Phase I/II study of neoadjuvant bevacizumab, erlotinib and 5-fluorouracil with concurrent external beam radiation therapy in locally advanced rectal cancer.

BACKGROUND: To determine the maximal tolerated dose of erlotinib when added to 5-fluorouracil (5-FU) chemoradiation and bevacizumab and safety and efficacy of this combination in patients with locally advanced rectal cancer. PATIENTS AND METHODS: Patients with Magnetic resonance imaging (MRI) or ultrasound defined T3 or T4 adenocarcinoma of the rectum and without evidence of metastatic disease were enrolled. Patients received infusional 5-FU 225 mg/M2/day continuously, along with bevacizumab 5 mg/kg days 14, 1, 15 and 29. Standard radiotherapy was administered to 50.4 Gy in 28 fractions. Erlotinib started at a dose of 50 mg orally daily and advanced by 50 mg increments in the subsequent cohort. Open total mesorectal excision was carried out 6-9 weeks following the completion of chemoradiation. RESULTS: Thirty-two patients received one of three dose levels of erlotinib. Erlotinib dose level of 100 mg was determined to be the maximally tolerated dose. Thirty-one patients underwent resection of the primary tumor, one refused resection. Twenty-seven patients completed study therapy, all of whom underwent resection. At least one grade 3-4 toxicity occurred in 46.9% of patients. Grade 3-4 diarrhea occurred in 18.8%. The pathologic complete response (pCR) for all patients completing study therapy was 33%. With a median follow-up of 2.9 years, there are no documented local recurrences. Disease-free survival at 3 years is 75.5% (confidence interval: 55.1-87.6%). CONCLUSIONS: Erlotinib added to infusional 5-FU, bevacizumab and radiation in patients with locally advanced rectal cancer is relatively well tolerated and associated with an encouraging pCR.

Phase II study of capecitabine and mitomycin C as first-line treatment in patients with advanced colorectal cancer.

This study was designed to assess the safety and efficacy of capecitabine and mitomycin C (MMC) in previously untreated patients with advanced colorectal cancer (CRC). Patients received capecitabine 2500 mg m(2) day 1, orally divided in two doses of 1250 mg m(-2) in the morning and evening for 14 days every 21 days and MMC 7 mg m(-2) (maximum total dose 14 mg) as an intravenous bolus every 6 weeks for a total of four courses. The median age was 70 years (range 24-85) and the majority of patients (86.9%) were of performance status 1/2. The most common metastatic site was liver. In all, 84 patients were assessable for response. The overall response rate was 38% (95% CI: 27.7-49.3) and a further 33.3% of patients achieved stable disease over 12 weeks. There was good symptom resolution ranging from 64 to 86%. Grade 3/4 toxicity was as follows: hand-foot syndrome 19.7%; diarrhoea 10%; neutropenia 2.4%; infection 2.3%. Capecitabine and MMC have shown encouraging activity with a favourable toxicity profile, a convenient administration schedule, and could be considered for patients deemed unsuitable for oxaliplatin and irinotecan combinations.

Intraoperative radiation therapy for locally advanced recurrent rectal or rectosigmoid cancer.

BACKGROUND AND PURPOSE: To update and summarize the experience at the Massachusetts General Hospital of a treatment program of high-dose preoperative irradiation, surgical re-resection, and intraoperative radiation therapy (IORT) as a salvage treatment for patients with recurrent rectal or rectosigmoid carcinoma. PATIENTS AND METHODS: From June 1978 to February 1997, the records of 69 patients with locally recurrent rectal carcinomas or rectosigmoid carcinomas without metastases referred for consideration of IORT were reviewed. Forty-nine patients received IORT and local control and disease-free survival curves were calculated using the actuarial method of Kaplan-Meier. RESULTS: The 5-year overall survival, local control and disease-free survival rates of 49 patients receiving IORT were 27, 35, and 20%, respectively. Thirty-four patients who underwent a macroscopic complete resection had a significantly better 5-year overall survival than the remaining 15 patients with gross residual disease (33 vs. 13%, P=0.05, log rank). For those patients, local control and disease-free survival rates were 46 and 27%, respectively. Patients with a microscopic complete resection had a superior 5-year overall survival than partially resected patients (40 vs. 14%, P=0.0001, log rank). Chemotherapy had no significant influence on overall or disease-free survival. CONCLUSION: The current analysis shows the importance of a microscopic complete resection in a multi-modality approach with IORT for survival and local control. Salvage is rare for patients undergoing subtotal resection.

