Neuroendocrine carcinoma of the ampulla of Vater causing ectopic adrenocorticotropic hormone-dependent Cushing's syndrome.

Ectopic adrenocorticotropic hormone (ACTH) is rarely secreted by neuroendocrine tumors. Although neuroendocrine tumors may occur at any site in the gastrointestinal system, they very rarely occur in the ampulla of Vater and have a poor prognosis. The present study described the first Cushing's syndrome as a result of ectopic ACTH arising from the ampulla of Vater neuroendocrine carcinoma. A 69-year-old female was admitted with clinical features of Cushing's syndrome, confirmed biochemically by hypokalemia, and elevated levels of ACTH and cortisol. In further investigations, a tumor of the ampulla of Vater and liver metastases were detected. Pathological analysis of the biopsy confirmed a neuroendocrine carcinoma, which was immunohistochemically positive for chromogranin A, synaptophysin, cluster of differentiation 56 and ACTH. Therefore, the present study diagnosed a functional and metastatic neuroendocrine carcinoma of the ampulla of Vater with ectopic ACTH production causing Cushing's syndrome. The patient succumbed to mortality 4 months later, despite administration of combined chemotherapy with irinotecan and cisplatin.

Clinical features of acute obstructive suppurative pancreatic ductitis: A retrospective review of 20 cases.

BACKGROUND AND AIMS: The clinical features of acute obstructive suppurative pancreatic ductitis (AOSPD) have not been elucidated. We aimed to clarify the clinical features of AOSPD. METHODS: We retrospectively reviewed the clinical features of 20 patients with AOSPD at two tertiary referral centers between 1993 and 2012. We compared 17 AOSPD patients with chronic pancreatitis (CP) and 42 patients with acute-on-CP in terms of clinical characteristics, presentation, and laboratory and imaging findings. RESULTS: The etiology of AOSPD involved CP in 17 (85%) patients, pancreatic ductal adenocarcinoma in 2 (10%), and intraductal papillary mucinous neoplasm in 1 (5%). Endoscopic pancreatic drainage was effective in 19 (95%) patients. Body temperature was significantly higher in AOSPD with CP than acute-on-CP patients (median: 38.2 vs 36.9 °C; P < 0.001). Serum amylase levels at onset were significantly lower (median: 133 vs 364.5 U/L; P = 0.009), and C-reactive protein was significantly higher (median: 9.42 vs 1.06 mg/dL; P < 0.001) in AOSPD with CP patients. Enlargement of the pancreatic parenchyma (18 vs 93%; P < 0.001) and stranding of the surrounding fat (12 vs 93%; P < 0.001) on computed tomography were observed less frequently in patients with AOSPD with CP patients. The diameter of the main pancreatic duct was significantly greater in AOSPD with CP than acute-on-CP patients (median: 7 vs 5 mm; P = 0.006). CONCLUSIONS: The major etiology of AOSPD involved CP, and endoscopic pancreatic drainage was effective. The clinical features differ between AOSPD with CP and acute-on-CP.

Predictive factors for positive diagnosis of malignant biliary strictures by transpapillary brush cytology and forceps biopsy.

OBJECTIVE: The diagnostic yields of endoscopic transpapillary brush cytology and forceps biopsies for malignant biliary strictures (MBS) remain unclear and predictive factors for diagnosis have not been established. We aimed to clarify the diagnostic yields of both methods and the predictive factors METHODS: We reviewed 241 patients with biliary strictures who underwent transpapillary brush cytology (n = 202) or forceps biopsy (n= 208) between 2004 and 2014 at a single academic center. RESULTS: The sensitivity of forceps biopsy for MBS was significantly higher than that of brush cytology [60.6% (97/160) vs 36.1% (57/158), P < 0.01). The sensitivity of forceps biopsy was significantly higher in diagnosing bile duct cancer than pancreatic cancer [78.8% (52/66) vs 42.4% (28/66), P < 0.01). Multivariate analysis revealed that serum total bilirubin (TB) level (T-Bil) ≥ 4 mg/dL [odds ratio (OR) 2.506, 95% confidence interval (CI): 1.139-5.495, P = 0.022) was an independent predictor for positive diagnosis by brush cytology, while bile duct cancer (OR 4.926, 95% CI 2.183-11.111, P < 0.001), stricture length ≥ 30 mm (OR 2.941, 95% CI 1.119-7.752, P = 0.029) and TB ≥ 4 mg/dL (OR 2.252, 95% CI 1.052-4.831, P = 0.037) were significant indicators of a positive diagnosis by forceps biopsy. CONCLUSIONS: Endoscopic transpapillary forceps biopsy shows higher sensitivity than that of brush cytology for MBS. Bile duct cancer, stricture length ≥ 30 mm and TB ≥ 4 mg/dL are good indicators of forceps biopsy.

