Zoltán Berger

[Bedside index for severity in acute pancreatitis (BISAP) score as predictor of clinical outcome in acute pancreatitis: retrospective review of 128 patients].

BACKGROUND Identification of patients at risk for severe disease early in the course of acute pancreatitis (AP) is essential to optimize management and to improve outcomes. AIM To assess BISAP score as a predictor of severity of AP. PATIENTS AND METHODS Retrospective review of AP patients between January 2009 and December 2010. BISAP, APACHE II and Balthazar scores were calculated. Length of stay, local complications, organ failure and mortality were registered. Accuracy of the scoring system for predicting severity was measured by the area under the receiver operating curve (AUC). RESULTS The medical records of 128 patients, median age 46.5 years (55.5% men), were reviewed. Mean hospital stay was 15 days, 18 patients (14%) had local complications, 7 patients (5.4%) developed organ failure and 2 patients died (1.6%). The AUC for BISAP score to detect organ failure was 0.977 (95% IC 0.947-1.000). A BISAP score > 3 had a sensitivity, specificity, positive and negative predictive value of 71.4, 99.1, 83.3 and 98.3% respectively. An APACHE II score > 8 had a sensitivity and specificity of 71.5 and 86.8% respectively. The figures for a Balthazar score > 6 were 42.8 and 98.3% respectively. There was a significant correlation between BISAP score and length of hospital stay. CONCLUSIONS BISAP score was a useful method for predicting the severity of PA, with the advantage of being simple and based on parameters obtained on the first day of hospitalization. Its sensitivity and specificity were superior to APACHE II and Balthazar score in this cohort.

Cystic Lesions in Autoimmune Pancreatitis.

Autoimmune pancreatitis (AIP) can be chronic or recurrent, but frequently completely reversible after steroid treatment. A cystic lesion in AIP is a rare finding, and it can mimic a pancreatic cystic neoplasm. Difficulties in an exact diagnosis interfere with treatment, and surgery cannot be avoided in some cases. We report the history of a 63-year-old male presenting with jaundice and pruritus. AIP was confirmed by imaging and elevated IgG4 blood levels, and the patient completely recovered after corticosteroid therapy. One year later, he presented with a recurrent episode of AIP with elevated IgG4 levels, accompanied by the appearance of multiple intrapancreatic cystic lesions. All but 1 of these cysts disappeared after steroid treatment, but the remaining cyst in the pancreatic head was even somewhat larger 1 year later. Pancreatoduodenectomy was finally performed. Histology showed the wall of the cystic lesion to be fibrotic; the surrounding pancreatic tissue presented fibrosis, atrophy and lymphoplasmacytic infiltration by IgG4-positive cells, without malignant elements. Our case illustrates the rare possibility that cystic lesions can be part of AIP. These pseudocysts appear in the pancreatic segments involved in the autoimmune disease and can be a consequence of the local inflammation or related to ductal strictures. Steroid treatment should be initiated, after which these cysts can completely disappear with recovery from AIP. Surgical intervention may be necessary in some exceptional cases.

Mortalidad de la pancreatitis aguda: experiencia de 20 años en el Hospital Clínico Universidad de Chile

Background: Mortality for acute pancreatitis (AP) in Chile has fluctuated between 7 ana 10% in last years. Aim: To evaluate AP mortality over a period of 20 years in a clinical hospital in Santiago, Chile. Material and Methods: Review of the database of hospital discharges with the diagnosis of acute pancreatitis, between 1990 and 2010 and the medical records of those patients. Age, gender, length of hospital stay, surgeries, percutaneous interventions and mortality were registered. To compare the evolution of the disease over time, patients were divided in two groups: those hospitalized between 1990 and 1999 and those hospitalized between 2000 and 2010. Results: We reviewed the records of 1367 patients with a median age of 48 years (48% men). In the first period, 93 of637 (14.6%) patients died, whereas in the second period, 22 of 730 patients died (3.0%). In the first and second period, 41.9 and 25.3% of patients were subjected to surgical procedures. The hospital stay was shorter in the second group, compared with the first (14.2 and 25.9 days respectively). Conclusions: There was a decrease in mortality caused by AP in the last 10 years, probably associated with a better interdisciplinary management of these patients.

