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Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer

Myerson, Robert J; Tan, Benjamin; Hunt, Steven; Olsen, Jeffrey; Birnbaum, Elisa; Fleshman, James; Gao, Feng; Hall, Lannis; Kodner, Ira; Lockhart, A Craig; Mutch, Matthew; Naughton, Michael; Picus, Joel; Rigden, Caron; Safar, Bashar; Sorscher, Steven; Suresh, Rama; Wang-Gillam, Andrea; Parikh, Parag
BACKGROUND:Preoperative radiation therapy with 5-fluorouracil chemotherapy is a standard of care for cT3-4 rectal cancer. Studies incorporating additional cytotoxic agents demonstrate increased morbidity with little benefit. We evaluate a template that: (1) includes the benefits of preoperative radiation therapy on local response/control; (2) provides preoperative multidrug chemotherapy; and (3) avoids the morbidity of concurrent radiation therapy and multidrug chemotherapy. METHODS AND MATERIALS/METHODS:Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed to be candidates for pelvic surgery, provided response was sufficient. Preoperative treatment was 5 fractions radiation therapy (25 Gy to involved mesorectum, 20 Gy to elective nodes), followed by 4 cycles of FOLFOX [5-fluorouracil, oxaliplatin, leucovorin]. Extirpative surgery was performed 4 to 9 weeks after preoperative chemotherapy. Postoperative chemotherapy was at the discretion of the medical oncologist. The principal objectives were to achieve T stage downstaging (ypT < cT) and preoperative grade 3+ gastrointestinal morbidity equal to or better than that of historical controls. RESULTS:76 evaluable cases included 7 cT4 and 69 cT3; 59 (78%) cN+, and 7 cM1. Grade 3 preoperative GI morbidity occurred in 7 cases (9%) (no grade 4 or 5). Sphincter-preserving surgery was performed on 57 (75%) patients. At surgery, 53 patients (70%) had ypT0-2 residual disease, including 21 (28%) ypT0 and 19 (25%) ypT0N0 (complete response); 24 (32%) were ypN+. At 30 months, local control for all evaluable cases and freedom from disease for M0 evaluable cases were, respectively, 95% (95% confidence interval [CI]: 89%-100%) and 87% (95% CI: 76%-98%). Cases were subanalyzed by whether disease met requirements for the recently activated PROSPECT trial for intermediate-risk rectal cancer. Thirty-eight patients met PROSPECT eligibility and achieved 16 ypT0 (42%), 15 ypT0N0 (39%), and 33 ypT0-2 (87%). CONCLUSION/CONCLUSIONS:This regimen achieved response and morbidity rates that compare favorably with those of conventionally fractionated radiation therapy and concurrent chemotherapy.
PMCID:4028157
PMID: 24606849
ISSN: 1879-355x
CID: 5272122

Accordion complication grading predicts short-term outcome after right colectomy

Klos, Coen L; Safar, Bashar; Hunt, Steven R; Wise, Paul E; Birnbaum, Elisa H; Mutch, Matthew G; Fleshman, James W; Dharmarajan, Sekhar
BACKGROUND:The Accordion severity grading system is a novel system to score the severity of postoperative complications in a standardized fashion. This study aims to demonstrate the validity of the Accordion system in colorectal surgery by correlating severity grades with short-term outcomes after right colectomy for colon cancer. METHODS:This is a retrospective cohort review of patients who underwent right colectomy for cancer between January 1, 2002, and January 31, 2007, at a single tertiary care referral center. Complications were categorized according to the Accordion severity grading system: grades 1 (mild), 2 (moderate), 3-5 (severe), and 6 (death). Outcome measures were hospital stay, 30-d readmission rate and 1-y survival. Correlation between Accordion grades and outcome measures is reflected by Spearman rho (ρ). One-year survival was obtained per Kaplan-Meier method and compared by logrank test for trend. Significance was set at P ≤ 0.05. RESULTS:Overall, 235 patients underwent right colectomy for cancer of which 122 (51.9%) had complications. In total, 52 (43%) had an Accordion grade 1 complication; 44 (36%) grade 2; four (3%) grade 3; 11 (9%) grade 4; seven (6%) grade 5; and four (3%) grade 6. There was significant correlation between Accordion grades and hospital stay (ρ = 0.495, P < 0.001) and 30-d readmission rate (ρ = 0.335, P < 0.001). There was a significant downward trend in 1-y survival as complication severity by Accordion grade increased (P = 0.02). CONCLUSIONS:The Accordion grading system is a useful tool to estimate short-term outcomes after right colectomy for cancer. High-grade Accordion complications are associated with longer hospital stay and increased risk of readmission and mortality.
PMID: 24485152
ISSN: 1095-8673
CID: 5272112

