Computed diffusion-weighted magnetic resonance imaging with high b-values in the diagnosis of gallbladder lesions.

PURPOSE: The diagnosis of gallbladder lesions remains challenging. The efficacy of computed diffusion-weighted imaging (DWI) with high b-values and apparent diffusion coefficient (ADC) for the diagnosis of gallbladder cancer remains unknown. We aimed to investigate the usefulness of computed DWI with high b-values and the combination of computed DWI and ADC in differentiating malignant and benign gallbladder lesions. METHODS: Sixty patients (comprising 30 malignant and 30 benign lesions) who underwent magnetic resonance imaging for gallbladder lesions were included in this retrospective study. Qualitative evaluations were performed using conventional DWI with b1000, computed DWI with b1500, b1000 DWI/ADC, and computed b1500 DWI/ADC, and their diagnostic performances were compared. RESULTS: The sensitivity, specificity, and accuracy of computed b1500 DWI/ADC were 90% (27/30), 80% (24/30), and 85% (51/60), respectively. The accuracy of computed b1500 DWI/ADC was higher than that of conventional b1000 DWI (52%, 31/60, p < 0.001), computed b1500 DWI (72%, 43/60, p = 0.008), and b1000 DWI/ADC (78%, 47/60, p = 0.125). The specificity of computed b1500 DWI/ADC was also higher than that of conventional b1000 DWI (7%, 2/30, p < 0.001), computed b1500 DWI (47%, 14/30, p = 0.002), and b1000 DWI/ADC (67%, 20/30, p = 0.125). No significant difference was observed in the sensitivity between the groups. CONCLUSION: This study shows that computed DWI with high b-values combined with ADC can improve diagnostic performance when differentiating malignant and benign gallbladder lesions. Computed diffusion-weighted magnetic resonance imaging with high b-values in the diagnosis of gallbladder lesions. *Computed DWI with b1500 combined with ADC can improve diagnostic performance when differentiating gallbladder lesions compared with conventional methods (b1000 DWI).

IgG4-related sclerosing cholangitis may be a risk factor for cancer.

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 <1 year, 1-5 years, and >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 <1 year and >5 years after diagnosis of IgG4-SC. Therefore, IgG4-SC patients may require careful long-term follow-up.

Effect of preventive closure of the frenulum after endoscopic papillectomy: A prospective pilot study.

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 < 0.001) were significantly reduced in the closure group. There was no difference in the procedure time between the two groups. Furthermore, the incidence rates of pancreatitis and perforation were comparable in the two groups. The bleeding was noted in the frenulum area rather than at any other site in 90.9% of cases. CONCLUSION: Preventive closure of the frenulum after EP is an effective, safe, rational, and economical method to reduce the incidence of delayed bleeding, without prolonging the procedure time or increasing the risk of post-procedure pancreatitis perforation.

Clinical features of isolated proximal-type immunoglobulin G4-related sclerosing cholangitis.

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.

Associations of Mental Health and Physical Function with Colonoscopy-related Pain.

Objective To clarify the effects of mental health and physical function in association with colonoscopy-related pain. Methods The mental health and physical function were evaluated using the Japanese version of the SF-8 Health Survey questionnaire. Poor physical status was defined as a physical component summary (PCS) <40 and poor mental status as a mental component summary (MCS) <40. Pain was assessed using a visual analogue scale (VAS), with significant pain defined as VAS ≥70 mm and insignificant pain as VAS <70 mm. The background and colonoscopic findings were compared in patients with significant and insignificant pain. Patients This study evaluated consecutive Japanese patients who were positive on fecal occult blood tests and underwent total colonoscopy. Results Of the 100 patients, 23 had significant and 77 had insignificant colonoscopy-related pain. A multiple logistic regression analysis showed that MCS <40 [odds ratio (OR) 6.03; 95% confidence interval (CI) 1.41-25.9, p=0.0156], PCS <40 (OR 5.96; 95% CI 1.45-24.5, p=0.0133), and ≥300 seconds to reach the cecum (OR 4.13; 95% CI 1.16-14.7, p=0.0281) were independent risk factors for colonoscopy-related pain. Conclusion The mental health and physical function are important determinants of colonoscopy-related pain. Evaluating the mental health and physical function of patients prior to colonoscopy may effectively predict the degree of colonoscopy-related pain.

