PWWP2B promotes DNA end resection and homologous recombination.

Genome instability is one of the leading causes of gastric cancers. However, the mutational landscape of driver genes in gastric cancer is poorly understood. Here, we investigate somatic mutations in 25 Korean gastric adenocarcinoma patients using whole-exome sequencing and show that PWWP2B is one of the most frequently mutated genes. PWWP2B mutation correlates with lower cancer patient survival. We find that PWWP2B has a role in DNA double-strand break repair. As a nuclear protein, PWWP2B moves to sites of DNA damage through its interaction with UHRF1. Depletion of PWWP2B enhances cellular sensitivity to ionizing radiation (IR) and impairs IR-induced foci formation of RAD51. PWWP2B interacts with MRE11 and participates in homologous recombination via promoting DNA end-resection. Taken together, our data show that PWWP2B facilitates the recruitment of DNA repair machinery to sites of DNA damage and promotes HR-mediated DNA double-strand break repair. Impaired PWWP2B function might thus cause genome instability and promote gastric cancer development.

Endoscopic ultrasound-rendezvous versus percutaneous-endoscopic rendezvous endoscopic retrograde cholangiopancreatography for bile duct access: Systematic review and meta-analysis.

OBJECTIVES: Endoscopic ultrasound (EUS) or percutaneous-assisted antegrade guidewire insertion can be used to achieve biliary access when standard endoscopic retrograde cholangiopancreatography (ERCP) fails. We conducted a systematic review and meta-analysis to evaluate and compare the effectiveness and safety of EUS-assisted rendezvous (EUS-RV) and percutaneous rendezvous (PERC-RV) ERCP. METHODS: We searched multiple databases from inception to September 2022 to identify studies reporting on EUS-RV and PERC-RV in failed ERCP. A random-effects model was used to summarize the pooled rates of technical success and adverse events with 95% confidence interval (CI). RESULTS: In total, 524 patients (19 studies) and 591 patients (12 studies) were managed by EUS-RV and PERC-RV, respectively. The pooled technical successes were 88.7% (95% CI 84.6-92.8%, I2 = 70.5%) for EUS-RV and 94.1% (95% CI 91.1-97.1%, I2 = 59.2%) for PERC-RV (P = 0.088). The technical success rates of EUS-RV and PERC-RV were comparable in subgroups of benign diseases (89.2% vs. 95.8%, P = 0.068), malignant diseases (90.3% vs. 95.5%, P = 0.193), and normal anatomy (90.7% vs. 95.9%, P = 0.240). However, patients with surgically altered anatomy had poorer technical success after EUS-RV than after PERC-RV (58.7% vs. 93.1%, P = 0.036). The pooled rates of overall adverse events were 9.8% for EUS-RV and 13.4% for PERC-RV (P = 0.686). CONCLUSIONS: Both EUS-RV and PERC-RV have exhibited high technical success rates. When standard ERCP fails, EUS-RV and PERC-RV are comparably effective rescue techniques if adequate expertise and facilities are feasible. However, in patients with surgically altered anatomy, PERC-RV might be the preferred choice over EUS-RV because of its higher technical success rate.

Systematic review and meta-analysis of percutaneous transluminal forceps biopsy for diagnosing malignant biliary strictures.

OBJECTIVES: To perform a systematic review and meta-analysis to determine the diagnostic performance of percutaneous transluminal forceps biopsy (PTFB) for differentiating malignant from benign biliary stricture. METHODS: A comprehensive literature search of the PubMed, EMBASE, and Ovid MEDLINE databases was conducted to identify original articles published between January 2001 and January 2021 reporting the diagnostic accuracy of PTFB. A random-effects model was used to summarize the diagnostic odds ratio and other measures of accuracy. RESULTS: Fourteen studies involving 1762 patients met the inclusion criteria and were included in the meta-analysis. The meta-analysis summary estimates of PTFB for diagnosis of malignant biliary strictures were as follows: sensitivity 81% (95% confidence interval [CI], 78-81%); specificity 100% (95% CI, 98-100%); diagnostic odds ratio 85.34 (95% CI, 38.37-189.81). The area under the curve of PTFB was 0.948 in the diagnosis of malignant biliary strictures. The diagnostic sensitivity was higher in intrinsic (85%) than in extrinsic (73%) biliary strictures. The pooled rate of all complications was 10.3% (95% CI, 7.0-14.2%), including a major complication rate of 3.1%. CONCLUSION: These data demonstrate that PTFB is sensitive and highly specific for diagnosing malignancy in biliary strictures. PTFB should be incorporated into future guidelines for tissue sampling in biliary cancer, especially in cases with failed endoscopic management. KEY POINTS: • PTFB had a good overall diagnostic performance for differentiating malignant from benign biliary strictures, with a meta-analysis summary estimate of 81% for sensitivity and 100% for specificity. • PTFB had higher sensitivity for cholangiocarcinoma (85%) than for other cancers (73%). • PTFB had a 100% technical success rate and a 10.3% rate for complications, including a 3.1% rate for major complications.

