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Background and Aim Several studies have identified postinduction therapy predictors of long‐term outcomes of ulcerative colitis (UC) in patients who experienced the first attack of the disease or relapsed after therapy. We aimed to identify the preinduction therapy predictors at admission that predicted early colectomy in patients with moderate to severe UC. Methods Ninety‐five patients with moderate to severe UC who underwent induction therapy at the Kyoto Prefectural University of Medicine hospital between August 2008 and March 2020 were retrospectively included and categorized into two groups: the colectomy group (n = 27) and the noncolectomy group (n = 68). The clinical parameters (age, gender, disease extent, and disease activity on admission), induction therapies administered [including 5‐aminosalicylic acid, steroids, immunomodulators, calcineurin inhibitor, and anti‐Tumor Necrosis Factor (TNF)‐α antibodies], and laboratory data (hemoglobin, albumin, C‐reactive protein, and cytomegalovirus reactivation on admission) were evaluated and compared between the two groups. Multivariate logistic regression analyses were performed to identify significant predictors of early colectomy, and P, We investigated the pre‐induction therapy predictors at admission that predicted early colectomy in patients with moderate to severe UC. UC patients were retrospectively categorized into the colectomy group and the non‐colectomy group, and clinical parameters, induction therapy administered, and laboratory data were compared between these two groups. Low serum albumin level (less than 2.45 g/dL) on admission were identified to be significant independent predictors of colectomy.

Objectives Preoperative grading of pancreatic neuroendocrine tumors (PanNET) is challenging. The aim of this study was to prospectively evaluate the use of a 25-gauge needle with a core trap for diagnosis and grading of PanNET. Methods This multicenter prospective trial was registered with the University Hospital Medical Information Network (UMIN000021409). Consecutive patients with suspected PanNET between June 2016 and November 2017 were enrolled. All patients underwent endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) using a 25-gauge needle with a core trap. Samples obtained after the first needle pass were used for central pathological review. EUS-FNB was evaluated in terms of (i) technical success rate, (ii) adequacy for histological evaluation, (iii) complication rate during the procedure, and (iv) concordance between PanNET grading on EUS-FNB and that after analysis of the resected tumor. Results Fifty-two patients were enrolled. Of the 36/52 patients who underwent surgical resection, 31 were finally diagnosed with PanNET and were eligible for analysis. The technical success rate of EUS-FNB was 100%. The rate of adequacy for histological evaluation was 90.3%. There were no complications related to EUS-FNB. The concordance rate between PanNET grading on EUS-FNB and that after analysis of the resected tumor was 82.6% (95% confidence interval = 61.22–95.05, P = 0.579). Conclusions EUS-FNB using a 25-gauge needle with a core trap is feasible, providing histological samples are of sufficient quality for diagnosis and grading of PanNET.

Background and Purpose— The treatment and prognosis of acute large vessel occlusion with mild symptoms have not been sufficiently studied. The present study aimed to investigate the clinical or radiological predictors of clinical outcome in patients with stroke with mild symptoms due to acute large vessel occlusion. Methods— Of 2420 patients with acute large vessel occlusion in the RESCUE-Japan Registry 2 (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism-Japan Registry 2), a multicenter prospective registry in Japan, patients with modified Rankin Scale scores of 0 to 2 before onset and initial National Institutes of Health Stroke Scale (NIHSS) scores of 0 to 5 were examined in post hoc analysis. We examined the clinical and radiological characteristics associated with a favorable outcome (modified Rankin Scale score, 0–2 at 90 days) using multivariate analysis, as well as the factors associated with a favorable outcome in patients treated with endovascular therapy. Results— We analyzed 272 patients (median age, 73 years; median NIHSS score on admission, 3). Eighty-six (31.6%) patients were treated with intravenous recombinant tissue-type plasminogen activator, 54 (19.9%) underwent endovascular therapy, and 208 (76.5%) showed a favorable outcome. In multivariate analysis, age P Conclusions— Younger age, lower initial NIHSS score, intravenous recombinant tissue-type plasminogen activator, and absence of hyperglycemia were independently associated with a favorable outcome in patients with acute large vessel occlusion with low NIHSS scores. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02419794.

Immune checkpoint inhibitors (ICIs) show promising clinical activity in advanced cancers. However, the safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies (ANA) are unclear. 191 patients treated with nivolumab, pembrolizumab, atezolizumab, or durvalumab for unresectable advanced cancers between September 2014 and December 2018 were identified retrospectively. Patients were divided into positive (ANA titers ≥ 1:160) and negative ANA groups (ANA titers

