Deep learning analysis for differential diagnosis and risk classification of gastrointestinal tumors.

OBJECTIVES: Recently, artificial intelligence (AI) has been applied to clinical diagnosis. Although AI has already been developed for gastrointestinal (GI) tract endoscopy, few studies have applied AI to endoscopic ultrasound (EUS) images. In this study, we used a computer-assisted diagnosis (CAD) system with deep learning analysis of EUS images (EUS-CAD) and assessed its ability to differentiate GI stromal tumors (GISTs) from other mesenchymal tumors and their risk classification performance. MATERIALS AND METHODS: A total of 101 pathologically confirmed cases of subepithelial lesions (SELs) arising from the muscularis propria layer, including 69 GISTs, 17 leiomyomas and 15 schwannomas, were examined. A total of 3283 EUS images were used for training and five-fold-cross-validation, and 827 images were independently tested for diagnosing GISTs. For the risk classification of 69 GISTs, including very-low-, low-, intermediate- and high-risk GISTs, 2,784 EUS images were used for training and three-fold-cross-validation. RESULTS: For the differential diagnostic performance of GIST among all SELs, the accuracy, sensitivity, specificity and area under the receiver operating characteristic (ROC) curve were 80.4%, 82.9%, 75.3% and 0.865, respectively, whereas those for intermediate- and high-risk GISTs were 71.8%, 70.2%, 72.0% and 0.771, respectively. CONCLUSIONS: The EUS-CAD system showed a good diagnostic yield in differentiating GISTs from other mesenchymal tumors and successfully demonstrated the GIST risk classification feasibility. This system can determine whether treatment is necessary based on EUS imaging alone without the need for additional invasive examinations.

Effectiveness of endoscopic ultrasound-guided tissue acquisition with stereomicroscopic on-site evaluation for preoperative diagnosis of resectable or borderline resectable pancreatic cancer: a prospective study.

Background/Aims: To validate endoscopic ultrasound-guided tissue acquisition (EUS-TA) used in conjunction with stereomicroscopic on-site evaluation (SOSE) as a preoperative diagnostic tool for resectable pancreatic cancer (R-PC) and borderline resectable PC (BR-PC). Methods: Seventy-eight consecutive patients who underwent EUS-TA for suspected R-PC or BR-PC were enrolled. The primary endpoint was the sensitivity of EUS-TA together with SOSE based on the stereomicroscopically visible white core (SVWC) cutoff value. One or two sites were punctured by using a 22-gauge biopsy needle for EUS-TA, based on the SOSE findings. Results: We collected 99 specimens from 56 and 22 patients with R-PC and BR-PC, respectively. Based on the SOSE results, we performed 57 procedures with one puncture. The SVWC cutoff values were met in 73.7% and 73.1% of all specimens and in those obtained during the first puncture, respectively. The final diagnoses were malignant and benign tumors in 76 and two patients, respectively. The overall sensitivity, specificity, and accuracy of EUS-TA for the 78 lesions were 90.8%, 100%, and 91.0%, respectively. The sensitivity for malignant diagnosis based on the SVWC cutoff value were 89.5% and 90.4% for the first puncture and all specimens, respectively. Conclusions: The sensitivity of EUS-TA in conjunction with SOSE for malignancy diagnosis in patients with suspected R-PC or BR-PC was 90.4%.

Endoscopic Ultrasound-Guided Tissue Acquisition Using Fork-Tip Needle for Subepithelial Lesions: A Single-Center Validation Study.

