Gastric volvulus and giant Bochdalek hernia in an adult patient that were safely repaired by endoscopic reduction and elective laparoscopic surgery.

A Bochdalek hernia (BH) is a congenital abnormality with incomplete closure of the diaphragm. It is usually manifested in infants but rarely in adults. Here, we report an adult patient with gastric volvulus and giant BH that were safely repaired by endoscopic reduction and elective laparoscopic surgery, respectively. A 79-year-old woman presented with left upper abdominal pain but no history of trauma. CT revealed a giant BH with gastric volvulus. After emergency endoscopic reduction of the volvulus, elective laparoscopic repair of the BH was performed. The 8 × 8-cm defect was repaired with interrupted nonabsorbable sutures and a mesh. The patient's postoperative course was uneventful, and no complications or recurrence were observed in the 6 months that followed.

Prototype single-balloon enteroscopy with passive bending and high force transmission improves depth of insertion in the small intestine.

BACKGROUND/AIMS: We retrospectively analyzed Crohn's disease (CD) patients with small intestinal strictures who underwent single-balloon enteroscopy (SBE) to ascertain whether prototype SBEs with a passive bending mechanism and high force transmission insertion tube had better insertability in the small intestine than a conventional SBE. METHODS: Among 253 CD patients who underwent SBE, we identified 94 CD patients who had undergone attempted endoscopic balloon dilatation (EBD) for small intestinal stenosis for inclusion in this study. We analyzed whether the type of scope used for their initial procedure affected the cumulative surgery-free rate. For the insertability analysis, patients who underwent SBE at least twice were divided into 3 groups according to the type of scope used: conventional SBE only, prototype SBE only, and both conventional and prototype SBEs. For each group, depth of insertion, procedure time, and number of EBDs were compared in the same patient at different time points. RESULTS: The success rate of EBD was 88.3%. The 5- and 10-year cumulative surgery-free rate was 75.7% and 72.8%, respectively. Cox regression analysis indicated that the factors contributing to surgery were long stricture (≥2 cm), EBD failure, and elevated Crohn's Disease Activity Index, but not the type of scope used for EBD. The prototype SBEs significantly improved the depth of insertion (P=0.03, Wilcoxon's signed-rank test). CONCLUSIONS: In CD patients with small intestinal stenosis, the prototype SBEs with a passive bending mechanism and high force transmission insertion tube did not improve long-term EBD outcome but did improve deep insertability. (Clinical Trial Registration No. UMIN000037102).

Clinical relevance of innovative immunoassays for serum ustekinumab and anti-ustekinumab antibody levels in Crohn's disease.

BACKGROUND AND AIM: Ustekinumab is a human monoclonal antibody to the p40 subunit of human IL-12/IL-23. The purpose of this report is to verify the newly developed immunoassays for serum ustekinumab and anti-ustekinumab antibody (AUA) concentrations and assess their clinical utility. METHODS: Serum ustekinumab trough levels and AUA levels were measured using new immunoassays in 38 patients with Crohn's disease under ustekinumab maintenance injection. RESULTS: Mean ustekinumab trough levels were 2.54 ± 2.1 µg/mL, and 3 of 38 patients (7.9%) were positive for AUAs. There was no association between ustekinumab trough levels and AUA levels. The optimal trough level of ustekinumab to maintain negative C-reactive protein levels (≤ 0.3 mg/dL) was 1.67 µg/mL determined by receiver operating characteristic curve analysis. Ustekinumab trough level negatively but significantly correlated with C-reactive protein, erythrocyte sedimentation rate, and Crohn's disease activity index and positively and significantly correlated with serum albumin levels. Ustekinumab trough levels were significantly higher in biologics-naïve patients than in biologics-experienced patients, although there was no difference in AUA levels. CONCLUSIONS: We developed new assays for serum ustekinumab trough and AUA levels. These assays might provide new insights into therapeutic drug monitoring-based management of Crohn's disease patients under ustekinumab therapy.

Blood concentrations and renal clearance of water-soluble vitamins in outpatients with ulcerative colitis.