Clinical significance and long-term prognosis of ulcerative colitis patients with appendiceal orifice inflammation.

BACKGROUND: Appendiceal orifice inflammation (AOI) or peri-appendiceal red patch is a skip lesion with segments of continuous colitis from the rectum. Frequently observed in ulcerative colitis (UC) patients, this lesion might be associated with proximal extension in some studies. However, the clinical significance of this lesion and long-term outcomes including therapy remain unclear. Thus, the aim of this study was to evaluate the clinical implication of AOI during long-term periods in patients with UC. METHODS: We retrospectively reviewed 376 patients with UC who performed complete colonoscopic examinations between April 2000 and December 2020. We compared clinical characteristics and outcomes of patients manifesting AOI with those who did not show AOI during a mean follow-up period of 66.1 months. Long-term outcomes included maximal extent of colitis, proximal extension, therapeutic medical histories, UC-related hospitalization, and relapse. RESULTS: Ninety-eight (26.1%) patients showed AOI without evidence of inflammation in the right colon. Mild disease activity at the diagnosis of UC was more included in patients with AOI than in those without AOI. Other baseline characteristics including disease extent, smoking history, external intestinal manifestation, and terminal ileal ulceration were not significantly different between the two groups. During follow-up periods, patients with and without AOI showed no significant difference in proximal extension, Mayo endoscopic score at the last endoscopic examination, UC-related hospitalization, or relapse. Of medication history, patients with AOI were less included in the group treated with high-dose aminosalicylates than those without AOI. However, therapeutic histories of steroids, immunosuppressive agents, and biologics were not significantly different. Of 62 patients with AOI who underwent follow-up colonoscopy, 36 (58.1%) showed resolution of AOI. Clinical outcomes of the resolution group were not different than those of the non-resolution group. Biopsy results of 77 patients with AOI showed chronic active or erosive colitis. CONCLUSIONS: Long-term outcomes of UC patients with AOI were not different from those without AOI. Outcomes of resolution and non-resolution groups of AOI patients were not different either. Thus, AOI might have no prognostic implication in distal UC patients.

Discrete terminal ileal ulcers in patients diagnosed with ulcerative colitis: clinical significance and natural course.

BACKGROUND: Terminal ileal (TI) ulcers are occasionally detected in asymptomatic individuals and mostly resolve without any treatment. In patients with ulcerative colitis (UC), TI ulcers are infrequently observed without evidence of backwash ileitis. However, the clinical significance and natural course of the lesions are unclear. The aim of our study was to evaluate the frequency and clinical implications of TI ulcers in patients with UC. METHODS: We retrospectively reviewed 397 patients with UC via successful TI intubation during colonoscopy. We compared the clinical characteristics of patients manifesting TI ulcers with those who did not. The natural course of TI lesions was also investigated during the follow-up periods. RESULTS: Forty-one patients (10.3%) showed TI ulcers without evidence of inflammation in the right colon. The patients with and without TI ulcers were not different in terms of baseline characteristics, disease activity and extent at the time of the UC diagnosis, proximal extension, Mayo endoscopic score at the last endoscopic examination, medication history, UC-related hospitalization, and relapse during follow-up periods. Of the 30 patients who underwent follow-up colonoscopy in patients with TI ulcers, 23 (76.7%) showed resolution of TI ulcer. In addition, patients with remaining TI ulcers did not differ in disease activity and biopsy results compared with those with resolving TI ulcers. CONCLUSIONS: Discrete TI ulcers are more common in patients with UC, compared with the healthy cohort. No significant clinical impact on disease extension and severity is found.