Recently, CAD EYE (Fujifilm, Tokyo, Japan), an artificial intelligence for the lesion recognition (CADe) and the optical diagnosis (CADx) of colorectal polyps, was released. We evaluated the function of CADe and CADx of CAD EYE. In this single-center retrospective study, we examined consecutive polyps ≤ 10 mm detected from March to April 2021 to determine whether CAD EYE could recognize them live with both normal- and high-speed observation using white-light imaging (WLI) and linked-color imaging (LCI). We then examined whether the polyps were neoplastic or hyperplastic live with magnified or non-magnified blue-laser imaging (BLI-LASER) or blue-light imaging (BLI-LED) under CAD EYE, comparing the retrospective evaluations with 5 experts and 5 trainees using still images. All polyps were histopathologically examined. We analyzed 100 polyps (mean size 3.9 ± 2.6 mm; 55 neoplastic and 45 hyperplastic lesions) in 25 patients. Regarding CADe, the respective detection rates of CAD EYE with normal- and high-speed observation were 85.0% and 67.0% for WLI (p = 0.002) and 89.0% and 75.0% for LCI (p = 0.009). Regarding CADx for differentiating neoplastic and hyperplastic lesions, the diagnostic accuracy values of CAD EYE with non-magnified and magnified BLI-LASER/LED were 88.8% and 87.8%. Regarding magnified BLI-LASER/LED, the diagnostic accuracy value of CAD EYE was not significantly different from that of experts (92.0%, p = 0.17), but that of trainees (79.0%, p = 0.04). We also found no significant differences in CADe or CADx between LED (53 lesions) and LASER (47 lesions). CAD EYE was a helpful tool for CADe and CADx in clinical practice.

BACKGROUND Hemophilia A causes a bleeding tendency due to the congenital absence of coagulation factor VIII or the production of antibodies against it. It is challenging to perform invasive procedures in patients with hemophilia A. Walled-off necrosis (WON) is a serious complication of acute pancreatitis. Recently, a new metallic stent has been used to drain WON. CLINICAL COURSE We treated a 32-year-old man who developed WON due to acute pancreatitis and has severe congenital hemophilia A. Since conservative treatment was ineffective, he underwent endoscopic ultrasonography (EUS)-guided transgastric WON drainage using a new metallic stent Hot AXIOS System. The procedure was successful without any severe hemorrhagic complications. Before and after the procedure, his clotting factors were strictly monitored by a hemophilia specialist. CONCLUSION EUS-guided pancreatic cyst drainage can be an effective option for WON in patients with severe congenital hemophilia, under adequate management.

BACKGROUNDIdiopathic dissecting cerebral aneurysms (IDCAs) are male dominant but are extremely rare in children. Many IDCAs in children are located in the posterior cerebral artery and the supraclinoid internal cervical artery. No cases of IDCA of the distal anterior cerebral artery (ACA) have been reported.OBSERVATIONSA previously healthy 7-month-old boy experienced afebrile seizures and presented at the authors’ hospital 1 week after the first seizure. He was not feeling well but had no neurological deficits. The authors diagnosed a ruptured aneurysm of the right distal ACA based on imaging results. He underwent emergency craniotomy to prevent re-rupture of the aneurysm. Using intraoperative indocyanine green videoangiography, the authors confirmed peripheral blood flow and then performed aneurysmectomy. Pathological examination of the aneurysm revealed a thickened intima, fragmentation of the internal elastic lamina, and a hematoma in the aneurysmal wall. The authors ultimately diagnosed IDCA because no cause was indicated, including a history of trauma. The boy recovered after surgery and was subsequently discharged with no complications.LESSONSThe authors reported, for the first time, IDCA of the distal ACA in an infant. The trapping technique is often used for giant fusiform aneurysms in infants. Indocyanine green videoangiography is useful for evaluating peripheral blood flow during trapping in this case.

Background Statins have been associated with reduced recurrence and better functional outcomes in patients with acute ischemic stroke. However, the effect of statins in patients with acute large vessel occlusion (LVO) is not well scrutinized. Methods and Results RESCUE (Recovery by Endovascular Salvage for Cerebral Ultra‐Acute Embolism)‐Japan Registry 2, a physician‐initiated registry, enrolled 2420 consecutive patients with acute LVO who were admitted to 46 centers across Japan within 24 hours of onset. We compared patients with and without statin use after acute LVO onset (statin group and nonstatin group, respectively) in terms of the modified Rankin scale at 90 days. We estimated that the odds ratios for the primary outcome was modified Rankin scale and we estimated the odds ratios for a 1‐scale lower modified Rankin scale adjusting for confounders. After excluding 12 patients without LVO and 9 patients without follow‐up, the mean age of 2399 patients was 75.9 years; men accounted for 55% of patients. Statins were administered to 447 (19%) patients after acute LVO onset. Patients in the statin group had more atherothrombotic cerebral infarctions (34.2% versus 12.1%, P P P P =0.02). The mortality at 90 days was lower in the statin group (4.7%) than the nonstatin group (12.5%; P P =0.02). Conclusions Statin administration after acute LVO onset is significantly associated with better functional outcome and mortality at 90 days.

Inflammation-based prognostic indicators have been developed to predict the prognosis in patients with pancreatic cancer. However, prognostic indices have not been established in patients with unresectable pancreatic cancer, including those without indication for chemotherapy at diagnosis. This study aimed to identify the predictors in all patients with unresectable pancreatic cancer. We retrospectively analyzed data of 119 patients with unresectable pancreatic cancer from June 2006 to September 2018. The following laboratory parameters were evaluated: the Glasgow Prognostic Score (GPS), modified GPS, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein albumin (CRP/Alb) ratio, and prognostic nutritional index (PNI). We performed time-dependent receiver operating characteristic analysis, overall survival (OS) analysis, and univariate and multivariate analyses to determine the prognostic factors in patients with unresectable pancreatic cancer. The cut-off value for NLR was determined to be 3.74. The 6-month OS rates in low and high NLR groups were 75.5% and 18.8% (P P = 0.003), metastatic pancreatic cancer (P = 0.037), no treatment (P P P P P P = 0.002), high CRP/Alb ratio (P P P = 0.046), no treatment (P P = 0.002), and high NLR (P