Factors associated with poor therapeutic response in outpatients with irritable bowel syndrome: a multicenter study in Japan.

BACKGROUND: Some patients with irritable bowel syndrome (IBS) show poor response to treatment. However, risk factors associated with poor therapeutic response have not been determined. METHODS: This multicenter trial evaluated consecutive outpatients with IBS undergoing treatment for more than 1 month. Mental health status and physical function were evaluated using the Japanese version of the SF-8. Therapeutic response was evaluated using the IBS severity index-Japanese version (IBS-SIJ). Patients with IBS-SIJ scores ≥175 were defined as poor responders to treatment, whereas those with IBS-SIJ scores <175 were defined as good responders. The demographic and clinical characteristics of these two groups, along with medications, were compared. RESULTS: The study enrolled 131 participants, 75 with IBS-SIJ scores ≥175-56 with IBS-SIJ scores <175. Multiple logistic regression analysis showed that female sex [odds ratio (OR) 2.67, 95 % confidence interval (CI) 1.19-5.97, p = 0.0167] and mental component summary (MCS) of the SF-8 <40 (OR 2.58, 95 % CI 1.12-5.97, p = 0.0263) were independent risk factors for poor therapeutic response in patients with IBS. CONCLUSIONS: Lower MCS and female sex were risk factors for poor therapeutic response in patients with IBS. Ascertaining the mechanisms by which lower MCS and female sex are associated with poor therapeutic response in IBS may help design better treatments (Trial registration number: UMIN000016804).

Endoscopic inside stent placement is suitable as a bridging treatment for preoperative biliary tract cancer.

BACKGROUND: Endoscopic biliary stenting (EBS) is one of the most important palliative treatments for biliary tract cancer. However, reflux cholangitis arising from bacterial adherence to the inner wall of the stent must be avoided. We evaluated the use of EBS above the sphincter of Oddi to determine whether reflux cholangitis could be prevented in preoperative cases. METHODS: Fifty-seven patients with primary biliary tract cancer were retrospectively recruited for the evaluation of stent placement either above (n = 25; inside stent group) or across (n = 32; conventional stent group) the sphincter of Oddi. We compared the stent patency periods prior to the time of surgical resection. RESULTS: The preoperative periods were 96.3 days in the conventional stent group and 96.8 days in the inside stent group (P = 0.979). Obstructive jaundice and/or acute cholangitis occurred in 7 patients (28.0%) in the inside stent group and in 15 patients (46.9%) in the conventional stent group during the preoperative period (P = 0.150). The average patency periods of the stents were 85.2 days (range, 13-387 days) for the inside stent group and 49.1 days (range, 9-136 days) for the conventional stent group (log-rank test: P = 0.009). The mean numbers of re-interventions because of stent occlusion were 0.32 for the inside stent group and 1.03 for the conventional stent group (P = 0.026). Post-endoscopic retrograde cholangiopancreatography complications occurred in 2 patients in the inside stent group and 4 patients in the conventional stent group (P = 0.516). Postoperative liver abscess occurred in 1 patient in the inside stent group and 5 patients in the conventional stent group (P = 0.968). Inside stent placement was the only significant preventative factor associated with stent obstruction based on univariate (hazard ratio [HR], 0.286; 95% confidence interval [CI], 0.114-0.719; P = 0.008) and multivariate (HR, 0.292; 95% CI, 0.114-0.750; P = 0.011) analyses. CONCLUSION: Temporary plastic stent placement above the sphincter of Oddi is a better bridging treatment than conventional stent placement in preoperative primary biliary tract cancer.

Endoscopic treatment of postoperative benign bile duct stricture compared with malignant bile duct stricture.

