Definitive radiotherapy for squamous cell carcinoma of the anal canal.

PURPOSE: To review the outcomes of definitive radiotherapy (RT) alone or combined with chemotherapy (CT) in the treatment of squamous cell carcinoma of the anal canal. METHODS: Between November 1968 and June 2005, 69 patients were treated with curative intent at the University of Florida. Distribution according to T stage was: T1, 11 (16%); T2, 29 (42%); T3, 21 (30%); and T4, 8 (12%). Distribution according to N stage was: N0, 53 (77%); N1, 3 (4%); N2, 7 (10%); and N3, 6 (9%). RT consisted of external beam RT (EBRT) in 30 patients (43%) and EBRT plus brachytherapy in 39 patients (57%). Thirty-eight patients (55%) received adjuvant CT: mitomycin C and fluorouracil, 21 patients (30%); cisplatin plus fluorouracil, 16 patients (23%); and other, 1 patient (1%). Median follow-up for all patients was 7.9 years (range: 0.1-17.3 years). One patient who was disease-free was lost to follow-up at 129 months. RESULTS: The 5-year local control rates were: T1, 100%; T2, 93%; T3, 70%; T4, 88%; and overall, 86%. The 5-year regional control rates were: N0, 96%; N1 and N2, 89%; N3, 100%; and overall, 96%. The 5-year colostomy-free survival rates were: T1, 82%; T2, 89%; T3, 65%; T4, 38%; and overall, 74%. The 5-year cause-specific and overall survival rates were: stage I, 100% and 64%; stage II, 86% and 70%; stage III, 80% and 76%; and overall, 87% and 71%, respectively. Seven patients (10%) developed Radiation Therapy Oncology Group grade 3 late complications and 4 additional patients (6%) experienced grade 4 late complications. A fatal acute complication occurred in 1 patient (1%). CONCLUSION: The likelihood of cure and colostomy-free survival after EBRT alone or combined with brachytherapy is relatively high and likely improved by adjuvant CT. The acute toxicity of treatment is significant; the major risk is neutropenia and sepsis. Patients with advanced T4 cancers that result in sphincter dysfunction requiring a pretreatment colostomy will usually have a permanent colostomy.

Radiotherapy in the treatment of resectable rectal adenocarcinoma.

The goal of treatment is to cure whereas maintaining sphincter function and minimizing toxicity. Although the mainstay of the treatment is surgery, radiotherapy (RT) is used in a substantial proportion of patients depending on the location and extent of the tumor. The aim of this article is to discuss the role of RT in patients with resectable rectal adenocarcinoma. This article is a review of the pertinent literature. Results show that patients with T1N0 exophytic, well to moderately differentiated, mobile tumors < or = 3 cm in diameter may be treated with either transanal excision or endocavitary RT. The probability of cure with either approach is approximately 80% to 90% and depends on selection criteria. The advantages of endocavitary RT are that it is an outpatient procedure requiring, at most, local anesthesia and is suitable for elderly, infirm patients. The disadvantage is that few of these treatment units are available. Patients who experience a local-regional recurrence may be surgically salvaged. Patients who undergo transanal excision and have unfavorable pathologic findings including equivocal or close margins, poor differentiation, invasion of the muscularis propria, and/or endothelial-lined space invasion have a high risk of local-regional recurrence after surgery alone. The addition of postoperative RT improves the likelihood of cure from 85% to 90%. Patients presenting with unfavorable tumors that are borderline resectable with a transanal excision may be downstaged with preoperative RT and rendered suitable for a wide local excision. The addition of concomitant chemotherapy probably enhances downstaging and may improve the likelihood of sphincter preservation. Patients with T3 and/or N1 rectal cancers have a relatively high probability of local-regional recurrence after surgery alone. Preoperative RT and postoperative RT combined with adjuvant chemotherapy have been shown to significantly reduce the risk of local-regional recurrence and improve survival. Whether preoperative RT alone or combined with chemotherapy is more efficacious than postoperative chemoradiation remains unclear. Endocavitary RT or transanal excision is suitable for patients with T1N0 cancers. Depending on tumor location and extent, adjuvant RT may improve the probability of local-regional control and survival for patients with locally advanced rectal adenocarcinomas.

Soft tissue penetration of cefuroxime determined by clinical microdialysis in morbidly obese patients undergoing abdominal surgery.

