Search

Objectives The oncological outcomes, especially high recurrence rate, of bridge-to-surgery (BTS) self-expandable metallic stent (SEMS) placement remain concerning, emphasizing the necessity of standardized SEMS placement. However, its impact on long-term BTS outcomes is unknown. We investigated the long-term outcomes of BTS colonic stenting using standardized SEMS placement. Methods This prospective, multicenter cohort study conducted at 46 hospitals in Japan (March 2012-October 2013) included consecutive patients with stage II and III obstructive colorectal cancer managed with BTS SEMS placement. The SEMS placement technique was standardized by information dissemination among the participating hospitals. The primary outcome was overall survival (OS) after SEMS placement, and the secondary outcomes were relapse-free survival (RFS), recurrence, and short-term outcomes of SEMS placement and surgery. Results The 1-, 3-, and 5-year OS rates were 94.1%, 77.4%, and 67.4%(Kaplan-Meier), respectively, with high technical success (99.0%, 206/208) and low perforation (1.9%, 4/208) rates. The 1-, 3-, and 5-year RFS rates were 81.6%, 65.6%, and 57.9% (Kaplan-Meier), respectively, and the overall recurrence rate was 31.0% (62/200). The RFS rate was significantly poorer in patients with perforation (n = 4) than in those without perforation (n = 196) (log-rank p = 0.017); moreover, perforation was identified as an independent factor affecting RFS (hazard ratio: 3.31; 95% confidence interval: 1.03-10.71, multivariate Cox regression). Conclusions This large, prospective, multicenter study revealed satisfactory long-term outcomes of BTS colonic stenting using a standardized SEMS insertion method, which might be specifically due to reduced perforation rate. (UMIN000007953).

Noonan syndrome is an autosomal dominant developmental disorder. Although it is relatively common, and its phenotypical variability is well documented, its pathophysiology is not fully understood. Previously, with the aim of revealing the pathogenesis of genetic disorders, we reported the induction of cleidocranial dysplasia-specific human-induced pluripotent stem cells (hiPSCs) from patient’s dental pulp cells (DPCs) under serum-free, feeder-free, and integration-free conditions. Notably, these cells showed potential for application to genetic disorder disease models. Furthermore, using similar procedures, we reported the induction of hiPSCs derived from peripheral blood mononuclear cells (PBMCs) of healthy volunteers. These methods are beneficial, because they are carried out without invasive and painful biopsies. Using those procedures, we reprogrammed DPCs and PBMCs that were derived from a patient with Noonan syndrome (NS) to establish NS-specific hiPSCs (NS-DPC-hiPSCs and NS-PBMC-hiPSCs, respectively). The induction efficiency of NS-hiPSCs was higher than that of WT-hiPSCs. We hypothesize that this was caused by high NANOG expression. Here, we describe the experimental results and findings related to NS-hiPSCs. This is the first report on the establishment of NS-hiPSCs and their disease modeling. Supplementary Information The online version of this article (10.1007/s11626-020-00515-9) contains supplementary material, which is available to authorized users.

The clinical and pathological features of sporadic microsatellite instability-high (MSI) colorectal cancer (CRC) are still unclear. The present study aimed to clarify the clinicopathological features of sporadic MSI CRC in comparison with those of Lynch syndrome (LS) exploratorily. The present study was a single-center, retrospective cohort study. Sporadic MSI CRC was defined as MSI CRC with aberrant promoter hypermethylation of the MLH1 gene, while hereditary MSI CRC was defined colorectal cancer in patients with LS. In total, 2653 patients were enrolled; of these, 120 (4.5%) had MSI CRC, 98 had sporadic MSI CRC, and 22 had LS. Patients with sporadic MSI CRC were significantly older (p

BACKGROUND AND AIM Colorectal cancer patients often present with large bowel obstruction. Elective placement of a self-expandable metallic stent (SEMS) can relieve obstruction, but can be challenging. Previous studies have compared cases by outcomes only, but the present study investigated successful cases only to identify factors related to prolonged and difficult SEMS placement in patients with malignant colonic obstruction. METHODS A post-hoc analysis of a multicenter clinical trial conducted between March 2012 and October 2013 at 46 facilities across Japan (UMIN000007953) was carried out; 511 patients who required SEMS placement for acute colorectal obstruction or symptomatic stricture secondary to malignant neoplasm were enrolled. Technical success rates and procedure times were recorded. Clinical and interventional parameters were investigated for their potential effect on procedure time by univariate and multivariate analyses. RESULTS Technical success rate of SEMS placement was 98%. Median procedure time was 30 (range, 4-170) min. In 27% of patients, procedure time exceeded 45 min, indicating technically difficult placement. Multivariate analyses showed significant associations between technically difficult placement and a ColoRectal Obstruction Scoring System (CROSS) score of 0 before SEMS placement (odds ratio [OR], 1.6; P < 0.05), tumor site in the right colon (OR, 2.5; P < 0.0001), stricture length ≥5 cm (OR, 2.2; P < 0.001), peritoneal carcinomatosis (OR, 1.7; P < 0.05), and multiple SEMS placement (OR, 8.0; P < 0.01). CONCLUSION Clinicians must anticipate technical challenges in cases with peritoneal carcinomatosis, a CROSS score of 0, or expansive strictures; such cases require experienced clinicians to carry out SEMS placement.

