ABSTRACT
OBJECTIVES: To investigate the association between polymorphisms of DNA repair genes and xenobiotic with acute adverse effects in locally advanced rectal cancer patients treated with neoadjuvant radiochemotherapy. METHODS: Sixty-seven patients were analyzed for the current study. Genotypes in DNA repair genes XRCC1 (G28152A), XRCC3 (A4541G), XRCC3 (C18067T), RAD51 (G315C), and GSTP1 (A313G) were determined by pyrosequencing technology. RESULTS: The observed grade ≥3 acute toxicity rates were 23.8%. Chemotherapy and radiotherapy were interrupted for 46 and 14 days, respectively, due to critical complications. Four patients were hospitalized, 6 patients had been admitted to the ER, and 5 patients received invasive procedures (2 bladder catheters, 2 blood transfusions, and 1 growth factor therapy).RAD51 correlated with acute severe gastrointestinal toxicity in heterozygosity (Aa) and homozygosity (AA) (P=0.036). Grade ≥3 abdominal/pelvis pain toxicity was higher in the Aa group (P=0.017) and in the Aa+AA group (P=0.027) compared with homozygous (aa) patients. Acute skin toxicity of any grade occurred in 55.6% of the mutated patients versus 22.8% in the wild-type group (P=0.04) for RAD51. XRCC1 correlated with skin toxicity of any grade in the Aa+AA group (P=0.03) and in the Aa group alone (P=0.044). Grade ≥3 urinary frequency/urgency was significantly higher in patients with AA (P=0.01), Aa (P=0.022), and Aa+AA (P=0.031) for XRCC3 compared with aa group. CONCLUSIONS: Our study suggested that RAD51, XRCC1, and XRCC3 polymorphisms may be predictive factors for radiation-induced acute toxicity in rectal cancer patients treated with preoperative combined therapy.
Subject(s)
Adenocarcinoma/therapy , Antineoplastic Agents/therapeutic use , Chemoradiotherapy/adverse effects , Radiation Injuries/genetics , Radiotherapy, Conformal/adverse effects , Rectal Neoplasms/therapy , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Capecitabine/therapeutic use , Cystitis/etiology , Cystitis/genetics , DNA-Binding Proteins/genetics , Diarrhea/etiology , Diarrhea/genetics , Female , Fluorouracil/therapeutic use , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/genetics , Genotype , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Pelvic Pain/etiology , Pelvic Pain/genetics , Polymorphism, Single Nucleotide , Proctitis/etiology , Proctitis/genetics , Rad51 Recombinase/genetics , Radiation Injuries/etiology , Radiodermatitis/etiology , Radiodermatitis/genetics , Rectal Neoplasms/pathology , X-ray Repair Cross Complementing Protein 1/geneticsABSTRACT
Laparoscopic intersphincteric resection (ISR) after neoadjuvant chemoradiation is helpful in the management of patients with low rectal cancer. With the advent of this technique, the need for performance of abdominoperineal resection seems to have decreased in patients with very low rectal tumors. The aim of the present study was to evaluate the feasibility of laparoscopic ISR preceded by transanal rectal dissection low rectal cancer. Between December 2009 and June 2011, we performed laparoscopic ISR for 30 patients with very low rectal cancer. Patients received preoperative concurrent chemoradiation (5 days a week for 5 weeks). The surgical procedure was performed 6 weeks after radiotherapy and included total mesorectal excision, ISR, transanal coloanal anastomosis with coloplasty and loop ileostomy. Clinical data of 30 patients were analyzed retrospectively. Thirty patients (21 men, nine women) had a median age of 65 years (range, 37 to 75 years), a median body weight of 67 kg (range, 43 to 96 kg), and body mass index of 24 kg/m(2) (range, 19 to 33 kg/m(2)). The distance of the tumor from the anal verge was 5 cm (range, 2 to 11 cm). The operative time was from 240 to 360 minutes, and estimated blood loss was 100 to 520 mL. There were no conversions and no postoperative mortality. This procedure is feasible and has favorable short-term results for radical treatment of very low rectal disease while preserving anal function.
