Outcomes and Recurrence Rate of Esophageal Varices after Endoscopic Treatment in Patients with Alcoholic Cirrhosis and Viral Cirrhosis.

BACKGROUND: The incidence of alcoholic liver cirrhosis (ALC) is increasing. However, few reports have focused on ALC-derived esophageal varices (EV). We retrospectively examined differences in overall survival (OS) and EV recurrence rate in patients after endoscopic injection sclerotherapy (EIS) for ALC and hepatic B/C virus liver cirrhosis (B/C-LC). METHODS: We analyzed data from 215 patients (B/C-LC, 147; ALC, 68) who underwent EIS. The primary endpoints were OS and EV recurrence in patients with unsuccessful abstinence ALC and those with uncontrolled B/C-LC, before and after propensity score matching (PSM) to unify the patients' background. The secondary endpoints were predictors associated with these factors, as determined by multivariate analysis. RESULTS: The observation period was 1,430 ± 1,363 days. In the analysis of all patients, OS was significantly higher in the ALC group than in the B/C-LC group (p = 0.039); however, there was no difference in EV recurrence rate (p = 0.502). Ascites and history of hepatocellular carcinoma (HCC) (p = 0.019 and p < 0.001, respectively) predicted OS, whereas age and EV size predicted recurrence (p = 0.011 and 0.024, respectively). In total, 96 patients without an HCC history were matched by PSM, and there was no significant difference in OS or EV recurrence rate (p = 0.508 and 0.246, respectively). CONCLUSION: When limited to patients without a history of HCC, OS and the EV recurrence rate were comparable in patients with ALC who continued to consume alcohol and those with B/C-LC without viral control.

Manual reduction for incarcerated obturator hernia.

Emergent surgery is a common approach for incarcerated obturator hernias, with high morbidity and mortality rates. Moreover, there have been reports of elective surgery cases after noninvasive manual reduction. For a decade, the initial approach in our institution is also manual reduction unless bowel viability is poor. This study aimed to clarify the efficacy and safety of manual reduction followed by elective surgery. We retrospectively reviewed 50 cases of incarcerated obturator hernia from 2010 to 2022 at Iwate Prefectural Iwai Hospital. Manual reduction was attempted in 31 (62%) patients. The reduction was successful in 21 (42%) patients, and most of them received mesh repair using the extraperitoneal approach as elective surgery. However, two patients underwent emergent surgery in the waiting period because of late-onset constriction and a small bowel perforation. Patients with irreducible hernia underwent emergent surgery, except for two patients who received the best supportive care. Postoperative complications were observed in 5% and 22% of reducible and irreducible cases, respectively. Postoperative mortality was zero in both groups. Manual reduction is useful in some cases, but careful observation is needed because late-onset constriction and perforation could occur.

Oxidative stress induces MUC5AC expression through mitochondrial damage-dependent STING signaling in human bronchial epithelial cells.

Oxidative stress increases the production of the predominant mucin MUC5AC in airway epithelial cells and is implicated in the pathogenesis of bronchial asthma and chronic obstructive pulmonary disease. Oxidative stress impairs mitochondria, releasing mitochondrial DNA into the cytoplasm and inducing inflammation through the intracytoplasmic DNA sensor STING (stimulator of interferon genes). However, the role of innate immunity in mucin production remains unknown. We aimed to elucidate the role of innate immunity in mucin production in airway epithelial cells under oxidative stress. Human airway epithelial cell line (NCI-H292) and normal human bronchial epithelial cells were used to confirm MUC5AC expression levels by real-time PCR when stimulated with hydrogen peroxide (H2O2). MUC5AC transcriptional activity was increased and mitochondrial DNA was released into the cytosol by H2O2. Mitochondrial antioxidants were used to confirm the effects of mitochondrial oxidative stress where antioxidants inhibited the increase in MUC5AC transcriptional activity. Cyclic GMP-AMP synthase (cGAS) or STING knockout (KO) cells were generated to investigate their involvement. H2O2-induced MUC5AC expression was suppressed in STING KO cells, but not in cGAS KO cells. The epidermal growth factor receptor was comparably expressed in STING KO and wild-type cells. Thus, mitochondria and STING play important roles in mucin production in response to oxidative stress in airway epithelial cells.

Enlargement of the Spleen Index Is a Predictor of the Occurrence of Esophageal Varices and Hepatocellular Carcinoma after Administering Direct-acting Antiviral Agents.

