Evaluation of the Validity of Endoscopic Transpapillary Gallbladder Drainage for Acute Cholecystitis Based on the Tokyo Guidelines 2018.

GOALS: We evaluated the validity of endoscopic transpapillary gallbladder drainage (ETGBD) as a bridging therapy prior to elective Lap-C for the patients with acute cholecystitis (AC). BACKGROUND: The Tokyo Guidelines 2018 recommend early laparoscopic cholecystectomy (Lap-C) for patients with AC, however, some patients require the preoperative drainage because of inadequate for early Lap-C du to background and comorbidities. STUDY: We performed a retrospective cohort analysis using data from our hospital records from 2018-2021. In total, 71 cases of 61 patients with AC underwent ETGBD. RESULTS: The technical success rate was 85.9%. Patients in the failure group had more complicated branching of the cystic duct. The length of time until feeding was started and until WBC levels normalized, and the length of hospital stay were significantly shorter in the success group. The median waiting period for surgery was 39 days in the ETGBD success cases. The median operating time, amount of bleeding, and length of postoperative hospital stay were 134 min, 83.2g, and 4 days, respectively. In patients who underwent Lap-C, the waiting period for surgery and the operating time were similar between the ETGBD success and failure groups. However, the temporary discharge period after drainage and the length of postoperative hospital stay were significantly longer in the patients with ETGBD failure. CONCLUSIONS: Our study revealed that ETGBD has equivalent efficacy prior to elective Lap-C despite some challenges that lower its success rate. Preoperativ ETGBD can improve patient quality of life by eliminating the need for a drainage tube.

Natural History of Small Gastric Subepithelial Lesions Less than 20 mm: A Multicenter Retrospective Observational Study (NUTSHELL20 Study).

BACKGROUND AND AIM: Small gastric subepithelial lesions (SELs) are sometimes encountered in daily esophagogastroduodenoscopy (EGD) practice, but whether once-annual or twice-annual endoscopy can provide sufficient follow-up remains unclear. Because follow-up based on small-SEL characteristics is important, this study clarified the natural history of gastric SELs less than 20 mm. METHODS: This retrospective multicenter observation study conducted at 24 Japanese hospitals during April 2000 to March 2020 examined small gastric SELs of ≤20 mm diameter. The primary outcome was the rate of size increase of those SELs detected using EGD, with growth times assessed irrespective of SEL pathological diagnoses. RESULTS: We examined 824 cases with tumors of 1-5 mm diameter in 298 (36.2%) cases, 6-10 mm in 344 (41.7%) cases, 11-15 mm in 112 (13.6%) cases, and 16-20 mm in 70 (8.50%) cases. An increase of small gastric SELs was observed in 70/824 patients (8.5%). The SELs larger than 6 mm increased, even after 10 years. No-change and increasing groups had no significantly different malignant findings at diagnosis. In cases of gastrointestinal stromal tumors (GISTs), internal cystic change in endoscopic ultrasound (EUS) is a risk factor for an increased tumor size. The predictive tumor growth cutoff size at initial diagnosis was 13.5 mm. CONCLUSIONS: Small gastric SELs less than 20 mm have an approximately 8.5% chance of increase. Predictive markers for GIST growth are tumor size ≥13.5 mm and internal cystic change in EUS.