Few studies have investigated the association between dietary intake and blood concentrations of water-soluble vitamins in patients with ulcerative colitis (UC). In the present study, vitamin concentrations were measured in the blood and urinary excretion of 23 outpatients with UC and compared against a control group of 20 healthy participants. A weighed food record procedure was used to ensure controlled macronutrient and vitamin intakes of the UC cohort. Individuals in the control group were given a semi-purified diet for 8 days prior to assessment. Multiple linear regression analysis was used to identify important differences in vitamin concentrations, independent of sex, age and other confounding variables. The blood concentrations of vitamins B2, C, niacin and folate were markedly lower in the patients with UC than those in the control group, and the renal clearance of vitamins B1, B6, B12 and folate was notably higher in the UC cohort. It was concluded that vitamins B2, C, niacin and folate were at significantly lower concentrations in patients with UC following adjustment for coexisting factors. The lower levels of niacin may be partially due to impaired reabsorption. Chronic inflammation, common in patients with UC, with may contribute to the lower levels of other vitamins by rendering amino acid and carbohydrate metabolism into a hypermetabolic state. As the role of vitamins in metabolic activity is constant and pervasive, nutritional management including the application of water-soluble vitamins appears important for patients suffering from UC.

Magnified single-balloon enteroscopy in the diagnosis of intestinal follicular lymphoma: a case series.

The objective of this study was to evaluate the magnified endoscopic findings in the diagnosis of follicular lymphoma in the small intestine in comparison with those of intestinal follicular lymphoma and lymphangiectasia. Four patients with follicular lymphoma and 3 with lymphangiectasia in the small intestine were retrospectively analyzed. A prototype magnifying singleballoon enteroscope was used. The findings of the intestinal follicular lymphoma and lymphangiectasia were retrospectively analyzed to determine the magnified endoscopic findings of follicular lymphoma in the small intestine. Opaque white granules were observed in 3 of the 4 patients with follicular lymphoma. Magnified narrow-band imaging (NBI) of the opaque white granules showed stretched microvessels, which had a diminutive tree-like appearance. The remaining patient had no opaque white granules and only displayed whitish villi. Magnified NBI observation of the whitish villi revealed the absence of marginal villus epithelium, which was confirmed by histology. The magnified NBI enteroscopy revealed the diminutive tree-like appearance on the opaque white granules and the absence of marginal villus epithelium of the whitish villi in intestinal follicular lymphoma. These findings may be useful in diagnosing follicular lymphoma.

Predicting outcomes to optimize disease management in inflammatory bowel disease in Japan: their differences and similarities to Western countries.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract, with increasing prevalence worldwide. IBD Ahead is an international educational program that aims to explore questions commonly raised by clinicians about various areas of IBD care and to consolidate available published evidence and expert opinion into a consensus for the optimization of IBD management. Given differences in the epidemiology, clinical and genetic characteristics, management, and prognosis of IBD between patients in Japan and the rest of the world, this statement was formulated as the result of literature reviews and discussions among Japanese experts as part of the IBD Ahead program to consolidate statements of factors for disease prognosis in IBD. Evidence levels were assigned to summary statements in the following categories: disease progression in CD and UC; surgery, hospitalization, intestinal failure, and permanent stoma in CD; acute severe UC; colectomy in UC; and colorectal carcinoma and dysplasia in IBD. The goal is that this statement can aid in the optimization of the treatment strategy for Japanese patients with IBD and help identify high-risk patients that require early intervention, to provide a better long-term prognosis in these patients.

Application of novel magnified single balloon enteroscopy for a patient with Cronkhite-Canada syndrome.

We present a case of Cronkhite-Canada syndrome (CCS) in which the entire intestine was observed using a prototype of magnifying single-balloon enteroscope (SIF Y-0007, Olympus). CCS is a rare, non-familial gastrointestinal polyposis with ectodermal abnormalities. To our knowledge, this is the first report showing magnified intestinal lesions of CCS. A 73-year-old female visited our hospital with complaints of diarrhea and dysgeusia. The blood test showed mild anemia and hypoalbuminemia. The esophagogastroduodenoscopy and colonoscopy revealed diffuse and reddened sessile to semi-pedunculated polyps, resulting in the diagnosis of CCS. In addition to the findings of conventional balloon-assisted enteroscopy or capsule endoscopy, magnifying observation revealed tiny granular structures, non-uniformity of the villus, irregular caliber of the loop-like capillaries, scattered white spots in the villous tip, and patchy redness of the villus. Histologically, the scattered white spots and patchy redness of the villus reflect lymphangiectasia and bleeding to interstitium, respectively.

Laparoscopic-endoscopic cooperative surgery for a duodenal neuroendocrine tumor: A case report.