BACKGROUND Rapid urinary trypsinogen-2 dipstick test and levels of urinary trypsinogen-2 and trypsinogen activation peptide (TAP) concentration have been reported as prognostic markers for the diagnosis of acute pancreatitis. AIM To reconfirm the validity of all these markers in the diagnosis of acute pancreatitis by undertaking a multi-center study in Japan. METHODS Patients with acute abdominal pain were recruited from 17 medical institutions in Japan from April 2009 to December 2012. Urinary and serum samples were collected twice, at enrollment and on the following day for measuring target markers. The diagnosis and severity assessment of acute pancreatitis were assessed based on prognostic factors and computed tomography (CT) Grade of the Japanese Ministry of Health, Labour, and Welfare criteria. RESULTS A total of 94 patients were enrolled during the study period. The trypsinogen-2 dipstick test was positive in 57 of 78 patients with acute pancreatitis (sensitivity, 73.1%) and in 6 of 16 patients with abdominal pain but without any evidence of acute pancreatitis (specificity, 62.5%). The area under the curve (AUC) score of urinary trypsinogen-2 according to prognostic factors was 0.704, which was highest in all parameter. The AUC scores of urinary trypsinogen-2 and TAP according to CT Grade were 0.701 and 0.692, respectively, which shows higher than other pancreatic enzymes. The levels of urinary trypsinogen-2 and TAP were significantly higher in patients with extended extra-pancreatic inflammation as evaluated by CT Grade. CONCLUSION We reconfirmed urinary trypsinogen-2 dipstick test is useful as a marker for the diagnosis of acute pancreatitis. Urinary trypsinogen-2 and TAP may be considered as useful markers to determine extra-pancreatic inflammation in acute pancreatitis.

Streptozocin (STZ) is a key agent for treating advanced pancreatic neuroendocrine tumors (pNET). Most STZ regimens for pNET are daily and also include 5-fluorouracil (5FU), whereas STZ monotherapy and weekly regimens have also been applied in daily practice in Japan. The present study aimed to evaluate responses to weekly regimens and to STZ monotherapy, and to identify a predictive marker of a response to STZ. Clinical data regarding STZ-based chemotherapy for pNET were collected between 2015 and 2017 at 25 facilities. We analyzed the effects, safety, progression-free survival (PFS), and factors that correlate with responses to STZ. The overall objective response rate (ORR) of 110 patients who underwent STZ-based chemotherapy (monotherapy, 81.8%; weekly regimen 46.4%) was 21.8%, and PFS was 9.8 months. The ORR of weekly vs. daily regimens was 21.6 vs. 22.0% (P = 1.000), and that of monotherapy vs. combination therapy was 21.1 vs. 25.0% (P = 0.766). A Ki67 proliferation index (Ki67) of > 5% was a predictive marker of a response to STZ (P = 0.017), whereas regimen type, mono- or combination therapy, treatment line and liver tumor burden were not associated with responses. The frequencies of Grade ≥ 3 nausea and hematological adverse events were significantly lower for monotherapy than combination therapy (P = 0.032). The effects of weekly STZ monotherapy on pNET are comparable to those previously reported and the toxicity profile was acceptable. Ki67 > 5% was the sole predictive marker of an objective response.

Simple Summary The psoas muscle mass index (PMI) is a simplified tool used in the quantification of skeletal muscle. The aim of our study was to investigate whether the PMI at diagnosis or its decrease during chemotherapy can influence the prognosis of unresectable pancreatic cancer. The median overall survival (OS) was 278.0 (95% confidence interval (CI), 199.1–356.9) days in the high-PMI group, and 221.0 (95% CI, 90.9–351.1) days in the low-PMI group (p = 0.329). The median OS was 347.0 (95% CI, 289.1–404.9) days in the group without PMI decrease and 172.0 (95% CI, 129.8–214.2) days in the group with PMI decrease (p = 0.001). We determined that the PMI at diagnosis was not associated with OS in patients with unresectable pancreatic cancer receiving systemic chemotherapy, whereas PMI decrease during chemotherapy influenced the OS. Abstract The impact of the psoas muscle mass index (PMI) on survival is still poorly understood in unresectable pancreatic cancer. Thus, we aimed to investigate whether the PMI at diagnosis or its decrease during chemotherapy can influence the prognosis of unresectable pancreatic cancer. The data of 100 patients were analyzed, and they were divided into two groups according to the median PMI in each sex. Subsequently, 72 patients undergoing computed tomography (CT) within 30–100 days from CT at diagnosis were evaluated in terms of PMI change rate, and divided into two groups based on the median. We evaluated the clinical characteristics and outcomes in terms of the PMI at diagnosis or its decrease during chemotherapy. The median PMI was 5.00 in males, and 3.66 in females. The median overall survival (OS) was 278.0 days in the high-PMI group and 221.0 days in the low-PMI group (p = 0.329). The median PMI change rate was −2.4%. The median OS was 347.0 days in the group without PMI decrease and 172.0 days in the group with PMI decrease (p = 0.001). We determined that a pivotal prognostic factor was not the PMI at diagnosis, but rather PMI decrease during chemotherapy in unresectable pancreatic cancer.

