Analysis of delay in adjuvant chemotherapy in locally advanced rectal cancer

BackgroundAdjuvant chemotherapy (AC) after neoadjuvant chemoradiation and surgical resection has been the standard of care for locally advanced rectal cancer. However, there are no evidence-based guidelines regarding the optimal timing of AC for rectal cancer. The objective of this study was to evaluate the effect of AC timing on overall survival for rectal cancer.MethodsThe National Cancer Database (NCDB) from 2004 to 2016 was queried for primary clinical stage II or III rectal cancer patients who had undergone neoadjuvant chemoradiation followed by surgery and AC. Patients were grouped based on AC initiation: early ≤ 4 weeks, intermediate 4-8 weeks, and delayed ≥ 8 weeks. The primary outcome was overall survival.ResultsWe identified 8722 patients, of which 905 (10.4%) received early AC, 4621 (53.0%) intermediate AC, and 3196 (36.6%) delayed AC. Pathological lymph-node metastasis (ypN +) was positive in 73% of early AC, 74% intermediate AC, and 63% delayed AC (p < 0.05). The 5-year survival probability was 71.1% (95% CI 68-74%) for early AC, 73.2% (95% CI 72-75%) intermediate AC, and 65.8% (95% CI 64-68%) delayed AC (p < 0.001). Using Cox proportional hazard modeling, patients undergoing delayed AC had an associated decreased survival compared to patients receiving early AC (HR 1.18; 95% CI 1.028-1.353, p = 0.018) or intermediate AC (HR 1.28; 95% CI 1.179-1.395, p < 0.01).ConclusionsDelay in AC administration may be associated with decreased 5-year survival. Compared to early or intermediate AC, patients in the delayed AC group were observed to have increased risk of death, despite having lower proportions with ypN + disease. Patients with higher socioeconomic and education status were more likely to receive early chemotherapy

EGFRvIV: a previously uncharacterized oncogenic mutant reveals a kinase autoinhibitory mechanism

Tumor cells often subvert normal regulatory mechanisms of signal transduction. This study shows this principle by studying yet uncharacterized mutants of the epidermal growth factor receptor (EGFR) previously identified in glioblastoma multiforme, which is the most aggressive brain tumor in adults. Unlike the well-characterized EGFRvIII mutant form, which lacks a portion of the ligand-binding cleft within the extracellular domain, EGFRvIVa and EGFRvIVb lack internal segments distal to the intracellular tyrosine kinase domain. By constructing the mutants and by ectopic expression in naive cells, we show that both mutants confer an oncogenic potential in vitro, as well as tumorigenic growth in animals. The underlying mechanisms entail constitutive receptor dimerization and basal activation of the kinase domain, likely through a mechanism that relieves a restraining molecular fold, along with stabilization due to association with HSP90. Phosphoproteomic analyses delineated the signaling pathways preferentially engaged by EGFRvIVb-identified unique substrates. This information, along with remarkable sensitivities to tyrosine kinase blockers and to a chaperone inhibitor, proposes strategies for pharmacological interception in brain tumors harboring EGFRvIV mutations.Goldhirsh FoundationNational Cancer Institute (U.S.) (CA118705)National Cancer Institute (U.S.) (CA141556)National Cancer Institute (U.S.) (U54-CA112967

Surgical treatments for rectal prolapse: How does a perineal approach compare in the laparoscopic era?

