A systematic review and meta-analysis of outcomes after elective surgery for ulcerative colitis.

AIM: Approximately 20%-30% of patients with ulcerative colitis (UC) will undergo surgery during their disease course, the vast majority being elective due to chronic refractory disease. The risks of elective surgery are reported variably. The aim of this systematic review and meta-analysis is to summarize the outcomes after elective surgery for UC. METHODS: A systematic review was conducted that analysed studies reporting outcomes for elective surgery in the modern era (>2002). It was prospectively registered on the PROSPERO database (ref: CRD42018115513). Searches were performed of Embase and MEDLINE on 15 January 2019. Outcomes were split by operation performed. Primary outcome was quality of life; secondary outcomes were early, late and functional outcomes after surgery. Outcomes reported in five or more studies underwent a meta-analysis of incidence using random effects. Heterogeneity is reported with I2 , and publication bias was assessed using Doi plots and the Luis Furuya-Kanamori index. RESULTS: A total of 34 studies were included (11 774 patients). Quality of life was reported in 12 studies, with variable and contrasting results. Thirteen outcomes (eight early surgical complications, five functional outcomes) were included in the formal meta-analysis, all of which were outcomes for ileal pouch-anal anastomosis (IPAA). A further 71 outcomes were reported (50 IPAA, 21 end ileostomy). Only 14 of 84 outcomes received formal definitions, with high inter-study variation of definitions. CONCLUSION: Outcomes after elective surgery for UC are variably defined. This systematic review and meta-analysis highlights the range of reported incidences and provides practical information that facilitates shared decision making in clinical practice

Oncogenic role of connective tissue growth factor is associated with canonical TGF-β cascade in colorectal cancer

TGF-β signaling pathways promote tumour development and control several downstream genes such as CTGF and MMPs. This study aimed to investigate the association between CTGF and MMP-1 mRNA expressions with clinicopathological status and survival rate in colorectal cancer patients. We investigated expression levels of CTGF and MMP-1 genes in paraffin-embedded tumours and adjacent normal tissue blocks (ADJ) by Real Time-PCR. Then, the expression of Smad2 and Smad4 proteins in the TGF-β canonical pathway was evaluated by immunohistochemistry. Finally, the correlation between CTGF, MMP-1, and the canonical TGF-β-signalling pathway with the clinicopathological features was investigated. Expression levels of MMP-1and CTGF were higher in tumours compared with adjacent normal tissues. Overexpression levels of MMP-1 and CTGF were associated with lymph node metastasis, distant metastasis, tumour histopathological grading, advanced stage, and poor survival (p 0.05). Additionally, a significant association between the upregulation of MMP-1 and tumour location was noted. Upregulation of Smad2 and Smad4 proteins were also significantly correlated with lymph node metastasis, distant metastasis, advanced stage, and poor survival (p 0.0001). This study showed that canonical TGF-β signalling regulates both CTGF and MMP-1 expression and CRC progression. Moreover, TGF-β signalling and its downstream genes could be used as novel biomarkers and novel approaches for targeted therapy in CRC

Evaluation of Colonoscopy Screening Results in the First-Degree Relatives of Patients with Familial Colorectal Cancer X-Type

BACKGROUND AND OBJECTIVE: Colorectal cancer is one of the growing cancers in Iran and one of the few preventable cancers in the World Health Organization. One of the most important ways to early diagnose this malignancy and its underlying lesions (polyps) and subsequently to prevent it is screening. Colorectal cancer is one of the growing cancers in Iran and one of the few preventable cancers in the World Health Organization. One of the most important ways of early detection of this malignancy and its underlying lesions (polyps) and consequently its prevention is screening. Different protocols have been developed for the diagnosis of first degree relatives of known hereditary cases such as HNPCC and FAP, but the diagnosis plan for first degree relatives has not been defined as a group of familial colorectal cancers without known mutations (type X colorectal cancer). The purpose of this study was to evaluate the results of colonoscopy screening in first-degree relatives of these patients. METHODS: This cross-sectional study was performed on the families of patients with suspected Lynch syndrome who had no deficiency in the expression of repair proteins. Data were collected from the medical records system of colorectal cancer patients who had been enrolled in the system for prevention and early detection of colorectal cancer at Shahid Beheshti University of Medical Sciences Research Center from 1387 to 1397. FINDINGS: The results of colonoscopy revealed that 18 out of 77 subjects had 23% polyps or tumors in their colon, out of which 55% were polyps and the rest were adenomas. About 60% of polyps were in the rectum and sigmoid and the rest in the colon and cecum. Also, 4 patients in this screening showed tumors in their colon, all of which were newly diagnosed, and 2 patients in this screening were diagnosed with inflammatory bowel disease. CONCLUSION: According to the results of this study, in the case of colon polyps, the families of these patients appear to be at high risk like those of Lynch syndrome families and need regular colonoscopy care

