Safety and efficacy of low-power pure-cut hot snare polypectomy for small nonpedunculated colorectal polyps compared with conventional resection methods: A propensity score matching analysis.

Objectives: Cold snare polypectomy (CSP) is widely performed for small colorectal polyps. However, small colorectal polyps sometimes include high-grade adenomas or carcinomas that require endoscopic resection with electrocautery. This study aimed to evaluate the efficacy and safety of a novel resection technique, hot snare polypectomy with low-power pure-cut current (LPPC-HSP) for small colorectal polyps, compared with CSP and conventional endoscopic mucosal resection (EMR). Methods: Records of patients who underwent CSP, EMR, or LPPC-HSP for nonpedunculated colorectal polyps less than 10 mm between April 2021 and March 2022 were retrospectively evaluated. We analyzed and compared the treatment outcomes of CSP and EMR with those of LPPC-HSP using propensity score matching. Results: After propensity score matching of 396 pairs, an analysis of CSP and LPPC-HSP indicated that LPPC-HSP had a significantly higher R0 resection rate (84% vs. 68%; p < 0.01). Delayed bleeding was observed in only two cases treated with CSP before matching. Perforation was not observed with either treatment. After propensity score matching of 176 pairs, an analysis of EMR and LPPC-HSP indicated that their en bloc and R0 resection rates were not significantly different (99.4% vs. 100%, p = 1.00; 79% vs. 81%, p = 0.79). Delayed bleeding and perforation were not observed with either treatment. Conclusions: The safety of LPPC-HSP was comparable to that of CSP. The treatment outcomes of LPPC-HSP were comparable to those of conventional EMR for small polyps. These results suggest that this technique is a safe and effective treatment for nonpedunculated polyps less than 10 mm.

Low-power pure-cut hot snare polypectomy for colorectal polyps 10-14 mm in size: a multicenter retrospective study.

BACKGROUND AND AIM: Hot snare excision using electrocautery is widely used for large colorectal polyps (>10 mm); however, adverse events occur due to deep thermal injury. Colorectal polyps measuring 10-14 mm rarely include invasive cancer. Therefore, less invasive therapeutic options for this size category are demanding. We have developed hot snare polypectomy with low-power pure-cut current (LPPC HSP), which is expected to contribute to less deep thermal damage and lower risk of adverse events. This study aimed to evaluate the efficacy and safety of LPPC HSP for 10-14 mm colorectal polyps, compared with conventional endoscopic mucosal resection (EMR). METHODS: In this multicenter, retrospective, observational study, clinical outcomes of EMR and LPPC HSP for 10-14 mm nonpedunculated colorectal polyps between January 2021 and March 2022 were compared using propensity score matching. RESULTS: We identified 203 EMR and 208 LPPC HSP cases. After propensity score matching, the baseline characteristics between the groups were comparable, with 120 pairs. The en bloc and R0 resection rates were not significantly different between EMR and LPPC HSP groups (95.8% vs 97.5%, P = 0.72; 90.0% vs 91.7%, P = 0.82). The rates of delayed bleeding and perforation did not differ between the groups. CONCLUSIONS: Compared with conventional EMR, LPPC HSP showed a similar resection ability without an increase in adverse events. These results suggest that LPPC HSP is a safe and effective treatment for 10-14 mm nonpedunculated colorectal polyps.

FOXA1/CK7-positive Esophageal Squamous Cell Carcinoma with Aggressive Liver Metastasis: A Case Report.

Cytokeratin (CK) is a specific marker of adenocarcinoma. However, cases of CK7-positive esophageal squamous cell carcinoma (ESCC) have only rarely been reported. We herein report a case of unresectable CK7-positive ESCC with aggressive liver metastasis following nivolumab treatment initiation. Nivolumab treatment was discontinued after one course because of complications. Notably, the liver metastases exhibited accelerated growth. Immunostaining of the necropsy specimens revealed diffuse positivity for forkhead box protein A1 (FOXA1)/CK7, thus indicating a potent poor immune response. The potential correlation between CK7 expression and the immune checkpoint inhibitor response may offer valuable insights into the development of effective therapeutic strategies.

Gel immersion endoscopic mucosal resection for early gastric neoplasms: a multicenter case series study.