Prophylactic clip application for large pedunculated polyps before snare polypectomy may decrease immediate postpolypectomy bleeding.

BACKGROUND: Although prophylactic clip application before polypectomy may prevent postpolypectomy bleeding (PPB), the usefulness of prophylactic clipping in the treatment of large pedunculated polyps is controversial in some prospective randomized studies. This study was conducted to evaluate the efficacy of prophylactic clip application and to investigate the predictors of PPB in large pedunculated colorectal polyps. METHODS: A total of 137 pedunculated polyps (size ≥1 cm) in 116 patients were prospectively included and randomized into group A (with clipping) and group B (without clipping), and resected. The occurrences of immediate PPB (graded 1-4) and delayed PPB were compared. RESULTS: Sixty-seven polyps were allocated in group A and 70 polyps in group B. In both groups, the median polyp diameter was 15 mm (P = 0.173) and the median stalk diameter was 3 mm (P = 0.362). Twenty-eight (20.4%) immediate PPB episodes in 137 polyps occurred, 6 (9.0%) in group A and 22 (31.4%) in group B (P = 0.001). However, the occurrence of delayed PPB was not different between the groups (P = 0.943). Prophylactic clip application decreased the occurrence of immediate PPB (odds ratio 0.215, 95% confidence interval 0.081-0.571). Moreover, polyp size ≥20 mm and stalk diameter ≥ 4 mm increased the risk of immediate PPB. CONCLUSIONS: Clip application before polypectomy of ≥1 cm pedunculated polyps is effective in decreasing the occurrence of immediate PPB. Thus, clip application should be considered before performing snare polypectomy, especially for large polyps with a thick stalk. TRIAL REGISTRATION: This research was studied a prospective maneuver and enrolled in a registry of clinical trials run by United States National Library of Medicine at the National Institutes of Health (ClinicalTrials.gov Protocol Registration and Results system ID: NCT01437631). This study was registered on September 19, 2011.

Relationship between angiography timing and angiographic visualization of extravasation in patients with acute non-variceal gastrointestinal bleeding.

BACKGROUND: Angiographic embolization is now considered the first-line therapy for acute gastrointestinal (GI) bleeding refractory to endoscopic therapy. The success of angiographic embolization depends on the detection of the bleeding site. This study aimed to identify the clinical and procedural predictors for the angiographic visualization of extravasation, including angiography timing, as well as analyze the outcomes of angiographic embolization according to the angiographic visualization of extravasation. METHODS: The clinical and procedural data of 138 consecutive patients (mean age, 66.5 years; 65.9% men) who underwent angiography with or without embolization for acute non-variceal GI bleeding between February 2008 and July 2018 were retrospectively analyzed. RESULTS: Of the 138 patients, 58 (42%) had active extravasation on initial angiography and 113 (81.9%) underwent embolization. The angiographic visualization of extravasation was significantly higher in patients with diabetes (p = 0.036), a low platelet count (p = 0.048), high maximum heart rate (p = 0.002) and AIMS65 score (p = 0.026), upper GI bleeding (p = 0.025), and short time-to-angiography (p = 0.031). The angiographic embolization was successful in all angiograms, with angiographic visualization of extravasation (100%). The clinical success of patients without angiographic visualization of extravasation (83.9%) was significantly higher than that of patients with angiographic visualization of extravasation (65.5%) (p = 0.004). In multivariate analysis, the time-to-angiography (odds ratio 0.373 [95% CI 0.154-0.903], p = 0.029) was the only significant predictor associated with the angiographic visualization of extravasation. The cutoff value of time-to-angiography was 5.0 h, with a sensitivity and specificity of 79.3% and 47.5%, respectively (p = 0.012). CONCLUSIONS: Angiography timing is an important factor that is associated with the angiographic visualization of extravasation in patients with acute GI bleeding. Angiography should be performed early in the course of bleeding in critically ill patients.

Delta neutrophil index as a prognostic marker in emergent abdominal surgery.

