Tumor location, clinicopathological features, and perioperative and prognostic outcomes in patients who underwent pancreatic resection following neoadjuvant chemoradiotherapy for resectable pancreatic cancer: A retrospective study.

BACKGROUND: /Objective: Preoperative treatment of resectable pancreatic ductal adenocarcinoma (PDAC) is gaining popularity worldwide. However, the characteristics of tumors located in the pancreatic head (Ph), or those in the body or tail (Pbt), after surgery following neoadjuvant chemoradiotherapy (NACRT) remain unclear. This study aimed to evaluate and compare the clinicopathological features, perioperative outcomes, and prognosis of patients with resectable PDAC who underwent NACRT followed by curative pancreatic resection, focusing on distinguishing between Ph and Pbt PDACs. METHODS: We included 107 patients with resectable PDAC who underwent curative resection following NACRT between 2009 and 2023. Clinicopathological features, perioperative and prognostic outcomes, recurrence patterns, and prognoses were compared between Ph and Pbt PDAC groups. RESULTS: Tumors were found in the Ph and Pbt in 64 and 43 patients, respectively. Albumin levels and lymphocyte-to-monocyte ratios after NACRT were significantly lower in the Ph group than in the Pbt group. The Pbt group showed significantly higher rates of positive peritoneal lavage cytology and serosal, arterial, and portal vein invasion than the Ph group did. Overall and recurrence-free survival were similar between the two groups. The most common site of initial postoperative recurrence was the lung only in both groups; however, the rate of peritoneal dissemination only was significantly higher in the Pbt group than in the Ph group. CONCLUSIONS: The prognoses based on tumor locations in the Ph and Pbt after surgery following NACRT are similar. Following the resection of resectable Pbt PDAC, the possibility of peritoneal dissemination recurrence should be considered.

Relationships between postoperative recurrences and standardized uptake value on 18F-fluorodeoxyglucose-positron emission tomography in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma who underwent curative pancreatic resection after neoadjuvant chemoradiotherapy.

BACKGROUND: This study aimed to examine postoperative recurrence after curative pancreatic resection following neoadjuvant chemoradiotherapy (NACRT) in patients with resectable (R-) and borderline resectable (BR-) pancreatic ductal adenocarcinoma (PDAC), focusing on its relationship with the standardized uptake value (SUV) on 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). METHOD: The postoperative initial recurrence patterns were examined in patients with R- and BR-PDAC who underwent NACRT followed by curative pancreatic resection. Data collected from three prospective clinical trials were retrospectively analysed. RESULTS: After a median follow-up of 29 months, 91 (60 %) of 151 patients experienced postoperative recurrence. The median recurrence-free survival (RFS) for all patients was 18 months. The sites of first recurrence were lung-only in 24 (26 %) patients, liver-only in 23 (25 %), local-only in 11 (12 %), peritoneum-only in 10 (11 %), other single site in 5 (5 %), and multiple sites in 19 (21 %) patients. Multivariate analysis identified the maximum standardized uptake value (SUVmax) on FDG-PET at diagnoses ≥5.40 (hazard ratio [HR], 1.62; 95 % confidence interval [CI], 1.01-2.61; p = 0.045) and node-positive pathology (HR, 2.01; 95 % CI, 1.32-3.08; p = 0.001) as significant predictors of RFS. Furthermore, the SUVmax at initial diagnosis and after NACRT correlated with liver metastasis. CONCLUSION: R- and BR-PDACs with high SUV on FDG-PET at diagnosis are risk factors for postoperative recurrence. Among patients who undergo surgery after NACRT, those with a high SUVmax at diagnosis or post-NACRT require careful attention for postoperative liver recurrence.

A Novel Fluorescence-Based Leak Test Method for Rectal Anastomoses Using Aerosolized Indocyanine Green.

