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Endoscopic ultrasound/endosonography-guided pancreaticogastrostomy (EUS-PGS) is a useful alternative when endoscopic retrograde pancreatography is difficult. Recently, many procedures, including peroral pancreatoscopy (POPS), have been performed through the mature fistula (MF) created by EUS-PGS. We evaluate the efficacy and safety of POPS to diagnose and treat pancreatic ductal stricture/pancreato-jejunal anastomotic stricture (PDS/PJAS) through the MF.Twenty patients underwent EUS-PGS; 13 of these underwent POPS through the MF at Juntendo University Hospital. All patients were studied retrospectively in terms of technical and clinical success rates and adverse events (AEs).The technical and clinical success rates of EUS-PGS were 95% and 100%. The early and late AEs rates were 20% and 15%. The technical success rate of POPS was 100%, with one AE. Biopsy of PDS/PJAS under POPS guidance revealed recurrent/residual intrapapillary mucinous adenoma (3 patients) and benign fibrotic stricture (10 patients). In the latter patients, multiple plastic stents were placed to dilate PDS/PJAS. Four patients with improvement of PDS/PJAS were stent free, but the remaining patients were not yet.Endoscopic ultrasound/endosonography-guided pancreaticogastrostomy and various procedures (including POPS) performed through the MF are feasible and effective and can diagnose and treat PDS/PJAS with acceptable AEs rates.

OBJECTIVE The aim of the study was to develop a formula for predicting the probability of malignancy of mucinous cystic neoplasm (MCN) of the pancreas with ovarian-type stroma. METHODS A total of 364 patients were enrolled. A total score was calculated as the sum of the approximate integers of the odds ratios of the predictive factors identified by multivariate analysis. The relationship between the total score and pathological results was assessed. RESULTS A total of 321 patients had benign MCN and 43 had malignant MCN. Five possible predictive factors were analyzed: 56 years or older, high serum carcinoembryonic antigen level, high carbohydrate antigen 19-9 level, tumor size of 51 mm or greater, and the presence of mural nodules. The total score was significantly higher in patients with malignant MCN (median, 24; range, 0-37) compared with benign MCN (median, 5; range, 0-33; P < 0.001). Receiver operating characteristic curve analysis demonstrated that the area under the curve was 0.86, and the sensitivity and specificity of the total score for discriminating malignant MCNs were 72% and 83%, respectively, using a cut-off value of 22. CONCLUSIONS The current simple formula can predict the malignancy of MCN and may thus contribute to the adequate management of patients with MCN.

Objectives This study aimed to assess the pitfalls of the current International Association of Pancreatology guidelines (IAPCG2017) for pancreatic intraductal papillary mucinous neoplasm (IPMN) and identify the criteria for future guidelines. Methods Eighty surgically resected, consecutive IPMN cases were analyzed. Data including tumor site, IPMN duct type, and surgery type were collected. Based on radiological data, cases were retrospectively classified as high-risk stigmata (HRS) and non-HRS. Pathological grades and histological subtypes of IPMN cases were determined. Severe stromal sclerosis of the IPMN septa/marked parenchymal atrophy in the upstream pancreas was investigated pathologically. Positive/negative predictive values of the IAPCG2017 were calculated. Clinicopathological features of HRS-benign cases (pathologically benign IPMN cases meeting the HRS criteria) were extracted. Results The positive/negative predictive values were 72.7%/64.0%, 70.0%/34.6%, and 54.0%/63.3% for IAPCG2017, HRS-main pancreatic duct, and HRS-nodule criteria, respectively. The 15 HRS-benign cases (18.8%) included 13 pancreatoduodenectomies and 10 cases of gastric pyloric (GP) gland subtype. Severe upstream atrophy was significantly related to IPMN malignancy, unlike the severe sclerosis of IPMN septa. Conclusions Benign IPMNs of GP subtype are sometimes categorized as HRS with the IAPCG2017. Collecting data on the natural course of GP-IPMN is necessary. To evaluate upstream atrophy may be of value to predict IPMN malignancy.

