive protein levels decreased significantly (133 [1, 287] to 88 [1, 267] ng/mL; P = 0.0236) in the GL group. No difference was observed in infectious complication, prealbumin value, hospital/intensive care unit stay, and mortality in both groups. CONCLUSIONS: No significant trend was identified for an effect of GL on gut permeability. Decreased inflammation and endotoxemia did not translate into reduced infectious complications in severe acute pancreatitis. However, the study was underpowered to detect the aforementioned difference (trial registration: CTRI/2009/000945).

Plasma cathepsin L: a prognostic marker for pancreatic cancer.

AIM: To assess the prognostic significance of cathepsin L, a cysteine protease that degrades the peri-tumoral tissue, in patients with pancreatic cancer. METHODS: Plasma samples from 127 pancreatic cancer patients were analyzed for cathepsin L levels by ELISA. Out of these patients, 25 underwent surgery and their paraffin-embedded tissue was analyzed for cathepsin L expression by immunohistochemistry. Survival of patients and clinicopathological parameters was correlated with cathepsin L expression in plasma and tissue using appropriate statistical analysis. RESULTS: The mean (± SD) cathepsin L in plasma samples of pancreatic cancer patients was 5.98 ± 2.5 ng/mL that was significantly higher compared to the levels in healthy controls (3.83 ± 0.45) or chronic pancreatitis patients (3.97 ± 1.06). Using ROC curve, a cut-off level of 5.0 ng/mL was decided for survival analysis. Elevated plasma levels of cathepsin L were found to be associated with poor prognosis (P = 0.01) in multivariate analysis. The plasma levels of the protease decreased after surgery. Though no significant correlation was seen between plasma and tissue expression of this protease, a trend did emerge that high cathepsin L expression in tissue correlated with its high levels in plasma. CONCLUSION: Cathepsin L levels in plasma of pancreatic cancer patients may be used as a potential prognostic marker for the disease.

Effect of antioxidant supplementation on surrogate markers of fibrosis in chronic pancreatitis: a randomized, placebo-controlled trial.

OBJECTIVES: This study aimed to determine the effect of antioxidant (AO) supplementation on surrogate markers of fibrosis in patients with chronic pancreatitis (CP). METHODS: In a randomized, placebo (PL)-controlled trial, patients with CP were randomized to groups that were given PL or AO for 3 months. Outcome measures were change in serum levels of transforming growth factor ß1 and platelet-derived growth factor AA (PDGF-AA) (primary outcome) as well as blood markers of oxidative stress (thiobarbituric acid-reactive substances) and AO status (ferric-reducing ability of plasma) (secondary outcome). Pain relief and analgesic requirement was also recorded. RESULTS: Patients (n = 61; mean [SD] age, 35.2 [10.0]; male patients, 43) were assigned to AO (n = 31) and PL (n = 30) groups. The median (range) percent reduction from baseline to 3 months in levels of PDGF-AA (17.1% [-25.3% to 88.7%] vs 2.8% [-243.1% to 30.2%]; P = 0.001), transforming growth factor ß1 (P = 0.573), and thiobarbituric acid-reactive substances (P = 0.207) as well as percent increment from baseline to 3 months in ferric-reducing ability of plasma (P = 0.003) were higher in the AO group compared with the PL group. Proportion of patients who had both reduced PDGF-AA and reduced pain was greater in AO as compared with PL group (17/31 vs 9/30, P = 0.05) CONCLUSIONS: Reduction in markers of fibrosis (PDGF-AA) translated into clinical outcome (reduction in pain and analgesic requirements) in those supplemented with AOs in CP (trial registration, CTRI/2011/05/001747).

Evaluation of early enteral feeding through nasogastric and nasojejunal tube in severe acute pancreatitis: a noninferiority randomized controlled trial.

OBJECTIVE: This study aimed to determine the noninferiority of early enteral feeding through nasogastric (NG) compared to nasojejunal (NJ) route on infectious complications in patients with severe acute pancreatitis (SAP). METHODS: Patients with SAP were fed via NG (candidate) or NJ (comparative) route. The primary outcome was the occurrence of any infectious complication in blood, pancreatic tissue, bile, or tracheal aspirate. Secondary end points were pain in refeeding, duration of hospital stay, intestinal permeability assessed by lactulose/mannitol excretion, and endotoxemia assessed by endotoxin core antibody types immunoglobulin G and M. RESULTS: Seventy-eight patients were randomized to feeding by either the NG or the NJ route. During the hospital stay, the presence of any infectious complication in the NG and NJ groups was 23.1% and 35.9% (significantly different), respectively. The effect size of the difference of infectious complications was -12.8 (95% confidence interval, -29.6 to 4.0). The upper limit of the 95% confidence interval was 4.0 and was within the 5% limit set for noninferiority. The value of 8.0 for the number needed to treat implies that 8 patients should be treated with NG compared with the NJ group to prevent 1 patient from any of the infectious complications. CONCLUSIONS: Early enteral feeding through NG was not inferior to NJ in patients with SAP. Infectious complications were within the noninferiority limit. Pain in refeeding, intestinal permeability, and endotoxemia were comparable in both groups.