BACKGROUND: The intraoperative air leak test is commonly performed during rectal surgery to evaluate anastomotic integrity. However, its drawbacks include occasional difficulties in visualizing the exact point of the leak while maintaining the pelvis under saline, the need for repeat testing to identify the leak point, and a lack of continuous visualization of the leak point. OBJECTIVE: To evaluate the feasibility and clinical applicability of using aerosolized indocyanine green, a fluorescent tracer, for detecting rectal anastomotic leakage. DESIGN: Animal preclinical study. SETTING: Animal laboratory at Kagawa University. PATIENTS: Six healthy adult female beagles were included. INTERVENTIONS: An anastomotic leakage model with a single air leak point was created in each dog. Indocyanine green was aerosolized using a nebulizer kit with a stream of carbon dioxide flowing at 1.5 to 2.0 L/min. The aerosol was administered into the rectum transanally, and laparoscopic observations were performed. MAIN OUTCOME MEASURES: Air leak points were observed using a near-infrared fluorescence laparoscope, after which the presence of corresponding indocyanine green fluorescence was verified. RESULTS: Aerosolized indocyanine green was visualized laparoscopically at all anastomosis sites but not elsewhere. The median time from the administration of the aerosol to its visualization was 4.5 seconds. Pathological examinations were performed 4 weeks postsurgery in all dogs, and no histological abnormalities related to aerosolized indocyanine green administration were observed at the anastomosis sites. LIMITATIONS: The leak points were surgically created and did not occur naturally. CONCLUSIONS: Visualization of air leaks at the sites of rectal anastomosis was laparoscopically achievable by administering aerosolized indocyanine green transanally into the rectum in our canine model. This novel fluorescent leak test could be a valid alternative to established methods.

Management of hepatocellular carcinoma, an important cause of death in Japanese autoimmune hepatitis patients.

BACKGROUND: Hepatocellular carcinoma (HCC) in autoimmune hepatitis (AIH) was considered rare but is increasing with prolonged prognosis. Its impact on the overall prognosis of AIH is unknown, and treatment has not been established. AIM: To investigate the risk factors and prognosis of HCC in patients with AIH and identify appropriate management strategies. METHODS: We studied patients with AIH including background liver disease, sex, age, complications, treatment, response to treatment, liver fibrosis, prognosis, and treatment. RESULTS: In 131 patients, deaths due to liver failure were more common early after the onset of AIH; however, deaths due to HCC increased gradually. HCC was observed in 12 patients (median age, 70 years; male/female, 4/8; cirrhosis at onset, 11; median time to carcinogenesis, 7 years). Cirrhosis at diagnosis was identified as a risk factor for carcinogenesis in the multivariate analysis (odds ratio, 41.36; p < 0.0001) and cumulative cancer rates were high. Multidisciplinary therapy other than immune checkpoint inhibitors was administered as treatment for HCC. Two of the three patients who used molecular-targeted drugs discontinued the treatment because of adverse events. CONCLUSION: HCC is an important cause of death in patients with AIH. Currently available drug therapies are limited and early detection is desirable. TRIAL REGISTRATION: This trial was retrospectively registered in the Ethics Committee of Kagawa University School of Medicine under the identifier 2019 - 238, registered on 4 Feb 2020.

Efficacy of endoscopic submucosal resection with a ligation device for small rectal neuroendocrine tumor: study protocol of a multicenter open-label randomized control trial (BANDIT trial).