Objective Direct-acting antiviral agents (DAAs) can eliminate hepatitis C virus at a high rate, although the long-term incidence of portal hypertension and hepatocellular carcinoma (HCC) has not yet been elucidated. In this observational study, we clarified the predictors associated with the incidence of esophageal varices (EVs) and HCC after DAAs treatment based on ultrasound findings and blood examinations. Methods A total of 78 patients treated with DAAs were enrolled in this study. The primary endpoint was to identify the predictors associated with EVs and HCC occurrence using univariate and multivariate analyses. Secondary endpoints were to extract the cutoff values for EVs and HCC occurrence and clarify the changes in liver stiffness (LS), spleen stiffness (SS), spleen index (SI), portal venous flow volume (PVF), and blood examination at 12 weeks after the end of DAAs treatment. Results The mean observation period was 1,402±546 days. SI change (SI after DAAs-SI before DAAs) was a predictor of EVs occurrence in multivariate analysis (p=0.045). The treatment history of HCC, albumin value before DAAs, and SI change were predictors of HCC occurrence in multivariate analysis (p=0.002, p=0.032, and p=0.009, respectively). LS, SS, PVF, SI, and liver function significantly improved after DAAs treatment. Conclusion Portal hypertension seems to improve after DAAs treatment over a long period. Patients with splenomegaly deterioration after DAAs treatment need to be carefully monitored for the occurrence of EVs and HCC.

Computer-aided diagnosis of early-stage colorectal cancer using nonmagnified endoscopic white-light images (with videos).

BACKGROUND AND AIMS: Differentiation of colorectal cancers (CRCs) with deep submucosal invasion (T1b) from CRCs with superficial invasion (T1a) or no invasion (Tis) is not straightforward. This study aimed to develop a computer-aided diagnosis (CADx) system to establish the diagnosis of early-stage cancers using nonmagnified endoscopic white-light images alone. METHODS: From 5108 images, 1513 lesions (Tis, 1074; T1a, 145; T1b, 294) were collected from 1470 patients at 10 academic hospitals and assigned to training and testing datasets (3:1). The ResNet-50 network was used as the backbone to extract features from images. Oversampling and focal loss were used to compensate class imbalance of the invasive stage. Diagnostic performance was assessed using the testing dataset including 403 CRCs with 1392 images. Two experts and 2 trainees read the identical testing dataset. RESULTS: At a 90% cutoff for the per-lesion score, CADx showed the highest specificity of 94.4% (95% confidence interval [CI], 91.3-96.6), with 59.8% (95% CI, 48.3-70.4) sensitivity and 87.3% (95% CI, 83.7-90.4) accuracy. The area under the characteristic curve was 85.1% (95% CI, 79.9-90.4) for CADx, 88.2% (95% CI, 83.7-92.8) for expert 1, 85.9% (95% CI, 80.9-90.9) for expert 2, 77.0% (95% CI, 71.5-82.4) for trainee 1 (vs CADx; P = .0076), and 66.2% (95% CI, 60.6-71.9) for trainee 2 (P < .0001). The function was also confirmed on 9 short videos. CONCLUSIONS: A CADx system developed with endoscopic white-light images showed excellent per-lesion specificity and accuracy for T1b lesion diagnosis, equivalent to experts and superior to trainees. (Clinical trial registration number: UMIN000037053.).

Regional differences in the prevalence of oral allergy syndrome among Japanese children: A questionnaire-based survey.

BACKGROUND: Oral allergy syndrome (OAS) is characterized by an immediate allergic reaction that mainly or partially affects the oral mucosa, pharynx, or lips, and it is usually caused by ingesting fresh fruits or vegetables. Most patients with OAS also have allergic rhinitis due to pollen. As allergic rhinitis is increasingly prevalent in the Japanese population and the age at disease development is decreasing, morbidity associated with OAS among the younger population is likely to increase. However, there is little information about the prevalence of this disease among Japanese children, specifically the influences of residency in regions with different environments. OBJECTIVE: To investigate the prevalence of OAS and seasonal allergic rhinitis (SAR) among Japanese children and evaluate the relationship between OAS and SAR. METHODS: We administered a questionnaire-based survey among children aged 7-15 years, living in 4 cities in central Japan. RESULTS: The questionnaires were administered to 4103 children and completed by 3365 (82.0%). Overall, 524 children (15.6%) reported OAS-like symptoms after ingesting fruits or vegetables. The prevalence of seasonal SAR and oral symptoms significantly differed among the 4 cities. The total prevalence of oral symptoms co-occurring with SAR was 24.4%, which was significantly higher than the prevalence of symptoms occurring without SAR (10.2%, p < 0.001). CONCLUSIONS: Herein, oral symptoms were more likely to occur in patients with SAR than in those without SAR. The prevalence of SAR and food-induced oral symptoms significantly differed among the regions, suggesting they might be affected by regional differences in lifestyles and flora.