BACKGROUND: The cutoff value for stereomicroscopic on-site evaluation (SOSE) in endoscopic ultrasound-guided tissue acquisition (EUS-TA) has high diagnostic sensitivity when a Franseen needle is employed for upper gastrointestinal subepithelial lesions (SELs) (stereomicroscopically visible white core [SVWC] ≥ 4 mm). AIM: We aimed to determine whether high diagnostic sensitivity could be obtained when EUS-TA was performed using a Fork-tip needle. METHODS: Twenty-one patients were prospectively registered. Patients underwent EUS-TA using a Fork-tip needle for upper gastrointestinal SELs at Kitasato University Hospital between January and November 2022. Punctures were made twice using the needle, and SOSE was conducted for each specimen. Blood and physical examination were performed to assess adverse events. Pathological diagnosis was made using hematoxylin and eosin-stained sections and immunohistochemical staining. Statistical comparisons were completed using Fisher's exact tests. RESULTS: The diagnostic rate of EUS-TA was 100% (21/21 cases). The final diagnosis was gastrointestinal stromal tumor in 17 (81.0%) and leiomyoma in 4 (19.0%) patients. SOSE was conducted on all 42 punctures, and the tissue sampling rate was 100% (42/42 punctures). Specimens with SVWC ≥ 4 mm were collected in 97.6% punctures (41/42 punctures) and the diagnostic sensitivity for these specimens was 100% (41/41 punctures), which is significantly higher (p < 0.0238) compared to the absence of cutoff value (diagnostic sensitivity of 0%). No EUS-TA-related adverse events occurred. CONCLUSIONS: EUS-TA combined with SOSE for upper gastrointestinal SEL using a fork-tip needle had a high diagnostic rate, and the cutoff value of SVWC ≥ 4 mm had high diagnostic sensitivity.

Lysophospholipid Acyltransferase 9 Promotes Emphysema Formation via Platelet-activating Factor.

Cigarette smoking is known to be the leading cause of chronic obstructive pulmonary disease (COPD). However, the detailed mechanisms have not been elucidated. PAF (platelet-activating factor), a potent inflammatory mediator, is involved in the pathogenesis of various respiratory diseases such as bronchial asthma and COPD. We focused on LPLAT9 (lysophospholipid acyltransferase 9), a biosynthetic enzyme of PAF, in the pathogenesis of COPD. LPLAT9 gene expression was observed in excised COPD lungs and single-cell RNA sequencing data of alveolar macrophages (AMs). LPLAT9 was predominant and upregulated in AMs, particularly monocyte-derived AMs, in patients with COPD. To identify the function of LPLAT9/PAF in AMs in the pathogenesis of COPD, we exposed systemic LPLAT9-knockout (LPALT9-/-) mice to cigarette smoke (CS). CS increased the number of AMs, especially the monocyte-derived fraction, which secreted MMP12 (matrix metalloprotease 12). Also, CS augmented LPLAT9 phosphorylation/activation on macrophages and, subsequently, PAF synthesis in the lung. The LPLAT9-/- mouse lung showed reduced PAF production after CS exposure. Intratracheal PAF administration accumulated AMs by increasing MCP1 (monocyte chemoattractant protein-1). After CS exposure, AM accumulation and subsequent pulmonary emphysema, a primary pathologic change of COPD, were reduced in LPALT9-/- mice compared with LPLAT9+/+ mice. Notably, these phenotypes were again worsened by LPLAT9+/+ bone marrow transplantation in LPALT9-/- mice. Thus, CS-induced LPLAT9 activation in monocyte-derived AMs aggravated pulmonary emphysema via PAF-induced further accumulation of AMs. These results suggest that PAF synthesized by LPLAT9 has an important role in the pathogenesis of COPD.

Rapidly progressive mucus plugs in allergic bronchopulmonary mycosis.

INTRODUCTION: Allergic bronchopulmonary mycosis (ABPM) is a chronic airway disease characterized by the presence of fungi that trigger allergic reactions and airway obstruction. Here, we present a unique case of ABPM in which a patient experienced sudden respiratory failure due to mucus plug-induced airway obstruction. The patient's life was saved by venovenous extracorporeal membrane oxygenation (VV-ECMO) and bronchoscopic removal of the plug. This case emphasizes the clinical significance of mucus plug-induced airway obstruction in the differential diagnosis of respiratory failure in patients with ABPM. CASE STUDY: A 52-year-old female clerical worker with no smoking history, presented with dyspnea. CT scan revealed mucus plugs in both lungs. Despite treatment, the dyspnea progressed rapidly to respiratory failure, leading to VV-ECMO placement. RESULTS: CT revealed bronchial wall thickening, obstruction, and extensive atelectasis. Bronchoscopy revealed extensive mucus plugs that were successfully removed within two days. The patient's respiratory status significantly improved. Follow-up CT revealed no recurrence. Fungal cultures identified Schizophyllum commune, confirming ABPM. Histological examination of the mucus plugs revealed aggregated eosinophils, eosinophil granules, and Charcot-Leyden crystals. Galectin-10 and major basic protein (MBP) staining supported these findings. Eosinophil extracellular traps (EETs) and eosinophil cell death (ETosis), which contribute to mucus plug formation, were identified by citrullinated histone H3 staining. CONCLUSION: Differentiating between asthma exacerbation and mucus plug-induced airway obstruction in patients with ABPM and those with acute respiratory failure is challenging. Prompt evaluation of mucous plugs and atelectasis using CT and timely decision to introduce ECMO and bronchoscopic mucous plug removal are required.

