Primary malignant non-epithelial tumours of the thoracic oesophagus and cardia in a 25-year surgical material.

During 25 years, 708 patients with primary malignant tumours of the thoracic oesophagus (n = 376) or cardia (n = 332) were referred to our department. Two hundred and forty-nine patients had squamous cell carcinoma and 425 adenocarcinoma. The other 34 tumours, which were primarily classified as undifferentiated carcinoma, malignant carcinoid or non-epithelial, were re-evaluated by means of a second microscopic histologic examination and immunohistologic investigation. This showed primary malignant non-epithelial tumours in seven patients (0.99%): two malignant melanomas, one leiomyosarcoma, one malignant fibrous histiocytoma in the oesophagus (1.06%), two malignant lymphomas, and one malignant melanoma in the cardia (0.90%). All but two of the patients with non-epithelial malignant tumours were 67 years of age or older, and oesophagogastrectomy was performed in all. All tumours were 5 cm or more in diameter (median, 8 cm). Distant metastases were found in three cases. Five died of postoperative complications, one of cancer recurrence 7 months after the operation, and one of an unrelated cause without cancer recurrence 16 months postoperatively. Except for two of the melanomas, the diagnosis was not established until histologic examination of the surgical specimen was performed and, for the third melanoma and the malignant fibrous histiocytoma, not until the present re-evaluation. The characteristics of these seven tumours are discussed, and the importance of obtaining a correct diagnosis from endoscopic biopsy specimens is emphasized.

Placebo-controlled, double-blind study of the effect of verapamil in intermittent claudication.

The clinical effect of verapamil was tested in 24 patients with intermittent claudication in a randomized, placebo-controlled, double-blind, crossover study. Slow-release verapamil or placebo was given for two periods of three weeks. The walking distance, systemic blood pressure, and ankle-brachial blood pressure index were measured. Furthermore, a possible change in peripheral vascular tone was provoked by hyperventilation. The walking distance rose after both verapamil (40%) and placebo (31%) (p less than 0.01 for both) but tended to increase only after verapamil (7%) as compared with placebo. Blood pressure fell equally after both verapamil and placebo (p less than 0.05 for both). Verapamil did not influence the ankle-branchial blood pressure index. No signs of vasoactivity in the lower extremities were seen after hyperventilation. Although the greatest individual improvements in walking distance were seen after verapamil administration, it was not possible to predict positive responders among the patients.

Independent predictors of operative mortality and postoperative complications in surgically treated carcinomas of the oesophagus and cardia--is the aggressive surgical approach worthwhile?

During the 25 years 1960-84, 657 patients were operated on for carcinomas of the thoracic oesophagus (n = 347) or gastric cardia (n = 310). Resection was carried out in 514 (78%) and oesophagogastrostomy in 481 (73%). Overall operative mortality (defined as death within 30 days) was 19% (n = 122). Pulmonary complications developed in 167 patients (25%), cardiovascular complications in 100 (15%), and anastomotic leakage and mediastinitis in 36 (6%). After radical resection of a localised tumour (n = 144), or non-localised tumour (n = 224), pallative resection (n = 146), or exploration (n = 143), the operative mortality and five year cumulative survival were 10% and 26%, 15% and 8%, 27% and 0, and 24% and 0, respectively (p less than 0.01 and p less than 0.0001). Using logistic regression analysis several variables were found to be independent predictors of operative mortality, pulmonary complications, cardiovascular complications, and anastomotic leakage. The predictor variables reflected both general preoperative status of the patients, preexisting cardio-pulmonary diseases, stage of the cancer, and surgical procedures. Based on the final logistic regression models the patients were stratified into risk groups (12 for operative mortality, pulmonary complications, and cardiovascular complications, and eight for anastomotic leakage). Operative mortality varied from 0 to 80%, pulmonary complications from 3 to 100%, cardiovascular complications from 0 to 100%, and anastomotic leakage from 0 to 50% (p less than 0.0001 in each case). Given the high operative mortality and complication rates, and the low five year survival rate after palliative procedures or exploratory operations, a more selective surgical approach seems warranted. Patients likely to have a good response should be identified before operation.

