Nader N. Massarweh

Comparative effectiveness of primary tumor resection in patients with stage IV colon cancer

Although the safety of combination chemotherapy without primary tumor resection (PTR) in patients with stage IV colon cancer has been established, questions remain regarding a potential survival benefit with PTR. The objective of this study was to compare mortality rates in patients who had colon cancer with unresectable metastases who did and did not undergo PTR.

Soft tissue sarcomas: Staging principles and prognostic nomograms

Soft tissue sarcomas (STS) are a rare and heterogenous group of tumors that often represent a management challenge. The American Joint Committee on Cancer system is currently used to stage tumors and direct treatment. Limitations of the current STS staging system, future potential direction for pre‐operative staging, as well as the benefit of predictive nomograms for filling current knowledge gaps are all discussed. J. Surg. Oncol. 2015 111:532–539. Published 2014. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

A Prospective Randomized Multicenter Trial of Distal Pancreatectomy with and Without Routine Intraperitoneal Drainage

Objective: The objective of this study was to test the hypothesis that distal pancreatectomy (DP) without intraperitoneal drainage does not affect the frequency of grade 2 or higher grade complications. Background: The use of routine intraperitoneal drains during DP is controversial. Prior to this study, no prospective trial focusing on DP without intraperitoneal drainage has been reported. Methods: Patients undergoing DP for all causes at 14 high-volume pancreas centers were preoperatively randomized to placement of a drain or no drain. Complications and their severity were tracked for 60 days and mortality for 90 days. The study was powered to detect a 15% positive or negative difference in the rate of grade 2 or higher grade complications. All data were collected prospectively and source documents were reviewed at the coordinating center to confirm completeness and accuracy. Results: A total of 344 patients underwent DP with (N = 174) and without (N = 170) the use of intraperitoneal drainage. There were no differences between cohorts in demographics, comorbidities, pathology, pancreatic duct size, pancreas texture, or operative technique. There was no difference in the rate of grade 2 or higher grade complications (44% vs. 42%, P = 0.80). There was no difference in clinically relevant postoperative pancreatic fistula (18% vs 12%, P = 0.11) or mortality (0% vs 1%, P = 0.24). DP without routine intraperitoneal drainage was associated with a higher incidence of intra-abdominal fluid collection (9% vs 22%, P = 0.0004). There was no difference in the frequency of postoperative imaging, percutaneous drain placement, reoperation, readmission, or quality of life scores. Conclusions: This prospective randomized multicenter trial provides evidence that clinical outcomes are comparable in DP with or without intraperitoneal drainage.

Epidemiology of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most frequently occurring types of primary liver cancer and together are among the most common incident cancers worldwide. There are a number of modifiable and nonmodifiable HCC and ICC risk factors that have been reported. A review of the existing literature the epidemiology and risk factors for HCC and ICC was performed. There are a number of major infectious, lifestyle, metabolic, and heritable risk factors for both HCC and ICC. Some of these risk factors are either potentially preventable (eg, alcohol and tobacco use) or are currently treatable (eg hepatitis infection). In most cases, the molecular pathway or mechanism by which these etiologic factors cause primary liver cancer has not been well delineated. However, in nearly all cases, it is believed that a given risk factor causes liver injury and inflammation which results in chronic liver disease. Given the rising prevalence of several common HCC and ICC risk factors in the western world, the best opportunities for improving the care of these patients are either through the prevention of modifiable risk factors that are associated with the development of chronic liver disease or the identification of at risk patients, ensuring they are appropriately screened for the development of primary liver cancer, and initiating treatment early.