Background Self-expandable metallic stenting (SEMS) for malignant colorectal obstruction (MCO) as a bridge to elective surgery (BTS) is a widely used procedure. The aim of this study was to assess short-term outcomes of SEMS for MCO as BTS. Methods This study analyzed pooled data from BTS patients who were enrolled in two multicenter prospective single-arm observational clinical studies that used different stent types. Both studies were conducted by the Japan Colonic Stent Safe Procedure Research Group (JCSSPRG). The first study evaluated the WallFlex™ colonic stent for BTS or palliative treatment (PAL) from May 2012 to October 2013 and the second evaluated the Niti-S™ colonic stent from October 2013 to May 2014. Fifty-three facilities in Japan participated in the studies. Before each study started, the procedure had been shared with the participating institutions by posting details of the standard methods of SEMS placement on the JCSSPRG website. Patients were followed until discharged after surgery. Results A total of 723 consecutive patients were enrolled in the two studies. After excluding nine patients, the remaining 714 patients were evaluated as a per-protocol cohort. SEMS placement was performed in 426 patients (312 WallFlex and 114 Niti-S) as BTS and in 288 as PAL. In the 426 BTS patients, the technical success rate was 98.1% (418/426). The clinical success rate was 93.8% (392/418). SEMS-related preoperative complications occurred in 8.5% of patients (36/426), perforations in 1.9% (8/426), and stent migration in 1.2% (5/426). Primary anastomosis was possible in 91.8% of patients (391/426), 3.8% of whom (15/393) had anastomosis leakage. The overall stoma creation rate was 10.6% (45/426). The postoperative complication rate was 16.9% (72/426) and mortality rate was 0.5% (2/426). Conclusions SEMS placement for MCO as BTS is safe and effective with respect to peri-procedural outcomes. Further investigations are needed to confirm long-term oncological outcomes. Electronic supplementary material The online version of this article (10.1007/s00464-018-6324-8) contains supplementary material, which is available to authorized users.

The field of immunotherapy has recently focused on cancers with microsatellite instability (MSI). These cancers include both Lynch-syndrome-associated tumors, which are caused by mismatch repair (MMR) germline mutations, and sporadic MSI tumors, which are mainly attributed to MLH1 promoter methylation. The present study aimed to clarify differences in the histological and PD-L1 expression profiles between these two types of MSI cancers in Japanese patients. Among 908 cases of colorectal cancer treated via surgical resection from 2008 to 2014, we identified 64 MSI cancers, including 36 sporadic MSI and 28 Lynch-syndrome-associated cancers, using a BRAF V600E mutation analysis and MLH1 methylation analysis. Of the latter subgroup, 21 (75%) harbored MMR germline mutations. The following were more frequent with sporadic MSI than with Lynch syndrome associated cancers: poor differentiation (50.0 vs. 7.1%, P = 0.0002), especially solid type (30.6 vs. 3.6%, P = 0.0061); medullary morphology (19.4 and 0%, P = 0.015), Crohn-like lymphoid reaction (50.0 vs. 25.0%, P = 0.042), and PD-L1 expression (25.0 vs. 3.6%, P = 0.034). However, the groups did not differ in terms of the mean invasive front and intratumoral CD8-positive cell densities. In a logistic regression analysis, PD-L1 expression correlated with poor differentiation (odds ratio: 7.65, 95% confidence interval: 1.55–37.7, P = 0.012), but not with the difference between sporadic MSI cancer and Lynch-syndrome-associated cancer (odds ratio: 4.74, 95% confidence interval: 0.50–45.0, P = 0.176). Therefore, compared with Lynch-syndrome-associated cancers, sporadic MSI cancers are more frequently solid, poorly differentiated medullary cancers that express PD-L1.

Highlights • A 64-year-old man underwent head and neck surgery for oral squamous cell carcinoma. • Multiple suture granulomas mimicking tumor recurrence developed in the radiation field. • The suture granulomas developed shortly after adjuvant chemoradiation therapy. • Suspect suture granulomas when nodules appear during postoperative radiotherapy. • Suture granulomas may show spontaneous resolution., Introduction Suture granuloma is a benign tumor that develops because of the presence of surgical suture materials. It commonly occurs several years after different types of surgeries. Here we report a case involving a 64-year-old man who underwent head and neck surgery for oral squamous cell carcinoma and developed multiple suture granulomas mimicking tumor recurrence in the radiation field just a few days after the completion of adjuvant chemoradiation therapy. Presentation of case The patient underwent surgery for lymph node metastasis in the neck at 6 months after the resection of primary oral squamous cell carcinoma. Fifteen days after the completion of adjuvant chemoradiation therapy at a total dose of 50 Gy, small nodules appeared in the radiation field, along the areas of the subcutaneous surgical sutures. Cancer recurrence was initially suspected, but histopathological analysis of a biopsy specimen confirmed foreign body granuloma. Discussion Chemoradiation therapy may enhance the immunoreaction of macrophages in the radiation field and promote the formation of granulation tissue in a short period of time. In addition, cisplatin, which was concurrently administered with radiation in our case, could have influenced the development of the suture granuloma. Conclusion In addition to tumor recurrence, suture granulomas should be considered a differential diagnosis for nodules occurring after surgery, even if they develop in the field of radiation.

Self-expandable metallic stents (SEMSs) are used for the management of malignant colorectal obstruction. A patient who underwent colonic uncovered SEMS insertion for extraluminal stenosis in the splenic flexure of the transverse colon due to advanced gastric cancer is herein reported. The patient presented with a fracture of the colonic SEMS 494 days after SEMS insertion. Although various complications of stenting have previously been reported, the details of fractures of colonic SEMSs have not yet been reported. Because the improvement in the prognosis for patients who undergo palliative SEMS insertion leads to long-term SEMS placement, diverse complications can thus be expected, and new events like stent fracture are expected to increase in the future.

