Prolonged stabilization of progressive squamous cell cancer of the cervix with interferon-alpha and 13-cis-retinoic acid: report of two cases and review of the literature.

Recurrent and metastatic cervical carcinoma has very poor prognosis, mainly because there is no effective systemic therapy which would increase the duration of survival. Biologic agents have recently been found to have activity in cervical carcinoma. The combination of interferon (IFN)-alpha and 13-cis-retinoic acid had additive and synergistic antitumor activity. Both have antiviral, immunoregulatory and antiangiogenic properties, and are known to modulate malignant cell differentiation and proliferation. We report two patients with recurrent squamous cell carcinoma (SCC) of the cervix who had small-volume progressive metastatic disease, and were treated with a combination of IFN-alpha and 13-cis-retinoic acid. The first patient had pelvic lymph node metastases and the other had lung metastases. The previously progressive diseases remained stable for a prolonged period of time, 3 and 4 years, with a good quality of life. These cases suggest the possibility of using IFN-alpha and 13-cis-retinoic acid as a treatment for small-volume residual disease or as postinduction therapy in patients at high risk for disease recurrence.

Prolonged chemotherapy for localised squamous carcinoma of the oesophagus.

We evaluated the feasibility of six courses of chemotherapy in 34 consecutive patients with localised squamous cell carcinoma of the oesophagus. All 32 evaluable patients first received at least two courses of chemotherapy. There were 18 patients with resectable carcinomas who underwent surgery and 14 patients with unresectable carcinomas who received definitive chemoradiotherapy. After two courses of 5-fluorouracil and cisplatin 21 (66%) of 32 patients had either a complete or major response. A median of five courses (range, 1-6 courses) was administered. 17 out of 18 (94%) patients with resectable carcinoma had a 'curative' resection (negative proximal, distal, and radial margins by histopathology in an en-block resection specimen) and 2 patients had a complete pathological response. The median survival duration of all patients was 28 months (range, 2-46+ months). The median survival duration of 14 patients with unresectable carcinoma was 23 months (range, 8-36+ months), and the median survival duration of 18 patients with resectable carcinoma has not been reached at a median follow-up of 24+ months (range, 10+ to 46+ months). No deaths occurred because of chemotherapy or chemoradiation therapy. Our data suggest that prolonged chemotherapy is feasible in patients with locoregional squamous carcinoma of the oesophagus. An ongoing controlled trial will determine the contribution of chemotherapy to patients' survival.

High dose endobronchial irradiation in recurrent bronchogenic carcinoma.

Between November 1988 and March 1990, 24 patients with endobronchial tumors that had recurred after external beam radiation therapy were treated with high dose rate intraluminal irradiation. A remote afterloading high dose rate unit was used, and most patients received two endobronchial treatments, separated by a two week interval. All patients were given the same dose and dose specification to assess the feasibility and complications of the therapy. At each treatment, 15 Gy were delivered with dose specified at a radius of 6 mm from the center of the source, which corresponds to a dose of 9 Gy at a radius of 1 cm. Overall, 21 of 24 patients (88%) showed good symptomatic improvement. Of 18 patients whose chest x-ray showed evidence of collapse or atelectasis caused by tumor obstruction, 15 (83%) had evidence of reaeration. The median duration of palliation, marked by symptoms or a chest x-ray that worsened, was 26 weeks, the range varying from seven to 40 weeks. No patient died as a result of therapy and only one had a complication, bronchospasm, which responded well to bronchodilators. One patient died of hemoptysis approximately three months after treatment. Five additional patients, who were treated off protocol because they had an Eastern Cooperative Oncology Group performance status of greater than two, also received endobronchial irradiation. All five died within one month from worsening pulmonary disease, and we do not recommend endobronchial irradiation for patients with an Eastern Cooperative Oncology Group performance status of greater than two. We conclude that high dose rate endobronchial brachytherapy effectively relieves the symptoms of endobronchial obstruction due to recurrent lung cancer and can be given safely as an outpatient procedure. As the complications were minimal in this series treated with a uniform dose of 15 Gy per treatment, future studies should aim at determining the maximum tolerated dose. This technique may also be helpful as a boost after maximal external beam irradiation or to open up areas of atelectasis prior to external beam irradiation.