Several cases have been reported that suggest the efficacy of gel immersion endoscopic mucosal resection (GI-EMR) for gastric neoplasms. However, no study has evaluated treatment outcomes of GI-EMR for gastric neoplasms. This study aimed to investigate the efficacy and safety of GI-EMR for early gastric neoplasms. Nine patients (17 lesions) undergoing gastric GI-EMR were included, with a median lesion size of 10 mm (interquartile range [IQR] 5-13 mm). All lesions were protruding or flat elevated. The median procedure time was 3 minutes (IQR 2-5) and en bloc resection was achieved in all cases. Among 15 neoplastic lesions, the R0 resection rate was 86.7% (13/15 lesions). Adverse events included immediate bleeding requiring hemostasis in two cases, which was controlled endoscopically. No delayed bleeding or perforation occurred. In conclusion, GI-EMR may be a safe and effective treatment for early, small gastric neoplasms. However, due to the small sample in the present study, further investigation is required regarding the indication for this technique.

A case of early gastric cancer with metastatic recurrence following curative endoscopic submucosal dissection.

A 70-year-old man was diagnosed with early gastric cancer with ulcerative findings. Endoscopic submucosal dissection as an absolute indication was performed, and en bloc resection was achieved. Pathological examination revealed a well-differentiated adenocarcinoma, 3 × 2 mm in size, intramucosal, with an ulcerative scar, no lymphovascular invasion, and a tumor-free margin. We diagnosed it as a curative resection and followed up with annual endoscopy. Sixteen months after endoscopic submucosal dissection, esophagogastroduodenoscopy revealed a singular ulcer scar; however, serum carcinoembryonic antigen level was elevated. Computed tomography scan showed wall thickening of the gastric antrum and an irregular mass on the dorsal side. Additionally, 18F-fluorodeoxyglucose positron emission tomography/coomputed tomography showed 18F-fluorodeoxyglucose uptake in the gastric antrum, irregular mass, and liver. Endoscopic ultrasonography revealed an internally heterogeneous mass in the gastric antrum region extending from the submucosal layer to the muscularis propria layer. Using an endoscopic ultrasonography-guided fine needle biopsy with a 22-gauge needle for the mass, we diagnosed local recurrence with the submucosal tumor-like appearance, lymph node metastasis, and liver metastases. Unfortunately, the patient died of gastric cancer 3 months after the diagnosis. Here, we report a rare case of local recurrence in the submucosal layer, lymph node metastasis, and liver metastases 16 months after curative endoscopic submucosal dissection.

The diagnostic accuracy of endoscopic ultrasound-shear wave elastography in multiple pancreatic regions for chronic pancreatitis based on the Rosemont criteria.

PURPOSE: Although endoscopic ultrasound (EUS) has been widely used for diagnosing chronic pancreatitis (CP), the assessment of fibrosis using the Rosemont criteria (RC) is generally subjective. Shear wave elastography using EUS (EUS-SWE) has been advocated as an objective approach to evaluating pancreatic fibrosis; however, it is unknown which pancreatic region should be selected for measurement. This study aims to compare the diagnostic accuracy in diagnosing CP by measurement site. METHODS: Fifty patients with CP or suspected CP who underwent EUS-SWE were retrospectively analyzed. As per the RC, they were classified into two groups: CP and non-CP. Pancreatic stiffness was evaluated by measuring the velocities of the shear wave (Vs) in addition to determining the relevant cutoff value of Vs for diagnosing CP. The correlation between Vs and RC, and the RC factors affecting pancreatic stiffness were evaluated. RESULTS: In the CP group, the Vs were notably higher in all regions (P < 0.001). The Vs for diagnostic accuracy of CP were highest in the body [area under the curve (AUC): 0.87]. A significant correlation was seen between the number of RC and Vs in all regions, with the correlation coefficient being highest in the pancreatic body (rs = 0.55). Multivariate analysis revealed that lobularity with honeycombing was an independent factor for pancreatic stiffness (P = 0.02). CONCLUSION: The pancreatic body is a suitable region for assessing pancreatic stiffness using EUS-SWE. Additionally, quantifying Vs is a valuable objective indicator for diagnosing CP.

Efficacy of endoscopic samplings during initial biliary drainage for cases of pancreatic head cancer: United diagnostic yields of multiple pathological samplings.

