Value of perioperative brachytherapy in the management of non-oat cell carcinoma of the lung.

Nearly one-half of all patients with non-oat cell carcinoma of the lung are found to have mediastinal lymph node metastases at the time of initial presentation. There is no consensus today on what constitutes best treatment in patients whose disease is confined to the chest and in whom mediastinal lymph node metastases are the only evident site of tumor spread. The overall survival of these patients is so low that the majority have been either excluded from therapy or have been treated palliatively by external radiation therapy. In an attempt to improve the control of mediastinal lymph node metastases in the operable patients, we began a pilot study in 1977 at Memorial Hospital to determine the value of perioperative brachytherapy (permanent Iodine-125 implantation of primary lung and a temporary Iridium-192 implantation of the mediastinum) with or without resection followed by a moderate dose of postoperative external beam irradiation. Eighty-eight patients with disease limited to one hemithorax (N2 MO) were treated with this combined method during the period 1977 through 1980. Locoregional control was observed in 76% of the 88 patients. The median survival is 26 months and the 2 year actuarial survival is 51%. There was no post-operative mortality. This pilot study has demonstrated that the combination of surgery, perioperative brachytherapy and external beam irradiation in non-oat cell carcinoma of the lung, metastatic to mediastinal lymph nodes, can improve the locoregional control and prolong survival with minimal early or late morbidity.

Absorbable mesh in placement of temporary implants.

PURPOSE: To evaluate absorbable mesh for the suturing of afterloading catheters in patients with tumors involving the chest wall. METHODS AND MATERIALS: Patients underwent thoracotomy and resection of tumor; a layer of absorbable mesh was then sutured to the tumor bed. Nylon flexiguide afterloading catheters were sutured into the mesh at about 1.5 cm distance from each other. A second layer of mesh was then sutured on top of the catheters. The chest wall was closed. Orthogonal radiographs and CT scans of the area of implants were done to verify catheter position in each patient on day 1 and on the last day of implant. Computer dosimetry by digitization of dummy sources was performed on each set of radiographs. The same seed for both sets of films was chosen as the origin of digitization. All seed coordinates were compared directly to offset for any rotation of the patient during the two sets of films. The distances were calculated from all seed positions to the origin, then tabulated and compared. RESULTS: The distances agreed within a few millimeters (7-8 mm). The differences may be attributed to the patient's breathing and to the localization uncertainty. The resulting dose alteration was negligible. CONCLUSION: This technique appears to provide adequate anchorage of catheters with resulting constant seed position and dose distribution in areas of scant tissues or in surgical beds of considerable size.

Chemoradiation in advanced nonsmall cell lung cancer.

PURPOSE: Resectability, local control, and survival were evaluated in advanced stage nonsmall cell lung cancer treated with simultaneous chemoradiation therapy delivered in an accelerated, interrupted twice-a-day schedule. METHODS AND MATERIALS: Forty-seven consecutive patients with Stage IIIA or IIIB nonsmall cell lung cancer, consenting to participation in the study, received cisplatin, 30 mg/m2 for 3 days, etoposid, 80 mg/m2 for 3 days, and 5-fluorouracil, 900 mg/m2 for 4 days. Radiation therapy consisted of 2 Gy given twice a day for 5 days. Two weeks rest was planned between cycles. Patients were evaluated for resectability after the second cycle. Any patient with unresectable tumor received a third cycle of treatment. RESULTS: Forty-seven patients were evaluable for acute toxicity: eighteen (38%) required an extended rest period for esophagitis or low blood count; 3 (6%) had sepsis, of whom 1 (2%) expired. Three patients (6%) had multiple blood transfusions for low hemoglobin. Median follow-up is 23.6 months, with a range of 10-49 months. Nine patients (19%) failed locally; 15 (32%) had local and distant failure; 7 (15%) failed only at distant sites. Twelve patients (25.5%) are alive with no evidence of disease; 4 patients were lost to follow-up with disease. The 2-year actuarial survival is 49%, and the 4-year is 28.2%. CONCLUSION: Simultaneous chemoradiation is well tolerated with acceptable toxicity. The overall 2- and 4-year actuarial survival is somewhat better than that reported in the literature. Resectability in Stage IIIB patients was not increased with this regimen nor was any surgical specimen free of cancer. The 47% distant failure rate is not different from those reported by others.