BACKGROUND: Delta neutrophil index (DNI) is the fraction of circulating immature granulocytes provided by a routine, complete blood cell analyzer. It is known to be a useful prognostic marker of sepsis. The aim of this study was to evaluate the role of DNI in the diagnosis and prognosis of patients who had undergone emergent surgery for an acute abdomen. METHODS: A total of 694 patients who had visited the emergency room for acute abdominal pain and undergone emergent abdominal surgery from May 2015 to September 2016 were retrospectively reviewed. Clinical characteristics, laboratory findings on the day of hospital visit, hospital stay, postoperative complications, and 30-day mortality were investigated. RESULTS: In the analysis of patients who had undergone an operation for acute peritonitis, the DNI was a good predictor for predicting 30-day mortality rate (area under the curve [AUC]: 0.826). It was not inferior to other laboratory values, including activated partial thromboplastin time (AUC: 0.729), C-reactive protein (AUC: 0.727), albumin (AUC: 0.834), prothrombin time (AUC: 0.816), and creatinine (AUC: 0.837) known to be associated with sepsis. Patients with high DNI displayed higher incidence of bacteremia and sepsis, longer hospital stay, higher postoperative complication rate, and higher 30-day mortality rate than patients with low DNI. Among patients diagnosed with acute appendicitis, the DNI was a useful marker for differentiating appendiceal perforation. CONCLUSION: The DNI was a practical and useful marker for predicting the prognosis of patients who needed emergent abdominal surgery.

Effect of gastroprotective agents on upper gastrointestinal bleeding in patients receiving direct oral anticoagulants.

OBJECTIVES: Direct oral anticoagulants (DOACs) are effective in the prevention and treatment of thromboembolism; however, they are associated with upper gastrointestinal bleeding (UGIB). In this study, we evaluated the efficacy of gastroprotective agents (GPAs) in reducing the risk of UGIB in patients receiving DOACs. METHODS: We retrospectively reviewed the medical records of 2076 patients who received DOACs for the prevention or treatment of thromboembolic events between January 2008 and July 2016. A cumulative incidence analysis using the Kaplan-Meier method was performed to determine the rate of UGIB and its association with GPAs administration. RESULTS: Of the 2076 patients, 360 received GPAs. Over the follow-up period (1160 person-years), one patient in the GPA group (0.7 per 100 person-years) and 29 patients in the non-GPA group (2.8 per 100 person-years) developed UGIB (p = .189). In the multivariate analysis, UGIB was associated with older age (hazard ratio (HR), 1.041; p = .048), a history of peptic ulcer or UGIB (HR, 5.931; p < .001), and concomitant use of antiplatelet agents (HR, 3.121; p = .014). GPAs administration did not reduce the risk of UGIB (p = .289). However, based on the subgroup analysis of 225 patients with concomitant use of antiplatelet agents or a history of peptic ulcer or UGIB, the GPA group (0 per 100 person-years) showed reduced incidence of UGIB compared with the non-GPA group (11.3 per 100 person-years) (p = .065). CONCLUSIONS: The prophylactic use of GPAs could reduce the risk of UGIB in patients receiving DOACs who have risk factors, such as concomitant use of antiplatelet agents or a history of peptic ulcer or UGIB.

Phase II study of oxaliplatin, irinotecan and S-1 therapy in patients with advanced gastric cancer: the Korean Cancer Study Group ST14-11.

BACKGROUND: Doublet chemotherapy of platinum and 5-fluorouracil is a standard first-line treatment for patients with unresectable gastric cancer. Although the addition of taxane or irinotecan to this regimen has yielded promising efficacy, its use has been limited due to severe toxicities. To overcome this limitation, we evaluated the efficacy and safety of the combination of irinotecan, oxaliplatin, and S-1 (OIS) for the treatment of advanced gastric cancer. METHODS: Chemotherapy-naïve patients with pathologically proven advanced gastric adenocarcinoma were assessed for eligibility. Irinotecan (135 mg/m2) and oxaliplatin (65 mg/m2) were administered intravenously on day 1, and S-1 (80 mg/m2/day) was administered orally on days 1-7 of every 2-week cycle. RESULTS: Forty-four patients (median age 57 years) were enrolled and all but one patient had a good performance status (ECOG 0 or 1). A total of 529 cycles were administered, with a median of 9.5 (range 1-31) cycles per patient. The overall response rate was 61.4% (95% confidence interval [CI] 46.6-74.3). The median progression-free survival and overall survival were 10.8 months (95% CI 7.6-14.0) and 15.4 months (95% CI 12.6-18.2), respectively. Major toxicities included grade 3/4 neutropenia (38.6%), febrile neutropenia (13.6%), abdominal pain (9.1%), and diarrhea (9.1%). CONCLUSION: These data suggest that the OIS regimen is effective and relatively well tolerated in patients with advanced gastric cancer. Given that all the patients treated, but one, had a good performance status, these results must be confirmed in a patient population more representative of regular clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02527785.

