Prognostic signature and immune efficacy of m1 A-, m5 C- and m6 A-related regulators in cutaneous melanoma.

Cutaneous melanoma (CM) is an aggressive cancer; given that initial and specific signs are lacking, diagnosis is often late and the prognosis is poor. RNA modification has been widely studied in tumour progression. Nevertheless, little progress has been made in the signature of N1 -methyladenosine (m1 A), 5-methylcytosine (m5 C), N6 -methyladenosine (m6 A)-related regulators and the tumour microenvironment (TME) cell infiltration in CM. Our study identified the characteristics of m1 A-, m5 C- and m6 A-related regulators based on 468 CM samples from the public database. Using univariate, multivariate and LASSO Cox regression analysis, a risk model of regulators was established and validated by a nomogram on independent prognostic factors. The gene set variation analysis (GSVA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) clarified the involved functional pathways. A combined single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT approach revealed TME of regulator-related prognostic signature. The nine-gene signature stratified the patients into distinct risk subgroups for personalized prognostic assessment. Additionally, functional enrichment, immune infiltration and immunotherapy response analysis indicated that the high-risk group was correlated with T-cell suppression, while the low-risk group was more sensitive to immunotherapy. The findings presented here contribute to our understanding of the TME molecular heterogeneity in CM. Nine m1 A-, m5 C- and m6 A-related regulators may also be promising biomarkers for future research.

A novel NF-κB regulator encoded by circPLCE1 inhibits colorectal carcinoma progression by promoting RPS3 ubiquitin-dependent degradation.

BACKGROUND: Constitutive activation of nuclear factor-κB (NF-κB) signaling plays a key role in the development and progression of colorectal carcinoma (CRC). However, the underlying mechanisms of excessive activation of NF-κB signaling remain largely unknown. METHODS: We used high throughput RNA sequencing to identify differentially expressed circular RNAs (circRNAs) between normal human intestinal epithelial cell lines and CRC cell lines. The identification of protein encoded by circPLCE1 was performed using LC-MS. The function of novel protein was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by immunoprecipitation analyses. RESULTS: A novel protein circPLCE1-411 encoded by circular RNA circPLCE1 was identified as a crucial player in the NF-κB activation of CRC. Mechanistically, circPLCE1-411 promoted the ubiquitin-dependent degradation of the critical NF-κB regulator RPS3 via directly binding the HSP90α/RPS3 complex to facilitate the dissociation of RPS3 from the complex, thereby reducing NF-κB nuclear translocation in CRC cells. Functionally, circPLCE1 inhibited tumor proliferation and metastasis in CRC cells, as well as patient-derived xenograft and orthotopic xenograft tumor models. Clinically, circPLCE1 was downregulated in CRC tissues and correlated with advanced clinical stages and poor survival. CONCLUSIONS: circPLCE1 presents an epigenetic mechanism which disrupts NF-κB nuclear translocation and serves as a novel and promising therapeutic target and prognostic marker.

Endoscopic treatment of pouch inlet and afferent limb strictures: stricturotomy vs. balloon dilation.

BACKGROUND: Strictures are common complications after ileal pouch surgery. The aim of this study is to evaluate the efficacy and safety of endoscopic stricturotomy vs. endoscopic balloon dilation (EBD) in the treatment of pouch inlet strictures. METHODS: All consecutive ulcerative colitis patients with the diagnosis of pouch inlet or afferent limb strictures treated in our Interventional Inflammatory Bowel Disease Unit (i-IBD) from 2008 to 2017 were extracted. The primary outcomes were surgery-free survival and post-procedural complications. RESULTS: A total of 200 eligible patients were included in this study, with 40 (20.0%) patients treated with endoscopic stricturotomy and 160 (80.0%) patients treated with EBD. Symptom improvement was recorded in 11 (42.3%) patients treated with endoscopic stricturotomy and 16 (13.2%) treated with EBD. Subsequent surgery rate was comparable between the two groups (9 [22.5%] vs. 33 [20.6%], P = 0.80) during a median follow-up of 0.6 years (interquartile range [IQR] 0.4-0.8) vs. 3.6 years (IQR 1.1-6.2) in patients receiving endoscopic stricturotomy and EBD, respectively. The overall surgery-free survival seems to be comparable as well (P = 0.12). None of the patients in the stricturotomy group developed pouch failure, while 9 patients (5.6%) had pouch failure in the balloon dilation group (P = 0.17). Procedural bleeding was seen in three occasions (4.7% per procedure) in patients receiving endoscopic stricturotomy and perforation was seen in three occasions (0.8% per procedure) in patients receiving EBD (P = 0.02). In multivariable analysis, an increased length of the stricture (hazard ratio [HR] 1.4, 95% confidence interval [CI] 1.0-1.8) and concurrent pouchitis (HR 2.5, 95% CI 1.0-5.7) were found to be risk factors for the requirement of surgery. CONCLUSION: Endoscopic stricturotomy and EBD were both effective in treating patients with pouch inlet or afferent limb strictures, EBD had a higher perforation risk while endoscopic stricturotomy had a higher bleeding risk.