Purpose This study compared the feasibility and safety of endoscopic placement of self-expandable metallic stents (SEMSs) as a bridge to surgery (BTS) between patients with obstructive colorectal cancer (CRC) classified as ColoRectal Obstruction Scoring System (CROSS) 0 and those with CROSS 1 or 2. Methods We conducted a post hoc analysis of two prospective, observational, single-arm multicenter clinical trials and performed a pooled analysis of the data. In total, 336 consecutive patients with malignant colorectal obstruction underwent SEMS placement. The primary endpoint was clinical success, defined as resolution of symptoms and radiological findings within 24 h. Secondary endpoints were technical success and adverse events. Results High clinical (98.0% vs. 98.4%) and technical (96.7% vs. 97.8%) success rates were observed in both groups (CROSS 0 vs. CROSS 1 or 2). The adverse event rate was low. The mean stricture length was lower (3.8 ± 1.2 cm vs. 4.4 ± 1.8 cm) and laparoscopic surgery more common (56.7% vs 52.2%) in the CROSS 0 group than in the CROSS 1 and 2 group. Conclusion This study was the first to compare the degree of stricture in different CROSS groups and demonstrated comparable results with respect to the short-term efficacy and safety of SEMS placement as a BTS for obstructive CRC in CROSS 0, 1, and 2 patients.

This paper introduces a grid-purlin system, which was composed of secondary rectangular-hollow-section grids welded onto the top flange of I-shaped beams of moment frames. The welded grid-purlin itself may play a role of a lateral bracing member for the welded beam. However, the ultimate strength, plastic rotation capacity, or other structural characteristics of this grid-purlin system remain poorly understood. This paper presents two full-scale cyclic loading tests on specimens with I-shaped beams 700 mm deep, 240 mm wide, and 13 m long. The diagonal length of grids in the square grid-purlin of the specimen was 1.3 m on-center, and two different depths of the sections were selected for the purlin sections. Both specimens successfully achieved fully plastic moments at a plastic rotation exceeding 0.04 rad. This shows that the grid-purlin system provides reliable lateral bracing. Continuum finite-element (CFE) analysis was performed to simulate the hysteretic experimental response of the grid-purlin system. This CFE model was used to examine the plastic rotation capacity for a variety of combinations of I-shaped beams and grid-purlins.

Increasing evidence indicates that the gut microbiota is closely associated with acute graft-versus-host disease (aGVHD) in stem cell transplantation (SCT). Fecal microbiota transplantation (FMT) could represent an alternative treatment option for aGVHD. However, FMT for SCT patients carries a potential risk of infection by infused microbiota because of the severely immunosuppressed status. We therefore conducted a pilot study to evaluate the safety of FMT in SCT. A total of 4 patients with steroid-resistant (n = 3) or steroid-dependent gut aGVHD (n = 1) received FMT. No severe adverse events attributed to FMT were observed. All patients responded to FMT, with 3 complete responses and 1 partial response. Temporal dynamics of microbiota seemed to be linked to the gut condition of patients and peripheral effector regulatory T cells also increased during response to FMT. FMT was safely performed in our patients and might offer a novel therapeutic option for aGVHD. This trial was registered at the University Hospital Medical Information Network (https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000017575) as #UMIN000015115.

Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare and poorly understood ischemic colitis that occurs in the rectosigmoid colon of predominantly young, previously healthy, male patients. A 76-year-old Japanese man presented to our hospital with a 1-year history of worsening diarrhea, lower abdominal pain, and weight loss (−6 kg). Laboratory evaluation revealed white blood cell count of 13 200/μL, C-reactive protein level of 2.0 mg/dL (normal range, 0.0–0.3), and negative results for stool culture (including Clostridium difficile). Colonoscopy showed circumferential and edematous narrowing of the sigmoid colon with deep longitude ulceration. Biopsy was done and examination of the specimen demonstrated no specific ischemia. The patient was treated with bowel rest, antibiotics, and i.v. fluids; however, his symptoms worsened. Finally, sigmoidectomy was carried out. Histological examination demonstrated significant myointimal hyperplasia of mesenteric veins leading to thickening and stenosis of the venous lumen. Therefore, the final diagnosis was IMHMV. Three months following sigmoidectomy, he was asymptomatic.

The base excision repair gene MUTYH is the causative gene of colorectal polyposis syndrome, which is an autosomal recessive disorder associated with a high risk of colorectal cancer. Since few studies have investigated the genotype–phenotype association in Japanese patients with MUTYH variants, the aim of this study was to clarify the clinicopathological findings in Japanese patients with MUTYH gene variants who were detected by screening causative genes associated with hereditary colorectal polyposis. After obtaining informed consent, genetic testing was performed using target enrichment sequencing of 26 genes, including MUTYH. Of the 31 Japanese patients with suspected hereditary colorectal polyposis, eight MUTYH variants were detected in five patients. MUTYH hotspot variants known for Caucasians, namely p.G396D and p.Y179D, were not among the detected variants.Of five patients, two with biallelic MUTYH variants were diagnosed with MUTYH-associated polyposis, while two others had monoallelic MUTYH variants. One patient had the p.P18L and p.G25D variants on the same allele; however, supportive data for considering these two variants ‘pathogenic’ were lacking. Two patients with biallelic MUTYH variants and two others with monoallelic MUTYH variants were identified among Japanese colorectal polyposis patients. Hotspot variants of the MUTYH gene for Caucasians were not hotspots for Japanese patients.

