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The histological diagnosis of type 1 autoimmune pancreatitis (AIP) based on the findings obtained by an endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is feasible, but the diagnostic consistency of this method has not been confirmed. We determined the interobserver agreement among 20 pathologists regarding the diagnosis of type 1 AIP, including the distinction from pancreatic ductal adenocarcinoma (PDAC) using large tissue samples obtained by EUS-FNB. After guidance for diagnosing AIP with biopsy tissues was provided, a round 2 was performed. The median sensitivity and specificity for diagnosing PDAC vs. non-neoplastic diseases were 95.2% and 100%, respectively. In groups of specialists (n = 7) and the generalists (n = 13), Fleiss’ к-values increased from 0.886 to 0.958 and from 0.750 to 0.816 in round 2. The concordance was fair or moderate for obliterative phlebitis and storiform fibrosis but slight for ductal lesion of type 1 AIP. Discordant results were due to ambiguous findings and biopsy tissue limitations. Among the specialists, the ratio of cases with perfect agreement regarding the presence of storiform fibrosis increased in round 2, but agreement regarding obliterative phlebitis or ductal lesions was not improved. Although the histological definite diagnosis of type 1 AIP was achieved by most observers in > 60% of the cases, the confidence levels varied. Because some ambiguities exist, the histological diagnostic levels based on the diagnostic criteria of type 1 AIP should not be taken for granted. Guidance is effective for improving accurate PDAC diagnoses (notably by recognizing acinar-ductal metaplasia) and for evaluating storiform fibrosis.

The application of a load on the internal fixation of a trochanteric fracture exerts a moment along the lag screw, causing the proximal bone fragment to slide along the lag screw, allowing contact between the proximal and distal bone fragments, which promotes healing. However, excessive sliding is related to poor postoperative outcomes. We aimed to identify the risk factors for excessive sliding.We conducted a multicenter retrospective study including 115 trochanteric fractures sustained through low-energy trauma in 19 male and 96 female patients aged 60 years or older (mean age: 82.9 years) between September 2013 and December 2014. We measured the postoperative sliding distance after osteosynthesis using a sliding hip screw or intramedullary nailing, and classified participants with ≥8 mm of sliding into the excessive sliding group (ESG) and with8 mm into non-ESG. Finally, we investigated the risk factors of excessive postoperative sliding.Fifty participants were classified into the ESG and 65 participants into the non-ESG. Female sex (p = 0.0264), an A3 fracture type (p = 0.0003), greater tip-apex distance (p = 0.0250), and poor reduction in either the anteroposterior or lateral radiographic views (p = 0.0156) were identified as risk factors for excessive sliding by multivariate regression analysis.Female sex, an unstable fracture type, a greater tip-apex distance, and a poor reduction, in either the anteroposterior or lateral views, are associated with excessive postoperative sliding. Therefore, surgery should aim to achieve good reduction and stabilization from both radiographic views.

Background The clinical characteristics of IgG4-related sclerosing cholangitis (IgG4-SC) especially without autoimmune pancreatitis (AIP) have not been investigated in a large cohort. Aims To clarify the clinical characteristics of IgG4-SC and IgG4-SC without AIP. Methods We retrospectively reviewed imaging, serology, other organ involvement (OOI) and histology of 872 patients with IgG4-SC who participated in a Japanese nationwide survey in 2019, and compared these items between IgG4-SC with and without AIP. Results AIP was present in 83.7% (730/872) of IgG4-SC. In IgG4-SC, bile duct wall thickening was observed on ultrasound (528/650; 81.2%), computed tomography (375/525; 71.4%) and magnetic resonance imaging or cholangiopancreatography (290/440; 65.9%). An elevated serum IgG4 level (≥ 135 mg/dL) was found in 88.0% (322/366). IgG4-related OOI other than AIP was observed in 25.2% (211/836). The proportion of females was significantly higher in IgG4-SC without AIP (28.9% vs. 20.1%; p = 0.025). Hilar stricture was the most common cholangiographic type in IgG4-SC without AIP (39/107; 36.4%).There were no significant differences between IgG4-SC with and without AIP in the rates of bile duct wall thickening, elevated serum IgG4 level, or IgG4-related OOI. Conclusions The clinical characteristics of IgG4-SC was similar between IgG4-SC with and without AIP in a large cohort.

The utility of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) for gastric subepithelial lesions (SELs) has been reported. In this study, we examined the optimal number of needle punctures during EUS-FNB for gastric SELs without rapid on-site evaluation (ROSE). The factors that allowed for a single needle puncture to arrive at the correct diagnosis were also analyzed. We conducted a retrospective study of all patients who underwent EUS-FNB to evaluate gastric SELs between April 2015 and September 2020; 51 patients with 57 gastric SELs were enrolled. The optimal number of needle punctures was determined when additional needle passes did not increase diagnostic sensitivity by more than 10%. Factors allowing for only a single needle puncture to arrive at the correct diagnosis were identified by univariate and multivariate logistic regression analyses. EUS-FNB resulted in a definitive final diagnosis in 48 of 57 lesions (84%). Lesions in the gastric body (odds ratio [OR] 6.15, 95% confidence interval [CI] 1.75–21.6; P

Background Chronic pancreatitis is a known risk factor of pancreatic cancer (PDAC). A similar association has been suggested but not demonstrated for autoimmune pancreatitis (AIP). Objective The aim of our study was to identify and analyse all published cases of AIP and PDAC co-occurrence, focusing on the interval between the diagnoses and the cancer site within the pancreas. Methods Relevant studies were identified through automatic searches of the MEDLINE, EMBASE, Scopus, and Web of Science databases, and supplemented by manual checks of reference lists in all retrieved articles. Missing/unpublished data were obtained from the authors of relevant publications in the form of pre-prepared questionnaires. Results A total of 45 cases of PDAC in AIP patients were identified, of which 12 were excluded from the analysis due to suspicions of duplicity or lack of sufficient data. Thirty-one patients (94%) had type 1 AIP. Synchronous occurrence of PDAC and AIP was reported in 11 patients (33%), metachronous in 22 patients (67%). In the metachronous group, the median period between diagnoses was 66.5 months (2–186) and a majority of cancers (86%) occurred more than two years after AIP diagnosis. In most patients (70%), the cancer originated in the part of the pancreas affected by AIP. Conclusions In the literature, there are reports on numerous cases of PDAC in AIP patients. PDAC is more frequent in AIP type 1 patients, typically metachronous in character, and generally found in the part of the pancreas affected by AIP.