Impact of pelvic dimensions on anastomotic leak after anterior resection for patients with rectal cancer.

AIM: The impact of pelvis on the development of anastomotic leak (AL) in rectal cancer (RC) patients who underwent anterior resection (AR) remains unclear. The aim of this study was to evaluate the impact of pelvic dimensions on the risk of AL. METHODS: A total of 1058 RC patients undergoing AR from January 2013 to January 2016 were enrolled. Pelvimetric parameters were obtained using abdominopelvic computed tomography scans. RESULTS: Univariate analyses showed that pelvic inlet, pelvic outlet, interspinous distance, and intertuberous distance were significantly associated with the risk for AL (P < 0.05). Multivariate analysis confirmed that pelvic inlet and intertuberous distance were independent risk factors for AL (P < 0.05). Significant factors from multivariate analysis were assembled into the nomogram A (without pelvic dimensions) and nomogram B (with pelvic dimensions). The area under curve (AUC) of nomogram B was 0.72 (95% CI 0.67-0.77), which was better than the AUC of nomogram A (0.69, [95% CI 0.65-0.74]), but didn't reach a statistical significance (P = 0.199). Decision curve supported that nomogram B was better than nomogram A. CONCLUSION: Pelvic dimensions, specifically pelvic inlet and intertuberous distance, seemed to be independent predictors for postoperative AL in RC patients. Pelvic inlet and intertuberous distance incorporated with preoperative radiotherapy, preoperative albumin, conversion, and tumor diameter in the nomogram might provide a clinical tool for predicting AL.

circCAMSAP1 Promotes Tumor Growth in Colorectal Cancer via the miR-328-5p/E2F1 Axis.

Increasing studies indicated that circular RNAs (circRNAs) play important roles in cancer progression. However, the roles of circRNAs in colorectal cancer (CRC) remain largely unknown. In this study, we determined the circRNA expression profile by next-generation RNA sequencing from eight CRC and paired non-cancerous matched tissues. circCAMSAP1 (originating from exon 2 to exon 3 of the CAMSAP1 gene, hsa_circ_0001900) was significantly upregulated in CRC tissues. Increased circCAMSAP1 expression was significantly correlated with advanced tumor/node/metastasis (TNM) stage and shortened overall survival. An elevation of circCAMSAP1 expression was detected via droplet digital PCR in the serum of CRC patients prior to surgery. Functionally, circCAMSAP1 promoted the malignant behavior of CRC. Mechanism study of upstream biogenesis of circCAMSAP1 indicated that circCAMSAP1 cyclization in CRC was mediated by splicing factor epithelial-splicing regulatory protein 1. Moreover, circCAMSAP1 acted as a sponge for miR-328-5p and abrogated its suppression on transcription factor E2F1. Taken together, our data indicated an essential role of the circCAMSAP1/miR-328-5p/E2F1 axis in the progression of CRC, which implied that circCAMSAP1 could serve as a diagnostic and prognostic biomarker as well as a potential therapeutic target for CRC.

Enteral nutrition is associated with a decreased risk of surgical intervention in Crohn's disease patients with spontaneous intra-abdominal abscess.