Clinical effectiveness of the pocket-creation method for colorectal endoscopic submucosal dissection.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is a technically advanced procedure for colorectal tumors. Hayashi et al. invented the "pocket-creation method (PCM)," and reported that Is-type lesions with fibrosis could be efficaciously and safely resected. However, only case studies have been published, and there are no previous reports on the usefulness of PCM in colorectal ESD for all lesions, as compared with the conventional method. This study aimed to evaluate the effectiveness and safety of PCM in colorectal ESD. PATIENTS AND METHODS: Ninety-six colorectal tumors were treated: 47 using the PCM and the other 49, considered the control group, using the conventional method. Therapeutic effectiveness and safety were retrospectively assessed. RESULTS: The comparison between the PCM and control groups revealed higher rates of en bloc resection (100 % vs. 88 %, P  = 0.015) and curative endoscopic resection (100 % vs. 84 %, P  = 0.0030) with PCM. There was no significant difference in perforation as an adverse event (AE) between the two groups, though perforation was observed in only 6 % of the control group and none of the PCM group. Compared with the control group, the PCM group had lower incidences of perforation and post-ESD coagulation syndrome, and both AEs were associated with excessive thermal denaturation of the muscle layer (2 % vs. 16 %, P  = 0.018). CONCLUSIONS: This study demonstrated the effectiveness and safety of ESD with PCM for colorectal tumors. Although there is a possible learning curve, PCM enables the endoscopist to safely perform ESD in most cases without encountering the difficulties associated with conventional ESD.

Clinical importance of colonoscopy in patients with gastric neoplasm undergoing endoscopic submucosal dissection.

AIM: To evaluate the usefulness of total colonoscopy (TCS) for patients undergoing gastric endoscopic submucosal dissection (ESD) and to assess risk factors for colorectal neoplasms. METHODS: Of the 263 patients who underwent ESD at our department between May 2010 and December 2013, 172 patients undergoing TCS during a one-year period before and after ESD were targeted. After excluding patients with a history of surgery or endoscopic therapy for colorectal neoplasms, 158 patients were analyzed. Of the 868 asymptomatic patients who underwent TCS during the same period because of positive fecal immunochemical test (FIT) results, 158 patients with no history of either surgery or endoscopic therapy for colorectal neoplasms who were matched for age and sex served as the control group for comparison. RESULTS: TCS revealed adenoma less than 10 mm in 53 patients (33.6%), advanced adenoma in 17 (10.8%), early colorectal cancer in 5 (3.2%), and advanced colorectal cancer in 4 (2.5%). When the presence or absence of adenoma less than 10 mm, advanced adenoma, and colorectal cancer and the number of adenomas were compared between patients undergoing ESD and FIT-positive patients, there were no statistically significant differences in any of the parameters assessed. The patients undergoing ESD appeared to have the same risk of colorectal neoplasms as the FIT-positive patients. Colorectal neoplasms were clearly more common in men than in women (P = 0.031). Advanced adenoma and cancer were significantly more frequent in patients with at least two of the following conditions: hypertension, dyslipidemia, and diabetes mellitus (P = 0.019). CONCLUSION: In patients undergoing gastric ESD, TCS appears to be important for detecting synchronous double neoplasms. Advanced adenoma and cancer were more common in patients with at least two of the following conditions: hypertension, dyslipidemia, and diabetes mellitus. Caution is therefore especially warranted in patients with these risk factors.

Ulcerative Colitis-associated Cancer/Dysplasia Detected Using Surveillance Colonoscopy Performed in the Clinical Remission Phase: A Report of Five Cases.

We herein report five cases of ulcerative colitis-associated cancer/dysplasia. Although clinical remission had been achieved in all patients, mucosal inflammation had been resolved in only one patient. Thus, in order to prevent cancer from developing, appropriate medical therapy aiming not only to relieve the clinical symptoms, but also to suppress chronic inflammation appears to be necessary. Moreover, cancer occurred as early as 4 years after the diagnosis in one patient. In patients without complete resolution of mucosal inflammation, careful surveillance colonoscopy should be initiated in the early phase.

Comparison of the usefulness of endoscopic papillary large-balloon dilation with endoscopic sphincterotomy for large and multiple common bile duct stones.