Recurrence rate of lateral margin-positive cases after en bloc endoscopic submucosal dissection of colorectal neoplasia.

PURPOSE: We aimed to evaluate the recurrence rate of colorectal neoplasia showing histologic lateral margin involvement after en bloc endoscopic submucosal dissection (ESD). METHODS: We reviewed 527 colorectal lesions that were removed by en bloc ESD from 2005 to 2013 and followed by endoscopy. Based on the postprocedural pathologic reports, the lesions were categorized as follows: lesions with clear deep and positive lateral margins (n = 63) and lesions with R0 resection (n = 299). RESULTS: The tumor size was 45.7 ± 21.1 mm in the lateral margin-positive group and 30.6 ± 15.1 in the R0 group (P < 0.001). Procedure time was longer in the lateral margin-positive group than in the R0 group (94.3 ± 75.1 vs. 54.1 ± 48.9 min; P < 0.001). Lateral margin positivity was associated with ESD time ≥ 120 min in the multivariate analysis. Compared with 0-I morphology, LST-G was significantly associated with the lateral margin positivity. The volume of ESD experience in endoscopists may also be associated with the lateral margin positivity. Histologic reassessment of the specimen suggested that 32.2% of lateral margin-positive cases based on the initial pathology report were false-positive lateral margin involvement. The 5-year cumulative recurrence rate was 0.6% in the R0 group and 5% in the margin-positive group (P = 0.198). CONCLUSIONS: The local recurrence rate was not higher in lateral margin-positive cases than in R0 resection cases if the colorectal epithelial neoplasia was removed in an en bloc manner using ESD. Meticulous pathologic interpretation may reduce unnecessarily frequent surveillance after en bloc ESD.

Is it beneficial to perform surgical resection in elderly patients more than 80 years old with advanced gastric cancer?

OBJECTIVES: With the aging population, the number of elderly patients diagnosed with gastric cancer is increasing. However, determining treatment strategies for elderly patients with gastric cancer is controversial. The aim of this study is to evaluate the usefulness of surgical treatment on elderly patients aged ≥80 years with advanced gastric cancer. METHODS: A total of 147 elderly patients who were diagnosed with advanced gastric cancer from August 2001 to December 2015 were retrospectively analyzed. We compared the clinicopathological features and prognoses of 94 elderly patients (80-85 years) and 53 extreme-elderly patients (≥86 years) according to treatment modalities. RESULTS: In the elderly group, the 3-year overall survival (OS) rates of the surgical resection group and supportive care group were 42.1% and 4.0%, respectively (p < .001). In the extreme-elderly group, the 3-year OS rates of the surgical resection group and supportive care group were 36.4% and 8.0%, respectively (p = .028). The post-operative mortality rate of the elderly group and extreme-elderly group was 5.6% and 9.1%, respectively. In the analysis of risk factors associated with survival, surgical resection was a significantly good prognostic factor in the elderly group (hazard ratio [HR] = 0.277; p = .003) compared with supportive care. In the extreme-elderly group, surgical resection was associated with good prognosis but did not reach statistical significance (HR = 0.491; p = .099). CONCLUSIONS: These results suggest that elderly patients aged 80-85 years with advanced gastric cancer could expect a better prognosis with surgical resection. However, extreme-elderly patients aged ≥86 years should consider the risks and benefits of surgical treatment.

Treatment outcomes and recurrence following standard cold forceps polypectomy for diminutive polyps.

