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Background: Glue fixation of mesh has been explored for some time as a strategy for reducing postoperative chronic groin pain. Previous studies have come to different conclusions about the superiority of one method over another. We conducted a meta-analysis of randomized control trials comparing the performance of glue versus suture fixation of mesh in open inguinal hernioplasty. Methods: Studies published up to November 2012 were searched using PubMed, EMBASE, MEDLINE, Cochrane Library, and the international standard randomised controlled trials number (ISRCTN) register. Mean differences (MDs) were derived from secondary continuous outcomes and pooled risk ratios (RRs) for categoric outcomes. Meta-analysis was conducted utilizing the random-effects and fixed-effects models as appropriate. Results: Ten randomized controlled studies were selected, with a total of 1,623 patients. Glue fixation for open inguinal hernioplasty reduced chronic groin pain (RR 0.46, 95 % confidence interval (CI) 0.22-0.97), hematoma (RR 0.56, 95 % CI 0.34-0.90), acute postoperative pain (MD −7.92, 95 % CI, −13.17 to −2.66), and time taken to return to normal activities (MD −1.39, 95 % CI, −2.58 to −0.21). There was no evidence of an increase in adverse outcomes including recurrence with glue fixation (RR 0.83, 95 % CI 0.30-2.35). Conclusions: Glue fixation of mesh for open inguinal hernioplasty is superior in many outcomes including the reduction of chronic groin pain. Glue fixation was not associated with an increased risk of hernia recurrence. [ABSTRACT FROM AUTHOR]

Background: Sentinel lymph node biopsy (SLNB) has become the standard of care in axillary staging of clinically node-negative breast cancer patients. Aims: To analyze reasons for failure of SLN localization by means of a multivariate analysis of clinical and histopathological factors. Methods: We performed a review of 164 consecutive breast cancer patients who underwent SLNB. A superficial injection technique was used. Results: 9/164 patients failed to show nodes. In 7/9 patients no evidence of radioactivity or blue dye was observed. Age and nodal status were the only statistically significant factors (p < 0.05). For every unit increase in age there was a 9% reduced chance of failed SLN localization. Patients with negative nodal status have 90% reduced risk of failed sentinel node localization than patients with macro or extra capsular nodal invasion. Discussion: The results suggest that altered lymphatic dynamics secondary to tumour burden may play a role in failed sentinel node localization. We showed that in all failed localizations the radiocolloid persisted around the injection site, showing limited local diffusion only. While clinical and histopathological data may provide some clues as to why sentinel node localization fails, we further hypothesize that integrity of peri-areolar lymphatics is important for successful localization. [ABSTRACT FROM AUTHOR]

Objectives: Bleeding after endoscopic submucosal dissection (ESD) for gastric tumors in patients taking antithrombotic drugs, in particular direct oral anticoagulants (DOACs), remains unresolved; therefore, we evaluated the risk factors for post‐ESD bleeding and drug differences in patients taking DOACs. Methods: We included 278 patients taking antithrombotic drugs who underwent gastric ESD between January 2017 and March 2022. Antithrombotic drugs were withdrawn following the 2017 guidelines (Appendix on anticoagulants including DOACs). To further clarify differences in antithrombotic agents' effects, the peri‐cancerous mucosa in the resected specimen was pathologically evaluated according to the Updated Sydney System. Multivariate analysis was performed to assess the risk of post‐ESD bleeding. Results: The incidence of post‐ESD bleeding in patients taking DOACs was 19.6% (10/51). Among patients taking antithrombotic drugs, DOACs were identified as a possible factor involved in post‐ESD bleeding (odds ratio [OR] 4.92). Among patients taking DOACs, possible factors included resection length diameter ≥30 mm (OR 3.72), presence of neutrophil infiltration (OR 2.71), lesions occurring in the lower third of stomach (OR 2.34), and preoperative antiplatelet use (OR 2.22). Post‐ESD bleeding by DOAC type was 25.0% of patients (4/16) receiving apixaban, in 20.0% (3/15) receiving edoxaban, in 21.4% (3/14) receiving rivaroxaban, and in none of those receiving dabigatran. Conclusions: The administration of DOACs was shown to be a possible factor involved in post‐ESD bleeding, and risk factors for patients taking DOACs included neutrophil infiltration. The pharmacological differences in the effects of DOACs contributing to bleeding in gastric ulcers suggest comparatively less bleeding with dabigatran after ESD. [ABSTRACT FROM AUTHOR]