Efficacy of endoscopic ultrasound-guided tissue acquisition using stereo-microscopic on-site evaluation for possible comprehensive genome profile in patients with advanced pancreatic cancer.

BACKGROUND AND AIM: Stereomicroscopic on-site evaluation (SOSE) is a rapid evaluation method for endoscopic ultrasound-guided tissue acquisition (EUS-TA) with a high diagnostic sensitivity when the stereomicroscopically visible white core (SVWC) cut-off value (≥ 11 mm) is met. We prospectively examined the association between SVWCs and the adequacy of tissue specimens, assuming subsequent comprehensive genome profiling (CGP). METHODS: This study included 66 consecutive patients with suspected unresectable pancreatic cancer who underwent EUS-TA. The primary endpoint was the frequency of combined samples with ≥ 20% tumor cell content that met over twice the SVWC (T-SVWC) cut-off value, achieved through multiple punctures. The secondary endpoints were the number of punctures, the percentage of SVWC cut-off values, adverse events, the positive diagnosis rate, and the tissue section area. RESULTS: The median number of EUS-TA punctures for suspected unresectable pancreatic cancer was 3 (range, 3-4); SVWC and T-SVWC cut-off values were obtained in 171/206 specimens and 65/66 patients, respectively. There were no EUS-TA-related adverse events. The positive diagnosis rate of EUS-TA was 95.5%. Among the 63 patients meeting the T-SVWC cut-off value in pathological diagnoses, the median tumor cell content was 40% (range, 5-80%), with 57 patients having tumor cell content ≥ 20%. The median tissue section area was 15 (range, 3-40) mm2. CONCLUSIONS: When performing EUS-TA for unresectable pancreatic cancer with the intention of subsequent CGP, obtaining a high tumor cell content (≥ 20%) by assessing the T-SVWC cut-off value via SOSE may serve as a novel indicator for on-site estimation of CGP suitability for EUS-TA specimens.

Participant Selection from the General Japanese Population for Pulmonary Function Tests Using a Questionnaire on Symptoms and Smoking Habits during Annual Health Checkups: The Yamagata-Takahata Study.

Objective Pulmonary function tests are essential for diagnosing respiratory diseases, such as chronic obstructive pulmonary disease (COPD), but are typically not performed in Japan during annual health checkups, which hinders the early diagnosis of respiratory diseases. Methods Individuals who agreed to participate in the Yamagata-Takahata study during medical checkups in Takahata (Yamagata Prefecture, Japan) in 2011 were examined. We interviewed 669 participants (49.0% men; mean age, 67.7 years old) regarding their respiratory symptoms and smoking habits and performed pulmonary function tests during the study. Results Based on pulmonary function test results, 141 participants had pulmonary dysfunction, and 115 had obstructive pulmonary dysfunction. The risk of respiratory dysfunction, particularly obstructive respiratory dysfunction, was examined by referring to a questionnaire tool for an early COPD diagnosis. The associations between age, the smoking history, respiratory symptoms, and obstructive respiratory dysfunction were evaluated. Obstructive respiratory dysfunction was found in 17.6% of participants ≥50 years old and 19.5% ≥60 years old, 30.3% had a smoking history, and 32.8% had respiratory symptoms. Furthermore, the participants with multiple factors had a higher probability of obstructive respiratory dysfunction. Conclusion Subjects with obstructive pulmonary dysfunction are expected to be efficiently identified by extracting individuals by age and smoking habit and through a respiratory symptom questionnaire, although pulmonary function tests cannot be performed for all individuals during health checkups.

Stereomicroscopic on-site evaluation in endoscopic ultrasound-guided tissue acquisition of upper gastrointestinal subepithelial lesions.