BACKGROUND: Endoscopic resection is widely accepted as a local treatment for rectal neuroendocrine tumors sized ≤ 10 mm. However, there is no consensus on the best method for the endoscopic resection of rectal neuroendocrine tumors. As a simplified endoscopic procedure, endoscopic submucosal resection with a ligation device (ESMR-L) indicates a histologically complete resection rate comparable to that of endoscopic submucosal dissection (ESD). We hypothesized that ESMR-L than ESD would be preferred for rectal neuroendocrine tumors. Hence, this trial aimed to verify whether ESMR-L is non-inferior to ESD in terms of histologically complete resection rate. METHODS: This is a prospective, open-label, multicenter, non-inferiority, randomized controlled trial of two parallel groups, conducted at the Shizuoka Cancer Center and 31 other institutions in Japan. Patients with a lesion endoscopically diagnosed as a rectal neuroendocrine tumor ≤ 10 mm are eligible for inclusion. A total of 266 patients will be recruited and randomized to undergo either ESD or ESMR-L. The primary endpoint is the rate of en bloc resection with histologically tumor-free margins (R0 resection). Secondary endpoints include en bloc resection rate, procedure time, adverse events, hospitalization days, total devices and agents cost, adverse event rate between groups with and without resection site closure, outcomes between expert and non-expert endoscopists, and factors associated with R0 resection failure. The sample size is determined based on the assumption that the R0 resection rate will be 95.2% in the ESD group and 95.3% in the ESMR-L group, with a non-inferiority margin of 8%. With a one-sided significance level of 0.05 and a power of 80%, 226 participants are required. Assuming a dropout rate of 15%, 266 patients will be included in this study. DISCUSSION: This is the first multicenter randomized controlled trial comparing ESD and ESMR-L for the R0 resection of rectal neuroendocrine tumors ≤ 10 mm. This will provide valuable information for standardizing endoscopic resection methods for rectal neuroendocrine tumors. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs042210124. Registered on Jan 6, 2022.

Clinical outcomes of the over-the-scope clip closure after duodenal endoscopic submucosal dissection: A multicenter retrospective study.

BACKGROUND AND AIM: Prophylactic closure with the over-the-scope clip (OTSC) after endoscopic submucosal dissection (ESD) of superficial non-ampullary duodenal epithelial tumors (SNADETs) has been reported to reduce postoperative adverse events (AEs). However, there are few evidences regarding AEs-associated factors and long-term outcomes of OTSCs. METHODS: From January 2011 to December 2020, 139 consecutive patients with SNADETs who underwent ESD followed by OTSC closure in five institutions were extracted in this retrospective study. The primary endpoint was the rate of postoperative AEs after prophylactic OTSC closure. The secondary endpoints were the complete closure rate, residual rate, and long-term AEs associated with residual OTSCs. RESULTS: The rate of complete closure of the mucosal defect was 97.3% (142) in 146 SNADETs, which were completely resected by ESD. Postoperative AEs, including delayed bleeding, delayed perforation, and localized peritonitis, occurred in 6.2%, 3.4%, and 2.1% of patients, respectively; however, all of the cases improved without surgical treatment. In the multivariate logistic regression analysis, the use of two or more OTSCs was a significant independent risk factor for postoperative AEs (odds ratio, 2.94; 95% confidence interval, 1.02-8.46; P = 0.046). The residual OTSC rate was 46.4% at 1 year postoperatively, and long-term AEs included duodenal erosions and ulcers associated with residual OTSCs. CONCLUSIONS: Prophylactic closure with OTSCs after duodenal ESD can provide acceptable short-and long-term outcomes for preventing postoperative AEs. However, multiple OTSCs were the independent risk factors of postoperative AEs due to the gaps between and near the OTSCs.

A combined score for predicting clinically relevant postoperative pancreatic fistula based on inflammatory parameters and drainage fluid culture results on postoperative day 3.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatic resection can lead to severe postoperative complications. POPF is defined based on postoperative day (POD) 3 drainage fluid amylase level. POPF correlates with inflammatory parameters as well as drainage fluid bacterial infection. However, a standardized model based on these factors for predicting CR-POPF remains elusive. We aimed to identify inflammatory parameter- and drainage fluid culture-related risk factors for CR-POPF on POD 3 after pancreatoduodenectomy (PD) and distal pancreatectomy (DP). METHODS: Data from 351 patients who underwent PD or DP between 2013 and 2022 at a single institution were retrospectively analyzed. Risk factors for CR-POPF were investigated using multivariate analyses, and a prediction model combining the risk factors for CR-POPF was developed. RESULTS: Of the 351 patients, 254 and 97 underwent PD and DP, respectively. Multivariate analyses revealed that drainage fluid amylase level ≥722 IU/L, culture positivity, as well as neutrophil count ≥5473/mm3 on POD 3 were independent risk factors for CR-POPF in PD group. Similarly, drainage fluid, amylase level ≥500 IU/L, and culture positivity on POD 3 as well as pancreatic thickness ≥11.1 mm were independent risk factors in the DP group. The model for predicting CR-POPF achieved the maximum overall accuracy rate when the number of risk factors was ≥2 in both the PD and DP groups. CONCLUSIONS: Inflammatory parameters on POD 3 significantly influence the risk of CR-POPF onset after pancreatectomy. The combined models based on these values can accurately predict the risk of CR-POPF after pancreatectomy.