Antibiotic prophylaxis is intended to prevent postoperative wound infections, a major source of morbidity and mortality in surgical patients. Cefuroxime is a well-established second-generation cephalosporin that is given preoperatively in surgery units at a standard dose of 1.5 g. It is therefore important to determine whether cefuroxime distributes to the interstitial space fluid (ISF) of subcutaneous (s.c.) soft tissues, especially in obese patients who are at a higher risk of surgical site infections. In a single centre, prospective, open-label study, six morbidly obese patients [body mass index (BMI)> or =40] undergoing abdominal surgery received a single intravenous dose of 1.5 g cefuroxime within 1h of incision. Blood and microdialysis samples from the ISF of skeletal muscle and s.c. adipose tissue were collected before, throughout and after surgery for up to 6h post-dosing. Cefuroxime concentrations were determined by high-performance liquid chromatography-ultraviolet (HPLC-UV). Total peak concentrations in plasma (C(max)) (66.8+/-18.9 microg/mL) were higher than free C(max) levels in the ISF of muscle (60.1+/-15.2 microg/mL) and s.c. adipose tissue (39.2+/-26.4 microg/mL). Mean area under the free concentration-time curve ratios of muscle/total plasma (1.0+/-0.2) or s.c. adipose tissue/total plasma (0.6+/-0.5) indicate that cefuroxime distributes into the ISF of these tissues. In conclusion, the findings of this pilot study indicate that cefuroxime distributes into the ISF of muscle and s.c. adipose tissue of morbidly obese patients undergoing abdominal surgery. Concentrations in the ISF of soft tissues following a single 1.5 g dose may be high enough to prevent infections with Gram-positive organisms but may be insufficient to prevent infections with Gram-negative organisms.

Preoperative radiotherapy alone or combined with chemotherapy followed by transanal excision for rectal adenocarcinoma.

OBJECTIVE: To evaluate the efficacy of preoperative radiotherapy (RT) and chemoradiation (CRT) followed by transanal excision (TAE) for rectal adenocarcinoma. METHODS: Thirty-two patients were treated between July 1988 and April 2004 and followed from 2 to 123 months (median, 27 months). RESULTS: The 3-year outcomes were: locoregional control, 79%; distant metastasis-free survival, 80%; cause-specific survival, 88%; and overall survival, 75%. Outcomes were better for patients with T1-T2 tumors and those who experienced a complete response to preoperative RT or CRT. Two patients (6%) had chronic RT proctitis after treatment. CONCLUSION: A select subset of patients with T2/T3 tumors will experience similar outcomes after preoperative RT or CRT and TAE compared with radical proctectomy. Reliably predictive clinicopathologic features to define this subgroup would best be elicited in the context of large prospective randomized trials, as would the optimal combination and schedule of systemic agents delivered in conjunction with preoperative RT. Patients who experience a complete response (cCR) after preoperative CRT are excellent candidates for TAE; those with less than a cCR have a less-favorable prognosis and are probably better treated with a low anterior resection or abdominal-perineal resection.

Varying blood monocyte and dendritic cell responses after laparoscopic versus open gastric bypass surgery.

BACKGROUND: Laparoscopy may activate innate immunity less than conventional open surgery. This may be important in obese patients who have pre-existing low-grade inflammation. This study examined phenotypic changes in blood monocytes (Mcs) and dendritic cells (DCs) from patients undergoing laparoscopic (L) or open (O) Roux-en-Y gastric bypass (RYGBP) surgery. METHODS: 8 patients (3 male) had blood drawn before and after RYGBP, and on postoperative day (POD) 1, 3, and 28. Mc and DC quantity, phenotype, and activation status were determined by flow cytometry. RESULTS: Mean BMI was 53 +/- 4 and 46 +/- 1, and length of stay was 6.3 +/- 3.2 and 3.5 +/- 0.6 days, in the O (n=4) versus L (n=4) groups, respectively. Postoperative WBC count was 16 +/- 1 x 10(3)/mm3 after O and 10 +/- 1 x 10(3)/mm3 after LRYGBP (P<0.001). This was due to a greater rise in neutrophils and decline in lymphocytes after ORYGBP (P<0.001). Total Mcs increased in both groups at POD 1, but the number of CD18+ Mcs was reduced after ORYGBP (P=0.04). Mc human leukocyte antigen (HLA)-DR expression was lower in CD16+ Mcs after ORYGBP, suggesting decreased capacity to present antigen (P=0.002). Postoperatively, total DCs decreased in both groups, but recovered (P=0.04). The proportion and activation of the tolerogenic DC2 phenotype was lower, whereas the percentage of the ldDC phenotype was higher, in the O group (P=0.006). CONCLUSION: RYGBP changes the quantity and phenotype of circulating blood Mcs and DCs. Although there were overall similarities in the overall response to gastric surgery between open and laparoscopic, there were some notable differences, including a greater reduction in HLA-DR expression and increased number of immature DCs in the ORYGBP group. The findings suggest that RYGBP may have varying immunologic consequences depending upon the surgical procedure employed.

