Prognostic significance of postchemoradiation stage following preoperative chemotherapy and radiation for advanced/recurrent rectal cancers.

PURPOSE: To evaluate the prognostic significance of postchemoradiation pathologic stage and implications for further therapy following preoperative chemoradiation and surgery for advanced/recurrent rectal cancer. METHODS AND MATERIALS: Seventy-seven patients with advanced (fixed or tethered T4) or recurrent rectal cancer were treated with preoperative chemoradation followed by surgical resection of disease. Chemotherapy consisted of either of bolus 5-FU 500 mg/m(2) per day or continuous venous infusion 225 mg/m(2) per day for the duration of radiation. Radiation therapy was planned to be delivered to the whole pelvis to a dose of 45 Gy followed by a boost to the area of the tumor of 5-15 Gy. Total radiation doses ranged from 40 to 63 Gy with a median of 55.8 Gy. Surgical resection was then carried out 6-10 weeks following the completion of treatment (median, 7 weeks). Twenty-eight patients underwent abdominoperineal resection and and 49 patients had sphincter-sparing surgical procedures. None of the patients received postoperative chemotherapy. Follow-up in these patients ranges from 1 year to 8 years with a median of 3 years. RESULTS: Significant downstaging of disease was observed with 12/77 (16%) having no residual disease(pT0) and 13% (10/77) found to have pT1-2, N0 disease, 31% (24/77) with pT3-4, N0 and 40% (31/77) for pT0-4, N1-2 cancers. Survival by pathologic stage was 100% for pT0-2, N0 cancers, 80% for pT3-4, N0 and 73% for pTx, N1-2. Local recurrence of disease was observed in 0% of patients with pT0-2, N0 as compared with 13% (3/24) in pT3-4, N0 and 16% (5/31) in pT0-4, N1-2 patients. CONCLUSION: Downstaging following preoperative chemoradiation is a significant prognostic factor. Patients with pT0, T1, or T2 disease have an excellent prognosis and are unlikely to fail locally or with systemic disease. However, patient with T3/T4 or N+ disease may benefit from further adjuvant chemotherapy.

Curative surgical resection following reirradiation for recurrent rectal cancer.

PURPOSE: In spite of adjunctive radiation and chemotherapy, 10 to 25% of patients with resected rectal cancer develop local recurrence in the pelvis. This study evaluates the potential for curative surgical resection of residual disease following reirradiation for recurrent rectal cancer. METHODS AND MATERIALS: Thirty-nine patients with recurrent adenocarcinoma of the rectum following prior adjunctive therapy underwent reirradiation of the pelvis with concurrent intravenous infusion of 5-fluorouracil. Median time to recurrence following initial treatment was 18 months. Prior radiation doses to the pelvis ranged from 40 to 66 Gy with a median of 50.4 Gy. Reirradiation doses ranged from 20 Gy to 49.2 Gy with a median total dose of 36 Gy. Eight to 12 weeks following reirradiation patients underwent surgical resection of disease. Thirty-one patients had gross total resection of tumor. RESULTS: Patients have been followed for 24 months to 75 months after reirradiation for recurrent rectal cancer with a median follow-up of 3 years. Reirradiation was well tolerated, with seven patients requiring a significant treatment break. Early termination of reirradiation occurred in five patients because of diarrhea, moist desquamation, or mucositis. No surgical mortality was observed. Postoperatively, two patients developed delayed wound healing. Late complications included six patients who developed small bowel obstruction with three patients developing a bowel fistula. The median survival of patients is 45 months, with a 5-year actuarial survival of 24%. Actuarial local control at 5 years was 45%. The rate of distant metastases was 17%. CONCLUSION: Selected patients with rectal cancer who develop recurrent disease following previous adjuvant therapy can undergo successful curative surgical resection following reirradiation/chemotherapy with significant long-term survival.

A study of cell electrophoresis as a means of purifying growth hormone secreting cells.

Growth hormone secreting cells of the rat anterior pituitary are heavily laden with granules of growth hormone and can be partially purified on the basis of their resulting high density. Two methods of preparative cell electrophoresis were investigated as methods of enhancing the purification of growth hormone producing cells: density gradient electrophoresis and continuous flow electrophoresis. Both methods provided a two- to four-fold enrichment in growth hormone production per cell relative to that achieved by previous methods. Measurements of electrophoretic mobilities by two analytical methods, microscopic electrophoresis and laser-tracking electrophoresis, revealed very little distinction between unpurified anterior pituitary cell suspensions and somatotroph-enriched cell suspensions. Predictions calculated on the basis of analytical electrophoretic data are consistent with the hypothesis that sedimentation plays a significant role in both types of preparative electrophoresis and the electrophoretic mobility of the growth hormone secreting subpopulation of cells remains unknown.