Transarterial bland versus chemoembolization for hepatocellular carcinoma: rethinking a gold standard

BACKGROUND Transarterial chemoembolization (TACE) is the most common procedure for the treatment of hepatocellular carcinoma (HCC). However, HCC is generally considered chemoresistant and data demonstrating the superiority of TACE over bland embolization (TAE) are lacking. MATERIALS AND METHODS A nationwide, retrospective cohort study of HCC patients treated with first-line TACE or TAE within the Veterans Affairs health care system (2005-2012) was performed. The primary outcome was overall survival. Risk of death by treatment type (TACE or TAE) was evaluated using multivariate (adjusted for age, presence of cirrhosis, Barcelona Clinic Liver Cancer stage, and Charlson comorbidity score) and propensity score-adjusted Cox regression. RESULTS The cohort included 405 patients treated with first-line transarterial embolization. Among these patients, 32 (7.9%) underwent TAE. Most of the patients (76.8%) had intermediate or advanced stage at presentation. Similar proportions of patients (TACE 53.3% versus TAE 43.7%; P = 0.30) received more than one embolization procedure. There was no difference in median survival (20.1 versus 23.1 mo, respectively; log-rank P = 0.84). Compared to TACE, there was no difference in risk of death associated with TAE after multivariate (hazard ratio [HR] 0.92; 95% CI, 0.61-1.37) and propensity score adjustment (HR = 0.86; 95% CI = 0.58-1.29). CONCLUSIONS There is no clear benefit associated with chemotherapy infusion over bland embolization for HCC treatment. Given the rising incidence of HCC in the United States and considering the added costs associated with TACE compared to TAE, future work comparing these competing management strategies is needed.

Complications and Failure to Rescue After Inpatient Noncardiac Surgery in the Veterans Affairs Health System

Importance The quality of surgical care in the Veterans Health Administration improved markedly in the 1990s after implementation of the Veterans Affairs (VA) National Surgical Quality Improvement Program (now called the VA Surgical Quality Improvement Program). Although there have been many recent evaluations of surgical care in the private sector, to date, a contemporary global evaluation has not been performed within the VA health system. Objective To provide a contemporaneous report of noncardiac postoperative outcomes in the VA health system during the past 15 years. Design, Setting, and Participants A retrospective cohort study was conducted using data from the VA Surgical Quality Improvement Program among veterans who underwent inpatient general, vascular, thoracic, genitourinary, neurosurgical, orthopedic, or spine surgery from October 1, 1999, through September 30, 2014. Main Outcomes and Measures Rates of 30-day morbidity, mortality, and failure to rescue (FTR) over time. Results Among 704 901 patients (mean [SD] age, 63.7 [11.8] years; 676 750 [96%] male) undergoing noncardiac surgical procedures at 143 hospitals, complications occurred in 97 836 patients (13.9%), major complications occurred in 66 816 (9.5%), FTR occurred in 12 648 of the 97 836 patients with complications (12.9%), FTR after major complications occurred in 12 223 of the 66 816 patients with major complications (18.3%), and 18 924 patients (2.7%) died within 30 days of surgery. There were significant decreases from 2000 to 2014 in morbidity (8202 of 59 421 [13.8%] vs 3368 of 32 785 [10.3%]), major complications (5832 of 59 421 [9.8%] vs 2284 of 32 785 [7%]), FTR (1445 of 8202 [17.6%] vs 351 of 3368 [10.4%]), and FTR after major complications (1388 of 5832 [23.8%] vs 343 of 2284 [15%]) (trend test, P < .001 for all). Although there were no clinically meaningful differences in rates of complications and major complications across hospital risk-adjusted mortality quintiles (any complications: lowest quintile, 20 945 of 147 721 [14.2%] vs highest quintile, 18 938 of 135 557 [14%]; major complications: lowest quintile, 14 044 of 147 721 [9.5%] vs highest quintile, 12 881 of 135 557 [9.5%]), FTR rates (any complications: lowest quintile, 2249 of 20 945 [10.7%] vs highest quintile, 2769 of 18 938 [14.6%]; major complications: lowest quintile, 2161 of 14 044 [15.4%] vs highest quintile, 2663 of 12 881 [20.7%]) were significantly higher with increasing quintile (P < .001). However, across hospital quintiles, there were significant decreases in morbidity (20.6%-29.9% decrease; trend test, P < .001 for all) and FTR (29.2%-50.6% decrease; trend test, P < .001 for all) during the study period. After hierarchical modeling, the odds of postoperative mortality, FTR, and FTR after a major complication were approximately 40% to 50% lower in the most recent study year compared with 15 years ago (P < .001 for all). Conclusions and Relevance For the past 15 years, morbidity, mortality, and FTR have improved within the VA health system. Other integrated health systems providing a high volume of surgical care for their enrollees may benefit by critically evaluating the system-level approaches of the VA health system to surgical quality improvement.