BACKGROUND: Endoscopic sphincterotomy (EST) is currently recognized as the primary endoscopic treatment for common bile duct stones. However, it is difficult to remove multiple (≥ 3) or large (≥ 15 mm) common bile duct stones with EST alone. Recently, EST plus endoscopic papillary large-balloon dilation (EPLBD) was reported to be an effective treatment for such bile duct stones. We compared the results of EST and EST + EPLBD for multiple (≥ 3) or large (≥ 15 mm) stones that were difficult to treat using EST alone. We also compared the complication rates between the techniques. METHODS: Seventy patients with large (largest diameter, ≥ 15 mm) or ≥ 3 common bile duct stones treated in our department between April 2010 and March 2013 underwent EST + EPLBD (n = 34) or EST alone (n = 36). We compared final successful stone removal rates, rates of successful stone removal in the first session, procedure times, status of concurrent mechanical lithotripsy (ML), and complications between the EST + EPLBD and EST groups. RESULTS: The rates of final successful stone removal were similar between the two groups (EST + EPLBD: 100 % vs. EST: 89 %; p = 0.115). The rate of successful stone removal in the first session was significantly higher in the EST + EPLBD group (EST + EPLBD: 88 % vs. EST: 56 %; p = 0.03). Moreover, the procedure time was significantly shorter (EST + EPLBD: 42 min vs. EST: 67 min; p = 0.011) and the rate of ML use was significantly lower in the EST + EPLBD group (EST + EPLBD: 50 % vs. EST: 94 %; p < 0.001). Complications like pancreatitis and bleeding occurred in three patients in the EST + EPLBD group and in 10 patients in the EST group, but the differences were not statistically significant (EST + EPLBD: 9 % vs. EST: 25 %; p = 0.112). CONCLUSIONS: Our results suggest that EST + EPLBD is an effective therapy for patients with difficult-to-treat multiple or large common bile duct stones, because it requires fewer sessions and shorter operative times than EST alone.

Relationship between the degree of endoscopic atrophy of the gastric mucosa and carcinogenic risk.

BACKGROUND: The relationship between Helicobacter pylori infection and gastric cancer has been demonstrated, and the risk of gastric cancer occurrence is known to increase with the progression of atrophic changes associated with chronic gastritis. Endoscopic evaluation of the degree and extent of atrophy of the gastric mucosa is a simple and very important means of identifying a group at high risk for gastric cancer. This study aimed to clarify the carcinogenic risk in relation to the degree of atrophy. METHODS: A total of 27,777 patients (272 with early gastric cancer and 135 with advanced gastric cancer) were included in this study. Endoscopically evaluated atrophy of the gastric mucosa was classified as C-0 to O-3 according to the Kimura and Takemoto classification system. RESULTS: The cancer detection rate in relation to the degree of gastric mucosal atrophy was 0.04% (2/4,183 patients) for C-0, 0% (0/4,506) for C-1, 0.25% (9/3,660) for C-2, 0.71% (21/2,960) for C-3, 1.32% (75/5,684) for O-1, 3.70% (140/3,780) for O-2 and 5.33% (160/3,004) for O-3. As to the proportions of differentiated and undifferentiated cancers, the latter were relatively frequent in the C-0 to C-2 groups, but differentiated cancers became predominant as atrophy progressed. On the other hand, the number of both differentiated and undifferentiated cancers detected increased as gastric mucosal atrophy progressed. In addition, open-type atrophy was found in 29 (96.7%) of 30 patients with synchronous multiple gastric cancers and in all 20 patients with metachronous multiple gastric cancers. CONCLUSION: Endoscopic evaluation of gastric mucosal atrophy can provide a simple and reliable predictive index for both current and future carcinogenic risk.

A second-look endoscopy may not reduce the bleeding after endoscopic submucosal dissection for gastric epithelial neoplasm.