Transperineal minimally invasive surgery during laparoscopic abdominoperineal resection for low rectal cancer could improve short-term outcomes: A single-institution retrospective cohort study.

PURPOSE: Transperineal minimally invasive surgery (TpMIS) during laparoscopic abdominoperineal resection (APR) is an emerging approach that allows for the precise treatment of lower rectal cancer. However, evidence regarding the efficacy of TpMIS is insufficient. This study evaluated the efficacy of TpMIS during laparoscopic APR for patients with lower rectal cancer. METHODS: Patients who underwent laparoscopic APR with TpMIS (TpMIS group; n = 12) and those who underwent conventional laparoscopic APR for low rectal cancer (conventional group; n = 13) were enrolled consecutively in this retrospective study. Standardized TpMIS was performed at our institution. Patient and tumor characteristics and intraoperative, postoperative, and pathological outcomes were compared between groups. The primary outcome was postoperative perineal wound infection. RESULTS: No patients in the TpMIS group experienced postoperative perineal wound infection; however, five (38.5%) patients in the conventional group experienced postoperative perineal wound infection (significant difference; p = 0.016). The estimated blood loss (median, 81 mL vs. 463 mL) and incidence of postoperative urinary dysfunction (8.3% vs. 46.1%) were significantly lower in the TpMIS group than in the conventional group. The postoperative hospital stay (median, 13 vs. 20 days) of the TpMIS group was significantly shorter than that of the conventional group. Pathological outcomes did not differ between groups. The positive circumferential resection margin rates of the TpMIS and conventional groups were 8.3% and 15.4%, respectively. CONCLUSION: TpMIS during laparoscopic APR was associated with significant improvements in the postoperative outcomes of patients with low rectal cancer.

Novel endoscopic duodenal observation protocol based on Seven Pictures Rule for detecting duodenal neoplasms during esophagogastroduodenoscopy: Prospective observational study.

OBJECTIVES: No protocol for esophagogastroduodenoscopic examination of the duodenum has been established. We examined the feasibility and ability to detect neoplasms of a novel duodenal examination protocol. METHODS: This was a two-facility, prospective, observational study. Our protocol, the Seven Pictures Rule (7PR), requires pictures of the following seven locations: anterior and posterior to the bulb, area of and contralateral to the superior duodenal angle, area of and contralateral to the ampulla, and the transverse duodenum. The primary outcome was rate of completion of 7PR. Secondary outcomes were overall rates of detecting neoplasms, rates of detecting neoplasms for each location, examination time, and completion rates for standard or ultrathin endoscopes. RESULTS: There were 1549 participants. The 7PR completion rate was 81.1% and the detection rates of overall neoplasms, adenomas, and carcinomas were 0.84%, 0.71%, and 0.06%, respectively. The area in which most neoplasms was detected was contralateral to the ampulla (69.2%), and the fewest the transverse duodenum (0%). Mean duration of duodenal examination was 53.1 s. Completion rates for standard vs. ultrathin were 84.4% (1077/1276) vs. 65.6% (179/273) (P < 0.01), respectively. CONCLUSIONS: Seven Pictures Rule is acceptable for duodenal examination and a potential quality indicator.

Tumor-to-blood pool ratio of 18F-fluorodeoxyglucose-positron emission tomography's standardized uptake value as a useful parameter indicating malignant transformation in pancreatic branch-duct intraductal papillary mucinous neoplasm compared to the international Fukuoka guidelines: a retrospective cohort study from surgical resections.

