Radiotherapy, concomitant protracted-venous-infusion 5-fluorouracil, and surgery for ultrasound-staged T3 or T4 rectal cancer.

BACKGROUND: A prospective study was undertaken to evaluate the response and toxicity of neoadjuvant chemoradiotherapy for ultrasound-staged T3 or T4 rectal cancer. PATIENTS AND METHODS: Since 1995, 30 patients (18 males; median age, 56 (range, 25-83) years) have received preoperative chemoradiotherapy for ultrasound-staged T3 or T4 rectal cancer. All patients underwent an endorectal ultrasound, CT scan, and review in our multidisciplinary Gastrointestinal Tumor Board before treatment. All patients had pathology-demonstrated invasive adenocarcinoma of the rectum. Eleven patients were Stage T3N0, 14 were T3N1, and five were T4N1. Patients received radiotherapy to the primary tumor and draining lymph nodes (45 Gy) followed by a tumor boost (50.4-54 Gy). Protracted-venous-infusion 5-fluorouracil (225 mg/m2 per day, seven days per week) was administered throughout treatment. Surgical resection was performed six to ten weeks after completing chemoradiotherapy. Using endorectal ultrasound measurements, the primary tumor was a median of 4 (range, 0-12) cm from the anal verge, encompassed 50 (range, 20-90) percent of the rectal circumference, and was 6 (range, 3-12) cm in diameter. RESULTS: No Grade 4 toxicity was observed during chemoradiotherapy. Three patients experienced Grade 3 toxicity (diarrhea), and four patients required a treatment interruption of greater than three days. All patients completed at least 90 percent of the prescribed radiotherapy dose. All patients underwent surgical resection. Ninety-four percent had clear surgical margins. All pathologic specimens had significant evidence of necrosis, hyalinization, and fibrosis. Thirty-three percent of the specimens had a complete pathologic response (defined as no evidence of viable tumor cells). Of the 19 patients with ultrasound-staged N1 disease, only five had pathologic evidence of nodal involvement after chemoradiotherapy. Of the 25 patients with ultrasound-staged T3 disease, pathologic staging revealed eight with T0, two with T1, five with T2, and ten with T3 disease. Of the five patients with ultrasound-staged T4 disease, pathologic staging revealed two with T0, one with T2, and two with T3 disease. No patient developed progressive disease while on treatment. Two patients have experienced local failure at 6 and 20 months, and one patient failed in the liver at seven months. Twenty-seven patients remain free of disease with a median follow-up of 20 (range, 3-53) months. CONCLUSION: Our experience suggests that preoperative chemoradiotherapy is well tolerated, down-stages tumors, and sterilizes regional lymph nodes.

Carcinoid tumor: an extremely unusual presacral lesion. Report of a case.

PURPOSE: Use of endorectal ultrasonography in preoperative evaluation of a presacral lesion is demonstrated. METHOD: The natural history, presentation, evaluation, and treatment of presacral lesions in adult patients are presented. The case of a female patient with a presacral carcinoid tumor is presented and discussed. RESULTS: The patient underwent preoperative evaluation including physical examination, hematologic studies, proctosigmoidoscopy, magnetic resonance imaging, computed tomographic scanning, and endorectal ultrasonography. Ultrasonography proved to be extremely valuable in differentiating tumor compression from tumor invasion of the rectal wall. The patient underwent en bloc excision of the lesion, surrounding tissue, and coccyx. Pathologic diagnosis was carcinoid tumor, possibly replacing a presacral lymph node. Postoperative complete gastrointestinal tract work-up and urinary 5-hydroxyindoleacetic acid analysis along with preoperative imaging revealed no evidence of synchronous lesions or additional metastases. CONCLUSIONS: Presacral lesions are extremely rare entities. The role of endorectal ultrasonography has not been clearly defined. This case demonstrates the value of this simple and safe imaging procedure in detecting bowel wall compression vs. invasion, greatly assisting in planning an operative approach.

Modulation of cisplatin sensitivity and growth rate of an ovarian carcinoma cell line by bombesin and tumor necrosis factor-alpha.

A twofold change in the cisplatin (DDP) sensitivity of 2008 human ovarian carcinoma cells is sufficient to reduce tumor response in vivo. The DDP sensitivity of these cells can be enhanced by activation of the epidermal growth factor and protein kinase C signal transduction pathways. We report here that two endogenous growth factors, bombesin and tumor necrosis factor alpha (TNF alpha), enhanced DDP sensitivity by factors of 1.7 +/- 0.1 (SD)-fold and 1.8 +/- 0.1 (SD)-fold, respectively. Both agents also produced sensitization in an 11-fold DDP-resistant 2008 subline. Neither bombesin nor TNF alpha changed the accumulation of DDP, glutathione content, or glutathione-S-transferase activity in 2008 cells. However, a 2-h exposure to both bombesin and TNF alpha was sufficient to increase 2008 cloning efficiency by up to 2.6 +/- 0.1 (SD)-fold and 2.2 +/- 0.1 (SD)-fold, and it increased average colony size by 1.35 +/- 0.1 (SD)-fold and 1.55 +/- 0.1 (SD)-fold, respectively. Bombesin increased intracellular free calcium, and this was blocked by the bombesin receptor-specific antagonist SC196, demonstrating that 2008 cells have functional bombesin receptors. These results indicate that bombesin and TNF alpha can enhance sensitivity to DDP in both DDP sensitive and resistant variants of a human ovarian carcinoma and that both agents serve as growth factors for this tumor.

Altered intracellular calcium regulation in human colorectal cancers and in "normal" adjacent mucosa.

Intracellular calcium [(Ca2+)i] was measured in human colonic epithelia derived from control mucosa from noncancer patients, from grossly "normal" mucosa taken 10-30 cm proximal to primary colorectal cancers, and from colorectal cancers. (Ca2+)i was measured first in cells bathed by calcium-free solution and again after adding 1 mM calcium. Compared to control mucosa, (Ca2+)i was 27% lower in cancer cells in the presence of 1 mM extracellular calcium, whereas (Ca2+)i was elevated more than 3-fold in the adjacent "normal" mucosa from cancer patients in both media. These results suggest altered (Ca2+)i levels in malignant cells and the presence of a "field defect" in (Ca2+)i regulation in "normal" colonic mucosa adjacent to colorectal cancers.