Background The aim of this study was to clarify clinicopathological features, frequencies of molecular biomarkers, and prognoses in Japanese colorectal cancer patients and compare them with right-sided colon cancer (RCC) and left-sided colorectal cancer (LCRC). Methods We consecutively selected 575 colorectal cancer patients who underwent surgical resection from 2008 to 2011. RCC was located from the cecum to the transverse colon, and LCRC was located from the splenic flexure to the rectum. Frequencies of KRAS gene mutation, BRAF gene mutation, microsatellite instability (MSI), l18qLOH and CpG island methylator phenotype (CIMP) were statistically analyzed between groups. Results Tumors were located in the RCC in 26.3% of patients and in the LCRC in 73.7%. Elderly patients, females and advanced diseases were significantly more frequent in the RCC group than in the LCRC group. However, venous invasion was significantly more frequent in LCRC than in RCC. Between groups, BRAF mutant type, KRAS mutant type, MSI and CIMP+ were significantly more frequent in RCC, whereas 18qLOH was significantly more frequent in LCRC. In overall survival, RCC demonstrated poor prognosis compared with LCRC; however, age, gender, stage, lymphatic invasion, KRAS status and BRAF status rather than tumor location were independent prognostic factors. In addition, the independent prognostic factors in RCC were different from those in LCRC in each stage. However, the consistency between OS and DFS was not observed in this study, excluding lymphatic invasion in LCRC. Conclusion Comparing RCC with LCRC, RCC is different from LCRC in clinicopathological features, molecular biomarkers and prognostic factors in Japanese colorectal cancer patients. Since the proportions of molecular biomarkers of CRC in this study are different from Western CRCs, further studies are required to clarify the clinicopathological differences between Japanese CRCs and Western CRCs.

BACKGROUND/AIMS Diffuse or segmental irregular narrowing of the main pancreatic duct (MPD), as observed by endoscopic retrograde cholangiopancreatography (ERCP), is a characteristic feature of autoimmune pancreatitis (AIP). METHODS ERCP findings were retrospectively examined in 40 patients with AIP in whom irregular narrowing of the MPD was detected near the orifice. The MPD opening sign was defined as the MPD within 1.5 cm from the orifice being maintained. The distal common bile duct (CBD) sign was defined as the distal CBD within 1.5 cm from the orifice being maintained. Endoscopic findings of a swollen major papilla and histological findings of specimens obtained from the major papilla were examined in 26 and 21 patients, respectively. RESULTS The MPD opening sign was detected in 26 of the 40 patients (65%). The distal CBD sign was detected in 25 of the 32 patients (78%), which showed stenosis of the lower bile duct. The patients who showed the MPD opening sign frequently showed the distal CBD sign (p=0.018). Lymphoplasmacytic infiltration, but not dense fibrosis, was histologically detected in biopsy specimens obtained from the major papilla. CONCLUSIONS On ERCP, the MPD and CBD adjacent to the major papilla are frequently maintained in patients with AIP involving the pancreatic head. These signs are useful for diagnosing AIP on ERCP. (Gut Liver 2015;9113-117).

Background/Aims: Ulcerative colitis (UC) is sometimes associated with autoimmune pancreatitis (AIP). Infiltration of immunoglobulin G4 (IgG4)-positive plasma cells is sometimes detected in the colonic mucosa of AIP or UC patients. This study aimed to clarify the relation between UC and IgG4. Methods: Associations with UC were reviewed in 85 AIP patients. IgG4 immunostaining was performed on biopsy specimens from the colonic mucosa of 14 AIP and 32 UC patients. Results: UC was confirmed in two cases (type 1 AIP, n=1; suspected type 2 AIP, n=1). Abundant infiltration of IgG4-positive plasma cells in the colonic mucosa was detected in the case of suspected type 2 AIP with UC and two cases of type 1 AIP without colitis. Abundant infiltration of IgG4-positive plasma cells was detected in 10 UC cases (IgG4-present, 31%). Although 72% of IgG4-absent UC patients showed mild disease activity, 70% of IgG4-present patients showed moderate to severe disease activity (p

Background/aims Coexistence of autoimmune pancreatitis (AIP) and pancreatic cancer, elevation of serum IgG4 levels in pancreatic cancer patients, and infiltration of IgG4-positive plasma cells in peritumorous pancreatitis have been described in a few reports. This study examined the relationship between intraductal papillary mucinous neoplasm (IPMN) of the pancreas and peritumorous IgG4-positive lymphoplasmacytic infiltrates. Methods Serum IgG4 levels were measured in 54 patients with IPMN (median 70 years, 26 males and 28 females; 13 main duct type and 41 branch duct type). Histological findings focusing on dense lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis were reviewed, and immunostaining with IgG4 and IgG was performed in 23 surgically resected IPMN cases (18 main duct type and 5 branch duct type). The presence of IgG4-positive plasma cells >10/hpf and an IgG4-positive/IgG-positive plasma cell ratio >40% were considered significant. Results Serum IgG4 levels were elevated in 2 (4%) IPMN patients. Significant infiltration of IgG4-positive plasma cells was detected in 4 IPMN cases (17%). The IgG4-positive/IgG-positive plasma cell ratio was >40% in all 4 cases. In one case with a markedly elevated serum IgG4 level (624 mg/dL), typical lymphoplasmacytic sclerosing pancreatitis (AIP type 1) lesions surrounded the whole IPMN. In the 3 other cases, infiltration of IgG4-positive plasma cells with fibrosis was focally detected mainly in the periductal area around the IPMN. Conclusions In a few patients with IPMNs, IgG4-positive plasma cell infiltration can occur in the peritumorous area. The association of an IPMN with AIP type 1-like changes seems to be exceptional and coincidental.