BACKGROUND: The impact of enteral nutrition (EN) on surgical risk in Crohn's disease (CD) patients suffering from spontaneous intra-abdominal abscess (IAA) was evaluated. METHODS: CD patients diagnosed with spontaneous IAA from 2008 to 2015 were included in the study. The impact of EN on surgical risk was evaluated using both univariate and multivariate analyses. RESULTS: A total of 87 patients were enrolled, 66 (75.9%) were male. The mean age at the development of an abscess was 30.2 ± 10.1 years and the median duration of illness from CD diagnosis until the development of an abscess was three (2-6) years. After a median follow-up of 1.9 (1.1-2.9) years, surgical intervention was performed in 42 patients (48.3%). Patients treated with EN were less likely to require surgical intervention (26.1% vs 56.3%, p = 0.01). Multivariate analysis showed that EN was an independent protective factor for the risk of surgery with a hazard ratio of 0.27 (95% confidence interval: 0.11-0.65, p = 0.004) after adjusting for abdominal pain, history of abdominal surgery, concomitant intestinal stenosis and prior use of antibiotics within three months. CONCLUSIONS: Surgical intervention is common for CD patients with IAA. Appropriate application of EN may help obviate the need for surgical treatment.

Restorative proctocolectomy with a handsewn IPAA: S-pouch or J-pouch?

BACKGROUND: The efferent limb on the S-pouch fits well into the anal canal while the body of the pouch lies on the levators. In contrast, the blunt end of a J-pouch may be distorted as it is forced into the muscular tube of the stripped anus. OBJECTIVE: The aim of this study is to compare the clinical outcomes and quality of life between patients with S- and J-pouches with a handsewn IPAA. DESIGN: This study was retrospective. SETTING: This study was conducted at a high-volume tertiary referral center. PATIENTS: Patients undergoing a primary handsewn IPAA from 1983 to 2012 were identified. MAIN OUTCOMES MEASURES: Demographics, operative details, functional outcomes, and quality of life were abstracted. RESULTS: A total of 502 patients, including 169 patients with an S-pouch (33.7%) and 333 patients with J-pouch (66.3%), met our inclusion criteria; 55.8% (n = 280) were men. Mean age at pouch construction was 37.8 ± 12.5 years. Patients with an S-pouch were younger (p = 0.004) and had a higher BMI (p = 0.035) at pouch surgery. There was no significant difference between patients with S- or J-pouches in other demographics. The frequencies of short-term complications in the 2 groups were similar (p > 0.05), but pouch fistula or sinus (p = 0.047), pelvic sepsis (p = 0.044), postoperative partial small-bowel obstruction (p = 0.003), or postoperative pouch-related hospitalization (p = 0.021) occurred in fewer patients with an S-pouch. At a median follow-up of 12.2 (range, 4.3-20.1) years, patients with an S-pouch were found to have fewer bowel movements (p < 0.001), less frequent pad use (p = 0.001), and a lower fecal incontinence severity index score (p = 0.015). The pouch failed in 62 patients (12.4%), but neither univariate nor multivariate analysis showed a significant association with pouch configuration. LIMITATIONS: The use of data from a single tertiary referral center was a limitation of this study. CONCLUSION: We recommend using an S-pouch when constructing an IPAA with a handsewn technique.

Management of sessile malignant polyps: is colonoscopic polypectomy enough?

BACKGROUND: The role of endoscopy in the management of malignant-pedunculated polyps has been well studied, but endoscopic management of malignant sessile polyps has not. Sometimes patients with malignant sessile polyps have comorbidities that make surgery exceptionally risky, and endoscopy beckons as a definitive management option. The aim of this study is to evaluate the potential role of endoscopy in the management of malignant sessile polyps. METHODS: Patients undergoing colonoscopic polypectomy for malignant sessile polyps by a single endoscopist from 1997 to 2010 were evaluated. Demographic data, clinicopathological variables as well as long-term outcomes were recorded. RESULTS: Sixteen patients had malignant sessile polyps. Six (37.5 %) were male and 10 (62.5 %) were female. Mean age at diagnosis was 72.9 ± 12.2 years. Six polyps were proximal to the splenic flexure (37.5 %) and 10 (62.5 %) were distal. The mean size of the polyps was 30.5 ± 15.9 mm. All polyps were removed endoscopically but 7 patients (43.8 %) had formal colectomy following colonoscopic resection. There were no demographic differences between patients with and without surgery. Piecemeal polypectomy was necessary in 8 patients, 4 from the surgery group, and 4 from the endoscopy group. More patients in the surgery group had poorly differentiated cancers (4/6 vs. 0/6) and incomplete margins (5/6 vs. 1/6) and more patients in the endoscopically treated group had serious comorbidity (5/9 vs. 3/7). There was no procedure-related morbidity or mortality. After a mean follow-up of 48.4 ± 27.2 months, one patient from the polypectomy group patient had a local recurrence and a liver metastasis, after originally declining surgery. In the surgery group, one patient had lung metastasis. The two patients who recurred with distant metastasis died. CONCLUSION: Endoscopic management of sessile colorectal polyps appears to be feasible and safe in patients with well/moderately differentiated cancer and negative margins. Larger studies are needed to confirm these findings.

