Emmanuel Gabriel

Enhanced Recovery After Surgery for Noncolorectal Surgery?: A Systematic Review and Meta-analysis of Major Abdominal Surgery.

Objective: To evaluate the impact of enhanced recovery after surgery (ERAS) protocols across noncolorectal abdominal surgical procedures. Background: ERAS programs have been studied extensively in colorectal surgery and adopted at many centers. Several studies testing such protocols have shown promising results in improving postoperative outcomes across various surgical procedures. However, surgeons performing major abdominal procedures have been slower to adopt these ERAS protocols. Methods: A systematic review was performed using “enhanced recovery after surgery” or “fast track” as search terms and excluded studies of colorectal procedures. Primary endpoints for the meta-analysis include length of stay (LOS) and complication rate. Secondary endpoints were time to first flatus, readmission rate, and costs. Results: A total of 39 studies (6511 patients) met inclusion and exclusion criteria. Among them 14 studies were randomized trials, and the remaining 25 studies were cohort studies. Meta-analysis showed a decrease in LOS of 2.5 days (95% confidence interval, CI: 1.8–3.2, P < 0.001) and a complication rate of 0.70 (95% CI: 0.56–0.86, P = 0.001) for patient treated in ERAS programs. There was also a significant reduction in time to first flatus of 0.8 days (95% CI: 0.4–1.1, P < 0.001) and cost reduction of

Association Between Clinically Staged Node-Negative Esophageal Adenocarcinoma and Overall Survival Benefit From Neoadjuvant Chemoradiation.

5109.10 (95% CI:

The Role of Regional Therapies for in-Transit Melanoma in the Era of Improved Systemic Options

4365.80–

Overexpression of suppressive microRNAs, miR-30a and miR-200c are associated with improved survival of breast cancer patients

5852.40, P < 0.001). There was no significant increase in readmission rate (OR 1.03, 95% CI: 0.84–1.26, P = 0.80) in our analysis. Conclusions: ERAS protocols decreased length of stay and cost by not increasing complications or readmission rates. This study adds to the evidence that ERAS protocols are safe to implement and are beneficial to surgical patients and the healthcare system across multiple abdominal procedures.

Ceramide species are elevated in human breast cancer and are associated with less aggressiveness

IMPORTANCE While neoadjuvant chemoradiation for esophageal cancer improves oncologic outcomes for a broad group of patients with locally advanced and/or node-positive tumors, it is less clear which specific subset of patients derives most benefit in terms of overall survival (OS). OBJECTIVE To determine whether neoadjuvant chemoradiation based on esophageal adenocarcinoma histology has similar oncologic outcomes for patients treated with surgery alone when stratified by clinical nodal status. DESIGN, SETTING, AND PARTICIPANTS A retrospective analysis using the American College of Surgeons National Cancer Database from 1998 to 2006. Patients with esophageal adenocarcinoma histology and clinical stage T1bN1-N3 or T2-T4aN-/+M0 were divided into 2 treatment groups: (1) neoadjuvant chemoradiation followed by surgery and (2) surgery alone. Subset analysis within each treatment group was performed for clinically node-negative patients (cN-) vs node-positive patients (cN+) in conjunction with pathological nodal status. A propensity score-adjusted analysis, which included patient demographics, comorbidity status, and clinical T stage, was also performed. MAIN OUTCOME AND MEASURES The primary outcome was 3-year OS. Secondary outcomes included margin status, postoperative length of stay, unplanned readmission rate, and 30-day mortality. RESULTS A total of 1309 patients were identified, of whom 539 received neoadjuvant chemoradiation followed by surgery and 770 received surgery alone. Of the 1309 patients, 41.2% (n = 539) received neoadjuvant chemoradiation and 47.2% (n = 618) were cN+. Median follow-up for the entire cohort was 73.3 months (interquartile range, 64.1-93.5 months). The 3-year OS was better for neoadjuvant chemoradiation followed by surgery compared with surgery alone (49% vs 38%, respectively; P < .001). Stratifying based on clinical nodal status, the propensity score-adjusted OS was significantly better for cN+ patients who received neoadjuvant chemoradiation (hazard ratio, 0.52; 95% CI, 0.42-0.66; P < .001). In contrast, there was no difference in OS for cN- patients based on treatment (hazard ratio, 0.84; 95% CI, 0.65-1.10; P = .22). CONCLUSIONS AND RELEVANCE Patients with cN+ esophageal adenocarcinoma benefit significantly from neoadjuvant chemoradiation. However, patients with cN- tumors treated with neoadjuvant chemoradiation plus surgery do not derive a significant OS benefit compared with surgery alone. This finding may have significant implications on the use of neoadjuvant chemoradiation in patients with cN- disease.

