Local excision of rectal carcinoma: a safe alternative for more advanced tumors?

BACKGROUND AND OBJECTIVES: Local excision of rectal carcinoma has primarily been limited to patients with small (< or =3 cm), early rectal carcinoma. We wanted to determine whether local excision (transanal or transacral), when combined with selective chemoradiation therapy, would be adequate treatment for patients with larger (>3 cm) and more advanced T3 and N1 tumors. METHODS: A prospective study of 20 patients with clinical T1-T3, N0-N1 rectal carcinoma was initiated in 1990. Local excision (transanal or transacral) was performed on all patients. Sixteen patients were treated with postoperative 5-fluorouracil (5-FU) and leucovorin (LV) combined with radiation therapy; six high-risk patients (T3 or N1) received an additional 6 months of 5-FU and LV. All patients were followed for a minimum of 4 years. RESULTS: Tumor size ranged from 2 to 5.5 cm (mean, 3.6 cm). Histology revealed well or moderate differentiation (19/20), gross or microscopic ulceration (14/20), and vessel invasion (5/20). Mucosal margins were 3-12 mm (mean, 8.3 mm); radial margins were clear in all patients except one (microscopically positive). Five patients had T3 tumors; two had node positive tumors (N1). With a median follow-up of 56 months (48-71), there have been no local or regional failures and two patients have died from metastatic disease. CONCLUSIONS: Local excision, when combined with selective chemoradiation therapy, can be safely applied to patients with large (>3 cm) and more advanced T3 and N1 rectal carcinomas.

Local excision of rectal carcinoma. Early results with combined chemoradiation therapy using 5-fluorouracil and leucovorin.

PURPOSE: This study was undertaken to evaluate the treatment morbidity, functional outcome, and recurrence risk of patients undergoing local excision and combined chemoradiation therapy for rectal carcinoma. METHODS: Eighteen patients underwent local excision of their rectal carcinoma. Four patients underwent local excision alone (T1-2, N0-X, low risk), 10 patients underwent local excision with postoperative chemoradiation therapy using 5-fluorouracil and leucovorin (T1-2, N0-X, high risk), and 4 patients underwent local excision, chemoradiation therapy, and six months of additional 5-fluorouracil and leucovorin (T3 or N1). RESULTS: Of the four patients undergoing local excision alone, there was no treatment morbidity or alteration in functional outcome. Of the 14 patients receiving chemoradiation therapy, three reported early Grade 3-4 toxicity manifested by cystitis, proctitis, or perineal skin desquamation. At six months, two patients reported persistent rectal urgency and occasional fecal incontinence, and 11 patients reported increasing stool frequency (average, 3: range, 2-8). The six months of additional 5-fluorouracil and leucovorin were well tolerated and did not appear to further affect functional outcome. There were no local recurrences, although one patient developed distant metastatic disease. CONCLUSION: This treatment regimen, while generally well tolerated, is associated with significant acute toxicity in certain patients. We have identified specific causative factors which can be modified to decrease acute morbidity, including the elimination of leucovorin during the combined chemoradiation therapy.

Biochemical markers for colorectal cancer. Diagnostic and therapeutic implications.

The development of the understanding of oncogenes, tumor suppressor genes, and signal transduction has provided a significant advance in the concepts of the mechanisms of carcinogenesis in the colon and rectum. The tools provided by the molecular geneticist and the immunobiologist may yield powerful new techniques for screening individuals at risk, for identifying those patients with biologically more aggressive tumors, for developing novel therapies targeted directly at tumor cells, and for providing the means for more sensitive and specific detection of recurrence of disease.

Intra-abdominal sepsis: a medical-surgical dilemma.

Much progress has been made in our understanding of the pathophysiology of intra-abdominal infection over the past 100 years. By 1900, investigators had evidence of both an aerobic and an anaerobic component in these infections. By the 1970s, the role of gram-negative aerobic organisms in peritonitis and the role of anaerobes in abscess formation were emerging. Improved culture techniques have demonstrated the true polymicrobial nature of intra-abdominal infection. In our most recent study, an average of 3.9 isolates per patient was cultured. Because of the mixed flora present in these infections, antibiotic regimens must be active against both aerobes and anaerobes. This coverage has usually been accomplished with combinations of antibiotics, although some newer, single-agent regimens may also be effective. Even with our increased knowledge, intra-abdominal infection followed by sepsis remains the most common cause of death among patients in the intensive care unit. Mortality is associated with multiple, recurrent, or persisting abscess; positive blood cultures; and organ failure. Surgery, if indicated, should be undertaken before the onset of significant organ failure. Reducing the mortality from organ failure will depend more on the ability to modulate the metabolic and immune pathways that lead to sepsis than on the development of broader-spectrum antibiotics and more aggressive surgical algorithms.

Prospective study comparing imipenem-cilastatin with clindamycin and gentamicin for the treatment of serious surgical infections.