BACKGROUND/AIMS: Endoscopic treatment for postoperative benign bile duct stricture (BBS) is a therapeutic challenge. No previous studies have compared endoscopic treatments for BBS and malignant bile duct stricture (MBS). The aim of this study was to compare endoscopic treatments for postoperative BBS and MBS. METHODOLOGY: This study enrolled 22 consecutive patients with a diagnosis of postoperative BBS and 110 patients diagnosed with MBS. Cases involving digestive tract reconstruction were excluded. We compared the length of the bile duct strictures, the success rate of endoscopic treatment, and the incidence of complications. RESULTS: The following results were obtained for the postoperative BBS and MBS groups, respectively: length of bile duct stricture, 6.50 mm vs. 24.3 mm (P<0.0001); success rate of endoscopic treatment, 90.9% vs. 93.6% (P=0.6551). Post-ERCP pancreatitis occurred after 11 sessions (10.7%) vs. 7 sessions (1.83%) (P=0.0002), and post-ERCP cholangitis occurred after 7 sessions (6.80%) vs. 4 sessions (1.04%) (P=0.0021). BBS was a significant risk factor for post-ERCP pancreatitis and cholangitis based on a multivariate analysis (OR, 10.732; P=0.0022; OR, 6.443; P=0.0260). CONCLUSIONS: Post-ERCP-related complications were more frequent after postoperative BBS than after MBS. The need for careful endoscopic treatment may be greater for postoperative BBS cases than for MBS cases.

Covered self-expandable metal stent deployment promises safe neoadjuvant chemoradiation therapy in patients with borderline resectable pancreatic head cancer.

BACKGROUND: Patients with borderline resectable pancreatic head cancer (BRPHC) have been treated with neoadjuvant chemoradiation therapy (NACRT) using metallic stents. The aim of the present study was to evaluate the efficacy and complications of covered self-expanding metallic stents (CSEMS) during the NACRT and surgical period. PATIENTS AND METHODS: We reviewed the outcomes of patients with BRPHC, then divided them chronologically into three groups as follows. Group A: upfront surgery with plastic stent (PS) deployment; group B: PS deployment plus neoadjuvant chemotherapy (NAC) and/or NACRT; group C: CSEMS deployment plus NAC/NACRT. Patients were categorized as borderline resectable based on National Comprehensive Cancer Network Guidelines, 2010. Days to reintervention (DR), reintervention rate, and the rate of R0 and complications were studied. Safe margin-negative resection (R0) surgery was defined as R0 surgery without reintervention during the NACRT period and no postoperative complications. RESULTS: DR were as follows. Groups A, B and C were 32, 55 and 97 days, respectively (P < 0.05). R0 surgery obtained in groups A, B and C was 53% (9/17), 100% (17/17) and 93% (14/15), respectively. CSEMS did not interfere with surgery. Safe R0 surgery obtained in groups B and C was 11% (2/19) and 67% (10/15), respectively (P < 0.05). Multivariate analysis showed that the odds ratio for safe R0 surgery was 16.210 (95% CI 2.457-106.962, P = 0.003) for CSEMS placement. CONCLUSION: CSEMS should be considered to relieve symptomatic biliary obstruction in patients with BRPHC receiving NACRT in view of the high attainability rate of safe R0 surgery compared to that with PS deployment.

Positioning of nasobiliary tube using magnet-loaded catheters.

BACKGROUND AND STUDY AIMS: In endoscopic nasobiliary drainage (ENBD), repositioning the catheter from the mouth to the nose is complicated. We devised a method using catheters with magnets and verified its utility and safety. PATIENTS AND METHODS: We prospectively enrolled 20 patients undergoing ENBD at Yokohama City University Hospital. RESULTS: The procedures were successful in all 20 cases and no case required a change of operators to a senior doctor. The mean time for the procedure was 36.6 seconds. The emetic reflex was induced 0.5 times on average using the magnet method. The mean X-ray exposure time was 29.6 seconds. No complications occurred. CONCLUSIONS: The magnet-loaded catheter method for positioning the ENBD catheter before finally leading it through the nose took little time and was performed successfully and safely. Therefore, the magnet method could become the first choice among techniques for ENBD catheter placement.

aPKCλ/ι is a beneficial prognostic marker for pancreatic neoplasms.

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.

Postpyloric decompression tube placement through a gastrostomy for malignant bowel obstruction.