The role of surgery and adjuvant therapy in lymph node‐positive cancers of the gallbladder and intrahepatic bile ducts

Lymph node metastasis is a poor prognostic factor for biliary tract cancers (BTCs). The optimal management of patients who have BTC with positive regional lymph nodes, including the impact of surgery and adjuvant therapy (AT), is unclear.

Management of Stage I Squamous Cell Carcinoma of the Anal Canal

Importance The incidence of squamous cell carcinoma of the anal canal (SCCAC) is increasing. Although standard management of SCCAC includes the use of concurrent chemotherapy and radiotherapy (chemoradiotherapy), data are lacking on potentially less morbid, alternative management strategies, such as local excision, among patients with node-negative T1 disease. Objectives To examine the use of local excision among patients with T1 SCCAC and to compare overall survival relative to those who received standard treatment with chemoradiotherapy. Design, Setting, and Participants This retrospective cohort study assessed 2243 patients in the National Cancer Database (2004-2012) between 18 and 80 years of age with T1N0M0 SCCAC. The association between the type of treatment received and overall risk of death was evaluated using multivariable Cox proportional hazards regression models. Data analysis was performed from June 29, 2016, to April 17, 2017. Main Outcomes and Measures Overall survival. Results Among 2243 patients with T1N0 SCCAC, 503 (22.4%) were treated with local excision alone (mean [SD] age, 54.5 [12.1] years; 240 [47.7%] male; 419 [83.3%] white) and 1740 with chemoradiotherapy (mean [SD] age, 57.0 [10.6] years; 562 [32.3%] male; 1547 [88.9%] white). Among those treated with chemoradiotherapy, 12 patients underwent a subsequent abdominoperineal resection. There was a statistically significant increase in the use of local excision during the study period (34 [17.3%] in 2004 to 68 [30.8%] in 2012; trend test, P < .001). This increase in use was observed among patients with primary tumors that measured 1 cm or smaller and greater than 1 cm to 2 cm or smaller (trend test, P < .001 for both). Overall survival at 5 years was not significantly different for the 2 management strategies (85.3% in the local excision cohort and 86.8% in the chemoradiotherapy cohort; log-rank test, P = .93). Overall risk of death was not significantly different for local excision alone relative to that for treatment with chemoradiotherapy (hazard ratio, 1.06; 95% CI, 0.78-1.44). These findings were robust when stratified by tumor size and when patients who underwent abdominoperineal resection after chemoradiotherapy were excluded. Conclusions and Relevance The use of local excision alone for the management of T1N0 SCCAC has significantly increased over time, with no clear decrement in overall survival. Because local excision may represent a lower-cost, less morbid treatment option for select patients with SCCAC, future studies are needed to better delineate its role and efficacy relative to the current standard of chemoradiotherapy.