Frequency, manifestations and management of bezoars in ileal pouches

Background and Aim To evaluate the frequency, diagnosis and management of ileal pouch bezoars. Methods Patients diagnosed with ileal pouch bezoars at the P ouch C enter at Cleveland Clinic from 2002 to 2013 were included. Demographic, clinical and endoscopic features, management and outcomes were evaluated. Results Twelve patients with ileal pouch bezoars were enrolled, including five (0.4%) of 1390 patients with J ­pouch and seven (13.0%) of 54 with continent ileostomy (P < 0.001). Males accounted for 25% (n = 3) of the cohort. Mean age at time of detection was 61.5 ± 10.3 years. Of the 12 patients, six (50.0%) had phytobezoars, four (33.3%) had lithobezoars, one (8.3%) had pharmacobezoar and one (8.3%) had a retained­J ackson­P ratt drain. Median number of harvested bezoars was one (range: 1­224), and mean diameter was 4.0 ± 2.4 cm. Bezoars were located at the pouch body in eight (66.7%) patients, pouch inlet in two (16.7%), pouch­anal anastomosis in one (8.3%) and efferent limb in one (8.3%). Ten patients (83.3%) were symptomatic, including seven (58.3%) with partial bowel obstructive symptoms. Eleven patients (91.7%) were initially managed with endoscopic treatment including basket, R othN et® , mechanical lithotripsy T ripod and snares. After a median of one (1­3) endoscopic therapy, bezoars were successfully removed in seven patients (58.3%). Surgical intervention was required in the remaining five patients (41.7%). Conclusions Ileal pouch bezoars appeared to be more frequently encountered in patients with continent ileostomies than in those with J ­pouches. Endoscopic management seemed to be effective in some patients, whereas surgical intervention was needed in others.

Comparable pouch retention rate between pediatric and adult patients after restorative proctocolectomy and ileal pouches.

BACKGROUND & AIMS: We compared long-term outcomes between adult and pediatric patients with inflammatory bowel disease (IBD) who underwent restorative proctocolectomy with ileal pouch-anal anastomosis. METHODS: We performed a retrospective study that analyzed data from consecutive patients with ileal pouches who presented to the subspecialty Pouch Center at the Cleveland Clinic from 2002-2011. Pouch outcomes of 104 pediatric patients (having pouch surgery at age <18 years; 53 male) were compared with those of 1135 adults (having pouch surgery at an age 18 years or older; 632 male). RESULTS: Pediatric patients had a shorter duration from time of IBD diagnosis to colectomy than adult patients. Fewer pediatric than adult patients had a history of smoking, concomitant extraintestinal manifestations, or dysplasia as the indication for colectomy. However, pediatric patients had higher rates of pouch procedure-related complications, postoperative pouch-associated hospitalization, and postoperative use of anti-tumor necrosis factor (TNF) agents. In multivariate analysis, risk factors for pouch failure included preoperative use of anti-TNF agents (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.05-3.13; P = .032), postoperative use of anti-TNF agents (HR, 2.07; 95% CI, 1.31-3.27; P = .002), Crohn's disease of the pouch (HR, 2.21; 95% CI, 1.28-3.82; P = .005), pouch procedure-related complications (HR, 2.68; 95% CI, 1.55-4.64; P < .001), and postoperative pouch-associated hospitalization (HR, 25.20; 95% CI, 14.44-43.97; P < .001). Being a pediatric patient was not significantly associated with pouch failure in univariate or multivariate analyses (HR, 0.6; 95% CI, 0.32-1.16; P = .13). CONCLUSIONS: On the basis of an analysis of patients with IBD who underwent restorative proctocolectomy and presented at a subspecialized Pouch Center, patients who had the surgery at a pediatric age tend to have a higher incidence of postoperative pouch complications than adults. However, long-term rates of pouch retention were comparable.