Lymphovascular and perineural invasion are associated with poor prognostic features and outcomes in colorectal cancer: A retrospective cohort study

The incidence of melanoma has been increasing at a rapid rate, with 4%–11% of all melanoma recurrences presenting as in-transit disease. Treatments for in-transit melanoma of the extremity are varied and include surgical excision, lesional injection, regional techniques and systemic therapies. Excision to clear margins is preferred; however, in cases of widespread disease, this may not be practical. Historically, intralesional therapies were generally not curative and were often used for palliation or as adjuncts to other therapies, but recent advances in oncolytic viruses may change this paradigm. Radiation as a regional therapy can be quite locally toxic and is typically relegated to disease control and symptom relief in patients with limited treatment options. Regional therapies such as isolated limb perfusion and isolated limb infusion are older therapies, but offer the ability to treat bulky disease for curative intent with a high response rate. These techniques have their associated toxicities and can be technically challenging. Historically, systemic therapy with chemotherapies and biochemotherapies were relatively ineffective and highly toxic. With the advent of novel immunotherapeutic and targeted small molecule agents for the treatment of metastatic melanoma, the armamentarium against in-transit disease has expanded. Given the multitude of options, many different combinations and sequences of therapies can be offered to patients with in-transit extremity melanoma in the contemporary era. Reported response and survival rates of the varied treatments may offer valuable information regarding treatment decisions for patients with in-transit melanoma and provide rationale for these decisions.

Predicting Individualized Postoperative Survival for Stage II/III Colon Cancer Using a Mobile Application Derived from the National Cancer Data Base.

Some microRNAs (miRNAs) are known to suppress breast cancer. However, whether the expressions of these tumor suppressive miRNAs translate to patient survival were not investigated in large cohort. Nine miRNAs (miR-30a, miR-30c, miR-31, miR-126, miR-140, miR-146b, miR-200c, miR-206, and miR-335) known to be tumor suppressive miRNAs in breast cancer were investigated in Genomic Data Common data portal miRNA-Seq dataset and The Cancer Genome Atlas (TCGA) (n = 1052). Of the 9 miRNAs, miR-30a, miR-30c, miR-126, miR-140, miR-206, and miR-335 were found to have significantly lower expression in breast cancer tissues compared to paired normal breast tissue. High expression of miR-30a or miR-200c was associated with significantly better overall survival (OS). Gene Set Enrichment Analysis (GSEA) demonstrated that low expression levels of miR-30a had the tendency to associate with gene enrichment of EMT, while miR-200c did not, in TCGA cohort, and our findings support the need of validation using large cohort to use miRNA as prognostic biomarker for patients with breast cancer.

Intravital microscopy in the study of the tumor microenvironment: from bench to human application