BACKGROUND: Identifying malignant transformation in pancreatic branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) remains challenging, but the standardized uptake value (SUV) obtained from 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT has the potential to become a valuable parameter for differentiation. This study aimed to assess the effectiveness of SUV of FDG-PET/CT in distinguishing low-grade dysplasia (LGD), high-grade dysplasia (HGD), and intraductal papillary mucinous carcinoma (IPMC) within BD-IPMNs. METHODS: We assessed 58 patients with confirmed BD-IPMN undergoing surgery between 2008 and 2022. Receiver operating characteristic curves were plotted using the tumor-to-blood pool ratio (TBR) of FDG-PET/CT in two scenarios: one considering HGD + IPMC as positive and the other considering only IPMC as positive. RESULTS: In the cohort of 58 cases, there were 39 females, and the median age was 71 years. The median TBR value was 1.45 (range, 0.35-25.44). The TBRs exhibited a significant correlation with each histopathology (p < 0.001). Furthermore, in the multivariate analysis, TBR was independently significant in both scenarios, with HGD + IPMC defined as malignant (p = 0.001) and with only IPMC defined as malignant (p = 0.024). CONCLUSIONS: TBR might have the potential to serve as a valuable parameter for indicating malignant transformation in pancreatic BD-IPMNs.

Validation of fatty liver index as a predictor of hepatic steatosis in Asian populations: Impact of alcohol consumption and sex.

AIM: This study was undertaken to investigate the utility of the fatty liver index (FLI) as a noninvasive tool for predicting hepatic steatosis based on alcohol consumption and sex in a large Asian population. METHODS: We carried out a single-center observational cohort study at the HITO Medical Center in Japan and enrolled 1976 Asian subjects. The subjects were categorized into nondrinkers and light drinkers (0-19 g/day) and moderate drinkers (20-59 g/day) based on their self-reported alcohol intake. We used physical examinations, laboratory tests, and a questionnaire to collect information on various factors related to the FLI, including body mass index, waist circumference, and levels of γ-glutamyl transferase and triglycerides. RESULTS: The diagnostic accuracy of the FLI was assessed by calculating the area under the receiver operating characteristic curve (AUROC), and optimal cut-off values were determined using Youden's index. The FLI had an acceptable performance index of >0.7 both overall and in all subgroups, with an overall AUROC of 0.844. The AUROCs were higher in women and moderate drinkers of both sexes. We also compared the cut-off values obtained in the present study with the previously reported values of 30 and 60. Optimal cut-off values for the FLI were calculated for the total population and subgroups and were found to differ from the previously established values in other countries. CONCLUSIONS: Our study suggests that the FLI is a useful noninvasive marker for predicting hepatic steatosis in a large Asian population, irrespective of alcohol consumption and sex.

Current Status of Endoscopic Full-Thickness Resection for Gastric Subepithelial Tumors: A Literature Review Over Two Decades.

BACKGROUND: With the development of endoscopic technology and devices, endoscopic full-thickness resection (EFTR) has been challengingly introduced for gastric subepithelial tumors (SETs). The resection and closure strategies are under investigation. This systematic review was performed to assess the current status and limitations of EFTR for gastric SETs. SUMMARY: MEDLINE was searched using the keywords "endoscopic full-thickness resection" or "gastric endoscopic full-thickness closure" AND "gastric" or "stomach" from January 2001 to July 2022. The outcome variables were the complete resection rate, major adverse event (AE) rate including delayed bleeding and delayed perforation, and closure-associated outcomes. Among 288 studies, 27 eligible studies involving 1,234 patients were included in this review. The complete resection rate was 99.7% (1,231/1,234). The major AE rate was 1.13% (14/1,234), with delayed bleeding in two (0.16%) patients, delayed perforation in one (0.08%), panperitonitis or abdominal abscess in three (0.24%), and other AEs in eight (0.64%). Surgical interventions were required intraoperatively or postoperatively in 7 patients (0.56%). Three patients underwent intraoperative conversion to surgery, due to intraoperative massive bleeding, technical difficulty of closure, and retrieval of falling tumor in the peritoneal cavity. Postoperative surgical rescues for AEs were required in four (0.32%). Subgroup analysis of AE outcomes showed no significant differences among closure techniques consisting of endoclips, purse-string suturing, and over-the-scope clips. KEY MESSAGES: This systematic review demonstrated acceptable outcomes of EFTR and closure for gastric SETs, indicating that EFTR is a promising forthcoming procedure.

