Deterioration in renal function after stoma creation: a retrospective review from a Middle Eastern tertiary care center.

BACKGROUND: Stomas are associated with multiple complications including dehydration which ultimately affects renal function. These complications begin with changes in the estimated glomerular filtration rate (GFR). OBJECTIVES: Evaluate changes in GFR after stoma creation by stoma type and identify how different types of stoma affect GFR. DESIGN: Retrospective, analytical cohort SETTING: Tertiary care center in Saudi Arabia PATIENTS AND METHODS: The colorectal surgery database was reviewed for all adult patients who underwent stoma creation (permanent and temporary ileostomies and colostomies) or reversal in 2000-2015. GFR was estimated at the first encounter, before the index surgery, at the time of stoma reversal, and upon the last follow-up. Patients with renal impairment, including low GFR before stoma creation, patients who had a temporary stoma converted to a permanent stoma, and patients who died with a stoma were excluded. We studied the association of several demographic and clinical factors on changes in GFR by univariate and multivariate analysis. MAIN OUTCOME MEASURES: Estimated GFR at the last clinic visit for the permanent stoma group and at stoma closure for the temporary stoma group. SAMPLE SIZE: 394 patients (149 ileostomates, 245 colostomates) RESULTS: Thirty-three (8.4%) of the 394 patients had a low GFR: 11 (7.4%) in the ileostomy group and 22 (9%) in the colostomy group (P= .579). The rate of readmissions with ileostomies was higher (11.4%) than with colostomies (3.3%) (P≤.001). The number of temporary ileostomies (n=9, 7.0%) differed from temporary colostomies (n=2, 1.9%) but the difference was not statistically significant (P=.06). In the multivariate analysis, stoma permanency, hypertension, chemotherapy and nephrotoxic drugs were risk factors associated with low GFR. CONCLUSION: Ileostomies were not associated with a high rate of renal function deterioration in comparison to colostomies, but had a significantly higher rate of readmission due to dehydration and electrolytes imbalance possibly due to the hot climate in Saudi Arabia. LIMITATIONS: Retrospective nature and limited sample size which may have resulted in a type 2 statistical error. CONFLICTS OF INTEREST: None.

Long-term outcomes after complete mesocolic excision for colon cancer at a tertiary care center in Saudi Arabia.

BACKGROUND: Data on long-term survival and recurrence of cancer after complete mesocolic excision (CME) for colon cancer has not been reported from our center and related to international data. OBJECTIVE: Describe overall and disease-free survival, survival by surgery site and stage, and recurrence rates after curative surgery. DESIGN: Retrospective chart review. SETTINGS: Academic tertiary care center. PATIENTS AND METHODS: The study included all patients who underwent either laparoscopic or open surgery for colon cancer with curative intent between 2001 and 2011. The colorectal database was reviewed for the following: demographic data, comorbidities, radiologic investigations, clinical stage, type of operation, complications, pathologic assessment, adjuvant treatment, recurrence and survival. Survival and recurrence rates were calculated, and survival curves were generated. MAIN OUTCOME MEASURES: 5-year overall survival, secondary endpoints were 5-year disease-free survival, survival by surgery site and stage, and recurrence rates. SAMPLE SIZE: 220. RESULTS: The mean (SD) age at diagnosis was 57 (13) years (CI 95%: 55-59 years). There were 112 males. Mean (SD) body mass index was 27.6 (5.7) kg/m2 (CI 95%: 27-28). Pathological assessment revealed R0 (microscopically margin-negative) resection in 207 (94%). The overall 5-year survival and disease-free survival was 77.9% and 70%, respectively. The 5-year disease-free survival was 69% for the sigmoid/left colon and 69% for the right colon (difference statistically nonsignificant). Stages at the time of resection were stage 0 for 2 (0.01%) patients, stage I for 18 (8%), stage II for 92 (42%), stage III for 100 (46%), and stage IV for 6 (3%). The 5-year overall survival by stages I, II, III and IV was 94%, 80%, 75% and 50%, respectively (difference statistically non-significant). The overall 5-year recurrence rate was 23.4%. CONCLUSION: The outcomes of surgical treatment for colon cancer at our institution are equivalent to international sites. No difference was noted between left and right colon in terms of survival after CME. LIMITATIONS: Single center, retrospective, small sample size. CONFLICT OF INTEREST: None.