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

Background and aims Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is used for the histopathological diagnosis of any type of gastrointestinal disease. Few adverse events are experienced with this procedure; however, the actual rate of adverse events remains unclear. This study aimed to clarify the current status of cases that experienced adverse events related to the EUS-FNA procedure used for histopathologic diagnoses. Methods A retrospective analysis of cases with EUS-FNA-related adverse events in Japanese tertiary centers was conducted by assessing the following clinical data: basic case information, FNA technique, type of procedural adverse events, and prognosis. Results Of the 13,566 EUS-FNA cases overall, the total number of cases in which adverse events related to EUS-FNA occurred was 234. The incidence of EUS-FNA-related adverse events was ~1.7%. Bleeding and pancreatitis cases accounted for ~49.1% and 26.5% of all adverse events, respectively. Bleeding was the most common adverse event with only seven cases requiring blood transfusion. In cases with neuroendocrine tumors, pancreatitis was the most frequent adverse event. Needle tract seeding because of EUS-FNA was observed during the follow-up period in only ~0.1% of cases with pancreatic cancer. There was no mortality because of adverse events caused by EUS-FNA. Conclusions This study revealed that the adverse events-related EUS-FNA for histopathologic diagnoses were not severe conditions, and had low incidence.

Background/purpose Epidemiological data on immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) are scarce. Method We randomly selected healthcare facilities from a list of all facilities in Japan. The selection rate was determined according to a stratification based on the facility characteristics and scale. We sent questionnaires to the selected facilities enquiring about the number and sex of patients with IgG4-SC in 2018. Among responding facilities, we further inquired about the clinical characteristics of the patients with IgG4-SC. Results We selected 1,180 departments from health centers across Japan. Of them, 532 (45.1%) responded to the questionnaires. The number of reported patients with IgG4-SC was 1,045, and the estimated point prevalence was 2.18 (95% confidence interval, 2.13-2.23) per 100,000 population. In addition, we enrolled 1,096 patients with IgG4-SC, combining data from previously and newly registered patients. Male patients comprised 79.5% of the population and patients aged 60-80 years had the highest risk for developing the disease. The follow-up period was 5.1±4.0 years and the 5- and 10-year overall survival rates were 95.3% and 89.0%, respectively. Conclusions The point prevalence of IgG4-SC was 2.18 per 100,000 population. The epidemiological features were similar to those observed in previous studies.

The biopsy-based diagnosis of autoimmune pancreatitis (AIP) is difficult but is becoming imperative for pathologists due to the increased amount of endoscopic ultrasound-guided biopsy tissue. To cope with this challenge, we propose guidance for the biopsy diagnosis of type 1 AIP. This guidance is for pathologists and comprises three main parts. The first part includes basic issues on tissue acquisition, staining, and final diagnosis, and is intended for gastroenterologists as well. The second part is a practical guide for diagnosing type 1 AIP based on the AIP clinical diagnostic criteria 2018. Inconsistent histological findings, tips for evaluating IgG4 immunostaining and key histological features including the ductal lesion and others are explained. Storiform fibrosis and obliterative phlebitis are diagnostic hallmarks but are sometimes equivocal. Storiform fibrosis is defined as spindle-shaped cells, inflammatory cells and fine collagen fibers forming a flowing arrangement. Obliterative phlebitis is defined as fibrous venous obliteration with inflammatory cells. Examples of each are provided. The third part describes the differentiation of AIP from pancreatic ductal adenocarcinoma (PDAC), focusing on histological features of acinar-ductal metaplasia in AIP, which is an important mimicker of PDAC. This guidance will help standardize pathology reports of pancreatic biopsies for diagnosing type 1 AIP.

Background and aim In chronic pancreatitis (CP) patients, diagnosis of small pancreatic lesions by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is challenging. Thus, the aim of the present study was to investigate whether CP influences the diagnostic ability of EUS-FNA for pancreatic lesions ≤10 mm. Methods One hundred and seventeen patients who underwent EUS-FNA for pancreatic lesions ≤10 mm in size were enrolled. Patients were classified into two groups based on features of CP observed by EUS (EUS-CP features) in accordance with the Rosemont classification. The CP group was defined as cases consistent with CP or suggestive of CP, and the non-CP group was defined as cases indeterminate for CP or normal. Factors influencing the diagnostic accuracy of EUS-FNA and CP status in pancreatic tumors were also investigated. Results Diagnostic ability of EUS-FNA (overall cases, non-CP vs CP) had sensitivity (80.4%, 96.7% vs 57.1%; P 0.05), and accuracy (91.5%, 98.6% vs 80.4%; P = 0.001). In multivariate analysis of factors influencing the accuracy of EUS-FNA, CP significantly lowered the accuracy (P = 0.048; odds ratio [OR] = 9.21). Among pancreatic cancer patients, the number of CP patients was significantly higher than the number of patients with benign lesions (P = 0.023). In multivariate analysis, lobularity without honeycombing was more frequently observed in cases of pancreatic cancer (P = 0.018; OR, 12.65). Conclusion Endoscopic ultrasound-guided FNA offers high accuracy for small pancreatic lesions ≤10 mm. However, in cases with CP, the diagnostic ability of EUS-FNA is significantly reduced.