Chemopreventive effect of resveratrol and apocynin on pancreatic carcinogenesis via modulation of nuclear phosphorylated GSK3ß and ERK1/2.

Despite progress in clinical cancer medicine in multiple fields, the prognosis of pancreatic cancer has remained dismal. Recently, chemopreventive strategies using phytochemicals have gained considerable attention as an alternative in the management of cancer. The present study aimed to evaluate the chemopreventive effects of resveratrol (RV) and apocynin (AC) in N-Nitrosobis(2-oxopropyl)amine-induced pancreatic carcinogenesis in hamster. RV- and AC-treated hamsters showed significant reduction in the incidence of pancreatic cancer with a decrease in Ki-67 labeling index in dysplastic lesions. RV and AC suppressed cell proliferation of human and hamster pancreatic cancer cells by inhibiting the G1 phase of the cell cycle with cyclin D1 downregulation and inactivation of AKT-GSK3ß and ERK1/2 signaling. Further, decreased levels of GSK3ß(Ser9) and ERK1/2 phosphorylation and cyclin D1 expression in the nuclear fraction were observed in cells treated with RV or AC. Nuclear expression of phosphorylated GSK3ß(Ser9) was also decreased in dysplastic lesions and adenocarcinomas of hamsters treated with RV or AC in vivo. These results suggest that RV and AC reduce phosphorylated GSK3ß(Ser9) and ERK1/2 in the nucleus, resulting in inhibition of the AKT-GSK3ß and ERK1/2 signaling pathways and cell cycle arrest in vitro and in vivo. Taken together, the present study indicates that RV and AC have potential as chemopreventive agents for pancreatic cancer.

Photodynamic Therapy using Talaporfin Sodium for the Recurrence of Cholangiocarcinoma after Surgical Resection.

We herein report the case of a 72-year-old man who underwent photodynamic therapy (PDT) with talaporfin sodium for recurrent cholangiocarcinoma after surgical resection. Endoscopic retrograde cholangiography (ERC) showed severe stenosis with an irregular surface measuring approximately 1 cm in length from the anastomotic site, and a recurrent nodular lesion was observed at the anastomotic site of the right anterior intrahepatic bile duct on gastrointestinal endoscopy. ERC after PDT revealed a dramatic improvement in the bile duct stenosis, and the nodular lesion had disappeared. No adverse events from the PDT were detected. PDT using talaporfin sodium may be a safe alternative treatment for cholangiocarcinoma.

Correlation between long-term outcome and steroid therapy in type 1 autoimmune pancreatitis: relapse, malignancy and side effect of steroid.

OBJECTIVES: Autoimmune pancreatitis (AIP) responds well to corticosteroid therapy (CST), and CST is essential to induce remission. However, the correlation between long-term outcome and CST has not been evaluated. We aimed to clarify the correlation between long-term outcome of AIP and CST. MATERIAL AND METHODS: We retrospectively evaluated relapse, risk of malignancy and side effects of CST by focusing on the correlation with CST in 84 patients with type 1 AIP. RESULTS: The incidence of relapse was 23.8%. The frequency of relapse after CST administration was significantly lower in patients taking CST for >6 months than in those who did not (22% versus 67%; p = 0.036). The incidence of malignancy was 10.7%. The standardized incidence ratio of malignancy was 2.14 [95% confidence interval 0.74-3.54]. There were no significant correlations between development of malignancy and CST. The incidences of total and serious side effects due to CST were 75% and 19.1%, respectively. Relapse was the only significant independent predictive risk factor for serious side effects in a multivariate analysis (odds ratio 4.065; 95% confidence interval 1.125-14.706; p = 0.032). The cumulative dose of corticosteroid was significantly higher in patients with serious side effects than in those without (12,645 mg versus 7322 mg; p = 0.041). CONCLUSIONS: CST reduces relapse of AIP. However, CST causes serious side effects, particularly in relapsing patients. Alternative maintenance therapy to prevent relapse is needed.