Post-embolization syndrome as an early predictor of overall survival after transarterial chemoembolization for hepatocellular carcinoma

BACKGROUND Transarterial chemoembolization (TACE) is the most common treatment for patients with unresectable hepatocellular carcinoma (HCC). Post-embolization syndrome (PES) is a common post-TACE complication. The goal of this study was to evaluate PES as an early predictor of the long-term outcome. METHODS A retrospective cohort study of HCC patients treated with TACE at a tertiary referral centre was performed (2008-2014). Patients were categorized on the basis of PES, defined as fever with or without abdominal pain within 14 days of TACE. The primary outcome was overall survival (OS). Multivariate Cox regression was done to examine the association between PES and OS. RESULTS Among 144 patients, 52 (36.1%) experienced PES. The median follow-up for the cohort was 11.4 months. The median and 3-year OS rates were 16 months and 18% in the PES group versus 25 months and 41% in the non-PES group (log rank, P = 0.027). After multivariate analysis, patients with PES had a significantly increased risk of death [hazard ratio 2.0 (95%CI 1.2-3.3), P = 0.011]. CONCLUSIONS PES is a common complication after TACE and is associated with a two-fold increased risk of death. Future studies should incorporate PES as a relevant early predictor of OS and examine the biological basis of this association.

Association of the Addition of Oral Antibiotics to Mechanical Bowel Preparation for Left Colon and Rectal Cancer Resections With Reduction of Surgical Site Infections

Importance Surgical site infections (SSIs) after colorectal surgery remain a significant complication, particularly for patients with cancer, because they can delay the administration of adjuvant therapy. A combination of oral antibiotics and mechanical bowel preparation (MBP) is a potential, yet controversial, SSI prevention strategy. Objective To determine the association of the addition of oral antibiotics to MBP with preventing SSIs in left colon and rectal cancer resections and its association with the timely administration of adjuvant therapy. Design, Setting, and Participants A retrospective review was performed of 89 patients undergoing left colon and rectal cancer resections from October 1, 2013, to December 31, 2016, at a single institution. A bowel regimen of oral antibiotics and MBP (neomycin sulfate, metronidazole hydrochloride, and magnesium citrate) was implemented August 1, 2015. Patients receiving MBP and oral antibiotics and those undergoing MBP without oral antibiotics were compared using univariate analysis. Multivariable logistic regression controlling for factors that may affect SSIs was used to evaluate the association between use of oral antibiotics and MBP and the occurrence of SSIs. Main Outcomes and Measures Surgical site infections within 30 days of the index procedure and time to adjuvant therapy. Results Of the 89 patients (5 women and 84 men; mean [SD] age, 65.3 [9.2] years) in the study, 49 underwent surgery with MBP but without oral antibiotics and 40 underwent surgery with MBP and oral antibiotics. The patients who received oral antibiotics and MBP were younger than those who received only MBP (mean [SD] age, 62.6 [9.1] vs 67.5 [8.8] years; P = .01), but these 2 cohorts of patients were otherwise similar in baseline demographic, clinical, and cancer characteristics. Surgical approach (minimally invasive vs open) and case type were similarly distributed; however, the median operative time of patients who received oral antibiotics and MBP was longer than that of patients who received MBP only (391 minutes [interquartile range, 302-550 minutes] vs 348 minutes [interquartile range, 248-425 minutes]; P = .03). The overall SSI rate was lower for patients who received oral antibiotics and MBP than for patients who received MBP only (3 [8%] vs 13 [27%]; P = .03), with no deep or organ space SSIs or anastomotic leaks in patients who received oral antibiotics and MBP compared with 9 organ space SSIs (18%; P = .004) and 5 anastomotic leaks (10%; P = .06) in patients who received MBP only. Despite this finding, there was no difference in median days to adjuvant therapy between the 2 cohorts (60 days [interquartile range, 46-73 days] for patients who received MBP only vs 72 days [interquartile range, 59-85 days] for patients who received oral antibiotics and MBP; P = .13). Oral antibiotics and MBP (odds ratio, 0.11; 95% CI, 0.02-0.86; P = .04) and minimally invasive surgery (odds ratio, 0.22; 95% CI, 0.05-0.89; P = .03) were independently associated with reduced odds of SSIs. Conclusions and Relevance The combination of oral antibiotics and MBP is associated with a significant decrease in the rate of SSIs and should be considered for patients undergoing elective left colon and rectal cancer resections.