TGFß-induced SMAD4-dependent Apoptosis Proceeded by EMT in CRC.

Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. In Saudi Arabia, colorectal cancer is more aggressive and presents at younger age, warranting new treatment strategies. Role of TGFß/Smad4 signaling pathway in initiation and progression of colorectal cancer is well documented. This study examined the role of TGFß/Smad4 signaling pathway in a large cohort of Saudi patients with colorectal cancer, followed by in vitro analysis to dissect the dual role of TGFß on inducing epithelial-to-mesenchymal transition (EMT) and apoptosis. Our study demonstrated high frequency of Smad4 alterations with low expression of Smad4 protein identifying a subgroup of aggressive colorectal cancer to be an independent marker for poor prognosis. Functional studies using colorectal cancer cells show that TGFß induces Smad4-dependent EMT followed by apoptosis. Induction of mesenchymal transcriptional factors, Snail1 and Zeb1, was essential for TGFß-induced apoptosis. Our results indicate that KLF5 acts as an oncogene in colorectal cancer cells regardless of Smad4 expression and inhibition of KLF5 is requisite for TGFß-induced apoptosis. Furthermore, TGFß/Smad4 signal inhibits the transcription of KLF5 that in turn switches Sox4 from tumor promoter to suppressor. A high incidence of Smad4 alterations were found in the Saudi patients with colorectal cancer. Functional study results indicate that TGFß induces Smad4-dependent EMT followed by apoptosis in colorectal cancer cells.

Evaluating operative risk in colorectal cancer surgery: ASA and POSSUM-based predictive models.

OBJECTIVE: To review two predictive models, based on the American Society of Anaesthesiologists (ASA) and the Physiological and Operative Severity Score for the enumeration of Mortality and morbidity (POSSUM)-used for estimating postoperative mortality in patients, undergoing surgery for colorectal disease, in the UK. METHODS: Data was derived from three multicentre, UK-based studies involving a total of 16,006 patients with malignant or non-malignant bowel pathologies. Data sources were: The Colorectal-POSSUM (CR-POSSUM) Study population, comprising 6883 patients undergoing colorectal surgery in 15 UK hospitals between 1993 and 2001; The Association of Coloproctology of Great Britain and Ireland (ACPGBI) Colorectal Cancer (CRC) Database, encompassing 8077 newly diagnosed CRC patients, undergoing surgical resections in 79 hospitals, between April 2000 and March 2002; The ACPGBI Malignant Bowel Obstruction (MBO) Study, encompassing 1046 patients with MBO in 148 hospitals, treated between April 1998 and March 1999. Multifactorial logistic regression analyses were used to adjust for case-mix, identify risk factors for in-hospital/30-day operative mortality and to accommodate the variability of outcomes between hospitals. RESULTS: In the ACPGBI CRC study, 7374 patients had surgery, 6622(89.8%) a major bowel resection and 1465(19.9%) emergency surgery. Nine hundred and eighty-nine (94.6%) patients with MBO had surgery and 854(86.3%) underwent bowel resection. In the CR-POSSUM study, of the 6790(98.6%) patients undergoing surgery, 3451(50.8%) had a major colorectal resection, including 2107(31.0%) as an emergency. The operative mortality was 7.5% for the ACPGBI CRC study, 15.7% for patients with MBO and 5.7% for patients in the CR-POSSUM study. When tested, the predictive models showed good discrimination, with an area under the receiver-operator characteristic curve of 77.5% for the ACPGBI CRC, 80.1% for the MBO and 89.8% for the CR-POSSUM. CONCLUSIONS: Prediction of postoperative death can be made by the clinician using simple, numerical, tables derived from the ACPGBI CRC, MBO and CR-POSSUM models. The models can be used in everyday practice for pre-operative counselling of patients and their carers, as a part of the process of informed consent. They may also be used to compare the outcomes between multidisciplinary CRC teams.