Exocrine pancreatic insufficiency may impair the nutritional status in pancreatic cancer (PC), but the role of pancreatic enzyme replacement therapy (PERT) is not fully evaluated. Therefore, we conducted this multicenter open-label randomized controlled trial to evaluate the role of PERT in PC patients.Patients with unresectable PC receiving chemotherapy were randomly assigned to pancrelipase and nonpancrelipase groups. Patients in the pancrelipase group took oral pancrelipase of 48,000 lipase units per meal. N-benzoyl-tryrosyl para-aminobenzoic acid (NBT-PABA) test was performed at baseline. Our primary endpoint was change in body mass index (BMI) at 8 weeks. Secondary endpoints were change in other nutritional status at 8 weeks and overall survival.A total of 88 patients were enrolled between May 2014 and May 2016. The NBT-PABA test was lower than the normal range in 90%. There were no significant differences in change in BMI at 8 weeks: 0.975 and 0.980 in the pancrelipase and the nonpancrelipase groups, respectively (P = 0.780). The other nutritional markers were also comparable. The median overall survival was 19.0 and 12.0 months (P = 0.070).In this randomized controlled trial, pancrelipase failed to improve the change in BMI at 8 weeks in PC patients receiving chemotherapy.

Although patients with pancreatic cancer (PC) are prone to exocrine pancreatic insufficiency, there are little evidence about pancreatic enzyme replacement therapy (PERT) in patients with PC, especially those receiving chemotherapy.This is a prospective consecutive observational study of PERT in patients with unresectable PC. We prospectively enrolled patients receiving chemotherapy for unresectable PC from April 2012 to February 2014 and prescribed oral pancrelipase of 48,000 lipase units per meal (pancrelipase group). N-benzoyl-tryrosyl para-aminobenzoic acid test was performed at baseline. Patients receiving chemotherapy before April 2012 were retrospectively studied as a historical cohort. Data on the nutritional markers at baseline and 16 weeks were extracted, and serial changes, defined as the ratio of markers at 16 weeks/baseline, were compared between 2 groups.A total of 91 patients (46 in the pancrelipase group and 45 in the historical cohort) were analyzed. N-benzoyl-tryrosyl para-aminobenzoic acid test was low in 94% of the pancrelipase group. Serial change in the pancrelipase group versus historical cohort was 1.01 versus 0.95 in body mass index (P0.001) and 1.03 versus 0.97 in serum albumin (P = 0.131).The rate of exocrine pancreatic insufficiency in unresectable PC was high, and PERT can potentially improve the nutritional status during chemotherapy.

Objectives The aim of this study was to assess prevailing treatment of pancreatolithiasis in Japan. Methods We surveyed clinical data from 1834 patients (1479 men and 355 women) at 125 hospitals. Results Extracorporeal shock-wave lithotripsy (ESWL) was performed alone in 103 patients (5.6%), ESWL plus an endoscopic procedure in 446 (24.3%), endoscopic treatment alone in 261 (14.2%), and surgery in 167 (9.1%). Other treatments were given to 358 (19.5%), whereas 499 (27.2%) received no treatment. Symptoms were relieved in 85.7% after ESWL, 80.8% after endoscopic treatment alone, and 92.8% after surgery. Early complication rates within 3 months after ESWL, endoscopic treatment alone, and surgery were 8%, 4.5%, and 27.1%, respectively. Late complications after ESWL, endoscopic procedures alone, and surgery were 1.7%, 2.5%, and 8.2%, respectively. Symptom relief but also early and late complications were greater after surgery than after ESWL and endoscopic treatment. Among 417 patients undergoing ESWL, 61 (14.6%) required surgery, as did 32 (16%) of 200 patients treated endoscopically. Surgery was required less frequently following initial operative treatment (11/164 patients [6.7%]). Nonsurgical initial treatments were chosen more frequently. Conclusions First-line treatment of pancreatolithiasis should be ESWL with or without endoscopy because of minimal invasiveness and fewer complications.

