Search

Objective The effectiveness of everolimus for the management of pancreatic neuroendocrine neoplasms (PNENs), including the G3/NEC types, remains unclear. We therefore investigated the effectiveness of the drug for the management of PNENs. Methods We analyzed the progression-free survival (PFS) and overall survival (OS) associated with everolimus and factors influencing the PFS and OS. Results One hundred patients were evaluated. The PFS associated with the G1/G2 types tended to be significantly longer than that associated with the G3/NEC types (hazard ratio [HR], 0.45; p =0.005). A multivariate analysis showed that the significant factors influencing the PFS were age (65 years old; HR, 0.44; p =0.002), grade (G1/G2; HR, 0.42; p =0.006), everolimus treatment line (≤2nd; HR, 0.55; p =0.031), and presence of treatment with metformin (yes; HR, 0.29; p =0.044). The median OS was 63.8 months. In the multivariate analysis, the significant factors influencing the OS were grade (G1/G2; HR, 0.21; p0.001), volume of liver metastasis (≤25%; HR, 0.27; p0.001), everolimus treatment line (≤2nd; HR, 0.27; p0.001), and presence of primary tumor resection (yes; HR, 0.33; p =0.005). Conclusions The effectiveness of everolimus in the management of G3/NEC types and prognoses tended to be poorer than those associated with the G1/G2 types. Everolimus combined with metformin and early-line treatment with everolimus may be effective for managing advanced PNENs.

Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy is technically difficult. Extensive training is required to develop the ability to perform this procedure.To investigate the learning curve of single-balloon-assisted enteroscopy ERCP (SBE-ERCP).We conducted a retrospective, observational case series at a single center. We evaluated the SBE-ERCP procedures between April 2011 and February 2021. The main outcomes were the rate of reaching the target site and the success rate of the entire procedure. These parameters were additionally expressed as a learning curve.A total of 687 SBE-ERCP procedures were analyzed. The learning curve was analyzed in blocks of 10 cases. In this study, seven endoscopists, experts in conventional ERCP, were included. The overall SBE-ERCP procedural success rate was 92.2% (634/687 cases). Combining all data from individual endoscopists' evaluation periods, the insertion and success rates of the SBE-ERCP procedures gradually increased with increased experience performing SBE-ERCP. The insertion success rates for the number of SBE-ERCP cases ( 20, 21-30, 30) were 82.9%, 92.9%, and 94.3%, respectively; the procedure success rates were 74.3%, 81.4%, and 92.9%, respectively. The endoscopists who had performed 30 SBE-ERCP cases had a success rate of ≥ 90%.Our results suggest that performing 30 cases is one of the targets for conventional ERCP experts to become competent in performing SBE-ERCP in patients with a surgically altered anatomy.

Background and Purpose: During endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS), tract dilation is one of the most important steps, and the placement of conventional metal stents with 8.5 Fr delivery devices is difficult due to the large outer shape of the device. Fine-gauge balloon catheters have become popular because of their stricture penetration ability and ease of dilation. This study aimed to evaluate the utility of fine-gauge balloon catheters. Patients and Methods: This retrospective study involved 38 patients who underwent conventional metal stent placement. The patients were classified into two groups: those who underwent dilation with a fine-gauge balloon catheter before initial metal stenting (balloon dilation group) and those who underwent bougie dilation only (non-balloon dilation group). We evaluated the stenting success rate after initial dilation and adverse events. Results: Seventeen and twenty-one patients were included in the balloon dilation and non-balloon dilation groups, respectively. The stenting success rate after initial dilation was 100% (17/17) in the balloon dilation group and 71.4% (15/21) in the non-balloon dilation group (p = 0.024). As adverse events, peritonitis was observed in one case (4.8%) in the balloon dilation group, and in three cases (14.3%) in the non-balloon dilation group (p = 0.613). Conclusions: Dilation using a fine-gauge balloon catheter before conventional metal stent with 8.5 Fr delivery device placement is considered effective in EUS-HGS.

This study aimed to investigate the efficacy of intensive fluid-loading therapy post-endoscopic retrograde cholangiopancreatography (ERCP) for the prevention of post-ERCP pancreatitis (PEP) in at-risk patients.In this retrospective study, data of 1200 patients at risk for PEP were investigated. After propensity score matching, 404 patients were included in the normal (n = 202) and hydration (n = 202) groups. On the day of ERCP, patients in both groups were infused with 2000 ml/24 h of fluid before ERCP. Meanwhile, the hydration group received an additional 1000 ml/10 h of lactated Ringer's solution postoperatively.The incidence of PEP was lower in the hydration group (12.4%) than in the normal group (24.3%) (odds ratio [OR]: 0.44; 95% CI: 0.26-0.75, p = .003). The incidence of severe PEP was 2.0% and 6.9% in the hydration and normal groups (OR: 0.27; 95% CI: 0.09-0.84, p = .027), respectively. The incidence of fatal PEP was 0% and 2.0% in the hydration and normal groups (OR: N.A.: p = .123), respectively.Post-ERCP hydration may be an effective method of preventing PEP, including severe PEP, in at-risk patients.