Background and Objectives: Differential diagnosis to estimate the malignant potential of gastric submucosal tumor (g-SMT) is important for decision-making. This study evaluated the use of a 20G needle with a core trap for EUS-guided fine-needle biopsy (EUS-FNB) for g-SMT. Methods: This multicentric prospective trial was registered in the University Hospital Medical Information Network (UMIN000021410). Consecutive patients with g-SMT who presented at one of the nine Japanese Referral Centers between June 2017 and November 2018 were enrolled. All patients underwent EUS-FNB using a 20G needle with a core trap. Samples obtained with the first-needle pass were used for central pathological review. EUS-FNB was evaluated in terms of (i) technical success rate, (ii) adequacy for histological evaluation, (iii) rate of complications, (iv) accuracy for histological diagnosis of gastrointestinal stromal tumor (GIST), and (v) concordance between GIST mitotic index determined by EUS-FNB and after tumor resection. Results: The study included 52 patients. The technical success rate of EUS-FNB was 100%. The adequacy rate for histological evaluation was 90.4% (P < 0.001). There were no complications related to EUS-FNB. Of the 38/52 patients who underwent surgical resection, 36 were finally diagnosed with GIST. The sensitivity, specificity, and accuracy of EUS-FNB for the histological diagnosis of g-SMT were 80.6%, 100%, and 81.6%, respectively. The concordance rate between the mitotic index on EUS-FNB and that after analysis of the resected tumor was 89.7%. Conclusions: EUS-FNB using a 20G needle with a core trap is feasible, providing histological samples of sufficient quality for diagnosing g-SMT.

Background Endovascular therapy has been shown to be effective in patients with acute cerebral large‐vessel occlusion, but real‐world efficacies are unknown. Methods and Results We conducted a prospective registry at 46 centers between October 2014 and January 2017. Eligible patients were those who were aged 20 years or older, with acute cerebral large‐vessel occlusion, and who were hospitalized within 24 hours of the onset. We enrolled both consecutive patients who were treated with or without endovascular therapy. Endovascular therapy included thrombectomy, balloon angioplasty, stenting, local fibrinolysis, and piercing. The primary outcome was a favorable outcome as defined by a modified Rankin Scale of 0 to 2 at 90 days after onset. Secondary outcomes were modified Rankin Scale of 0 to 1 and mortality. Safety outcomes were intracerebral hemorrhage or a recurrence of ischemic stroke. We constructed the 2242 (1121 each) propensity score–matched patients cohort based on a propensity score for endovascular therapy and estimated the adjusted odds ratio, followed by sensitivity analyses on original 2399 (1278 in endovascular therapy versus 1121 in no endovascular therapy) patients. In the propensity score–matched cohort, favorable outcomes were observed in 35.3% and 30.7% of patients in the endovascular therapy and no endovascular therapy groups, respectively ( P= 0.02). The adjusted odds ratio for the favorable outcome was 1.44 (95% confidence interval, 1.10–1.86, P =0.007). The efficacy of endovascular therapy in achieving favorable outcomes did not differ between our subgroups and in the sensitivity analyses. Conclusions Endovascular therapy decreased disabilities at 90 days in real‐world patients with acute cerebral large‐vessel occlusion. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT02419794.

Chronic pancreatitis is considered to be an irreversible progressive chronic inflammatory disease. The etiology and pathology of chronic pancreatitis are complex; therefore, it is important to correctly understand the stage and pathology and provide appropriate treatment accordingly. The newly revised Clinical Practice Guidelines of Chronic Pancreatitis 2015 consist of four chapters, i.e., diagnosis, staging, treatment, and prognosis, and includes a total of 65 clinical questions. These guidelines have aimed at providing certain directions and clinically practical contents for the management of chronic pancreatitis, preferentially adopting clinically useful articles. These revised guidelines also refer to early chronic pancreatitis based on the Criteria for the Diagnosis of Chronic Pancreatitis 2009. They include such items as health insurance coverage of high-titer lipase preparations and extracorporeal shock wave lithotripsy, new antidiabetic drugs, and the definition of and treatment approach to pancreatic pseudocyst. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the publication of the first edition.

Background and aims Development of high-performance submucosal injection materials (SIMs) contribute to the advancement of endoscopic therapy for early-stage gastrointestinal neoplasms. This study aimed to develop a new ex vivo model that mimics the human gastrointestinal tract to evaluate the performance (the height and duration of the submucosal elevation) of various SIMs in detail. Methods A new ex vivo model that applies a constant tension to the tested specimen (the porcine gastric specimen) was developed. SIMs were injected into the submucosa at the center or edge of the tested specimen, and submucosal elevation heights (SEHs) were measured over time. Results The average value and standard deviation of SEH determined using the conventional model (the tested specimen was fixed with pins) were higher than those obtained using the new model, which showed that the new model could precisely measure the SEH of a given SIM. In addition, the performance (SEH) of SIMs decreased with increasing tension applied to the specimen, suggesting that the performance of SIMs deteriorates with the over-expansion of the gastrointestinal tract. The submucosal elevation formed at the specimen edge disappeared faster than that formed at the specimen's center. Conclusions The proposed new ex vivo model allows accurate SEH measurement under uniform conditions and detailed comparison of the performances of various types of SIMs and can contribute to the development of high-performance materials.

