Jorge D. Machicado

Quality of Life in Chronic Pancreatitis is Determined by Constant Pain, Disability/Unemployment, Current Smoking, and Associated Co-Morbidities

Objectives:Chronic pancreatitis (CP) has a profound independent effect on quality of life (QOL). Our aim was to identify factors that impact the QOL in CP patients.Methods:We used data on 1,024 CP patients enrolled in the three NAPS2 studies. Information on demographics, risk factors, co-morbidities, disease phenotype, and treatments was obtained from responses to structured questionnaires. Physical and mental component summary (PCS and MCS, respectively) scores generated using responses to the Short Form-12 (SF-12) survey were used to assess QOL at enrollment. Multivariable linear regression models determined independent predictors of QOL.Results:Mean PCS and MCS scores were 36.7±11.7 and 42.4±12.2, respectively. Significant (P<0.05) negative impact on PCS scores in multivariable analyses was noted owing to constant mild–moderate pain with episodes of severe pain or constant severe pain (10 points), constant mild–moderate pain (5.2), pain-related disability/unemployment (5.1), current smoking (2.9 points), and medical co-morbidities. Significant (P<0.05) negative impact on MCS scores was related to constant pain irrespective of severity (6.8–6.9 points), current smoking (3.9 points), and pain-related disability/unemployment (2.4 points). In women, disability/unemployment resulted in an additional 3.7 point reduction in MCS score. Final multivariable models explained 27% and 18% of the variance in PCS and MCS scores, respectively. Etiology, disease duration, pancreatic morphology, diabetes, exocrine insufficiency, and prior endotherapy/pancreatic surgery had no significant independent effect on QOL.Conclusions:Constant pain, pain-related disability/unemployment, current smoking, and concurrent co-morbidities significantly affect the QOL in CP. Further research is needed to identify factors impacting QOL not explained by our analyses.

Epidemiology of Recurrent Acute and Chronic Pancreatitis: Similarities and Differences

Emerging data in the past few years suggest that acute, recurrent acute (RAP), and chronic pancreatitis (CP) represent a disease continuum. This review discusses the similarities and differences in the epidemiology of RAP and CP. RAP is a high-risk group, comprised of individuals at varying risk of progression. The premise is that RAP is an intermediary stage in the pathogenesis of CP, and a subset of RAP patients during their natural course transition to CP. Although many clinical factors have been identified, accurately predicting the probability of disease course in individual patients remains difficult. Future studies should focus on providing more precise estimates of the risk of disease transition in a cohort of patients, quantification of clinical events during the natural course of disease, and discovery of biomarkers of the different stages of the disease continuum. Availability of clinically relevant endpoints and linked biomarkers will allow more accurate prediction of the natural course of disease over intermediate- or long-term-based characteristics of an individual patient. These endpoints will also provide objective measures for use in clinical trials of interventions that aim to alter the natural course of disease.

An Unusual Cause of Odynophagia in a Patient With Eosinophilic Esophagitis

Department of Internal Medicine, Department of Pathology and Laboratory Medicine, and Division of Gastroenterology, University of Texas Medical School at Houston, Houston, Texas 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 Question: An 18-year-old white man presented with 3 days of epigastric pain, odynophagia, vomiting, and fevers. He also reported 4 months of dysphagia with solids. His history included heartburn, allergic rhinitis, and wheat allergy. There was no personal or family history of recent infection. On admission, he was febrile (101.8 F) and tachycardic (110 bpm). Physical examination revealed a 2-mm ulcer in the lower lip and epigastric tenderness. Blood counts, biochemistry, and liver function tests were normal. Esophagogastroduodenoscopy (EGD) revealed esophagitis with multiple discrete shallow round, 3to 4-mm ulcers starting in upper esophagus and distributed throughout its circumference (Figure A, B). Histopathology revealed necroinflammatory tissue and squamous epithelium with intercellular edema, basal zone hyperplasia, and 56 eosinophils per high-power field (Figure C). Immunoperoxidase staining was negative for herpes simplex virus (HSV) and cytomegalovirus. Serum HSV antibodies, HIV, and cytomegalovirus polymerase chain reaction were negative. The histologic findings were interpreted as eosinophilic esophagitis (EoE) and treatment with pantoprazole was administered. Odynophagia persisted and repeated EGD at day 5 showed persistent coalescent esophageal ulcers along with white exudates and erythema (Figure D). Several specimens were obtained from the edge of the biopsy. A representative histopathology is shown (Figure E, F). What is the diagnosis? Look on page 000 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. 111 112 113 114 115 116 Conflicts of interest The authors disclose no conflicts.