BACKGROUND/PURPOSE The role of endoscopic preoperative biliary drainage for pancreatic head cancer is controversial because of the high incidence of stent occlusion before surgery. We sought to validate a suitable stent for biliary drainage in patients with pancreatic cancer undergoing neoadjuvant chemotherapy (NAC)/neoadjuvant chemoradiotherapy (NAC-RT). METHODS We evaluated patients who received preoperative neoadjuvant therapy for pancreatic head cancer between January 2013 and December 2019. A covered metal (CMS) or plastic stent (PS) was inserted in symptomatic patients for biliary drainage. Recurrent biliary obstruction (RBO), success rate of endoscopic drainage, adverse events, and surgical outcomes were compared between the CMS and PS groups. RESULTS Occurrence rate of RBO was significantly higher with PS (97%) vs CMS (15%, P

OBJECTIVES: Gastrointestinal endoscopy (GIE) is useful for the early detection and treatment of many diseases; however, GIE is considered a high-risk procedure in the coronavirus disease 2019 (COVID-19) pandemic era. This study aimed to explore the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity in saliva and gastrointestinal fluids to which endoscopy medical staff are exposed. METHODS: The study was a single-center cross-sectional study. From June 1 to July 31, 2020, all patients who underwent GIE at Yokohama City University Hospital were registered. All patients provided 3 mL of saliva. For upper GIE, 10 mL of gastric fluid was collected through the endoscope. For lower GIE, 10 mL of intestinal fluid was collected through the endoscope. The primary outcome was the positive rate of SARS-CoV-2 in saliva and gastrointestinal fluids. We also analyzed serum-specific antibodies for SARS-CoV-2 and patients' background information. RESULTS: A total of 783 samples (560 upper GIE and 223 lower GIE samples) were analyzed. Polymerase chain reaction (PCR) on saliva samples did not show any positive results in either upper or lower GIE samples. However, 2.0% (16/783) of gastrointestinal fluid samples tested positive for SARS-CoV-2. No significant differences in age, sex, purpose of endoscopy, medication, or rate of antibody test positivity were found between PCR positive and PCR negative cases. CONCLUSIONS: Asymptomatic patients, even those with no detectable virus in their saliva, had SARS-CoV-2 in their gastrointestinal tract. Endoscopy medical staff should be aware of infection when performing procedures. The study was registered as UMIN000040587.

In IgG4-related sclerosing cholangitis (IgG4-SC), the necessity of biliary drainage (BD) is unclear. In this study, we aimed to retrospectively investigate the improvement of liver damage and jaundice in cases of IgG4-SC with and without BD, before starting steroids.A total of 52 patients with IgG4-SC were investigated in the study. The study endpoints were the normalization rate of alkaline phosphatase (ALP)/total bilirubin (T-Bil) after 8 weeks of steroids, with and without BD.Propensity score matching was performed based on ALP and T-Bil, and 28 patients were included. There were 14 patients each in the BD and non-BD groups. Before initiation of steroids, the mean ALP in the BD group and the non-BD group was 378/461 (P = .541); the mean T-Bil was 2.5/1.8 (P = .401). Eight weeks after initiation of steroids, ALP improvement rate in the BD group/non-BD group was 69.2%/61.5% (P = 1.000), and T-Bil improvement rate was 100%/100% (P = Ns).Steroids for IgG4-SC could prove effective in improving liver damage and jaundice, regardless of the presence or absence of BD. BD for IgG4-SC aimed to improve jaundice may not be necessary.

Objective Neuroendocrine neoplasms (NENs) are rare and indolent diseases, but the efficacy of treatment without surgical resection is temporary and limited. Targeted immunotherapy is an important treatment strategy in several cancers. However, the tumor and host immune reactions in the NEN microenvironment are poorly understood. Therefore, we investigated the immune checkpoint system and host immune response in pathological NEN specimens. Methods The expression of the mismatch repair proteins MSH2, MSH6, PMS2, and MLH1 was immunohistochemically detected in archival tissue samples obtained from 20 patients with gastroenteropancreatic NENs. We additionally assessed the expression of programmed death (PD)-1, PD-L1, and the tumor-infiltrating lymphocyte (TIL) markers CD8 and family of transcription factor P3 (FOXP3). Results All 20 NENs expressed the mismatch repair proteins MSH2, MSH6, PMS2, and MLH1. The PD-L1 and/or PD-1 expression in the tumor cells and/or TILs was confirmed in 75% of the cases. PD-1-, CD8-, and FOXP3-positive TILs were more frequently associated with PD-L1-positive tumors than with PD-L1 negative tumors (PD-1: 19.5 vs. 7.3, CD8: 18.1 vs. 7.1, FOXP3: 13.2 vs. 3.2, p=0.438, p=0.419, P=0.603, respectively). The number of cells positive for PD-1 tended to gradually increase in increasing grade of NENs but did not reach significance (Grade 1: 5.8, Grade 2: 10.2, NEC: 18.1, p=0.903). Conclusion NENs consistently express mismatch repair proteins but have a high expression of PD-L1 and/or PD-1 in the tumor microenvironment. NEC and PD-L1-positive NENs may be immunologically "hot" tumors, so an immunological approach may be an appropriate treatment strategy for these tumors.