N (1),N (12)-Diacetylspermine (DiAcSpm) is a tumor marker featured by increase in the urine of patients with cancers, including early colorectal cancer, but where and how DiAcSpm is made remains unclear. We aimed to clarify whether colorectal cancer tissues produce increased amounts of DiAcSpm, and if they do, to examine whether tissue DiAcSpm level may serve as a criterion of tissue malignancy.Tissue samples were obtained from 140 patients (13 low-grade intraepithelial neoplasia, 98 high-grade intraepithelial neoplasia and 29 colorectal cancer) treated for colorectal cancer and intraepithelial neoplasia at Tokyo Metropolitan Komagome Hospital between November 2007 and April 2011. The DiAcSpm level in cancer and adjacent normal tissue extracts was compared, and its relationship with clinical stages of the diseases was analyzed.DiAcSpm levels were higher in colorectal cancer tissue (p0.01, n = 12) and its liver metastasis (p0.05, n = 5) than in adjacent normal tissues. The tumor/normal ratio of tissue DiAcSpm content was examined for endoscopically obtained tumor and adjacent normal tissues from patients with intraepithelial neoplasia. The ratio was greater than 1.5 in 38 % (5/13) and 78 % (84/108) of low-grade intraepithelial neoplasia and high-grade intraepithelial neoplasia, respectively.Tissue DiAcSpm levels increase in the tissue of colorectal cancer and also in precancerous lesion, such as high-grade intraepithelial neoplasia. The increase is considered a sign that a tissue is acquiring malignant characteristics. It is likely that the DiAcSpm produced by cancer cells is responsible for the frequent increase in urinary DiAcSpm in early cancer patients.

Background/Aims The objective of this study was to compare the clinical characteristics of patients with autoimmune pancreatitis (AIP) with or without Mikulicz's disease (MD) and with MD alone. Methods We investigated the clinical findings in 15 AIP patients with MD (group A+M), 49 AIP only patients (group A), and 14 MD only patients (group M). Results The male-female ratio was significantly higher in group A+M (73%, p

Background and Aim: The role of the accessory pancreatic duct (APD) in pancreatic pathophysiology has been unclear. We previously examined the patency of the APD in 291 control cases who had a normal pancreatogram in the head of the pancreas by dye-injection endoscopic retrograde pancreatography (ERP). APD patency was 43% and was closely related with the shape of the terminal portion of the APD. The present study aimed to clarify the clinical implications of a patent APD. Methods: Based on the underlying data, the patency rate of the APD was estimated from the terminal shape of the APD on ERP in 167 patients with acute pancreatitis. Results: In patients with acute pancreatitis, stick-type APD, spindle-type APD, and cudgel-type APD, which showed a high patency, were rare, and branch-type APD and halfway-type or no APD, which showed quite low patency, were frequent in acute pancreatitis patients. Accordingly, the estimated patency of the APD in acute pancreatitis patients was only 21%. There was no significant relationship between the estimated APD patency and etiology or severity of acute pancreatitis. Conclusions: The terminal shapes of the APD with low patency were frequent in acute pancreatitis patients, and estimated APD patency was only 21% in acute pancreatitis. A patent APD may function as a second drainage system to reduce the pressure in the main pancreatic duct and prevent acute pancreatitis.

A 67-year-old man with a history of low anterior resection and diverting loop transverse colostomy for rectal carcinoma developed fulminant pseudomembranous colitis after stoma closure. Oral administration of vancomycin at 0.5 g every 6 h and colonoscopy with intracolic vancomycin administration was unsuccessful, but continuation of intracolic vancomycin with postural change resulted in dramatic recovery. Postural change may extend the efficacy of intracolic vancomycin, and intracolic vancomycin should be considered as an option between conventional therapy and surgical intervention for pseudomembranous colitis.

Background Lynch syndrome (LS) patients have a high risk of developing various tumors. This study aimed to clarify the characteristics of tumors developing in LS patients. Methods This is a retrospective review of 55 LS patients treated at Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital. Results The median age at the diagnosis of the first malignant tumor and first LS-related tumor was 44 (range, 19−65) and 44 (range, 24−66) years, respectively. Of the 55 LS patients with developing malignant tumors, 45 (93.8%) developed an LS-related tumor as the first malignant tumor. Colorectal cancer (CRC) developed in 47 patients (85.4%), followed by endometrial cancer (n = 13, 56.5%) in females and gastric cancer (n = 10, 18.1%). In 6 gastric cancer patients, Helicobacter pylori was detected in resected specimens. Twenty-nine patients (52.7%) developed CRC and extra-colonic tumors; of these, 15 patients (48.3%) had mutations in MLH1, 10 (58.8%) in MSH2, and 4 (57.1%) in MSH6. At the age of 50, the cumulative incidence was 50.9% [95% confidence interval (CI), 36.9−63.3%] for CRC, 17.4% (95% CI, 5.2−35.6%) for endometrial cancer, and 5.5% (95% CI, 1.4−13.8%) for gastric cancer. Eight gastric cancer, one breast cancer patient, five bladder cancer patients, and one prostate cancer patient demonstrated loss of expression of the mismatch repair (MMR) protein; patients with thyroid cancer, spindle cell sarcoma, and giant cell tumors did not demonstrate this. Conclusion Gastric cancer incidence was high in Japanese patients with LS and associated with H. pylori infection. MMR protein deficiency caused the development of malignant tumors in LS patients.

Objectives Photodynamic therapy (PDT) is a very effective treatment for superficial malignancies that does not result in loss of normal tissue. Here, we report successful PDT treatment of superficial oral cancers and its clinical outcome with long-term follow up. Materials and methods Thirty-four superficial oral squamous cell carcinomas were treated with PDT, and the effects were evaluated. Each patient received Photofrin (2 mg/kg) intravenously 48 h prior to light irradiation. Photoradiation was performed at doses of 100–150 J/cm2 using a 630-nm wavelength excimer dye laser. Results Six months after PDT, 30 patients (88.2%) showed complete responses while 9 patients (26.5%) had local relapses during long-term follow-up. The 5-year overall survival, disease-specific survival, and disease-free survival rates were 76.5%, 84.6%, and 63.3%, respectively. Lesions with red patches had a significantly higher recurrence rate than lesions with white patches. Accurate evaluation of the extent of lesions and appropriate photoradiation were important in improving outcomes. Adverse events observed included sunburn and sequestrum formation of alveolar bone. No abnormal laboratory values or systemic complications were observed. Conclusion PDT using Photofrin as the photosensitizer is an effective treatment modality for superficial oral carcinomas, with excellent healing and minimal side effects.

