E. Laterza

Endoscopic ultrasonography in the staging of esophageal carcinoma after preoperative radiotherapy and chemotherapy

BACKGROUND In past years multimodal neoadjuvant treatment for carcinoma of the esophagus has been used with increased frequency. Staging of the neoplasm still remains fundamental in evaluating the response to therapy and in planning operation. The aim of the present study was to assess the accuracy of endoscopic ultrasonography (EUS) in a group of patients with squamous cell carcinoma of the thoracic esophagus after undergoing radiotherapy and chemotherapy. METHODS Among a group of 111 patients with squamous cell carcinoma of the thoracic esophagus and treated with preoperative radiotherapy and chemotherapy, 87 were operated. In these patients it was possible to compare the results of EUS, with regard to depth of invasion of esophageal wall (T) and lymph node involvement (N), with the results of operation and histopathologic study. RESULTS Feasibility of EUS before and after neoadjuvant treatment was 71.2% and 83.9%, respectively. The overall accuracy of EUS regarding the wall invasion was 47.9%. The more frequent error was overstaging, especially in patients with complete response and in patients with minimal residual disease. In the assessment of lymph node involvement, EUS showed an overall accuracy of 71.2% with a moderate kappa value. Sensitivity for N1 and NO was 73.7% and 68.6%, respectively. CONCLUSIONS Endoscopic ultrasonography was feasible in most patients after preoperative radiotherapy and chemotherapy, but our study documented a worsening of accuracy of EUS in the evaluation of T attributable to the confounding presence of radiation fibrosis and soft tissue reaction after radiotherapy and chemotherapy.

Manual compared with mechanical cervical oesophagogastric anastomosis: a randomised trial

OBJECTIVE To compare the short and medium term result of hand-sewn and stapled anastomoses after oesophagectomy. DESIGN Randomised study. SETTING Teaching hospital, Italy. SUBJECTS 41 patients who required oesophagectomy between February 1993 and December 1996. INTERVENTIONS Oesophagectomy and left cervical gastroplasty. MAIN OUTCOME MEASURES Mortality and morbidity. RESULT 21 patients were randomised to have the anastomosis hand-sewn, and 20 to have it stapled. The two groups were comparable. 3 patients died in hospital (2 in the hand-sewn and 1 in the stapled group), and the remainder were followed up a mean of 21 months (range 6-34). There was one clinical leak in the hand-sewn group compared with 3 in the stapled group, and 1 further radiological leak in the stapled group. 2 patients in the hand-sewn and 3 in the stapled group developed strictures. CONCLUSION Though the numbers are too small to be assessed statistically, we think that these result are sufficient to persuade us that oesophagogastric anastomoses should be hand-sewn rather than stapled.

Classification of lymph node metastases from carcinoma of the stomach: Comparison of the old (1987) and new (1997) TNM systems

Abstract. The pN classification of gastric cancer is currently based on the distance of metastatic nodes from the primary tumor (TNM—1987). The UICC (Union Internationale Contre le Cancer) has recently proposed a new classification system based on the number of the involved nodes (TNM—1997). The present prospective study is aimed at verifying whether the two classifications (1) assign approximately a similar rank to individual patients and (2) give comparable prognostic information. The Cox regression model was used to evaluate the prognostic significance of either the distance or the number of positive nodes, controlling for sex, age, site, histology and depth of tumor invasion, in a group of 175 patients who underwent curative surgery for gastric cancer from March 1988 to October 1997. Among the patients classified as N1 and N2 according to TNM—1987, 81.8% (36/44) and 35.8% (19/53), respectively, were coded as N1 and N2 by the new classification. The survival probabilities of N1 and N2 categories were similar in both classifications. The N2 category of TNM—1987 comprised also 10 cases with >15 positive nodes (N3 category of TNM—1997), who presented a large excess mortality (RR = 35.14 with respect to N0). When the site and number of positive nodes are combined in a new variable, both appear to be important from a prognostic point of view. Both anatomic location and number of nodes with metastasis are important predictors of survival in gastric cancer patients. Caution should be used when replacing the old classification with the new one, as they group patients in a different way.

Induction Chemo-Radiotherapy for Squamous Cell Carcinoma of the Thoracic Esophagus: Long-Term Results of a Phase II Study

Background: This study was done to evaluate the results of the combined use of chemo- and radiotherapy before surgery in a group of patients with squamous cell esophageal carcinoma after a median follow-up period of more than 5 years.Methods: Between June 1987 and January 1995, 111 patients with squamous cell carcinoma of the thoracic esophagus were submitted to a preoperative course of radiotherapy (3000 cGy) and chemotherapy (cisplatin and 5-FU) before surgery in the First Division of General Surgery at the University of Verona.Results: The neoadjuvant treatment was completed in 90.9% of the cases (101/111). After an average of 29 days, 87 patients underwent surgery (operability rate: 78.3%) and, of these, 80 underwent esophagectomy (resectability rate: 91.9%). Histopathologic studies showed no residual disease in the specimen (T0) in 17 cases (21.2%), only microscopic clusters of neoplastic cells within the esophageal wall (Minimal Residual Disease, MRD) in 14 cases (17.5%) and in 5 cases the tumor did not extend beyond the submucosal layer (T1). The median overall survival time of the 111 patients who were eligible for the study protocol was 14 months, and the 2- and 5-year survival rates were 32.0% and 17.5%, respectively. Kaplan-Meier determination of survival showed a statistically significant difference between the good responders (T0, T1, and MRD) to the neoadjuvant treatment and the remaining cases. The 2- and 5-year survival rates were 50.3% and 34.9%, respectively, in the good responder group compared with 26.7% and 10.7%, respectively, in the other cases, with a median survival time of 24 months vs. 13 months, respectively.Conclusions: The neoadjuvant treatment showed promising results, especially in the group of patients that had a good response. The identification of these patients may be the key to selecting which patients should be submitted to preoperative radio- and chemotherapy.