Summary Background IgG4-related disease is a newly recognised immunopathological entity that includes autoimmune pancreatitis, IgG4-related sialadenitis, and IgG4-related kidney disease. To understand the genetic landscape of IgG4-related disease, we did a genome-wide association study. Methods We did a genome-wide association study of Japanese individuals, initially screening 857 patients with IgG4-related disease at 50 Japanese research institutions and DNA samples from 2082 healthy control participants from the Nagahama Prospective Genome Cohort for the Comprehensive Human Bioscience. From Oct 27, 2008, to July 22, 2014, we enrolled 835 patients and used data from 1789 healthy participants. Only patients with confirmed diagnosis of IgG4-related disease according to the international diagnostic criteria were included. Genotyping was done with the Infinium HumanOmni5Exome, HumanOmni2.5Exome, or HumanOmni2.5 Illumina arrays, and genomic distributions were compared between case and control samples for 958 440 single nucleotide polymorphisms. The HLA region was extensively analysed using imputation of HLA alleles and aminoacid residues. Fine mapping of the FCGR2B region was also done. Associations between clinical manifestations of disease and the genetic variations identified in these two genes were examined. Findings We identified the HLA-DRB1 (p=1·1×10−11) and FCGR2B (p=2·0×10−8) regions as susceptibility loci for IgG4-related disease. We also identified crucial aminoacid residues in the β domain of the peptide-binding groove of HLA-DRB1, in which the seventh aminoacid residue showed the strongest association signal with IgG4-related disease (p=1·7×10−14), as has been reported with other autoimmune diseases. rs1340976 in FCGR2B showed an association with increased FCGR2B expression (p=2·7×10−10) and was in weak linkage disequilibrium with rs1050501, a missense variant of FCGR2B previously associated with systemic lupus erythematosus. Furthermore, rs1340976 was associated with the number of swollen organs at diagnosis (p=0·011) and IgG4 concentration at diagnosis (p=0·035). Interpretation Two susceptibility loci for IgG4-related disease were identified. Both FCGR2B and HLA loci might have important roles in IgG4-related disease development. Common molecular mechanisms might underlie IgG4-related disease and other immune-related disorders Funding The Japanese Ministry of Health, Labour, and Welfare, the Japanese Agency of Medical Research and Development, and Kyoto University Grant for Top Global University Japan Project.

Chronic pancreatitis (CP) is a fibro-inflammatory disease of the pancreas. Early diagnosis and intervention, before CP becomes established and irreversible, are essential to improve the long-term outcomes. The world’s first diagnostic criteria for early CP were proposed in Japan in 2009, but their clinical utility remains elusive. This study aimed to clarify whether patients with early CP progress to definite CP. This is a multicenter, prospective study. Patients diagnosed as having early CP according to the Japanese diagnostic criteria were prospectively followed for 2 years. Clinical profiles including symptoms, drinking and smoking status, laboratory data, imaging findings and treatments were analyzed. Among the 83 patients who completed the 2-year follow-up period, four (4.8%) patients progressed to definite CP. The diagnosis of 48 (57.8%) patients was unchanged, and that of 31 (37.3%) patients was downgraded. All the four progressive patients were male, alcohol-related, smokers (3 current and 1 ever), and continued drinking. Comparison of the clinical profiles between the progression group (n = 4) and non-progression group (n = 79) revealed that etiology (alcohol-related), smoking status and presence of acute pancreatitis episodes were associated with the progression to definite CP. The Japanese diagnostic criteria could identify some patients before the progression to definite CP, while the majority of the patients did not progress. Trial registration number: UMIN000015992.

Objective: To investigate the usefulness of the combination of neurological findings and magnetic resonance imaging (MRI) as a prognostic predictor in patients with motor complete cervical spinal cord injury (CSCI) in the acute phase. Design: A cross-sectional analysis Setting: Department of Orthopaedic Surgery, Spinal Injuries Center Participants/Methods: Forty-two patients with an initial diagnosis of motor complete CSCI (AIS A, n = 29; AIS B, n = 13) within 72 h after injury were classified into the recovery group (Group R) and the non-recovery group (Group N), based on the presence or absence of motor recovery (conversion from AIS A/B to C/D) at three months after injury, respectively. The Neurological Level of Injury (NLI) at the initial diagnosis was investigated and the presumptive primary injured segment of the spinal cord was inferred from MRI performed at the initial diagnosis. We investigated whether or not the difference between the presumptive primary injured segment and the NLI exceeded one segment. The presence of a difference between the presumptive primary injured segment and the NLI was compared between Groups R and N. Results: The number of cases with the differences between the presumptive primary injured segment and the NLI was significantly higher in Group N than in Group R. Conclusion: The presence of differences between the presumptive primary injured segment and the NLI might be a poor improving prognostic predictor for motor complete CSCI. The NLI may be useful for predicting the recovery potential of patients with motor complete CSCI when combined with the MRI findings.

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

Swallowing dysfunction, which may cause aspiration pneumonia, is one of the most important complications of treatment of traumatic cervical spinal cord injury (CSCI); however, the mechanism of dysphagia is not well understood. No previous studies have reported the association between morphological changes of the soft tissue and dysphagia. We aimed to determine the factors associated with severity of dysphagia after CSCI and elucidate its mechanism. We conducted a prospective analysis of patients with acute traumatic CSCI who were admitted within 2 weeks of the injury. Dysphagia was evaluated using the Dysphagia Severity Scale (DSS) 2 weeks after the injury. The widths of the retropharyngeal and retrotracheal spaces were measured to assess soft tissue damage owing to the injury using sagittal images of computed tomography. We also assessed age, surgery of the injured cervical spine, presence of tracheostomy, osteophyte behind the pharynx, level of injury, and motor score 2 weeks after the injury. A total of 136 persons met our criteria. Given that 44 persons were categorized under grades

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

Autoimmune pancreatitis (AIP) has the potential to transform into chronic pancreatitis with pancreatic stone involvement. This retrospective investigation sought to clarify the risk factors for stone formation in type 1 AIP.Questionnaires on patients with type 1 AIP were sent to 22 high-volume medical centers across Japan to compare the clinical features of patients with and without pancreatic stone formation.Of the completed records on 624 type 1 AIP patients, 31 (5%) had experienced pancreatic stones. Median follow-up duration was 1853 days. Bentiromide test values at diagnosis were significantly lower, and hemoglobin A1c values after corticosteroid treatment were significantly higher in patients with pancreatic stones. Imaging results disclosed that pancreatic atrophy and hilar or intrahepatic bile duct stenosis were significantly more frequent in patients with pancreatic stone formation. Pancreatic head swelling tended to be more frequent in this group as well. On the other hand, a shorter follow-up period was associated with the nonformation of pancreatic stones.The increased frequency of pancreatic head swelling in type 1 AIP patients exhibiting pancreatic stones indicated a propensity for pancreatic juice stasis with subsequent stone development and pancreatic dysfunction occurring over longer periods of disease duration.