Clinical outcomes of open and closed management after surgical treatments in patients with medication-related osteonecrosis of the jaw.

CONTEXT AND PURPOSE: To achieve success following surgical treatment of MRONJ, complete wound closure has been considered necessary; open wound management has not been generally recommended. Therefore, various closure techniques using local flaps have been reported. However, these techniques often increase surgical invasiveness, and there is minimal evidence regarding whether complete wound closure is preferable to open wound management following surgical treatment of MRONJ. The aim of this study was to clarify whether complete wound closure is necessary for successful healing following surgical treatment of MRONJ. PROCEDURES: This retrospective study included 52 patients with stage 2 and 3 MRONJ who underwent surgical treatment. Twenty-seven of the 52 patients received open wound management, while the remaining 25 received complete wound closure management. The outcomes of both groups were evaluated at the 6-month follow-up visit; 'success' was defined as complete mucosal covering without symptoms and 'failure' was defined as the presence of residual bone exposure or progression of disease. MAIN FINDINGS: In the open wound group, 23 patients (85.1%) exhibited 'success' and four patients (14.8%) exhibited 'failure'; in the closed wound group, 21 patients (84.0%) exhibited 'success' and four patients (16.0%) exhibited 'failure'. These outcomes were not significantly different between groups. PRINCIPAL CONCLUSIONS: Although complete wound closure has many advantages with respect to the healing process, open wound management is also acceptable for patients with difficulty achieving complete wound closure, as well as for surgeons who wish to reduce surgical invasiveness.

Expression of Leucine-rich Repeat-containing Protein 32 Following Lymphocyte Stimulation in Patients with Non-IgE-mediated Gastrointestinal Food Allergies.

The lymphocyte stimulation test (LST) facilitates the diagnosis of non-IgE-mediated gastrointestinal food allergies (non-IgE-GI-FAs). However, LSTs require large volumes of blood and prolonged culture durations. Recently, we found that IL2RA mRNA expression in peripheral blood mononuclear cells (PBMCs) of patients with non-IgE-GI-FAs increased after a 24 h stimulation with milk proteins. We designated this gene expression test as the instant peripheral blood allergen stimulation test (iPAST). In this study, we investigated whether other activated T cell-associated genes are superior to IL2RA in the iPAST for the supplementary diagnosis of non-IgE-GI-FAs. After incubating PBMCs with milk proteins for 24 h, the mRNA levels of three genes, LRRC32, TNFRSF4, and CD69, were assessed using quantitative RT-PCR. The diagnostic significance of the mRNA expression was evaluated by analyzing the receiver operating characteristic (ROC) curve. Upon stimulation with α-casein, κ-casein, α-lactalbumin, or a mixture of four milk protein components (Pmix), LRRC32 expression in the PBMCs of 16 patients with non-IgE-GI-FAs was found to be higher than that in their 17 control counterparts, whereas TNFRSF4 and CD69 levels remained unaltered. Except for ß-lactoglobulin and cow's milk (CM), the area under the ROC curve (AUC) for LRRC32 mRNA expression upon stimulation was >0.7, which validated the diagnostic ability of this test. Notably, α-casein and Pmix had higher AUC scores of 0.820 and 0.842, respectively, than other antigens. iPAST assessed by LRRC32 as well as IL2RA may be useful for the supplementary diagnosis of non-IgE-GI-FAs as an alternative to LSTs and provide insight into the pathogenesis of non-IgE-GI-FAs.

Successful treatment with laparoscopy-assisted surgery for ileal perforation due to an ingested foreign body: A report of two cases.