Un desafío clínico: diagnóstico diferencial de pancreatitis autoinmune y cáncer de páncreas. El valor del tratamiento esteroidal de prueba

Background: The differential diagnosis of pancreatic cancer and focal forms of autoimmune pancreatitis is complicated since serological tests, IgG4 and CA 19-9 have a low sensibility and specificity. CT scan and magnetic resonance imaging provide clear differentiation in the majority, but not in all cases. Endosonography is the most precise diagnostic procedure and allows to obtain samples for cytology or even histological studies. Aim: To report the experience with 18 cases of focal autoimmune pancreatitis and three cases of pancreatic cancer. Material and methods: Review of medical records of 18 patients with focal autoimmune pancreatitis and 3 cases of pancreatic cancer. Results: The eighteen patients with focal autoimmune pancreatitis were treated with prednisone 0.5 mg/kg/day obtaining a complete clinical and morphological recovery in all. However, 3 had a relapse and one was operated. During follow up, none has developed a pancreatic cancer. The 3 patients with pancreatic cancer did not respond to steroidal treatment. Conclusions: The quick and dramatic response to steroids of autoimmune pancreatitis, may be useful and is recommended for the differential diagnosis with pancreatic cancer.BACKGROUND The differential diagnosis of pancreatic cancer and focal forms of autoimmune pancreatitis is complicated since serological tests, IgG4 and CA 19-9 have a low sensibility and specificity. CT scan and magnetic resonance imaging provide clear differentiation in the majority, but not in all cases. Endosonography is the most precise diagnostic procedure and allows to obtain samples for cytology or even histological studies. AIM To report the experience with 18 cases of focal autoimmune pancreatitis and three cases of pancreatic cancer. MATERIAL AND METHODS Review of medical records of 18 patients with focal autoimmune pancreatitis and 3 cases of pancreatic cancer. RESULTS The eighteen patients with focal autoimmune pancreatitis were treated with prednisone 0.5 mg/kg/day obtaining a complete clinical and morphological recovery in all. However, 3 had a relapse and one was operated. During follow up, none has developed a pancreatic cancer. The 3 patients with pancreatic cancer did not respond to steroidal treatment. CONCLUSIONS The quick and dramatic response to steroids of autoimmune pancreatitis, may be useful and is recommended for the differential diagnosis with pancreatic cancer.

Prevalence of clarithromycin resistance in Helicobacter pylori in Santiago, Chile, estimated by real-time PCR directly from gastric mucosa

BackgroundCurrent available treatments for Helicobacter pylori eradication are chosen according to local clarithromycin and metronidazole resistance prevalence. The aim of this study was to estimate, by means of molecular methods, both clarithromycin and metronidazole resistance in gastric mucosa from patients infected with H.pylori.MethodsA total of 191 DNA samples were analyzed. DNA was purified from gastric mucosa obtained from patients who underwent an upper gastrointestinal endoscopy at an university hospital from Santiago, Chile, between 2011 and 2014. H.pylori was detected by real-time PCR. A 5’exonuclease assay was developed to detect A2142G and A2143G mutations among H.pylori-positive samples. rdxA gene was sequenced in samples harboring A2142G and A2143G mutations in order to detect mutations that potentially confer dual clarithromycin and metronidazole resistance.ResultsNinety-three (93) out of 191 DNA samples obtained from gastric mucosa were H.pylori-positive (48.7%). Clarithromycin-resistance was detected in 29 samples (31.2% [95%CI 22.0–41.6%]). The sequencing of rdxA gene revealed that two samples harbored truncating mutations in rdxA, one sample had an in-frame deletion, and 11 had amino acid changes that likely cause metronidazole resistance.ConclusionsWe estimated a prevalence of clarithomycin-resistance of 31.8% in Santiago, Chile. Three of them harbor inactivating mutations in rdxA and 11 had missense mutations likely conferring metronidazole resistance. Our results require further confirmation. Nevertheless, they are significant as an initial approximation in re-evaluating the guidelines for H.pylori eradication currently used in Chile.