Background Endoscopic papillary large balloon dilation (EPLBD) has been increasingly used for the management of large common bile duct (CBD) stones. Although EPLBD is often preceded by endoscopic sphincterotomy (EST), EPLBD alone without EST has been increasingly reported as an alternative to EST for large CBD stones. Methods This multicenter randomized trial was conducted at 19 Japanese institutions to compare the efficacy and safety of EPLBD alone versus EST for the removal of large (≥ 10 mm) CBD stones. The primary end point was complete stone removal in a single session. The secondary end points included: overall complete stone removal, lithotripsy use, procedure time, adverse events, and cost. Results 171 patients with large CBD stones were included in the analysis. The rate of single-session complete stone removal was significantly higher in the EPLBD-alone group than in the EST group (90.7 % vs. 78.8 %; P = 0.04). Lithotripsy use was significantly less frequent in the EPLBD group than in the EST group (30.2 % vs. 48.2 %; P = 0.02). The rates of early adverse events were comparable between the two groups: rates of overall adverse events were 9.3 % vs. 9.4 % and of pancreatitis were 4.7 % vs. 5.9 % in the EPLBD and EST groups, respectively. The procedure costs were $1442 vs. $1661 in the EPLBD and EST groups, respectively (P = 0.12). Conclusion EPLBD without EST for the endoscopic treatment of large CBD stones achieved a significantly higher rate of complete stone removal in a single session compared with EST, without increasing adverse events.

Background/purpose Placement of uncovered self-expandable metallic stents (U-SEMSs) of patients with unresectable perihilar cholangiocarcinoma (UPHC) is recommended as the treatment of first choice to address bile stasis. The aim of this study was to determine which of the following two endoscopic stents might be the stent of first choice for the treatment of biliary stasis in patients with UPHC: plastic stents (PSs) or U-SEMSs. Methods U-SEMSs, deployed as a stent-in-stent, were selected as the stents of first choice from 2013 and 2014, while PSs began to be selected as the stents of first choice from 2015 onward. Results The median time to recurrent biliary obstruction were 66 days in the PS group (N = 38) and 105 days in the U-SEMS group (N = 37; P = .04). Emergency endoscopy was necessitated in 76.3% (29/38) of patients of the PS group and 54.1% (20/37) of patients of the U-SEMS group (P = .0434). The success rate of the first reintervention was 96.5% (27/29) in the PS group and 55% (11/20) in the U-SEMS group (P = .0002). Sustainable chemotherapy could be carried out in 55.2% of patients in the PS group and 32.4% of patients in the U-SEMS group (P = .0472). Multivariate analysis identified selection of U-SEMS as the stent of first choice as the only independent factor predictive of successful reintervention (P = .0016, odds ratio = 0.058). However, the stent selection was not an independent factor for feasible chemotherapy. Conclusions Plastic stent placement could enhance the success rate of reintervention in patients with UPHC and might be facilitated by sustainable chemotherapy. However, stent selection might not have an influence on the prognosis.

Diffuse idiopathic skeletal hyperostosis (DISH) is a relatively common progressive noninflammatory entheses disease. Patients are often asymptomatic or are undiagnosed due to minor chronic symptoms. We herein report a rare case in which the primary symptom was sudden-onset upper airway obstruction due to exuberant osteophytosis in the cervical spine. Treatment was successful with careful airway management and surgical osteophyectomy. Most DISH cases in the literature with airway obstruction have been managed with tracheotomy. However, the safety and necessity of this approach remain questionable. We herein discuss the possibility of conservative management as a choice of airway control. Airway obstruction due to DISH may be underrecognized. This highlights the importance of including DISH in the differential diagnosis of airway obstruction. In addition, a detailed evaluation and personalized care for each individual case is essential.

The overall objective of these guidelines is to provide evidence-based recommendations for the diagnosis and management of immunoglobulin G4 (IgG4)-related digestive disease in adults and children. IgG4-related digestive disease can be diagnosed only with a comprehensive work-up that includes histology, organ morphology at imaging, serology, search for other organ involvement, and response to glucocorticoid treatment. Indications for treatment are symptomatic patients with obstructive jaundice, abdominal pain, posterior pancreatic pain, and involvement of extra-pancreatic digestive organs, including IgG4-related cholangitis. Treatment with glucocorticoids should be weight-based and initiated at a dose of 0.6–0.8 mg/kg body weight/day orally (typical starting dose 30-40 mg/day prednisone equivalent) for 1 month to induce remission and then be tapered within two additional months. Response to initial treatment should be assessed at week 2–4 with clinical, biochemical and morphological markers. Maintenance treatment with glucocorticoids should be considered in multi-organ disease or history of relapse. If there is no change in disease activity and burden within 3 months, the diagnosis should be reconsidered. If the disease relapsed during the 3 months of treatment, immunosuppressive drugs should be added.

Background and Objectives: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and fine needle biopsy (FNB) are effective techniques that are widely used for tissue acquisition. However, it remains unclear how to obtain high-quality specimens. Therefore, we conducted a survey of EUS-FNA and FNB techniques to determine practice patterns worldwide and to develop strong recommendations based on the experience of experts in the field. Methods: This was a worldwide multi-institutional survey among members of the International Society of EUS Task Force (ISEUS-TF). The survey was administered by E-mail through the SurveyMonkey website. In some cases, percentage agreement with some statements was calculated; in others, the options with the greatest numbers of responses were summarized. Another questionnaire about the level of recommendation was designed to assess the respondents' answers. Results: ISEUS-TF members developed a questionnaire containing 17 questions that was sent to 53 experts. Thirty-five experts completed the survey within the specified period. Among them, 40% and 54.3% performed 50–200 and more than 200 EUS sampling procedures annually, respectively. Some practice patterns regarding FNA/FNB were recommended. Conclusion: This is the first worldwide survey of EUS-FNA and FNB practice patterns. The results showed wide variations in practice patterns. Randomized studies are urgently needed to establish the best approach for optimizing the FNA/FNB procedures.