Does postoperative irradiation play a role in the adjuvant therapy of stage T4 colon cancer?

PURPOSE: This study analyzes the long-term outcome of patients with stage T4 colon cancer who receive postoperative irradiation. The purpose of the study is to define the potential role of this modality with current systemic therapies. PATIENTS AND METHODS: A retrospective analysis was performed of 152 patients undergoing resection of T4 colon cancer followed by moderate- to high-dose postoperative tumor bed irradiation with and without 5-fluorouracil-based chemotherapy. Of the 152 patients, 110 patients (T4N0 or T4N+) were treated adjuvantly, whereas 42 patients received irradiation for the control of gross or microscopic residual local tumor. RESULTS: For 79 adjuvantly treated patients with stage T4N0 or T4N+ cancer with one lymph node metastasis, the 10-year actuarial rates of local control and recurrence-free survival were 88% and 58%, respectively. Results were less satisfactory for patients with more extensive nodal involvement. The 10-year actuarial rates of local control and recurrence-free survival of 39 patients with T4 tumors complicated by perforation or fistulas were 81% and 53%, respectively. For 42 patients with incompletely resected tumors, the 10-year actuarial recurrence-free survival was 19%. CONCLUSIONS: In comparison with historical controls, postoperative tumor bed irradiation improves local control for some subsets of patients. In addition to standard 5-fluorouracil-based chemotherapy, adjuvant tumor bed irradiation should be considered when colon cancers invade adjoining structures, when they are complicated by perforation or fistulas, or when they are incompletely excised at the primary site.

Long-term follow-up of patients with rectal cancer managed by local excision with and without adjuvant irradiation.

OBJECTIVE: The long-term outcomes of patients undergoing local excision with or without pelvic irradiation were examined to define the role of adjuvant irradiation after local excision of T1 and T2 rectal cancers. METHODS: Ninety-nine patients with T1 or T2 rectal cancers underwent local excision with or without adjuvant irradiation at Massachusetts General Hospital and Emory University Hospital between January 1966 and January 1997. Of these, 52 patients were treated by local excision alone and 47 patients by local excision plus adjuvant irradiation. Twenty-six of these 47 patients were treated by irradiation in combination with 5-fluorouracil chemotherapy. The outcomes of these groups were compared. RESULTS: The 5-year actuarial local control and recurrence-free survival rates were 72% and 66%, respectively, for the local excision alone group and 90% and 74%, respectively, for the adjuvant irradiation group. This improvement in outcome was evident despite the presence of a higher-risk patient population in the adjuvant irradiation group. Adverse pathologic features such as poorly differentiated histology and lymphatic or blood vessel invasion decreased local control and recurrence-free survival rates in the local excision only group. Adjuvant irradiation significantly improved 5-year outcomes in patients with high-risk pathologic features. Four cases of late local recurrence were seen at 64, 72, 86, and 91 months in the adjuvant irradiation group. CONCLUSIONS: The authors recommend adjuvant chemoradiation for all patients undergoing local excision for T2 tumors, and for T1 tumors with high-risk pathologic features. The four cases of late local failures beyond 5 years in the adjuvant irradiation group underscores the need for careful long-term follow-up in these patients.

Prognostic factors in stage T3N0 rectal cancer: do all patients require postoperative pelvic irradiation and chemotherapy?