IgG4-related disease is a newly recognized fibroinflammatory condition characterized by tumefaction consisting of fibrosis with dense infiltration of IgG4-positive plasma cells; affecting various organs. A case of IgG4-related sclerosing mesenteritis is reported. A 64-year-old man was admitted to our hospital with a suspected tumor of the small intestine. Abdominal computed tomography demonstrated a 6-cm soft tissue mass in the right lower mesentery compressing the jejunum, which also showed accumulation of fluorodeoxyglucose uptake on fluorine-18 fluorodeoxyglucose positron emission tomography. With a preoperative diagnosis of suspected malignant lymphoma with lymphadenopathy in the mesentery, partial small bowel resection was performed. Macroscopically, a hard mass, including several swollen lymph nodes, was detected in the mesentery. Microscopically, marked fibrosis showing partially storiform pattern, obstructive phlebitis, follicular hyperplasia, and abundant infiltration of IgG4-positive plasma cells were detected. IgG4-related mesenteritis was diagnosed histopathologically, but the serum IgG4 level was 81 mg/dl postoperatively. Five months after the surgery, an 11-cm soft tissue mass involving the left ureter appeared. Histological examination of a biopsy specimen from the retroperitoneal mass showed fibrosis with inflammatory infiltration. Although IgG4-related retroperitoneal fibrosis could not be confirmed histologically, the tumor responded well to steroid therapy.

Endoscopic stenting with a self-expandable metallic stent (SEMS) is a widely accepted procedure for malignant colonic obstruction. The Colonic Stent Safe Procedure Research Group conducted the present prospective feasibility study. Our objectives were to estimate the safety and feasibility of SEMS placement as a bridge to surgery (BTS) for malignant colorectal obstruction. We conducted a prospective, observational, single-arm, multicenter clinical trial from March 2012 to October 2013. Each patient was treated with an uncovered WallFlex enteral colonic stent. Patients were followed up until discharge after surgery. A total of 518 consecutive patients were enrolled in this study. The cohort intended for BTS consisted of 312 patients (61 %), and the stent could be released in 305 patients. Technical and clinical success rates were 98 and 92 %, respectively. Elective surgery was performed in 297 patients, and emergency surgery was performed in eight patients for the treatment of complications. The overall preoperative complication rate was 7.2 %. Major complications, including perforation, occurred in 1.6 %, persistent colonic obstruction occurred in 1.0 %, and stent migration occurred in 1.3 % patients. The median time from SEMS to surgery was 16 days. Silent perforations were observed in 1.3 %. Open and laparoscopic surgery was performed in 121 and 184 patients, respectively. The tumor could be resected in 297 patients. The primary anastomosis rate was 92 %. The rate of anastomotic leakage was 4 %, and the overall stoma creation rate was 10 %. The median duration of hospitalization following surgery was 12 days. Overall postoperative morbidity and mortality rates were 16 and 0.7 %, respectively. This largest, multicenter, prospective study demonstrates the feasibility of SEMS placement as a BTS for malignant colorectal obstruction. SEMS serves as a safe and effective BTS with acceptable stoma creation and complication rates in patients with acute malignant colonic obstruction.

Objective To clarify the allergic manifestations in patients with autoimmune pancreatitis (AIP). Methods We assessed 67 AIP patients, before they received steroid therapy, for a past history of allergic disease, the peripheral eosinophil count (n=62) and the serum IgE level (n=53). Allergen-specific IgE antibody serologic assays were performed in 15 patients. Results A positive past history and/or the presence of active allergic disease were found in 24 AIP patients (36%), including 15 patients with acute allergic rhinitis and eight patients with bronchial asthma. Peripheral eosinophilia and elevation of the serum IgE level were detected in 16% (10/62) and 60% (32/53) of the patients, respectively. Allergen-specific IgE antibody serologic assays were positive in 13 patients (87%). There were no differences between the assay-positive and -negative patients regarding the clinical profiles. Conclusion In conclusion, 87% of the 15 AIP patients tested had positive allergen-specific IgE antibody serologic assays. Allergic mechanisms may be related to the occurrence of AIP.

The clinical situation of familial adenomatous polyposis (FAP) in Japan has changed in the period since the last analysis of data of the Japanese Polyposis Center. To reevaluate our data and elucidate the changes we analyzed the records of the 1390 FAP patients in 900 families registered with the Polyposis Committee of the Japanese Society for Cancer of the Colon and Rectum. In the 13-year period 1990-2003, clinical differences between men and women with FAP diminished. The postoperative prognosis was substantially better in patients without advanced colorectal cancer (stageor = T2) than in those with early cancer or no cancer. Mean age at death improved from 42.5 years in the period before 1990 to 46.0 years, and it was a result of a decreased proportion of deaths from colorectal cancer. The distribution of colorectal cancer in FAP patients was similar to that in the general population. Desmoid tumors accounted for about 10% of deaths in the recent 13 years (1990-2003). The cumulative risk of rectal cancer in the preserved rectum was 12% at 10 years and 23% at 15 years. The registry system in Japan revealed a new clinical situation in FAP patients, and the findings of this study will be useful to improve the prognosis of patients with FAP.