The detection ability and role of different imaging modalities to detect pancreatic neuroendocrine neoplasms (PNENs) including small lesions is unclear. This study aimed to compare the ability of endoscopic ultrasound (EUS) and computed tomography (CT) to detect PNENs.Data of patients who underwent EUS and contrast-enhanced CT and were diagnosed with PNENs were analyzed. The detection rates of pancreatic lesions with EUS and CT based on tumor size and influencing factors were investigated.For 256 PNEN lesions, the detection rate of EUS was better than that of CT (94.5% vs 86.3%; P .001). EUS was significantly superior to CT for PNENs ≤5 mm (58.3% vs 16.7%; P = .006) and 5-10 mm (97.7% vs 79.5%; P = .008). There was no significant difference in the detection rate between EUS and CT for PNENs10 mm (98.4% vs 96.4%; P = .375). Size (≤5 mm) and insulinoma were independent factors associated with poor EUS and CT detection rates.Endoscopic ultrasound exhibited better detection ability than CT, with an excellent detection rate for PNENs5 mm, except for insulinomas. CT could detect PNENs10 mm, which are amenable to treatment.

Background and aim Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) presents as isolated proximal-type sclerosing cholangitis (i-SC). The present study sought to clarify the imaging differences between i-SC and Klatskin tumor. Differences between i-SC and IgG4-SC associated with autoimmune pancreatitis (AIP-SC) were also studied. Methods Differentiating factors between i-SC and Klatskin tumor were studied. Serum IgG4 level, CA19-9 level, computed tomography (CT) findings, cholangiography findings (symmetrical smooth long stricture extending into the upper bile duct [SSLS]), endosonographic features (continuous symmetrical mucosal lesion to the hilar part [CSML]), endoscopic biopsy results, treatment, relapse, and survival were also compared between patients with i-SC and those with AIP-SC. Results For a differential diagnosis between i-SC (N = 9) and Klatskin tumor (N = 47), the cut-off value of serum IgG4 level was 150 mg/dL (sensitivity, 0.857, specificity, 0.966). Logistic regression analysis indicated that serum IgG4 level, presence of SSLS, presence of CSML, and presence of swollen ampulla are independent factor for identifying i-SC. Relapse rate was significantly higher in the IgG4-SC with AIP group than in the i-SC group (log rank, P = 0.046). Conclusion Isolated proximal-type sclerosing cholangitis presents as a nodular lesion with SSLS and/or CSML mimicking a Klatskin tumor. Those endoscopic features might provide a diagnostic clue for i-SC. i-SC is likely to have a more favorable prognosis than IgG4-SC with AIP.

BACKGROUND/PURPOSE The relationship between autoimmune pancreatitis (AIP) and malignancy has been reported. However, the potential risk for cancer in patients with immunoglobulin 4 (IgG4)-related sclerosing cholangitis (IgG4-SC) is unclear. The present study aimed to evaluate the incidence of cancer in IgG4-SC patients. METHODS We retrospectively collected clinical data for 121 patients diagnosed with IgG4-SC from 7 hospitals. We calculated the standardized incidence ratio (SIR) of cancer in IgG4-SC patients based on the national cancer rates. The SIR of the period after the diagnosis of IgG4-SC were calculated. RESULTS The mean follow-up period was 6.4 years, with 121 IgG4-SC patients. During the follow-up period, 26 patients had cancer, and 29 cancers were diagnosed. The SIR of cancer after the diagnosis of IgG4-SC was 1.90 (95% confidence interval [CI] 1.67-2.21). The SIR of pancreatic and bile duct cancer was 10.30 and 8.88, respectively. The SIR of cancer in 5 years after diagnosis of IgG4-SC were 2.58, 1.01, and 2.44, respectively. CONCLUSIONS IgG4-SC patients have a high risk of cancer including pancreatic and bile duct cancer. The risk of cancer was high less 5 years after diagnosis of IgG4-SC. Therefore, IgG4-SC patients may require careful long-term follow-up.