Impact of TP53 codon 72 and MDM2 SNP 309 polymorphisms in pancreatic ductal adenocarcinoma.

Single-nucleotide polymorphisms (SNPs) of TP53 (codon 72, rs1042522) and MDM2 promoter (SNP 309, rs2279744) have been associated with risk for various human cancers. However, studies analyzing these polymorphisms in pancreatic ductal adenocarcinoma (PDAC) are lacking. We investigated TP53 codon 72 and MDM2 SNP 309 polymorphisms in 32 patients with PDAC, 16 patients with chronic pancreatitis (CP), and 32 normal controls, using formalin-fixed paraffin-embedded tissue. We also examined TP53 and MDM2 protein immunohistochemistry (IHC) to assess the involvement of these differences in malignant transformation and disease progression. TP53 Pro/Pro genotype was significantly more frequent in PDAC patients than in controls (65.6 vs. 15.6%, p < 0.001) and no significant difference was found between CP patients (37.5%) and controls. In MDM2 SNP 309, there were no significant differences among the three groups. Based on the Kaplan-Meier analysis, overall survival was significantly shorter in MDM2 G/G genotypes compared with other genotypes (G/T and T/T) (359 vs. 911 days, p = 0.016) whereas no significant differences in TP53 genotypes were observed (638 vs. 752 days, p = 0.471). Although TP53 IHC was frequent in PDAC patients (53.1%), TP53 and MDM2 protein expression was not correlated with polymorphisms. Our study demonstrated TP53 codon 72 polymorphism is potentially a genetic predisposing factor while MDM2 SNP 309 polymorphism might be useful in predicting survival outcome.

Stent under-expansion on the procedure day, a predictive factor for poor oral intake after metallic stenting for gastric outlet obstruction.

BACKGROUND AND AIM: Self-expandable metallic stents (SEMS) have been widely accepted as palliation therapy for malignant gastric outlet obstruction (GOO). However, the factors predictive of poor oral intake after SEMS placement have not been elucidated sufficiently. We aimed to clarify both the patient and stent-related predictive factors. METHODS: We retrospectively reviewed 126 consecutive patients who underwent uncovered SEMS placement for malignant GOO between April 2010 and March 2013 at a university hospital and two tertiary care referral centers. RESULTS: Technical success of SEMS placement was achieved in all 126 (100%) patients. Improved oral intake was observed in 111 (88.1%) patients. A Karnofsky performance status ≤ 40 (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.02-1.28; P = 0.041), peritoneal dissemination (OR, 1.20; 95% CI, 1.01-1.26; P = 0.038), and under-expansion of the SEMS on the procedure day (OR, 1.55; 95% CI, 1.26-1.62; P < 0.001) were independent predictive factors for poor improvement on the GOO scoring system, according to multivariate analysis. CONCLUSIONS: SEMS under-expansion was a stent related, while poor performance status and peritoneal dissemination were patient related, predictive factors for poor oral intake after SEMS placement for malignant GOO.

Safety and benefits of self-expandable metallic stents with chemotherapy for malignant gastric outlet obstruction.

BACKGROUND AND AIM: The influence of chemotherapy on placement of self-expandable metallic stents (SEMS) for malignant gastric outlet obstruction (MGOO) has not been evaluated extensively. We investigated the influence of chemotherapy on the clinical outcomes of SEMS placement for MGOO. METHODS: A total of 152 cancer patients with MGOO from a university hospital and affiliate hospitals were included. The patients were classified according to chemotherapy status and evaluated for palliative efficacy and safety of SEMS placement. RESULTS: Technical success rate, time to oral intake, and parameters indicating improvement of physical condition did not differ between the with- and without-chemotherapy groups after stent placement. Re-intervention and stent migration were significantly more frequent in the with-chemotherapy group than in the without-chemotherapy group after stent placement (re-intervention, 32.4% vs 7.8%, P = 0.0005; stent migration, 13.5% vs 1.7%, P = 0.0097). The frequency of adverse events did not differ between the with- and without-chemotherapy groups. Although chemotherapy after stent placement was an independent predictive factor for shortening the stent patency period (hazard ratio [HR], 3.10; P = 0.0264), the use of additional stents facilitated uneventful recovery and further prolonged survival time (HR, 0.60; P = 0.0132). CONCLUSIONS: Various cancer patients with MGOO can undergo SEMS placement safely regardless of chemotherapy, and concurrent chemotherapy after stent placement can prolong survival time, although re-intervention and stent migration may be increased.

