Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment.

BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens. METHODS: We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP. RESULTS: We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose. CONCLUSIONS: Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.

Sunitinib induced colitis manifesting as invasive diarrhea in a patient with renal cell carcinoma.

INTRODUCTION: Sunitinib is a tyrosine kinase inhibitor that binds to vascular endothelial factor receptor currently used for the treatment of renal cell carcinoma, as well as for several other conditions such as gastrointestinal stromal tumors and pancreatic neuroendocrine tumors. We present a patient with invasive diarrhea who was treated with sunitinib for metastatic renal cell carcinoma. CASE REPORT: Drug induced colitis was confirmed with colonoscopy from histopathological specimens. Clinical recovery of diarrhea was achieved with oral budesonide. Remarkably, the pathologic findings were observed in both the macroscopically normal mucosa and the mucosa with aphthous ulcers in the colon. MANAGEMENT & OUTCOME: The patient was treated for sunitinib associated diarrhea, after exclusion of the other reasons. Metronidazole and piperacillin/tazobactam treatment were prescribed. DISCUSSION: Diarrhea is a frequent symptom in patients treated with tyrosine kinase inhibitors, however the described pathologic findings have rarely been reported. Our aim is to emphasize the importance of close follow-up in patients treated with tyrosine kinase inhibitors, and to raise awareness on the management of sunitinib induced colitis.

Pembrolizumab-induced immune-mediated fatal colitis with concurrent giardia infection.

Advancements in medicine have enabled the use of monoclonal antibodies in the field of oncology. However, the new adverse effects of immunotherapeutic agents are still being reported. We present the first case of pembrolizumab-induced fatal colitis with concurrent Giardia infection in a patient with metastatic ovarian cancer. A 47-year-old woman with metastatic ovarian cancer who was being treated with pembrolizumab admitted to our clinic complaining of persisting bloody diarrhoea. Her stool antigen test was positive for Giardia. The patient received metronidazole. A colonoscopy with mucosal biopsy was performed upon no clinical or laboratory improvement. Colonoscopy detected deep exudative ulcers in sigmoid colon and rectum. The cytopathological evaluation revealed immune-mediated ischemic colitis. The treatment was rearranged with methylprednisolone. Upon an increase in bloody diarrhoea frequency and C-reactive protein levels, infliximab was started. However, the patient became refractory to infliximab therapy after the second dose and was deceased due to septic shock.

Familial chylomicronemia syndrome related chronic pancreatitis: a single-center study.

BACKGROUND: Hypertriglyceridemia induces acute recurrent pancreatitis, but its role in the etiology of chronic pancreatitis (CP) is controversial. This study aimed to evaluate the clinical, laboratory and radiological findings of 7 patients with CP due to type 1 hyperlipidemia compared to CP patients with other or undefined etiological factors. METHODS: We retrospectively analyzed the clinical, laboratory and radiological findings of 7 CP patients with type 1 hyperlipidemia compared to CP patients without hypertriglyceridemia. These 7 patients had multiple episodes of acute pancreatitis and had features of CP on abdominal CT, endoscopic retrograde cholangiopancreatography and/or endoscopic ultrasonography. RESULTS: All CP patients were classified into two groups: a group with type 1 hyperlipidemia (n=7) and a group with other etiologies (n=58). The mean triglyceride level was 2323+/-894 mg/dL in the first group. Age at the diagnosis of CP in the first group was significantly younger than that in the second group (16.5+/-5.9 vs 48.3+/-13.5, P<0.001). The number of episodes of acute pancreatitis in the first group was significantly higher than that in the second group (15.0+/-6.8 vs 4.0+/-4.6, P=0.011). The number of splenic vein thrombosis in the first group was significantly higher than that in the second group (4/7 vs 9/58, P=0.025). Logistic regression analysis found that younger age was an independent predictor of CP due to hypertriglyceridemia (r=0.418, P=0.000). CONCLUSIONS: Type 1 hyperlipidemia appears to be an etiological factor even for a minority of patients with CP. It manifests at a younger age, and the course of the disease might be severe.

The role of EUS and EUS-FNA in the management of pancreatic masses: five-year experience.