TGF-β/Smad signaling pathway as a candidate for EMAST phenotype in colorectal cancer patients

Objective: Elevated microsatellite alteration at selected tetranucleotide repeats (EMAST) is a prognostic biomarker in colorectal cancer (CRC). EMAST phenotype appears to be linked to deficiency in DNA mismatch repair (MMR) proteins including MSH3. The TGF-β signaling pathway has a pivotal role in tumorigenesis of CRC. Since the biological causes of EMAST phenomenon has remained a matter of debate, this study aimed to investigate the association between Smad-dependent canonical signaling TGF-β pathway and EMAST phenotype in colorectal cancer patients. Patients and Methods: EMAST status was analyzed in normal and paraffin-embedded tumor tissues of 122 CRC patients using QIAxcel capillary PCR and electrophoresis. Immunohistochemical method was used to determine the expression of canonical TGFβ-signaling pathway and MSH3 proteins. Eventually, the relationship between canonical TGF-β signaling pathway activation and EMAST phenotype and, therefore, MSH3 expression, was evaluated. Results: 40.2% of CRC tumors had EMAST+ phenotype. The canonical TGF-β signaling pathway was activated in 27.9% of patients. Furthermore, 43.4% of patients indicated low expression of MSH3. 64.7% of tumors characterized with activated canonical TGF-β signaling pathway were EMAST+. Finally, a significant relationship between TGF-ß signaling pathway activation and MSH3 expression was observed. Conclusions: In current study, the activation of canonical TGF-β signaling pathway in CRC tumors mediated by Smad proteins was significantly associated with EMAST phenotype and MSH3 expression

Downregulation of human leukocyte antigen Class I expression: An independent prognostic factor in colorectal cancer

Aim: In the present study, we evaluated the clinical prognostic value of human leukocyte antigen (HLA (Class I tumor cell expression in a series of colorectal cancer (CRC) patients and also explored the association of this expression profile with molecular features such as mutation status of KRAS and BRAF, microsatellite stability status, and clinicopathological characteristics of the patients. Patients and Methods: Formalin-fixed paraffin-embedded tumor tissue of 258 CRC patient's sections were immunohistochemically stained and subsequently quantified for HLA Class I expression by the tumor cells. Determination of microsatellite instability (MSI) tumor status was ascertained using mononucleotide repeat microsatellite targets. KRAS and BRAF mutations were screened by polymerase chain reaction (PCR)-sequencing and cast-PCR, respectively. Results: HLA Class I expression was normal in 91 cases (35.3%), downregulated in 119 (46.1%), and loss of expression in 48 (18.6%) cases. Forty (15.5%) tumors were MSI-H (MSH), 49 were MSI-L (19%), and 169 were microsatellite stable (MSS) (65.5%). Thirty-six (14%) and 15 (5.8%) of the patients exhibited mutation in the KRAS and BRAF, respectively. It was found that patients with downregulated expression of HLA Class I were associated with Stage II tumors (P < 0.001) and a MSS tumor status (P < 0.001), while patients with loss of expression were associated with MSH status (P < 0.001). Univariate and multivariate analyses revealed that HLA Class I downregulated expression was an independent prognostic parameter for shorter overall patient survival time (hazard ratio: 1.8, P = 0.003). Conclusions:HLA Class I expression is an independent and sensitive clinical prognostic marker that might be used in CRC patients.Surgical oncolog

How Does COVID-19 Pandemic Impact on Incidence of Clostridioides difficile Infection and Exacerbation of Its Gastrointestinal Symptoms?