BACKGROUND: The recurrence rate after standard cold forceps polypectomy (CFP) of diminutive polyps of ≤5 mm has not been fully determined. The aim of this study was to analyze the long-term follow-up results and recurrence rate after CFP of diminutive polyps. METHODS: We retrospectively reviewed the medical records of 884 (738 men; age 53 years) asymptomatic subjects who underwent surveillance colonoscopy after CFP of 1-2 diminutive adenomatous polyps. Cumulative recurrence at the CFP site and risk factors for recurrence were analyzed. RESULTS: Overall recurrence over 59.7 months was 17 % after CFP of 1111 diminutive polyps. The rate of definite recurrence was 4 %, and probable recurrence was 13 %. Recurrence as advanced adenoma was 0.5 % (5/1111). The cumulative probabilities of recurrence at 3, 5, and 7 years after CFP were 10.0, 16.0, and 21.1 %, respectively. Multivariate analysis revealed that polyp 4-5 mm in size and right colonic polyp were risk factors for recurrence (hazard ratio [HR] 1.37; 95 % confidence interval [CI] 1.01-1.86 and HR 1.49; 95 % CI 1.08-2.04, respectively). The recurrence rate for 10 endoscopists who performed at least 50 CFPs ranged from 11.0 to 25.2 %; the probability of recurrence in those in the top half in terms of recurrence rate was 1.6-fold higher than that of those in the bottom half (95 % CI 1.17-2.19). CONCLUSIONS: Although recurrence may develop after standard CFP of diminutive polyps, recurrence as advanced adenoma is rare. Large polyp size, right colon polyp, and endoscopist are risk factors for recurrence after standard CFP.

Optimized hybrid endoscopic submucosal dissection for colorectal tumors: a randomized controlled trial.

BACKGROUND AND AIMS: Colorectal endoscopic submucosal dissection (ESD) is difficult and time consuming. Optimization of ESD with snaring (optimized hybrid ESD) may shorten the procedure time. The purpose of this study was to prospectively compare ESD and optimized hybrid ESD in the colorectum. METHODS: We prospectively enrolled 70 patients with colorectal neoplasia ≥20 mm. The patients were randomized to receive either ESD (36 patients) or optimized hybrid ESD (34 patients). In the optimized hybrid ESD group, snare resection was performed after an adequate amount of submucosal dissection. The primary outcome was procedure time. Secondary outcomes were en bloc and complete resection rates and adverse event rates. RESULTS: ESD could not be completed in 5 patients (13.9%) in the ESD group because of technical difficulties. We tried hybrid ESD to finish the resection, and en bloc resection was achieved in 4 patients (80%). The mean procedure time was shorter in the optimized hybrid ESD group compared with the ESD group (27.4 vs 40.6 minutes; P = .005). The en bloc resection rates were similar (94.1% vs 100%; P = .493), as were the complete resection rates (91.2% vs 93.5%; P > .999) and perforation rates (3 patients [8.8%] vs 2 patients [6.5%]; P > .999). CONCLUSIONS: Optimized hybrid ESD achieves shorter procedure times than ESD, with similar en bloc resection rates and adverse event rates. Optimized hybrid ESD in the colorectum may offer an easy alternative to colorectal ESD and a rescue method for failed ESD cases. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01944540.).

Comparison of endoscopic submucosal dissection and surgical resection for treating gastric subepithelial tumours.

OBJECTIVE: For subepithelial tumours (SETs) of the stomach, surgical resection is the gold standard treatment. With the recent advent of endoscopic resection techniques and devices, endoscopic submucosal dissection (ESD) has been considered as an alternative treatment for SETs. The aim of our study was to evaluate the clinical outcomes of ESD for treating gastric SETs compared with surgical resection. METHODS: Between January 2006 and September 2014, 55 patients with gastric SETs (13 gastrointestinal stromal tumours (GISTs), 27 leiomyomas, and 15 others) were treated by ESD and 27 patients (19 GISTs, two leiomyomas, and six others) underwent surgical resection. We retrospectively reviewed the therapeutic outcomes, procedure-related complications, post-procedure hospital stays, and medical costs of the two groups. RESULTS: The complete resection rate of the ESD group was lower than that of the surgery group (81.8% vs. 100%, p = 0.026). Although the incidence of complications that occurred with ESD was higher than that associated with surgical resection, there were no significant between-group differences (12.5% vs. 3.7%, p = 0.261), and all complicated cases were successfully treated without mortality. The ESD group had significantly shorter post-procedural hospital stays (median five days vs. eight days, p = 0.034) and lower medical costs (median $2374 vs. $4954, p <0.001) than the surgery group. There were no recurrences in either group during the follow-up period. CONCLUSIONS: ESD is an efficient treatment tool for gastric SETs in selected patients. Additionally, ESD has the advantages of shorter hospital stays and lower medical costs compared with surgery.