Occult axillary lymph node metastases from breast cancers with intramammary lymphatic tumor emboli.

Serial sections were performed on the axillary lymph nodes from 28 women with mammary carcinoma and intramammary lymphatic tumor emboli. Occult metastases were demonstrated in nine women (32%), all less than 2 mm in diameter. During the 10 years of follow-up, no difference in recurrences was found between this group (33%) and those without occult metastases (37%). Serial sectioning of lymph nodes in this group of patients does not appear to be helpful in prognosis.

Results of surgical treatment in Stage I lung cancer.

One hundred fifteen patients underwent resection for Stage I non-oat cell carcinoma of the lung. Each of these patients was evaluated carefully for extent of disease and classified as having a Stage I cancer only after the resected specimen was reviewed histologically and all regional nodes in the mediastinum were assessed. There were no deaths following operation. At 1 year of follow-up 75 of 81 patients (93 percent) were alive, and at 3 years, 77 percent were alive and free of disease. No patient had local recurrence and none was lost to follow-up. Patient with correctly staged early lung cancers have an excellent survival rate at 2 and 3 years with surgery alone. Merits of various adjuvant programs in this group of patients can be assessed correctly only if follow-up periods are prolonged and the numbers of patients evaluated are large.

Pulmonary resection in metastatic carcinoma.

Resection of pulmonary metastases in osteogenic sarcoma has been reported by us to result in a five-year survival rate of 27 percent. A later report of surgical management of pulmonary metastases from all types of sarcomas showed a five-year survival rate of 26%. This report reviews the experience with 188 patients treated surgically for pulmonary metastasis from a variety of carcinomas, demonstrating that a similar rate of survival is obtainable by surgical excision of these metastases. A total of 188 patients underwent 242 thoractomies for metastatic pulmonary carcinomas. The most frequent sites of origin were the colon, melanoma, breast, and testicular carcinoma. Surgical treatment of these metastases is justified when the following criteria are adhered to: (1) primary site controlled or controllable; (2) no extrapulmonary metastatic sites demonstrable; (3) good surgical risk; and (4) no effective treatment available by nonsurgical means.

High dose-rate endobronchial irradiation in malignant airway obstruction.

We evaluated the effectiveness of high dose rate (HDR) endobronchial irradiation for palliation of malignant airway obstruction. Between May 1989 and February 1992, 39 patients were treated in our department. Thirty-two patients (82 percent) had primary lung neoplasms and 7 (18 percent) had metastatic disease. Thirty-three patients (85 percent) had prior external irradiation (either alone or in combination with chemotherapy), and 9 patients (23 percent) received laser excision before treatment. Of the 39 patients, 14 (36 percent) presented with hemoptysis, 20 (51 percent) with cough, 15 (38.5 percent) had dyspnea, and 15 patients (38.5 percent) had pneumonia or atelectasis. There were 57 applications performed in the 39 patients. Patients with hemoptysis had 93 percent complete response (CR), 20 percent with cough had CR; 60 percent improved (partial response [PR]); no response was seen in 20 percent. Atelectasis and pneumonia resolved in 20 percent of patients. Eighteen patients (46 percent) underwent a second procedure and were evaluated for objective response; 34 percent had CR, 44 percent had PR, and 22 percent did not respond. There were two acute (one bronchospasm, one pneumothorax) and three late (two strictures, and one exsanguination) complications. In our experience, HDR was highly effective in the palliation of airway symptoms caused by malignant tumors, with acceptable toxicity.

Lack of efficacy of intrapleural bupivacaine for postoperative analgesia following thoracotomy.