The treatment of small (≤ 2 cm), sporadic localized non-functional pancreatic neuroendocrine neoplasms (PNENs) is often controversial. This study aimed to investigate the clinical outcomes with observation and surgical resection in small PNENs. Seventy-five patients with small localized sporadic non-functional PNENs ≤ 2 cm, who underwent observation or surgical resection, were retrospectively reviewed. Changes in tumor size during follow-up in the observation group were also investigated. The median age of the cohort was 61 (range 35–81) years. The tumor grades were G1, G2, and unknown, in 61 (81.3%), 8 (10.7%), and 6 (8.0%) patients, respectively. The mean follow-up periods in the observation (n = 23) and surgical resection groups (n = 52) were 52.3 (range 6.8–133.3) months and 73.0 (range 9.1–179.9) months, respectively. The median overall survival was not reached. During follow-up, no patient died of PNENs, two died of other diseases, three had lymph node metastases, and one experienced recurrence after surgical resection. There was no significant difference in overall survival between the observation and surgical resection groups (hazard ratio: 0.031, P = 0.417). The mean change in tumor size in the observation group was + 0.30 mm (range − 1.6 to + 3.0 mm). No deaths, tumor progression, lymph node metastases, distant metastases, or recurrence were noted in patients with PNENs ≤ 1 cm (n = 36). The prognosis of small localized PNENs is good. Observation may be an alternative to surgery in high-risk patients and those with small G1 tumors, particularly those measuring ≤ 1 cm.

Experimental study with mice. Spasticity is a common complication after spinal cord injury (SCI) and has detrimental aspects, such as persistent pain and involuntary muscle spasms. This study aimed to assess the influence of antispastic therapy on locomotor function after SCI. University-based laboratory in Fukuoka, Japan. A mouse model of spasticity was developed by producing incomplete SCI at the 9th thoracic level. At 8 weeks after SCI, an antispastic drug, baclofen, was intraperitoneally administered to six injured and two sham-operated mice. The severity of spasticity was evaluated by the modified Ashworth scoring (MAS) system, and locomotor function was evaluated by the Basso–Beattie–Bresnahan (BBB) scale/Basso mouse score (BMS). The administration of baclofen significantly improved spasticity in the SCI mice and the mean MAS decreased to from 6.2 to 2.8. However, at the same time, it significantly exacerbated the locomotor dysfunction of the SCI mice and the mean BMS decreased from 4.7 to 2.3. The time-course of the changes in locomotor function coincided with the time-course of the spasticity score. We also confirmed that the administration of baclofen was not associated with any changes in either locomotor function or spasticity of the sham-operated control mice. Our results suggest that spasticity has a certain beneficial effect on ambulation ability. It is important to note that antispastic treatments may be associated with a risk of impairing the preserved function of chronic SCI patients.

Retrospective chart audits. To investigate the optimal timing at which permanent complete cervical spinal cord injury (CSCI) can be confirmed when evaluating paralysis caused by traumatic CSCI. Department of Orthopedic Surgery, Spinal Injuries Center, Japan. Two-hundred and three patients with CSCI that was classified with an American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade A (AIS A) within 72 h of the initial diagnosis of traumatic CSCI were included in the present study. Neurological data from the time of the initial diagnosis to 1 year after the injury were extracted. The number of those with recovery from AIS A and changes of AIS in the recovery were examined. Thirty-five of 203 (17%) patients whose injuries were initially classified with an AIS A showed recovery from AIS A. Thirty-four of 35 (97%) patients showed recovery from AIS A within 8 weeks after injury. If CSCI patients with AIS A have not recovered by 8 weeks, the likelihood that they will recover from AIS A is marginal. However, this conversely means that we must consider the possibility that a patient with a traumatic CSCI classified with an AIS A may still show recovery from AIS A within the first 8 weeks after injury.

The diagnosis of pancreatic cystic lesions remains challenging. This study aimed to investigate the diagnostic ability of carcinoembryonic antigen (CEA), cytology, and artificial intelligence (AI) by deep learning using cyst fluid in differentiating malignant from benign cystic lesions. We retrospectively reviewed 85 patients who underwent pancreatic cyst fluid analysis of surgical specimens or endoscopic ultrasound-guided fine-needle aspiration specimens. AI using deep learning was used to construct a diagnostic algorithm. CEA, carbohydrate antigen 19-9, carbohydrate antigen 125, amylase in the cyst fluid, sex, cyst location, connection of the pancreatic duct and cyst, type of cyst, and cytology were keyed into the AI algorithm, and the malignant predictive value of the output was calculated. Area under receiver-operating characteristics curves for the diagnostic ability of malignant cystic lesions were 0.719 (CEA), 0.739 (cytology), and 0.966 (AI). In the diagnostic ability of malignant cystic lesions, sensitivity, specificity, and accuracy of AI were 95.7%, 91.9%, and 92.9%, respectively. AI sensitivity was higher than that of CEA (60.9%, p = 0.021) and cytology (47.8%, p = 0.001). AI accuracy was also higher than CEA (71.8%, p

Migration of macrophages via IRF8 toward a core lesion is important for the spontaneous recovery after spinal cord injury., Traumatic spinal cord injury (SCI) brings numerous inflammatory cells, including macrophages, from the circulating blood to lesions, but pathophysiological impact resulting from spatiotemporal dynamics of macrophages is unknown. Here, we show that macrophages centripetally migrate toward the lesion epicenter after infiltrating into the wide range of spinal cord, depending on the gradient of chemoattractant C5a. However, macrophages lacking interferon regulatory factor 8 (IRF8) cannot migrate toward the epicenter and remain widely scattered in the injured cord with profound axonal loss and little remyelination, resulting in a poor functional outcome after SCI. Time-lapse imaging and P2X/YRs blockade revealed that macrophage migration via IRF8 was caused by purinergic receptors involved in the C5a-directed migration. Conversely, pharmacological promotion of IRF8 activation facilitated macrophage centripetal movement, thereby improving the SCI recovery. Our findings reveal the importance of macrophage centripetal migration via IRF8, providing a novel therapeutic target for central nervous system injury.