Risk stratification and long-term results after surgical treatment of carcinomas of the thoracic esophagus and cardia. A 25-year retrospective study.

During 25 years (1960 to 1984), 657 patients (aged 22 to 91, mean 66 years) were operated on for carcinomas (squamous cell, n = 230; adenocarcinoma, n = 399; anaplastic, n = 28) of the thoracic esophagus (n = 347) or gastric cardia (n = 310). Esophagogastrectomy was accomplished in 514 patients, of whom 94% (n = 481) had an "inkwell" esophagogastrostomy performed. The hospital mortality rate (less than or equal to 30 days) was 19% and the 5-year cumulative survival rate was 9% +/- 1% (standard error). A Cox regression analysis enabled a detailed risk stratification of the patients. T, N, and M class and age were the strongest predictor variables. The general status of the patients, including pulmonary disease, also had a strong prognostic influence. Eight risk groups were identified having 1-year and 5-year survival rates of 71%/41% (n = 35), 69%/24% (n = 80), 47%/11% (n = 125), 30%/6% (n = 139), 12%/0% (n = 105), 6%/0% (n = 71), 2%/0% (n = 57), and 0%/0% (n = 45) (p less than 0.0001). Hospital mortality (from 6% to 42%) and complication rates increased significantly from the low-risk to high-risk groups. Comparisons with survival rates of background populations matched to each of the first four risk groups indicated that the benefit of surgical treatment may be underestimated if only patient survivals are judged. Use of modern endoscopic and noninvasive tests may yield a reliable TNM classification without surgical exploration. Given the extremely poor prognostic outlook together with high hospital mortality and complication rates of the four last risk groups, an aggressive surgical approach with resection whenever possible can no longer be regarded rational. Selection for surgical treatment should be based on a detailed risk estimation that takes into account both TNM classification and general patient status.

Time-related changes in characteristics of prognostic significance in carcinomas of the oesophagus and cardia.

During 25 years (1960-84) 657 patients were operated on for squamous cell carcinomas (n = 230), adenocarcinomas (n = 399) or anaplastic carcinomas (n = 28) of the thoracic oesophagus or cardia. The male:female ratio was 2.8:1 and the mean age was 66 years (range 22-91 years). Oesophagogastrectomy (n = 514) was performed whenever technically possible. From the first (1960-64) to the last (1980-84) 5-year period the proportion of adenocarcinomas increased from 56 to 78 per cent (P less than 0.001), poorly differentiated cancers increased from 34 to 65 per cent (P less than 0.0001), and stage III-IV tumours increased from 72 to 88 per cent (P less than 0.05). Five-year cumulative rates(s.e.) were 11(3) per cent for operations during 1960-69 (n = 262), 8(2) per cent during 1970-79 (n = 256) and 3(2) per cent during 1980-84 (n = 139; P less than 0.05). Hospital mortality rates (less than or equal to 30 days) and 5-year cumulative survival rates(s.e.) were 6.5 per cent and 36(7) per cent (n = 46) for stage I, 14.0 per cent and 21(4) per cent (n = 114) for stage II, 17.8 per cent and 5(1) per cent (n = 258) for stage III and 23.8 per cent and 3(1) per cent (n = 239) for stage IV tumours (P less than 0.05 and P less than 0.001). Well differentiated (n = 70) cancers, those of medium differentiation (n = 239) and poorly differentiated cancers (n = 348) had 5-year survival rates(s.e.) of 24(5), 10(2) and 5(1) per cent, respectively (P = 0.0007). Squamous cell carcinomas had a better prognosis than adenocarcinomas, even after stratification according to location of primary tumour. The 657 patients who underwent surgery constituted 50 per cent of a total of 1316 cases with cancer of the oesophagus and cardia reported from our catchment area during the study period. Frequency of surgery decreased with age. The annual incidence (number per 100,000 inhabitants aged 20 years or more) of adenocarcinomas of the lower oesophagus and cardia doubled to 5.9 in 1980-84, while that of squamous cell carcinomas tended to decrease (to 2.9). A successive worsening of long-term survival after surgery was explained by significant changes in cancer characteristics having pronounced prognostic significance. Over the 25 years the carcinomas changed towards the present pattern where poorly differentiated adenocarcinomas of the lower third of the oesophagus and cardia in stages III-IV have become predominant.