Twenty-year-old stapled pouches for ulcerative colitis without evidence of rectal cancer: implications for surveillance strategy?

BACKGROUND: The risk of anal transition zone dysplasia/cancer after stapled IPAA for ulcerative colitis might be cumulative over time. OBJECTIVE: The purpose of this work was to assess the long-term incidence and risk factors of anal transition zone dysplasia. DESIGN: This was a retrospective study from a prospectively maintained database. SETTINGS: The study was conducted at a tertiary referral center. PATIENTS: Participants included those in our surveillance program of serial anal transition zone biopsies after stapled IPAA from 1986 to 1992. MAIN OUTCOME MEASURES: Anal transition zone dysplasia was the main measured outcome. RESULTS: Of 532 patients, 285 had 2 or more anal transition zone surveillance biopsies, including 73 with ≥20 years of regular follow-up. No adenocarcinoma was detected, and 15 patients died of unrelated causes after a median follow-up of 13.4 years (range, 2.9-19.5 years) without dysplasia. The estimated survival rates at 10, 15, and 20 years were 99.6% (95% CI, 96.9-99.9), 98.9% (95% CI, 95.7-99.7), and 92.6% (95% CI, 86.5-96.0). The estimated rates of anal transition zone dysplasia based on the 9 patients were 2.9% (95% CI, 1.5-5.7) and 3.4% (95% CI, 1.8-6.4) at 10 and 15 years. No new-onset dysplasia was identified beyond 125 months. Postoperative anal transition zone dysplasia was significantly associated with both preoperative and pathology findings of colorectal dysplasia (p < 0.001 for each) or cancer (p = 0.025 and p <0.001) and was managed expectantly or with mucosectomy (5 and 4 patients), depending on the number of positive biopsies and degree of dysplasia. Continued surveillance after detection of anal transition zone dysplasia showed no evidence of recurrent dysplasia during a median follow-up of 125 months (range, 9-256 months). LIMITATIONS: Approximately half of the eligible patients were excluded from the analysis because of insufficient follow-up. CONCLUSIONS: Long-term follow-up data corroborate the use of stapled IPAA for ulcerative colitis. Future studies should assess whether a less intensive surveillance strategy is safe 10 years after surgery.

Endoscopic and histologic abnormalities of gastrointestinal tract in patients with hereditary hemochromatosis.

BACKGROUND: Patients with iron overload frequently complained of upper gastrointestinal (GI) symptoms. This study aimed to systemically evaluate the association between hereditary hemochromatosis (HH) and gut inflammation. PATIENTS AND METHODS: HH patients were identified using the ICD-9 codes. Inclusion criteria were patients with primary HH who had esophagogastroduodenoscopy (EGD) and/or colonoscopy with GI biopsies (N=39). Patients undergoing EGD with duodenal biopsy for the indication of "rule out celiac disease" were included in the control group (N=40). GI biopsy specimens were rereviewed and scored. RESULTS: Of the 39 patients with genetically confirmed primary HH in the study group, 28 (71.8%) had liver biopsy and 25 (89.3%) of them showed iron deposition. Twenty-five patients (64.1%) had EGD and 23 (59.0%) had colonoscopy. Histologic inflammation was identified in the esophagus in 2 patients (8.0%), stomach in 11 (44.0%), duodenum in 2 (8.7%), and colon in 3 (13.0%). Duodenal biopsy specimen was available for rereview in 16 patients (41.0%). Patient demographics were comparable between the 16 cases in the study group and the 40 cases in the control group. On histology, the frequency of intraepithelial lymphocytosis of small intestine was 25.5% in the HH cases versus 2.5% in controls (P=0.020). HH patients also had a greater proportion of intraepithelial neutrophil infiltration (31.2% vs. 2.5%, P=0.006) and lamina propria lymphocyte infiltration (31.2% vs. 0%, P=0.001) than controls. CONCLUSIONS: GI inflammation was common in HH patients, which from the different perspective, supports the notion that iron overload may lead to GI inflammation.

