Can normalized carcinoembryonic antigen following neoadjuvant chemoradiation predict tumour recurrence after curative resection for locally advanced rectal cancer?

AIM: The aim of this work was to evaluate whether normalized carcinoembryonic antigen (CEA) following neoadjuvant chemoradiation predicts the prognosis following curative resection in locally advanced rectal cancer. METHOD: Patients who underwent neoadjuvant chemoradiation and curative resection for locally advanced rectal cancer between 2010 and 2015 were divided into three groups: Group A (n = 119, normal-to-normal): normal CEA before and after neoadjuvant chemoradiation; Group B (n = 37, high-to-normal): elevated CEA before and normal CEA after neoadjuvant chemoradiation; Group C (n = 36, high-to-high): elevated CEA before and after neoadjuvant chemoradiation. Overall and disease-free survival were compared. Univariate and multivariate analyses identified potential predictors for recurrence. RESULTS: One hundred and ninety two patients [median age 59 years (range 31-87), 65.1% male] were identified: 54.7% had low rectal cancer: 12.5% were clinical stage T4 and 70.3% were clinically node positive; 21.9% achieved complete pathological response; 24.5% had abdominoperineal resection (APR); and 70.3% underwent adjuvant chemotherapy following curative resection. Significantly more patients in Group C underwent APR (p = 0.0209), had advanced pathological T stage (P = 0.0065) and a higher prevalence of perineural invasion (p = 0.0042). Overall and disease-free survival were significantly higher for Group A than for Group C [hazard ratio (HR) = 4.32, 95% CI = 1.66-11.21, p = 0.0026 and HR=2.68, 95% CI = 1.33-5.40, p = 0.0057, respectively]. No significant difference was noted between Groups A and B for overall (p = 0.0591) or disease-free (p = 0.2834) survival. Another risk factor associated with recurrence and death was clinical T4 stage; nodal positivity was a risk factor only for recurrence. CONCLUSION: Elevated CEA after neoadjuvant chemoradiation and clinical stage T4 disease were unfavourable predictors for overall and disease-free survival. Normalized CEA during neoadjuvant chemoradiation may serve as a prognosticator, although pretreatment CEA may significantly affect survival.

Peptides as Therapeutic Agents for Dengue Virus.

Dengue is an important global threat caused by dengue virus (DENV) that records an estimated 390 million infections annually. Despite the availability of CYD-TDV as a commercial vaccine, its long-term efficacy against all four dengue virus serotypes remains unsatisfactory. There is therefore an urgent need for the development of antiviral drugs for the treatment of dengue. Peptide was once a neglected choice of medical treatment but it has lately regained interest from the pharmaceutical industry following pioneering advancements in technology. In this review, the design of peptide drugs, antiviral activities and mechanisms of peptides and peptidomimetics (modified peptides) action against dengue virus are discussed. The development of peptides as inhibitors for viral entry, replication and translation is also described, with a focus on the three main targets, namely, the host cell receptors, viral structural proteins and viral non-structural proteins. The antiviral peptides designed based on these approaches may lead to the discovery of novel anti-DENV therapeutics that can treat dengue patients.

Cytoreductive Surgery and Hyperthermic Peritoneal Chemotherapy in Appendiceal and Colorectal Cancer: Outcomes and Survival.