8-mm versus 10-mm diameter self-expandable metallic stent in bilateral endoscopic stent-in-stent deployment for malignant hilar biliary obstruction.

BACKGROUND: We aimed to clarify the clinical benefits of using 8-mm versus 10-mm diameter self-expandable metallic stent (SEMS) in bilateral endoscopic stent-in-stent (SIS) deployment for malignant hilar biliary obstruction (MHBO). METHODS: A total of 72 consecutive patients with MHBO treated by endoscopic bilateral SIS deployment were enrolled. The 8-mm and 10-mm diameter SEMSs were used in 37 patients (8-mm group) and 35 patients (10-mm group), respectively. We retrospectively compared technical success, functional success, complications, successful re-intervention, time to recurrent biliary obstruction (RBO) and survival time between two groups. RESULTS: There were no significant inter-group differences in terms of technical success (8-mm vs. 10-mm group, both 100%), functional success (96% vs. 100%), early (5% vs. 9%) and late (19% vs. 14%) complications other than RBO, and successful endoscopic re-intervention (94% vs. 100%), respectively. Time to RBO (median: 198 days vs. 222 days; log-rank, P = 0.440) and survival time (median: 186 days vs. 235 days; log-rank, P = 0.883) did not differ significantly between the two groups. However, the success rate of endoscopic bilateral revisionary stent insertion for RBO was significantly higher in the 10-mm compared to the 8-mm group (68% vs. 31%; P = 0.044). CONCLUSIONS: The 10-mm diameter SEMS is more suitable with regard to endoscopic re-intervention.

Comparison study of immunohistochemical staining for the diagnosis of type 1 autoimmune pancreatitis.

BACKGROUND: Various methods to evaluate immunohistochemical staining (IHC) for the diagnosis of type 1 autoimmune pancreatitis (AIP) have been proposed. Our goal was to determine the most useful IHC method for the diagnosis of AIP. METHODS: Specimens of AIP (18 patients), chronic pancreatitis (CP, 24 patients), and pancreatic ductal adenocarcinoma (PDA, 45 patients) were evaluated with IHC for immunoglobulin G (IgG), IgG1, IgG4, and CD138 (syndecan-1). The number of IHC-positive cells was counted in 3, 5, and 10 different high-power fields (HPFs) by selecting fields with the most numerous positive cells (hotspot) or by randomly selecting fields in the affected areas (random). We evaluated the mean number of IgG4-positive plasma cells (IgG4+)/HPF (mean IgG4+), the number of fields with >10 and >50 IgG4+ (NOF >10 and NOF >50 IgG4+), the ratio of IgG4+/IgG+, IgG4+/IgG1+, and IgG4+/CD138+. RESULTS: Analysis with receiver operator characteristic curves revealed that accurate and practical parameters in 3 HPFs were mean IgG4+ with the hotspot method (sensitivity, 88.9; specificity, 92.8 %), mean IgG4+ with the random method (100, 95.7 %), and NOF >10 IgG4+ with the random method (94.4, 97.1 %). These results were as accurate as results from 5 HPFs to 10 HPFs. The combination of mean IgG4+ and IgG4+/IgG+ did not provide more accurate diagnosis for AIP than a single criterion itself. CONCLUSIONS: Mean IgG4+ or NOF >10 IgG4+ with the random method in 3 HPFs was a useful and simple diagnostic method for AIP. The combined criteria of mean IgG4+ and IgG4+/IgG+ might not be required for accurate diagnosis of AIP.

Locus/chromosome aberrations in intraductal papillary mucinous neoplasms analyzed by fluorescence in situ hybridization.