Endoscopic Ligation with O-Ring Closure for Mucosal Defects after Rectal Endoscopic Submucosal Dissection: A Feasibility Study (with Video).

INTRODUCTION: Mucosal defect closure after colorectal endoscopic submucosal dissection (ESD) may prevent post-ESD adverse events. Delayed bleeding is a particular concern in the rectum due to the presence of numerous blood vessels. However, rectal defect closure often fails due to the thick rectal wall. This study aimed to examine the feasibility of our newly developed endoscopic ligation with O-ring closure (E-LOC) for defects after rectal ESD. METHODS: This was a prospective observational study conducted at a single institution. After excluding 2 patients with tumors mostly extending into the anal canal, the study cohort comprised 30 consecutive patients who underwent ESD of rectal neoplasms between July 2020 and July 2021. E-LOC using an endoscopic variceal ligation device was performed for closing mucosal defects after rectal ESD. The primary outcome was the complete closure rate. The secondary outcomes were the delayed bleeding rate, E-LOC procedure time, sustained closure rates on postoperative day (POD) 3, and E-LOC-associated complications. RESULTS: Complete closure of the defect (median defect size 29.0 mm) was successfully achieved in 24 cases (80%). Delayed bleeding occurred in one case with incomplete closure (3.3%). The median E-LOC procedure time was 25.5 min (interquartile range, 20.0-30.0 min). The sustained closure rates were 83.3% (20/24) on POD 3 in the 24 cases with complete closure. No E-LOC-associated complications occurred. DISCUSSION/CONCLUSIONS: E-LOC was feasible for defect closure after rectal ESD, and probably led to a decreased incidence of delayed bleeding.

Comparison of purse-string suture versus over-the-scope clip for gastric endoscopic full-thickness closure: traction and leak pressure testing in ex vivo porcine model.

BACKGROUND: The recently developed endoscopic full-thickness resection technique requires reliable closure. The main closure methods are the purse-string suture (PSS) technique and over-the-scope clip (OTSC) technique; however, basic data on the closure strength of each technique are lacking. This study was performed to compare the closure strengths of these two methods in an ex vivo porcine model. METHODS: In the traction test, a virtual 5-cm full-thickness closure line was closed by the following six methods three times each: conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture. The primary endpoint was the tension at the starting point of dehiscence, measured in Newtons (N) by an automatic traction machine. In the leak test, a 15-mm gastric full-thickness defect was closed by PSS or OTSC six times each, and the closed stomach was then pressurized in a water container. The primary endpoint was the leak pressure when air bubbles appeared. The secondary endpoints were the procedure time and presence of complete inverted closure. RESULTS: The mean tension was 2.16, 3.68, 5.15, 18.30, 19.30, and 62.40 N for conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture, respectively. Complete inverted closure was observed for seromuscular PSS, seromuscular OTSC, and surgical suture. The mean leak pressure was 13.7 and 24.8 mmHg in the PSS and OTSC group, respectively (P < 0.01). The mean procedure time was 541 and 169 s in the PSS and OTSC group, respectively (P < 0.01). Complete inverted closure was observed in OTSC alone. CONCLUSION: The OTSC, which allows complete inverted closure, showed greater closure strength than PSS. Considering the size limitation suitable for single OTSC, a therapeutic strategy for closing the larger size is further warranted.

Clinical and technical outcomes of endoscopic closure of postendoscopic submucosal dissection defects: Literature review over one decade.