Pancreatic cancer is reported to be highly associated with thromboembolism (TE). The aim of this analysis is to clarify risk factors for TE and its clinical impact in Japanese patients with pancreatic cancer.Data on consecutive pancreatic cancer patients receiving systemic chemotherapy between August 1999 and July 2015 were retrospectively studied. Both symptomatic and asymptomatic, arterial and venous TEs were included in the analysis. Risk factors for TE development were analyzed using a proportional hazards model with death without TE as a competing risk. The impact of TE on survival was also evaluated using a time-dependent covariate multiple Cox model.A total of 475 patients were included in the analysis, and 57 TEs (12%) were identified: 45 venous TEs and 12 arterial TEs. The median time to TE was 169 days and the median survival from TE was 65 days. Liver metastasis was the only significant risk factor for TE (subdistribution hazards ratio, 2.15; P = 0.01), and TE was significantly associated with poor prognosis (hazards ratio, 3.31; P0.01).Thromboembolism was not uncommon in Japanese patients receiving chemotherapy for advanced pancreatic cancer and was associated with poor prognosis. Liver metastasis was the risk factor for TE.

Pancreatic cystic lesions (PCLs) are considered precursors of pancreatic cancer. Diabetes mellitus (DM) and obesity are known as risk factors for pancreatic cancer. We investigated the prevalence of PCLs in the general population and the relationship between PCLs and DM/obesity.This cross-sectional analysis included 5296 individuals who underwent a preventive medical examination between October 2006 and June 2013 at our institution. Magnetic resonance imaging, including magnetic resonance cholangiopancreatography, was performed using a 3.0-T system as part of a comprehensive health screening program. We investigated the prevalence and risk factors of PCLs.The prevalence of PCLs was 13.7%, which was increased according to age. Individuals with PCLs were more prone to obesity (body mass index, 24.0 vs 23.7 kg/m [P = 0.015]; waist circumference, 87.4 vs 85.5 cm [P0.001]). DM was more prevalent in individuals with PCLs (18.4% vs 10.5%, P0.001). In a multivariate analysis, age (odds ratio [OR], 1.06; P0.001), excess body mass index (OR, 1.26; P = 0.039), and DM (OR, 1.39; P = 0.005) were associated with PCLs.The prevalence of PCLs detected by magnetic resonance imaging in a preventive medical examination was 13.7%. Pancreatic cystic lesions were significantly associated with DM and obesity.

A subpopulation of patients with pancreas divisum experience symptomatic events such as recurrent acute pancreatitis and chronic pancreatitis. Minor papilla sphincterotomy has been reported as being an effective treatment. The aim of this study was to evaluate the safety and efficacy of endoscopic balloon dilation for the minor papilla.Between 2000 and 2012, 16 patients were retrospectively included in this study. After endoscopic balloon dilation for the minor papilla was received, a pancreatic stent or a nasal pancreatic drainage catheter was placed for 1 week. If a stricture or obstruction was evident, it was treated with balloon dilation followed by long-term stent placement (1 year). When an outflow of pancreatic juice was disturbed by a pancreatic stone, endoscopic stone extraction was performed.Balloon dilation and stent placement were achieved and were successful in all the cases (16/16; 100%). Clinical improvement was achieved in 7 (84.7%) of the 9 patients with recurrent acute pancreatitis and in 6 (85.7%) of the 7 patients with chronic pancreatitis. Early complications were observed in 1 (6.3%) patient. Pancreatitis or bleeding related to balloon dilation was not observed.Endoscopic balloon dilation for the minor papilla is feasible for the management of symptomatic pancreas divisum.

The long-term prognosis in patients with intraductal papillary mucinous neoplasm (IPMN) has not been determined. The aim of this study was to elucidate the risk for nonpancreatic cancer-specific mortality in patients with IPMN.Seven hundred ninety-three patients with IPMN who were followed up more than 1 year were included in this study. Fine and Gray competing risk regression was used to assess the risk for mortality unrelated to pancreatic cancer. A comorbidity score at diagnosis was assigned using the Adult Comorbidity Evaluation 27.After a median follow-up of 50 months, a high comorbidity score and age at diagnosis were significantly associated with a risk for mortality unrelated to pancreatic cancer. Adjusted hazards ratio and 95% confidence interval of each comorbidity burden were as follows: none, 1; mild, 2.68 (0.76-9.45; P = 0.124); moderate, 10.9 (3.19-37.1; P0.001); and severe, 32.0 (9.41-108.8; P0.001). Comorbidity burden did not affect the risk for pancreatic cancer-specific mortality.Comorbidity and age at diagnosis was significantly related to mortality unrelated to pancreatic cancer in patients with IPMN. For patients at high risk for nonpancreatic cancer mortality, a follow-up management may be more reasonable than surgery.