Association of Fasciola hepatica Infection with Liver Fibrosis, Cirrhosis, and Cancer: A Systematic Review

Background Fascioliasis has been sporadically associated with chronic liver disease on previous studies. In order to describe the current evidence, we carried out a systematic review to assess the association between fascioliasis with liver fibrosis, cirrhosis and cancer. Methodology and Principal Findings A systematic search of electronic databases (PubMed, LILACS, Scopus, Embase, Cochrane, and Scielo) was conducted from June to July 2015 and yielded 1,557 published studies. Among 21 studies that met inclusion and exclusion criteria, 12 studies explored the association of F. hepatica with liver fibrosis, 4 with liver cirrhosis, and 5 with cancer. Globally these studies suggested the ability of F. hepatica to promote liver fibrosis and cirrhosis. The role of F. hepatica in cancer is unknown. Given the heterogeneity of the studies, a meta-analysis could not be performed. Conclusions Future high-quality studies are needed to determine the role of F. hepatica on the development of liver fibrosis, liver cirrhosis, and cancer in humans.

Detection of Advanced Neoplasia with FIT Versus Flexible Sigmoidoscopy Versus Colonoscopy: More Is More

Flexible sigmoidoscopy visualizes the rectum and the sigmoid colon and, at times, the descending colon and even the splenic flexure. Unlike colonoscopy, it does not permit inspection of the entire transverse and the right colon. As a result, the efficacy of flexible sigmoidoscopy in preventing colorectal cancer in the proximal colon is dependent on identifying abnormalities in the distal colon, which will predict neoplasia in the proximal colon. Individuals with a negative flexible sigmoidoscopy do not go on to colonoscopy, so subjects with isolated proximal neoplasia are not detected and flexible sigmoidoscopy cannot prevent colorectal cancer in that circumstance.

Acute pancreatitis patient registry to examine novel therapies in clinical experience (APPRENTICE): an international, multicenter consortium for the study of acute pancreatitis

Background We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials. Methods The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients. Results Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results. Conclusion APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials.

A Rare Cause of Gastrointestinal Bleeding in the Intensive Care Unit

Question: A 48year-old Hispanic man developed melena after 25 days of hospitalization. He was initially brought to the emergency department after a motor vehicle accident that resulted in hemopneumothorax, multiple fractures, and blunt abdominal trauma. No past medical history was reported. After emergent endotracheal intubation and chest tubes placement, he underwent splenectomy, subtotal colectomy, and distal ileum resection. In the intensive care unit (ICU), he developed septic shock requiring broad-spectrum antibiotics, vassopressors, corticosteroids, and hemodialysis. Repeat laparotomy on day 9 revealed colocolostomy disruption, requiring additional bowel resection. Vassopressors and steroids were stopped after 5 days. His course was complicated by pulmonary embolism and persistent hyperglycemia. Multiple intra-abdominal washouts were required and abdominal cavity was closed on day 24. On day 25, melena was noted. He was tachycardic, afebrile, and normotensive. Surgical wound was clean, and abdominal examination revealed diffuse tenderness. Hemoglobin acutely dropped from 9 to 6.7 g/dL. Anticoagulation was stopped and an inferior vena cava filter placed. Upper endoscopy showed diffuse friable mucosa of the entire stomach. Large exudative ulceration was found in the gastric body (Figure A) from where biopsy specimens were taken. Other, scattered, clean-based ulcers were seen in the antrum and fundus (Figure B). The esophagus and duodenum were normal. A representative histopathology is provided (Figure C, D). What is the diagnosis? Look on page 1136 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.

Acute Pancreatitis Has a Long-term Deleterious Effect on Physical Health Related Quality of Life

BACKGROUND & AIMS: It is not clear how acute pancreatitis (AP) affects health related quality of life (HRQOL). We aimed to determine the long‐term independent effect of AP on physical and mental HRQOL. METHODS: We analyzed data from 91 patients (mean 52 years of age, 54% women) admitted with AP to the University of Pittsburgh Medical Center from 2011 to 2015 who responded to telephone surveys at a median of 14 months after hospital discharge (interquartile range, 12–16 months). Individuals who did not answer the telephone survey were sent a questionnaire by regular mail. Patients answered questions from the 12‐Item Short‐Form Survey, and answers were used to calculate mental component summary (MCS) and physical component summary (PCS) scores with norm‐based scoring (normal ≥50). HRQOL for these subjects was compared with that of age‐ and sex‐matched individuals without pancreatitis (1:2) identified from the North American Pancreatitis Study. We controlled for other covariates using multivariable regression analysis. RESULTS: At follow‐up, individuals with AP had a significantly lower PCS score (46.2 ± 11.8) than did control subjects (51.1 ± 9.5; P < .01), but a similar MCS score. A 4‐point reduction of the PCS was attributed to AP after controlling for sociodemographic factors and medical comorbidities. The only pancreatitis‐related factor associated with low PCS score was multisystem organ failure. Presence of abdominal pain, analgesic use, disability, and current smoking at the time of follow‐up were also associated with lower PCS scores. Etiology of AP, disease severity (by Revised Atlanta classification), use of nutritional support, and performance of pancreatic interventions did not affect HRQOL at follow‐up. CONCLUSIONS: In a 14‐month follow‐up of patients hospitalized with AP, we found a meaningful, independent, and deleterious effect of AP in the physical HRQOL of these patients, compared to individuals without AP. Further research is needed to determine the duration of this impairment and to evaluate the effects of modifying risk factors.