Evaluation of pre- and postoperative chemotherapy for resectable adenocarcinoma of the esophagus or gastroesophageal junction.

Thirty-five consecutive patients with resectable adenocarcinoma of the esophagus or gastroesophageal junction were treated with two preoperative and three or four postoperative chemotherapy courses consisting of etoposide, fluorouracil, and cisplatin (EFP) to evaluate the rate of curative resection, clinical and pathologic response, toxic effects, and survival. One hundred thirty-seven courses with a median number of five courses (range, one to six) were administered. Preoperative EFP resulted in 17 (49%) major responses, including six patients who did not have carcinoma cells in the repeat endoscopic biopsy specimens and cytologic brushings. Among 32 patients who had surgery, 25 (78%) had curative resection, one patient had a complete pathologic response, and one had microscopic carcinoma in the resected specimen. Six patients had microscopic carcinoma at the resection margins and received postoperative radiotherapy. At a median follow-up of 20 months, the projected survival of 35 patients is 23 months (range, 6 to 33+). Fifteen patients died of their carcinomas, and 15 patients were alive (median follow-up, 20+ months; range, 15+ to 33+ months) with no evidence of relapse. There were no deaths related to chemotherapy, surgery, or radiotherapy. EFP-induced toxic reactions were moderate. Our data suggest that multiple courses of EFP are feasible. Future strategies for this disease should consider prolonged chemotherapy with regimens that result frequently in pathologic complete responses.

Determinants of perioperative morbidity and mortality after pneumonectomy.

A total of 197 consecutive patients undergoing pneumonectomy at the M.D. Anderson Cancer Center from 1982 to 1987 were reviewed. Sixty-five variables were analyzed for the predictive value for perioperative risk. The operative mortality rate was 7% (14/197). Patients having a right pneumonectomy (n = 95) had a higher operative mortality rate (12%) than patients having a left pneumonectomy (1%, p less than 0.05). The extent of resection correlated with the operative mortality rate (chest wall resection or extrapleural pneumonectomy, n = 39, 15%; versus simple or intrapericardial pneumonectomy, n = 158, 5%; p less than 0.05). Patients whose predicted postoperative pulmonary function, by spirometry and xenon 133 regional pulmonary function studies, was a forced expiratory volume in 1 second greater than 1.65 L, forced expiratory volume in 1 second greater than 58% of the preoperative value, forced vital capacity greater than 2.5 L, or forced vital capacity greater than 60% of the preoperative value had a lower operative mortality rate (p less than 0.05). Atrial arrhythmia was the most common postoperative complication (23%). Xenon 133 regional pulmonary function studies are useful in predicting the risks of pneumonectomy.

Fine needle aspiration cytology of thymolipoma. A case report.

A case of thymolipoma in a 14-year-old girl diagnosed prospectively by fine needle aspiration (FNA) biopsy is reported. The cellular constituents of the aspirate, lymphocytes and epithelial cells, were characterized by routine cytology and immunocytochemistry. Although primarily based on the FNA cytology, the diagnosis was supported by the patient's clinical history and the radiographic demonstration of a fat density mass. This appears to be the first description of thymolipoma in a fine needle aspirate.

Typical and atypical carcinoids within the pulmonary APUD tumor spectrum.