The aim of this study was to clarify the impact of diabetes mellitus (DM) as well as antidiabetic, antihypertensive, and antihyperlipidemic medications such as metformin and statins on survival in patients with advanced pancreatic cancer receiving chemotherapy.We retrospectively reviewed the medical records of 250 patients with advanced pancreatic cancer receiving chemotherapy. Multivariate analyses of prognostic factors for survival were performed both in overall population and in subgroups with and without DM.Diabetes mellitus was diagnosed in 124 patients (50%) who had less distant metastasis and more hypertension. Thirty patients received statin for hyperlipidemia. Overall survival was 13.3 versus 10.0 months with and without DM (P = 0.084), but hazard ratio of DM was 1.05 (P = 0.758) in the multivariate analysis. Subgroup analysis of diabetic patients, but not in non-diabetic patients, demonstrated use of statins (hazard ratio, 0.40; P = 0.010) as a prognostic factor, as well as distant metastasis, performance status, combination therapy with gemcitabine and S-1, and use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. No antidiabetic medications were prognostic factors.Neither DM nor antidiabetic treatment had prognostic impact on advanced pancreatic cancer. Statin use was associated with better survival in the diabetic patients.

OBJECTIVES Malignant ascites (MA) caused by peritoneal carcinomatosis is not uncommon in patients with pancreatic cancer. However, the clinical features and outcomes in these patients remain to be elucidated. METHODS Baseline characteristics and overall survival (OS) of consecutive patients with advanced pancreatic cancer who presented with MA were retrospectively evaluated. RESULTS Of 494 patients with advanced pancreatic cancer, 73 (15%) presented with MA. Patients with synchronous MA (n = 21), compared with those with metachronous MA (n = 52), had better performance status (P = 0.02), smaller amount of ascites (P < 0.01), and higher chance of receiving chemotherapy (57% vs 17%, P < 0.01), and resulted in longer OS (115 vs 42 days, P < 0.01). Overall survival was significantly longer in patients receiving chemotherapy than in those with best supportive care alone (124 vs 50 days, P < 0.01). In a multivariate analysis, chemotherapy was prognostic in addition to performance status, CRP, and small amount of MA; the hazard ratio of chemotherapy was 0.46, compared with best supportive care alone (P = 0.02). CONCLUSIONS Although the prognosis of pancreatic cancer patients with MA remains poor, selected patients may be candidate for chemotherapy, regardless of the timing of appearance of MA.

The aim of this study was to examine the association of risk factors including diabetes mellitus (DM) with the age of onset in Japanese pancreatic cancer (PC) patients.We retrospectively reviewed 688 PC patients diagnosed at our institute. We analyzed the association between the age of onset of PC and the following variables: sex, smoking, alcohol, DM, and a family history of cancer especially PC.The mean age of PC diagnosis was 67.6 years. The onset of PC occurred earlier in current smokers (63.6 years old, P0.001) compared with past smokers (69.5 years old) and never smokers (68.6 years old). Patients with long-standing DM (2 years) were older (70.5 years, P0.001) when diagnosed with PC than patients with new-onset DM (within 2 years) (66.9 years old) and patients without DM (66.7 years old). In the multivariate analysis, current smokers and a family history of cancer other than PC were associated with earlier onset. Conversely, long-standing DM was associated with later onset.In Japanese PC patients, current smokers and a family history of cancer other than PC were associated with a younger age of onset. Conversely, long-standing DM was associated with a later onset.

This study aimed to investigate risk factors for pancreatic stones and atrophy in autoimmune pancreatitis (AIP).Seventy-one patients with AIP observed for more than 1 year were enrolled. The frequency of pancreatic stone development and atrophy on computed tomography as well as their risk factors were examined.Pancreatic stones and atrophy were observed in 13 and 43 patients, respectively. Alcohol consumption of greater than 50 g/d was the only significant risk factor for pancreatic atrophy in univariate analysis. Alcohol intake of greater than 50 g/d was observed in 6 of 13 patients with stones and 10 of 58 patients without stones (46% vs 17%, P = 0.059). Alcohol intake of greater than 50 g/d was observed in 14 of 43 patients with atrophy and 2 of 28 patients without atrophy (33% vs 7.1%, P = 0.018). In multivariate analysis, alcohol consumption was a significant risk factor both for pancreatic stone formation (odds ratio [OR], 7.47; P = 0.040) and atrophy (OR 6.24; P = 0.034). Higher age at onset was another significant risk factor for pancreatic atrophy (OR 1.07 per year; P = 0.029).Alcohol consumption of greater than 50 g/d increases the risk of pancreatic stone development and atrophy in patients with AIP.