In fracture treatment, biological bone union generally depends on the bone's natural fracture healing capacity, even in surgically treated cases. Hydroxyapatite/collagen composite (HAp/Col) has high osteoconductivity and stimulates osteogenic progenitors. Furthermore, it has the potent capacity to adsorb bone morphogenetic proteins (BMPs). In this study, we prepared an injectable HAp/Col paste and evaluated its augmentation of bone union. Furthermore, the effect of HAp/Col paste combined with BMP-2 was also evaluated. We used a rat femur osteotomy model with a defect size of 1 mm. Male Wistar rats were assigned to one of the following four groups; a control group without any implant, a HAp/Col implant group, a group that received an absorbable collagen sponge (ACS) implant impregnated with BMP-2 (1 μg), and a group that received a HAp/Col implant impregnated with BMP-2 implant. Micro-CT analysis, three-point bending tests, and histological evaluation were performed. Bone union was achieved in two of eight cases in the HAp/Col group, five of eight cases in the ACS + BMP-2 group, and all cases in the HAp/Col + BMP-2 group at 8 weeks post-surgery. The control group did not achieve bone union. In addition, in the HAp/Col + BMP-2 group, the biomechanical strength of the fused femurs was comparable to that of the contralateral intact femur; the ratio of the mechanical load at the breaking point of the osteotomy side relative to that of the contralateral side was 1.00 ± 0.151 (SD). These results indicate that HAp/Col paste with or without BMP-2 augments bone union. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:129-137, 2018.

We investigated the efficacy of a Wilms' tumor gene 1 (WT1) vaccine combined with gemcitabine (GEMWT1) and compared it with gemcitabine (GEM) monotherapy for advanced pancreatic ductal adenocarcinoma (PDAC) in a randomized phase II study. We randomly assigned HLA-A*02:01– or HLA-A*24:02–positive patients with advanced PDAC to receive GEMWT1 or GEM. We assessed WT1-specific immune responses via delayed-type hypersensitivity (DTH) to the WT1 peptide and a tetramer assay to detect WT1-specific cytotoxic T lymphocytes (WT1-CTL). Of 91 patients enrolled, 85 were evaluable (GEMWT1: n = 42; GEM: n = 43). GEMWT1 prolonged progression-free survival [PFS; hazard ratio (HR), 0.66; P = 0.084] and improved overall survival rate at 1 year (1-year OS%; GEMWT1: 35.7%; GEM: 20.9%). However, the difference in OS was not significant (HR: 0.82; P = 0.363). These effects were particularly evident in metastatic PDAC (PFS: HR 0.51, P = 0.0017; 1-year OS%: GEMWT1 27.3%; GEM 11.8%). The combination was well tolerated, with no unexpected serious adverse events. In patients with metastatic PDAC, PFS in the DTH-positive GEMWT1 group was significantly prolonged, with a better HR of 0.27 compared with the GEM group, whereas PFS in the DTH-negative GEMWT1 group was similar to that in the GEM group (HR 0.86; P = 0.001). DTH positivity was associated with an increase in WT1-CTLs induced by the WT1 vaccine. GEM plus the WT1 vaccine prolonged PFS and may improve 1-year OS% in advanced PDAC. These clinical effects were associated with the induction of WT1-specific immune responses. Cancer Immunol Res; 6(3); 320–31. ©2018 AACR.

Background and Aims Histologic diagnosis of autoimmune pancreatitis (AIP) using EUS-guided FNA (EUS-FNA) is difficult. To address this issue, new fine-needle biopsy (FNB) needles were recently developed. Here, we prospectively evaluated 2 newly designed EUS-FNB needles for histologic evaluation in patients with type 1 AIP. Methods This was a prospective, randomized, multicenter trial comparing biopsy specimens obtained with a 22-gauge Franseen needle or a 20-gauge forward-bevel needle in patients with suspected type 1 AIP. AIP was diagnosed according to international consensus diagnostic criteria. The primary endpoint was the sensitivity of EUS-FNB needles, and secondary endpoints were the amount of specimen obtained, histology of the pancreas based on evaluation of lymphoplasmacytic sclerosing pancreatitis (LPSP), and contribution of histologic findings to the diagnosis of AIP. Results One hundred ten patients were randomly assigned to the Franseen group (22-gauge Franseen needle) or the forward-bevel group (20-gauge forward-bevel needle). EUS-FNB sampling was successful in all patients. Nine patients were excluded because of diagnoses other than AIP. Compared with the forward-bevel needle, the Franseen needle obtained a significantly greater number of high-power fields. Of 101 patients, 39 patients (78%) in the Franseen group and 23 patients (45%) in the Forward-bevel group were diagnosed with level 1 or 2 LPSP (P = .001). Thirty-six patients could not be diagnosed with type 1 AIP without EUS-FNB specimen results. Conclusions The 22-gauge Franseen needle should be routinely used for histologic diagnosis of type 1 AIP. (Clinical trial registration number: UMIN 000027668.)