The behavior of pulmonary APUD tumors is not constant; management is controversial, and morphology has reached its limit as a tool for prognostic assessment and therapeutic planning. We have studied 24 patients with carcinoids; 17 patients with typical carcinoids presented with Stage I disease, but one patient later died most probably of small cell undifferentiated lung cancer (SCLC). Seven patients with atypical carcinoids included three with Stage III cancers, one patient with simultaneous bilateral carcinoids, and one patient with simultaneous adenocarcinoma. Of 17 patients with typical carcinoids, 16 or 92% are disease free or died of unrelated causes. Of seven patients with atypical carcinoids, five or 71% are disease free. Tumor doubling time of atypical carcinoids, was 79.6 months (45 to 120) or six times shorter than that of typical carcinoids (p less than 0.05). Two of the three deaths from cancer were probably from SCLC and one from a synchronous adenocarcinoma. Review of diagnostic material from 12 patients with SCLC who survived a mean of 41 months (24 to 134) showed that diagnosis had rested on cytology alone in four patients and that, in seven patients, the quality or extent of the original diagnostic material was adequate to make the diagnosis of a malignant tumor but inadequate to permit reclassification. Tumor cells from 11 patients with carcinoids (seven typical and four atypical) and 28 patients with SCLC had DNA measurement by image analysis. The mean DNA content of typical and atypical carcinoids and SCLC is 1.17, 1.25, and 1.94 respectively (p less than 0.001). These findings strongly suggest a relationship between DNA content and atypia or malignancy in APUD lung tumors. We conclude that there are at least two levels of virulence among carcinoids represented by typical and atypical carcinoids. The prognosis for treated Stage I typical and atypical carcinoids is excellent. When deaths occur, they are from systemic cancer. Current evidence indicates that DNA measurements by image analysis may help to discriminate levels of malignancy among APUD pulmonary cancers and thereby help to clarify therapeutic controversies.

Intraoperative cytodiagnosis of lung tumors by needle aspiration.

Rapid-stain cytologic evaluation of needle aspirates are a recent adjunct to diagnosis and staging of lung neoplasms. The benefits of this approach include ease of sampling from deep and remote lesions and the fact that the results are generally available within 10 minutes. In the past 2 years, we did 187 needle aspirations for cytopathological evaluation in 70 patients at 51 thoracotomies and 21 mediastinoscopies. The cytologic findings from aspirates of lymph nodes, mediastinal masses, and intrapulmonary lesions were compared with diagnosis obtained by histopathological techniques. Quick-stain cytopathological evaluation discriminated cancer among all 55 lung masses from which aspirates were taken; specific diagnosis as to the type of neoplasm, lymphoproliferative disorder, or infection was achieved in 60 of 70 patients (85%). We conclude that intraoperative needle aspirations for cytologic evaluation facilitates the practice of modern general thoracic surgery.

When and how to invade for the diagnosis and staging of primary lung cancer.

In search of perspectives pertaining to the selection of invasive procedures for evaluating patients with lung cancer, data from other centers were considered, and our recent consecutive experience with 40 lung cancer patients was reviewed. Cost estimates for the least and the most complete use of invasive procedures were done. An average of three procedures per patient was used. Information judged beneficial was obtained from 94 for 120 procedures (78 percent). By retrospective analysis, 15 procedures (0.38 per patient) provided no useful information. An approach to the use of invasive procedures in the management of patients with suspected lung cancer is proposed.

Lung cancer in young persons.

Lung cancer in patients under 40 years old is rare. Among 718 patients with lung cancer, 5% or 35 patients were younger than 40. All but one were heavy smokers. Twelve young patients who had operations survived 41.7 (SD 46.3) months: they included six who had resections of Stage 3 disease and who survived 19.2 (SD 16.0) months. The other six young patients treated operatively were free of nodal metastasis N0); all survived more than 3 years and three of them are apparently cured. The 23 young patients who were not treated operatively survived for 5.6 (SD 3.1) months. The 5 year survival rate of these young operated patients was not different from that of 201 operated patients over 40 years of age. Young nonoperated patients survived for a significantly shorter time (p less than 0.0001) than did the older patients who also received only chemotherapy and/or radiation as a treatment. In young patients adenocarcinomas predominated (48.6%), and the incidence of small cell undifferentiated cancers was high (28.6%). These significant differences as compared to the control group did not explain the short survival time of the young patients treated nonsurgically. We conclude that lung cancer in young persons is virulent and that diagnosis is frequently delayed. Therapy, in selected patients, should include aggressive resection, sometimes despite advanced local disease. This group of patients justifies innovative, intensive efforts at more prompt diagnosis and experimental multimodal therapy.