For neuroendocrine tumor G1, local resection is one of the primary treatment options. Endoscopic submucosal dissection has been proven to ensure complete resection with sufficient margins. However, duodenal endoscopic submucosal dissection has a high risk of duodenal perforation because of the thin duodenal wall and poor endoscopic maneuverability. During laparoscopic dissection, suturing can resolve perforation. Therefore, laparoscopic-endoscopic cooperative surgery (LECS) can ensure complete resection with a minimal margin to prevent stenosis, and suturing can resolve perforation. In short, LECS combines the advantages of both techniques. In the present case, a duodenal neuroendocrine tumor G1 in a 75-year-old man was successfully treated using LECS. The patient remained free from recurrence at 21 months postoperatively. LECS is feasible for a neuroendocrine tumor G1 ≤20 mm in size that has not invaded the muscularis propria or the lymphatic and venous vessels.

Risk factors for developing colorectal cancer in Japanese patients with ulcerative colitis: a retrospective observational study-CAPITAL (Cohort and Practice for IBD total management in Kyoto-Shiga Links) study I.

BACKGROUND AND AIMS: Patients with ulcerative colitis (UC) are at risk for developing colorectal cancer (CRC), despite the development of new therapeutic agents. Stratification of the individual UC-patient's risk would be helpful to validate the risk factors for CRC. The aim of this study was to evaluate the risk factors for the development of CRC in a large cohort of patients with UC. METHODS: Data were obtained from 12 hospitals in the Kyoto-Shiga region during 2003-2013. We performed a retrospective cohort study of 2137 patients with UC. RESULTS: In total, 60 lesions of CRC were detected in 43 (2.0%) of 2137 patients. 30 of the 43 patients were male. The median age was 53 years. The median duration of disease was 13 years, and 67.4% of these patients had a disease duration >10 years. Of the 43 patients, 34 (79.1%) had extensive colitis. Primary sclerosing cholangitis was detected in 2 patients (4.7%). The median corticosteroids (CS) dose was 6.4 g, and 4 patients were treated with a total of more than 10 g of CS. 18 of these patients underwent more than 1 year CS treatment. Of all 60 CRC lesions, 43 (71.7%) were located in the distal colon and 35 (58.3%) were of the superficial type. Moreover, the stage of CRC was stage 0 or I in 55.8% of the 43 patients with CRC. Multivariate analysis suggested that extensive colitis could be a risk factor for the development of advanced CRC in patients with UC. CONCLUSIONS: Our findings indicated that male, extensive colitis, long-term duration of UC and family history of CRC, but not concomitant primary sclerosing cholangitis, are important factors for predicting CRC in Japanese patients with UC. Moreover, long-standing extensive colitis might contribute to the progression of CRC. Further studies are required to establish CRC surveillance in Japanese patients with UC.

Evaluation of performance of the Omni mode for detecting video capsule endoscopy images: A multicenter randomized controlled trial.

BACKGROUND AND STUDY AIMS: Olympus recently developed a new algorithm called Omni mode that discards redundant video capsule endoscopy (VCE) images. The current study aimed to demonstrate the non-inferiority of the Omni mode in terms of true positives (TPs) and the superiority of the Omni mode with regard to reading time against a control (ordinary ES-10 system). PATIENTS AND METHODS: This multicenter prospective study included 40 patients with various small bowel diseases. VCE images were evaluated by 7 readers and 3 judging committee members. Two randomly allocated readers assessed the VCE images obtained using the 2 modalities for each patient. The order of the modalities was switched between the 2 readers and the interval between readings by the same reader was 2 weeks. The judging committee predefined clinically relevant lesions as major lesions and irrelevant lesions as minor lesions. The number of TPs for major and minor lesions and the reading times were compared between the modalities. The predefined non-inferiority margin for the TP ratio of the Omni mode compared with the control was 0.9. RESULTS: The estimated TP ratios and 95 % confidence intervals for total, major, and minor lesions were 0.87 (0.80 - 0.95), 0.93 (0.83 - 1.04), and 0.83 (0.74 - 0.94), respectively. Although non-inferiority was not demonstrated, the rate of detection of major lesions was not significantly different between the modalities. The reading time was significantly lower when using the Omni mode than when using the control. CONCLUSIONS: The Omni mode may be only appropriate for the assessment of major lesions.

Prognostic factors affecting early colectomy in patients with moderate to severe ulcerative colitis treated with calcineurin inhibitors.