Familial pancreatic cancer (FPC) is broadly defined as two first-degree-relatives with pancreatic cancer (PC) and accounts for 4%-10% of PC. Several genetic syndromes, including Peutz-Jeghers syndrome, hereditary pancreatitis, hereditary breast-ovarian cancer syndrome (HBOC), Lynch syndrome, and familial adenomatous polyposis (FAP), also have increased risks of PC, but the narrowest definition of FPC excludes these known syndromes. When compared with other familial tumors, proven genetic alterations are limited to a small proportion (< 20%) and the familial aggregation is usually modest. However, an ethnic deviation (Ashkenazi Jewish > Caucasian) and a younger onset are common also in FPC. In European countries, “anticipation” is reported in FPC families, as with other hereditary syndromes; a trend toward younger age and worse prognosis is recognized in the late years. The resected pancreases of FPC kindred often show multiple pancreatic intraepithelial neoplasia (PanIN) foci, with various K-ras mutations, similar to colorectal polyposis seen in the FAP patients. As with HBOC patients, a patient who is a BRCA mutation carrier with unresectable pancreatic cancer (accounting for 0%-19% of FPC patients) demonstrated better outcome following platinum and Poly (ADP-ribose) polymerase inhibitor treatment. Western countries have established FPC registries since the 1990s and several surveillance projects for high-risk individuals are now ongoing to detect early PCs. Improvement in lifestyle habits, including non-smoking, is recommended for individuals at risk. In Japan, the FPC study group was initiated in 2013 and the Japanese FPC registry was established in 2014 by the Japan Pancreas Society.

Background: Gastrointestinal endoscopy (GIE) is useful for the early detection and treatment of many diseases; however, GIE is considered a high-risk procedure in the coronavirus disease 2019 (COVID-19) pandemic era. This study aimed to explore the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity in saliva and gastric and intestinal fluids to which endoscopy medical staff are exposed. Methods: The study was a single-center cross-sectional study. From June 1 to July 31, 2020, all patients who underwent GIE at Yokohama City University Hospital endoscopy center were registered. All patients provided 3 ml of saliva. For upper GIE, 10 ml of gastric fluid was collected through the endoscope. For lower GIE, 10 ml of intestinal fluid was collected through the endoscope. The primary outcome was the positive rate of SARS-CoV-2 in saliva and gastric and intestinal fluids. We also analyzed serum-specific antibodies for SARS-CoV-2 and patients’ background information. Findings: A total of 783 samples (560 upper GIE and 223 lower GIE samples) were analyzed. Polymerase chain reaction (PCR) on saliva samples did not show any positive results in either upper or lower GIE samples. However, 2.0% (16/783) of gastrointestinal fluid samples tested positive for SARS-CoV-2. No significant differences in age, sex, purpose of endoscopy, medication, or rate of antibody test positivity were found between PCR positive and PCR negative cases. Interpretation: Asymptomatic patients, even those with no detectable virus in their saliva, had SARS-CoV-2 in their gastrointestinal tract. Endoscopy medical staff should be aware of infection when performing procedures. Trial Registration: The study was registered in the University Hospital Medical Information Network Clinical Trials Registry as UMIN000040587. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of Interests: The authors declare that they have no conflicts of interests. Ethics Approval Statement: The institutional review board at YCU Hospital approved this prospective study on May 17, 2020 (approval number: B200500054). Written consent for participation in the study was obtained from all patients.

BACKGROUND AND AIM The usefulness of preventive closure of the frenulum after endoscopic papillectomy (EP) could reduce bleeding. The feasibility and safety of clipping were evaluated in this prospective pilot study. METHODS This study involved 40 consecutive patients who underwent preventive closure of the frenulum by clipping just after EP. The outcome data were compared with those of the previous 40 patients in whom no preemptive closure had been performed (no-closure group) (UMIN000014783). Additionally, the bleeding sites were examined. RESULTS The clipping procedure was successful in all patients. As compared to the no-closure group, the rate of bleeding (P = 0.026) and period of hospital stay (P

Background/Aims. The “Resect and Discard” strategy is a potentially useful strategy. At present, only the lesion size and accuracy of diagnosis are cited as considerations for clinical adoption of this strategy. On the other hand, histopathology of the resected specimens after Endoscopic Mucosal Resection (EMR) reveals often an unclear or positive-margin status, implying Incomplete Polyp Resection (IPR). If IPR indeed increased the risk of local recurrence, histopathological evaluation of the margin would be indispensable and clinical adoption of this strategy is difficult. The aim of this study is to verify the association between IPR and the risk of local recurrence. Methods. The 1872 polyps and 603 EMR cases in 597 patients who had EMR between May 2013 and May 2014 were enrolled. The local recurrence rate until 3 years after the EMR in cases with the target lesions of the “Resect and Discard” strategy was determined in the negative-margin and IPR groups. Results. The final analysis was performed using the data of 1092 polyps, and 222 were categorized into the IPR group. There were no cases of recurrence in either of the groups. Conclusion. This is the world’s first report conducted to examine the correlation of IPR and the local recurrence rate for clinical practice of “Resect and Discard” strategy. There is the possibility that pathological evaluation of the margins after EMR in patients with small polyps can be skipped.