Study design Retrospective single-center study. Objective To investigate whether a preoperative index predicts clinical outcome after laminoplasty for cervical spondylotic myelopathy. Summary of background data This is the first study using the modified K-line, which connects the midpoints of the spinal cord at the C2 and C7 levels on midsagittal magnetic resonance imaging, to assess the relationship between postoperative clinical outcome and anticipated degree of spinal cord shifting. Methods Sixty-one consecutive patients who underwent laminoplasty for the treatment of cervical spondylotic myelopathy between 2000 and 2011 at our hospital were retrospectively reviewed. The interval between the preoperative mK-line and the anterior structure of the spinal canal at each segment of the C3 to C6 levels (INTn, n = 3-6) were measured on sagittal T1-weighted magnetic resonance imaging, and the sum of the INTn (INTsum) was then calculated. The degree of posterior cord shift was defined as follows: %Csum = ΣCn; Cn = (Bn-An) × 100/An (n = 3-6; An and Bn represent the preoperative and postoperative intervals between the midpoint of the spinal cord and the anterior impingement at each segment on sagittal T1-weighted magnetic resonance imaging, respectively). In addition, we defined INTmin as the minimum interval of the INTn in each patient. All patients were divided into lordotic and nonlordotic groups on the basis of lateral neutral radiography. The Japanese Orthopaedic Association (JOA) scoring system and recovery rate of the JOA score for cervical myelopathy was evaluated as clinical outcomes. Results The recovery rate of the JOA score was 48.1%. The lordotic and nonlordotic groups contained 38 and 23 patients, respectively. Linear regression analysis revealed that INTmin was significantly correlated with the recovery rate of the patients in the nonlordotic group, whereas INTsum was not associated with recovery of the JOA score. Conclusion We identified INTmin as a predictive factor for clinical outcomes in patients with nonlordotic alignment after laminoplasty. Level of evidence 4.

Although viral RNA or infectious virions have been detected in the feces of individuals infected with human influenza A and B viruses (IAV/IBV), the mechanism of viral survival in the gastrointestinal tract remains unclear. We developed a model that attempts to recapitulate the conditions encountered by a swallowed virus. While IAV/IBV are vulnerable to simulated digestive juices (gastric acid and bile/pancreatic juice), highly viscous mucus protects viral RNA and virions, allowing the virus to retain its infectivity. Our results suggest that virions and RNA present in swallowed mucus are not inactivated or degraded by the gastrointestinal environment, allowing their detection in feces.

ObjectiveCorticosteroid has been established as the standard therapy for autoimmune pancreatitis (AIP), but the requirement for maintenance corticosteroid therapy is controversial. We conducted a randomised controlled trial to clarify the efficacy of maintenance corticosteroid therapy in patients with AIP.DesignWe conducted a multicentre, tertiary setting, randomised controlled trial. After the induction of remission with the initial oral prednisolone (PSL) treatment, maintenance therapy with PSL at 5–7.5 mg/day was continued for 3 years or withdrawn at 26 weeks. The primary endpoint was relapse-free survival over 3 years and the secondary endpoint was serious corticosteroid-related complications. All analyses were performed on an intention-to-treat basis.ResultsBetween April 2009 and March 2012, 49 patients with AIP were randomly assigned to the maintenance therapy group (n=30) or the cessation group (n=19). Baseline characteristics were not different between the two groups. Relapses occurred within 3 years in 11 out of 19 (57.9%) patients assigned to the cessation group, and in 7 of 30 (23.3%) patients in the maintenance therapy group. The relapse rate over 3 years was significantly lower in the maintenance therapy group than that in the cessation group (p=0.011). The relapse-free survival was significantly longer in the maintenance therapy group than that in the cessation group (p=0.007). No serious corticosteroid-related complications requiring discontinuation of PSL were observed.ConclusionsMaintenance corticosteroid therapy for 3 years may decrease relapses in patients with AIP compared with those who discontinued the therapy at 26 weeks.Trial registration numberUMIN000001818; Results.

We present the case of a 62-year-old Japanese man whose histological diagnosis was adenoendocrine cell carcinoma of the gallbladder at autopsy, but whose antemortem diagnosis was squamous cell carcinoma. The patient was admitted to hospital with complaints of occasional vomiting and abdominal pain. Abdominal computed tomography revealed a large tumor on the gallbladder involving the adjacent liver, colon, and duodenum, with multiple metastases in the greater omentum and paraportal lymph nodes. The serum level of squamous cell carcinoma antigen (SCCA) was high, whereas that of carbohydrate antigen (CA) 19-9, as well as that of carcinoembryonic antigen (CEA) was within the normal range. Due to these clinical features, we first suspected advanced squamous cell carcinoma of the gallbladder. After two cycles of gemcitabine monotherapy, the tumor had become enlarged and the regimen was changed to a combination of docetaxel and cisplatin. Though tumor regression was achieved and his serum SCCA level normalized after 3 months, the patient rejected additional chemotherapy and died 8 months after the diagnosis. The histopathological findings made by autopsy demonstrated the tumor to be an adenoendocrine cell carcinoma without squamous carcinoma cells. The case is interesting in that the clinical features were similar to those of squamous cell carcinoma of the gallbladder.

We present a case of systemic sarcoidosis. A 72-year-old Japanese woman, who was diagnosed with asymptomatic enlarged abdominal para-aortic lymph nodes in April 2000, was admitted to our hospital in December 2003 because of multiple mass lesions of the liver and spleen. She had hepatosplenomegaly and asymptomatic pulmonary fibrosis. Blood examination revealed cholestasis and progressing liver synthetic dysfunction. In laparoscopic photographs, various sizes of whitish flat lesions were scattered on the surface of the liver. Liver biopsy showed non-caseating epithelioid cell granulomas. These lesions of the spleen disappeared on contrast-enhanced computed tomography imaging, and serum liver dysfunction was improved rapidly after steroid therapy. Laparoscopy may be useful for the diagnosis of granulomatous liver disease, such as hepatobiliary sarcoidosis.