Medical Student Knowledge of Neglected Tropical Diseases in Peru: A Cross-Sectional Study.

In developing countries, education to health-care professionals is a cornerstone in the battle against neglected tropical diseases (NTD). Studies evaluating the level of knowledge of medical students in clinical and socio-demographic aspects of NTD are lacking. Therefore, a cross-sectional study was conducted among students from a 7 year-curriculum medical school in Peru to assess their knowledge of NTD by using a pilot survey comprised by two blocks of 10 short questions. Block I consisted of socio-demographic and epidemiological questions whereas block II included clinical vignettes. Each correct answer had the value of 1 point. Out of 597 responders (response rate: 68.4%), 583 were considered to have valid surveys (male:female ratio: 1:1.01; mean age 21 years, SD ± 2.42). Total knowledge showed a raising trend through the 7-year curriculum. Clinical knowledge seemed to improve towards the end of medical school whereas socio-demographic and epidemiological concepts only showed progress the first 4 years of medical school, remaining static for the rest of the curricular years (p = 0.66). Higher mean scores in socio-demographic and epidemiological knowledge compared to clinical knowledge were seen in the first two years (p<0.001) whereas the last three years showed higher scores in clinical knowledge (p<0.001). In conclusion, students from this private medical school gained substantial knowledge in NTD throughout the career which seems to be related to improvement in clinical knowledge rather than to socio-demographic and epidemiological concepts. This study assures the feasibility of measuring the level of knowledge of NTD in medical students and stresses the importance of evaluating education on NTD as it may need more emphasis in epidemiological concepts, especially at developing countries such as Peru where many people are affected by these preventable and treatable diseases.

Gastrointestinal Bleeding Caused by Pancreatic Arteriovenous Malformation

A48-year-old African American man presented to the emergency department with hematemesis. He complained of abdominal pain and weight loss for the past 6 months. His history was significant for type 2 diabetes mellitus. On physical examination, the abdomen was tender to palpation in the left upper quadrant. Laboratory data showed mild anemia (hemoglobin level, 11.7) and transaminitis (alanine aminotransferase level, 125; aspartate aminotransferase level, 220). The rest of the biochemistry, hepatobiliary, and coagulation studies were normal. Esophagogastroduodenoscopy was normal. Computed tomography of the abdomen (Figure A) showed a heterogenous pancreatic head, a dilated portal vein of 1.9 cm (Figure A, asterisk) and early portal venous filling during the arterial phase. Magnetic resonance imaging of the abdomen showed dilated portal and splenic vein filling during the arterial phase and extensive peripancreatic vasculature. A 1.8-cm choledochal cyst was found in the head of the pancreas, communicating with the second portion of the duodenum. Endoscopic ultrasound showed collateral vessels from the head to the tail of the pancreas. Endoscopic retrograde cholangiopancreatography showed a type III choledochal cyst (Figure B, arrow) with a fistulous connection to the duodenum. In light of the continued decrease in hemoglobin level, the patient underwent conventional angiography, which showed a diffuse vascular blush in the body of the pancreas (Figure C, superior mesenteric artery), with early filling of the portal vein during the arterial phase (Figure C, asterisk). A final diagnosis of pancreatic arteriovenous malformation (AVM) was made. Transjugular liver biopsy showed a hepatic venous pressure gradient of 3 mm Hg and normal histopathology. Although a Whipple procedure was considered, it ultimately was not attempted because there was no disease-free pancreas available for anastomosis and extensive pancreatic vascularization was present. The patient was managed symptomatically, and at the 1-year follow-up evaluation, his pain was well controlled without recurrence of gastrointestinal bleeding. Pancreatic AVM is a rare condition in which blood flows directly from the arterial to venous circuit while bypassing capillary vessels. Since the first description by Halpern in 1968, approximately 80 cases have been reported in the literature. Although its etiology is unknown, proposed causes include congenital malformation (90%) and acquired causes such as trauma, tumor, or inflammation. Half of the patients present with gastrointestinal bleeding, 40% complain of abdominal and/or back pain, and 20% are asymptomatic. The mechanisms of GI bleeding in patients with pancreatic AVM include ischemia of the duodenal mucosa leading to duodenal ulcer (50%), esophageal or gastric varices from portal hypertension (42%), hemobilia (12%), or pancreatic duct bleeding (8%). None of these causes was identified in our patient. Erosion of the AVM into the choledochal cyst was the most plausible mechanism of GI bleeding. The diagnostic modality of choice for