Background: Patients with rectal prolapse often have significant comorbidities that lead surgeons to select a perineal resection for treatment despite a reported higher recurrence rate over abdominal approaches. There is a lack of data to support this practice in the laparoscopic era. The objective of this study was to evaluate if risk-adjusted morbidity of perineal surgery for rectal prolapse is actually lower than laparoscopic surgery. Design: A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database as performed for patients undergoing surgical treatment of rectal prolapse between 2005 and 2011. Outcomes were analyzed according to procedure-type: laparoscopic rectopexy (LR), laparoscopic resection/rectopexy (LRR), open rectopexy (OR), open resection/rectopexy (ORR), and perineal resection (PR). A multivariate logistic regression was used to compare risk-adjusted morbidity and mortality between each procedure. Main outcome measures were 30-day morbidity and mortality. Results: Among 3,254 cases sampled, a laparoscopic approach was used in 22 %, an open abdominal approach in 30 %, and PR in 48 %. Patients undergoing PR were older (76) and had a higher ASA (3) compared to laparoscopic (58, 2) and open abdominal procedures (58, 2). Risk-adjusted mortality could not be assessed due to a low overall incidence of mortality (0.01 %). Overall morbidity was 9.3 %. ORR was associated with a higher risk-adjusted morbidity compared to PR (OR: 1.89 CI (1.19–2.99), p = 0.03). There were no significant differences in risk-adjusted morbidity found between LR and LRR compared to PR (OR 0.44 CI (0.19–1.03), p = 0.18; OR 1.55 CI (0.86–2.77), p = 0.18). Laparoscopic cases averaged 27 min longer than open cases (p < 0.001). Conclusion: Laparoscopic rectal prolapse surgery has comparable morbidity and mortality to perineal surgery. A randomized trial is indicated to validate these findings and to assess recurrence rates and functional outcomes

Surgical treatments for rectal prolapse: how does a perineal approach compare in the laparoscopic era?

BACKGROUND: Patients with rectal prolapse often have significant comorbidities that lead surgeons to select a perineal resection for treatment despite a reported higher recurrence rate over abdominal approaches. There is a lack of data to support this practice in the laparoscopic era. The objective of this study was to evaluate if risk-adjusted morbidity of perineal surgery for rectal prolapse is actually lower than laparoscopic surgery. DESIGN: A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database as performed for patients undergoing surgical treatment of rectal prolapse between 2005 and 2011. Outcomes were analyzed according to procedure-type: laparoscopic rectopexy (LR), laparoscopic resection/rectopexy (LRR), open rectopexy (OR), open resection/rectopexy (ORR), and perineal resection (PR). A multivariate logistic regression was used to compare risk-adjusted morbidity and mortality between each procedure. Main outcome measures were 30-day morbidity and mortality. RESULTS: Among 3,254 cases sampled, a laparoscopic approach was used in 22 %, an open abdominal approach in 30 %, and PR in 48 %. Patients undergoing PR were older (76) and had a higher ASA (3) compared to laparoscopic (58, 2) and open abdominal procedures (58, 2). Risk-adjusted mortality could not be assessed due to a low overall incidence of mortality (0.01 %). Overall morbidity was 9.3 %. ORR was associated with a higher risk-adjusted morbidity compared to PR (OR: 1.89 CI (1.19-2.99), p = 0.03). There were no significant differences in risk-adjusted morbidity found between LR and LRR compared to PR (OR 0.44 CI (0.19-1.03), p = 0.18; OR 1.55 CI (0.86-2.77), p = 0.18). Laparoscopic cases averaged 27 min longer than open cases (p < 0.001). CONCLUSION: Laparoscopic rectal prolapse surgery has comparable morbidity and mortality to perineal surgery. A randomized trial is indicated to validate these findings and to assess recurrence rates and functional outcomes

Repair of complex parastomal hernias.

Development of parastomal hernias (PH) is very common after stoma formation and carries a risk of subsequent bowel incarceration, obstruction and strangulation. The management of PH remains a challenge for the colorectal surgeon, and there are currently no standardized guidelines for the treatment of PH. Even more difficult is the management of complex parastomal hernias (CPH). We conducted a review of the literature to identify recent developments in the treatment of CPH, including analysis of the use of synthetic and biologic mesh prostheses, method of mesh placement and surgical approach

Risk factors for conversion of laparoscopic colorectal surgery to open surgery: Does conversion worsen outcome?