BACKGROUND/AIMS: In stereomicroscopic sample isolation processing, the cutoff value (≥4 mm) of stereomicroscopically visible white cores indicates high diagnostic sensitivity. We aimed to evaluate endoscopic ultrasound-guided tissue acquisition (EUS-TA) using a simplified stereomicroscopic on-site evaluation of upper gastrointestinal subepithelial lesions (SELs). METHODS: In this multicenter prospective trial, we performed EUS-TA using a 22-gauge Franseen needle in 34 participants with SELs derived from the upper gastrointestinal muscularis propria, requiring pathological diagnosis. The presence of stereomicroscopically visible white core (SVWC) in each specimen was assessed using stereomicroscopic on-site evaluation. The primary outcome was EUS-TA's diagnostic sensitivity with stereomicroscopic on-site evaluation based on the SVWC cutoff value (≥4 mm) for malignant upper gastrointestinal SELs. RESULTS: The total number of punctures was 68; 61 specimens (89.7%) contained stereomicroscopically visible white cores ≥4 mm in size. The final diagnoses were gastrointestinal stromal tumor, leiomyoma, and schwannoma in 76.5%, 14.7%, and 8.8% of the cases, respectively. The sensitivity of EUS-TA with stereomicroscopic on-site evaluation based on the SVWC cutoff value for malignant SELs was 100%. The per-lesion accuracy of histological diagnosis reached the highest level (100%) at the second puncture. CONCLUSION: Stereomicroscopic on-site evaluation showed high diagnostic sensitivity and could be a new method for diagnosing upper gastrointestinal SELs using EUS-TA.

Cardiac tamponade during pregnancy due to primary lung cancer: A case report.

We report a rare case of cardiac tamponade caused by lung cancer in a pregnant woman. A 32-year-old multiparous pregnant woman was admitted to the hospital at 15 weeks of gestation with a persistent cough and dyspnea. Transthoracic echocardiography revealed a pericardial effusion with evidence of tamponade physiology. Computed tomography (CT) revealed a massive pericardial effusion and a left lung tumor. Pericardial tamponade was successfully treated using pericardiocentesis. She was diagnosed with lung adenocarcinoma stage IVB based on bronchoscopic lung biopsy, which showed adenocarcinoma and CT, which showed brain metastasis. Pregnancy was terminated at 18 weeks of gestation, followed by molecular-targeted therapy with alectinib hydrochloride and whole-brain irradiation. 24 months after treatment initiation the patient is alive without disease progression. Although pericardial tamponade caused by a malignant tumor during pregnancy is a rare and serious life-threatening condition, appropriate diagnosis and prompt treatment can improve maternal prognosis.

Pancreatic Cancer Cells May Adhere to the External Surface of the Puncture Needle After Endoscopic Ultrasound-Guided Fine-Needle Aspiration.

OBJECTIVE: We prospectively investigated whether cells derived from pancreatic cancers adhered to the puncture needle's external surface after endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and whether wiping the needle with alcohol swabs removed residual cancer cells. METHODS: The participants were 100 consecutive patients who underwent EUS-FNA for suspected pancreatic ductal adenocarcinoma. In the first pass of EUS-FNA, we prepared aspiration and lavage cytological diagnosis materials from the lumen and external surface of the puncture needle, respectively. This was repeated in the second pass, although the needle's external surface was wiped with an alcohol swab. RESULTS: The positivity rates of aspiration cytological diagnosis for the first and second passes were 67% and 72%, respectively. The positivity rates of lavage cytological diagnosis of the needle's external surface on the first and second passes were 20% and 3%, respectively. Wiping the needle's external surface with alcohol swabs significantly reduced the proportion of cancer cells detected ( P < 0.001). The accuracy rate based on all the collected specimens was 90%. There were no EUS-FNA-related adverse events. CONCLUSION: Pancreatic cancer cells may adhere to the puncture needle's external surface after EUS-FNA. Wiping the needle with alcohol swabs after each puncture effectively removes residual cancer cells.

Allogeneic T cells cause acute renal injury after hematopoietic cell transplantation.