Anti-Saccharomyces cerevisiae antibody does not differentiate between Crohn's disease and intestinal tuberculosis.

The clinical, morphological, and histological features of intestinal tuberculosis (IT) and Crohn's disease (CD) mimic so much, that it becomes difficult to differentiate between them. The sensitivity of anti-Saccharomyces cerevisiae antibody (ASCA) IgG and ASCA IgA in CD is 60%-80%, whereas the specificity is almost 90%. There are no reports of study of ASCA in patients with IT, nor has it ever been used to differentiate CD from IT. Patients with ulcerative colitis (UC; n=25), CD (n=59), and IT (n=30) and 21 healthy controls were included in this study. The location and behavior of CD were classified according to the Modified Montreal classification. Five milliliters of blood was taken from them and serum was stored at -70 degrees C. ASCA antibodies (both IgG and IgA) were estimated using commercially available ELISA kits (AESKU Diagnostics, Germany). Anti-neutrophilic cytoplasmic antibody was measured by indirect immunofluorescence test. ASCA IgA was positive in 4.7%, 28%, 33.9%, and 43.3% and ASCA IgG was positive in 4.7%, 24%, 50.8%, and 46.6% of healthy controls and patients with UC, CD, and IT, respectively. Either ASCA IgG or ASCA IgA was positive in 9.5%, 40%, 61% and 66.6% of healthy controls, UC, CD, and IT, respectively. ANCA was positive in 0%, 32%, 10.1%, and 6.6% of healthy controls, UC, CD, and IT, respectively. ASCA IgG was positive in a significantly higher number of patients with CD (P<0.0001) and IT (P<0.0001) in comparison to healthy controls. ASCA IgA was positive in a significantly higher number of patients with UC (P<0.04), CD (P<0.013), and IT (P<0.006) in comparison to healthy controls. In comparisons between diseases, ASCA IgG was positive in significantly more patients with CD (P<0.001) and IT (P<0.001) in comparison to UC. There was no significant difference in ASCA IgA (33.9% vs. 43.3%), ASCA IgG (50.86% vs. 46.6%), or ANCA (10.7%, 7.4%) in patients with CD and IT, respectively. There was no correlation between ASCA and duration, location and behavior of CD, and IT. We conclude that ASCA IgG and ASCA IgA do not help to differentiate between IT and CD.

Leptin and its correlation with exocrine and endocrine pancreatic function in idiopathic chronic pancreatitis: implications for pathophysiology.

OBJECTIVES: Leptin alters pancreatic exocrine and beta-cell secretion in animal studies. We hypothesized that leptin might be important in the pathogenesis of idiopathic chronic pancreatitis (ICP) and/or the development of diabetes in ICP. METHODS: Fifty patients with ICP (25 with diabetes, 25 without diabetes) and 25 healthy controls were included in a prospective, case-control study. Fasting plasma leptin concentration was measured by enzyme-linked immunosorbent assay. Exocrine and endocrine pancreatic functions were assessed by fecal chymotrypsin and serum C-peptide, respectively. Anthropometric parameters and body fat mass (FM) were measured. RESULTS: Patients with ICP (mean age, 30 years; 33 men) had significantly lower body mass index (19.5 +/- 2.6 kg/m2) and FM (10.6 +/- 4.2 kg) as compared with controls (body mass index, 21.7 +/- 4.1 kg/m2; FM, 19.0 +/- 16.6 kg; P < 0.01). Fecal chymotrypsin (median, 5.2 [range, 0.3-42.6] U/kg) and C-peptide (median, 1.7 [range, 0.2-9.5] ng/mL) were significantly lower in patients than in controls (12.9 [range, 2.5-33.0] U/kg and 3.5 [range, 0.3-10.3] ng/mL; P < 0.01). Plasma leptin concentration was slightly lower but statistically insignificant in patients with ICP (median, 4.0 [range, 2.0-62.5] ng/mL) as compared with controls (median, 5.0 [range, 2.0-63.0] ng/mL). Patients with and those without diabetes were also comparable with regard to their leptin concentration, pancreatic functions, and anthropometric parameters. CONCLUSIONS: Leptin does not seem to have a pathophysiological role in either ICP or the development of diabetes in ICP.