Faraz Bishehsari

Comparison of Existing Clinical Scoring Systems to Predict Persistent Organ Failure in Patients With Acute Pancreatitis

BACKGROUND & AIMS It is important to identify patients with acute pancreatitis who are at risk for developing persistent organ failure early in the course of disease. Several scoring systems have been developed to predict which patients are most likely to develop persistent organ failure. We head-to-head compared the accuracy of these systems in predicting persistent organ failure, developed rules that combined these scores to optimize predictive accuracy, and validated our findings in an independent cohort. METHODS Clinical data from 2 prospective cohorts were used for training (n = 256) and validation (n = 397). Persistent organ failure was defined as cardiovascular, pulmonary, and/or renal failure that lasted for 48 hours or more. Nine clinical scores were calculated when patients were admitted and 48 hours later. We developed 12 predictive rules that combined these scores, in order of increasing complexity. RESULTS Existing scoring systems showed modest accuracy (areas under the curve at admission of 0.62-0.84 in the training cohort and 0.57-0.74 in the validation cohort). The Glasgow score was the best classifier at admission in both cohorts. Serum levels of creatinine and blood urea nitrogen provided similar levels of discrimination in each set of patients. Our 12 predictive rules increased accuracy to 0.92 in the training cohort and 0.84 in the validation cohort. CONCLUSIONS The existing scoring systems seem to have reached their maximal efficacy in predicting persistent organ failure in acute pancreatitis. Sophisticated combinations of predictive rules are more accurate but cumbersome to use, and therefore of limited clinical use. Our ability to predict the severity of acute pancreatitis cannot be expected to improve unless we develop new approaches.

Epidemiological transition of colorectal cancer in developing countries: environmental factors, molecular pathways, and opportunities for prevention.

Colorectal cancer (CRC) is one of the leading causes of cancer and cancer-related mortality worldwide. The disease has been traditionally a major health problem in industrial countries, however the CRC rates are increasing in the developing countries that are undergoing economic growth. Several environmental risk factors, mainly changes in diet and life style, have been suggested to underlie the rise of CRC in these populations. Diet and lifestyle impinge on nuclear receptors, on the intestinal microbiota and on crucial molecular pathways that are implicated in intestinal carcinogenesis. In this respect, the epidemiological transition in several regions of the world offers a unique opportunity to better understand CRC carcinogenesis by studying the disease phenotypes and their environmental and molecular associations in different populations. The data from these studies may have important implications for the global prevention and treatment of CRC.

Pneumatic balloon dilatation in achalasia: a prospective comparison of safety and efficacy with different balloon diameters

Background : Pneumatic dilatation is considered to be the first line therapy for achalasia, but long‐term outcome studies are scarce and limited by their retrospective design. There is also no consensus on the optimal method for performing pneumatic dilation as regard to balloon diameter, amount and the rate inflation pressure.

Applying a Natural Language Processing Tool to Electronic Health Records to Assess Performance on Colonoscopy Quality Measures

BACKGROUND Gastroenterology specialty societies have advocated that providers routinely assess their performance on colonoscopy quality measures. Such routine measurement has been hampered by the costs and time required to manually review colonoscopy and pathology reports. Natural language processing (NLP) is a field of computer science in which programs are trained to extract relevant information from text reports in an automated fashion. OBJECTIVE To demonstrate the efficiency and potential of NLP-based colonoscopy quality measurement. DESIGN In a cross-sectional study design, we used a previously validated NLP program to analyze colonoscopy reports and associated pathology notes. The resulting data were used to generate provider performance on colonoscopy quality measures. SETTING Nine hospitals in the University of Pittsburgh Medical Center health care system. PATIENTS Study sample consisted of the 24,157 colonoscopy reports and associated pathology reports from 2008 to 2009. MAIN OUTCOME MEASUREMENTS Provider performance on 7 quality measures. RESULTS Performance on the colonoscopy quality measures was generally poor, and there was a wide range of performance. For example, across hospitals, the adequacy of preparation was noted overall in only 45.7% of procedures (range 14.6%-86.1% across 9 hospitals), cecal landmarks were documented in 62.7% of procedures (range 11.6%-90.0%), and the adenoma detection rate was 25.2% (range 14.9%-33.9%). LIMITATIONS Our quality assessment was limited to a single health care system in western Pennsylvania. CONCLUSIONS Our study illustrates how NLP can mine free-text data in electronic records to measure and report on the quality of care. Even within a single academic hospital system, there is considerable variation in the performance on colonoscopy quality measures, demonstrating the need for better methods to regularly and efficiently assess quality.