PURPOSE: To further define the indications for postoperative pelvic irradiation and chemotherapy, an analysis of the influence of extent of tumor invasion into perirectal fat, lymphatic or venous vessel invasion, and tumor grade on the clinical course of patients with Stage T3N0 rectal cancer undergoing surgery was undertaken. METHODS: From 1968 to 1985, 117 patients with Stage T3N0 rectal cancer underwent resection with curative intent. No patient received neoadjuvant or adjuvant irradiation or chemotherapy. Surgical specimens were assessed for maximum depth of tumor invasion into perirectal fat, lymphatic or venous involvement, and tumor grade. After surgery the clinical course of these patients was assessed for local control, distant metastases, and survival rate. RESULTS: For 25 patients with tumors exhibiting favorable histologic features (well-differentiated or moderately well-differentiated carcinomas invading less than 2 mm into perirectal fat, without lymphatic or venous vessel involvement), the ten-year actuarial rates of local control and recurrence-free survival were 95 and 87 percent, respectively. In contrast, the ten-year actuarial rates of local control and recurrence-free survival were inferior (71 and 55 percent, respectively) for 88 patients with tumors exhibiting moderate to deep perirectal fat invasion, vessel involvement, or poor differentiation. CONCLUSIONS: In the design of future trials of rectal cancer, selection of patients with rectal cancer for postoperative adjuvant therapy should be based not only on stage, but also on depth of invasion into the perirectal fat, vessel involvement, tumor grade, and integrity of the radial resection margin. For subsets of patients with Stage T3N0 rectal cancer, there may be little benefit to adjuvant therapy after surgery.

Complications of abdominal stoma surgery.

PURPOSE: This study was undertaken to review and summarize the complications of ileostomy and colostomy creation and subsequent closure. METHODS: The English-language medical literature for at least the past 15 years was reviewed comprehensively. RESULTS: Complications of surgery for the creation of end, loop, and "end loop" stomas are presented. Technical factors, which might influence complication rates, are discussed. Optimal management of ostomy complications is presented, especially for peristomal hernias. Similarly, techniques and complications for stoma closure are analyzed. CONCLUSIONS: Stoma creation is not a trivial undertaking; careful surgical technique minimizes complications (which are relatively frequent), and promotes good ostomy function. Peristomal hernias are difficult to cure permanently. The morbidity of ileostomy and colostomy closure is also appreciable.

The impact of 5-fluorouracil and intraoperative electron beam radiation therapy on the outcome of patients with locally advanced primary rectal and rectosigmoid cancer.

OBJECTIVE: To analyze the effects of 5-fluorouracil (5-FU) chemotherapy combined with preoperative irradiation and the role of intraoperative electron beam irradiation (IOERT) on the outcome of patients with primary locally advanced rectal or rectosigmoid cancer. METHODS: From 1978 to 1996, 145 patients with locally advanced rectal cancer underwent moderate- to high-dose preoperative irradiation followed by surgical resection. Ninety-three patients received 5-FU as a bolus for 3 days during the first and last weeks of radiation therapy (84 patients) or as a continuous infusion throughout irradiation (9 patients). At surgery, IOERT was administered to the surgical bed of 73 patients with persistent tumor adherence or residual disease in the pelvis. RESULTS: No differences in sphincter preservation, pathologic downstaging, or resectability rates were observed by 5-FU use. However, there were statistically significant improvements in 5-year actuarial local control and disease-specific survival in patients receiving 5-FU during irradiation compared with patients undergoing irradiation without 5-FU. For the 73 patients selected to receive IOERT, local control and disease-specific survival correlated with resection extent. For the 45 patients undergoing complete resection and IOERT, the 5-year actuarial local control and disease-specific survival were 89% and 63%, respectively. These figures were 65% and 32%, respectively, for the 28 patients undergoing IOERT for residual disease. The overall 5-year actuarial complication rate was 11%. CONCLUSIONS: Treatment strategies using 5-FU during irradiation and IOERT for patients with locally advanced rectal cancer are beneficial and well tolerated.