Segmental versus extended resection for sporadic colorectal cancer in young patients

Klos, Coen L; Montenegro, Grace; Jamal, Nida; Wise, Paul E; Fleshman, James W; Safar, Bashar; Dharmarajan, Sekhar
BACKGROUND AND OBJECTIVES/OBJECTIVE:Guidelines on the management of colon cancer state that extensive colectomy should be "considered" for patients of young age (<50). This study aimed to compare the risk of metachronous cancer, overall recurrence and mortality between segmental and extended colon resections in patients under the age of 50 with sporadic CRC. METHODS:We performed a retrospective review of patients age <50 undergoing surgery for CRC from 1991 to 2009. Patients were divided into two groups based on extent of resection: segmental versus extended. The primary outcomes analyzed were metachronous tumors, disease recurrence, and overall survival. RESULTS:Two hundred seventy one patients underwent segmental resection and 30 underwent extended resection. 3.3% in the segmental resection group developed metachronous CRC versus 0% in the extended resection group (P = 0.61). There was no significant difference in the risk of recurrence or mortality for those who underwent a segmental resection compared to those with an extended resection. In a regression model, type of surgery was not an independent risk factor for recurrence or mortality. CONCLUSIONS:Extended colectomy for sporadic CRC in patients younger than 50 does not improve disease-free or overall survival. Further study to determine if segmental resection is appropriate oncologic treatment is warranted.
PMID: 24888987
ISSN: 1096-9098
CID: 5272132

Atlas of surgical techniques for the colon, rectum, and anus

Fleshman, James; Birnbaum, Elisa H; Hunt, Steven R; Mutch, Matthew G; Kodner, Ira J; Safar, Bashar
Philadelphia, PA : Elsevier/Saunders, c2013
Extent: xii, 412 p.
ISBN: 9781416052227
CID: 5339932

Management of radiation proctitis

Sarin, Ankit; Safar, Bashar
Radiation damage to the rectum following radiotherapy for pelvic malignancies can range from acute dose-limiting side effects to major morbidity affecting health-related quality of life. No standard guidelines exist for diagnosis and management of radiation proctitis. This article reviews the definitions, staging, and clinical features of radiation proctitis, and summarizes the modalities available for the treatment of acute and chronic radiation proctitis. Because of the paucity of well-controlled, blinded, randomized studies, it is not possible to fully assess the comparative efficacy of the different approaches to management. However, the evidence and rationale for use of the different strategies are presented.
PMID: 24280407
ISSN: 1558-1942
CID: 5272102

Is an elective diverting colostomy warranted in patients with an endoscopically obstructing rectal cancer before neoadjuvant chemotherapy?

Patel, Jitesh A; Fleshman, James W; Hunt, Steven R; Safar, Bashar; Birnbaum, Elisa H; Lin, Anne Y; Mutch, Matthew G
BACKGROUND:Many surgeons prefer immediate diversion in patients with endoscopically obstructed rectal cancer before starting neoadjuvant chemotherapy. OBJECTIVE:The aim of this study was to compare immediate neoadjuvant chemoradiotherapy with diversion for endoscopically obstructed rectal cancer. DESIGN/METHODS:This study is a retrospective review of patients with rectal adenocarcinoma treated from January 2000 to December 2009. Demographic, tumor, treatment, and outcome data were obtained. Data were analyzed by the use of the Fisher exact probability test and the Student t test. SETTINGS/METHODS:This study was conducted at a tertiary care hospital/referral center. PATIENTS/METHODS:Included were patients with a rectal adenocarcinoma unable to be traversed endoscopically but without clinical evidence of obstruction before the initiation of neoadjuvant chemoradiotherapy. Patients with recurrent tumors or those who did not complete neoadjuvant chemoradiotherapy because of compliance were excluded. MAIN OUTCOME MEASURES/METHODS:The primary outcomes measured were the interval from diagnosis to neoadjuvant chemoradiotherapy initiation and resection and the incidence of complete obstruction. RESULTS:Eighty-five patients with endoscopically obstructed rectal cancer were identified; 16 underwent immediate diversion before neoadjuvant chemoradiotherapy (diverted group) and 69 were treated with immediate neoadjuvant chemoradiotherapy. Five patients undergoing immediate neoadjuvant chemoradiotherapy presented with bloating and distension; 2 were treated with dietary modification, and 3 (4.3%) progressed to complete obstruction following completion of neoadjuvant chemoradiotherapy and required diversion. Both groups were similar in age, tumor height, and surgical margin status. Patients undergoing diversion required a significantly greater number of permanent stomas and were associated with a higher rate of radical pelvic surgery. There was a significant delay in the initiation of neoadjuvant chemoradiotherapy (p < 0.05) and proctectomy (p < 0.001) from the time of diagnosis in the diverted group compared with the immediate neoadjuvant chemoradiotherapy group. The tumors of patients undergoing diversions were more likely to be unresectable following neoadjuvant chemoradiotherapy. LIMITATIONS/CONCLUSIONS:This study was limited by its retrospective design and possible selection bias. CONCLUSIONS:Immediate diversion is unnecessary in endoscopically obstructed rectal cancer without clinical signs of obstruction. There appears to be a relationship between immediate diversion and delay in initiation of neoadjuvant chemoradiotherapy and proctectomy. We conclude that immediate neoadjuvant chemoradiotherapy in patients with endoscopically obstructed rectal cancer is safe and feasible.
PMID: 22469790
ISSN: 1530-0358
CID: 5272082