BACKGROUND: We reviewed outcomes following cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with appendiceal or colorectal neoplasms and evaluated key prognostic indicators for treatment. METHODS: All patients who underwent cytoreductive surgery/HIPEC for appendiceal and colorectal neoplasms were identified from an IRB-approved database. Patient demographics, operative reports, and postoperative outcomes were reviewed. RESULTS: 110 patients [median age 54.5 (18-79) years, 55% male] were included. Primary tumor location was colorectal (58; 52.7%) and appendiceal (52; 47.3%). 28.2%, .9%, and 12.7% had right, left, and sigmoid tumors, respectively; 11.8% had rectal tumors. 12/13 rectal cancer patients underwent preoperative radiotherapy. Mean Peritoneal Cancer Index was 9.6 ± 7.7; complete cytoreduction was achieved in 90.9%. 53.6% developed postoperative complications. Reoperation, perioperative mortality, and 30-day readmission rates were 1.8%, .09%, and 13.6%, respectively. Recurrence at a median of 11.1 months was 48.2%; overall survival at 1 and 2 years was 84% and 56.8%, respectively; disease-free survival was 60.8% and 33.7%, respectively, at a median follow-up of 16.8 (0-86.8) months. Univariate analysis of preoperative chemotherapy, primary malignancy location, primary tumor perforated or obstructive, postoperative bleeding complication, and pathology of adenocarcinoma, mucinous adenocarcinoma and negative lymph nodes were identified as possible predictive factors of survival. Multivariate logistic regression analysis showed that preoperative chemotherapy (P < .001), perforated tumor (P = .003), and postoperative intra-abdominal bleeding (P < .001) were independent prognostic indicators for survival. CONCLUSIONS: Cytoreductive surgery/HIPEC for colorectal and appendiceal neoplasms has low mortality and high completeness of cytoreduction score. Preoperative chemotherapy, primary tumor perforation, and postoperative bleeding are adverse risk factors for survival.

Clinicopathological patterns and survival outcomes of colorectal cancer among young adults in Malaysia: an institutional cohort study.

INTRODUCTION: This study aimed to investigate the clinicopathological patterns and survival outcomes of patients with young-onset colorectal cancer (CRC) in Malaysia. METHODS: A total of 206 patients with young-onset CRC (age < 50 years at diagnosis) and 1,715 patients with late-onset CRC (age ≥ 50 years at diagnosis) diagnosed during 2002-2016 were included. The clinicopathological characteristics of patients with young-onset CRC were compared with those of patients with late-onset CRC during 2009-2013. Kaplan-Meier survival analysis was performed to determine the overall survival (OS) and disease-specific survival (DSS) in these patients. RESULTS: The overall proportion of young-onset CRC was 10.7%. The mean age for young-onset CRC was 39.5 ± 7.4 years, with a male-to-female ratio of 1.2:1. There were more Malay patients with young-onset CRC than late-onset CRC (44.0% vs. 19.9%, p = 0.004). Most CRCs were diagnosed at an advanced stage in both groups. However, young-onset CRC showed more aggressive tumour characteristics, such as poorer differentiation and mucinous subtype. Despite such differences, the OS and DSS in both groups were similar (five-year OS for young-onset CRC vs. late-onset CRC: 44.2% vs. 49.0%, p = 0.40; five-year DSS for young-onset CRC vs. late-onset CRC: 48.8% vs. 57.6%, p = 0.53; mean survival of young-onset CRC vs. late-onset CRC: 4.9 years vs. 5.4 years, p = 0.15). Advanced stage at diagnosis and the treatment modality used were independent prognostic factors. CONCLUSION: The unique ethnic and histological differences between patients with young- and late-onset CRC suggest that young-onset CRC may represent a distinct entity. However, despite such differences, both groups were equivalent.

Delayed Bowel Perforation after Routine Distal Loopogram Prior to Ileostomy Closure.

Ultra-low anterior resection for low rectal cancer is usually done with a covering ileostomy as a safety measure to reduce the consequences of distal anastomotic failure. In many centres, distal loopogram is performed routinely, prior to the closure of the loop ileostomy, to assess the integrity of anastomosis. Distal loopogram is generally considered a safe procedure with very low complication rates, especially when water-soluble contrast is used. We report two cases of delayed bowel perforation which led to severe sepsis and generalized peritonitis after distal loopogram prior to ileostomy closure. Our cases highlight the potential dangers of distal loopogram. Therefore, the routine usage of this procedure should be scrutinized and the patient needs to be properly counselled prior to the procedure.