Family history of colorectal cancer in Iran

BackgroundPrevious reports show a high proportion of young CRC patients in Iran. In this study we aim to look for the clustering of colorectal cancer in families of a series of CRC patients from Iran.MethodsThe family history of cancer is traced in 449 CRC patients of which 112 were 45 yrs or younger and 337 were older than 45 yrs at time of diagnosis. The patients were admitted in two hospitals in Tehran, during a 4-year period.ResultsClinical diagnosis of HNPCC was established in 21 (4.7%) probands. Family history of CRC was more frequently reported by early-onset than by late-onset patients (29.5% vs. 12.8%, p < 0.001).Distribution of tumor site differed significantly between those with and without family history of CRC. Right colon cancer was the most frequent site (23/45, 35.4%) observed in patients with positive family history of colorectal cancer.ConclusionThe relatively high frequency of CRC clustering along with HNPCC in our patients should be further confirmed with larger sample size population-based and genetic studies to establish a cost effective molecular screening for the future.

The Insulin Receptor Substrate 1 (Irs1) in Intestinal Epithelial Differentiation and in Colorectal Cancer

Colorectal cancer (CRC) is associated with lifestyle factors that affect insulin/IGF signaling, of which the insulin receptor substrate 1 (IRS1) is a key transducer. We investigated expression, localization and pathologic correlations of IRS1 in cancer-uninvolved colonic epithelium, primary CRCs with paired liver metastases and in vitro polarizing Caco2 and HT29 cells. IRS1 mRNA and protein resulted higher, relative to paired mucosa, in adenomas of familial adenomatous polyposis patients and in CRCs that overexpressed c-MYC, ß-catenin, InsRß, and IGF1R. Analysis of IRS1 immunostaining in 24 cases of primary CRC with paired colonic epithelium and hepatic metastasis showed that staining intensity was significantly higher in metastases relative to both primary CRC (P<0.01) and colonic epithelium (P<0.01). Primary and metastatic CRCs, compared to colonic epithelium, contained significantly higher numbers of IRS1-positive cells (P = 0.013 and P = 0.014, respectively). Pathologic correlations in 163 primary CRCs revealed that diffuse IRS1 staining was associated with tumors combining differentiated phenotype and aggressive markers (high Ki67, p53, and ß-catenin). In Caco 2 IRS1 and InsR were maximally expressed after polarization, while IGF1R was highest in pre-polarized cells. No nuclear IRS1 was detected, while, with polarization, phosphorylated IRS1 (pIRS1) shifted from the lateral to the apical plasma membrane and was expressed in surface cells only. In HT29, that carry mutations constitutively activating survival signaling, IRS1 and IGF1R decreased with polarization, while pIRS1 localized in nuclear spots throughout the course. Overall, these data provide evidence that IRS1 is modulated according to CRC differentiation, and support a role of IRS1 in CRC progression and liver metastatization.

P53 mutations in colorectal cancer from northern Iran: Relationships with site of tumor origin, microsatellite instability and K-ras mutations†

CRC‐associated P53 mutations have not been studied extensively in non‐Western countries at relatively low CRC risk. We examined, for the first time, 196 paraffin‐embedded CRC cases from Northern Iran for mutations in P53 exons 5–8 using PCR‐direct sequencing. P53 status and mutation site/type were correlated with nuclear protein accumulation, clinicopathologic variables and data on K‐ras mutations and high‐level microsatellite instability (MSI‐H). We detected 96 P53 mutations in 87 (44.4%) cases and protein accumulation in 84 cases (42.8%). P53 mutations correlated directly with stage and inversely with MSI‐H. Distal CRCs were more frequently mutated at major CpG hotspot codons [248 (8/66, 12.1%), 175 (7/66, 10.6%), and 245 (7/66, 10.6%)], while in proximal tumors codon 213, emerged as most frequently mutated (5/28, 17.9% vs. 3/66, 4.5%, P = 0.048). Transitions at CpGs, the most common mutation type, were more frequent in non‐mucinous (25% vs. 10.4% in mucinous, P = 0.032), and distal CRC (27% vs. 12.5% in proximal, P = 0.02), and correlated with K‐ras transversions. Transitions at non‐CpGs, second most common P53 mutation, were more frequent in proximal tumors (15.6% vs. 4.7% in distal, P = 0.01), and correlated with K‐ras transitions and MSI‐H. Overall frequency and types of mutations and correlations with P53 accumulation, stage and MSI‐H were as reported for non‐Iranian patients. However P53 mutation site/type and correlations between P53 and K‐ras mutation types differed between proximal and distal CRC. The codon 213 P53 mutation that recurred in proximal CRC was previously reported as frequent in esophageal cancer from Northern Iran. J. Cell. Physiol. 216: 543–550, 2008.

