Feasibility of comprehensive genomic profiling using endoscopic ultrasound-guided tissue acquisition with a 22-gauge Franseen needle.

Aim: Comprehensive genomic profiling (CGP) test for solid tumors is now increasingly utilized in clinical practice, especially in pancreatobiliary cancer, and specimens obtained by endoscopic ultrasound-guided tissue acquisition (EUS-TA) are often submitted for tissue-based CGP test. In this study, we evaluated the feasibility of EUS-TA using a 22-gauge Franseen needle for the CGP test. Methods: Consecutive patients with solid tumors who underwent EUS-TA using a 22-gauge Franseen needle, and whose tissue samples were pre-checked for suitability for CGP test, were included in this single-center, retrospective analysis. The success rates of appropriate sample collection for CGP evaluated by pathologists (1st quality control) and CGP test (2nd quality control) were evaluated. In addition, The EUS-TA slides were evaluated for the tissue area and tumor area content, using the image software. Results: A total of 50 cases, with 78% of pancreatic cancer, were included in the analysis. A median of 3 passes of EUS-TA were performed with an adverse event rate of 4%. The success rates for 1st and 2nd quality control for CGP tests were 86% and 76%, respectively. The image analyses suggested EUS-TA specimen did not always fulfill CGP test criteria, with 18% of tissue area ≥16 mm2 and 38% of tumor area content ≥20%, even in cases with successful CGP tests. The suction method yielded a significantly larger amount of DNA but without a significant difference in the multivariate analysis. Conclusions: The present study demonstrated the feasibility of EUS-TA using a 22-gauge Franseen needle for CGP test.

Kluyvera georgiana Bacteremia Due to Acute Cholangitis: A Report of the First Known Case and a Literature Review.

We herein present the first known case of bacteremia caused by Kluyvera georgiana in a 67-year-old female undergoing chemotherapy for recurrent pancreatic cancer. The patient underwent choledochojejunotomy and thereafter developed ascending cholangitis. The diagnosis of K. georgiana was confirmed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. A literature review of Kluyvera spp. infections indicated potential risk factors including an underlying malignancy and immunosuppression. Although Kluyvera spp. infections are typically sensitive to antibiotics, multidrug resistance is possible. This case highlights the importance of the early diagnosis and treatment of K. georgiana and its associated risk factors.

Skeletal muscle status and survival among patients with advanced biliary tract cancer.

BACKGROUND: Studies have demonstrated a prognostic role of sarcopenia (i.e., loss of skeletal muscle volume and functionality) in patients with various cancer types. In patients with biliary tract cancer, the quantity and quality of skeletal muscles and their serial changes have not been fully investigated in relation to survival outcomes. METHODS: We identified 386 patients with unresectable or recurrent biliary tract cancer and calculated skeletal muscle index (SMI) and skeletal muscle density (SMD) to estimate muscular quantity and quality, respectively, based on computed tomography images. Using the Cox regression model with adjustment for potential confounders, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) according to skeletal muscle status and its serial change. RESULTS: Compared to patients without sarcopenia, patients with sarcopenia were associated with shorter PFS (multivariable HR, 1.60; 95% CI, 1.15-2.22; P = 0.005), but not with OS (P = 0.027) at the adjusted α level of 0.013. SMD at baseline was associated with OS (multivariable HR comparing the extreme quartiles, 1.52; 95% CI, 1.07-2.14; Ptrend = 0.012), but not with PFS (Ptrend = 0.13). A reduction in SMI rather than that in SMD was associated with OS. Progressive disease was a risk factor for reductions in SMI and SMD. CONCLUSIONS: Skeletal muscle quantity and quality and their serial changes were associated with survival outcomes in patients with advanced biliary tract cancer. Our data highlight the importance of designing nutritional and physical interventions for improvements in skeletal muscle status.

Retrospective comparative study of new slim-delivery and conventional large-cell stents for stent-in-stent methods for hilar malignant biliary obstruction.

