Paul J. Speicher

The Preventive Surgical Site Infection Bundle in Colorectal Surgery An Effective Approach to Surgical Site Infection Reduction and Health Care Cost Savings

IMPORTANCE Surgical site infections (SSIs) in colorectal surgery are associated with increased morbidity and health care costs. OBJECTIVE To determine the effect of a preventive SSI bundle (hereafter bundle) on SSI rates and costs in colorectal surgery. DESIGN Retrospective study of institutional clinical and cost data. The study period was January 1, 2008, to December 31, 2012, and outcomes were assessed and compared before and after implementation of the bundle on July 1, 2011. SETTING AND PARTICIPANTS Academic tertiary referral center among 559 patients who underwent major elective colorectal surgery. MAIN OUTCOMES AND MEASURES The primary outcome was the rate of superficial SSIs before and after implementation of the bundle. Secondary outcomes included deep SSIs, organ-space SSIs, wound disruption, postoperative sepsis, length of stay, 30-day readmission, and variable direct costs of the index admission. RESULTS Of 559 patients in the study, 346 (61.9%) and 213 (38.1%) underwent their operation before and after implementation of the bundle, respectively. Groups were matched on their propensity to be treated with the bundle to account for significant differences in the preimplementation and postimplementation characteristics. Comparison of the matched groups revealed that implementation of the bundle was associated with reduced superficial SSIs (19.3% vs 5.7%, P < .001) and postoperative sepsis (8.5% vs 2.4%, P = .009). No significant difference was observed in deep SSIs, organ-space SSIs, wound disruption, length of stay, 30-day readmission, or variable direct costs between the matched groups. However, in a subgroup analysis of the postbundle period, superficial SSI occurrence was associated with a 35.5% increase in variable direct costs (

Role of Adjuvant Therapy in a Population-Based Cohort of Patients With Early-Stage Small-Cell Lung Cancer

13,253 vs

Robotic Low Anterior Resection for Rectal Cancer: A National Perspective on Short-term Oncologic Outcomes.

9779, P = .001) and a 71.7% increase in length of stay (7.9 vs 4.6 days, P < .001). CONCLUSIONS AND RELEVANCE The preventive SSI bundle was associated with a substantial reduction in SSIs after colorectal surgery. The increased costs associated with SSIs support that the bundle represents an effective approach to reduce health care costs.

Induction Therapy Does Not Improve Survival for Clinical Stage T2N0 Esophageal Cancer

PURPOSE Data on optimal adjuvant therapy after complete resection of small-cell lung cancer (SCLC) are limited, and in particular, there have been no studies evaluating the role of adjuvant chemotherapy, with or without prophylactic cranial irradiation, relative to no adjuvant therapy for stage T1-2N0M0 SCLC. This National Cancer Data Base analysis was performed to determine the potential benefits of adjuvant chemotherapy with and without prophylactic cranial irradiation in patients who undergo complete resection for early-stage small-cell lung cancer. PATIENTS AND METHODS Overall survival of patients with pathologic T1-2N0M0 SCLC who underwent complete resection in the National Cancer Data Base from 2003 to 2011, stratified by adjuvant therapy regimen, was evaluated using Kaplan-Meier and Cox proportional hazards analysis. Patients treated with induction therapy and those who died within 30 days of surgery were excluded from analysis. RESULTS Of 1,574 patients who had pT1-2N0M0 SCLC during the study period, 954 patients (61%) underwent complete R0 resection with a 5-year survival of 47%. Adjuvant therapy was administered to 59% of patients (n = 566), including chemotherapy alone (n = 354), chemoradiation (n = 190, including 99 patients who underwent cranial irradiation), and radiation alone (n = 22). Compared with surgery alone, adjuvant chemotherapy with or without radiation was associated with significantly improved survival. In addition, multivariable Cox modeling demonstrated that treatment with adjuvant chemotherapy (hazard ratio [HR], 0.78; 95% CI, 0.63 to 0.95) or chemotherapy with radiation directed at the brain (HR, 0.52; 95% CI, 0.36 to 0.75) was associated with improved survival when compared with no adjuvant therapy. CONCLUSION Patients with pT1-2N0M0 SCLC treated with surgical resection alone have worse outcomes than those who undergo resection with adjuvant chemotherapy alone or chemotherapy with cranial irradiation.

Use and Outcomes of Minimally Invasive Lobectomy for Stage I Non-Small Cell Lung Cancer in the National Cancer Data Base