Metastatic tumors of the oral region are rare, representing about 1 % of malignant tumors in the oral cavity. In this article, we report a case of carcinoma of the sigmoid colon that metastasized to the maxillary gingiva and review of literature. A 69-year-old man underwent extraction of the right first and second molars of the maxilla, and a rapidly proliferating lesion developed at the site. The patient had previously undergone surgical excision of adenocarcinoma of the sigmoid colon. Histological examination of the oral lesion revealed adenocarcinoma similar to the previous lesion in the colon. Moreover, the serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 were elevated. These findings suggested that the oral lesion was a metastatic adenocarcinoma from the sigmoid colon. Although computerized tomographic scans showed metastatic lesions of the liver and lung, the gingival tumor was excised to improve dysphagia induced by the rapidly growing tumor. He died of respiratory arrest 4 months after surgery.

Bisphosphonates (BPs) have been used in medical practice for the treatment of osteoporosis, bone metastasis, and multiple myeloma. Although many studies have been published, the treatment and prognosis of bisphosphonate-related osteonecrosis of the jaw (BRONJ) remain unclear. This study included 59 patients with BRONJ: 29 had taken oral BPs and 30 had taken intravenous (IV) BPs. All received conservative treatments. When separated sequestra were seen, a sequestrectomy was performed. Segmental mandibular resection was performed when pathological fractures were diagnosed. The outcomes of treatments were compared between groups. For patients treated with oral rinses or mandibular resection, the number in whom clinical healing was observed did not differ between the oral BP and IV BP groups. With regard to sequestrectomy, 94% of patients in the oral BP group showed improvement with this treatment compared to 50% in the IV BP group. The number of patients in whom clinical healing of BRONJ was achieved was statistically better in the oral BP group than in the IV BP group after 6 months of treatment (P0.001). The results showed that90% of patients treated with oral BPs could be cured. However, 50% of patients treated with IV BPs did not show an improvement. Additional research is needed to further increase the therapeutic efficacy for the resolution of BRONJ.

Objective The objective of this study was to evaluate picture of the major and minor duodenal papillae in patients with autoimmune pancreatitis (AIP). Methods Endoscopic features of the major and minor papillae were examined in 59 and 13 patients with AIP. After steroid therapy, changes of the major and minor papillae were observed in 5 and 6 patients. The major and minor papillae were observed with narrow band imaging in 24 and 6 patients. Biopsy specimens from the major (n = 50) and minor (n = 13) papillae were immunostained using an anti-IgG4 antibody. Results Endoscopic features of the major and minor papillae were abnormal in 26 patients (44%; swelling [n = 20] and redness [n = 14]) and 5 patients (38%; swelling [n = 5]). Swelling of the pancreatic head, irregular narrowing of the main pancreatic duct of the pancreatic head, stenosis of the lower bile duct, and abundant infiltration of IgG4-positive plasma cells were more frequent in the patients with an abnormal major papilla compared with those with a normal major papilla. On narrow band imaging, dilated vessels were observed in abnormal papillae. After therapy, swelling of the major and minor papillae improved in all 4 and 2 patients. Conclusions Endoscopic features of the major and minor papillae were abnormal in 44% and 38% of the patients with AIP.

Because a diagnostic serological marker is unavailable, autoimmune pancreatitis (AIP) is diagnosed based on unique features. The diagnostic capabilities and potential limitations of four sets of diagnostic criteria for AIP (Japanese diagnostic criteria 2006 and 2011, Asian diagnostic criteria, and international consensus diagnostic criteria (ICDC)) were compared among 85 patients who were diagnosed AIP according to at least one of the four sets. AIP was diagnosed in 87%, 95%, 95%, and 95% of the patients according to the Japanese 2006, Asian, ICDC, and Japanese 2011 criteria, respectively. The ICDC can diagnose types 1 and 2 AIP independently and show high sensitivity for diagnosis of AIP. However, as the ICDC are rather complex, diagnostic criteria for AIP should perhaps be revised and tailored to each country based on the ICDC.

In immunoglobulin G4 (IgG4)-related disease (RD), organ enlargement or nodular lesions consisting of abundant infiltration of lymphocytes and IgG4-positive plasma cells and fibrosis are seen in various organs. Although infiltration of many IgG4-positive plasma cells is detected in the gastric and colonic mucosa and major duodenal papilla of patients with autoimmune pancreatitis, it cannot be diagnosed as a gastrointestinal lesion involved in IgG4-RD, because none of the following is observed in these lesions: a mass-like formation; dense fibrosis; or obliterative phlebitis. Based on our review of the literature, there appear to be two types of IgG4-related gastrointestinal disease. One is a gastrointestinal lesion showing marked thickening of the wall of the esophagus and stomach, consisting of dense fibrosis with abundant infiltration of IgG4-positive plasma cells, which usually show submucosal spreading. The other is an IgG4-related pseudotumor occurring in gastrointestinal regions such as the stomach, colon, and major duodenal papilla, showing polypoid or mass-like lesions. Most solitary IgG4-related gastrointestinal lesions that are not associated with other IgG4-RD appear to be difficult to diagnose. It is of utmost importance to rule out malignancy. However, these lesions may respond to steroid therapy. To avoid unnecessary resection, IgG4-related gastrointestinal diseases should be considered in the differential diagnosis.