We previously demonstrated the importance of quality management procedures for the handling of human bone marrow stromal cells (hBMSCs) and provided evidence for the existence of osteogenic inhibitor molecules in BMSCs. One candidate inhibitor is the ephrin type-A receptor 5 (EphA5), which is expressed in hBMSCs and upregulated during long-term culture. In this study, forced expression of EphA5 diminished the expression of osteoblast phenotypic markers. Downregulation of endogenous EphA5 by dexamethasone treatment promoted osteoblast marker expression. EphA5 could be involved in the normal growth regulation of BMSCs and could be a potential marker for replicative senescence. Although Eph forward signaling stimulated by ephrin-B-Fc promoted the expression of ALP mRNA in BMSCs, exogenous addition of EphA5-Fc did not affect the ALP level. The mechanism underlying the silencing of EphA5 in early cultures remains unclear. EphA5 promoter was barely methylated in hBMSCs while histone deacetylation could partially suppress EphA5 expression in early-passage cultures. In repeatedly passaged cultures, the upregulation of EphA5 independent of methylation could competitively inhibit osteogenic signal transduction pathways such as EphB forward signaling. Elucidation of the potential inhibitory function of EphA5 in hBMSCs may provide an alternative approach for lineage differentiation in cell therapy strategies and regenerative medicine.

OBJECTIVES Increased dispersion of the QT interval has been proposed to be a novel marker for increased risk of ventricular arrhythmia and sudden cardiac death. This study examined whether QT dispersion is affected in patients with alcoholic pancreatitis. METHODS We measured the QT interval, corrected QT interval, activation recovery interval, activation time, recovery time, and their respective dispersions in 3 age- and gender-matched groups: patients with alcoholic pancreatitis [age, 58.9 +/- 11.8 years; male/female (M/F), 33/3], patients with alcohol dependence (age, 59.3 +/- 8.9 years; M/F, 33/4), and a healthy control group (age, 55.8 +/- 8.8 years; M/F, 33/3). RESULTS The QT dispersions in patients with alcoholic pancreatitis (62.4 +/- 19.9 milliseconds; P < 0.001) or alcohol dependence (58.2 +/- 19.6 milliseconds; P < 0.001) were significantly greater than in the control group (41.4 +/- 13.3 milliseconds). Similarly, the corrected QT dispersions in patients with alcoholic pancreatitis (68.5 +/- 22.8 milliseconds; P < 0.001) or alcohol dependence (65.3 +/- 23.6 milliseconds; P < 0.001) were significantly greater than in the control group (42.8 +/- 13.2 milliseconds). Both QT dispersion and QTc dispersion were longer in patients with alcoholic pancreatitis than those with alcohol dependence (P = 0.011 and P = 0.039, respectively). Simple linear regression analysis of the relationship between the RR and QT intervals revealed that the regression lines for patients with alcoholic pancreatitis and alcohol dependence were almost parallel. However, the slope of the regression line for the control group was significantly greater (P < 0.05) than for the other 2 lines. CONCLUSION The findings demonstrate increased QT and QTc dispersions in patients with either alcoholic pancreatitis or alcohol dependence. The QT dispersion and QTc dispersion were longer in patients with alcoholic pancreatitis than those with alcohol dependence.

UNLABELLED:We evaluated whether dexamethasone augments the osteogenic capability of bone marrow-derived stromal cells (BMSCs) and muscle tissue-derived stromal cells (MuSCs), both of which are thought to contribute to ectopic bone formation induced by bone morphogenetic protein-2 (BMP-2), and determined the underlying mechanisms. Rat BMSCs and MuSCs were cultured in growth media with or without 10-7 M dexamethasone and then differentiated under osteogenic conditions with dexamethasone and BMP-2. The effects of dexamethasone on cell proliferation and osteogenic differentiation, and also on ectopic bone formation induced by BMP-2, were analyzed. Dexamethasone affected not only the proliferation rate but also the subpopulation composition of BMSCs and MuSCs, and subsequently augmented their osteogenic capacity during osteogenic differentiation. During osteogenic induction by BMP-2, dexamethasone also markedly affected cell proliferation in both BMSCs and MuSCs. In an in vivo ectopic bone formation model, bone formation in muscle-implanted scaffolds containing dexamethasone and BMP-2 was more than two fold higher than that in scaffolds containing BMP-2 alone. Our results suggest that dexamethasone potently enhances the osteogenic capability of BMP-2 and may thus decrease the quantity of BMP-2 required for clinical application, thereby reducing the complications caused by excessive doses of BMP-2. HIGHLIGHTS:1. Dexamethasone induced selective proliferation of bone marrow- and muscle-derived cells with higher differentiation potential. 2. Dexamethasone enhanced the osteogenic capability of bone marrow- and muscle-derived cells by altering the subpopulation composition. 3. Dexamethasone augmented ectopic bone formation induced by bone morphogenetic protein-2.