Locus and chromosome abnormalities have not been well clarified in intraductal papillary mucinous neoplasms (IPMNs). The aim of this study was to retrospectively examine these abnormalities using fluorescence in situ hybridization. IPMNs (n=28) were histopathologically classified into noninvasive IPMN (n=17) and IPMN with an associated invasive carcinoma (invasive IPMN, n=11) groups. Noninvasive IPMNs possessed non-neoplastic and noninvasive spots in their tissues, and invasive IPMN cases possessed non-neoplastic, noninvasive, and invasive spots. Non-neoplastic (n=28), noninvasive (n=28), and invasive (n=11) spots were then analyzed for aneuploidy of chromosomes 3, 6, 7, 8, 17, and 18 and deletions of p16 and p53 loci. Polysomy 6 and p16 deletion were significantly more frequent in noninvasive than in non-neoplastic spots. Polysomy 7, polysomy 18, p16 deletion, and p53 deletion were significantly more frequent in invasive than in noninvasive spots. Detection of polysomy 7 and p53 deletion gave a high diagnostic accuracy for invasive IPMN (sensitivity, 90.9%; specificity, 94.1%; and accuracy, 92.5%). Our study suggests that: (1) polysomy 6 and p16 deletion may contribute to adenomatous change of IPMN; (2) polysomy 7, polysomy 18, p16 deletion, and p53 deletion play roles in malignant transformation of noninvasive IPMN; and (3) polysomy 7 and p53 deletion may be excellent diagnostic markers for invasive IPMN.

Autoimmune pancreatitis presenting a short narrowing of main pancreatic duct with subsequent progression to diffuse pancreatic enlargement over 24 months; natural history of autoimmune pancreatitis.

CONTEXT: Initial pancreatogram and natural history of autoimmune pancreatitis (AIP) have not been clarified, and there were few recent studies concerning the association between AIP and intraductal papillary mucinous neoplasm (IPMN). CASE REPORT: We report an 81-year- old man with AIP associated with IPMN. Although the initial pancreatogram was normal, a short narrowing of the main pancreatic duct (MPD) appeared during a follow-up for IPMN after 6 months, which was highly suggestive of pancreatic cancer. A narrowing of the MPD extended after 15 months, and this progressed to diffuse narrowing of the MPD with an elevation in the serum IgG4 levels after 24 months. Finally, the patient was diagnosed with diffuse-type AIP, according to the Japanese diagnostic criteria 2011 and the International Consensus Diagnostic Criteria. Considering the natural history of AIP, this marked change of the MPD is indicative of this condition. CONCLUSION: We report a case of AIP presenting with a short narrowing of the MPD with subsequent progression to diffuse pancreatic enlargement during a follow-up for IPMN.

A comparison of the diagnostic efficacy in type 1 autoimmune pancreatitis based on biopsy specimens from various organs.

BACKGROUND: Comprehensive immunostaining evaluation of the biopsy specimens from various organs with type 1 autoimmune pancreatitis (AIP) has not been elucidated. Our aim was to clarify which of these biopsy specimens and counting method could be a useful tool for supporting the diagnosis of AIP. METHODS: We retrospectively evaluated biopsy specimens from pancreas (n = 19), stomach (n = 28), duodenum (n = 27), duodenal papilla (n = 25), colon (n = 19), liver (n = 11), bile duct (n = 24), and minor salivary gland (n = 13) in 36 patients with AIP. Positive IgG4 immunostaining (>10 plasma cells/high-power field [HPF]) and positive IgG4/IgG ratio (>40%) of biopsy specimens from 8 sites of 6 organs in one HPF and an average from 3 HPFs were compared between AIP and controls. RESULTS: The sensitivity of IgG4 immunostaining for AIP in one HPF were 16% in pancreas, 14% in stomach, 15% in duodenum, 52% in duodenal papilla, 11% in colon, 27% in liver, 21% in bile duct and 8% in minor salivary gland, respectively. The positive IgG4 immunostaining of the duodenal papilla in one HPF showed the highest sensitivity (52%) and accuracy (73%) among the 8 sites. It also showed the highest sensitivity among 4 different counting methods (IgG4 immunostaining in one HPF and 3 HPFs, both IgG4 immunostaining and IgG/IgG4 ratio in one HPF and 3 HPFs), but there were no significant differences with respect to specificity and accuracy. CONCLUSIONS: IgG4 immunostaining of swollen duodenal papilla with more than 10 IgG4-positive plasma cells in at least one HPF is useful for supporting the diagnosis of AIP.

Histiocytic sarcoma of the bile duct.