Intrapleural bupivacaine has been reported to be effective for analgesia following cholecystectomy and thoracic surgery. Twenty patients who had a posterolateral thoracotomy were studied in a randomized, double-blind, placebo-controlled fashion. Patients were assigned to receive intrapleural administration of either 0.5 percent bupivacaine or saline solution every 4 h for 12 doses postoperatively, as well as narcotic analgesics as needed for additional pain control. Pain was assessed using a visual analogue scale. Narcotic analgesic use, duration of hospitalization, and the development of complications were recorded. There were nine evaluable patients who received bupivacaine, and ten patients who received placebo. The age, sex, and type of operation were similar in the two groups, and the procedures were performed by the same two surgeons. The mean pain score at 24 h postoperatively was 5.8 +/- 0.8 in the bupivacaine group and 6.0 +/- 0.6 in the placebo group. At 48 h, the scores were 4.6 +/- 0.8 in the bupivacaine group and 5.1 +/- 0.9 in the placebo group. The mean dose of morphine sulfate or equianalgesic dose of meperidine during the first 24 h was 13.9 +/- 3.7 mg in the bupivacaine group and 12.6 +/- 1.8 mg in the placebo group, and during the next 24 h it was 40.0 +/- 13.4 mg in the bupivacaine group and 38.0 +/- 9.2 mg in the placebo group. The mean duration of hospitalization was 12.8 +/- 3.2 days in the bupivacaine group and 12.1 +/- 2.9 days in the placebo group. Two patients who received bupivacaine and three patients who received placebo had development of pneumonia or atelectasis postoperatively. There was no statistically significant difference in any parameter between those who received bupivacaine and those who received placebo. Thus, there was no subjective or objective clinical benefit of this method of postoperative analgesia compared with placebo following posterolateral thoracotomy.

Immune reactivity in primary carcinoma of the lung and its relation to prognosis.

Detailed studies of immune reactivity were performed in 154 patients with primary lung cancer, 20 patients with benign thoracic lesions, and 109 healthy persons. Reactions to the 2,4-dinitrochlorobenzene (DNCB) skin test were postive in 73 per cent of patients with lung cancer and all (100 per cent) of the patients with benign disease (p less than 0.05). The incidence of DNCB reactions was 78 per cent for Stage I and II cancers (37 patinets), 73 per cent for resectable Stage III cancer (22 patients), and 66 per cent in patients with unresectable or inoperable Stage III cancer. DNCB reactivity showed a relationship to primary histology. The incidence of DNCB positive reactions was 80 per cent in patients with epidermold carcinoma versus 57 per cent in patients with adenocarcinoma, 64 per cent in patients with oat cell cancer, and 80 per cent in patients with terminal bronchiolar carcinoma. In vitro immune studeis correlated best with stage of disease. These included the absolute lymphocyte count and absolute T cell count and lymphoxyte stimulation witalen A (Com A). These values were in the normal range in patients with Stage I cancer but were significantly depressed in patients with Stage III cancer. Svrvival curves were plotted in patients with Stage III disease according to the responses to three immune parameters: DNCB, absolute lymphocyte count, and PHS stimulation. Although patients with normal reactions generally had better survival rates, PHA responses showed the most significant correlation to survival. These tests support the usefulness of immune testing as an additional parameter of assessing biological risk in patients with primary lung cancer.

Elderly applicants to long-term care institutions. I. Their characteristics, health problems and state of mind.

As part of a study of long-term institutional care of the elderly, this report presents a comparison of the characteristics, health problems, and state of mind of 193 elderly applicants for such care (Group A) with those of 141 elderly persons living independently in the community (Group I). Group A members were older, living with a spouse less often, and had low incomes. They showed much more cerebrovascular disease, incontinence, recent loss of independence in the activities of daily living, dementia, recent hospitalization, loneliness, and depression. They had had much less recent involvement in social and recreational activities, although most had not been socially isolated. They had received more extensive help from relatives and friends, and it seemed unlikely that additional help from these sources would keep many more of these elderly persons out of institutions. Community agencies and services had been used by a relatively low proportion of Group A, and hardly at all by Group I.

Elderly applicants to long-term care institutions. II. The application process; placement and care needs.