Preoperative Clostridium difficile infection is not associated with an increased risk for the infection in ileal pouch patients.

BACKGROUND: Clostridium difficile infection (CDI) might contribute to a refractory course of pouchitis. However, the association between preoperative CDI and postoperative CDI in ileal pouch patients has not been investigated. AIM: Our study aimed to evaluate whether preoperative CDI had an impact on the occurrence of postoperative CDI in pouch patients. METHODS: Consecutive eligible ileal pouch patients from February 2005 to December 2012 were identified from the Pouchitis Registry at the Cleveland Clinic. Patients in the registry with known status of CDI of the pouch were surveyed with a structured questionnaire regarding preoperative C. difficile test and its treatment. Medical records were also reviewed. Demographics and clinical characteristics and outcomes were evaluated with univariable and multivariable analyses. RESULTS: A total of 102 patients with preoperative C. difficile test were identified for this study and 21 patients (20.6%) tested positive for C. difficile test after colectomy. In logistic regression analysis, male patients were 7.85 (P = 0.003) times more likely to have CDI than women. In addition, preoperative significant comorbidities (P = 0.037) and preoperative use antibiotics for other indications (P = 0.005) were found to be associated with postoperative CDI of the pouch. However, there was no evidence to suggest that the preoperative CDI was associated with the occurrence of postoperative CDI (P = 0.769). CONCLUSIONS: Postoperative CDI occurred frequently in male patients with IPAA. In addition, preoperative comorbidities and antibiotic use were found to be risk factors for CDI of the pouch. However, preoperative CDI did not appear to be associated with an increased risk for postoperative CDI in pouch patients.

Endoscopic needle-knife therapy for ileal pouch sinus: a novel approach for the surgical adverse event (with video).

BACKGROUND: Pouch sinus is an adverse event in patients undergoing ileal pouch surgery. OBJECTIVE: To evaluate the efficacy of needle-knife therapy in managing pouch sinus and to assess factors associated with the healing of pouch sinus. DESIGN: An historical cohort study from a prospectively collected database. SETTING: A high-volume specialized pouch center. PATIENTS: From tertiary-care pouch center. INTERVENTIONS: Endoscopic needle-knife therapy. RESULTS: This cohort consisted of 65 patients. Men accounted for 76.9% (n = 50). The median interval from colectomy to the diagnosis of pouch sinus was 4.0 years (interquartile range [IQR]: 2.0-7.5). Pouch sinus was located at the anastomosis in 59 patients (90.8%), at the mid pouch suture line in 4 patients (6.2%), and at the tip of "J" in 2 patients (3.1%). The mean depth of the pouch sinus was 4.4 ± 1.8 cm. Twenty patients (30.8%) had complex pouch sinuses. After a median of 2.0 needle-knife therapies (IQR: 1.5-3.5) during a follow-up period of 1.1 years (IQR: 0.4-2.8), 28 patients (43.1%) with pouch sinus experienced a complete response, 27 (41.5%) had a partial response, and 10 (15.4%) had persistent sinus. Fifty-three patients (81.5%) maintained a functional pouch at the last follow-up. Multivariate analysis showed that a longer duration from colectomy to diagnosis of pouch sinus (odds ratio: 0.85; 95% confidence interval: 0.73-0.99; P = .033) and complex sinuses (odds ratio: 0.17; 95% confidence interval: 0.04-0.70; P = .014) were inversely associated with the healing of pouch sinuses, whereas the increased sessions of needle-knife therapy (odds ratio: 1.36; 95% confidence interval: 1.01-1.81; P = .041) improved the healing of the pouch sinuses. LIMITATIONS: Single-center study with a relatively small number of patients. CONCLUSION: In experienced hands, endoscopic needle-knife therapy is an efficacious and safe procedure for pouch sinuses. A longer duration from colectomy to diagnosis of pouch sinus and complex pouch sinuses appeared to be associated with a higher risk for nonhealing of the sinus, suggesting that early diagnosis and intervention have an impact on outcomes.

Risk factors for delayed postpolypectomy bleeding: how to minimize your patients' risk.