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

Introduction Compressive-flexion type cervical spine fracture is typically accompanied by apparent dislocation of the facet joints, undesirable cervical alignment, and devastating neurological dysfunction, which provides strong rationale for rendering prompt operative treatment. However, the validity of conservative treatment for compressive-flexion cervical spine injury in cases with preserved congruity of the facet joints has yet to be elucidated. The purpose of this study is to evaluate the long-term outcome of cervical alignment following conservative treatment for compressive-flexion cervical spine injury with preserved congruity of the facet joints. Methods A total of 662 patients who experienced spinal cord injury from 2007 to 2017 were included and underwent retrospective review in a single institute. Thirteen patients were identified as receiving conservative therapy following compressive-flexion cervical spine fractures with spinal cord injury. Clinical and radiological results were collected, including vertical fractures of the vertebral column, laminar fractures, progression of local kyphosis, and neurological status. The degree of the local cervical kyphosis was evaluated with two methods: the posterior tangent method and the endplate method. Results All 13 patients were male, and the mean age at the time of injury was 28.4 years. The mean follow-up period was 3 years. Although none of the patients presented neurological deterioration after the injury, the degree of local kyphosis was increased at the time of final follow-up compared to what was observed at the time of injury. Patient age at the time of injury and concurrent vertical fracture of vertebral body could have been influencing factors for the progression of the kyphosis. While laminar fracture affected the kyphosis at the time of injury, it was not a strong influencing factor of the overall progression of local kyphosis. Conclusions The conservative option for the compressive-flexion cervical injury allowed us to treat without exacerbating neurological symptoms as long as the facet joints are preserved. However, in terms of cervical alignment, surgical stabilization may have been desirable for these patients. Notably, the younger patients and the patients with vertical fracture of the cervical vertebral column in this type of injury required closer observation to help prevent the progression of local kyphosis.

Prospective cohort study. To elucidate serial changes in dysphagia and elucidate the critical period for dysphagia following acute traumatic cervical spinal cord injury (CSCI). Spinal Injuries Center, Fukuoka, Japan. We prospectively examined individuals with acute traumatic CSCI admitted within 2 weeks after injury. Severity of dysphagia was evaluated using both the dysphagia severity scale (DSS) and functional oral intake scale (FOIS) at 2 weeks, 1 month, 2 months, and 3 months after injury. Condition of oral intake before injury was assessed by history taking. American Spinal Injury Association (ASIA) impairment scale grade and motor scores were also assessed at the same timepoints, and the correlation between dysphagia and paresis was analyzed. Sixty-five individuals with CSCI were assessed consecutively for 3 months after injury. Swallowing function, evaluated using both the DSS and FOIS, was significantly decreased at 2 weeks after injury, but significantly improved thereafter. Significant correlations between severity of dysphagia (DSS and FOIS scores) and motor scores were found at 2 weeks after injury (rs = 0.66 and 0.61; p

Background/Aims: There is no consensus for using endoscopic papillary large balloon dilation (EPLBD) in patients without dilatation of the lower part of the bile duct (DLBD). We evaluated the feasibility and safety of EPLBD for the removal of difficult bile duct stones (diameter ≥10 mm) in patients without DLBD. Methods: We retrospectively reviewed the records of 209 patients who underwent EPLBD for the removal of bile duct stones from October 2009 to July 2014. Primary outcomes were the clearance rate and additional mechanical lithotripsy. Secondary outcomes were the incidence of complications and recurrence rate. Results: Fiftyseven patients had DLBD (27.3%), and 152 did not have DLBD (72.7%). There were no significant differences in the overall success rate or the use of mechanical lithotripsy. Success rate during the first session and procedure time were better in the DLBD than the without-DLBD group (75.7% vs 66.7%, 48.1±23.0 minutes vs 58.4±31.7 minutes, respectively). As for complications, there were no significant differences in the incidence of pancreatitis, perforation or bleeding after endoscopic retrograde cholangiopancreatography. The recurrence rate did not differ significantly between the two groups. Conclusions: EPLBD is a useful and safe method for common bile duct stone removal in patients without DLBD. (Gut Liver 2017;11:149-155)

Toxic shock syndrome (TSS) is a critical illness associated with toxin from Staphylococcus aureus. Despite recent advances in critical care, mortality remains high and additional effective therapy is required. We report an adolescent case of TSS successfully treated with direct hemoperfusion using polymyxin-B immobilized fiber (PMX-DHP). The patient with spina bifida also had ischial pressure ulcer, and developed TSS associated with methicillin-resistant S. aureus. Despite conventional treatment, the patient developed refractory shock, which was immediately improved with PMX-DHP. PMX-DHP has been widely used for the treatment of sepsis to remove circulating endotoxins produced by Gram-negative bacteria, but beneficial effects have also been reported for Gram-positive bacterial infection. To our knowledge, this is the first report on PMX-DHP for TSS in an adolescent patient, and we propose that PMX-DHP could be a new treatment strategy for severe TSS in children as well.

Aim Sarcopenia has been increasingly reported as a prognostic factor for outcome in settings such as cirrhosis, liver transplantation, and emergent surgery. We aimed to elucidate the significance of sarcopenia in severe blunt trauma patients. Methods We retrospectively analyzed 84 patients emergently admitted to the intensive care unit at Kyushu University Hospital (Fukuoka, Japan) from May 2012 to April 2015. We assessed the amount of skeletal muscle present according to computed tomography and its relevance to ventilation-free days, patients' length of stay in the intensive care unit, and 28-day mortality. Results Twenty-five (29.7%) patients were defined as sarcopenic. Sixteen (19.7%) patients required 15 days or more in the intensive care unit. The major reason was a prolonged ventilation requirement due to flail chest (n = 7) or pneumonia (n = 3). Sarcopenic patients' stays in intensive care were significantly longer than those of non-sarcopenic patients (18.7 versus 6.4 days, respectively; P < 0.001). Univariate and multivariate analyses showed sarcopenia to be a significant risk factor for prolonged intensive care unit stay. Conclusion Sarcopenia is a risk factor that predicts prolonged intensive care unit stay in high-energy blunt trauma patients.