BACKGROUND: Gastric endoscopic submucosal dissection (ESD) has gradually come to be recommended as the optimal treatment for early gastric cancer; however, one of the primary issues is postoperative bleeding. Although second-look endoscopy is conventionally performed to reduce the risk of postoperative bleeding, its benefit has not yet been clearly elucidated. The objective of this study was to elucidate the benefit of second-look endoscopy. METHODS: A total of 459 lesions in patients were underwent gastric ESD from May 2004 to April 2013 at our hospital were included in the analysis. The patients were divided into those who had bleeding within 24 hours after ESD (immediate bleeding) and those in whom bleeding occurred 24 hours or more after the procedure (delayed bleeding); the underlying disease, age, lesion site, diameter of the resected specimen, and lesion diameter were analyzed to identify the risk factors for postoperative bleeding after ESD. RESULTS: Post-ESD immediate or delayed bleeding occurred in 23 of the 459 cases (5.0%). Second-look endoscopy was performed in 210 of 447 cases (47.0%) excluding 12 cases with immediate bleeding; in the remaining 237 of the 447 cases (53.0%), it was not performed. Post-ESD delayed bleeding occurred in 6 of the 210 cases (2.9%) and 5 of the 237 cases (2.1%), with no statistically significant difference between the two groups. Overall, the following factors were identified as the risk factors for postoperative bleeding: young age (P = 0.005), lesions in the L segment (P = 0.042), and large size of the resected specimen (P = 0.005). The risk factors identified in the immediate bleeding group were lesions in the L segment (P = 0.032), large size of the resected specimen (P < 0.001), and large tumor size (P = 0.011), and those in the delayed bleeding group were young age (P = 0.013) and concomitant renal disease (P = 0.011). CONCLUSIONS: The results of this study suggest that second-look endoscopy after gastric ESD may not be useful for preventing postoperative bleeding.

Frequency of nonsteroidal anti-inflammatory drug-associated ulcers.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for treatment of orthopedic diseases, inflammatory diseases, etc., and low-dose aspirin is a common antiplatelet therapy given mainly for secondary prevention of atherothrombosis (e.g., myocardial infarction and cerebral infarction). As to the history of NSAID-induced gastric mucosal injury in Japan, the first case of an aspirin-induced gastric ulcer was reported as early as 1934. Based on a meta-analysis of risk factors for peptic ulcers, Helicobacter pylori infection and NSAIDs are the main etiologies of peptic ulcers. NSAIDs alone increase the odds ratio for ulcer development to 19.4 and that for ulcer bleeding to 4.85. In fact, the Japan Rheumatism Foundation reported in 1991 that active gastric ulcers and active duodenal ulcers were detected in 15.5 and 1.9 % of 1008 patients, respectively, taking oral NSAIDs for 3 months or longer. In Japan, which is becoming an increasingly aged society, the numbers of patients taking NSAIDs and low-dose aspirin are expected to increase dramatically in the future. It is hoped that accumulation of evidence on gastrointestinal risk will allow many patients to rationally avoid gastrointestinal complications while receiving the benefits of NSAIDs and low-dose aspirin.

Matched case-control study comparing endoscopic submucosal dissection and endoscopic mucosal resection for colorectal tumors.

BACKGROUND AND AIM: For large colorectal tumors, the en bloc resection rate achieved by endoscopic mucosal resection (EMR) is insufficient, and this leads to a high rate of local recurrence. As endoscopic submucosal dissection (ESD) has been reported to achieve a higher rate of en bloc resection and a lower rate of local recurrence in the short-term, it is expected to overcome the limitations of EMR. We conducted a matched case-control study between ESD and EMR to clarify the effectiveness of ESD for colorectal tumors. METHODS: Between April 2005 and February 2009, a total of 28 colorectal tumors in 28 patients were resected by ESD and were followed up by colonoscopy at least once. As a control group, 56 EMR cases from our prospectively completed database were matched. En bloc resection, complication and recurrence rates were compared between the two groups. RESULTS: The mean sizes of the lesions were 27.1 mm in the ESD group and 25.0 mm in the EMR group. The en bloc resection rate was significantly higher in the ESD group (92.9% vs 37.5% with ESD vs EMR), and the rate of perforation was also significantly higher (10.7% vs 0%). All cases of perforation were managed conservatively. No recurrence was observed in the ESD group, whereas local recurrences were detected in 12 EMR cases (21.4%). Eleven of the 12 recurrences (91.7%) were managed endoscopically, and one required surgical resection. CONCLUSIONS: Endoscopic submucosal dissection is a promising technique for the treatment of colorectal tumors, giving an excellent outcome in comparison with EMR.