PURPOSE: Secondary bleeding after colonoscopic polypectomy is a serious complication. Most studies show polyp size, location, and shape to be important risk factors but other factors may allow refinement of risk. The aim of this study is to look for other factors associated with delayed postpolypectomy bleeding. METHODS: This case-matched study compares patients who developed postpolypectomy bleeding with those who underwent uncomplicated polypectomy. Matching was performed for known risk factors: polyp size, location and shape, with a ratio of three controls to one subject. RESULTS: Postpolypectomy bleeding occurred in 19/494 patients with polyps >2.0 cm diameter (3.8%) and 11/4161 patients with polyps <2.0 cm (0.3%). There was a median interval of 3 days (range 0-9 days) from polypectomy to hemorrhage. Twenty-five patients were readmitted to this institution. Ten (40.0%) were transfused and 19 (76.0%) were re-colonoscoped, with 13 needing either cautery (n = 7) or adrenaline injection (n = 6). Ninety patients were selected as controls, matched for polyp size, location, and shape. Mean age at polypectomy was 69.9 ± 9.2 years for patients and 64.9 ± 12.2 for controls (p = 0.042); 63.3% subjects were male, compared to 47.8% of controls (p = 0.140). Univariate analysis showed that older age, piecemeal polypectomy, need for additional sedation, concurrent diverticulosis and intraprocedural bleeding were significantly associated with increased risk of delayed bleeding. The associations between delayed bleeding and additional sedation, concurrent diverticulosis and intraprocedural bleeding were confirmed by multivariate logistic regression analysis. CONCLUSION: Difficult colonoscopy and intraprocedural bleeding identify patients with a particularly high risk of secondary postpolypectomy bleeding. Preventive measures should be considered in such cases.

Clinical value of surveillance pouchoscopy in asymptomatic ileal pouch patients with underlying inflammatory bowel disease.

BACKGROUND: There is no consensus on the need for and the interval of surveillance pouchoscopy in asymptomatic ileal pouch patients with underlying ulcerative colitis (UC). The purpose of this study was to evaluate the likelihood of finding dysplasia or incidental ileal pouch disorders in asymptomatic patients undergoing surveillance pouchoscopy. METHODS: This study included all eligible consecutive asymptomatic UC patients undergoing surveillance pouchoscopy to our subspecialty Pouchitis Clinic from 2002 to 2011. Univariable and multivariable analyses were performed. RESULTS: A total of 138 patients met the inclusion criteria, with 72 (52.2 %) being male. The mean age at pouch construction was 45.4 ± 15.0 years, and the mean interval from ileostomy closure to the inception of first surveillance pouchoscopy was 89.4 ± 78.8 months. One patient was found to have indefinite for dysplasia on pouch body mucosal biopsy (0.7 %), and two patients had non-caseating granulomas, suggesting Crohn's disease (CD) of the pouch. Of the 138 patients, 69 (50 %) had abnormal endoscopic findings, 102 (73.9 %) had acute and/or chronic inflammation on histology, and 62 (44.9 %) had both abnormal endoscopy and histology. The abnormal endoscopic findings included isolated pouch ulcer (n = 29, 21 %), active pouchitis (n = 31, 22.5 %), inflammatory polyps (n = 10, 7.2 %), strictures at the anastomosis (n = 5, 3.6 %), inlet (n = 10, 7.2 %) or outlet (n = 2, 1.4 %). Thirteen patients (13/17, 76.5 %) with pouch strictures underwent endoscopic balloon dilatation therapy and nine had (9/10, 90 %) endoscopic polypectomy. Multivariable analysis showed that patients with a preoperative diagnosis of CD and concomitant extraintestinal manifestations had a higher risk for abnormal pouch endoscopic findings with odds ratios of 2.552 (95 % confidence interval [CI] 1.108-16.545, p = 0.035) and 4.281 (95 % CI 1.204-5.409, p = 0.014), respectively. CONCLUSIONS: Dysplasia was rare in asymptomatic patients with restorative proctocolectomy who underwent surveillance pouchoscopy in this cross-sectional study. However, "incidental" abnormal endoscopic and/or histologic findings were common, which often needed endoscopic therapeutic intervention.

GAS6 From CD200+ Adipose-Derived Stem Cells Mitigates Colonic Inflammation in a Macrophage-Dependent Manner.