BACKGROUND/AIMS: The efficacy of endoscopic ultrasound with fine-needle aspiration (EUS-FNA) in the diagnosis and staging of pancreatic malignancy is quite well established. The aim of this study is to describe a single-centre's experience. METHODOLOGY: Data were collected retrospectively on all patients with solid pancreatic masses undergoing EUS-FNA from January 2006 to March 2011. In tumor cases, TNM staging using EUS was compared with the results of histopathological staging. RESULTS: EUS-FNA of pancreatic lesions was performed in 125 patients. Of these patients, data of 75 were available (69% men, mean age 59.97±11.12 (SD) years); 58 (76%) of the lesions were ductal adenocarcinoma, 11 (14.5%) were chronic pancreatitis, 4 (%5) were intraductal papillary mucinous carcinoma (IPMN) and 2 (%3) were insulinoma. Diagnostic yield of the EUS-FNA procedure was 74.7% (56/75). Specimens from six patients were inadequate. In multivariate analysis, lesion diameter below 2cm was an independent predictor for the inadequacy of material (p=0.04). CONCLUSIONS: In patients with pancreatic mass with suspected malignancy, EUS-FNA provided a diagnosis with accuracy rate of 75%. Inadequate material with EUS-FNA was significantly more frequent in lesions below 2cm.

Endoscopic ultrasound-guided liver biopsy using a 20-gauge fine needle biopsy needle with the wet-heparinized suction technique.

OBJECTIVES: The primary aim of this study was to evaluate the histological adequacy of the liver tissue specimens obtained with a 20-gauge fine-needle biopsy needle and the secondary aim was to test the safety endoscopic ultrasound-guided liver biopsy with a 20-gauge fine-needle biopsy needle with the wet-heparinized suction technique. METHODS: Forty patients who underwent endoscopic ultrasound-guided liver biopsy were included in the study. A 20-gauge fine-needle biopsy needle was used with the wet-heparinized suction technique to make one pass each from the left and the right lobe. Histologic characteristics of the specimens were evaluated, and patients were observed after the procedure in order to intervene in case of an adverse event. RESULTS: The median longest core fragment was 22 mm from the left lobe [first quartile-third quartile 20-25 mm, interquartile range (IQR) 5 mm], and 20 mm (first quartile-third quartile 17-22 mm, IQR 5 mm) from the right lobe. The median cumulative core length per patient was 103 mm (91-108 mm, IQR 17 mm). The median cumulative number of complete portal triads per patient was 69.50 (52.25-82.25, IQR 30). The rate of diagnostic yield was 100%. Post-biopsy self-limiting abdominal pain was reported in two patients (5%). The most common histologic diagnosis was fatty liver disease (25%). CONCLUSION: Endoscopic ultrasound-guided liver biopsy with the wet-heparinized suction technique using a 20-gauge fine-needle biopsy needle is a safe alternative method in clinical practice.

Predictors of endoscopic recurrence in resected patients with Crohn's disease in a long-term follow-up cohort: History of multiple previous resections and residual synchronous disease in the remnant intestine.

BACKGROUND/AIMS: This study aimed to determine the predictors of endoscopic recurrence in a cohort of patients with Crohn's disease (CD) with prior intestinal resections. MATERIALS AND METHODS: The charts of the patients with CD were reviewed in a retrospective manner. Eighty-three patients were eligible for the final analysis. Demographic features of these patients and time between resection and colonoscopy, presence of any macroscopic residual disease in the remnant intestine, and postoperative medications were noted. Rutgeerts score was used to define postoperative endoscopic recurrence. RESULTS: The patients' mean age±SD at their final colonoscopy was 42.81±11.99 yr; and 37 of 83 patients (45%) were female. The mean follow-up time between resection and the final colonoscopy was 51.16±51.08 months. A total of 51 of 83 patients (61%) were in endoscopic remission (i0, i1); whereas 32 (39%) had an endoscopic recurrence (i2, i3, i4). History of multiple resections (χ2=6.12; p=0.013) and the presence of any postoperative residual disease in the remnant intestine (χ2=5.86; p=0.015) were risk factors; whereas the regular use of azathioprine (AZA) was significantly more common among patients without recurrence (χ2=4.515; p=0.034). In an age-sex adjusted Cox regression analysis history of multiple resections, presence of any postoperative residual disease proved to be independent risk factor for endoscopic recurrence, whereas the regular use of AZA proved to be ineffective. CONCLUSION: In a retrospective long-term follow-up cohort of resected patients with CD, having multiple resections for CD and the presence of any residual synchronous disease after ileocolonic resection were identified as risk factors for endoscopic recurrence; the latter was never reported in previous studies.

Should pancreas cyst fluids be divided into two for cytological diagnosis and biochemical tests?