Acute kidney injury (AKI) is a frequent complication of allogeneic hematopoietic cell transplantation (allo-HCT). There are many causes of AKI after allo-HCT, but it is unknown whether renal acute graft-versus-host disease (aGVHD) caused by direct allogeneic donor T-cell-mediated renal damage contributes. Here, we tested whether allogeneic donor T cells attack kidneys in murine models of aGVHD. To avoid confounding effects of nephrotoxic agents, we did not administer immunosuppressants for GVHD prophylaxis. We found that urinary N-acetyl-ß-D-glucosaminidase, a marker of tubular injury, was elevated in allogeneic recipients on day 14 after allogeneic bone marrow transplantation. Donor major histocompatibility complex-positive cells were present and CD3+ T cells were increased in the glomerulus, peritubular capillaries, interstitium, and perivascular areas in the kidneys of allo-HCT recipient mice. These T cells included both CD4+ and CD8+ cells with elevated activation markers, increased exhaustion markers, and greater secretion of proinflammatory cytokines and cytotoxic proteins. Consistent with allo-T-cell-mediated renal damage, expression of neutrophil gelatinase-binding lipocalin, a marker of AKI, and elafin, a marker of aGVHD, were increased in renal tissue of allogeneic recipients. Because apoptosis of target cells is observed on histopathology of aGVHD target tissues, we confirmed that alloreactive T cells increased apoptosis of renal endothelial and tubular epithelial cells in cytotoxic T-lymphocyte assays. These data suggest that immune responses induced by donor T cells contribute to renal endothelial and tubular epithelial cell injury in allo-HCT recipients and that aGVHD may contribute to AKI after allo-HCT.

The effect of lifestyle on the mortality associated with respiratory diseases in the general population.

Lifestyle factors, including smoking habit, diet, and physical activity, affect the prognosis of various diseases. We elucidated the effect of lifestyle factors and health status on deaths from respiratory diseases in the general Japanese population using data from a community health examination database. Data of the nationwide screening program of the Specific Health Check-up and Guidance System (Tokutei-Kenshin), targeting the general population in Japan, from 2008 to 2010 were analyzed. The underlying causes of death were coded according to the International Classification of Diseases (ICD)-10. The hazard ratios of the incidence of mortality associated with respiratory disease were estimated using the Cox regression model. This study included 664,926 participants aged 40-74 years, who were followed up for 7 years. There were 8051 deaths, including 1263 (15.69%) deaths from respiratory diseases. The independent risk factors of mortality associated with respiratory diseases were male sex, older age, low body mass index, no exercise habit, slow walking speed, no drinking habit, smoking history, history of cerebrovascular diseases, high hemoglobin A1c and uric acid levels, low low-density lipoprotein cholesterol level, and proteinuria. Aging and decline of physical activity are significant risk factors for mortality associated with respiratory diseases, regardless of the smoking status.

Implication of Skeletal Muscle Loss in the Prognosis of Patients with Pancreatic Ductal Adenocarcinoma Receiving Chemotherapy.

Objective The effect of sarcopenia on the prognosis of patients undergoing chemotherapy for unresectable pancreatic ductal adenocarcinoma remains largely unexplored. In this retrospective study, we investigated the relationship between sarcopenia and the prognosis of patients receiving first-line nanoparticle albumin-bound paclitaxel plus gemcitabine for unresectable pancreatic ductal adenocarcinoma. Methods We enrolled 251 patients with unresectable metastatic or locally advanced pancreatic ductal adenocarcinoma who had received chemotherapy between January 2015 and December 2020 at Kitasato University Hospital. Univariate and multivariate analyses were performed using the stratified Cox proportional hazards model to determine variables significantly associated with the progression-free and overall survival. Propensity score matching was performed to mitigate selection bias effects. Results In the propensity score-matched cohort, the progression-free and overall survival were not significantly different between the sarcopenia and non-sarcopenia groups (p=0.335, and 0.679 respectively). The skeletal muscle index decreased by 4.4% and 6.5% in the sarcopenia and non-sarcopenia groups, respectively, during the early treatment phase (p=0.084). There were no significant differences between groups with regard to major adverse events or drug toxicity occurrences. Both the progression-free and overall survival were significantly shorter in the skeletal muscle index loss group than in the non-skeletal muscle index loss group (p=0.026 and 0.045, respectively). Conclusion Skeletal muscle index loss during the initial treatment phase may be an early marker for the long-term prognosis of patients receiving nanoparticle albumin-bound paclitaxel plus gemcitabine as first-line treatment for unresectable pancreatic ductal adenocarcinoma.

Association between lack of sexual interest and all-cause mortality in a Japanese general population: The Yamagata prospective observational study.