Changes in tumor proliferation of rectal cancer induced by preoperative 5-fluorouracil and irradiation.

PURPOSE: This study examines the effect of 5-fluorouracil administration during preoperative irradiation on rectal cancer tumor proliferation. PATIENTS AND METHODS: One hundred and fifty-three patients with locally advanced rectal cancer received 45 to 50 Gy of preoperative irradiation with (103 patients) and without (50 patients) concurrent 5-fluorouracil, followed by surgery. Pretreatment tumor biopsies and postirradiation surgical specimens were scored for proliferative activity by assaying the extent of Ki-67 and proliferating cell nuclear antigen immunostaining and the number of mitoses per ten high-powered fields. Postirradiation specimens were also assessed for downstaging. RESULTS: Although 5-fluorouracil did not improve downstaging rates, marked decreases in the activity of all three markers of proliferation (mitotic counts, Ki-67, and proliferating cell nuclear antigen immunostaining) were seen in rectal cancers of patients receiving the drug. No significant decreases were noted in patients undergoing irradiation only. CONCLUSION: The addition of 5-fluorouracil to preoperative irradiation resulted in a more complete inactivation of the proliferating population. Frequency of downstaging, however, was unaffected. Thus, the quiescent cell population appears to represent a substantial barrier to further downstaging. New treatment strategies should be aimed at controlled recruitment of quiescent tumor cells at the time of irradiation.

Appendiceal carcinoma: patterns of failure following surgery and implications for adjuvant therapy.

BACKGROUND AND OBJECTIVES: Primary adenocarcinoma of the appendix is rare, which makes an understanding of its natural history difficult. To date, it is treated predominantly with surgery alone. This review aims to elucidate the patterns of failure and treatment outcomes when adjuvant treatment is given after primary surgical resection. METHODS: Twenty-three patients were treated with either surgery alone, or with surgery and adjuvant radiation +/- chemotherapy. A review of the clinical course of these patients was undertaken with an analysis of the local control, distant failure, disease-free survival, and overall survival. RESULTS: Most patients presented with local invasion or metastatic disease often involving the peritoneum. Overall survival was 32%, similar to the results of other studies. Analysis of patients with locally advanced disease showed improvement in overall survival and local control with postoperative radiation therapy compared to surgery alone. CONCLUSIONS: Adenocarcinoma of the appendix is a rare disease that presents most often in an advanced stage. It has been shown by others that a right hemicolectomy provides the best outcome with respect to surgical procedure. Postoperative irradiation appears to provide a benefit for both local control and overall survival.

Postoperative perineal hernia.

PURPOSE: Perineal hernia is an uncommon complication following abdominoperineal resection. The aim of the study was to evaluate the predisposing factors and the optimum method of repair. METHODS: A retrospective review of patients with postoperative perineal hernia at the Massachusetts General Hospital between 1963 and 1995 was performed. RESULTS: Twenty-one patients with perineal hernias were found. The original perineal operations were as follows: abdominoperineal resection in 13 patients, pelvic exenteration in 5 patients, cystourethrectomy in 2 patients, and perineal resection of the rectal stump in 1 patient. The incidence of symptomatic perineal hernia following abdominoperineal resection was estimated to be 0.62 percent. A total of 69 percent of patients had the original perineal wound left partially open, and in 10 percent it was left completely open. The peritoneal defect was not closed in 53 percent of patients, and only 21 percent had closure of the levator defect. Of the 19 patients who had hernia repair, 13 were repaired transperineally and 3 transabdominally and 3 required a combined abdominoperineal approach. The repair methods were as follows: simple closure of the pelvic defect (10 patients), mesh closure (5 patients), gluteus flap (1 patient), and retroflexion of the uterus (2 patients) or bladder (1 patient). Four patients had postoperative complications (mostly wound infections), and the recurrence rate was 16 percent. There was no difference in length of hospitalization among transperineal, transabdominal, and combined approaches. CONCLUSIONS: Primary closure of the perineal wound, with careful avoidance of wound infection is the most important consideration for avoiding a perineal hernia. Repair via the perineum with simple closure of the defect or a mesh is successful in most cases.