Calcineurin inhibitors (CNIs) such as cyclosporine A (CSA) and tacrolimus (FK506) are often used as a second-line drug for steroid-refractory or steroid-dependent patients with ulcerative colitis (UC). The aim of the present study was to determine the prognostic factors for early colectomy. A total of 85 hospitalized patients with UC (CSA, 50 patients; FK506, 35 patients) were enrolled. Colectomy carried out within 60 days of starting CNI therapy was defined as 'early colectomy'. To assess the prognostic factors affecting early colectomy, clinical practical variables, including the Onodera-prognostic nutritional index (O-PNI): 10xAlb+0.005× (total lymphocyte count), were analyzed. The results demonstrated that the significant factors predicting early colectomy were i) disease severity, ii) immunomodulator-naïve history, iii) lower serum hematocrit, iv) lower serum albumin and v) lower O-PNI. In addition, the significant factors predicting overall colectomy were as follows: i) C7-HRP positivity and ii) >10,000 mg of prednisolone used prior to the initiation of CNI treatment. The combination of hematocrit and O-PNI enhanced the prediction of early colectomy. Clinical variables such as hematocrit and O-PNI were the significant factors predicting colectomy. These results may be used as a guide to predict the outcome of patients with UC in clinical settings.

Association between serum adalimumab concentrations and endoscopic disease activity in patients with Crohn's disease.

BACKGROUND AND AIMS: The serum trough level of adalimumab (ADA) associated with mucosal healing (MH) remains unclear. Our objective was to determine the association between ADA trough levels and the endoscopic activity in Crohn's disease. MATERIALS AND METHODS: This was a cross-sectional study including 42 patients with Crohn's disease. Endoscopic activity was assessed using the modified Rutgeerts scoring system. The primary outcome was mucosal healing, and the secondary outcomes were serum levels of C-reactive protein and albumin. RESULTS: Endoscopic disease activity negatively correlated with serum ADA trough levels (Spearman's rank correlation coefficient (ρ) = -0.42, P < 0.01). MH was achieved in 14 of 42 patients (33.3%). Serum ADA trough levels were significantly higher in the MH group than in the no-MH group (ADA mean trough level, 11.7 vs 7.5 µg/mL). The proportion of patients with ADA as the first biologic was significantly higher in the MH group than in the no-MH group (85.7% vs 53.5%, P = 0.04). The ADA trough levels that were best associated with normal C-reactive protein and albumin levels were 5.57 µg/mL (odds ratio [OR] 16.0, specificity 0.80) and 6.95 µg/mL (OR 9.2, specificity 0.81), respectively. The ADA trough level that was best associated with MH was 7.9 µg/mL (OR 13.5, specificity 0.86). The endoscopic disease activity was significantly higher in the patients with ADA as the second biologic as compared with those with ADA as the first biologic (P < 0.05). CONCLUSION: Mucosal healing requires higher ADA trough levels, compared with those required to normalization of routine clinical markers.

Prediction of clinical and endoscopic responses to anti-tumor necrosis factor-α antibodies in ulcerative colitis.

Objective In patients with ulcerative colitis (UC), the relationship between the initial endoscopic findings and the response to anti-tumor necrosis factor (TNF)-α antibodies remains unclear. We herein evaluated the potential of endoscopic assessment using the ulcerative colitis endoscopic index of severity (UCEIS) to predict the response to anti-TNF-α antibodies. Methods We enrolled 64 patients with UC undergoing anti-TNF-α maintenance therapy with infliximab (IFX) or adalimumab (ADA) between April 2010 and March 2015. Anti-TNF-α trough levels were determined by ELISA. Endoscopic disease activity was assessed using the UCEIS. Results The clinical response rate at 8 weeks was 77.4% for IFX and 66.7% for ADA. Serum albumin levels were significantly higher and the UCEIS bleeding descriptor before treatment was significantly lower in the responders than in the non-responders (p < 0.05 each). The CRP levels at 2 weeks were significantly lower in the responders (p < 0.001). The serum albumin levels before treatment were significantly higher and the UCEIS erosions and ulcers descriptor was significantly lower in the mucosal healing group than in the non-mucosal healing group (p < 0.05 each). A significant and negative correlation between the trough levels of anti-TNF-α antibodies and the UCEIS descriptors was observed. The trough levels of anti-TNF-α antibodies to achieve mucosal healing were 2.7 µg/mL for IFX and 10.3 µg/mL for ADA. Conclusions The UCEIS score, as well as some clinical markers (serum albumin and CRP levels), is useful for the prediction of the treatment outcome of UC patients in response to anti-TNF-α antibodies.

[Surgery for Multiple Gastrointestinal Stromal Tumors of the Small Intestine in Patients with Neurofibromatosis Type 1 - A Report of Three Cases].