Clinical outcomes of endoscopic submucosal dissection for large colorectal neoplasms: a comparison of protruding and laterally spreading tumors.

BACKGROUND AND AIMS: The therapeutic outcome of endoscopic submucosal dissection (ESD) for large protruding tumors has not yet been evaluated. We aimed to compare the outcomes of ESD in protruding tumors with those of laterally spreading tumors (LSTs). METHODS: Endoscopic submucosal dissection was attempted in 218 patients with 220 colorectal tumors ≥30 mm in diameter (67, protruding tumors; 153, LSTs) from July 2007 to June 2014. We retrospectively reviewed patient medical records, therapeutic outcomes, and procedure-related adverse events. This study defined lesions with a height of 10 mm or more as protruding tumors and those with a height under 10 mm as LSTs. RESULTS: The mean lesion diameter, height, and volume were 43.8, 9.5 mm, and 13.6 cm(3), respectively. The mean procedure time was 75.5 min. Deep submucosal cancer was more frequent in protruding tumors than in LSTs (11.9 vs. 2.6%, P = 0.005). Severe fibrosis was more common in protruding tumors than in LSTs (19.4 vs. 3.9%, P < 0.001). En bloc resection and complete resection rates were lower in protruding tumors than in LSTs (en bloc resection, 76.1 vs. 92.8%, P = 0.001; complete resection, 64.2 vs. 79.1%, P = 0.020). Intra- and post-procedural bleeding were more frequent in protruding tumors than in LSTs (22.4 vs. 2.6%, P < 0.001; 6.0 vs. 0.7%, P = 0.031, respectively). By multivariate analysis, protruding tumor morphology (odds ratio 1.919, P = 0.048) and tumor size ≥60 mm (odds ratio 2.490, P = 0.030) were associated with incomplete resection. CONCLUSIONS: Endoscopic submucosal dissection for protruding tumors is less effective than ESD for LSTs, with lower rate of complete resection occurring with protruding tumors.

The diagnostic value of a digital rectal examination compared with high-resolution anorectal manometry in patients with chronic constipation and fecal incontinence.

OBJECTIVES: Digital rectal examination (DRE) is a simple clinical method to diagnose anorectal disorders. High-resolution antorectal manometry (HRAM) based on a spatiotemporal plot is expected to promote improved diagnostic accuracy. However, there are no reports comparing the effectiveness of DRE and HRAM. The aim of our study was therefore to evaluate the diagnostic value of DRE compared with HRAM. METHODS: A total of 309 consecutive patients with chronic constipation (n=268) or fecal incontinence (n=41) who underwent a standardized DRE, HRAM, and balloon expulsion test were enrolled in this study. The diagnostic yield of DRE compared with HRAM was determined, and agreement between DRE and HRAM data was evaluated. RESULTS: Of the constipated patients, 207 (77.2%) were diagnosed with dyssynergia using HRAM. The sensitivity, specificity, and positive predictive value of DRE in the diagnosis of dyssynergia were 93.2%, 58.7%, and 91.0%, respectively, and moderate agreement was seen between the two modalities (κ-coefficient =0.542, P<0.001). In patients with fecal incontinence, there was moderate agreement in terms of anal squeeze pressure between the two modalities (κ-coefficient =0.418, P=0.006); however, there was poor agreement for anal resting tone (κ-coefficient =0.079, P=0.368). CONCLUSIONS: DRE shows high sensitivity and positive predictive value in detecting dyssynergia compared with HRAM, and could therefore be used as a bedside screening test for the diagnosis of this disorder. Further studies are warranted to evaluate the correlation between DRE and HRAM in assessing anal sphincter pressure.

The risk of colorectal cancer in inflammatory bowel disease: a hospital-based cohort study from Korea.