Endoscopic submucosal dissection in 100 lesions with early gastric carcinoma.

BACKGROUND/AIMS: ESD is a new diagnostic and treatment technique for early gastric cancer. This study aimed to evaluate the therapeutic effects observed at our department. METHODOLOGY: The subject group included 95 patients with 100 early-stage gastric cancers. According to the Gastric Cancer Treatment Guidelines published by the Japanease Gastric Cancer Association (JGCA) in 2001. Sixty-seven lesions presented a tumor measuring less than 20 mm and were concave (if not flat) without ulceration (specified indication of the guidelines of the Japanese Gastric Cancer Association), and 33 lesions were expanded indications. We then compared one-piece resection rates, en-bloc resection rates (one-piece resection that is lateral- and vertical-stump negative), curative en-bloc resection rates (en-bloc resection that fulfills the following three criteria: 1. differentiated adenocarcinoma; 2. no lymphtic or venous invasion, 3a. intramucosal cancer regardless of tumor size without ulceration, 3b. intramucosal cancer 30 mm in size with ulceration, 3c. minute submucosal cancer 30 mm in size). RESULTS: Among the specified indications and expanded indications, one-piece resection rates accounted for 97.0% and 75.8%, en-bloc resection rates for 83.6% and 60.6%, and curative en-bloc resection rates for 83.6% and 57.6%. The numbers of accident cases were three (postoperative hemorrhage; n = 1 perforation; n = 2) and four (postoperative hemorrhage; n = 1, perforation; n = 3), respectively. CONCLUSIONS: These studies indicated higher one-piece resection rates, en-bloc resection rates and curative en-bloc resection rates for lesions based on the guidelines than those based on the expanded guidelines.

A randomized prospective trial comparing unsedated endoscopy via transnasal and transoral routes using 5.5-mm video endoscopy.

We performed a randomized prospective trial to compare unsedated endoscopy via transnasal and transoral routes using a small-caliber endoscope. Two hundred patients referred for diagnostic esophagogastroduodenoscopy (EGD) were randomly allocated to two groups: those undergoing transnasal (TN) and transoral (TO) endoscopy. We examined the insertion rate, examination duration, nasal pain, pharyngeal pain, number of occurrences of pharyngeal reflex, severity of discomfort throughout the examination, and rate of adverse events. Patients were asked to rate the severity of their pain or discomfort on a 10-cm visual analog scale (VAS). We identified statistically significant differences between the TN and TO groups in rate of insertion (95% versus 100%, respectively, P < 0.05) and examination duration (9.7 +/- 3.0 min versus 8.4 +/- 2.7 min, respectively, P < 0.005). Severity of discomfort throughout the examination was comparable in the TN and TO groups (3.0 +/- 1.8 versus 2.9 +/- 2.3, NS). Nasal bleeding occurred as an adverse event in 4.1% of patients in the TN group. Patients in the TO group were more likely than those in the TN group to prefer the present method in the subsequent endoscopic examination (99.0% versus 82.1%, P < 0.00005). These results indicated that transoral insertion is superior to transnasal insertion in endoscopy procedures performed with small-caliber endoscope.

Inhibitory effects of the cyclooxygenase-2 inhibitor, etodolac, on colitis-associated tumorigenesis in p53-deficient mice treated with dextran sulfate sodium.