IL-8-251T>A (rs4073) Polymorphism Is Associated with Prognosis in Gastric Cancer Patients

Background/Aim: Inflammation is a key process in gastric carcinogenesis. Cytokines are mediators of inflammation and are involved in metastasis and tumorigenicity. We previously assessed the role of cytokine gene polymorphisms in gastric cancer risk in Chile. In the present study, we aimed to analyze whether these polymorphisms are associated with overall survival (OS) in gastric cancer (GC) patients. Patients and Methods: A total of 153 individuals with GC diagnosis were followed-up for at least 2 years. Hazard ratios (HR) were estimated from Cox regression models using SNPs as predictor variables. The following SNPs were genotyped for study using a TaqMan assay: rs16944 (IL1B -511C>T); rs4073 (IL8 -251 T>A); rs2275913 (IL-17 -197G>A); rs1800872 (IL10 -592 C>A); rs1800896 (IL10 -1082A>G); rs28372698 (IL32). Results: Interleukin-8 rs4073 (IL-8 -251T>A) showed association with OS under the dominant model (TA + AA) only when adjusted by clinicopathological variables (HR=1.64, 95%CI=1.05-2.55, p=0.030, q-value=0.18), but not with the univariate model (HR=1.51, 95%CI=0.98-2.31, p=0.062, q-value=0.37). No significant differences were observed after adjusting for population stratification (PC1 and PC2 from Principal Component Analysis using genotypes from Infinium Global Screening Array). After stratification by clinicopathological variables, the association with shorter overall survival was higher among patients with diffuse-type tumors (HR=2.24, 95%CI=1.16-4.45) and patients with tumor size >5 cm (HR=1.79, 95%CI=1.08-2.97). Conclusion: These results suggest a role of IL-8 rs4073 in cancer prognosis. Its use as a prognostic marker of GC survival warrants further investigation.

Polymorphisms inTWIST1andZEB1Are Associated with Prognosis of Gastric Cancer Patients

Background/Aim: Epithelial–mesenchymal transition (EMT) program has been linked as a driver of metastatic dissemination by conferring migratory and invasive capacity to cancer cells. Gastric cancer (GC) patients with tumors expressing altered levels of EMT markers have low survival. This study aimed to assess if polymorphisms of CDH1, TWIST1, SNAIL2, ZEB1 and ZEB2 genes are associated with survival in GC patients. Patients and Methods: A total of 153 individuals with diagnosis of GC were recruited in Santiago, Chile. All patients were genotyped using Infinium Global Screening Array (GSA). Twenty Tag SNPs of the studied genes were retrieved. Results: Three SNPs were associated with survival: rs2526614 (TWIST1) (genotype CA + AA, adjusted HR=0.58, 95%CI=0.37-0.93), rs6953766 (TWIST1) (genotype GG, crude HR=2.02, 95%CI=1.06-3.82, adjusted HR=2.14, 95%CI=1.07-4.25), and rs431073 (ZEB1) (genotype AC + CC, crude HR=1.62, 95%CI=1.01-2.59, adjusted HR=1.96, 95%CI=1.18-3.25). Conclusion: To the best of our knowledge, this is the first study proposing a role of these SNPs in cancer prognosis. Their use as prognostic markers of GC survival warrants further investigation.