Two types of autoimmune pancreatitis (AIP) have been reported, lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric chronic pancreatitis (IDCP), which are now recognized as type 1 and type 2 AIP, respectively. Since the clinical features of type 2 AIP have not been fully elucidated and this condition is frequently accompanied by inflammatory bowel disease (IBD), we performed a nationwide survey of patients with AIP complicated with IBD to precisely characterize this disease entity.We collected 138 cases of pancreatitis with complicating IBD from affiliated institutes specializing in AIP or IBD, and comparative study between the IDCP groups and type 1 AIP was performed.Histological examination revealed 15 AIP cases to be IDCP of institutional diagnosis, among which 11 cases were upgraded to IDCP of central diagnosis by an expert pathologist. The IDCP group exhibited younger onset age, no gender bias, frequent abdominal pain, and normal IgG4 value, similar to those of type 2 AIP reported previously. We also witnessed a lower prevalence of jaundice in type 2 AIP than in type 1 AIP that corresponded to imaging findings of less frequent pancreatic head swelling and scarce bile duct stenosis.A characteristic feature of type 2 AIP compared with type 1 AIP is a low frequency of obstructive jaundice that is related to rare lower bile duct stricture due to lower prevalence of pancreatic head swelling. Contrary to type 1 AIP, lower bile duct stricture in this condition has no apparent relation to sclerosing cholangitis.

The clinical diagnosis of chronic pancreatitis is usually based on imaging studies, pancreatic function tests, and the presence of characteristic clinical features. In Japan, diagnostic criteria for chronic pancreatitis were established in 1995. The secretin test (a duodenal intubation test) and the combination of noninvasive tests, N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA) and fecal chymotrypsin (FCT), have been recommended for evaluating exocrine pancreatic function in patients with chronic pancreatitis. In the present study, the diagnostic value of these two noninvasive tests was compared to the secretin test. Although noninvasive tests are less sensitive and specific for determining exocrine pancreatic dysfunction than the secretin test, greater reliability for diagnosing chronic pancreatitis can be obtained by performing the BT-PABA and FCT simultaneously. Assessment of exocrine pancreatic function is important not only to diagnose chronic pancreatitis but also to decide a treatment method with pancreatic enzyme preparation.

To investigate the origin of argyrophil small cell carcinoma (ASCC) of the uterine cervix, we examined the influence of dibutyryl cyclic adenosine 3',5'-monophosphate (dB-cAMP), a known differentiation inducer, on the characteristics of an ASCC cell line, TC-YIK, which has been shown to be a useful in vitro experimental model of ASCC. In TC-YIK cells after treatment with dB-cAMP, two specific antigenic markers of macrophages, CD14 and human leukocyte antigen-DR, were detected by flow cytometric analysis. In addition, interferon-gamma mRNA was detected by reverse transcription-polymerase chain reaction and interferon-gamma protein was detected by ELISA. More than 90% of the cells stained positive for alpha-naphthyl butyrate esterase, 1% of the cells showed phagocytotic activity against Micrococcus lysodeikticus, and 22% of the cells had M. lysodeikticus adsorbed on their surface. Furthermore, granulocyte-macrophage colony stimulating factor accelerated the proliferation of TC-YIK cells. These results indicate that dB-cAMP promotes differentiation of ASCC cells to macrophages. In contrast, less than 10% of the cells showed stellate morphology, suggesting differentiation to neuronal cells after treatment with dB-cAMP, as reported previously. Thus, TC-YIK cells have been shown to differentiate both into macrophage lineage cells and neuronal cells, suggesting that ASCC originates from undifferentiated stem cells.

BACKGROUND: Breast conserving therapy is being established as a standard therapeutic procedure for early breast cancer in Japan. However, the indications of radiotherapy and a standardized therapeutic procedure have not been established yet. In this study, complications following radiotherapy were evaluated in patients who had previously undergone breast conserving therapy at Tokushima University Hospital. METHODS From October 1989 to March 1996, 60 women with stage I or II breast cancer underwent radiation therapy after breast conserving surgery, and all patients were followed-up for a median of 27 months. Radiation morbidity scoring of the breast and adjacent organs was performed using the toxity criteria of the Radiation Therapy Oncology Group (RTOG) and European Organization for Research andTreatment of Cancer (EORTC). RESULTS: Only 1 patient developed local recurrence, and no distant metastasisor death was observed. The cause of recurrence in 1 case was considered to be due to extended intraductal component. Although transient dermal reaction was induced by irradiation of the breast, no side effects that may cause cosmetic problems were found. No serious radiation complications were found in the lungs, ribs, heart or other adjacent organs. CONCLUSION: The adverse reactions caused by irradiation does not reduce the merit of combined use of radiation therapy in breast conserving therapy, and therefore, are not the hesitation factor in application of radiotherapy.

Summary Background and purpose Brain swelling and/or hemorrhage can occur after carotid endarterectomy. This phenomenon is called the hyperperfusion syndrome. Several factors contribute to this syndrome. One is reperfusion in a maximally dilated vessel which means disappearance of cerebral reserve capacity (CRC). The aim of the study was to determine whether CRC measurement was useful for intraoperative and postoperative management of carotid endarterectomy. Patients and methods We studied 64 cases (male 53, female 11), 49-79 years. CRC was measured preoperatively using acetazolamide loading Xenon CT CBF examination (XeCT). Hypothermia (34-35°C) was induced during surgery in a patient with no CRC. Anesthesia was maintained the night after surgery and the systolic blood pressure was controlled below 120mmHg. Results CRC was absent in 10 patients. Postoperative CT did not reveal any hemorrhage or brain swelling. One patient experienced a transient restless state. Discussion and conclusions Cerebral hyperperfusion syndrome has been reported in 0.3∼6.0% of patients following carotid endarterectomy (vs 1.6% in our study without hemorrhage or brain swelling). These data suggest that information on CRC could be useful for selection and perioperative management of patients during carotid endarterectomy.