OBJECTIVES: Endoscopic management of unresectable hilar malignant biliary obstruction (HMBO) is technically challenging, and effectiveness of stent-in-stent using large-cell, metal stents was reported. A new, large-cell stent with a 6F tapered delivery system was recently developed. The aim of this study was to compare clinical outcomes of slim-delivery and conventional large-cell stents. METHODS: This was a multicenter retrospective comparative study of stent-in-stent methods using slim-delivery stents (Niti-S Large Cell SR Slim Delivery [LC slim-delivery]) and conventional stents (Niti-S large-cell D-type; LCD) for unresectable HMBO. RESULTS: Eighty-three patients with HMBO were included; 31 LC slim-delivery and 52 LCD. Overall technical and clinical success rates were 100% and 90% in LC slim-delivery group and 98% and 88% in LCD group. Use of the LC slim-delivery was associated with shorter stent placement time in the multiple regression analysis, with a stent placement time of 18 and 23 min in LC slim-delivery and LCD groups, respectively. The early adverse event (AE) rate of LC slim-delivery was 10%, with no cholangitis or cholecystitis as compared to 23% in the LCD group. Recurrent biliary obstruction (RBO) rates and time to RBO were comparable between the two groups: 35% and 44%, and 8.5 and 8.0 months in LC slim-delivery and LCD groups, respectively. The major cause of RBO was tumor ingrowth (82%) in the LC slim-delivery group and sludge (43%) and ingrowth (48%) in LCD group. CONCLUSION: Stent-in-stent methods using LC slim-delivery shortened stent placement time with low early AE rates and comparable time to RBO in patients with HMBO.

Second Covered and Uncovered Self-Expandable Metal Stents for Recurrent Gastric Outlet Obstruction: A Retrospective Comparative Study.

Background: Endoscopic self-expandable metal stent (SEMS) placement is a current mainstay for malignant gastric outlet obstruction (GOO), but symptomatic recurrence due to initial SEMS dysfunction commonly occurs. We aimed to compare the safety and effectiveness of second SEMS for recurrent GOO (RGOO). Methods: Between April 2006 and December 2022, a total of 95 cases with malignant RGOO undergoing second endoscopic SEMS placement were enrolled. Technical and clinical success rates, RGOO, time to RGOO (TRGOO), stent patency rate, adverse events (AE), and overall survival (OS) were retrospectively compared between covered and uncovered SEMS (cSEMS/uSEMS) groups. Risk factors for TRGOO were also explored. Results: Baseline characteristics were well balanced between cSEMS (n = 48) and uSEMS (n = 47) groups, except for the causes of the initial SEMS dysfunction. High technical and clinical success rates with a similar incidence of AE (15% vs. 17%, p = 0.78) and OS (median of 101 vs. 102 days, p = 0.68) were achieved in both groups. There were no statistical differences in cumulative incidence of RGOO (19% vs. 13%, p = 0.58), TRGOO (median, not reached in both groups, p = 0.57), and stent patency rates at 1, 2, and 3 months between the groups (60%, 47% and 26%, respectively vs. 70%, 55% and 38%, respectively). However, TRGOO tended to be longer in cSEMS in cases with RGOO due to tumor ingrowth (median, not reached vs. 111 days, p = 0.19). A Cox regression analysis demonstrated that chemotherapy after second SEMS placement was significantly associated with an improved TRGOO (the hazard ratio of 0.27 [95% confidence interval, 0.08-0.93], p = 0.03). Conclusions: Regardless of the type of SEMS, second SEMS placement was similarly safe and effective for RGOO. The type of second SEMS might be considered based on the cause of initial SEMS dysfunction.

Clinical trajectory of intraductal papillary mucinous neoplasms progressing to pancreatic carcinomas during long-term surveillance: a prospective series of 100 carcinoma cases.