BACKGROUND AND AIMS: Stem cell therapy is a promising cell-based treatment modality for inflammatory bowel diseases [IBD], but its application is limited by the nature of cell heterogeneity. METHODS: Single-cell RNA-sequencing was performed on the adipose-derived stem cells [ADSCs]. The in vitro immunomodulatory effect of ADSCs was evaluated by co-culturing with human CD4+ T cells or macrophages. The in vivo therapeutic value of ADSCs was assessed using a murine colitis model induced by dextran sulphate sodium [DSS] or 2,4,6-trinitrobenzene sulphonic acid [TNBS]. RESULTS: CD200+ ADSCs were identified as a novel subpopulation of ADSCs, based on gene ontology analysis of immunoregulatory functions. The immunoregulatory functions of these cells were further confirmed by co-culturing with CD4+ T cells or macrophages. Administration of CD200+ ADSCs effectively reduced intestinal inflammation in IBD mice models. Furthermore, we found CD200+ ADSCs-derived GAS6 exerted protective effects on experimental colitis by promoting macrophage M2 polarization via the Mer/PI3K/Akt/GSK3ß signalling pathway. CONCLUSIONS: This study uncovered the heterogeneity in ADSCs, in which CD200+ ADSCs presents as an alternative to conventional treatment of IBD.

High expression of CD73 as a poor prognostic biomarker in human colorectal cancer.

BACKGROUND AND OBJECTIVES: To investigate the expression dynamics of CD73 and its prognostic significance in human colorectal cancer (CRC). METHODS: CD73 expression dynamics were detected by Western blotting. Immunohistochemistry was used to examine the expression of CD73 in CRC tissues from two independent cohorts by tissue microarrays. The optimal cutpoint of CD73 expression was assessed by the X-tile program. RESULTS: Western blotting analysis demonstrated that CD73 expression in CRC was significantly higher than in normal colorectal tissues. According to the X-tile program, the cutpoint for high expression of CD73 in CRC was determined when CD73 expression index was more than 5.9. High expression of CD73 was observed in 44.8% and 50.4% of CRC in the training and validation cohorts, respectively. Overexpression of CD73 was significantly correlated with tumor differentiation, nodal status, American Joint Committee on Cancer stage. Patients with high expression of CD73 had a poorer overall survival rate compared with patients with low expression of CD73 in both cohorts. In multivariate Cox regression analysis, overexpression of CD73 was proven to be an independent prognostic biomarker for CRC. CONCLUSIONS: High expression of CD73 can be an independent and useful biomarker for predicting the poor survival of patients with CRC.

Extraperitoneal vs. intraperitoneal route for permanent colostomy: a meta-analysis of 1,071 patients.

BACKGROUND: Parastomal hernia is a common complication after colostomy construction. Whether an extraperitoneal route for colostomy creation can reduce the risk of parastomal hernia remains controversial. OBJECTIVE: A meta-analysis was performed to evaluate the value of extraperitoneal route in the prevention of parastomal hernia and other postoperative complications related to colostomy. DATA SOURCES: A literature search of Medline, Embase, Ovid, and Cochrane databases from the years 1966 to 2010 was performed. STUDY SELECTION: Studies comparing extraperitoneal colostomy with intraperitoneal colostomy were identified. INTERVENTION: Extraperitoneal colostomy was performed to prevent colostomy-related complications. MAIN OUTCOME MEASURES: Data on the following outcomes were sought: incidence of postoperative colostomy complications including parastomal hernia, prolapse, and bowel obstruction. RESULTS: Seven retrospective studies with a combined total of 1,071 patients (250 extraperitoneal colostomy and 821 intraperitoneal colostomy) were identified. There was a significantly lower rate of parastomal hernia (odds ratio, 0.41; 95% confidence interval, 0.23-0.73, p = 0.002) in the extraperitoneal colostomy group. However, the occurrences of bowel obstruction and prolapse were not significantly different between the two groups. LIMITATIONS: A limitation of the study lies on the meta-analysis of observational studies. CONCLUSION: Extraperitoneal colostomy is associated with a lower rate of postoperative parastomal hernia as compared to intraperitoneal colostomy. Prospective randomized controlled trial is warranted to further determine the role of extraperitoneal route in the prevention of parastomal hernia.