We report 3 cases of multiple GIST of the small intestine in 3 patients with NF1 who have been followed for over 5 years. All patients presented with melena, and tumors of the small intestine suspected to be GIST were found on endoscopy. We performed partial resections of the small intestine for all 3 patients. After surgery, 1 patient had residual tumors that gradually enlarged during 8 year 2 months and another had residual tumors that have been stable for 8 years. In the third patient, we resected all the tumors, and there has been no sign of recurrence in 6 year 1 month.

Practice Guidelines for Primary Care of Acute Abdomen 2015.

Since acute abdomen requires accurate diagnosis and treatment within a particular time limit to prevent mortality, the Japanese Society for Abdominal Emergency Medicine, in collaboration with four other medical societies, launched the Practice Guidelines for Primary Care of Acute Abdomen that were the first English guidelines in the world for the management of acute abdomen. Here we provide the highlights of these guidelines (all clinical questions and recommendations were shown in supplementary information). A systematic and comprehensive evaluation of the evidence for epidemiology, diagnosis, differential diagnosis, and primary treatment for acute abdomen was performed to develop the Practice Guidelines for Primary Care of Acute Abdomen 2015. Because many types of pathophysiological events underlie acute abdomen, these guidelines cover the primary care of adult patients with nontraumatic acute abdomen. A total of 108 questions based on nine subject areas were used to compile 113 recommendations. The subject areas included definition, epidemiology, history taking, physical examination, laboratory test, imaging studies, differential diagnosis, initial treatment, and education. Japanese medical circumstances were considered for grading the recommendations to assure useful information. The two-step methods for the initial management of acute abdomen were proposed. Early use of transfusion and analgesia, particularly intravenous acetaminophen, were recommended. The Practice Guidelines for Primary Care of Acute Abdomen 2015 have been prepared as the first evidence-based guidelines for the management of acute abdomen. We hope that these guidelines contribute to clinical practice and improve the primary care and prognosis of patients with acute abdomen.

The Practice Guidelines for Primary Care of Acute Abdomen 2015.

BACKGROUND: Since acute abdomen requires accurate diagnosis and treatment within a particular time limit to prevent mortality, the Japanese Society for Abdominal Emergency Medicine in collaboration with four other medical societies launched the Practice Guidelines for Primary Care of Acute Abdomen that were the first English guidelines in the world for the management of acute abdomen. Here we provide the highlights of these guidelines [all clinical questions (CQs) and recommendations are shown in supplementary information]. METHODS: A systematic and comprehensive evaluation of the evidence for epidemiology, diagnosis, differential diagnosis, and primary treatment for acute abdomen was performed to develop the Practice Guidelines for Primary Care of Acute Abdomen 2015. Because many types of pathophysiological events underlie acute abdomen, these guidelines cover the primary care of adult patients with nontraumatic acute abdomen. RESULTS: A total of 108 questions based on 9 subject areas were used to compile 113 recommendations. The subject areas included definition, epidemiology, history taking, physical examination, laboratory test, imaging studies, differential diagnosis, initial treatment, and education. Japanese medical circumstances were considered for grading the recommendations to assure useful information. The two-step methods for the initial management of acute abdomen were proposed. Early use of transfusion and analgesia, particularly intravenous acetaminophen, were recommended. CONCLUSIONS: The Practice Guidelines for Primary Care of Acute Abdomen 2015 have been prepared as the first evidence-based guidelines for the management of acute abdomen. We hope that these guidelines contribute to clinical practice and improve the primary care and prognosis of patients with acute abdomen.

[Cases of Three Patients with Gastric Cancer and Metastasis to the Skeletal Muscle].

Metastasis to the skeletal muscle from gastric cancer is relatively rare. We report cases of 3 patients undergoing chemotherapy for gastric cancer with metastasis to the skeletal muscle. Case 1: A man in his 70s was diagnosed with advanced gastric cancer (cT4N3M1P0, stage IV), with metastasis to the lung, brain, lymph node, and iliopsoas muscle. Case 2: A man in his 60s was diagnosed with advanced gastric cancer (cT3N3M1P0, stage IV), with metastasis to the brain, lung, lymph node, and iliopsoas muscle. Case 3: A man in his 50s was diagnosed with advanced gastric cancer (cT4N3M1P0, stage IV), with metastasis to the urinary duct, lymph node, back muscle, and iliopsoas muscle. All 3 patients died within 7-8 months after the diagnosis due to progressive disease despite chemotherapy. The prognosis of these 3 patients was significantly poorer than that of patients in our hospital with metastasis not involving the skeletal muscle (p<0.01). Accordingly, metastasis to the skeletal muscle may be an adverse prognostic factor in gastric cancer.