BACKGROUND: Malignant bowel obstruction affect a patient's quality of life, but, management of MBO is controversial. CASE PRESENTATION: A 51-year-old woman who had been diagnosed as uterine cervix cancer 2 years ago and had undergone surgery, chemotherapy and radiotherapy, was admitted to our hospital. She was diagnosed as having a recurrence of peritoneal metastasis and bowel obstruction. For her nasal pain, we considered insertion of a postpyloric decompression tube through the gastrostomy instead of via the nasal cavity. After insertion of a percutaneous gastrostomy tube was performed endoscopically, we introduced a postpyloric decompression tube through her gastrostomy. She could be discharged home, and 91 days later, she died in her home under hospice care, as she had wished. CONCLUSIONS: Insertion of a postpyloric decompression tube through a gastrostomy might be useful in the management of advanced cancer patients with bowel obstruction.

A novel scoring system for arterial invasion of pancreatic body and tail cancer based on multidetector row computed tomography and biomarkers.

BACKGROUND/OBJECTIVES: The absence of major-vessel involvement is a crucial factor in the resectability and prognosis of pancreatic cancer. However, arterial invasion cannot be evaluated adequately using imaging findings alone. We therefore developed a scoring system to assess arterial invasion by pancreatic adenocarcinoma using multidetector row computed tomography (MDCT) and serum tumor markers. METHODS: Twenty patients who underwent distal pancreatectomy and splenectomy for pancreatic adenocarcinoma were examined retrospectively using 4-, 16- or 64-row MDCT and serum tumor markers. Splenic arterial invasion was evaluated in terms of length of tumor contact, circumferential involvement (<180° or ≥180°) and deformity of vascular diameter. Preoperative expression of carbohydrate antigen 19-9 (CA19-9), DUPAN-2 and S-Pancreas-1 antigen (SPan-1) were also evaluated. The presence or absence of arterial invasion was confirmed histopathologically in all 20 cases. RESULTS: In 11 of 20 cases invasion into splenic arteries was observed histopathologically, mostly involving the external elastic lamina and periarterial nerves. Sensitivity, specificity and accuracy were 100%, 88.9% and 95%, respectively, for length of tumor contact (<16 mm or ≥16 mm), 90.9%, 77.8% and 85% for circumferential involvement (<180° or ≥180°), and 100%, 66.7% and 85% for deformity of vascular diameter. Furthermore, the sensitivity, specificity and accuracy were all increased to 100% when tumor markers were included in the score. CONCLUSIONS: MDCT is a useful technique for diagnosing arterial invasion of pancreatic body and tail cancer, even in comparison with pathological examination; however, this new scoring system can be further complemented and made more reliable by measurements of serous tumor markers.

Tumor diameter and Ki-67 expression in biopsy could be diagnostic markers discriminating from adenoma and early stage cancer in patients with ampullary tumors.

BACKGROUND: Ampullary early stage cancer (early CA) potentially harbors lymphovascular invasion; there are few data on markers that could differentiate adenoma and early CA. AIM: To investigate those markers, we compared the tumor diameter and Ki-67 expression in endoscopy biopsy specimens of adenoma with those of early CA. METHODS: 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. RESULTS: 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 %). CONCLUSIONS: 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.

Needle-knife precut papillotomy with a small incision over a pancreatic stent improves the success rate and reduces the complication rate in difficult biliary cannulations.

BACKGROUND: 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. AIMS: To validate the efficacy, feasibility and safety of NKPP-SIPS in DBC. METHODS: Therapeutic endoscopic retrograde cholangiopancreatography with a naïve 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. RESULTS: 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 < 0.001). CONCLUSIONS: NKPP-SIPS has significantly improved the success rate and reduced the complication rate of DBC, proving that a small incision starting at the orifice of the PS is sufficient, feasible and safe in DBC, when a pancreatic stent is inserted at the outset.

Imaging findings of pancreatic cystic lesions in von Hippel-Lindau disease.

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.

Risk factors for colonic diverticular hemorrhage: Japanese multicenter study.