Intraoperative radiation therapy for locally advanced recurrent rectal or rectosigmoid cancer.

Recurrent rectal or rectosigmoid cancer is a difficult therapeutic problem. A treatment program of external beam irradiation, surgery, and intraoperative irradiation has been used for 41 patients. The 5-year actuarial local control and disease-free survival of all 41 patients was 30% and 16%, respectively. Subset analysis demonstrated differences in outcome by extent of surgical resection. The 5-year actuarial local control and disease-free survival of 27 patients undergoing complete resection was 47% and 21%, respectively. By contrast, the outcome of 14 patients undergoing partial resection was poor, with a 5-year actuarial local control and survival of 21% and 7%, respectively. Late complications included soft tissue or peripheral nerve injury, with many of these resolving within 4-18 months. Local control and disease-free survival rates are favorable in comparison with the results achieved by aggressive surgery. Patients who achieve a gross total resection at intraoperative irradiation have a markedly better prognosis than that of patients with residual gross disease.

Tumor proliferation in rectal cancer following preoperative irradiation.

PURPOSE: This study examines the effect of preoperative irradiation on tumor proliferation in rectal cancer. PATIENTS AND METHODS: One hundred twenty-two patients with locally advanced rectal cancer received 45 to 50 Gy of preoperative irradiation followed by surgery. Pretreatment tumor biopsies and postirradiation surgical specimens were scored for proliferative activity by assaying the extent of Ki-67 and proliferating-cell nuclear antigen (PCNA) immunostaining and the number of mitoses per 10 high-power fields (hpf). Preirradiation and postirradiation proliferative activity was determined and correlated to clinical outcome. RESULTS: There was an overall reduction in the tumor proliferative activity of rectal cancer after irradiation compared with its preirradiation state. Decreases in the activity of all three markers of tumor proliferation (Ki-67 and PCNA immunostaining, and mitotic counts) were observed in irradiated tumors compared with pretreatment biopsies. Postirradiation tumor proliferative activity was associated with pathologic tumor stage. A high level of proliferative activity was observed in tumors downstaged to the rectal wall (T1-2) compared with tumors that retained transmural penetration (T3-4). Multivariate analysis indicated that postirradiation proliferative activity and stage were independently associated with survival following surgery. Patients with tumors that exhibited elevated proliferative activity postirradiation had improved survival compared with patients with tumors that showed less proliferative activity. CONCLUSION: Moderate- to high-dose preoperative irradiation decreases both the tumor size and proliferative activity of rectal cancers. Elevated postirradiation tumor proliferative activity correlates strongly with improved survival. This may aid in identifying high-risk patients following preoperative irradiation and surgery.

Rectal cancer: the influence of tumor proliferation on response to preoperative irradiation.

PURPOSE: Regression of rectal carcinoma after preoperative irradiation is variable, likely reflecting differences in the physical and biologic properties of these tumors. This study examines the association between the pathologic response of rectal cancer after irradiation and its pretreatment proliferative state as assayed by the activity of the proliferative dependent antigens (Ki-67, PCNA) and mitotic counts. METHODS AND MATERIALS: One hundred and twenty-two patients with locally advanced rectal cancer received preoperative irradiation followed by surgery. Pretreatment tumor biopsies were scored for the extent of Ki-67 and PCNA immunostaining and the number of mitoses per 10 high-powered fields. Postirradiation surgical specimens were examined for extent of residual disease. RESULTS: The tumors of 38 of 122 patients (31%) exhibited marked pathologic downstaging (no residual tumor or cancer confined to the rectal wall) after preoperative irradiation. Two features were associated with the likelihood of marked pathologic regression after preoperative irradiation: tumor proliferative activity and lesion size. When stratified by lesion size, marked tumor regression occurred most frequently in smaller tumors with high Ki-67, PCNA, and mitotic activity compared to larger tumors with lower Ki-67, PCNA, and mitotic activity. Intermediate downstaging rates were seen for small or large tumors with moderate Ki-67, PCNA, and mitotic activity. CONCLUSION: Tumor Ki-67, PCNA, and mitotic activity predicts the likelihood of response to irradiation, which may aid in formulating treatment policies for patients with rectal cancer.