BACKGROUND: Trajectories of serological and morphological signatures have not been documented in pancreatic carcinogenesis related to intraductal papillary mucinous neoplasms (IPMNs). METHODS: Using a prospective cohort of 3437 IPMN patients, we identified 100 IPMN patients who developed pancreatic carcinomas during long-term surveillance. We examined serial changes of blood markers (carbohydrate antigen 19-9 [CA19-9], hemoglobin A1c [HbA1c], and pancreatic enzymes) and morphological features (worrisome features and high-risk stigmata) during the prediagnostic period of pancreatic carcinomas, overall and by carcinoma types (IPMN-derived vs. concomitant pancreatic carcinomas). RESULTS: CA19-9 elevation was observed in 39 patients and was associated with a metastatic stage. Compared to IPMN-derived carcinomas, concomitant carcinomas were more likely to represent CA19-9 elevation (60% vs. 30%, respectively; P = 0.005). HbA1c levels elevated only in 3 patients. Pancreatic enzyme elevation was observed in 18 patients with no differences in frequencies between the carcinoma types. All patients with elevated levels of blood markers had positive findings on cross-sectional imaging. High-risk stigmata or worrisome features were observed in all patients but one with concomitant carcinoma. The most common types of worrisome features were the main pancreatic duct dilatation and CA19-9 elevation in IPMN-derived and concomitant carcinomas, respectively. Compared to IPMN-derived carcinomas, concomitant carcinomas were less likely to harbor high-risk stigmata (16% vs. 86%, respectively; P < 0.001). CONCLUSIONS: The usefulness of currently available blood biomarkers was limited in early detection of pancreatic carcinomas related to IPMNs. Morphological alterations were well correlated with long-term risk of IPMN-derived carcinomas, but not with that of concomitant carcinomas.

Application of MinION Amplicon Sequencing to Buccal Swab Samples for Improving Resolution and Throughput of Rumen Microbiota Analysis.

The Illumina MiSeq platform has been widely used as a standard method for studying the rumen microbiota. However, the low resolution of taxonomic identification is the only disadvantage of MiSeq amplicon sequencing, as it targets a part of the 16S rRNA gene. In the present study, we performed three experiments to establish a high-resolution and high-throughput rumen microbial profiling approach using a combination of MinION platform and buccal swab sample, which is a proxy for rumen contents. In experiment 1, rumen contents and buccal swab samples were collected simultaneously from cannulated cattle (n = 6) and used for microbiota analysis using three different analytical workflows: amplicon sequencing of the V3-V4 region of the 16S rRNA gene using MiSeq and amplicon sequencing of near full-length 16S rRNA gene using MinION or PacBio Sequel II. All reads derived from the MinION and PacBio platforms were classified at the species-level. In experiment 2, rumen fluid samples were collected from beef cattle (n = 28) and used for 16S rRNA gene amplicon sequencing using the MinION platform to evaluate this sequencing platform for rumen microbiota analysis. We confirmed that the MinION platform allowed species-level taxa assignment for the predominant bacterial groups, which were previously identified at the family- and genus-level using the MiSeq platform. In experiment 3, buccal swab samples were collected from beef cattle (n = 30) and used for 16S rRNA gene amplicon sequencing using the MinION platform to validate the applicability of a combination of the MinION platform and buccal swab samples for rumen microbiota analysis. The distribution of predominant bacterial taxa in the buccal swab samples was similar to that in the rumen samples observed in experiment 2. Based on these results, we concluded that the combination of the MinION platform and buccal swab samples may be potentially applied for rumen microbial analysis in large-scale studies.

Corticosteroid-induced Kaposi's Sarcoma Revealed by Severe Anemia: A Case Report and Literature Review.

We herein report a case of gastrointestinal (GI) Kaposi's sarcoma (KS) without cutaneous involvement in a 73-year-old man who had received immunosuppressive drugs for granulomatosis with polyangiitis. After one year of prednisolone use, he presented with tarry stool and severe anemia. Endoscopic and pathological examinations revealed bright-reddish protruding lesions with proliferating spindle cells positive for D2-40, CD34, and HHV-8, which are definitively diagnostic of GI-KS. Drug-induced KS without HIV infection or transplantation is extremely rare, and its clinical features remain unknown. Therefore, we conducted a literature review of steroid-induced KS.

Mental health of gatekeepers may influence their own attitudes toward suicide: A questionnaire survey from a suicide-prevention gatekeeper training program.