BACKGROUND/OBJECTIVES: The diagnostic ability of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been fully studied; however, the efficacy of other endoscopic samplings (OESs) is less clear. The aim of this study was to examine the diagnostic efficacies of OESs for pancreatic head cancer (PHC). METHODS: The diagnostic efficacies of endoscopic samplings were retrospectively analyzed in 448 PHC cases and 63 cases of mass-forming pancreatitis (MFP) during initial transpapillary biliary drainage. The OESs included duodenal biopsy (118 PHCs and 50 MFPs), biliary biopsy (218 and 51) with cytology (368 and 53), and pancreatic duct biopsy (23 and 13) with cytology (56 and 43). EUS-FNA was conducted in a different session (149 and 62). Factors associated with OES sensitivity were analyzed. The sensitivity of biliary biopsy was compared between 1.95 mm and 1.8 mm forceps. RESULTS: Cancer cells were confirmed in 87.9% of the EUS-FNA samplings and in 64.1% (268/418) obtained by combined OESs (average 1.7 OES types per case): 68.6% by duodenal biopsy, 59.6% by biliary biopsy, 32.6% by biliary cytology, 73.9% by pancreatic duct biopsy, and 33.9% by pancreatic duct cytology. No MFP cases revealed cancer by any sampling. OESs did not increase adverse events. Duodenal stenosis, serum bilirubin, tumor size, and pancreatic juice amounts were associated with OES sensitivity. Biliary biopsy had the same sensitivity with different forceps. CONCLUSION: EUS-FNA was the most diagnostic protocol; however, OESs can be safely applied during the initial biliary drainage to reduce the demand for EUS-FNA while providing good diagnostic yields.

Features of post-endoscopic submucosal dissection electrocoagulation syndrome for early gastric neoplasm.

BACKGROUND AND AIM: Post-endoscopic submucosal dissection electrocoagulation syndrome (PECS) has become a common adverse event after colorectal endoscopic submucosal dissection (ESD) and esophageal ESD. However, little is known about PECS after gastric ESD. Therefore, this study aimed to investigate the clinical features of PECS after gastric ESD. METHODS: Patients who underwent ESD for gastric cancer or adenoma between January 2016 and December 2017 were retrospectively investigated. PECS was clinically diagnosed based on the presence of upper abdominal pain and localized abdominal tenderness with a temperature of >37.5°C, without perforation. We analyzed the clinical features of PECS. RESULTS: A total of 637 ESD cases were enrolled; PECS occurred in 32 patients (5.0%), all of whom were diagnosed on postoperative Day 1. Among PECS cases, unplanned prolongation of hospitalization or fasting period was observed in 15 patients (47%). As a result, the median durations of hospitalization and fasting period were significantly longer in PECS cases (P = 0.008 and P < 0.001, respectively); however, the mean differences were less than a day. Additionally, all PECS cases recovered with conservative treatment. CONCLUSIONS: PECS is considered a common adverse event after gastric ESD. More than half of patients with PECS could start diets and be discharged as well as those without PECS.

Discovery of N-(6-(5-fluoro-2-(piperidin-1-yl)phenyl)pyridazin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)methanesulfonamide as a brain-permeable and metabolically stable kynurenine monooxygenase inhibitor.

Kynurenine monooxygenase (KMO) is expected to be a good drug target to treat Huntington's disease (HD). This study presents the structure-activity relationship of pyridazine derivatives to find novel KMO inhibitors. The most promising compound 14 resolved the problematic issues of lead compound 1, i.e., metabolic instability and reactive metabolite-derived side-effects. Compound 14 exhibited high brain permeability and a long-lasting pharmacokinetics profile in monkeys, and neuroprotective kynurenic acid was increased by a single administration of 14 in R6/2 mouse brain. These results demonstrated 14 may be a potential drug candidate to treat HD.

Long-term outcomes of salvage endoscopic submucosal dissection for local failure after chemoradiotherapy for esophageal squamous cell carcinoma.

