Daniel P. Nussbaum

Preoperative or postoperative radiotherapy versus surgery alone for retroperitoneal sarcoma: a case-control, propensity score-matched analysis of a nationwide clinical oncology database

BACKGROUND Recruitment into clinical trials for retroperitoneal sarcoma has been challenging, resulting in termination of the only randomised multicentre trial in the USA investigating perioperative radiotherapy. Nonetheless, use of radiotherapy for retroperitoneal sarcoma has increased over the past decade, substantiated primarily by its established role in extremity sarcoma. In this study, we used a nationwide clinical oncology database to separately compare overall survival for patients with retroperitoneal sarcoma who had surgery and preoperative radiotherapy or surgery and postoperative radiotherapy versus surgery alone. METHODS We did two case-control, propensity score-matched analyses of the National Cancer Data Base, which included adult patients with retroperitoneal sarcoma who were diagnosed from 2003 to 2011. Patients were included if they had localised, primary retroperitoneal sarcoma. Patients were classified into three groups based on use of radiotherapy: preoperative radiotherapy, postoperative radiotherapy, and no radiotherapy (surgery alone). Patients were excluded if they received both preoperative radiotherapy and postoperative radiotherapy, or if they received intraoperative radiotherapy. Parallel propensity score-matched datasets were created for patients who received preoperative radiotherapy versus those who received no radiotherapy and for patients who received postoperative therapy versus those who received no radiotherapy. Propensity scores were calculated with logistic regression, with multiple imputation and backwards elimination, with a significance level to stay of 0·05. Matching was done with a nearest-neighbour algorithm and matched 1:2 for the preoperative radiotherapy dataset and 1:1 for the postoperative radiotherapy dataset. The primary objective of interest was overall survival for patients who received preoperative radiotherapy or postoperative radiotherapy compared with those who received no radiotherapy within the propensity score-matched datasets. FINDINGS 9068 patients were included in this analysis: 563 in the preoperative radiotherapy group, 2215 in the postoperative radiotherapy group, and 6290 in the no radiotherapy group. Matching resulted in two comparison groups (preoperative radiotherapy vs no radiotherapy, and postoperative radiotherapy vs no radiotherapy) with negligible differences in all demographic, clinicopathological, and treatment-level variables. In the matched case-control analysis for preoperative radiotherapy median follow-up time was 42 months (IQR 27-70) for the preoperative radiotherapy group versus 43 months (25-64) for the no radiotherapy group; median overall survival was 110 months (95% CI 75-not estimable) versus 66 months (61-76), respectively. In the matched case-control analysis for postoperative radiotherapy median follow-up time was 54 months (IQR 32-79) for patients in the postoperative radiotherapy group and 47 months (26-72) for patients in the no radiotherapy group; median overall survival was 89 months (95% CI 79-100) versus 64 months (59-69), respectively. Both preoperative radiotherapy (HR 0·70, 95% CI 0·59-0·82; p<0·0001) and postoperative radiotherapy (HR 0·78, 0·71-0·85; p<0·0001) were significantly associated with improved overall survival compared with surgery alone. INTERPRETATION To the best of our knowledge, this is the largest study to date of the effect of radiotherapy on overall survival in patients with retroperitoneal sarcoma. Radiotherapy was associated with improved overall survival compared with surgery alone when delivered as either preoperative radiotherapy or postoperative radiotherapy. Together with the results from the ongoing randomised EORTC trial (62092-22092; NCT01344018) investigating preoperative radiotherapy for retroperitoneal sarcoma pending, these data might provide additional support for the increasing use of radiotherapy for patients with retroperitoneal sarcoma undergoing surgical resection. FUNDING Department of Surgery, Duke University School of Medicine.

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

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.

Thoracic Duct Ligation for Persistent Chylothorax After Pediatric Cardiothoracic Surgery