Indeterminant hilar biliary strictures (IHB) such as IgG4-related sclerosing cholangitis (IgG4-SC) and Klatskin tumor are leading causes and needed to differentiate from each other. Majority of IgG4-SC can be diagnosed without difficulty according to the JHBPS criterion 2012 [1] based on Nakazawa classification [2]. IgG4-SC patients are often associated with other organ involvements such as the pancreas (AIP), major salivary grounds, and/or retroperitoneal organs [1]. IgG4-SC can be divided into two types: the major is IgG4-SC associated with AIP (AIP-SC), and the minor is isolated IgG4-SC (i-SC). Moreover, i-SC consists of intrahepatic/hilar type (proximal, i-SC) and intrapancreatic type, and the characteristic features were still unknown. Proximal-type IgG4-SC, especially Klatskin tumor mimicker, should be excluded because it could be controlled by steroid treatment; besides, Klatskin tumor would be treated by radical surgery or poor prognosis after conservative treatment [3]. Most proximal-type IgG4-SC are associated with AIP; on the other hand, i-SC is cumbersome to rule out cancer. Some proximal IgG4-SC developed as recurrence after remission of AIP. IgG4-SC affects deep lesion of mucosa beyond the epithelium with abundant IgG4-positive lymphoplasma cell infiltration with lateral lesion; besides, Klatskin tumor invades through the mucosa sometimes associated with skip lesion (Fig. 13.1). As endoscopic biopsy tried to detect cancer in the diagnosis of IgG4-SC, it could not evaluate and diagnose IgG4-SC because true lesion is located further in the deep lesion, in which biopsy could not reach the lesion under the mucosa [4]. Steroid trial would be a better option under the situation [1]. This article showed the tips on how to differentiate indeterminant strictures; IgG4-SC and Klastkin tumor in especially on the view point of imaging diagnosis and supplement role of steroid trial.

Objective Some patients with malignant gastric outlet obstruction require combined biliary and gastroduodenal stenting (double stenting). However, biliary stent dysfunction can often disturb biliary route maintenance, thus making the optimal biliary stenting for these patients unclear. The present study was designed to assess the factors associated with the long-term maintenance of biliary drainage routes. Methods The clinical features and long-term outcomes were assessed in patients who underwent double stenting. Patients The outcomes were reviewed in 43 consecutive patients who successfully underwent endoscopic double stenting with metallic stents. Results An univariate analysis of all patients with biliary stent dysfunction showed the separate type of double stenting (two stents placed in a non-crossed position) to be the only predictive factor related to successful biliary re-intervention for stent dysfunction (odds ratio 73.67, p=0.001). A comparison of the clinical features in patients who underwent separate and cross (two stents placed in a crossed position) stenting showed the functional success rate to be higher for the separate (93.3%) than for the cross (61.5%) stent type, with the median times to biliary stent dysfunction differing significantly (330 vs. 298 days, respectively; p=0.048). The success rates of re-intervention in patients with separate and cross type stents were 88.9% and 0.0%, respectively (p=0.001), and the initial biliary route maintenance rates were 96.7% and 53.8%, respectively (p=0.002). Conclusion The separate type of double stenting may enhance successful biliary re-intervention for stent dysfunction and also maintain the initial drainage route longer. The biliary drainage outcomes should therefore be considered when choosing the type of double stenting.

Background The association of diverticula with bowel habits is unclear. We therefore analyzed the association between diverticula and bowel habits in over 1000 Japanese individuals. Methods Japanese subjects who underwent total colonoscopies at seven centers in Japan from June to September 2013 were analyzed. Bowel habits were evaluated using the Gastrointestinal Symptom Rating Scale, and stool form was assessed using a part of the Bristol Scale and Rome ΙΙΙ criteria. Diverticula were diagnosed by colonoscopy with a transparent soft-short hood. Key Results The study evaluated 1066 subjects, 648 males and 418 females (ratio, 1.55 : 1), of mean age 63.9 ± 13.0 years. After adjusting for age and sex, the presence of constipation was associated with a significantly reduced likelihood of diverticula (odds ratio [OR] = 0.70, 95% confidence interval [CI] 0.52–0.93). When assessed according to the location of diverticula, the presence of constipation was associated with a significantly decreased likelihood of left-sided (OR = 0.39, 95% CI 0.16–0.93), but not right-sided (OR = 1.10, 95% CI 0.48–2.53), diverticula. Furthermore, stool form was unrelated with the presence or absence of diverticula. Conclusions & Inferences The wide-spread hypothesis that constipation was associated with colonic diverticula was not supported. Rather, we found that the absence of diverticula was associated with constipation, suggesting the need to reassess the etiology of colonic diverticula.