BACKGROUND: Salvage endoscopic submucosal dissection is considered a minimally invasive treatment for local failure after chemoradiotherapy for esophageal squamous cell carcinoma. However, the long-term outcomes have not been fully evaluated. This study investigated the short-term and long-term outcomes of salvage endoscopic submucosal dissection. METHODS: Patients who underwent endoscopic submucosal dissection for local recurrence or residual tumor after chemoradiotherapy from January 2006 to December 2017 were retrospectively investigated. Follow-up included endoscopic examination and computed tomography at least once every 6 months after salvage endoscopic submucosal dissection. Risk factors for disease recurrence after salvage endoscopic submucosal dissection were assessed using the Cox hazards model. RESULTS: A total of 30 patients (33 cases of esophageal squamous cell carcinoma: local recurrence, n = 27; residual tumor, n = 6) were included. The median endoscopic submucosal dissection procedure time was 40 min (interquartile range [IQR], 33-58.5 min). En bloc resection was achieved in 31 (94%) of 33 esophageal squamous cell carcinoma cases. One patient with intraoperative perforation did not require surgical intervention and recovered with conservative treatment. A total of 16 patients (53%) had disease recurrence at a median follow-up of 51 months (IQR, 33-81 months). The 3-year overall, disease-specific, recurrence-free and local recurrence-free survival rates were 75%, 82%, 58% and 90%, respectively. The positive vertical margin, submucosal invasion in the endoscopic submucosal dissection specimen and piecemeal resection were significantly associated with disease recurrence after salvage endoscopic submucosal dissection. CONCLUSIONS: Salvage endoscopic submucosal dissection is a feasible treatment for local failure after chemoradiotherapy for esophageal squamous cell carcinoma with acceptable long-term outcomes. However, for cases with positive vertical margins and submucosal invasion in the endoscopic submucosal dissection specimen, salvage endoscopic submucosal dissection outcomes were insufficient and additional treatment might be required.

N-(6-phenylpyridazin-3-yl)benzenesulfonamides as highly potent, brain-permeable, and orally active kynurenine monooxygenase inhibitors.

Huntington's disease (HD) is one of the serious neurodegenerative diseases and no disease modifiers are available to date. The correction of unbalanced kynurenine pathway metabolites may be useful to treat disease progression and kynurenine monooxygenase (KMO) is considered an ideal drug target. A couple of KMO inhibitors have been reported, but their brain permeability was very poor. We found pyridazinylsulfonamide as a novel lead compound, and it was optimized to the brain-permeable and highly potent KMO inhibitor 12, which was equipotent with CHDI-340246 and superior to CHDI-340246 in terms of brain penetration. Compound 12 was effective in R6/2 mice (HD model mice), i.e. neuroprotective kynurenic acid was increased, whereas neurotoxic 3-hydroxykynurenine was suppressed. In addition, impaired cognitive function was improved. Therefore, the brain-permeable KMO inhibitor was considered to be a disease modifier for HD treatment.

Preoperative indicators of misdiagnosis in invasion depth staging of esophageal cancer: Pitfalls of magnifying endoscopy with narrow-band imaging.

OBJECTIVES: The Japan Esophageal Society classification has been widely applied for predicting the invasion depth of superficial esophageal squamous cell carcinomas (SESCCs). Although Type B2 of the classification clinically corresponds to SESCCs with muscularis mucosa or slight submucosal invasion (MM/SM1), diagnostic yield based on Type B2 is insufficient. This study aimed to investigate risk factors for misdiagnosis in preoperative invasion depth staging. METHODS: We included a total of 104 SESCCs in which Type B2 was observed by magnifying endoscopy. SESCCs were classified as either correct diagnosis (pMM/SM1, 39 lesions), overdiagnosis (epithelium or the lamina propria [pEP/LPM], 34 lesions), or underdiagnosis (deep invasion into the submucosa [pSM2-3], 31 lesions) based on pathological depth of invasion. The association between misdiagnosis and endoscopic features, including distinct features, was evaluated using logistic regression analysis. Distinct features were defined as nodular protrusion, thickness, and/or clearly depressed area. The diameter of type B2 area was endoscopically measured, and the cut-off value was determined using a receiver operating characteristic curve. RESULTS: Type B2 area <6 mm (area under the curve, 0.776) and Type B2 vessels around erosion were significantly associated with overdiagnosis (odds ratio, 16.6 and 11.0, respectively), while distinct features were significantly associated with underdiagnosis (odds ratio, 8.7). Adjusted by these misdiagnosis factors, positive predictive value of Type B2 significantly improved from 38% to 65% (P < 0.01). CONCLUSIONS: Lesions with a small Type B2 area (<6 mm) and/or Type B2 vessels around erosion should be diagnosed as EP/LPM and lesions with distinct features as SM2-3.