INTRODUCTION: Presently, the advantage of laparoscopic surgery is widely recognized and it is gaining popularity not only in elective abdominal surgeries but also in various kinds of emergent abdominal surgeries. This report describes two patients diagnosed with ileal perforation due to an ingested foreign body (FB)-a rare abdominal emergency-who were treated laparoscopically. PRESENTATION OF CASE: Both patients were brought in by an ambulance to our hospital, with complaints of increasing lower abdominal pain. Computed tomography scan revealed a small bowel perforation due to an ingested FB in both patients, and laparoscopy-assisted partial ileal resection was immediately performed. Their postoperative recoveries were uneventful. DISCUSSION: Both patients with this rare abdominal emergency were successfully treated with laparoscopic surgery. Its feasible diagnostic and therapeutic abilities and decreased invasiveness contributed to their uneventful and fast recoveries. Extracorporeal handling of the affected small bowel via mini-laparotomy was useful in this setting as it was safe, fast, and cost-effective. CONCLUSION: Laparoscopic surgery is effective, even for this rare abdominal emergency. Moreover, laparoscopy-assisted surgery accompanying mini-laparotomy is a rational treatment approach, especially for this condition.

[SWITCHING BIOLOGICS LED TO GOOD CONTROL IN SEVERE CHILDHOOD ASTHMA: A CASE REPORT].

The two biologic therapies, anti-IgE (omalizumab) and anti-IL-5 antibodies (mepolizumab), are used in the treatment of severe pediatric asthma. We present here a case study of a 13-year-old girl with severe asthma who switched from omalizumab to mepolizumab therapy and achieved good control over her asthma. The patient was diagnosed with asthma at one year of age and presented with poor disease control, even while taking high doses of inhaled corticosteroids (ICS). As such, she was considered to have severe persistent asthma. At 10 years old, she began omalizumab therapy which improved asthma control. However, after two years of this therapy, she manifested frequent acute exacerbations. At 12 years old, she switched to mepolizumab and has since maintained good control of asthma. Additionally, total serum IgE levels and peripheral eosinophil counts decreased. As the underlying mechanisms of omalizumab and mepolizumab therapy are distinct, it is recommended to use either one if the other proves ineffective.

Severity scales of non-IgE-mediated gastrointestinal food allergies in neonates and infants.

BACKGROUND: Non-IgE-mediated gastrointestinal food allergies (non-IgE-GI-FAs) are one type of food allergy found in neonates and infants. Few reports have defined the severity of non-IgE-GI-FAs in these populations. METHODS: Grading scales of the severity of non-IgE-GI-FAs according to extra-GI symptoms, such as poor weight gain, as well as systemic symptoms, including fever and shock, were developed and retrospectively applied to patients with non-IgE-GI-FAs. The relationship between the severity of non-IgE-GI-FAs and both clinical and laboratory findings were examined. RESULTS: Elevation of C-reactive protein levels and a decrease in total protein and albumin were observed in accordance with allergy severity. In an endoscopic examination, inflammatory findings were confirmed in large areas of the colonic mucosa in case of higher severity levels, and infiltration of inflammatory cells other than eosinophils was found in the severest grade. Extensively hydrolyzed milk or amino acid-based milk was required for all patients with the severest grade. In addition, the timing of acquiring tolerance tended to be late for this grade. CONCLUSIONS: Classification and determination of the severity of non-IgE-GI-FAs in neonates and infants may not only contribute to elucidation of the pathogenesis but may also be useful in the clinical setting.

A gastrointestinal stromal tumor of the jejunum presenting with an intratumoral abscess: A case report and a literature review.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. The small intestine is the second-most frequent location where GISTs occur after the stomach. Attention should be paid to small intestinal GISTs because they infrequently present with acute abdomen, which necessitates emergency surgery. This report describes a patient with a small intestinal GIST developing a giant intratumoral abscess, in whom emergency surgery was performed. PRESENTATION OF CASE: A 56-year-old woman presented with worsening abdominal pain. Computed tomography scan showed an approximately 9.5 cm × 9 cm tumor bearing a thick and hypervascularized wall with an internal air-fluid level. Emergency laparotomy revealed the tumor originated from the jejunum, and partial resection of the jejunum was performed. A large amount of pus was contained inside the tumor. Immunohistochemically, the tumor was diagnosed as a high risk GIST of the Cjejunum, and imatinib mesylate was initiated. DISCUSSION AND CONCLUSION: When an intratumoral abscess in the abdomen is confirmed, GISTs should be listed as differential diagnosis. Complete surgical resetcion with careful handling and adjuvant chemotherapy with imatinib mesylate are considered to be important for this state.

Development of Autoimmune Hepatitis during Direct-acting Antiviral Therapy for Chronic Hepatitis C Virus Infection.