Endoscopic submucosal dissection (ESD), which enables curative en bloc resection of early gastrointestinal neoplasms, has been an attractive minimally invasive surgery during the past two decades. Large post-ESD defects must be carefully managed to prevent adverse events (AEs). The major AEs comprise delayed bleeding (DB) and delayed perforation (DP), and overall AEs comprise DB plus DP. This review aimed to clarify the clinical efficacy and technical outcomes of endoscopic prophylactic closure for post-ESD defects. We identified studies involving ≥10 patients up to March 2022 in which endoscopic closure was applied for gastric, duodenal, and colorectal post-ESD defects. In the stomach, total rates of overall AEs and DB were significantly lower in the closure than non-closure group. In the duodenum, total rates of overall AEs, DB, and DP were significantly lower in the closure group. In the colorectum, total rates of overall AEs and DB were significantly lower in the closure group. Closure techniques, categorized into three groups (clip-based techniques, mechanical clipping, and surgical stitch-based techniques), were illustrated. Endoscopic closure demonstrated a certain ability to reduce DB after gastric, duodenal, and colorectal ESD as well as DP after duodenal ESD. Considering closure-associated costs, the indications and limitations of closure techniques should be further investigated.

Endoscopic resection for gastric submucosal tumors: Japanese multicenter retrospective study.

OBJECTIVES: Limited information is available on the efficacy and safety of endoscopic resection (ER) of gastric submucosal tumors (SMTs) in Japanese endoscopic practice where ER for gastric tumors is extremely popular. METHODS: We conducted this study to elucidate the current scenario of ER for gastric SMTs in Japanese endoscopic practice. Patients (from 12 institutions) with gastric SMTs who underwent ER were enrolled from the first case until August 2020. RESULTS: We enrolled 117 patients with 118 lesions. The number of patients who underwent ER increased over the years. The mean endoscopic tumor size was 20 ± 7.2 (8-40) mm. The growth type was primarily intraluminal (90%). The mean resection and wound closure times were 58 ± 38 (range, 12-254) min and 31 ± 41 (range, 3-330) min, respectively. Complete ER was achieved for 117 (99%) lesions. Full-thickness resection rate was 44%; however, only 12 (10%) patients required abdominal paracentesis for decompression. Endoscopic treatments were completed in 115 (97%) lesions, while three lesions required conversions to laparoscopic surgery due to luminal collapse, uncontrolled bleeding, and difficulty in defect closure. Gastrointestinal stromal tumors were the most common pathology (74%). No recurrence was observed during the mean follow-up period of 4.3 ± 2.9 years. The 5-year overall survival rate was 98.9% (95% confidence interval 97.8-100%). CONCLUSION: Performance of ER for gastric SMTs is increasing in Japan. The technique seems feasible in Japanese endoscopic practice, warranting further validation in a prospective study.

MicroRNAs and Nonalcoholic Steatohepatitis: A Review.

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathologic syndrome caused by fat deposition in hepatocytes. Patients with nonalcoholic steatohepatitis (NASH), an advanced form of NAFLD with severe fibrosis, are at high risk for liver-related complications, including hepatocellular carcinoma (HCC). However, the mechanism of progression from simple fat deposition to NASH is complex, and previous reports have linked NAFLD to gut microbiota, bile acids, immunity, adipokines, oxidative stress, and genetic or epigenetic factors. NASH-related liver injury involves multiple cell types, and intercellular signaling is thought to be mediated by extracellular vesicles. MicroRNAs (miRNAs) are short, noncoding RNAs that play important roles as post-transcriptional regulators of gene expression and have been implicated in the pathogenesis of various diseases. Recently, many reports have implicated microRNAs in the pathogenesis of NALFD/NASH, suggesting that exosomal miRNAs are potential non-invasive and sensitive biomarkers and that the microRNAs involved in the mechanism of the progression of NASH may be potential therapeutic target molecules. We are interested in which miRNAs are involved in the pathogenesis of NASH and which are potential target molecules for therapy. We summarize targeted miRNAs associated with the etiology and progression of NASH and discuss each miRNA in terms of its pathophysiology, potential therapeutic applications, and efficacy as a NASH biomarker.

Efficacy of neoadjuvant chemoradiotherapy followed by pancreatic resection for older patients with resectable and borderline resectable pancreatic ductal adenocarcinoma.