AIMS: We aimed to investigate the association between general mental health and attitudes toward suicide of participants in suicide-prevention gatekeeper training programs. METHODS: We conducted a number of half day training seminars within a suicide prevention program addressing gatekeepers. Participants filled in two questionnaires, one measuring general health (General Health Questionnaire, GHQ-12), and one measuring attitudes towards suicide (ATTS). RESULTS: The total sample size of participants was 230, of whom 115 completed questionnaires. There were no significant differences in demographic backgrounds between the good mental health (GHQ-12 ≤ 4) and the poor mental health (GHQ-12 ≥ 5) groups. The poor mental health group was more likely to think that people have the right to commit suicide. CONCLUSION: There was a difference in attitudes toward suicide between the good mental health and the poor mental health groups, indicating that attention should be paid to participants' mental health when conducting suicide-prevention gatekeeper training.

Network analysis for motives in suicide cases: a cross-sectional study.

AIM: Suicide victims have various distresses or motives. There are few studies on how these motives toward suicide relate with each other. We used network analyses to extract the structures of correlations among the motives for suicide. METHODS: We obtained datasets of suicide victims from 2007-2009 in Japan in cooperation with Ibaraki Prefectural Police Headquarters. The data were analyzed by network centrality measures and a structural analysis by block modeling. RESULTS: Among the motives, depression and physical illness showed relatively high scores of 'degree centrality', whereas depression and unemployment showed relatively high scores of 'betweenness centrality'. Structural analysis by block modeling resulted in eight blocks. The most important block comprised eight motives, including conflict between parent and child, marital conflict, economic hardship, and overloaded with debt. CONCLUSION: Depression and physical illness were important and priority areas for completed suicides, although these two motives had different influences on suicide behaviors. Furthermore, structural analysis revealed the important role of a block, including some familial and financial motives, which induced hopelessness. Our results suggest that it might be useful to consider the common ways in which motivations for suicide are tied together when suicide intervention is launched from a social model point of view.

How perceived social support relates to suicidal ideation: a Japanese social resident survey.

BACKGROUND: The loss of social support is one of the major risk factors for suicide. However, there are few empirical studies that have examined how a person's suicide ideation relates to their social support. AIMS: To examine the relationship between social support and suicidal ideation. METHODS: Self-report questionnaires were sent to 2,200 randomly selected adults in Japan. The questionnaire inquired the participants about the severity of suicidal ideation, the details of current perceived social support and their degree of satisfaction with this social support. Social support and related indicators were compared among three groups of participants that varied in severity of suicidal ideation. RESULTS: People in the group that had suicide ideation during their lives reported receiving significantly less support from their family and had greater feelings of dissatisfaction with that support than those in the other groups. Furthermore, people who had suicide ideation during the month immediately preceding the survey reported providing less support to their family, relatives or friends, as well as receiving less support from family than other groups, and having stronger feelings of dissatisfaction with social support. CONCLUSION: Our study identified a strong relationship between the severity of suicidal ideation and perceived social support.

[A case of Brugada syndrome with convulsive seizure during antidepressant administration: relation of antidepressant agents and arrhythmia leading to sudden death].

Brugada syndrome is an arrhythmogenetic disease characterized by electrocardiographic ST segment elevation in right precordial leads, which is called "coved type", and an increased risk of sudden death as the result of ventricular fibrillation. We presented a case of Brugada syndrome with a convulsive seizure, during administration of a tricyclic antidepressant for the treatment of a depressive state. A 43-year-old man with bipolar II disorder and obsessive-compulsive disorder was admitted to our hospital for the treatment of a depressive state. There was no medical history of heart failure. Nortriptyline was effective for his depressive as well as for obsessive symptoms. During the treatment, however, he presented a convulsive syncope. Electrocardiography (ECG) showed "coved type" ST segment elevation, and the patient consulted a cardiologist. Electrophysiological study revealed Brugada syndrome, and an implantable cardioverter defibrillator was placed. An overdose of antidepressants has been reported to produce a Brugada-type ECG because of its Na channel antagonism. However, in the present case, the abnormal ECG findings occurred following a usual dosage of nortriptyline. Thus, it is suggested that Brugada syndrome is related to a susceptibility to antidepressants in the present case. Every psychiatrist managing antidepressant therapy should be aware of Brugada syndrome and this ECG pattern, which may be a marker of sudden death.