Background and Aim Self-expandable metallic stents have mainly been used for the palliation of malignant gastric outlet obstruction (GOO). However, their use in long-term survivors and the feasibility, safety and benefit of additional intervention for stent dysfunction remain controversial. The present study examined the long-term benefits of endoscopic gastroduodenal stenting. Methods We reviewed 61 patients treated with Niti-S stents at several hospitals and estimated the efficacy of stent intervention, stent patency, eating period and factors related to poor effectiveness. Results All 61 first stent interventions and 14 additional stent interventions (11 second interventions and 3 third interventions) were successfully carried out. Clinical success rates were 83.6% and 85.7%, and median stent patency was 214 days and 146 days (P = 0.47), respectively. Fifty patients could be treated with a first stent only, and 11 patients received additional stents. At the time of study termination or death, 70.0% of the former group and 63.6% of the latter group maintained oral intake (P = 0.71), and each 86% and 100% among the group could maintain oral intake for a period exceeding half of their remaining lives after first stent intervention. Karnofsky performance status ≤50 (P = 0.03), ascites (P = 0.009), and peritoneal dissemination (P = 0.001) appeared to be factors related to poor effectiveness. Conclusions Despite the presence of factors related to poor effectiveness, endoscopic gastroduodenal stenting would be the first treatment of choice for GOO and provide long-term benefits. If stent dysfunction occurs, additional stent intervention enables continued oral intake safely.

Pancreatic cancer is a lethal disease. Overall survival is typically 6 months from diagnosis. Determination of prognostic factors in pancreatic cancer that would allow identification of patients who could potentially benefit from aggressive treatment is important. However, until date, there are no established reliable prognostic factors for pancreatic cancer patients. Herein, we propose a beneficial biomarker which is significantly correlated with the prognosis in pancreatic cancer patients. Atypical protein kinase C λ/ι (aPKCλ/ι) is overexpressed and has been implicated in the progression of several cancers. We tested the expression levels of aPKCλ/ι in two types of pancreatic neoplasm, pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs), by immunohistochemistry. Examination of the aPKCλ/ι expression levels in surgically resected specimens of PDCA (n = 115) demonstrated that the expression levels of aPKCλ/ιin PDAC had prognostic implications, independent of the Tumor-Node-Metastasis classification and World Health Organization tumor grade. In the case of IPMNs (n = 46) also, the expression levels of aPKCλ/ιin IPMN were found to be of prognostic importance, independent of the World Health Organization histological grade or morphological type. Interestingly, high expression levels of aPKCλ/ι were significantly correlated with a worse histological grade (p = 0.010) and advanced stage of the tumor (p = 0.0050) in IPMN patients. These findings suggest that high expression levels of aPKCλ/ι could be involved in the malignant transformation of IPMNs. Based on these observations, we propose the expression level of aPKCλ/ι as a prognostic marker common to different types of pancreatic neoplasms.

Ampullary early stage cancer (early CA) potentially harbors lymphovascular invasion; there are few data on markers that could differentiate adenoma and early CA. To investigate those markers, we compared the tumor diameter and Ki-67 expression in endoscopy biopsy specimens of adenoma with those of early CA. Patients on whom endoscopic papillectomy (EP) was performed (n = 35) with histopathologically proven adenomas and with low/high grade dysplasia and early CA were studied. We made pre-procedure evaluations of ampullary tumors by using endoscopic ultrasonography (EUS) and transpapillary intraductal ultrasonography. Tumor diameter was measured by EUS. Endoscopic biopsy using immunostaining of Ki-67 labeling index (LI) prior to EP were evaluated. The areas under the receiver-operating characteristic (AUROC) curves for tumor diameter and Ki-67 expression were 0.824 and 0.873, respectively. Cut-off values calculated based on AUROC data were 15 mm in tumor diameter and 32 cells/high-power field (HPF) in Ki-67. Early CA (n = 11) was diagnosed by using a cut-off value for tumor diameter in 8 out of 11 patients (sensitivity 72.7 %, specificity 66.7 %, accuracy 68.6 %). Significant infiltration of the major duodenal papilla by Ki-67 positive tumor cells (>31/HPF) was recognized in 8 of the 11 patients with early CA (sensitivity 100 %, specificity 54.2 %, accuracy 62.9 %). Observation of tumor diameter and Ki-67 LI would be helpful for safety EP. EP should not be indicated for ampullary tumors more than 15 mm in diameter and/or Ki-67 LI 31/HPF.