As part of a study of long-term institutional care of the elderly, this report presents salient data concerning 193 elderly applicants. Physicians play an important role in decisions to apply for such care. More than half of the applicants and about 80% of their family members approved of the proposed move. The number applying to homes for the aged vs. other institutions seemed much greater than appropriate; many of these applicants appeared more elibible for placement in foster homes and specialized facilities for the demented, or for remaining in their own homes. About a fifth of the applicants could have continued living independently if they had received a reasonable amount of community assistance. Action implications include: 1) expansion and more informed use of community services, 2) more programs of supervised foster homes for the elderly, 3) construction of specialized institutions for the demented, and 4) a greater effort by institutions to satisfy the desire of many new residents to be involved there in useful tasks.

Chest wall stabilization using plate fixation.

Large defects of the chest wall require stabilization of the remaining thorax to prevent paradoxical movement. A technique of fixation using rib grafts and compression plates is presented.

High-frequency jet ventilation in major airway or pulmonary disruption.

High-frequency jet ventilation is an experimental method of mechanical support, which achieves satisfactory alveolar ventilation and oxygenation at low peak-inspiratory pressures of 5 to 8 cm H2O and low end-expiratory pressures of 3 to 5 cm H2O. This characteristic was used to advantage in 23 patients with cancer, 12 of whom had tracheal or bronchial disruption complicated by pneumonia. Eight patients who could not be supported by conventional means were salvaged. Barotrauma complicated the very high peak airway pressures required to ventilate 8 of 11 patients with respiratory failure associated with diffuse interstitial pneumonia or pulmonary fibrosis. There were only 2 survivors despite temporary normalization of arterial blood gas values in 7 patients. Earlier use of high-frequency jet ventilation in patients with poor compliance may prevent pulmonary disruption in addition to deleterious hemodynamic and systemic effects of conventional high-pressure ventilation. Other applications under study include the role of jet ventilation in resection of the trachea or carina, and in major airway trauma.

New trends in skeletal reconstruction after resection of chest wall tumors.

Involvement of the chest wall in malignant tumors, either primary or resulting from contiguous or metastatic spread, occurs in less than 5% of thoracic malignancies. From 1963 through 1978, 155 patients had chest wall resection in continuity with the tumor. Eighty-five tumors were carcinomas, and 70 were sarcomas. Since 1973 reconstruction of chest wall defects in 12 patients has included the use of a composite of Marlex mesh and methyl methacrylate. It provides an excellent replacement both physiologically and esthetically. Such a reconstructed chest wall has obviated the need for postoperative respiratory support. The overall mortality was 4.5% (7 out of 155). The 5-year survival in this varied group of patients is 20%. We believe excellent palliation can be achieved even in patients who are not potentially curable.

Aortoesophageal fistula after reconstruction of the thoracic spine.

Aortoesophageal fistula is a rare complication after neurosurgical repair of the thoracic spine. We report an instance of a lethal aortoesophageal fistula caused by a pseudoaneurysm that developed after long contact between the prosthetic material from a spinal reconstruction procedure and the thoracic aorta. Pathologic examination showed that the mesh formed the roof of the pseudoaneurysm and was the most probable cause of the lesion.

Treatment of esophageal carcinoma combined preoperative chemotherapy.

Thirty-four patients with epidermoid carcinoma of the esophagus received a triple-drug regimen preoperatively consisting of cisplatin, vindesine, and bleomycin. Partial response to chemotherapy (greater than 50% reduction in measurable tumor size with concomitant improvement in swallowing function) was noted in 65% of the patients. Of the 34 patients, 28 (82%) had resectable disease. A one-stage high esophagogastrectomy utilizing the end-to-end anastomosis stapling device was performed on all 28 patients. Operation was followed by external radiation therapy to the esophageal bed, to a tumor dose of 5,500 rads delivered in 5 weeks. The postoperative median follow-up is now 14 months (range, 7 to 36 months). Thirteen patients are alive and well, and 10 patients have relapsed, 4 of whom are still alive with disease. Two patients died of postoperative complications, and 1 death was drug related. On the other hand, 5 of the 6 patients with unresected tumors died within 5 months. While the preliminary results are encouraging, longer follow-up will be required to determine whether the response rate to chemotherapy will result in a longer disease-free interval and longer survival.