Objective: This study examines short-term outcomes and pathologic surrogates of oncologic results among patients undergoing robotic versus laparoscopic low anterior resection for rectal cancer. A total of 6403 patients met inclusion criteria. Although the robotic approach required significantly fewer conversions to open, surrogates for proper oncologic surgery were nearly identical between the 2 approaches. Background: Although laparoscopic low anterior resection (LLAR) has gained popularity as an acceptable approach, the robotic low anterior resection (RLAR) remains largely unproven. We compared short-term oncologic outcomes between rectal cancer patients undergoing either RLAR or LLAR. Study Design: All patients with rectal cancer in the National Cancer Data Base undergoing RLAR or LLAR from 2010 to 2011 were included. Predictors of RLAR were modeled with multivariable logistic regression. Groups were matched on propensity to undergo RLAR. Primary endpoints included lymph node retrieval and margin status, whereas secondary 30-day outcomes were mortality, hospital length of stay (LOS), and unplanned readmission rates. Results: A total of 6403 patients met inclusion criteria, of which 956 (14.9%) underwent RLAR. RLAR patients were more likely to be treated at academic centers, receive neoadjuvant therapy, and have higher T-stage and longer time to surgery (all P < 0.001). Neoadjuvant therapy and treatment at an academic/research center remained the only significant predictors of robotic use after multivariable adjustment. After propensity matching, RLAR was associated with lower conversion (9.5 vs 16.4%, P < 0.001). There were no significant differences in lymph node retrieval, margin status, 30-day mortality, readmission, or hospital LOS. Conclusions: In this largest series to date, we demonstrated equivalent perioperative safety and patient outcomes for robotic compared to LLAR in the setting of rectal cancer. Although the robotic approach required significantly fewer conversions to open, surrogates for proper oncologic surgery were nearly identical between the 2 approaches, suggesting that a robotic approach may be a suitable alternative. Further studies comparing long-term cancer recurrence and survival should be performed.

Expectations and Outcomes in Geriatric Patients With Do-Not-Resuscitate Orders Undergoing Emergency Surgical Management of Bowel Obstruction

Introduction: This study compared survival after initial treatment with esophagectomy as primary therapy to induction therapy followed by esophagectomy for patients with clinical T2N0 (cT2N0) esophageal cancer in the National Cancer Database (NCDB). Methods: Predictors of therapy selection for patients with cT2N0 esophageal cancer in the NCDB from 1998 to 2011 were identified with multivariable logistic regression. Survival was evaluated using Kaplan-Meier and Cox proportional hazards methods. Results: Surgery was used in 42.9% (2057 of 4799) of cT2N0 patients. Of 1599 esophagectomy patients for whom treatment timing was recorded, induction therapy was used in 44.1% (688). Pretreatment staging was proven accurate in only 26.7% of patients (210 of 786) who underwent initial surgery without induction treatment and had complete pathologic data available: 41.6% (n = 327) were upstaged and 31.7% (n = 249) were downstaged. Adjuvant therapy (chemotherapy or radiation therapy) was given to 50.2% of patients treated initially with surgery who were found after resection to have nodal disease. There was no significant difference in long-term survival between strategies of primary surgery and induction therapy followed by surgery (median 41.1 versus 41.9 months, p = 0.51). In multivariable analysis, induction therapy was not independently associated with risk of death (hazard ratio [HR], 1.16, p = 0.32). Conclusions: Current clinical staging for early-stage esophageal cancer is highly inaccurate, with only a quarter of surgically resected cT2N0 patients found to have had accurate pretreatment staging. Induction therapy for patients with cT2N0 esophageal cancer in the NCDB is not associated with improved survival.

Impact of mesothelioma histologic subtype on outcomes in the Surveillance, Epidemiology, and End Results database

BACKGROUND Previous studies have raised concerns that video-assisted thoracoscopic (VATS) lobectomy may compromise nodal evaluation. The advantages or limitations of robotic lobectomy have not been thoroughly evaluated. METHODS Perioperative outcomes and survival of patients who underwent open versus minimally-invasive surgery (MIS [VATS and robotic]) lobectomy and VATS versus robotic lobectomy for clinical T1-2, N0 non-small cell lung cancer from 2010 to 2012 in the National Cancer Data Base were evaluated using propensity score matching. RESULTS Of 30,040 lobectomies, 7,824 were VATS and 2,025 were robotic. After propensity score matching, when compared with the open approach (n = 9,390), MIS (n = 9,390) was found to have increased 30-day readmission rates (5% versus 4%, p < 0.01), shorter median hospital length of stay (5 versus 6 days, p < 0.01), and improved 2-year survival (87% versus 86%, p = 0.04). There were no significant differences in nodal upstaging and 30-day mortality between the two groups. After propensity score matching, when compared with the robotic group (n = 1,938), VATS (n = 1,938) was not significantly different from robotics with regard to nodal upstaging, 30-day mortality, and 2-year survival. CONCLUSIONS In this population-based analysis, MIS (VATS and robotic) lobectomy was used in the minority of patients for stage I non-small cell lung cancer. MIS lobectomy was associated with shorter length of hospital stay and was not associated with increased perioperative mortality, compromised nodal evaluation, or reduced short-term survival when compared with the open approach. These results suggest the need for broader implementation of MIS techniques.

Mitogen-activated protein kinase (MAPK) hyperactivation and enhanced NRAS expression drive acquired vemurafenib resistance in V600E BRAF melanoma cells.