BACKGROUND: Sexual interest is essential for maintaining positive sexual relationships and sexual function, which have recently been recognized as important indicators of good health and quality of life. Here, we prospectively investigated associations between sexual interest and mortality in a community-based population. METHODS: This study enrolled 20,969 subjects (8,558 males and 12,411 females) aged ≥ 40 years who participated in annual health check-ups in Yamagata Prefecture. Sexual interest was assessed by a self-report questionnaire. Associations between sexual interest and increased all-cause mortality, cardiovascular disease mortality, and cancer mortality were investigated by Cox proportional hazards modeling. RESULTS: During follow-up (median: 7.1 years), 503 subjects died; 67 deaths were due to cardiovascular disease, and 162 were due to cancer. Kaplan-Meier analysis showed that all-cause mortality and cancer mortality were significantly elevated among men who lacked sexual interest (log-rank P<0.0001, P<0.05). Cox proportional hazards model analysis with adjustment for age, hypertension, diabetes, dyslipidemia, smoking, alcohol drinking status, BMI, education, marital status, frequency of laughter, and psychological distress showed that the risk of all-cause mortality was significantly higher among men who lacked sexual interest than men who had sexual interest (hazard ratio [HR] 1.69; 95% confidence interval [CI], 1.17-2.44). CONCLUSION: Lack of sexual interest is suggested to be a risk factor for all-cause mortality in Japanese males over 40 years old. This finding has implications for the importance of sexual interest in increasing longevity in this population.

Effect of hyperhomocysteinemia on a murine model of smoke-induced pulmonary emphysema.

Hyperhomocysteinemia was reported to enhance endoplasmic reticulum (ER) stress and subsequent apoptosis in several cells. However, the precise mechanisms of smoking susceptibility associated with hyperhomocysteinemia has not been fully elucidated. This study included 7- to 9-week-old C57BL6 male mice induced with hyperhomocysteinemia and were exposed to cigarette smoke (CS). A549 cells (human alveolar epithelial cell line) were cultured with homocysteine and were exposed to cigarette smoke extract (CSE) to observe cell viability and expression of proteins related to the ER stress. After 6 months of CS exposure, pulmonary emphysema was more severely induced in the group under the condition of hyperhomocysteinemia compared to that in the control group. The apoptotic A549 cells increased as homocysteine concentration increased and that was enhanced by CSE. Protein expression levels of ER stress markers were significantly increased after simultaneous stimulation. Notably, vitamin B12 and folate supplementation improved ER stress after simultaneous stimulation of A549 cells. In this study, we showed that hyperhomocysteinemia exacerbates CS exposure-induced emphysema in mice, suggesting that hyperhomocysteinemia and CS stimulation enhance ER stress and subsequent induced apoptosis in alveolar epithelial cells. It was suggested that there is a synergistic effect between homocysteine and CS.

New image-processing technology for endoscopic ultrasound-guided fine-needle aspiration biopsy specimen evaluation in patients with pancreatic cancer.

Objectives: We evaluated the usefulness of a newly developed system with which the total amount of whitish cores in endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) samples is automatically calculated (automated multiband imaging system [AMUS]). Methods: From 30 prospectively enrolled patients suspected of having pancreatic cancer, four EUS-FNAB specimens per patient were obtained. Following AMUS calculations, two specimens were prepared after stereomicroscopy-guided manual division into whitish and reddish sections (isolation group), and the other two were prepared without such division (no-isolation group). The relation of the AMUS results pertaining to the length of the manually measured whitish cores (stereo-microscopically visible white core [SVWC]) and the sample suitability for pathologic evaluation were analyzed. Results: Histological diagnostic accuracy was 90%; median SVWC length, 14 mm; and median area of whitish core calculated using the AMUS, 13 mm2. The SVWC length correlated with whitish core amount (ρ = 0.83, p < 0.01) and adequacy score (ρ = 0.50, p < 0.01). The whitish core amount correlated with the adequacy score (ρ = 0.40, p < 0.01). The area under the receiver-operating characteristic curve calculated for whitish core amount with respect to the histological diagnosis was 0.84 (p < 0.01; cutoff ≥ 8 mm2, sensitivity 92.5%). Subgroup analysis (isolation vs. no-isolation group) revealed no significant between-group differences in the median histological adequacy (p = 0.27) or tumor cell content ratio (p = 0.28). The median scores for degree of blood contamination were significantly lower in the isolation group than in the no-isolation group (p < 0.01). Conclusion: AMUS is a simple on-site verification procedure for determining the appropriate sampling tissue quantity for high diagnostic accuracy.