Surgical infection remains a leading cause of hospital morbidity and mortality. We compared the efficacy and toxicity of imipenem-cilastatin sodium in 32 patients with that of clindamycin phosphate and gentamicin sulfate in 25 patients. In the imipenem-cilastatin group, 87.5% had a favorable outcome, with a 12.5% failure rate and 13 adverse reactions. In the clindamycin-gentamicin group, 80% had a favorable outcome, with a 20% failure rate and ten adverse reactions. Two significant superinfections with Pseudomonas and Candida were noted in patients treated with impenem-cilastatin. Each group had one case of Clostridium difficile-associated colitis. Cost analysis showed no differences between treatment arms, except in the appendicitis subgroup. For serious surgical infections, single-agent therapy with imipenem-cilastatin appears to be as efficacious as combination therapy with clindamycin and gentamicin.

An isolated perfused model for the study of colonic metabolism and transport.

The murine colonic perfusion model allows for the examination of absorption, metabolism, and portal transfer by the colon under physiologic conditions. This model was characterized by the use of four radiolabeled compounds: estradiol and Vitamin D3, both physiologically active circulating steroid compounds, and benzo[a]pyrene and N-acetylaminofluorene, xenobiotic carcinogens of the aromatic hydrocarbon and aromatic amide classes, respectively. Hemodynamic parameters and oxygen consumption of the preparation were stable throughout perfusion. Estradiol and N-acetylaminofluorene entered the portal vein at a rate of 2% of the lumenal dose per hour. Benzo[a]pyrene crossed at 0.4% of the lumenal dose per hour. The rate of transfer of Vitamin D3 was negligible. Analysis of the lumenal label revealed only substrate. In all experiments less than 0.02% of the applied substrate remained in the tissue compartment. Analysis of the vascular perfusate demonstrated evidence for sulfates of estradiol and N-acetylaminofluorene. Three conjugate classes were found associated with benzo[a]pyrene, constituting 42% of the portal label. Hydrolysis data suggests the presence of double conjugates of benzo[a]pyrene involving glutathione. In the case of aromatic hydrocarbons, conjugation, particularly thioether formation, implies hydroxylation and epoxide formation. For sulfation an N-acetylamino-fluorene ring or N-hydroxylation is required. The latter process could allow for the delivery of highly carcinogenic N-O sulfates to the liver.

Surgical management of complicated diverticulitis. The Lahey Clinic experience, 1967 to 1982.

One hundred forty patients who had complicated diverticular disease were identified in a retrospective review at the Lahey Clinic between 1967 and 1982. Of these patients, 86 underwent resection with primary anastomosis with a 1 percent mortality rate and an 18 percent morbidity rate; 13 had resection with anastomosis and creation of a proximal colostomy with no death and a 22 percent morbidity rate; 19 had the Hartmann operation or colostomy with mucous fistula with a 16 percent mortality rate and a 23 percent morbidity rate; and 22 underwent a traditional three-stage operation with 14 percent mortality and 24 percent morbidity rates. The average duration of hospitalization was 21 days for patients who underwent the one-stage procedure, 31 and 39 days for those who had a two-stage operation, and 52 days for patients who underwent the three-stage procedure. Primary resection for complicated disease is associated with acceptable morbidity and mortality rates under appropriate circumstances.

Diverticular disease of the colon. Current concepts and management.

Diverticular disease of the colon is being seen with increasing frequency. An acute complicated presentation of the disease occurs in a minority of patients. In contrast to a previous study in which we found that 70 per cent of patients had had prior episodes, our most recent study revealed that for nearly 50 per cent of the patients with acute diverticular disease a complicated attack was the initial manifestation of the disease. Because these patients are more likely to have concomitant medical problems, aggressive elective surgical management is appropriate. This approach is now associated with a mortality rate of less than 1 per cent in patients with uncomplicated disease. Even in patients with complicated active disease, a mortality rate of less than 4 per cent can be anticipated when bowel preparation can be achieved. In patients below the age of 55 resection is advocated after a single attack because the rate of recurrence in this group may be as high as 50 per cent. In the setting of stage I or stage II disease primary resection with anastomosis is safe and should be performed. Proximal colostomy formation may be carried out at the discretion of the surgeon if warranted by such local circumstances as contiguous inflammation or macroscopic contamination. For patients with stage III and stage IV disease end-colostomy with Hartmann closure of the rectum is the procedure of choice, although anastomosis with proximal stoma may prove to be an acceptable alternative. The morbidity and mortality rates associated with the classic three-stage approach are similar to those with two-stage management, but the latter is associated with a substantially shorter duration of hospitalization and disability. The best form of management of diverticular disease is prevention. It is appealing to embrace high-bulk dietary management as a prophylaxis based on current knowledge of pathophysiologic principles, but good prospective randomized data are not yet forthcoming.