Coronavirus disease 2019 (COVID-19) has rapidly spread all over the world with a very high rate of mortality. Different symptoms developed by COVID-19 infection and its impacts on various organs of the human body have highlighted the importance of both coinfections and superinfections with other pathogens. The gastrointestinal (GI) tract is vulnerable to infection with COVID-19 and can be exploited as an alternative transmission route and target for virus entry and pathogenesis. The GI manifestations of COVID-19 disease are associated with severe disease outcomes and death in all age groups, in particular, elderly patients. Empiric antibiotic treatments for microbial infections in hospitalized patients with COVID-19 in addition to experimental antiviral and immunomodulatory drugs may increase the risk of antibiotic-associated diarrhea (AAD) and Clostridioides difficile infection (CDI). Alterations of gut microbiota are associated with depletion of beneficial commensals and enrichment of opportunistic pathogens such as C. difficile. Hence, the main purpose of this review is to explain the likely risk factors contributing to higher incidence of CDI in patients with COVID-19. In addition to lung involvement, common symptoms observed in COVID-19 and CDI such as diarrhea, highlight the significance of bacterial infections in COVID-19 patients. In particular, hospitalized elderly patients who are receiving antibiotics might be more prone to CDI. Indeed, widespread use of broad-spectrum antibiotics such as clindamycin, cephalosporins, penicillin, and fluoroquinolones can affect the composition and function of the gut microbiota of patients with COVID-19, leading to reduced colonization resistance capacity against opportunistic pathogens such as C. difficile, and subsequently develop CDI. Moreover, patients with CDI possibly may have facilitated the persistence of SARS-CoV-2 viral particles in their feces for approximately one month, even though the nasopharyngeal test turned negative. This coinfection may increase the potential transmissibility of both SARS-CoV-2 and C. difficile by fecal materials. Also, CDI can complicate the outcome of COVID-19 patients, especially in the presence of comorbidities or for those patients with prior exposure to the healthcare setting. Finally, physicians should remain vigilant for possible SARS-CoV-2 and CDI coinfection during the ongoing COVID-19 pandemic and the excessive use of antimicrobials and biocides

Transcultural Adaptation and Validation of Persian Version of Celiac Disease Questionnaire (CDQ); A Specific Questionnaire to Measure Quality of Life of Iranian Patients

Background: The assessment of health-related quality of life has become an important primary or secondary outcome measure in clinical and epidemiologic studies. The aim of this study was to validate a Persian version of Celiac Disease Questionnaire (CDQ) for Celiac disease (CD) among Iranian patients. Materials and Methods: The English version of the CDQ adapted to the Persian language by a forward-backward translation by 3 professional bilingual translators (1 medical, 2 nonmedical). The content validity of translated questionnaire were studied by 5 experts who complete the validity form regarding the questionnaire. Then in a pilot study, translated CDQ completed by 81 CD patients who referred to Taleghani Hospital, Tehran. For assessing the validity and reliability of the questionnaire, confirmatory factor analysis and Cronbach's alpha coefficient have been done, using Lisrel and SPSS software. Results: Of 81 CD patients entered to this study with mean age of 30.54 years old, 71.6 were female. Also, 56.8 were married and 45.7 were high educated. The mean of CDQ total score was 119.18 +/- 34. The calculated Cronbach's alpha coefficient for CDQ questionnaire was 0.9. Also, for each subgroups the Cronbach's alpha coefficient were calculated as the following; emotion: 0.92, Social: 0.89, Worries: 0.73, Gastrointestinal: 0.78. Confirmatory factor analysis indicated that all questions could be remain in questionnaire respectively. Conclusion: The reliability of the Persian version of CDQ was excellent with Cronbach's alpha coefficients and Persian version of CDQ retains the psychometric properties of the original instrument and should be useful to assess outcome in studies and clinical trials involving Iranian patients with CD