Objective To elucidate the clinical characteristics of IgG4-related retroperitoneal fibrosis (RF). Methods IgG4-related RF was diagnosed when all of the following three criteria were fulfilled: retroperitoneal soft tissue masses surrounding the aorta and/or adjacent tissues, elevation of the serum IgG4 levels, and abundant infiltration of IgG4-positive plasma cells in at least one organ or site. Ten patients were diagnosed as having IgG4-related RF. Results The mean age at diagnosis was 70.1 years, and the male-to-female ratio was 1:0.6. Only two patients had initial symptoms predominantly related to RF (back pain and edema of the lower extremities), while the remaining eight patients reported initial symptoms due to associated diseases. On laboratory examination, a severe inflammatory reaction was observed in one patient. Elevation of the levels of serum IgG and IgE, eosinophilia and positivity of antinuclear antibodies were detected in seven, five, two and seven patients, respectively. The retroperitoneal masses were detected primarily in the left renal hilus in four patients, in the periaortic region in five patients and in both regions in one patient. Hydronephrosis was present in five patients. The histological diagnosis was confirmed in the retroperitoneal masses (resection, n=1 biopsy, n=2) and extraretroperitoneal lesions (n=7). Twenty-four other IgG4-related diseases were found to be associated with IgG4-related RF in nine patients (autoimmune pancreatitis (n=2), sialadenitis (n=4), dacryoadenitis (n=5), lymphadenopathy (n=9), pulmonary pseudotumor (n=1) and pituitary pseudotumor (n=1)). Seven patients underwent steroid therapy, all of whom responded well and showed no instances relapse. Conclusion IgG4-related RF has several clinical characteristic features. Our diagnostic criteria may be helpful in obtaining a correct diagnosis.

We examined the anatomy of the pancreatic duct system in patients with autoimmune pancreatitis (AIP) from the standpoint of embryological pancreatic primordial.The pancreatic duct system involved in 83 AIP patients was embryologically divided into both ventral and dorsal pancreatic ducts (VD type), only the dorsal pancreatic duct (D type), or only the ventral pancreatic duct (V type).The 83 AIP patients were divided into 62 VD type, 20 D type, and 1 V type. Obstructive jaundice was significantly more frequent in VD type (87%) than in D type (0%; p0.01), and abdominal pain was more frequent in D type (24%) than in VD type (2%; p0.01). Stenosis of the lower bile duct was detected in 98% of VD type and 15% of D type (p0.01). In the 67 patients with involvement of the pancreatic head, only the dorsal pancreatic duct was involved with a normal ventral pancreatic duct in four patients (D type). In the four D-type patients, the pancreatic duct system showed complete pancreas divisum (n = 1), incomplete pancreas divisum (n = 2), or normal pancreatic duct system (n = 1). Stenosis of the lower bile duct was seen in three patients, but was mild, resulting in no obstructive jaundice. Three patients reported abdominal pain and one patient developed acute pancreatitis.We propose a new entity of "autoimmune dorsal pancreatitis" in which only the dorsal pancreas is involved, and involvement of the lower bile duct and obstructive jaundice is rare.

The case of a 63-year-old male with a large mass in the pancreatic tail and multiple liver metastases, diagnosed as acinar cell carcinoma of the pancreas with a few scattered endocrine cells by liver biopsy is presented. The S-1 chemotherapy was effective, and partial response was obtained with decreased levels of serum CA19.9 and NSE. Ten months after starting chemotherapy, the tumor began to grow accompanied by marked elevation of serum NSE levels (266 ng/ml). The patient died of liver failure due to multiple liver metastasis 18 months after the initiation of the S-1 chemotherapy. Histological findings at autopsy were acinar cell carcinoma with an endocrine component of more than 30 %; the final diagnosis was mixed acinar-endocrine carcinoma of the pancreas. This pathological change and clinical course may imply that S-1 was effective against the acinar component but less effective against the neuroendocrine component caused by tumor differentiation.

Although pancreatic cancer produces upstream obstructive pancreatitis, acute pancreatitis is a less common manifestation of pancreatic cancer. This study aimed to clarify the subgroup of pancreatic cancer patients who present with an episode of acute pancreatitis (Group I) in comparison with a matched group of pancreatic cancer patients without pancreatitis (Group II) and another group of acute pancreatitis patients without pancreatic cancer (Group III).This was a retrospective comparative study of 18 patients in Group I, 300 patients in Group II and 141 patients in Group III.The mean age of Group I was 63.7 years and the male to female ration was 1:0.3. Serum CA 19-9 levels were elevated in 80 %. The main pancreatic duct was incompletely obstructed in 7 patients. There were no significant differences in location of tumor, clinical stage, resection rate and survival months between Group I and II. Acute pancreatitis secondary to pancreatic cancer was more likely to be mild (94 vs. 72 %,p0.05) and relapsed (39 vs. 16 %,p0.05) compared with Group III.Anatomic evaluation of the pancreas should be performed in patients with acute pancreatitis with no obvious etiology, even if the pancreatitis is mild, to search for underlying malignancy.

大腸のeosinophilic granulomaの報告は極めて稀である.今回,上行結腸のIIa+IIc様のeosinophilic granulomaの1例を経験したので報告する.症例は59歳の男性で,便潜血反応のため精査の結果,横行結腸に2型の進行癌を認めるとともに,上行結腸にIIa+IIc様の病変を認めた.後者は25×25mm大で,病理組織学的にはeosinophilic granulomaであった.本症の報告の多くはpolypoidの形態を呈し,自験例のごとき表面型の早期癌に類似した形態を示すものはなかった.またinflammatory fibroid polypとeosinophili cgranulomaは同義語であるが,本例の形態はpolypoidではないことから後者を用いた.

A 79-year-old man had a 3.5-year history of edema of the lower extremities of unknown etiology. Abdominal computed tomography showed a soft tissue mass around the abdominal aorta, and the biopsy revealed dense fibrosis with abundant infiltration of IgG4-positive plasma cells. His serum IgG4 level was increased to 188 mg/dL. His lower extremity edema was induced by stenosis of the inferior vena cava (IVC) due to the mass. With a diagnosis of IgG4-related retroperitoneal fibrosis, he was treated with steroid, and the leg edema decreased with improvement of patency of the IVC and reduction of the soft tissue mass.