BACKGROUND AND AIM: Diverticular hemorrhage is the common cause of lower gastrointestinal bleeding, and its incidence has been increasing in Japan. However, the exact cause of diverticular hemorrhage is not well understood. We investigated the risk factors for diverticular hemorrhage. METHODS: We selected 103 patients with diverticular hemorrhage as cases and patients with colonic diverticulosis without a history of bleeding were selected as control subjects, exactly matched for age and gender. We collected the data from the medical records of each of the patients, such as those related to the comorbidities, medications and findings of colonoscopy, and conducted a matched case-control study to analyze the risk factors for diverticular hemorrhage. RESULTS: Both groups were composed of 75 men and 28 women. The median age of the patients in both groups was 72.0 years (47.0-87.0). The body weight (p = 0.0065), body mass index (p = 0.006), prevalence of hypertension (p = 0.0242), prevalence of ischemic heart disease (p = 0.0015), and frequency of use of low-dose aspirin (p = 0.042) were significantly different between the two groups. The percentage of patients with bilateral diverticula, that is, diverticula on both the right and left hemicolon, was significantly higher in the diverticular hemorrhage group (p = 0.0011). Multiple regression analysis identified only the diverticular location as being significantly associated with the risk of diverticular hemorrhage (p = 0.0021). CONCLUSIONS: Only the diverticular location (bilateral) was found to be an independent risk factor for diverticular hemorrhage.

Endoscopic ultrasonographic findings predict the risk of carcinoma in branch duct intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND: The preoperative diagnosis of branch duct intraductal papillary mucinous neoplasm (IPMN) of the pancreas can be very difficult, since low-risk and high-risk lesions can be difficult to differentiate even after cytological analysis. The purpose of this study was to evaluate the preoperative diagnostic value of endoscopic ultrasonography (EUS) in differentiating low-risk and high-risk IPMNs. METHODS: We retrospectively identified 36 patients who underwent preoperative EUS for branch duct IPMNs. The pathological diagnosis after surgical resection was low-grade dysplasia (n = 26), moderate dysplasia (n = 1), high-grade dysplasia or carcinoma in situ (n = 5), and invasive carcinoma (n = 4). We divided the patients into two groups: low risk (low-grade dysplasia or moderate dysplasia) and high risk (high-grade dysplasia or carcinoma). We focused on the diameter of the cystic dilated branch duct, the main pancreatic duct, and the mural nodule as measured using the EUS findings. RESULTS: The cystic dilated branch duct diameter (31.5 mm vs. 41.9 mm, P = 0.0225) was significantly correlated with low-risk and high-risk IPMNs, but the main pancreatic duct diameter (5.37 mm vs. 5.44 mm, P = 0.9418) was not significantly correlated with the low-risk and high-risk IPMNs. The mural nodule diameter of the papillary protrusions (4.3 mm vs. 16.4 mm, P < 0.0001) and the width diameter of the mural nodule (5.7 mm vs. 23.2 mm, P < 0.0001) were significantly correlated with low-risk and high-risk IPMNs. CONCLUSIONS: The mural nodule of papillary protrusions diameter and width diameter observed using EUS was a reliable preoperative diagnostic finding capable of distinguishing low-risk and high-risk IPMNs.

Semaphorin 4D, a lymphocyte semaphorin, enhances tumor cell motility through binding its receptor, plexinB1, in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor, for which the development of new biomarkers and therapeutic targets has become critical. The main cause of poor prognosis in PDAC patients is the high invasive and metastatic potential of the cancer. In the present study, we report a new signaling pathway that was found to mediate the enhanced tumor cell motility in pancreatic cancer. Semaphorin 4D (Sema4D) is a ligand known to be expressed on different cell types, and has been reported to be involved in the regulation of immune functions, epithelial morphogenesis, and tumor growth and metastasis. In this study, we revealed for the first time that the cancer tissue cells expressing Sema4D in PDAC are tumor-infiltrating lymphocytes. The overexpression of Sema4D and of its receptor, plexinB1, was found to be significantly correlated with clinical factors, such as lymph node metastasis, distant metastasis, and poor prognosis in patients with PDAC. Through in vitro analysis, we demonstrated that Sema4D can potentiate the invasiveness of pancreatic cancer cells and we identified the downstream molecules. The binding of Sema4D to plexinB1 induced small GTPase Ras homolog gene family, member A activation and resulted in the phosphorylation of MAPK and Akt. In addition, in terms of potential therapeutic application, we clearly demonstrated that the enhanced-cell invasiveness induced by Sema4D could be inhibited by knockdown of plexinB1, suggesting that blockade of plexinB1 might diminish the invasive potential of pancreatic cancer cells. Our findings provide new insight into possible prognostic biomarkers and therapeutic targets in PDAC patients.