BACKGROUND/AIMS: The aim of the present study was to investigate whether pancreas cyst fluids should be divided into two for cytological diagnosis and biochemical tests. MATERIALS AND METHODS: The present study was conducted with fluids aspirated from 12 pancreas cysts. The fluids were divided into two and sent to the cytopathology (fluid 1) and biochemistry (fluid 2) laboratories. Fluid 1 was centrifuged at the cytopathology laboratory. Cytology slides were prepared from the deposit, and the supernatant was sent to the biochemistry laboratory. Fluid 2 was centrifuged at the biochemistry laboratory, and amylase, carcinoembryonic antigen, and cancer antigen 19.9 levels were determined in the supernatant. These procedures were repeated for fluid 1 from the cytopathology laboratory. The remaining fluid 2 was sent to the cytopathology laboratory. Fluid 1-like slides were prepared from fluid 2 in the cytopathology laboratory. Cytological diagnoses of fluid 1 and fluid 2 were compared, and the Pearson correlation coefficient for biochemical test results was identified. RESULTS: 92% of fluid 1 and 50% of fluid 2 were diagnostic. Biochemical test results of fluid 1 and fluid 2 were similar, and the Pearson correlation coefficient was high. CONCLUSION: Our results showed that pancreatic cyst fluids did not need to be divided into two for cytological diagnosis and biochemical tests. Following centrifugation of the whole fluid at the cytopathology laboratory, the deposit and the supernatant can be used for cytological diagnosis and for biochemical tests, respectively. With this protocol, the sensitivity of cytological diagnoses and biochemical tests of pancreatic cyst fluids may increase.

Liver involvement is associated with blood culture positivity and high agglutination titre in patients with brucellosis in Turkey.

We investigated the incidence of and risk factors for liver involvement (LI) in patients with brucellosis in Turkey. Diagnosis was established by blood cultures (BCs) or compatible clinical presentation accompanied by serological evidence. Patients received either a combination of doxycycline plus rifampin for 6 weeks or doxycycline for 6 weeks plus streptomycin intramuscularly for the first 2 weeks. Liver function tests, including those for alanine (ALT) and aspartate aminotransferase (AST) levels, were monitored before and at the end of treatment. One hundred and ninety-five patients were included in the study. Seventy patients had elevated transaminases before treatment. Twenty-six patients had a positive BC for brucellosis. In multivariate analysis, BC positivity (OR=2.44, 95 % CI: 1.03-5.78, P=0.043) and serum agglutination titre (SAT) (OR=1.001, 95 % CI: 1.00-1.002, P=0.018) were found to be associated with LI. Serum aminotransferase levels were normalized in all patients with brucellosis. BC positivity and high SAT are independent factors that are associated with LI in patients with brucellosis.

Demographic characteristics of chronic pancreatitis patients in the era of endosonography: Experience of a single tertiary referral center in Turkey.

BACKGROUND/AIMS: There are no clinical data available about chronic pancreatitis (CP) on a series of patients of sufficient number in Turkey. In this study, the etiology and clinical features of CP were evaluated in one center, which is a tertiary referral hospital. MATERIALS AND METHODS: The files of 168 patients who had been diagnosed with CP in our Medical Faculty between October 2007 and May 2013 were retrospectively analyzed. The etiological factors, symptoms, complications, and treatment methods were analyzed. RESULTS: The most common etiological factor was alcohol abuse (39%). The average age±SD was 46±15.2 years, and the male:female ratio was 4.2:1 (it was 2.6:1 for other etiologies except alcohol abuse and 15.5:1 in alcoholic CP patients, p<0.05). The most frequent complication was diabetes mellitus (44%). The smoking rate was significantly higher in CP patients with pancreatic calcification (p<0.05). One-third of the patients received various types of endoscopic treatment. During a mean follow-up period of 42±13 months (range, 6-55), pancreatic cancer was detected in four patients (2.3%). CONCLUSION: In majority of the CP patients, the etiology is alcohol abuse in Turkey. The development of diabetes is the most frequent complication of CP, which is independent of the etiology.

Placement of a Self-Expanding Metal Stent to Treat Esophagogastric Benign Anastomotic Stricture via Retroflexed Ultrathin Endoscopy: A Case Report with a Video.

Previous studies reported that ultrathin endoscope (UE) provides endoscopic guidance during insertion of a self-expanding metal stent (SEMS) without fluoroscopic monitoring in patients with upper gastrointestinal stenosis (benign or malignant) or postoperative esophageal leakage. According to the type of SEMS and level of the stenosis, the technique of the procedure is variable. Herein, we report a patient who underwent placement of a distal release esophageal SEMS to treat an esophagogastric anastomotic stricture via retroflexed UE.