Background: With the establishment of the oncological safety and due to the potential of low anterior resection (LAR) with sphincter salvage in improving the quality of life of patients with low and mid rectal cancers, it has become a popular treatment modality. A potential complication of the procedure is anastomotic dehiscence which results in a significant increase in postoperative morbidity and mortality. Methods: A literature search for randomized controlled trials (RCTs) that compared the role of protective diversion stoma with no stoma in LAR of the rectum was performed in PubMed. The effect size for dichotomous and continuous data was displayed as relative risk (RR) and weighted mean difference (WMD), respectively, with their corresponding 95% confidence intervals. A fixed effect or random effects model was used to pool the data according to the result of a statistical heterogeneity test. Results: Five RCTs were identified and included in the analysis. These yielded 390 patients who had undergone a protective diversion ileostomy at the time of the surgery (LAR) and 378 who had not, resulting in a total of 768 patients, all of whom were included in the meta-analysis. The fashioning of an ileostomy significantly decreased the anastomotic leak (AL) rates (RR 0.33, 95% CI 0.21–0.51, p < 0.000) and the reoperation rates (RR 0.26, 95% CI 0.15–0.45, p < 0.000). Conclusion: This meta-analysis found that a protective diversion ileostomy in LAR for rectal cancer decreases the AL rates by one third and the reoperation rates by one fourth. Thus, we conclude that fashioning such a stoma is beneficial.
Bone morphogenetic proteins (BMPs) regulate cell fate during development and mediate cancer progression. In this study, we investigated the role of BMP4 in proliferation, anoikis resistance, metastatic migration, and drug resistance of breast cancer cells. We utilized breast cancer cell lines and clinical samples representing different subtypes to understand the functional effect of BMP4 on breast cancer. The BMP pathway was inhibited with the small molecule inhibitor LDN193189 hydrochloride (LDN). BMP4 signaling enhanced the expression of stem cell genes CD44, ALDH1A3, anti‐apoptotic gene BCL2 and promoted anoikis resistance in MDA‐MB‐231 breast cancer cells. BMP4 enhanced self‐renewal and chemoresistance in MDA‐MB‐231 by upregulating Notch signaling while LDN treatment abrogated anoikis resistance and proliferation of anoikis resistant breast cancer cells in the osteogenic microenvironment. Conversely, BMP4 downregulated proliferation, colony‐forming ability, and suppressed anoikis resistance in MCF7 and SkBR3 cells, while LDN treatment promoted tumor spheroid formation and growth. These findings indicate that BMP4 has a context‐dependent role in breast cancer. Further, our data with MDA‐MB‐231 cells representing triple‐negative breast cancer suggest that BMP inhibition might impair its metastatic spread and colonization.
Esophageal cancer is an aggressive malignancy associated with dismal treatment outcomes. Presence of two distinct histopathological types distinguishes it from other gastrointestinal tract malignancies. Surgery is the cornerstone of treatment in locally advanced esophageal cancer (T2 or greater or node positive); however, a high rate of disease recurrence (systemic and loco-regional) and poor survival justifies a continued search for optimal therapy. Various combinations of multimodality treatment (preoperative/perioperative, or postoperative; radiotherapy, chemotherapy, or chemoradiotherapy) are being explored to lower disease recurrence and improve survival. Preoperative therapy followed by surgery is presently considered the standard of care in resectable locally advanced esophageal cancer as postoperative treatment may not be feasible for all the patients due to the morbidity of esophagectomy and prolonged recovery time limiting the tolerance of patient. There are wide variations in the preoperative therapy practiced across the centres depending upon the institutional practices, availability of facilities and personal experiences. There is paucity of literature to standardize the preoperative therapy. Broadly, chemoradiotherapy is the preferred neo-adjuvant modality in western countries whereas chemotherapy alone is considered optimal in the far East. The present review highlights the significant studies to assist in opting for the best evidence based preoperative therapy (radiotherapy, chemotherapy or chemoradiotherapy) for locally advanced esophageal cancer.
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