BACKGROUND There is considerable literature on incidence and medical management of postsurgical chylothorax in children but little is known about outcomes of thoracic duct ligation (TDL) for patients refractory to medical therapy. METHODS A retrospective review of patients undergoing TDL after cardiothoracic surgery (1992 through 2007) was done. Data on demographics including cardiac morphology, characteristics of chylous drainage, medical management, and post-TDL course were collected. When available, imaging studies of the upper body venous drainage vessels were examined. RESULTS Twenty patients (median age, 0.65 years; range, 0.03 to 11 years; weight, 7.0 kg; range, 2.6 to 30 kg) had a diagnosis of chylothorax made 8.5 days (range, 2 to 118 days) after initial operation. Median duration of pre-TDL medical management was 17.5 days (range, 7 to 69 days). Median drainage for 5 days preceding TDL was 34.5 mL x kg(-1) x d(-1) (range, 15 to 135 mL x kg(-1) x d(-1)) with maximal output of 65 mL x kg(-1) x d(-1) (range, 30 to 200 mL x kg(-1) x d(-1)). After TDL, there was a decrease in median drainage to 13 mL x kg(-1) x d(-1) (range, 4 to 160 mL x kg(-1) x d(-1); p = 0.003). Chest tubes were removed 8.5 days (range, 4 to 34 days) after TDL. There were 4 deaths (none attributed to TDL), 2 treatment failures (post-TDL chest tube drainage > 2 mL x kg(-1) x d(-1) > 14 days), and 2 recurrences (after initial chylothorax resolution and hospital discharge). Three patients had documented upper body venous thrombosis. Univariate analysis demonstrated thrombosis of upper body venous vessels (p = 0.02) and prolonged post-TDL chest tube drainage (p = 0.01) were risk factors for death, treatment failure, or chylothorax recurrence. CONCLUSIONS Thoracic duct ligation leads to a major reduction in chest tube drainage and prompt tube removal in most pediatric patients and should be considered early in refractory postoperative chylothorax. Patients with upper body venous thrombosis associated with chylothorax are at a high risk for failure of TDL and mortality.

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

BACKGROUND The purpose of this study was to examine the impact of the sequential implementation of the enhanced recovery program (ERP) and surgical site infection bundle (SSIB) on short-term outcomes in colorectal surgery (CRS) to determine if the presence of multiple standardized care programs provides additive benefit. STUDY DESIGN Institutional ACS-NSQIP data were used to identify patients who underwent elective CRS from September 2006 to March 2013. The cohort was stratified into 3 groups relative to implementation of the ERP (February 1, 2010) and SSIB (July 1, 2011). Unadjusted characteristics and 30-day outcomes were assessed, and inverse proportional weighting was then used to determine the adjusted effect of these programs. RESULTS There were 787 patients included: 337, 165, and 285 in the pre-ERP/SSIB, post-ERP/pre-SSIB, and post-ERP/SSIB periods, respectively. After inverse probability weighting (IPW) adjustment, groups were balanced with respect to patient and procedural characteristics considered. Compared with the pre-ERP/SSIB group, the post-ERP/pre-SSIB group had significantly reduced length of hospitalization (8.3 vs 6.6 days, p = 0.01) but did not differ with respect to postoperative wound complications and sepsis. Subsequent introduction of the SSIB then resulted in a significant decrease in superficial SSI (16.1% vs 6.3%, p < 0.01) and postoperative sepsis (11.2% vs 1.8%, p < 0.01). Finally, inflation-adjusted mean hospital cost for a CRS admission fell from

Laparoscopic versus open low anterior resection for rectal cancer: results from the national cancer data base.

31,926 in 2008 to

Long-term Oncologic Outcomes After Neoadjuvant Radiation Therapy for Retroperitoneal Sarcomas

22,044 in 2013 (p < 0.01). CONCLUSIONS Sequential implementation of the ERP and SSIB provided incremental improvements in CRS outcomes while controlling hospital costs, supporting their combined use as an effective strategy toward improving the quality of patient care.

Going the Extra Mile: Improved Survival for Pancreatic Cancer Patients Traveling to High-volume Centers

BackgroundWhile the use of laparoscopy has increased among patients undergoing colorectal surgery, there is ongoing debate regarding the oncologic equivalence of laparoscopy compared to open low anterior resection (LAR) for rectal cancer.MethodsThe 2010–2011 NCDB was queried for patients undergoing LAR for rectal cancer. Subjects were grouped by laparoscopic (LLAR) versus open (OLAR) technique. Baseline characteristics were compared. Subjects were propensity matched, and outcomes were compared between groups.ResultsA total of 18,765 patients were identified (34.3 % LLAR, 65.7 % OLAR). After propensity matching, all baseline variables were highly similar except for carcinoembryonic antigen (CEA) level. Complete resection was more common in patients undergoing LLAR (91.6 vs. 88.9 %, p < 0.001), and statistically significant benefits were observed for gross, microscopic, and circumferential (>1 mm) margins (all p < 0.001). There was no difference in median number of lymph nodes obtained (15 vs. 15). Patients undergoing LLAR had shorter lengths of stay (5 vs. 6 days, p < 0.001) without a corresponding increase in 30-day readmission rates (6 vs. 7 %, p = 0.02).ConclusionsLaparoscopic LAR appears to result in equivalent short-term oncologic outcomes compared to the traditional open approach as measured via surrogate endpoints in the NCDB. While these results support the increasing use of laparoscopy in rectal surgery, further data are necessary to assess long-term outcomes.