OBJECTIVE: Limited data are available on the incidence and risk factors of colorectal cancer (CRC) in Asian patients with inflammatory bowel disease (IBD). MATERIAL AND METHODS: Information on 5212 Korean patients with IBD (2414 with Crohn's disease [CD] and 2798 with ulcerative colitis [UC]) was retrieved from the IBD registry of Asan Medical Center. Data on CRC incidence for the entire Korean population were derived from the Korean Statistical Information Service. RESULTS: During 39,951 person-years of follow-up (17,679 for CD and 22,272 for UC), 30 patients (12 with CD and 18 with UC) developed CRC. The standardized incidence ratio (SIR) of CRC was 6.0 (95% confidence interval [CI], 3.10-10.48) for CD and 1.68 (95% CI, 1.00-2.66) for UC; it was 9.69 (95% CI, 5.01-16.93) for CD with colonic involvement and 4.31 (95% CI, 2.46-7.00) for extensive UC. The SIR was also increased in patients diagnosed with IBD at younger than 30 years old. CRC location was the low rectum in 11 of 12 CD patients (91.7%). The cumulative probability of rectal cancer was higher in CD patients with a perianal fistula than in those without a perianal fistula (p = 0.02). CONCLUSIONS: A high prevalence of perianal fistulas in Korean CD patients may be the cause of the predominance of low rectal cancer in this population and the higher SIR of CRC in Koreans than in Westerners. In contrast, the SIR of CRC in Korean UC patients may be similar to that in Western UC patients.

Appendectomy and the clinical course of ulcerative colitis: a retrospective cohort study and a nested case-control study from Korea.

BACKGROUND AND AIM: Appendectomy protects against the development of ulcerative colitis (UC). However, the relationship between appendectomy and the clinical course of UC is complex, and could be impacted by a number of variables. The aim of this study was to compare the clinical course of UC between appendectomized patients and nonappendectomized patients in Korea. METHODS: Data on 2648 UC patients were retrieved from the Inflammatory Bowel Disease registry at Asan Medical Center. This retrospective cohort study compared the clinical course of UC in 68 patients who received an appendectomy before their UC diagnosis and 2544 patients who did not receive this procedure. A nested case-control study was also conducted to compare the disease course before and after appendectomy in 36 patients who received this surgery after UC diagnosis. To control for potential confounders, 144 matched controls were retrieved from among 2544 nonappendectomized patients RESULTS: In the retrospective cohort study, an appendectomy before UC diagnosis demonstrated no influence on disease extent at diagnosis, rates of medication use, proximal disease extension, or colectomy. The 10- and 20-year probabilities of receiving a colectomy were 12.7% and 20.6%, respectively, in appendectomized patients, in comparison with 8.9% and 16.4%, respectively, in nonappendectomized patients (P = 0.81). According to the nested case-control study, an appendectomy after UC diagnosis did not change the subsequent disease course in terms of medication use, proximal disease extension, or hospital admission rate. The adjusted ratio of hospital admissions after appendectomy versus before appendectomy was 1.01 (95% confidence interval = 0.46-2.23; P = 0.97). CONCLUSIONS: Appendectomies performed before or after UC diagnosis do not affect its clinical course in the Korean population.

PD-1-positive cells contribute to the diagnosis of inflammatory bowel disease and can aid in predicting response to vedolizumab.

Differentiating inflammatory bowel disease (IBD) from other inflammatory diseases is often challenging. Programmed cell death protein-1 (PD-1) is expressed in T cells and is an indicator of their exhaustion. The role of PD-1 expression in diagnosing IBD and predicting the response of biologic agents remains inconclusive. In this study, endoscopic biopsy samples of 19 patients diagnosed with IBD, intestinal tuberculosis, and intestinal Behcet's disease were analyzed using multiplexed immunohistochemistry. Additionally, a separate "vedolizumab (VDZ) cohort" established in ulcerative colitis patients who underwent endoscopic biopsy before VDZ administration was analyzed to predict response to VDZ. In the immunohistochemistry analysis, the cell density of T cell subsets, including PD-1 + cells, was investigated and compared between IBD and other inflammatory diseases (OID). Cell densities of PD-1 + cells (p = 0.028), PD-1 + helper T cells (p = 0.008), and PD-1 + regulatory T cells (p = 0.024) were higher in IBD compared with OID. In the VDZ cohort, patients with a 14-week steroid-free clinical response had higher levels of PD-1 + cells (p = 0.026), PD-1 + helper T cells (p = 0.026), and PD-1 + regulatory T cells (p = 0.041) than the no response group. PD-1 + immune cells may contribute to the diagnosis of IBD and could be used to predict response to VDZ in ulcerative colitis patients.