Prevalence of dual clarithromycin and metronidazole resistance in Helicobacter pylori estimated by molecular methods in Santiago, Chile

Background Current available treatments for Helicobacter pylori eradication are chosen according to local clarithromycin and metronidazole resistance prevalence. The aim of this study was to estimate, by means of molecular methods, both clarithromycin and metronidazole resistance in gastric mucosa from patients infected with H.pylori. Methods A total of 191 DNA samples were analyzed. DNA was purified from gastric mucosa obtained from patients who underwent an upper gastrointestinal endoscopy at an university hospital from Santiago, Chile, between 2011 and 2014. H.pylori was detected by real-time PCR. A 5’exonuclease assay was developed to detect A2142G and A2143G mutations among Hpylori-positive samples. rdxA gene was sequenced in samples harboring A2142G and A2143G mutations in order to detect mutations that potentially confer dual clarithromycin and metronidazole resistance. Results Ninety-three (93) out of 191 DNA samples obtained from gastric mucosa were H. pylori-positive (48.7%). Clarithromycin-resistance was detected in 29 samples (31.2% [95%CI 22.0%-41.6%]). The sequencing of rdxA gene revealed that two samples harbored truncating mutations in rdxA, one sample had an in-frame deletion, and 11 had amino acid changes that likely cause metronidazole resistance. Conclusions We estimated a prevalence of clarithomycin-resistance of 31.8% in Santiago, Chile. The proportion of dual clarithromycin and metronidazole resistance could be, at least, 15.0%. Our results require further confirmation. Nevertheless, they are significant as an initial approximation in re-evaluating the guidelines for H.pylori eradication currently used in Chile.

Racial Differences in Chronic Pancreatitis. An Explanation for South America

With the aim to search some diff erences, we compared our clinical experience in a Chilean cohort of patients with CP ( 5 ) with the data published by the US group ( Table 1 ). We found a major male predominance, smaller proportion of clearly alcoholic etiology than in American Blacks, but not in Whites and more cases considered as idiopathic. However, the most striking diff erences were noted in two aspects: 1 . Morphological and functional damage were more advanced in our patients. Calcifi cation, ductal strictures and dilations (99 of 121), and exocrine (66%) and endocrine (55%) insuffi ciency were present, in the majority already at the fi rst visit. Th is observation could support the thesis concerning the defi ciencies in diagnosis. In spite of this, local CP is considered a rare, almost exceptional disease in South America, with the exception of Brazil. Experts from Europe and United States consider that this observation could be a mistake and derives from defi ciencies in diagnosis. In an earlier report, we studied exocrine pancreatic function in diabetic patients and found two patients with advanced morphological changes consistent with CP, controlled by diabetologists, with no awareness of pancreatic disease ( 2 ). Genetically, Chilean population is a mixture of European and Mapuche genes. While Mapuche population exhibits one of the highest prevalence of cholelithiasis in the world, diabetes and hypertension are very rare in this group ( 3,4 ). We hypothesize that genetic and racial factors can explain low prevalence of CP in South America. article to be published. Sanders DS approved the fi nal version of the article to be published. Financial support: None. Potential competing interests: None.

Association of Chronic Pancreatitis and Malignant Main Duct IPMN: A Rare but Difficult Clinical Problem

We report the case of a 70-year-old woman who consulted for recurrent short episodes of mild-to-moderate abdominal pain. Dilated main pancreatic duct was seen on CAT scan and magnetic resonance, with multiple calcifications and intraductal stones, typical in CP. However, for a more pronounced cystic dilatation in the pancreatic head, we could not exclude the coexistence of a main duct IPMN. ERCP was performed, with pancreatic sphincterotomy and extraction of pancreatic stones, but, at the same time, mucin extrusion was seen from the dilated duct through the papilla. Pancreatoduodenectomy was performed. Surgery and histology confirmed malignant IPMN with the typical image of chronic pancreatitis and intraductal stones in the vicinity. The patient is doing well 4 years after the surgery, without recurrence of the malignant disease, with changes of chronic pancreatitis in the pancreatic remnant. This paper discusses the possible relationships between the two entities and emphasizes the need of differential diagnosis.