Introduction: The utilization of laparoscopy in colorectal surgery is increasing. However, conversion to open surgery remains relatively high. Objective: We evaluated (1) conversion rates in laparoscopic colorectal surgery; (2) the outcomes of converted cases compared with successful laparoscopic and open colorectal operations; (3) predictive risk factors of conversion of laparoscopic colorectal surgery to open surgery. Methods: Using the National Inpatient Sample database, we examined the clinical data of patients who underwent colon and rectal resection from 2009 to 2010. Multivariate regression analysis was performed to identify factors predictive for conversion of laparoscopic to open operation. Results: A total of 207,311 patients underwent intended laparoscopic colorectal resection during this period. The conversion rate was 16.6 %. Considering resection type and pathology, the highest conversion rates were observed in proctectomy (31.4 %) and Crohn's disease (20.2 %). Using multivariate regression analysis, Crohn's disease (adjusted odds ratio [AOR], 2.80), prior abdominal surgery (AOR, 2.45), proctectomy (AOR, 2.42), malignant pathology (AOR, 1.90), emergent surgery (AOR, 1.82), obesity (AOR, 1.63), and ulcerative colitis (AOR, 1.60) significantly impacted the risk of conversion. Compared with patients who were successfully completed laparoscopically, converted patients had a significantly higher complication rate (laparoscopic: 23 %; vs. converted: 35.2 % vs. open: 35.3 %), a higher in-hospital mortality rate (laparoscopic: 0.5 %; vs. converted: 0.6 %; vs. open: 1.7 %) and a longer mean hospital stay (laparoscopic: 5.4 days; vs. converted: 8.1 days; vs. open: 8.4 days); however, converted patients had better outcomes compared with the open group. Conclusions: The conversion rate in colorectal surgery was 16.6 %. Converted patients had significantly higher rates of morbidity and mortality compared to successfully completed laparoscopic cases, although lower than open cases. Crohn's disease, prior abdominal surgery, and proctectomy are the strongest predictors for conversion of laparoscopic to open in colorectal operations

Risk factors for conversion of laparoscopic colorectal surgery to open surgery: Does conversion worsen outcome?

Introduction: The utilization of laparoscopy in colorectal surgery is increasing. However, conversion to open surgery remains relatively high. Objective: We evaluated (1) conversion rates in laparoscopic colorectal surgery; (2) the outcomes of converted cases compared with successful laparoscopic and open colorectal operations; (3) predictive risk factors of conversion of laparoscopic colorectal surgery to open surgery. Methods: Using the National Inpatient Sample database, we examined the clinical data of patients who underwent colon and rectal resection from 2009 to 2010. Multivariate regression analysis was performed to identify factors predictive for conversion of laparoscopic to open operation. Results: A total of 207,311 patients underwent intended laparoscopic colorectal resection during this period. The conversion rate was 16.6 %. Considering resection type and pathology, the highest conversion rates were observed in proctectomy (31.4 %) and Crohn's disease (20.2 %). Using multivariate regression analysis, Crohn's disease (adjusted odds ratio [AOR], 2.80), prior abdominal surgery (AOR, 2.45), proctectomy (AOR, 2.42), malignant pathology (AOR, 1.90), emergent surgery (AOR, 1.82), obesity (AOR, 1.63), and ulcerative colitis (AOR, 1.60) significantly impacted the risk of conversion. Compared with patients who were successfully completed laparoscopically, converted patients had a significantly higher complication rate (laparoscopic: 23 %; vs. converted: 35.2 % vs. open: 35.3 %), a higher in-hospital mortality rate (laparoscopic: 0.5 %; vs. converted: 0.6 %; vs. open: 1.7 %) and a longer mean hospital stay (laparoscopic: 5.4 days; vs. converted: 8.1 days; vs. open: 8.4 days); however, converted patients had better outcomes compared with the open group. Conclusions: The conversion rate in colorectal surgery was 16.6 %. Converted patients had significantly higher rates of morbidity and mortality compared to successfully completed laparoscopic cases, although lower than open cases. Crohn's disease, prior abdominal surgery, and proctectomy are the strongest predictors for conversion of laparoscopic to open in colorectal operations