Dasatinib, a second-generation tyrosine kinase inhibitor, is widely used in patients with haematological malignancies. The main side effects of dasatinib are myelosuppression and pleural effusion; however, colitis, such as haemorrhagic colitis and cytomegalovirus (CMV) colitis, have been reported as rare side effects. There are only a few studies conducted on dasatinib-induced colitis. This study aimed to clarify the clinical, endoscopic and pathological features of dasatinib-induced colitis. This retrospective study included 51 consecutive patients who received dasatinib therapy between June 2009 and July 2020. Dasatinib-induced colitis was defined as the presence of colitis symptoms, exclusion of other diseases that could cause colitis, and improvement in symptoms after dasatinib withdrawal or dose reduction. CMV positivity was determined based on the positive result of CMV immunostaining. Dasatinib-induced colitis was diagnosed in nine of 51 patients (17.6%), and most of the symptoms were mild diarrhoea and bloody stools. The endoscopic findings were characterised by loss of vascular pattern (100%) and multiple small erosions (83.3%) which were mainly found in the transverse and descending colon. In a patient who underwent follow-up colonoscopy once a year while taking dasatinib, endoscopic findings changed from initial erythematous spots to multiple erosions, and finally to multiple small round elevations with erosion on the top that disappeared after discontinuation of dasatinib. Anti-CMV therapy was administered to one patient, but the treatment failed. All patients with dasatinib-induced colitis were cured after the discontinuation of dasatinib. Physicians should consider CMV reactivation to manage dasatinib-induced colitis. [ABSTRACT FROM AUTHOR]

Introduction: Non-curative endoscopic resection of T1 colorectal cancer (CRC) carries a substantial risk of recurrence. However, previous studies have reported a significant proportion of cases in which the deep margin of endoscopic resection was positive for cancer due to the technical difficulties of colorectal endoscopic submucosal dissection (ESD). With the advancement of endoscopic technology and techniques resulting in the reduction of positive resection margins, it is important to reassess the long-term prognosis and major risk factors for recurrence in cases of negative deep margins. Methods: We conducted a retrospective cohort study of consecutive patients with T1 CRC who underwent endoscopic resection between January 2006 and December 2021 with negative deep margins. The histological findings of the resected specimens were analyzed to determine the risk factors associated with the primary outcomes of this study, including recurrence and cancer-related deaths. Results: The median age of the 190 patients was 70 years, of which 63% were male, and endoscopic treatment was performed in 64% by endoscopic mucosal resection and 36% by ESD. Eighty-two patients were in the curative resection (CR) group and 108 were in the non-curative resection (NCR) group, wherein the latter comprised 79 patients who underwent additional surgery (AS) and 29 patients who did not receive AS. Five-year recurrence-free survival rates were 98.4% (95% CI: 89.3–99.8) for CR, 98.3% (95% CI: 88.8–99.8) for NCR with AS, and 73.7% (95% CI: 46.5–88.5) for NCR without AS. Lymphatic invasion and budding grade 2/3 were the major risk factors for recurrence, with hazard ratios of 40.7 (p < 0.001) and 23.1 (p = 0.007), respectively. Of the patients in the NCR group without AS, the 5-year recurrence-free rate was 85.6% (95% CI: 52.5–96.3) if there were no major risk factors (i.e., no lymphatic invasion or budding grade 2/3) (n = 21), whereas the prognosis was poor in the presence of one or more of the major risk factors, with a median recurrence-free survival and disease-specific survival of 2.5 and 3.1 years, respectively (n = 8). Discussion: In endoscopically resected T1 CRC with negative deep margins, lymphatic invasion or budding grade 2/3 may indicate a higher risk of recurrence when followed up without AS. [ABSTRACT FROM AUTHOR]

Background: Serum anti-proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) is a disease-specific antibody against granulomatosis with polyangiitis. PR3-ANCA is a useful serological marker for disease severity in ulcerative colitis (UC). The purpose of this study was to investigate whether PR3-ANCA levels could also predict the success of induction therapy and to compare its performance against other markers, including serum CRP and fecal hemoglobin.Methods: This was a multicenter retrospective study. In total, 159 patients with active-phase UC underwent colonoscopy. Disease activity was measured using the Mayo endoscopic subscore (MES). PR3-ANCA positivity and the response to induction therapy, either 5-aminosalicylic acid or steroid, were assessed. PR3-ANCA, CRP, and fecal hemoglobin were measured during the active phase, and during clinical remission.Results: Eighty-five (53.5%) of 159 patients with active UC were positive for PR3-ANCA. PR3-ANCA titers were significantly higher in the group of patients with MES 3 compared to patients with MES 1 (P = 0.002) or MES 2 (P = 0.035). Steroid therapy was administered to 56 patients with a median partial Mayo score of 7 (5-9), which is equivalent to moderate-to-severe disease activity. PR3-ANCA positivity of non-responders to steroid therapy was significantly higher than that of responders (71.9% vs, 41.7%, P = 0.030), whereas CRP and fecal hemoglobin were not predictive of steroid response. Multivariate analysis demonstrated that PR3-ANCA positivity was associated with non-response to steroid therapy (odds ratio 5.19; 95% confidence interval, 1.54-17.5; P = 0.008). Of the 37 patients treated to clinical remission who were also positive for PR3-ANCA during the active phase, 27 had an MES of ≥ 1, and 10 patients had an MES of 0. In clinical remission, the proportion of patients with MES 0 in 17 patients whose PR3-ANCA became negative was significantly higher than that in 20 patients whose PR3-ANCA remained positive (47.1% vs. 10.0%, P = 0.023).Conclusions: PR3-ANCA not only serves as a marker of disease activity, but also predicts the failure of steroid therapy in moderate-to-severe UC.Trial Registration: This study was retrospectively registered in the UMIN Clinical Trials Registry System (000039174) on January 16, 2020. [ABSTRACT FROM AUTHOR]