Usefulness of the automated multiband imaging system for EUS-FNA biopsy specimen evaluation in patients with upper gastrointestinal subepithelial lesions.

Background and Objectives: Sample isolation processing by stereomicroscopy (SIPS) was recently introduced as an alternative to rapid on-site cytologic evaluation and showed high accuracy for use in pathologic diagnoses. SIPS is a useful, but slightly complicated procedure; therefore, a new, more straightforward method for the objective estimation of the core tissue amount required during the sampling is desirable. We evaluated the usefulness of the automated multiband imaging system (AMUS) for calculating whitish core amounts in EUS-FNA biopsy (EUS-FNAB) samples from patients with subepithelial lesions (SELs). Methods: Four EUS-FNAB specimens per patient were obtained from 20 patients with upper gastrointestinal SELs. The correlation between the whitish core amount calculated by AMUS, length of the manually measured whitish cores (stereomicroscopically visible white core [SVWC]), and sample suitability for pathologic evaluation were analyzed. Results: We identified 13 patients with gastrointestinal stromal tumors, five with leiomyomas, one with a schwannoma, and one with an ectopic pancreas. The histological diagnostic accuracy was 100%, median SVWC length was 9 mm, and median whitish core area, calculated using AMUS, was 10 mm2. SVWC length correlated with whitish core amount (ρ = 0.81, P < 0.01) and adequacy score (ρ = 0.54, P < 0.01). Whitish core amount correlated with adequacy score (ρ = 0.54, P < 0.01). The area under the receiver-operating characteristic curve calculated for whitish core amount with respect to the histological diagnosis was 0.83 (P < 0.01; cutoff ≥4 mm2, sensitivity 98.4%). Conclusions: AMUS, a simple on-site verification instrument, is an alternative to SIPS for determining the appropriate SEL tissue sampling quantity with high diagnostic accuracy.

Endoscopic re-intervention after stent-in-stent versus side-by-side bilateral self-expandable metallic stent deployment.

BACKGROUND AND AIM: Endoscopic bilateral self-expandable metallic stent (SEMS) placement for unresectable malignant hilar biliary obstruction (MHBO) is widely performed; however, re-intervention after recurrent biliary obstruction (RBO) is often challenging. We compared stent-in-stent (SIS) and side-by-side (SBS) SEMS placement for MHBO considering re-intervention for RBO. METHODS: One hundred five consecutive patients with MHBO who underwent endoscopic bilateral SEMS placement in our hospital and its affiliated institutions were enrolled in this study; 75 patients underwent partial SIS deployment between December 2005 and December 2012; and 30 underwent SBS deployment between January 2013 and March 2019. Initial treatments and re-interventions in each group were retrospectively evaluated. RESULTS: Technical success rate (92% vs 100%, P = 0.179), procedure duration (46 vs 35 min, P = 0.382), functional success rate (97.1% vs 100%, P = 1.00), complication rate (24.6% vs 20.0%, P = 0.797), time to RBO (260 vs 312 days; Gray test, P = 0.815), and rate of RBO (59.4% vs 70.0%, P = 0.371) were not significantly different between the SIS and SBS groups. However, bilateral re-stenting with plastic stents through SEMS was successful in 63.4% of patients in the SIS group compared with 100% of patients in the SBS group (P = 0.0013). Median time to RBO upon first re-stenting with a plastic stent was 75 days (range, 11-195 days). CONCLUSIONS: Endoscopic re-stenting after RBO was significantly more successful in the SBS group than in the SIS group. SBS method is suitable for MHBO considering revisionary stent placement.

Ivabradine as an Adjuvant Agent for Severe Heart Failure Occurring in the Early Phase after Allogeneic Hematopoietic Cell Transplantation.

Cardiotoxicity is a critical complication of allogeneic hematopoietic cell transplantation (allo-HCT). In particular, management of severe cardiotoxicity occurring in the early phases of allo-HCT is challenging. We encountered a case of severe cardiotoxicity resulting from AHF six days after allo-HCT, which resisted catecholamines and diuretics. The patient was treated with anthracycline-containing regimens and underwent myeloablative conditioning, including high-dose cyclophosphamide. As invasive circulatory assisting devices were contraindicated because of his immunocompromised status and bleeding tendency, we successfully treated the patient with ivabradine-containing medications. Ivabradine may therefore be considered an alternative drug for the treatment of severe cardiotoxicity induced by cytotoxic agents.