Background and aims The barrier function of the small intestinal mucosa prevents the introduction of undesired pathogens into the body. Breakdown of this barrier function increases intestinal permeability. This has been proposed to induce not only gastrointestinal diseases, including inflammatory bowel disease and irritable bowel syndrome, but also various other diseases, including allergies, diabetes mellitus, liver diseases, and collagen diseases, which are associated with this so called "leaky gut syndrome." As such, a method to prevent leaky gut syndrome would have substantial clinical value. However, no drugs have been demonstrated to improve disturbed intestinal permeability in humans to date. Therefore, we investigated whether a drug used to treat chronic constipation, lubiprostone, was effective for this purpose. Methods Healthy male volunteers were treated with lubiprostone (24 μg/day) for 28 days. Intestinal permeability was evaluated by measuring the lactulose-mannitol ratio (LMR) after administration of diclofenac and compared with an untreated group. The examination was conducted three times in total, i.e., at baseline before diclofenac administration and after 14 and 28 days of lubiprostone treatment. Blood endotoxin activity was also evaluated at the same time points. Results The final analysis was conducted on 28 subjects (14 in the lubiprostone group and 14 in the untreated group). The LMR after 28 days of treatment was significantly lower in the lubiprostone group than that in the untreated group (0.017 vs. 0.028, respectively; 95% confidence interval, -0.022--0.0001; p = 0.049). Blood endotoxin activity exhibited almost no change over time in the lubiprostone and untreated groups and displayed no significant differences at any time point of examination. Conclusions This study is the first to report an improvement in leaky gut using an available drug in humans. The result suggests that lubiprostone may prevent and ameliorate "leaky gut syndrome". However, a pivotal trial is needed to confirm our finding.

Successful precut sphincterotomy (PS) in difficult biliary cannulation (DBC) requires a large incision for deroofing the papilla. However, the high complication rate poses a substantial problem, in addition to the need for expert skills. Pancreatic stent placement could facilitate this procedure. Needle-knife precut papillotomy with a small incision using a layer-by-layer method over a pancreatic stent (NKPP-SIPS) could potentially improve the success rate and reduce the complication rate of PS. To validate the efficacy, feasibility and safety of NKPP-SIPS in DBC. Therapeutic endoscopic retrograde cholangiopancreatography with a naive papilla was performed in 1619 cases between May 2004 and July 2011. We prospectively divided the patients chronologically, in terms of the period during which the procedure was performed, into two groups: group A; needle-knife precut papillotomy (NKPP) performed between April 2004 and October 2006; group B; NKPP-SIPS performed between November 2006 and July 2011. The success rates and complication rates were evaluated. NKPP was performed without pancreatic stent placement and the cut was made starting at the papillary orifice, extended upward over a length of more than 5–10 mm for deroofing the papilla. On the other hand, in NKPP-SIPS, a pancreatic stent was placed initially as a guide, and to prevent post-ERCP pancreatitis, the incision was begun at the papillary orifice in a layer-by-layer fashion and extended upward in 1–2 mm increments, not going beyond the oral protrusion, finally measuring less than 5 mm in length. PS was performed in 8.3 % of the patients (134/1619). The cannulation success rate of PS in the entire group was 94.0 % (126/134). NKPP and NKPP-SIPS were performed in 36 and 98 of the patients, respectively. There was one case of major bleeding in group A, and no severe complications in group B. The success rates of bile duct cannulation increased from 86.1 % (31/36) in group A to 96.9 % (95/98) in group B (p = 0.0189). The overall complication rate of PS was YC 33 % (12/36) in group A (major bleeding 8.3 %; mild to moderate pancreatitis 19.4 %; perforation requiring surgery 2.8 %), and 7.1 % (7/98) in group B (mild to moderate pancreatitis 6.1 %; minor perforation 1 %) (p

Objectives The aim of this study was to characterize the pancreatic cystic lesions in von Hippel-Lindau (VHL) disease and to document the changes that occur in the pancreas. Methods We retrospectively analyzed the medical records and the computed tomography (CT) and magnetic resonance imaging (MRI) findings of 20 VHL patients who were diagnosed between 1996 and 2010 at our hospital. The clinical findings, family history and type of tumors and/or cysts were reviewed for each patient. We also analyzed the imaging findings for the pancreas in detail. Results Pancreatic involvement was noted in 16 of the 20 patients (80%). Eleven patients had multiple cysts diffusely distributed in the pancreas, and one patient had a single cyst in the pancreas head. Two patients had serous cystic neoplasms (SCNs) with multiple cysts, and another two patients had neuroendocrine tumors (NETs) which were conventional radiological findings. The largest cysts of four patients (26.7%) increased in size and that of three patients (20%) decreased in size during the follow-up period. We performed surgical resections for the pancreatic tumors (one NET and one SCN) and also performed endoscopic treatment for a pancreatic cyst in one VHL patient with obstructive jaundice. None of the patients died as a result of pancreatic disease. Conclusion The most common type of pancreatic lesions was multiple cysts. SCNs were present in only 10% of the VHL patients. Pancreatic cysts showed positive and/or negative growth according to the CT and MRI findings. The pancreatic cystic lesions did not influence the outcome of the VHL patients.