Purpose: Laparoscopic surgery is now practiced widely because of its lower postoperative morbidity. As flexible endoscopy during laparoscopic surgery minimizes surgical trauma further, training in endoscopy will become more important for surgeons. Thus, we designed a physical simulator, the Noda-Kitada-Suzuki (NKS) model, which could provide the more realistic insertion of a colonoscope. Methods: We designed a colonoscopy simulator, based on information from computed tomography colonography scans of the anatomy and kinetic properties of the colon and rectum. Results: The transparent skeleton body of the NKS model provides instant visual feedback to the operator and the trainer. Our novel colonoscopy simulator replicates the realistic and reproducible insertion of a colonoscope from the rectum to cecum, providing authentic views of the Houston's valves, the flexures, and mucosal folds. This was verified through an objective questionnaire, with 14 of 16 colonoscopists preferring the NKS model over the previous CM15 model for training purposes. Moreover, the Modified Colonoscopy Simulator Realism Questionnaire analysis confirmed that the NKS model was significantly more realistic than the CM15 for 7 (21.2%) of the 33 items when assessed by 12 colonoscopists. Conclusion: The NKS model provides a realistic training platform and may improve the quality of training in colonoscopy. [ABSTRACT FROM AUTHOR]

Metabolism may determine the biologically malignant behavior of pancreatic cancer. To investigate the significance and prognostic value of cancer metabolism in cancer patients, we investigated the expression of two key enzymes in anaerobic glycolysis, hexokinase 2 (HK2) and pyruvate kinase isoenzyme type M2 (PKM2), in surgical specimens obtained from 36 patients who underwent curative resection of pancreatic ductal carcinoma. The HK2-glycolysis axis is a key system in the clinical imaging of tumors via positron emission tomography. Immunohistochemical staining for HK2 and PKM2 was performed and the data were statistically analyzed to evaluate their prognostic power. The expression of HK2 and PKM2 was associated with clinicopathological variables and patient prognosis, including overall survival, local recurrence-free survival and distant metastasis-free survival. Staining for HK2 was negative and positive in 42 and 58% of the patients, respectively, whereas staining for PKM2 was negative and positive in 56 and 44%, respectively; HK2-positive staining was correlated with progressive pathological tumor stage (pT3 vs. pT1 and pT2; P=0.017). In the univariate analysis, the positive expression of HK2 and PKM2, pathological stage (pT3 vs. pT1 and pT2) and nodal metastasis were significantly correlated with poor prognosis (P<0.03). In the multivariate analysis, pathological nodal metastasis was an independent prognostic factor for overall survival, whereas the positive expression of HK2 and PKM2 exhibited borderline significance (P=0.08 and 0.12, hazard ratio = 2.57 and 2.16, respectively). In addition, the combination of high expression of HK2 as well as PKM2 was found to be significant (P<0.05). These results suggested that the expression of HK2 and PKM2, particularly their combination, in surgical specimens obtained during curative resection, may predict an unfavorable clinical outcome in patients with pancreatic cancer. [ABSTRACT FROM AUTHOR]

Tumor cells respond to their microenvironment, which can include hypoxia and malnutrition, and adapt their metabolism to survive and grow. Some oncogenes are associated with cancer metabolism via regulation of the related enzymes or transporters. However, the importance of metabolism and precise metabolic effects of oncogenes in colorectal cancer remain unclear. We found that colorectal cancer cells survived under the condition of glucose depletion, and their resistance to such conditions depended on genomic alterations rather than on KRAS mutation alone. Metabolomic analysis demonstrated that those cells maintained tricarboxylic acid cycle activity and ATP production under such conditions. Furthermore, we identified pivotal roles of GLUD1 and SLC25A13 in nutritional stress. GLUD1 and SLC25A13 were associated with tumor aggressiveness and poorer prognosis of colorectal cancer. In conclusion, GLUD1 and SLC25A13 may serve as new targets in treating refractory colorectal cancer which survive in malnutritional microenvironments. [ABSTRACT FROM AUTHOR]