Injection of botulinum toxin before pneumatic dilatation in achalasia treatment: a randomized-controlled trial.

Pneumatic dilatation is the first line therapy in achalasia, but half of patients relapse within 5 years of therapy and require further dilatations.

TNF-alpha gene (TNFA) variants increase risk for multi-organ dysfunction syndrome (MODS) in acute pancreatitis

BACKGROUND/OBJECTIVES Acute pancreatitis (AP) is a complex inflammatory syndrome with unpredictable progression to systemic inflammation and multi-organ dysfunction syndrome (MODS). Tumor necrosis factor alpha (TNF-α) is a cytokine that may link inflammation to the systemic inflammatory response syndrome (SIRS), which usually precedes MODS. Small genetic cohort studies of the TNFA promoter in AP produced ambiguous results. We performed a comprehensive evaluation of TNFA promoter variants to assess both susceptibility to AP and risk of progression to MODS. METHODS We prospectively ascertained 401 controls and 211 patients with AP that were assessed for persistent SIRS (>48 h) and MODS. MODS was defined as failure of ≥2 organ systems (cardiovascular, pulmonary, and/or renal) persisting more than 48 h. Subjects were genotyped by DNA sequencing and analyzed for SNPs at -1031 C/T (rs1799964), -863 A/C (rs1800630), -857 C/T (rs1799724), -308 A/G (rs1800629), and -238 A/G (rs361525). RESULTS Twenty-three of 211 AP patients (11%) developed MODS. TNFA promoter variants were not associated with susceptibility to AP, but progression to MODS was associated with the minor allele at -1031C (56.5% vs. 32.4% P = 0.022, OR: 2.7; 95%CI: 1.12-6.51) and -863A (43.5% vs. 21.8% P = 0.022, OR: 2.76; 95%CI: 1.12-6.74). CONCLUSION TNFA promoter variants do not alter susceptibility to AP, but rather the TNF-α expression-enhancing -1031C and -863A alleles significantly increased the risk of AP progression to MODS. These data, within the context of previous studies, clarify the risk of specific genetic variants in TNFA and therefore the role of TNF-α in the overall AP syndrome.

Gender effect on clinical features of achalasia: a prospective study.

BackgroundAchalasia is a well-characterized esophageal motor disorder but the rarity of the disease limits performing large studies on its demographic and clinical features.MethodsProspectively, 213 achalasia patients (110 men and 103 women) were enrolled in the study. The diagnosis established by clinical, radiographic, and endoscopic as well as manometry criteria. All patients underwent a pre-designed clinical evaluation before and within 6 months after the treatment.ResultsSolid dysphagia was the most common clinical symptom in men and women. Chest pain was the only symptom which was significantly different between two groups and was more complained by women than men (70.9% vs. 54.5% P value= 0.03). Although the occurrence of chest pain significantly reduced after treatment in both groups (P < 0.001), it was still higher among women (32% vs. 20.9% P value= 0.04). In both sexes, chest pain did not relate to the symptom duration, LES pressure and type of treatment patients received. Also no significant relation was found between chest pain and other symptoms expressed by men and women before and after treatment. Chest pain was less frequently reported by patients over 56 yrs of age in comparison to those less than 56 yrs (p < 0.05).ConclusionIt seems that chest pain is the distinct symptom of achalasia which is affected by sex as well as age and does not relate to the duration of illness, LESP and the type of treatment achalasia patients receive.