Elevated serum levels of calcitonin gene-related peptide (CGRP) but no evidence for CGRP gene expression in non-small cell lung carcinomas.

Calcitonin gene-related peptide (CGRP) is a hormone formed by alternative post-transcriptional processing of the calcitonin gene. It is a neuropeptide localized to discrete regions of the central nervous system (CNS) and in nerve fibres associated with blood vessels. It is also expressed in medullary carcinomas of the thyroid and lung carcinoma cell lines. The latter finding suggests a possible value for CGRP as tumour marker in lung carcinomas. In this investigation of 22 patients undergoing operation for lung tumours, pre and post-operative levels of serum CGRP were measured. Preoperative as well as postoperative serum CGRP levels were significantly elevated when compared to age-matched normals. However, no evidence could be found for CGRP gene expression in tumour tissue from the same patients as judged by immunocytochemistry or in-situ hybridization using CGRP cRNA probes. CGRP has been localized to nerve fibres in relation to pulmonary blood vessels and has been shown to be a potent vasodilator. These findings, and the absence of evidence for synthesis in tumours, as opposed to cell lines derived from lung carcinomas, suggests that the lack of post-operative normalization of serum CGRP concentrations may be related to physiological changes in cardiovascular haemodynamics following surgery. Elevated pre-operative serum CGRP levels may also reflect a consequence of the lung carcinoma leading to increased release of CGRP from sites in the vasculature yet to be determined, but does not indicate synthesis de novo and secretion of CGRP by the tumours.

Radiological evaluation of early pleural and pulmonary changes in light asbestos exposure.

In a case-control study of 209 workers from a local railway maintenance and repair workshop, pleuropulmonary lesions were studied on chest radiographs. All workers were known to have been exposed to asbestos fibers of all kinds for a long period of time, but the exposure was light. A "dose index" of every worker was calculated based upon the type of working process and cumulated time spent in the working process. We found a certain dose-effect relationship between asbestos exposure and pleural thickening.

Prophylactic vancomycin versus placebo in arterial prosthetic reconstructions.

Vascular reconstructive surgery with the placement of prosthetic material caudal to the diaphragm is occasionally associated with postoperative wound infection. These infections often lead to amputation and can be lethal. Only a few published reports contain information on the value of prophylactic antibiotic treatment with these operations, but its use is common throughout the world. To investigate this problem, a prospective, double blind, randomized study of vancomycin versus placebo in 128 vascular graft operations caudal to the diaphragm was conducted from June, 1982 to July, 1984. The difference in infection rate was significant (2 p = 0.0008) in favor of the vancomycin group. Fourteen wound infections (21.2%) were found in the placebo group, 3 of which (4.5%) were prosthesis infections. Among the 62 vancomycin-treated patients, one case of superficial wound infection (1.6%) and no cases of prosthesis infection were found. The most common pathogen was Staphylococcus aureus. The study has demonstrated that vancomycin, a narrow spectrum antibiotic, in an ultra-short regimen (one gram one hour before surgery and one gram 4 hours later) is an effective prophylactic agent against postoperative wound infection. Temporary and, in most cases, doses-related side effects were seen in 7.9% of the patients treated with vancomycin.

Chronic constrictive pericarditis treated with total pericardiectomy.

The early and late results of total pericardiectomy performed during a 30-year period in 34 patients with chronic constrictive pericarditis are presented. The overall hospital mortality was 8.8%. The cumulative 5-, 10-, and 30-year survival rates were 79%, 65% and 53%, respectively. Preoperatively, 94% of the patients were classified in functional class III or IV (NYHA classification). After 3 months' follow-up, 94% of the surviving patients were in functional class I or II. After an average 14.2 year follow-up period, 94% of the surviving patients were in functional class I, and of these 72% were in fulltime jobs. It is concluded that the tendency towards early surgery should be encouraged, especially because the chronic state is accompanied by deleterious effects.