Hemerocallis esculenta suffered frost damage during a night of remarkably low temperatures at Sarobetsu Mire, northern Japan, on 5 June 2002. A numerical model simulation was conducted to evaluate how groundwater conditions affected the nocturnal air temperature at the mire. The numerical model developed in this study reproduced the nighttime cooling process of the air temperature profile at high resolution. The lowest water table level occurred at the site several days before 5 June. The numerical simulation suggested that if the lowest water table occurred on 5 June, under the same water table level, the minimum air temperature 0.2 m above the peat surface would have been 1.2°C higher because of the difference of volumetric water content. The rate of air temperature decrease at 0.2 m height to the water table decrease would be 0.7°C cm−1. Therefore, the minimum air temperature near the peat surface of the mire is affected by both decreases in the water table level and the lowest depth prior to the observation day. Ensuring a high water table level could mitigate extreme low temperatures and frost damage at the mire.

Background and study aims: Neoadjuvant chemotherapy (NAC) may lead to a successful margin-negative resection in patients with initially unresectable locally advanced Klatskin tumor (IULAKT). Use of removable plastic stents is preferable for the safe implementation of NAC in patients with IULAKT to reduce the risk of recurrent cholangitis. Our aim was to evaluate the efficacy associated with the use of plastic stents placed across the stenosis and above the papilla (above stent) during NAC. Patients and methods: In this study, we stratified the patients into two groups chronologically with respect to the period of stent placement: above stent group (n = 17) and across stent group (n = 23) (plastic stent across the sphincter of Oddi). Results: The median stent patency period was 99 days in the above stent group and 31 days in the across stent group (P

The modified Glasgow prognostic score (mGPS) is known to be useful in determining the prognosis of cancers. However, the utility of mGPS for pancreatic cancer (PC) has been examined based primarily on a surgical series of early-stage cancers. The purpose of this study was to examine the utility of mGPS for PC of all stages using a retrospective cohort design.We conducted a retrospective cohort study using data from a computerized database. A total of 807 patients with pathologically confirmed PC were analyzed (mGPS-0, n = 620; mGPS-1, n = 153; mGPS-2, n = 34).Median overall survival (OS) was significantly worse for the mGPS-1 group than for the mGPS-0 group (5.8 vs 15.8 months, respectively) but was comparable between the mGPS-2 and mGPS-1 groups (4.8 vs 5.8 months, respectively). After adjustment, both mGPS-1 and mGPS-2 were independent predictive factors of OS (mGPS-1: hazard ratio, 1.772; 95% confidence interval, 1.417-2.215; mGPS-2: hazard ratio, 2.033; 95% confidence interval, 1.284-3.219). Subgroup analysis showed that OS was significantly worse in the mGPS-1 and mGPS-2 groups than in the mGPS-0 group for all except the following 2 subgroups: localized disease and curative resection.The present results show that the mGPS is an independent prognostic factor in patients with PC, especially for advanced-stage disease.

Recently there has been a marked increase in wind power generation. From a power system point of view, because a wind turbine is an intermittent generator with large output fluctuation, any increase in the number of wind turbines gives rise to concerns about the adverse effects of wind turbines on power quality. The smoothing effects of wind turbine output fluctuation are of great importance in assessing the impacts of a large number of wind turbines. With regard to impacts on power system frequency (generation‐demand balance), smoothing effects on a power system-wide scale need to be examined in greater detail, because impacts of wind turbines on power system frequency are dominated by the total power output of wind turbines interconnected to the system. This article examines smoothing effects of wind power output on a power system-wide scale. First a summary of wind measurements, in which observations were made at 16 sites, is presented. Next, correlation coefficients of wind power output of distant wind turbines are analysed; considerable differences are observed in the correlation coefficients from day to day. Then a new indicator for assessing the smoothing effects—average coherence—is introduced to resolve difficulties of conventional indicators such as coherence. Average coherence is evaluated for the measured data; the results show that smoothing effects among wind farms distributed over some hundreds of kilometres may not be so significant for periods of more than about 100 min. Copyright © 2004 John Wiley & Sons, Ltd.

Recently there has been a marked increase in wind power generation. From a power system point of view, because a wind turbine is an intermittent generator with large output fluctuation, any increase in the number of wind turbines gives rise to concerns about the adverse effects of wind turbines on power quality. The smoothing effects of wind turbine output fluctuation are of great importance in assessing the impacts of a large number of wind turbines. This article examines smoothing effects at a wind farm. First it presents a summary of wind measurements taken at two locations with six masts over a period of 1 year on both flat and complex terrain. Then the spatial coherence of wind speed is analysed, paying special attention to its dependence on the distance between observation points, wind direction, wind velocity and fluctuation frequency. Approximation equations for coherence of frequency and distance are obtained by applying Davenport's expression to the observed data. Second, coherence between turbine output at a wind farm is investigated; the results indicate that coherence for wind speed and turbine output shows a considerable resemblance. The article also examines smoothing effects at a wind farm using power spectral density through a theoretical approach. The study proves that smoothing effects can be approximated with a lowpass filter and that the effects at a wind farm should not be taken into account for periods of more than 10 min in case of assessing them on the safe side. Copyright © 2004 John Wiley & Sons, Ltd.