M Gignoux

BACKGROUND: The benefits of preoperative chemotherapy and radiation for esophageal carcinoma are under investigation. A pilot study was undertaken to determine if pathologic assessment of tumor regression correlated with disease free survival. METHODS: Ninety-three resected specimens from patients treated with cis-dichloro-diamino cisplatin and irradiation before surgery were examined on semiserial sections. Patients selected for surgery were all Status 1 according to the World Health Organization (WHO) classification. Histologic typing was based on the WHO classification. Tumor regression grade (TRG) was quantitated in five grades: TRG 1 (complete regression) showed absence of residual cancer and fibrosis extending through the different layers of the esophageal wall; TRG 2 was characterized by the presence of rare residual cancer cells scattered through the fibrosis; TRG 3 was characterized by an increase in the number of residual cancer cells, but fibrosis still predominated; TRG 4 showed residual cancer outgrowing fibrosis; and TRG 5 was characterized by absence of regressive changes. Survival curves were estimated according to the Kaplan-Meier method. A quantification of the relationship between treatment failure and confounding variables (age, tumor location, tumor size, esophageal wall involvement by residual cancer and/or regressive changes, histology, treatment, adequacy of surgery, pathologic lymph node status, and tumor regression grade) was done using Cox's proportional hazards model. RESULTS: Forty-two percent of specimens were TGR 1-2; 20%, TGR 3; and 33%, TGR 4-5. Univariate analysis found that tumor size, pathologic lymph node status, tumor regression grade, and esophageal wall involvement were highly correlated with disease free survival (P < 0.05). After multivariate analysis, only tumor regression (i.e., TRG 1-3 versus TRG 4-5) remained a significant (P < 0.001) predictor of disease free survival. CONCLUSIONS: This study highlights the importance of tumor regression in the survival of patients with esophageal carcinoma treated with preoperative chemoradiotherapy. These findings suggest that tumor regression grade should be considered when evaluating therapeutic results.

BACKGROUND: We conducted a multicenter, randomized trial to compare preoperative chemoradiotherapy followed by surgery with surgery alone in patients with stage I and II squamous-cell cancer of the esophagus. METHODS: The preoperative combined therapy consisted of two one-week courses; each involved radiotherapy, in a dose of 18.5 Gy delivered in five fractions of 3.7 Gy each, and 80 mg of cisplatin per square meter of body-surface area, administered 0 to 2 days before the first day of radiotherapy. The surgical plan included one-stage en bloc esophagectomy and proximal gastrectomy by the abdominal and right thoracic routes, to be performed immediately after randomization in the group assigned to surgery alone and two to four weeks after the completion of preoperative chemoradiotherapy in the group assigned to combined therapy. RESULTS: A total of 297 patients entered the study; 11 were found to be ineligible, and 4 were lost to follow-up. Of the remaining 282, 139 were assigned to surgery alone and 143 to combined therapy. After a median follow-up of 55.2 months, no significant difference in overall survival was observed; the median survival was 18.6 months for both groups. As compared with the group treated with surgery alone, the group treated preoperatively had longer disease-free survival (P=0.003), a longer interval free of local disease (P=0.01), a lower rate of cancer-related deaths (P=0.002), and a higher frequency of curative resection (P=0.017). However, there were more postoperative deaths (P=0.012) in the group treated preoperatively with chemoradiotherapy. Three prognostic factors were found to influence survival in a multivariate analysis: the disease stage, based on computed tomography; the location of the tumor; and whether the surgical resection was curative. CONCLUSIONS: In patients with squamous-cell esophageal cancer, preoperative chemoradiotherapy did not improve overall survival, but it did prolong disease-free survival and survival free of local disease.

A randomized clinical trial was conducted by the European Organization for Research and Treatment for Cancer (EORTC) Gastrointestinal Cancer Cooperative Group to study the effectiveness of irradiation therapy administered in a dosage of 34.5 Gy, divided into 15 daily doses of 2.3 Gy each before radical surgery for rectal cancer (T2, T3, T4, NX, MO). Four hundred sixty-six patients were entered in the clinical trial between June 1976 and September 1981. Tolerance and side effects of preoperative irradiation were acceptable. The overall 5-year survival rates were similar in both groups. When considering only the 341 patients treated by surgery with a curative aim, the 5-year survival rates were 59.1% and 69.1% in the control group and in the combined modality group, respectively (p = 0.08). The local recurrence rates at 5 years were 30% and 15% in the control group and the adjuvant radiotherapy group, respectively (p = 0.003). Although this study did not show preoperative radiotherapy to have a statistically significant benefit on overall survival, it does have a clear effect on local control of rectal cancer. Therefore, before performing radical surgery, this adjuvant therapy should be administered to patients who have locally extended rectal cancer.

Abstract Attempts to combine radiation therapy and surgery in patients with operable carcinoma of the esophagus began 30 years ago. The first reported surgical series showed a low rate of resectability and a high postoperative mortality. Results of radiation therapy alone were also disappointing in the long run, especially in patients who appeared to be excellent operative risks with small localized tumors. The rationale for a combined approach was that x‐ray therapy could bring about a reduction of tumor activity and bulk, an improvement in nutritional state through the restoration of the ability to swallow, a reduction of transplantability of the tumor, and a curative effect on periesophageal regional disease which is not treated well by surgery. On the other hand, surgery often allowed an extended resection, clearing residual foci or distant esophageal wall extension. The limit of a combined approach is the toxicity of the preoperative radiation which must be mild enough to allow surgery to proceed without excessive delay or increased mortality. Numerous radiotherapy schedules were tried using different fields, doses, and fractionations, most of them in nonrandomized studies. Two prospective randomized trials have been recently reported. The final results of a third prospective trial, run by the E.O.R.T.C., will be presented .

OBJECTIVE: Liver adenomatosis (LA) is a rare disease originally defined by Flejou et al in 1985 from a series of 13 cases. In 1998, 38 cases were available for analysis, including eight personal cases. The aim of this study was to review and reappraise the characteristics of this rare liver disease and to discuss diagnosis and therapeutic options. BACKGROUND: LA was defined as the presence of >10 adenomas in an otherwise normal parenchyma. Neither female predominance nor a relation with estrogen/progesterone intake has been noted. Natural progression is poorly known. METHODS: The clinical presentation, evolution, histologic characteristics, and therapeutic options and results were analyzed based on a personal series of eight new cases and an updated review of the literature. RESULTS: From a diagnostic standpoint, two forms of liver adenomatosis with different presentations and evolution can be defined: a massive form and a multifocal form. The role of estrogen and progesterone is reevaluated. The risks of hemorrhage and malignant transformation are of major concern. In the authors' series, liver transplantation was indicated in two young women with the massive, aggressive form, and good results were obtained. CONCLUSION: Liver adenomatosis is a rare disease, more common in women, where outcome and evolution vary and are exacerbated by estrogen intake. Most often, conservative surgery is indicated. Liver transplantation is indicated only in highly symptomatic and aggressive forms of the disease.