Background and study aims: Several meta-analyses and randomized control trials have demonstrated the efficacy of rectal nonsteroidal anti-inflammatory drugs for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Diclofenac or indomethacin was administered at a dose of 100 mg in those studies, which may be too high for Asian population. In addition, rectal administration can be considered complicated. Patients and methods: This study was a prospective, randomized, placebo-controlled trial. Patients with a PEP risk score ≥ 1 were randomly assigned to receive intravenous injection of 50 mg flurbiprofen axetil (flurbiprofen group) or saline only (placebo group). The primary outcome was reduced PEP. The secondary outcome was amylase level after 2 hours of ERCP as a predictor of PEP. (Clinical Trials.gov, ID UMIN000011322) Results: In total, 144 patients were enrolled from August 2013 to March 2015. We performed an interim analysis of the first 100 patients: 47 received flurbiprofen axetil and 53 received placebo. PEP occurred in 11 patients (11 %): 2 of 47 (4.3 %) in the flurbiprofen group and 9 of 53 (17 %) in the placebo group (P = 0.042). Relative risk reduction was 62.4 %. Hyperamylasemia did not differ significantly (17.0 % vs. 26.4 %, P = 0.109). This analysis resulted in early termination of the study for ethical reasons. Conclusions: Intravenous injection of low-dose flurbiprofen axetil after ERCP can reduce the incidence of PEP in high-risk patients

ObjectiveIgG4-related disease (IgG4-RD) is a heterogeneous, multiorgan condition of unclear aetiology that can cause organ failure. Difficulty recognising IgG4-RD contributes to diagnostic delays. We sought to identify key IgG4-RD phenotypes.MethodsWe used two cross-sectional studies assembled by an international, multispecialty network of IgG4-RD specialists who submitted 765 cases to derive and replicate phenotypic groups. Phenotype groups of disease manifestations and key covariate distributions across the identified groups were measured using latent class analysis.ResultsIn the derivation cohort (n=493), we identified four groups with distinct manifestations: Group 1 (31%), Pancreato-Hepato-Biliary disease; Group 2 (24%), Retroperitoneal Fibrosis and/or Aortitis; Group 3 (24%), Head and Neck-Limited disease and Group 4 (22%), classic Mikulicz syndrome with systemic involvement. We replicated the identification of four phenotype groups in the replication cohort. Compared with cases in Groups 1, 2 and 4, respectively, cases in Group 3 were more likely to be female (OR 11.60 (95% CI 5.39 to 24.98), 10.35 (95% CI 4.63 to 23.15) and 9.24 (95% CI 3.53 to 24.20)) and Asian (OR 6.68 (95% CI 2.82 to 15.79), 7.43 (95% CI 2.97 to 18.56) and 6.27 (95% CI 2.27 to 17.29)). Cases in Group 4 had a higher median serum IgG4 concentration (1170 mg/dL) compared with groups 1–3 (316, 178 and 445 mg/dL, respectively, pConclusionWe identified four distinctive IgG4-RD phenotypes according to organ involvement. Being Asian or female may predispose individuals to head and neck-limited disease. These phenotypes serve as a framework for identifying IgG4-RD and studying its aetiology and optimal treatment.

Traumatic spinal cord injury (SCI) causes serious disruption of neuronal circuits that leads to motor functional deficits. Regeneration of disrupted circuits back to their original target is necessary for the restoration of function after SCI, but the pathophysiological condition of the caudal spinal cord has not been sufficiently studied. Here we investigated the histological and biological changes in the distal part of the injured spinal cord, using a mice model of complete thoracic SCI in the chronic stage (3 months after injury). Atrophic changes were widely observed in the injured spinal cord both rostral and caudal to the lesion, but the decrease in area was mainly in the white matter in the rostral spinal cord while both the white and gray matter decreased in the caudal spinal cord. The number of the motor neurons was maintained in the chronic phase of injury, but the number of presynaptic boutons decreased in the lumbar motor neurons caudal to the lesion. Using laser microdissection, to investigate gene expressions in motor neurons caudal to the lesion, we observed a decrease in the expressions of neuronal activity markers. However, we found that the synaptogenic potential of postsynapse molecules was maintained in the motor neurons after SCI with the expression of acetylcholine-related molecules actually higher after SCI. Collectively, our results show that the potential of synaptogenesis is maintained in the motor neurons caudal to the lesion, even though presynaptic input is decreased. Although researches into SCI concentrate their effort on the lesion epicenter, our findings suggest that the area caudal to the lesion could be an original therapeutic target for the chronically injured spinal cord. Electronic supplementary material The online version of this article (10.1186/s13041-018-0422-3) contains supplementary material, which is available to authorized users.

Background Spinal cord injury (SCI) is a devastating disorder for which the accurate prediction of the functional prognosis is urgently needed. Due to the lack of reliable prediction methods, the acute evaluation of SCI severity and therapeutic intervention efficacy is extremely difficult, presenting major obstacles to the development of acute SCI treatment. We herein report a novel method for accurately predicting the functional prognosis using the acute-phase serum zinc concentration after SCI. Methods We produced experimental animal SCI models with different prognoses and examined the relationship among the SCI severity, functional outcome, and acute-phase serum zinc concentration. We also examined whether we could predict the functional prognosis by evaluating the serum zinc concentration within 72 h after SCI in a human prospective study. Findings In a mouse model, the acute serum zinc concentrations decreased in proportion to SCI severity and the serum zinc concentrations at 12 h after SCI accurately predicted the functional prognosis. We clarified the mechanism underlying this serum zinc proportional decrease, showing that activated monocytes took up zinc from blood-serum and then infiltrated the lesion area in a severity-dependent manner. A non-linear regression analysis of 38 SCI patients showed that the serum zinc concentrations in the acute-phase accurately predicted the long-term functional outcome (R2 = 0·84) more accurately than any other previously reported acute-phase biomarkers. Interpretation The acute-phase serum zinc concentration could be a useful biomarker for predicting the functional prognosis. This simple method will allow for more objective clinical trials and the development of patient-tailored treatment for SCI.