1.5:1 meshed AlloDerm bolsters for stapled rectal anastomoses does not provide any advantage in anastomotic strength in a porcine model

Fajardo, Alyssa D; Chun, Jonathan; Stewart, David; Safar, Bashar; Fleshman, James W
INTRODUCTION/BACKGROUND:The most feared complication of colorectal anastomoses is leaks resulting in severe morbidity. The concept of staple-line reinforcement is a growing area of interest. In this study, the authors evaluated the feasibility and effect of using 1.5:1 meshed AlloDerm to bolster end-to-end stapled rectal anastomoses in a porcine model. METHODS:A total of 30 female 45-kg domestic pigs were studied, and each served as its own control by creating a bolstered and unbolstered anastomosis in each animal. All anastomoses were created with a 29-mm end-to-end stapling device. Bolstered anastomoses were randomized to proximal and distal positions along the rectum, and each rectorectal anastomosis was separated by an average of 10 cm. The animals were survived to 3, 5, and 30 days. Barium enemas were then performed and the 2 anastomotic sites harvested. Each anastomosis underwent burst testing. The internal diameter of each anastomosis was measured, and a biochemical analysis was performed for elastin and collagen content. RESULTS:Bolstered anastomoses offered no strength advantage as burst pressures were no different when compared with unbolstered anastomoses. There was also no difference in anastomotic internal diameter, biochemical analysis of elastin or collagen, or presence of adhesions when comparing bolstered with unbolstered anastomoses. There were 4 subclinical leaks-1 in the unbolstered group and 3 in the bolstered group. CONCLUSIONS:The routine use of 1.5:1 meshed AlloDerm sandwich bolsters in stapled rectal anastomosis does not confer any detectable advantage in anastomotic strength. Further studies are needed to determine equivalence to traditional stapled anastomoses.
PMID: 20542954
ISSN: 1553-3514
CID: 5272072

Surgical management of pyogenic complications of Crohn's disease

Cellini, Christina; Safar, Bashar; Fleshman, James
Patients with Crohn's disease are prone to the development of pyogenic complications. These complications are most commonly in the form of perianal or intraabdominal abscesses and/or fistulas. Complications in these 2 distinct areas are managed differently; however, they are similar in the fact that initial treatment relies on medical or minimally invasive management to achieve a nonacute condition prior to definitive surgical procedure. This article reviews the current surgical management of obtaining pyogenic control in both anorectal and intraabdominal Crohn's disease.
PMID: 20049952
ISSN: 1536-4844
CID: 5272062

Laparoscopic Total Mesorectal Excision for Rectal Cancer

Safar, Bashar; Fleshman, James
ISI:000421940300004
ISSN: 1043-1489
CID: 5272602

Laproscopic resection for carcinoma of the rectum

Chapter by: Safar, Bashar; Wexner, SD
in: Mastery of endoscopic and laparoscopic surgery by Soper, Nathaniel J; Swanstrom, Lee L; Eubanks, Steve [Eds]
pp. -
ISBN: 9780781771986
CID: 5339942