EFFICACY AND TOXICITY OF VINORELBINE-CARBOPLATIN COMBINATION IN THE TREATMENT OF ADVANCED ADENOCARCINOMA OR LARGE-CELL CARCINOMA OF THE LUNG

Aims and background The aim of the study was to assess the activity and toxicity of the vinorelbine-carboplatin combination in advanced adenocarcinoma or large-cell carcinoma of the lung. The new vinca derivative, vinorelbine, shows promising activity when combined with cisplatin, but toxicity of the combination is substantial. Methods Accordingly, we substituted carboplatin for cisplatin in the combination in order to improve the therapeutic index. From March 1992 to March 1994, 55 untreated patients with undifferentiated unresectable or metastatic adenocarcinoma or large-cell carcinoma of the lung were recruited. The treatment consisted of a course of carboplatin (300 mg/m2) and vinorelbine (25 mg/m2) repeated every 4 weeks. The only grade 3 toxicity observed was 16 cases of grade 3 vomiting and 2 cases of grade 3 stomatitis. Results The positive response rate was 40% (partial response, 22 patients). In conclusion, the vinorelbine-carboplatin combination may be regarded as an active, safe regimen for the palliative treatment of advanced adenocarcinoma or large-cell carcinoma of the lung.

Acute cholecystitis: Ultrasonographic staging and percutaneous cholecystostomy

Experience in the treatment of acute cholecystitis with percutaneous cholecystostomy in 29 high-risk and elderly patients is reported. The treatment group included 14 men and 15 women, 21 of whom were over 70 years of age. The suspected clinical diagnosis of acute cholecystitis was confirmed in all cases by ultrasonography (accuracy: 95.6%). The percutaneous cholecystostomy was successful in 27 of 29 cases and these patients had a sudden improvement in their clinical condition; failure of the procedure was due in one patient to dislodgement of the catheter and in another patient to the guide-wire slipping out of the gallbladder. Six patients complained of pain radiating to the right shoulder which disappeared within 30-60 minutes after the procedure. Twenty-three of the 27 patients subsequently underwent elective cholecystectomy. In 22 patients the ultrasonographic findings were compared with the histology; thus enabling us to establish an ultrasonographic staging of acute cholecystitis related to the seriousness of the disease. Percutaneous cholecystostomy is the treatment of choice in high-risk patients, in the elderly, as well as in young patients with impending perforation.

Perigastric lymph node metastases in gastric cancer: comparison of different staging systems

Background. Perigastric lymph node metastases in gastric cancer are classified differently by different staging systems: the distance of positive nodes from the primary tumor is considered by the 1987 International Union Against Cancer (UICC)-TNM system, but not by the Japanese staging system (of the Japanese Research Society for Gastric Cancer [JRSGC]); the new UICC-TNM system of 1997 is based on the number of involved nodes without differentiating perigastric from regional nodes. The aim of the present study was to assess which classification was more useful to predict prognosis in gastric cancer patients with metastases to the perigastric nodes. Methods. The results for 107 patients with lymph node metastases to the first and second tiers who underwent curative gastrectomy for gastric cancer from March 1988 to October 1997 were analyzed. In particular, we compared the clinical characteristics and the survival probabilities of: (1) patients with metastases to perigastric nodes located within 3 cm from the primary tumor, classified as N1; (2) patients with metastases to perigastric nodes located 3 cm beyond the primary tumor (N2 in the UICC-TNM and N1 in the Japanese classification), classified by us as N1–N2; and (3) patients with metastases to the second tier (classified by us as N2). We also assessed the number of positive nodes dividing the patients into groups according to the 1997 UICC TNM system. Results. On multivariate survival analysis, the mortality risks in the N1 and N1–N2 patients were comparable (relative risk [RR], N1–N2 versus N1, 1.32; 95% confidence interval [CI], 0.53–3.51) and were half the mortality risk in N2 patients (RR, N2 versus N1, 2.52; 95% CI, 1.33–4.79). The N1 and N1–N2 categories, while presenting markedly different distributions in the number of metastatic nodes (patients with more than seven metastatic nodes constituted less than 20% of the N1 group and more than 60% of the N1–N2 group), showed similar prognostic significance. Conclusion. In the present series, the distance of perigastric nodes from the primary tumor did not seem to exert a significant effect on prognosis, and the use of a combined classification based on anatomical location (JRSGC) and number of node metastases (UICC-TNM 1997) could be more useful than either system alone for prognostic purposes.

Endosonography and Computerized Tomography in the Evaluation of Tumor Invasion in Esophageal Cancer After Preoperative Chemo- and Radiotherapy

Esophageal carcinoma presents a poor prognosis with 5-year survival rates not exceeding 5%, but rising to 18% for resected patients [1,2]. Surgery is currently the most valid form of therapy for the disease, though the morbidity and mortality rates are still high [3–5].

Neoadjuvant Treatment for Squamous Carcinoma of the Thoracic Esophagus

Cancer of the esophagus has a poor prognosis. Survival rates appear to be correlated with depth of tumor invasion (T), lymph node involvement (N) and the presence of distant metastases (M). The biological behavior of the disease, characterized by early regional lymphatic spread, make it a systemic disease and explains the poor results of surgery and radiotherapy. In the last 20 years, survival rates for esophageal cancer have been less than 10% [1–2]. To obtain better results, several authors suggested many trials of different treatments including chemotherapy.