Non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors are representative agents for the chemoprevention of sporadic colorectal neoplasia. However, few reports have described the chemopreventive effects of such agents on colitis-associated tumorigenesis. To clarify whether treatment with the COX-2 inhibitor may reduce the risk of colitis-associated neoplasia, we investigated the effect of one such agent, etodolac, on tumorigenesis in the colitis-associated neoplasia model using p53-deficient mice treated with dextran sulfate sodium (DSS). The p53-/- mice were divided into four groups: i) treatment with DSS + etodolac, then after two cycles of DSS, the mice were given distilled water for 84 days. In addition, etodolac was administered three times a week at a dose of 10 mg/kg body weight throughout the experiment. ii) Treatment with two cycles of DSS only, followed by distilled water for 84 days. iii) Treatment with etodolac alone. iv) Distilled water alone was administered to the control group. The incidence of mice with neoplasia was 82.4% in the DSS + etodolac group and 100% in the DSS-alone group. No neoplasia was observed in the etodolac-alone and control groups. The mean (+/- SEM) number of total neoplasias per mouse was 1.29+/-0.2 in the DSS + etodolac group and 3.0+/-0.52 in the DSS-alone group, the inter-group difference being significant (p<0.01). There was no significant difference in the inflammation score between these two groups. These results showed that treatment with etodolac significantly reduced the occurrence of neoplasia, suggesting that this COX-2 inhibitor has chemopreventive activity against colitis-associated tumorigenesis.

Colonic expression of heme oxygenase-1 is associated with a better long-term survival in patients with colorectal cancer.

OBJECTIVE: Heme oxygenase-1 (HO-1) has emerged as a crucial mediator of mucosal defense in the gastrointestinal tract. Its metabolic pathway products, biliverdin/bilirubin and carbon monoxide, can reduce oxidative stress and inflammation, and promote resistance to apoptosis. The role of HO-1 in gastrointestinal malignancies, however, remains to be elucidated. The purpose of this study was to analyze HO-1 expression in human colon adenoma and cancer samples. MATERIAL AND METHODS: Fifty-five paraffin-embedded surgical specimens of colorectal cancer and 19 colonic adenoma samples were stained immunhistochemically for HO-1 expression using an anti-HO-1 monoclonal antibody. HO-1 expression was evaluated independently by two different investigators and subsequently correlated to clinical data and patients' life expectancy. RESULTS: Focal HO-1 expression could be documented in 41.8% (23/55) of patients with colorectal cancer. HO-1 expression in colonic adenoma was detectable in 36.8% (7/19) of cases. The rate of lymphatic tumor invasion was significantly lower in colorectal cancer samples expressing HO-1 (p=0.048). Additionally, fewer lymph node metastases were found in colorectal cancer samples with HO-1 expression, but these differences did not reach statistical significance. Mean observation period was 65.87+/-3.96 months. Kaplan-Meier analysis showed a significantly better survival for colorectal cancer patients with colonic HO-1 expression (p=0.018). CONCLUSIONS: This study demonstrates that colonic HO-1 may be a prognostic marker of colorectal-cancer outcome.

Mutational analysis of the BRAF gene in colorectal mucinous carcinoma in association with histological configuration.

Genetic alterations and their association with clinicopathological features in colorectal mucinous carcinoma (MC) remain unknown. In particular, little is known about the mutational status of the BRAF gene, which is activated by oncogenic Ras. This study aimed to evaluate the status of BRAF together with K-ras, p53 and mismatch-repair deficiency to clarify their association with tumorigenesis of colorectal MC. BRAF and K-ras mutations were determined in 43 colorectal MCs by direct sequencing. p53 alteration was investigated immunohistochemically. The status of mismatch-repair deficiency was assessed by microsatellite analyses and immunohistochemistry for hMLH1. We also examined the association between these molecular alterations and clinicopathological features including histological configuration. BRAF mutation was detected in 4 (9.3%) tumors and was located at codon 599 of exon 15 in all cases. K-ras mutation was detected in 13 tumors (30.2%). No BRAF and K-ras mutations were identified simultaneously in the same tumor. The incidence of mismatch-repair deficiency tended to be higher in MC with BRAF mutation than without. In terms of histological configuration, we classified the cases according to growth type by tumor edge morphology. All MCs with BRAF mutation and 9 of 13 MCs (69.2%) with K-ras mutation were classified as polypoid type. BRAF and K-ras mutation did not affect patient prognosis, but non polypoid type was significantly more aggressive than polypoid type. Our findings indicate that BRAF mutation plays an important role in the tumorigenesis of colorectal MC and in tumor edge morphology, similar to K-ras mutation.