Staging of colon carcinoma using water enema CT.

OBJECTIVE: To determine the accuracy of water enema CT (WECT) for staging colon carcinoma. MATERIALS AND METHODS: Thirty patients with colon cancer, diagnosed by barium enema and/or colonoscopy, underwent preoperative WECT. Dynamic contrast enhanced CT studies were performed after rectal administration of < or = 2 L lukewarm tap water. Images were prospectively analyzed for depth of tumor invasion, nodal involvement, and distant metastases by investigators blinded to the results of barium enema and colonoscopy. Surgical/pathologic proof was obtained in all cases. RESULTS: Using WECT, 23 of 30 patients were correctly staged. Correct staging occurred in 2 of 2 patients with Stage A, 3 of 3 patients with Stage B1, 6 of 9 patients with Stage B2, 1 of 2 patients with Stage C1, 5 of 8 patients with Stage C2, and 6 of 6 patients with Stage D tumors. Of the patients incorrectly staged, 4 were understaged and 3 were overstaged; all were due to errors in predicting lymph node involvement. Sensitivity and specificity for evaluating nodal involvement were 60 and 79%, respectively. CONCLUSIONS: Water enema CT allows for accurate depiction and staging of colon carcinoma. Aqueous distention of the colon avoids artifacts seen with positive contrast agents yet allows accurate evaluation of the bowel wall and pericolonic structures.

Surgery for radiation injury to the large intestine. Variables influencing outcome.

PURPOSE: Surgery for colorectal radiation injury is technically difficult and often followed by complications. This study evaluates factors affecting outcome. METHODS: A retrospective 30-year review was carried out. Preoperative characteristics and operative variables were correlated with morbidity, mortality, and success in providing symptomatic relief. RESULTS: A total of 60 cases and 75 colon and rectal lesions were analyzed. After surgery, the morbidity rate was 65 percent, and the mortality was 6.7 percent. A successful outcome in providing symptomatic relief was achieved in 71.7 percent of cases. When comparing success after operations for the different lesions (stricture, 78.1 percent; hemorrhage, 64.3 percent; perforation, 100 percent; and fistula, 54.5 percent), the presence of a fistula was associated with symptomatic relief significantly less often than the remainder (P = 0.03). The type of operation had no effect on success rate: 72 percent for diversion, 66.7 percent for resection, and 83.3 percent for bypass. Morbidity and mortality rates were not significantly influenced by site of lesions, type of lesions, or choice of surgical operation. A permanent stoma was necessary in 70 percent of patients. CONCLUSIONS: The morbidity for surgical treatment of large bowel radiation injury is substantial, and largely unrelated to the type and location of the radiation lesion, as well as the type of operation. Success rates are reasonably high, but worst after fistula repair. The selection of therapy (medical, endoscopic, surgical) for radiation-induced colorectal lesions must take into account numerous factors and be highly individualized.

Selection factors for local excision or abdominoperineal resection of early stage rectal cancer.