An 80-year-old man was admitted with anorexia, a high fever and general icterus. Laboratory examinations revealed remarkable inflammation and elevation of liver/biliary enzymes. Computed tomography (CT) showed a high-density lesion in the bile duct, and endoscopic retrograde cholangiopancreatography (ERCP) disclosed an oval filling defect mimicking choledocholithiasis. Plastic stents were inserted to treat the acute cholangitis; however, the patient's symptoms recurred. An erythematous hypervascular mass obtained with a balloon catheter contained numerous pleomorphic histiocytic cells with eosinophilic cytoplasm, remarkable anisonucleosis and occasional mitoses. A diagnosis of histiocytic sarcoma (HS) was made based on the results of intensive immunohistochemistry. Monoclonal rearrangement of the IGH and TCRG genes, IGH split and IGH/BCL2 fusion was negative, although polysomy 8, 14, and 18 was detected. The patient was treated conservatively and died of the disease 20 months after the initial diagnosis. To the best of our knowledge, this is the first case of bile duct HS. This case, which involved numerical alterations of chromosomes, presented with CT and ERCP findings similar to those of choledocholithiasis.

Clinical evaluation of international consensus diagnostic criteria for type 1 autoimmune pancreatitis in comparison with Japanese diagnostic criteria 2011.

OBJECTIVES: The objective of this study was to evaluate the International Consensus Diagnostic Criteria (ICDC) for type 1 autoimmune pancreatitis (AIP) in comparison with the Japanese criteria 2011 (JPS2011). METHODS: We retrospectively investigated the usefulness of ICDC in comparison with JPS2011 in 64 patients with AIP and 90 patients with pancreatic cancer. RESULTS: The sensitivity and specificity of ICDC for AIP were 98.4% (63/64) and 100% (90/90), respectively. The sensitivities and specificities of ductal imaging, serology, other organ involvement, and pancreatic histology were 74.1%, 89.1%, 53.1%, and 26.1% and 94.7%, 94.5%, 100%, and 100%, respectively. On the other hand, the sensitivities and specificities of JPS2011 for AIP were 84.4% (54/64) and 100% (90/90), respectively. The condition of all the 10 patients who were deniable or possible under the JPS2011 could be diagnosed as definitive AIP under the ICDC. The sensitivities and specificities of Japanese criteria 2006, Asian Diagnostic Criteria, and HISORt criteria were 80.6%, 84.4%, and 92.2% and 95.8%, 87.8%, and 100%, respectively. CONCLUSIONS: The sensitivity and specificity of ICDC are higher than those of previous criteria. The JPS2011 is easy to handle for general practice, and specificity is very high. However, the sensitivity of JPS2011 is lower than that of ICDC, and improvement of sensitivity is to be hoped in the future.

Predictive factors for pancreatitis and cholecystitis in endoscopic covered metal stenting for distal malignant biliary obstruction.

BACKGROUND AND AIM: Pancreatitis and cholecystitis are major complications after self-expandable metal stent (SEMS) placement in distal malignant biliary obstruction. We aimed to clarify predictive factors for pancreatitis and cholecystitis after covered SEMS placement. METHODS: We retrospectively reviewed 74 consecutive patients with distal malignant biliary obstruction who underwent initial endoscopic drainage using covered SEMS. Predictive factors for pancreatitis and cholecystitis were evaluated in the 74 patients described above and in 66 patients who had not undergone cholecystectomy. RESULTS: The incidences of pancreatitis and cholecystitis were 10.8% (8/74) and 6.1% (4/66), respectively. Univariate analysis revealed that non-pancreatic cancer (P = 0.018) and contrast injection into the pancreatic duct (P = 0.030) were significant predictive factors for pancreatitis. Multivariate analysis revealed that non-pancreatic cancer (odds ratio [OR], 4.21; 95% confidence interval [CI], 1.63-14.18; P = 0.007) and contrast injection into the pancreatic duct (OR, 3.34; 95% CI, 1.33-9.60; P = 0.016) were significant independent predictive factors for pancreatitis. On the other hand, univariate and multivariate analyses revealed that tumor involvement to the orifice of the cystic duct (OCD) was a significant independent predictive factor for cholecystitis (OR, 5.85; 95% CI, 1.91-27.74; P = 0.005). CONCLUSIONS: Non-pancreatic cancer and contrast injection into the pancreatic duct were predictive factors for pancreatitis, and tumor involvement to the OCD was a positive predictive factor for cholecystitis after endoscopic covered SEMS placement for distal malignant biliary obstruction.