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

Introduction Avascular necrosis of the femoral capital epiphysis is the most serious complication after traumatic dislocation of the hip in children. This case report discusses the localization and revascularization of the necrotic femoral head following rarely experienced traumatic open anterior hip dislocation in children. Case presentation Our patient was an 11-year-old Japanese boy who had open anterior hip dislocation sustained in a traffic accident. Reduction of the hip joint was performed in an emergency operation, and he was evaluated using serial gadolinium-enhanced magnetic resonance imaging. T1-weighted magnetic resonance images showed two bands with low signal intensity in the femoral capital epiphysis on coronal and oblique axial planes, indicating the existence of avascular osteonecrosis of the femoral head. We observed gadolinium enhancement in the central region of the epiphysis, where the area between the two bands with low signal intensity was located. Serial assessment with enhanced magnetic resonance images during a non-weight-bearing period of 1.5 years after injury showed revascularization starting from the central region and converging toward the peripheral region. Although the patient had leg-length discrepancy due to the early epiphyseal closure, non-weight-bearing treatment for the avascular osteonecrosis of the femoral head achieved a favorable outcome without any hip joint dysfunction, pain, or sign of secondary osteoarthritic change within 4.5 years after injury. Conclusion We confirmed the revascularization process of the necrotic lesion in the femoral capital epiphysis in an 11-year-old boy using serial gadolinium-enhanced magnetic resonance imaging. Conservative non-weight-bearing treatment achieved a favorable outcome.

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

A. Khosroshahi, Z. S. Wallace, J. L. Crowe, T. Akamizu, A. Azumi, M. N. Carruthers, S. T. Chari, E. Della-Torre, L. Frulloni, H. Goto, P. A. Hart, T. Kamisawa, S. Kawa, M. Kawano, M. H. Kim, Y. Kodama, K. Kubota, M. M. Lerch, M. L€ ohr, Y. Masaki, S. Matsui, T. Mimori, S. Nakamura, T. Nakazawa, H. Ohara, K. Okazaki, J. H. Ryu, T. Saeki, N. Schleinitz, A. Shimatsu, T. Shimosegawa, H. Takahashi, M. Takahira, A. Tanaka, M. Topazian, H. Umehara, G. J. Webster, T. E. Witzig, M. Yamamoto, W. Zhang, T. Chiba, and J. H. Stone

BACKGROUND Sporadic autoimmune pancreatitis (AIP) cases showing remission without steroid treatment have been reported, however, the clinical course of these patients has not been clarified. This study sought to clarify the clinical course in AIP patients with hesitation for steroid treatment. METHODS We collected clinical data for AIP patients from high-volume centers in Japan. Data for AIP patients with and those without steroid treatment (steroid treatment vs. wait and see policy or W&S) were then compared. The primary point was the relapse-free survival rate (RFS) in patients with and those without steroid treatment, as determined using Kaplan-Meier curve. The secondary point was the identification of predictors of remission and risks of relapse in AIP patients without steroid treatment. RESULTS There were 510 AIP patients in the steroid treatment group and 97 patients in the W&S group. Overall, 55.7% (54/97) of type 1 AIP patients in the W&S group experienced transient remission without steroid treatment. The W&S group had a significantly higher patient age and significantly lower incidences of jaundice, diffuse pancreas swelling, proximal-type sclerosing cholangitis, and stent placement and a lower remission rate than the steroid treatment group (each P

Background: Spinal cord injury (SCI) is a devastating disorder for which the accurate prediction of the functional prognosis is urgently needed. Due to the lack of reliable prediction methods, the acute evaluation of SCI severity and therapeutic intervention efficacy is extremely difficult, presenting major obstacles to the development of acute SCI treatment. We herein report a novel method for accurately predicting the functional prognosis using the acute-phase serum zinc concentration after SCI. Methods: We produced experimental animal SCI models with different prognoses and examined the relationship among the SCI severity, functional outcome, and acute-phase serum zinc concentration. We also examined whether we could predict the functional prognosis by evaluating the serum zinc concentration within 72 h after SCI in a human prospective study. Findings: In a mouse model, the acute serum zinc concentrations decreased in proportion to SCI severity and the serum zinc concentrations at 12 h after SCI accurately predicted the functional prognosis. We clarified the mechanism underlying this serum zinc proportional decrease, showing that activated monocytes took up zinc from blood-serum and then infiltrated the lesion area in a severity-dependent manner. A non-linear regression analysis of 38 SCI patients showed that the serum zinc concentrations in the acute-phase accurately predicted the long-term functional outcome (R2=0·84) more accurately than any other previously reported acute-phase biomarkers. Interpretation: The acute-phase serum zinc concentration could be a useful biomarker for predicting the functional prognosis. This simple method will allow for more objective clinical trials and the development of patient-tailored treatment for SCI. Funding Statement: This study was supported by JSPS KAKENHI Grant Number JP18K16680 (K.K.); a Grant-in-Aid for Scientific Research (B) (16H05450) (S.O.); Challenging Exploratory Research from the Ministry of Education, Science, and Sports (16K15668) (S.O.); and research foundations from the general insurance association of Japan (K.K.). Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: All animal studies were approved by the Committee of Ethics on Animal Experimentation of our institute and conducted in accordance with the National Institutes of Health guidelines for the care and use of animals. All human study involving the analysis of medical record data was conducted according to the principles expressed in the Declaration of Helsinki and was approved by the Institutional Review Board. Informed consent was obtained from each subject.

Both fully covered (FC) and partially covered (PC) self-expandable metal stents (SEMSs) are now commercially available for distal malignant biliary obstruction (MBO). While FCSEMS can be easily removed at the time of re-interventions, it is theoretically prone to migration. However, few comparative data between FC and PC SEMSs have been reported. The aim of this study was to compare clinical outcomes of FCSEMS with those of PCSEMS. This was a multicenter, prospective study of FCSEMS for unresectable distal MBO with a historical control of PCSEMS, which was previously reported as the WATCH study. The primary outcome was recurrent biliary obstruction (RBO), and secondary outcomes were stent migration, stent removal, stent-related adverse events, and survival. A total of 151 cases with unresectable distal MBO undergoing FCSEMS placement were enrolled and compared with a historical cohort of 141 cases undergoing PCSEMS placement. No significant differences were found in the rate of RBO (29 vs. 33%; P = 0.451), time to RBO (318 vs. 373 days; P = 0.382), and survival (229 vs. 196 days; P = 0.177) between FCSEMS and PCSEMS. The rate of stent migration also did not differ significantly between the two groups (14 vs. 8%; P = 0.113). The removal of FCSEMSs was successful in all 24 attempted cases (100%). FCSEMSs appeared comparable to PCSEMSs in terms of RBO without a significant increase in stent migration rate in patients with unresectable distal MBO. UMIN000007131.