Sphingolipids have emerged as key regulatory molecules in cancer cell survival and death. Although important roles of sphingolipids in breast cancer progression have been reported in experimental models, their roles in human patients are yet to be revealed. The aim of this study was to investigate the ceramide levels and its biosynthesis pathways in human breast cancer patients. Breast cancer, peri-tumor and normal breast tissue samples were collected from surgical specimens from a series of 44 patients with breast cancer. The amount of sphingolipid metabolites in the tissue were determined by mass spectrometry. The Cancer Genome Atlas was used to analyze gene expression related to the sphingolipid metabolism. Ceramide levels were higher in breast cancer tissue compared to both normal and peri-tumor breast tissue. Substrates and enzymes that generate ceramide were significantly increased in all three ceramide biosynthesis pathways in cancer. Further, higher levels of ceramide in breast cancer were associated with less aggressive cancer biology presented by Ki-67 index and nuclear grade of the cancer. Interestingly, patients with higher gene expressions of enzymes in the three major ceramide synthesis pathways showed significantly worse prognosis. This is the first study to reveal the clinical relevance of ceramide metabolism in breast cancer patients. We demonstrated that ceramide levels in breast cancer tissue were significantly higher than those in normal tissue, with activation of the three ceramide biosynthesis pathways. We also identified that ceramide levels have a significant association with aggressive phenotype and its enzymes have prognostic impact on breast cancer patients.

Age-related rates of colorectal cancer and the factors associated with overall survival

BACKGROUND Lymphovascular and perineural invasion (LVI and PNI) are associated with poor outcomes in several cancers. We sought to identify clinical variables associated with LVI and PNI in colorectal cancer (CRC) and to determine their impact on survival. METHODS A retrospective review was performed of the National Cancer Data Base (NCDB), 2004-2011. Patients with CRC and a documented LVI or PNI status were included. Multivariate analysis was conducted to examine the associations between clinical variables and LVI/PNI, PNI and survival, and LVI/PNI and lymph node (LN) status in patients with T1 and T2 tumors. RESULTS In total, 158,777 patients were included. LVI status was documented for 139,026 patients, 26.3% of whom were positive. PNI status was documented in 142,034 patients, 11.1% of whom were positive. The multivariable model identified a number of pathologic and clinical characteristics associated with the presence of LVI and PNI, including a number of features of advanced CRC. PNI was independently associated with reduced survival (HR 3.55, 95%CI 1.78-7.09). In T1 or T2 tumors, LVI and PNI were significantly associated with LN involvement. CONCLUSIONS LVI and PNI are associated with advanced CRC. PNI is an independent poor prognostic marker for survival in CRC. LVI and PNI are associated with LN involvement in T1 and T2 tumors. Documentation of LVI and PNI status on biopsy specimens may help in prognostication and decision-making in the management of these early tumors.

Novel Calculator to Estimate Overall Survival Benefit from Neoadjuvant Chemoradiation in Patients with Esophageal Adenocarcinoma

BACKGROUND Prediction calculators estimate postoperative survival and assist the decision-making process for adjuvant treatment. The objective of this study was to create a postoperative overall survival (OS) calculator for patients with stage II/III colon cancer. Factors that influence OS, including comorbidity and postoperative variables, were included. STUDY DESIGN The National Cancer Data Base was queried for patients with stage II/III colon cancer, diagnosed between 2004 and 2006, who had surgical resection. Patients were randomly divided to a testing (nt) cohort comprising 80% of the dataset and a validation (nv) cohort comprising 20%. Multivariable Cox proportional hazards regression of nt was performed to identify factors associated with 5-year OS. These were used to build a prediction model. The performance was assessed using the nv cohort and translated into mobile software. RESULTS A total of 129,040 patients had surgery. After exclusion of patients with carcinoma in situ, nonadenocarcinoma histology, more than 1 malignancy, stage I or IV disease, or missing data, 34,176 patients were used in the development of the calculator. Independent predictors of OS included patient-specific characteristics, pathologic factors, and treatment options, including type of surgery and adjuvant therapy. Length of postoperative stay and unplanned readmission rates were also incorporated as surrogates for postoperative complications (1-day increase in postoperative stay, hazard ratio [HR] 1.019, 95% CI 1.018 to 1.021, p < 0.001; unplanned readmission vs no readmission HR 1.35, 95% CI 1.25 to 1.45, p < 0.001). Predicted and actual 5-year OS rates were compared in the nv cohort with 5-year area under the curve of 0.77. CONCLUSIONS An individualized, postoperative OS calculator application was developed for patients with stage II/III colon cancer. This prediction model uses nationwide data, culminating in a highly comprehensive, clinically useful tool.