We examined whether the presence of pancreatic cysts could be a risk for pancreatic cancer by comparing the incidence and characteristics of cysts found by magnetic resonance (MR) imaging in patients with and without pancreatic cancer.Half-Fourier rapid acquisition with relaxation enhancement images and MR cholangiopancreatography were performed in 116 patients with pancreatic cancer (PC group) and 1226 with nonpancreatic disease (NP group). Incidence and characteristics of cysts were analyzed.Pancreatic cysts were detected in 65 patients (56%) of the PC group and in 123 patients (10%) of the NP group. According to the multivariate analysis, cyst presence was a significant risk factor for pancreatic cancer (odds ratio [OR], 10.27; P0.01), especially cysts larger than 10 mm (OR, 4.718; P0.01). When the definition of cyst presence in the PC group was restricted to the 33 cases with cysts considered to have existed before the development of cancer, the incidence was still high (OR, 2.976; P0.01) and size remained significant (OR, 4.428; P0.01).Patients with pancreatic cysts, especially larger than 10 mm, were considered to be at an increased risk of pancreatic cancer over the entire pancreas.

Objective Glucose intolerance is often observed in autoimmune pancreatitis (AIP), although its long-term prognosis after steroid treatment (ST) is still unclear. Methods A total of 47 patients with AIP were enrolled. On the basis of the change in hemoglobin A1c (HbA1c) and the use of diabetic medication, prognosis was classified into 3 categories, namely, "improved," "aggravated," and "unchanged." The relation between the result of an initial glucagon tolerance test (ΔCPR) and the later use of insulin during maintenance ST was examined in 20 patients. The transitions of homeostasis model assessment β cell and insulin resistance (HOMA-β and HOMA-R) were analyzed in 16 patients. Results Glucose tolerance was improved in 6 patients (13%), aggravated in 9 patients (19%), and unchanged in 32 patients (68%). All patients with ΔCPR less than 0.6 ng/mL were obliged to use insulin even after long-term observation, whereas all patients with ΔCPR more than 1.0 ng/mL were free from insulin therapy. Moreover, HOMA-β showed significant improvement after ST (43.9% → 56.0% in median, P = 0.030), and HOMA-R showed significant aggravation (1.30 → 1.78, P = 0.039). Conclusions Glucose tolerance that is too severely damaged may not recover fully even after ST. Thus, ST should be performed to preserve insulin secretion at the early stage of AIP.

The aim of this study was to investigate the effect of S-1 on the prognosis of advanced pancreatic cancer.In total, 112 patients with pancreatic cancer who received chemotherapy between April 2001 and April 2007 were divided into 2 groups: PreS-1 (53 patients who started chemotherapy before January 2005) and PostS-1 (59 patients who started chemotherapy after February 2005, the time of S-1 introduction). Patient characteristics and clinical outcomes were compared, and prognostic factors were analyzed.Patient characteristics did not significantly differ between the 2 groups. S-1 was administered as a second-line monotherapy in 5.7% of the PreS-1 group and combined with gemcitabine as a first-line therapy in 27.1% or as second-line monotherapy in 23.7% in the PostS-1 group. Both progression-free survival and overall survival improved after introduction of S-1 (median progression-free survival, 4.4 and 5.3 months; P = 0.043; median overall survival, 9.5 and 13.1 months; P = 0.048 in PreS-1 and PostS-1 groups, respectively). Multivariate analysis revealed that the PostS-1 group (hazards ratio, 0.52; P = 0.003), performance status, and carcinoembryonic antigen were significant prognostic factors for survival.Introduction of S-1 may improve the prognosis of Japanese patients with advanced pancreatic cancer.