Interstitial irradiation for unresectable carcinoma of the lung.

From 1963 to 1971, 105 patients with histologically proved cancer of the lung were explored at Memorial Hospital and underwent interstitial implantation using encapsulated sources of radon 222 (53 patients) or iodine 125 (52 patients). These lung cancers were considered unresectable because of extension of the disease into the mediastinum with fixation or invasion of the major vessels, trachea, and esophagus or chest wall involvement. No apical lesions, which have a better prognosis, are included in this review. Sixty-nine patients had epidermoid cancer, 24 had adenocarcinoma, and the remaining 12 had various other histological types. All patients were staged according to the criteria proposed by the American Joint Committee using the TNM definitions (standing for tumor, nodes, and metastasis). Local control was obtained in 8 of 10 patients (80% with clinical Stage I and II unresectable cancers of the lung and in 44 of the 95 (46%) with clinical Stage III lung cancer. The two-year survival was 50% for Stages I and II and 7% for Stage III. Five patients have survived for five years or more. The complications, disease-free interval, local recurrences, distant metastases, and survival are presented and indications for this type of therapy outlined.

Management of malignant pleural effusions with pleuroperitoneal shunting.

Malignant pleural effusions are often debilitating conditions for the patient with advanced carcinoma. Traditionally, treatment has been repeated thoracentesis or tube thoracostomy with instillation of sclerosing agents. However, this required the patient to be hospitalized and to have pain and inconveniences of the chest tubes. The drainage also had to be low enough for sclerotherapy to be effective. In 1982, the pleuroperitoneal shunt became a feasible alternative to sclerotherapy. We began using the Denver pleuroperitoneal shunt in July 1991. Twenty shunts were inserted into 19 patients during a two year period ending June 30, 1993. All patients but one were relieved of dyspnea. The mean duration of patency was 26 months and fewer than 25 percent of the shunts clotted before the death of the patient. Our favorable experience with the shunt has resulted in us recommending the Denver pleuroperitoneal shunt for treatment of recurrent malignant pleural effusions and selectively as primary treatment.

Surgical treatment of brain metastases from lung cancer.

Thirty-five patients underwent surgical resection of brain metastases from non-oat-cell lung cancer between 1978 and 1981. Twenty-nine patients received postoperative radiation therapy to the brain. Twenty-three patients were male and 12 were female. Intracranial metastases occurred as the initial symptom of malignancy in 14 patients, and at varying periods following treatment of the primary tumor in 21 patients. The primary tumor and involved nodes were treated by definitive surgery in 18 patients, palliative resection and interstitial radiation in 10 patients, and by radiation therapy or chemotherapy alone in seven patients. The overall median survival time was 14 months. Favorable prognostic variables included: 1) absence of local or systemic disease at time of craniotomy (median 23 months survival time); 2) aggressive treatment of the primary tumor (median 18 months survival time); and 3) metachronous onset of brain metastases (median 15 months survival time). These survival data represent a considerable improvement over the historical 6 months median period of survival in such patients.

Brain metastases in malignant pleural mesothelioma. Case report and review of the literature.

Recent advances in pleural malignant mesothelioma include the sequential use of palliative surgery, perioperative radiation therapy, and systemic chemotherapy. Radical treatments may not only palliate but also improve survival in some patients. The latter may be associated with the appearance of metastases in unusual sites including the central nervous system. In malignant mesothelioma, brain metastases were previously reported in 19 patients at autopsy and in only 1 patient antemortem. We detail the clinical presentation in the second patient with pleural malignant mesothelioma thus far reported to develop brain metastases. The difficulties in diagnosis, the role of immunoperoxidase stains in malignant mesothelioma, excellent tolerance of different modalities of treatment, and a review of the literature of brain metastases in mesothelioma are discussed. Based on our report, the possibility of brain metastases should be investigated by careful clinical examination prior to a radical treatment in patients with progressive refractory mesothelioma.