BACKGROUND: The benefit of preoperative treatment followed by pancreatic resection in older patients with pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this retrospective analysis of prospectively collected data, we evaluated the significance and safety of preoperative treatment followed by curative resection for older PDAC patients. METHODS: We evaluated 122 patients with resectable and borderline resectable PDAC who received neoadjuvant chemoradiotherapy (NACRT) followed by curative resection between 2009 and 2019. Changes in the prognostic nutritional indices during NACRT, surgical outcomes, and prognosis were compared between older (≥75 years, n = 44) and younger patients (<75 years, n = 78). RESULTS: The completion rate, adverse event rate, changes in prognostic nutritional indices during NACRT, and prognosis were similar between the groups. In multivariate analysis, an elevated C-reactive protein/albumin ratio (CRP/Alb) ≥ 33.1% during NACRT (p = 0.035) and no postoperative adjuvant chemotherapy (p = 0.041) were identified as significant predictors of overall survival. CONCLUSIONS: NACRT followed by pancreatic resection could be safely performed in older patients, with a similar prognosis as that of younger patients, despite an increased frequency of postoperative complications. Elevated CRP/Alb during NACRT and no postoperative adjuvant chemotherapy were poor prognostic factors for older patients.

Efficacy of endoscopic ligation with O-ring closure for prevention of bleeding after gastric endoscopic submucosal dissection under antithrombotic therapy: a prospective observational study.

BACKGROUND: We examined the efficacy of a novel endoscopic ligation technique with O-ring closure (E-LOC) to prevent bleeding after gastric endoscopic submucosal dissection (ESD) under antithrombotic therapy. METHODS: This single-center prospective study involved consecutive patients who were taking antithrombotic agents and underwent gastric ESD. E-LOC was performed by anchoring the nylon loop with hemoclips on both defect edges and/or the exposed muscle layer, and using O-ring band ligation around these deployed clips. The primary outcome was post-ESD bleeding rate. Secondary outcomes were complete closure rate, procedure time, sustained closure rate, and complications. RESULTS: 48 patients were finally analyzed. The post-ESD bleeding rate was 0 %, the complete closure rate was 97.9 %, and the mean closure time was 29.9 minutes. The sustained closure rate was 95.8 % at postoperative day 2-3 and 33.3 % at postoperative day 10-11. No complications occurred. CONCLUSION: E-LOC may be an effective option for closing mucosal defects after gastric ESD under antithrombotic therapy. However, the preventive effect on post-ESD bleeding should be further investigated in high risk groups.

Effectiveness of second-look endoscopy after gastric endoscopic submucosal dissection in patients taking antithrombotic agents: a multicenter propensity score matching analysis.

BACKGROUND: The risk of bleeding after gastric endoscopic submucosal dissection (ESD) in antithrombotic agent users has increased, and its management remains a problem. Second-look endoscopy (SLE) following gastric ESD in antithrombotic agent users may be effective in preventing delayed bleeding, but this requires elucidation. Therefore, this study aimed to investigate the efficacy of SLE in reducing bleeding after gastric ESD in patients receiving antithrombotic agents. METHODS: This retrospective cohort study was conducted at 19 referral hospitals in Japan. A total of 1,245 patients who were receiving antithrombotic agents underwent gastric ESD between January 2013 and July 2018. The incidence of delayed bleeding was compared between SLE and non-SLE groups using propensity score matching analysis. RESULTS: Overall, 858 patients (SLE group, 657 patients; non-SLE group, 201 patients) were analyzed. After matching, 198 pairs were created. Delayed bleeding occurred in 10 patients (5.1%) in the SLE group and 16 patients (8.1%) in the non-SLE group [odds ratio (OR) 0.605, 95% confidence interval (CI) 0.23-1.46, p = 0.310]. In the subgroup analysis, SLE reduced the incidence of delayed bleeding in patients receiving heparin bridging therapy (6.3% and 40.0%, respectively; p = 0.004). In the SLE group, prophylactic coagulation did not significantly reduce delayed bleeding compared to the no treatment group (14.6% and 8.6%, respectively; p = 0.140). CONCLUSIONS: SLE was ineffective in reducing bleeding after gastric ESD in antithrombotic agent users, overall. A prospective comparative study is warranted to definitively evaluate the effectiveness of SLE in reducing bleeding in high-risk patients.