An 81-year-old woman developed liver dysfunction after two months' treatment with direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection. She was positive for serum anti-nuclear antibody, with an elevated immunoglobulin G level. A liver biopsy revealed high-grade interface hepatitis and infiltrate of lymphocytes and plasma cells. DAA-associated drug-induced autoimmune hepatitis (DI-AIH) was considered. Her liver dysfunction improved after discontinuing DAA therapy and starting prednisolone treatment. The differential diagnosis for AIH should include liver injury during DAA therapy for chronic HCV infection.

Antegrade jejunogastric intussusception and common bile duct stones at 14 months after gastrectomy and cholecystectomy: A case report.

INTRODUCTION: Intussusception after gastrectomy is a minor complication after gastrectomy, while common bile duct stone (CBD) is also a rare complication post cholecystectomy. We report a case that simultaneously caused both intussusception and CBD stone following gastrectomy with prophylactic cholecystectomy. CASE PRESENTATION: A 74-year-old woman underwent distal gastrectomy with Roux-en-Y reconstruction and prophylactic cholecystectomy for gastric cancer. After 14 months, the patient reported nausea and vomiting. Abdominal computed tomography scanning showed antegrade intussusception of the Roux limb of the gastrojejunostomy and calculi in the common bile duct, with a diagnosis of jejunogastric intussusception and common bile duct stones. The patient was hospitalized and endoscopic examination was performed on day 3. Endoscopic treatment did not resolve the intussusception, which also obstructed the bile duct stones. Elective surgery was performed on day 10, in which the invaginated Roux limb of the gastrojejunostomy was resected after manual reinstatement to its original position. This was followed by open exploration of the common bile duct and T-tube drainage. The patient was discharged 25days post- surgery. DISCUSSION: Jejunogastric intussusception and CBD stone may require operative management, although the operation could be elective after sufficient examination and preparation. CONCLUSION: Jejunogastric intussusception and bile duct stones are rare after distal gastrectomy, physicians should be alerted to the possibility of these complications.

Intrahepatic cholangiocarcinoma producing granulocyte colony-stimulating factor and parathyroid hormone-related protein.

A 78-year-old man was referred to our hospital with suspected liver abscess. Fever and inflammatory reaction resolved after percutaneous drainage and administration of antibiotics. However, leukocyte count was remarkably increased, and hypercalcemia was noted. The liver mass was also enlarged, as observed in the follow-up abdominal CT scans. Therefore, a percutaneous needle biopsy was performed, and the histopathological findings indicated the presence of adenocarcinoma. Additional blood examination revealed high serum levels of granulocyte colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP). Lastly, the patient was diagnosed with cholangiocarcinoma producing G-CSF and PTHrP. Chemoradiotherapy with S-1 was initiated, which was partially effective. However, the patient died 134 days after initiating the therapy. Only two cases of cholangiocarcinoma producing G-CSF and PTHrP have been reported to date. Here we reported an additional case of cholangiocarcinoma producing G-CSF and PTHrP.

A prospective randomized study of the use of an ultrathin colonoscope versus a pediatric colonoscope in sedation-optional colonoscopy.

BACKGROUND: Ultrathin colonoscopes (UTC) reportedly produce less pain during colonoscopy than standard colonoscopes. The aim of this study was to assess the tolerability of an UTC compared with that of a pediatric colonoscope. METHODS: A total of 270 adult patients scheduled to undergo colonoscopy were randomized, with 134 allocated to the UTC group and 136 to the pediatric colonoscope group. Pain was assessed using a visual analog scale. For all procedures, sedation was administered only if requested. Overall pain, rate and time of cecal and terminal ileum intubation, number of patients requesting sedation, adenoma detection rates (ADR), and rate of complications were measured and analyzed. RESULTS: Among all patients, the medians of maximum pain and overall pain were significantly lower in the UTC group than in the pediatric colonoscope group (23 vs. 38, P < 0.001; 12 vs. 22, P = 0.0003, respectively). Significantly fewer patients requested sedation in the UTC group than in the pediatric colonoscope group (1.4 vs. 6.6%; P = 0.0269). No significant differences were seen in either the rate and time of successful cecal and terminal ileum intubation, or in other procedure-related outcomes, including ADR. CONCLUSIONS: Compared with a pediatric colonoscope, the UTC was associated with reduced overall and maximum pain during colonoscopy, with no difference in ADR.