Pretreatment predictive factors for feasibility of oral intake in adjuvant concurrent chemoradiotherapy for patients with locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Prophylactic percutaneous endoscopic gastrostomy (PEG) has been widely performed before concurrent chemoradiotherapy (CCRT) for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) because severe oral mucositis and dysphagia induced by CCRT lead to difficulty with oral intake. However, it is controversial whether all patients require prophylactic PEG for adjuvant CCRT. This study evaluated predictive factors for the feasibility of oral intake in adjuvant CCRT for patients with LASCCHN. METHODS: This study retrospectively analyzed 117 LASCCHN patients who underwent surgery followed by adjuvant CCRT with cisplatin at Shizuoka Cancer Center between April 2008 and December 2018. To investigate predictive factors for the feasibility of oral intake, tumor factors, treatment factors and social factors were included in multivariate analyses. RESULTS: Of the 117 patients, 25 received total laryngectomy and 92 received other surgery. In multivariate analysis, total laryngectomy [HR (hazard ratio) 0.09, P = 0.001] and oral cavity of primary tumor location (HR 0.21, P = 0.031) were significantly associated with the feasibility of oral intake. Difficulty obtaining adequate nutrition via oral intake from initiation of CCRT until 1 year after its completion was significantly rarer in the total laryngectomy group than in the other surgery group (16% vs. 57%, P < 0.001). CONCLUSION: Our study suggests that majority of patients who underwent total laryngectomy are able to maintain oral intake during adjuvant chemoradiotherapy.

Mathematical modeling of septic shock based on clinical data.

BACKGROUND: Mathematical models of diseases may provide a unified approach for establishing effective treatment strategies based on fundamental pathophysiology. However, models that are useful for clinical practice must overcome the massive complexity of human physiology and the diversity of patients' environmental conditions. With the aim of modeling a complex disease, we choose sepsis, which is highly complex, life-threatening systemic disease with high mortality. In particular, we focused on septic shock, a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality. Our model includes cardiovascular, immune, nervous system models and a pharmacological model as submodels and integrates them to create a sepsis model based on pathological facts. RESULTS: Model validation was done in two steps. First, we established a model for a standard patient in order to confirm the validity of our approach in general aspects. For this, we checked the correspondence between the severity of infection defined in terms of pathogen growth rate and the ease of recovery defined in terms of the intensity of treatment required for recovery. The simulations for a standard patient showed good correspondence. We then applied the same simulations to a patient with heart failure as an underlying disease. The model showed that spontaneous recovery would not occur without treatment, even for a very mild infection. This is consistent with clinical experience. We next validated the model using clinical data of three sepsis patients. The model parameters were tuned for these patients based on the model for the standard patient used in the first part of the validation. In these cases, the simulations agreed well with clinical data. In fact, only a handful parameters need to be tuned for the simulations to match with the data. CONCLUSIONS: We have constructed a model of septic shock and have shown that it can reproduce well the time courses of treatment and disease progression. Tuning of model parameters for each patient could be easily done. This study demonstrates the feasibility of disease models, suggesting the possibility of clinical use in the prediction of disease progression, decisions on the timing of drug dosages, and the estimation of time of infection.

[A case of liver Mycobacterium avium complex syndrome, diagnosed by liver biopsy].

A man in his 70s was referred to our hospital for evaluation of low-grade fever, weight loss, and liver dysfunction. Serological tests for viral hepatitis or autoimmune diseases were negative. No significant findings were observed on whole-body computed tomography (CT). Histopathologic examination of a liver biopsy sample revealed a non-caseating granuloma with acid-fast bacillus using the Ziehl-Neelsen stain. Serum Mycobacterium avium complex (MAC) antibody was positive. We started treatment for pulmonary MAC disease. His clinical condition and liver function improved within two months. He was diagnosed with liver MAC disease.

A mathematical model of type 1 diabetes involving leptin effects on glucose metabolism.

Leptin, a hormone released from fat cells in adipose tissues, was recently found to be capable of normalizing glucose metabolism in animals. Clinical data on patients with lipodystrophy indicates that leptin may have a positive effect on glucose metabolism in individuals with diabetes. There are growing expectations that leptin can improve the current insulin treatment for patients with type 1 diabetes. We investigated this possibility through in silico experiments based on a mathematical model of diabetes, which is currently the only mode of research that eliminates human risk. A model of the brain-centered glucoregulatory system, in which leptin plays a central role, was constructed and integrated within a conventional model of insulin/glucose dynamics. The model has been validated using experimental data from animal studies. The in silico combination experiments showed excellent therapeutic performance over insulin monotherapy.