Analysis of perioperative radiation therapy in the surgical treatment of primary and recurrent retroperitoneal sarcoma.

OBJECTIVE To evaluate long-term survival among patients undergoing radiation therapy (RT), followed by surgical resection of retroperitoneal sarcomas (RPS). BACKGROUND Despite a lack of level 1 evidence supporting neoadjuvant RT for RPS, its use has increased substantially over the past decade. METHODS The 1998-2011 National Cancer Data Base was queried to identify patients who underwent resection of RPS. Subjects were grouped by use of neoadjuvant RT. Perioperative variables and outcomes were compared. Multivariable logistic regression was performed to assess predictors of neoadjuvant RT. Groups were propensity matched using a 2:1 nearest neighbor algorithm and short-term outcomes were compared. Finally, long-term survival was evaluated using the Kaplan-Meier method, with comparisons based on the log-rank test. RESULTS A total of 11,324 patients were identified. Neoadjuvant RT was administered to 696 patients (6.1%). During the study period, preoperative RT use increased from 4% to nearly 15%. Male sex, tumor size larger than 5 cm, treatment at an academic/research program, and higher tumor grade all predicted neoadjuvant RT administration. After propensity matching, the only difference in baseline characteristics was the use of neoadjuvant chemotherapy. Although neoadjuvant RT was associated with a higher rate of negative margins (77.5% vs 73.0%; P = 0.014), there was no corresponding improvement in 5-year survival (53.2% vs 54.2%; P = 0.695). CONCLUSIONS Despite the increasing use of neoadjuvant RT for patients with RPS, the survival benefit associated with this treatment modality remains unclear. Continued investigation is needed to better define the role of RT among patients with RPS.

Minimally Invasive Versus Open Low Anterior Resection: Equivalent Survival in a National Analysis of 14,033 Patients With Rectal Cancer.

Objective: This study compares outcomes following pancreaticoduodenectomy (PD) for patients treated at local, low-volume centers and those traveling to high-volume centers. Background: Although outcomes for PD are superior at high-volume institutions, not all patients live in proximity to major medical centers. Theoretical advantages for undergoing surgery locally exist. Methods: The 1998 to 2012 National Cancer Data Base was queried for T1–3N0–1M0 pancreatic adenocarcinoma patients who underwent PD. Travel distances to treatment centers were calculated. Overlaying the upper and lower quartiles of travel distance with institutional volume established short travel/low-volume (ST/LV) and long travel/high-volume (LT/HV) cohorts. Overall survival was evaluated. Results: Of 7086 patients, 773 ST/LV patients traveled ⩽6.3 (median 3.2) miles to centers performing ⩽3.3 PDs yearly, and 758 LT/HV patients traveled ≥45 (median 97.3) miles to centers performing ≥16 PDs yearly. LT/HV patients had higher stage disease (P < 0.001), but lower margin positivity (20.5% vs 25.9%, P = 0.01) and improved lymphadenectomy (16 vs 11 nodes, P < 0.01). Moreover, LT/HV patients had shorter hospitalizations (9 vs 12 days, P < 0.01) and lower 30-day mortality (2.0% vs 6.3%, P < 0.01) with similar 30-day readmission rates (10.1% vs 9.8%, P = 0.83). Despite more advanced disease, LT/HV patients had superior unadjusted survival (20.3 vs 15.7 months). After adjustment, travel to a high-volume center remained associated with reduced long-term mortality (hazard ratio 0.75, P < 0.01). Conclusions: Despite an increased travel burden, patients treated at high-volume centers had improved perioperative outcomes, short-term mortality, and overall survival. These data support ongoing efforts to centralize care for patients undergoing PD.

Ureteral stenting in laparoscopic colorectal surgery

Radiation therapy (RT) is increasingly utilized in conjunction with surgery for the treatment of retroperitoneal soft tissue sarcomas (RPS). Despite multiple theoretical advantages of RT, its role in the surgical management of this disease remains ill defined.