BACKGROUND: This study reviews the experience of patients with early stage rectal cancer managed by local excision or abdominoperineal resection to clarify the relative indications and results of these two approaches. METHODS: From 1962 to 1991, 125 patients with T1 and T2 rectal cancer underwent local excision (56 patients) or abdominoperineal resection (69 patients). Outcome was analyzed by stage, treatment, and pathologic features of tumor grade and vessel involvement. RESULTS: The 5-year actuarial recurrence-free survival and local control was 87% and 96%, respectively, for 28 patients undergoing local excision with favorable histologic features (well or moderately well differentiated histologic findings without venous/lymph vessel involvement). These results were 57% and 68% for 28 patients with unfavorable histologic features (poorly differentiated histology and/or venous/lymph vessel involvement). For patients undergoing abdominoperineal resection, the 5-year actuarial recurrence-free survival and local control of 49 patients with favorable histologic features was 91% and 91%, respectively. These results were 79% and 89%, respectively, for patients with poorly differentiated histology or venous/lymph vessel involvement. CONCLUSIONS: For patients with T1 and T2 tumors having favorable histologic features, a satisfactory survival and local control was achieved for patients undergoing local excision or abdominoperineal resection. In contrast, patients with T1 and T2 tumors having poorly differentiated histologic features and/or venous/lymph vessel involvement undergoing local excision or abdominoperineal resection appeared to have decreased rates of survival and of local control. For these patients, radical resection combined with pelvic irradiation and 5-fluorouracil-based chemotherapy should be investigated.

Proliferating cell nuclear antigen and mitotic activity in rectal cancer: predictor of response to preoperative irradiation.

PURPOSE: This study examines the association between the pathologic response of rectal cancer after irradiation and its pretreatment proliferative state as assayed by proliferating cell nuclear antigen (PCNA) and mitotic activity. PATIENTS AND METHODS: Ninety patients with clinical stage T3 and T4 rectal cancer received preoperative irradiation followed by surgery. Pretreatment tumor biopsies were scored for PCNA activity (number of tumor cells staining immunohistochemically with an anti-PCNA monoclonal antibody) and the number of mitoses per 10 high-powered fields (hpf). Postirradiation surgical specimens were examined for extent of residual disease. RESULTS: The tumors of 33 of 90 patients (37%) exhibited marked pathologic downstaging (no residual tumor or cancer confined to the rectal wall) after preoperative irradiation. Two features were independently associated with the likelihood of marked pathologic regression after preoperative irradiation: lesion size and PCNA/mitotic activity. When stratified by tumor size, marked tumor regression occurred most frequently in smaller tumors with high PCNA/mitotic activity compared with larger tumors with lower PCNA/mitotic activity. Intermediate downstaging rates were seen for small or large tumors with moderate PCNA/mitotic activity. CONCLUSION: Tumor PCNA/mitotic activity predicts the likelihood of response to irradiation, which may aid in formulating treatment policies for patients with rectal cancer.

Quantitative cultures of the mucosal-associated bacteria in the mechanically prepared colon and rectum.

Little is known about the mucosal microflora of the colon and rectum at the time of elective surgery. Our objective was to determine the concentrations of anaerobic and aerobic bacteria associated with the mucosa of the mechanically prepared large bowel. Ten patients were studied after a standard polyethylene glycol-electrolyte lavage preparation. No patient had taken antibiotics in the preceding four weeks. Sterile wire brushes passed through the colonoscope during advancement were used to culture the rectal, transverse colon, and cecal mucosa. Total anaerobic, aerobic, Gram-positive, and enteric bacterial counts were determined along with specific cultures for Bacteroides fragilis, Clostridium difficile, Escherichia coli, Pseudomonas aeruginosa, enterococcus, and staphylococcus species. The results showed that there was a significant increase (P < 0.01) in aerobes, anaerobes, enterics, Gram positives, B. fragilis, and E. coli mucosal counts with proximal progression. Aerobes showed a steady gradient, while anaerobes demonstrated an increase from the rectum to the transverse colon but no change between the transverse colon and cecum. We conclude that, in the prepared bowel, there is an increase in the mucosal bacterial counts in the more proximal portions of the bowel. The results may serve as a baseline for future studies on the mucosal-associated bacteria of the large intestine.