OBJECTIVE To describe the outcomes and the expected postoperative course for patients with do-not-resuscitate (DNR) orders (DNR patients) who undergo emergency surgical management of bowel obstruction. DESIGN We retrospectively identified all patients who underwent emergency surgical management of intestinal obstruction and who were classified previously as DNR using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) Participant Use Data File for 2005 through 2009. We constructed a forward stepwise multivariate logistic regression model to determine predictors of postoperative mortality. We used propensity score analysis to determine the effect of DNR status on postoperative outcomes. SETTING Institutions participating in the NSQIP. PATIENTS All patients entered in the NSQIP database. MAIN OUTCOME MEASURES Thirty-day postoperative mortality and complication rates. RESULTS We identified 242 patients who met the study criteria. Mean age was 80.9 years. Thirty-day mortality was 29.8%, with 47.1% of patients experiencing a postoperative complication. The presence of a postoperative complication was an independent predictor of postoperative mortality. Comparison of matched cohorts revealed a significantly higher postoperative mortality in DNR patients even after adjusting for comorbidities and overall complication rate. CONCLUSIONS Outcomes are poor after emergency surgical intervention for bowel obstruction in elderly DNR patients, with high postoperative complication and mortality rates. The presence of a DNR order is an independent risk factor for postoperative mortality. Patients, their families, and their physicians must be counseled on surgical expectations preoperatively and made aware of the significantly higher risks involved when a DNR order exists in the setting of emergency surgical management of bowel obstruction.

Traveling to a High-volume Center is Associated With Improved Survival for Patients With Esophageal Cancer

BACKGROUND This study was conducted to determine how malignant pleural mesothelioma (MPM) histology was associated with the use of surgery and survival. METHODS Overall survival of patients with stage I-III epithelioid, sarcomatoid, and biphasic MPM in the Surveillance, Epidemiology, and End Results database from 2004-2010 was evaluated using multivariate Cox proportional hazards models. RESULTS Of 1183 patients who met inclusion criteria, histologic subtype was epithelioid in 811 patients (69%), biphasic in 148 patients (12%), and sarcomatoid in 224 patients (19%). Median survival was 14 mo in the epithelioid group, 10 mo in the biphasic group, and 4 mo in the sarcomatoid group (P < 0.01). Cancer-directed surgery was used more often in patients with epithelioid (37%, 299/811) and biphasic (44%, 65/148) histologies as compared with patients with sarcomatoid histology (26%, 58/224; P < 0.01). Among patients who underwent surgery, median survival was 19 mo in the epithelioid group, 12 mo in the biphasic group, and 4 mo in the sarcomatoid group (P < 0.01). In multivariate analysis, surgery was associated with improved survival in the epithelioid group (hazard ratio [HR] 0.72; P < 0.01) but not in biphasic (HR 0.73; P = 0.19) or sarcomatoid (HR 0.79; P = 0.18) groups. CONCLUSIONS Cancer-directed surgery is associated with significantly improved survival for MPM patients with epithelioid histology, but patients with sarcomatoid and biphasic histologies have poor prognoses that may not be favored by operative treatment. The specific histology should be identified before treatment, so that surgery can be offered to patients with epithelioid histology, as these patients are most likely to benefit.

Improving Outcomes in Colorectal Surgery by Sequential Implementation of Multiple Standardized Care Programs

Background: The response to vemurafenib in V600E BRAF+ve melanoma is short lived due to acquisition of vemurafenib resistance. Results: NRAS expression and increased MAPK activation drive vemurafenib resistance in V600E BRAF+ve melanoma. Conclusion: Resistance to vemurafenib in melanoma is complex and can be mitigated by MAPK and NRAS inhibition. Significance: These findings could lead to improved therapy of V600E BRAF+ve melanoma by targeting MAPKs and NRAS. Although targeting the V600E activating mutation in the BRAF gene, the most common genetic abnormality in melanoma, has shown clinical efficacy in melanoma patients, response is, invariably, short lived. To better understand mechanisms underlying this acquisition of resistance to BRAF-targeted therapy in previously responsive melanomas, we induced vemurafenib resistance in two V600E BRAF+ve melanoma cell lines, A375 and DM443, by serial in vitro vemurafenib exposure. The resulting approximately 10-fold more vemurafenib-resistant cell lines, A375rVem and D443rVem, had higher growth rates and showed differential collateral resistance to cisplatin, melphalan, and temozolomide. The acquisition of vemurafenib resistance was associated with significantly increased NRAS levels in A375rVem and D443rVem, increased activation of the prosurvival protein, AKT, and the MAPKs, ERK, JNK, and P38, which correlated with decreased levels of the MAPK inhibitor protein, GSTP1. Despite the increased NRAS, whole exome sequencing showed no NRAS gene mutations. Inhibition of all three MAPKs and siRNA-mediated NRAS suppression both reversed vemurafenib resistance significantly in A375rVem and DM443rVem. Together, the results indicate a mechanism of acquired vemurafenib resistance in V600E BRAF+ve melanoma cells that involves increased activation of all three human MAPKs and the PI3K pathway, as well as increased NRAS expression, which, contrary to previous reports, was not associated with mutations in the NRAS gene. The data highlight the complexity of the acquired vemurafenib resistance phenotype and the challenge of optimizing BRAF-targeted therapy in this disease. They also suggest that targeting the MAPKs and/or NRAS may provide a strategy to mitigate such resistance in V600E BRAF+ve melanoma.