Esophageal perforation in adults: aggressive, conservative treatment lowers morbidity and mortality.

OBJECTIVE: To evaluate the outcome of aggressive conservative therapy in patients with esophageal perforation. SUMMARY BACKGROUND DATA: The treatment of esophageal perforation remains controversial with a bias toward early primary repair, resection, and/or proximal diversion. This review evaluates an alternate approach with a bias toward aggressive drainage of fluid collections and frequent CT and gastographin UGI examinations to evaluate progress. METHODS: From 1992 to 2004, 47 patients with esophageal perforation (10 proximal, 37 thoracic) were treated (18 patients early [<24 hours], 29 late). There were 31 male and 16 females (ages 18-90 years). The etiology was iatrogenic (25), spontaneous (14), trauma (3), dissecting thoracic aneurysm (3), and 1 each following a Stretta procedure and Blakemore tube placement. RESULTS: Six of 10 cervical perforations underwent surgery (3 primary repair, 3 abscess drainage). Nine of 10 perforations healed at discharge. In 37 thoracic perforations, 2 underwent primary repair (1 iatrogenic, 1 spontaneous) and 4 underwent limited thoracotomy. Thirty-4 patients (4 cervical, 28 thoracic) underwent nonoperative treatment. Thirteen of the 14 patients with spontaneous perforation (thoracic) underwent initial nonoperative care. Overall mortality was 4.2% (2 of 47 patients). These deaths represent 2 of 37 thoracic perforations (5.4%). There were no deaths in the 34 patients treated nonoperatively. Esophageal healing occurred in 43 of 45 surviving patients (96%). Subsequent operations included colon interposition in 2, esophagectomy for malignancy in 3, and esophagectomy for benign stricture in 2. CONCLUSIONS: Aggressive treatment of sepsis and control of esophageal leaks leak lowers mortality and morbidity, allow esophageal healing, and avoid major surgery in most patients.

Adjuvant postoperative radiotherapy for colon carcinoma.

BACKGROUND: The objective of this report was to review the role of adjuvant postoperative radiotherapy (RT) for patients with adenocarcinoma of the colon. METHODS: The authors reviewed the pertinent literature. RESULTS: Data suggested that locoregional postoperative RT improves both local control and survival for patients with T4N0-N1 tumors. There also may be a benefit for patients with T3N1-N2 tumors, but the data were equivocal. Whole abdominal RT may result in a similar benefit but is associated with increased toxicity. CONCLUSIONS: Postoperative RT should be considered for patients with T4N0-N1 colon carcinoma. Locoregional fields should be used.

Phase I study of 5-fluorouracil and leucovorin by continuous infusion chronotherapy and pelvic radiotherapy in patients with locally advanced or recurrent rectal cancer.

PURPOSE: To determine the maximal tolerated dose of chronomodulated 5-fluorouracil (5-FU) and leucovorin (LV) given concurrently with radiotherapy in patients with rectal cancer. METHODS AND MATERIALS: Forty-five patients with T3, T4 or recurrent rectal cancer received concurrent radiotherapy to a minimal dose of 4500 cGy. Chemotherapy was administered by a programmable pump in chronomodulated fashion, with 62.5% of the total dose given within 7 hours around 9:30 pm. The starting doses were LV at 5 mg/m2/d and 5-FU at 150 mg/m2/d. LV was escalated in 5-mg/m2 increments to 20 mg/m2/d; 5-FU was then escalated in 25 mg/m2 increments to the maximal tolerated dose. RESULTS: Diarrhea and stomatitis were dose limiting, with Grade 3 or worse toxicity occurring in 16% and 5% of patients, respectively. Thirty-seven patients (84%) received their scheduled dose of radiotherapy (range, 4500-6000 cGy). Thirty-two patients had clinical T3 disease; all were treated with definitive surgery; 23 (71%) underwent sphincter-sparing surgery with complete resection in 28 (87%). Ten patients (31%) had no evidence of tumor in the pathologic specimen. CONCLUSION: Preoperative chemoradiotherapy in rectal cancer using chronomodulated 5-FU and LV is feasible. The recommended Phase II dose is 5-FU 200 mg/m2 and LV 20 mg/m2 daily for 5 weeks.

Role of radiation therapy in the treatment of resectable rectal adenocarcinoma.

The purpose of this study is to review the role of radiation therapy in the treatment of resectable rectal adenocarcinoma. Selection criteria, treatment techniques, and results are discussed.