A randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer.

BACKGROUND: Patients with resectable stage IIIA non-small-cell lung cancer have a low survival rate following standard surgical treatment. Nonrandomized trials in which induction chemotherapy or a combination of chemotherapy and radiation prior to surgery were used to treat patients with regionally advanced primary cancers have suggested that survival is improved when compared with treatment by surgery alone. PURPOSE: We performed a prospective, randomized study of patients with previously untreated, potentially resectable clinical stage IIIA non-small-cell lung cancer to compare the results of perioperative chemotherapy and surgery with those of surgery alone. METHODS: This trial was designed to test the null hypothesis that the proportion of patients surviving 3 years is 12% for either treatment group against the alternate hypothesis that the 3-year survival rate would be 12% in the surgery alone group and 32% in the perioperative chemotherapy group. The estimated required sample size was 65 patients in each group. The trial was terminated at an early time according to the method of O'Brien and Fleming following a single unplanned interim analysis. The decision to terminate the trial was based on ethical considerations, the magnitude of the treatment effect, and the high degree of statistical significance attained. In total, 60 patients were randomly assigned between 1987 and 1993 to receive either six cycles of perioperative chemotherapy (cyclophosphamide, etoposide, and cisplatin) and surgery (28 patients) or surgery alone (32 patients). For patients in the former group, tumor measurements were made before each course of chemotherapy and the clinical tumor response was evaluated after three cycles of chemotherapy; they then underwent surgical resection. Patients who had documented tumor regression after preoperative chemotherapy received three additional cycles of chemotherapy after surgery. RESULTS: After three cycles of preoperative chemotherapy, the rate of clinical major response was 35%. Patients treated with perioperative chemotherapy and surgery had an estimated median survival of 64 months compared with 11 months for patients who had surgery alone (P < .008 by log-rank test; P < .018 by Wilcoxon test). The estimated 2- and 3-year survival rates were 60% and 56% for the perioperative chemotherapy patients and 25% and 15% for those who had surgery alone, respectively. CONCLUSIONS: In this trial, the treatment strategy using perioperative chemotherapy and surgery was more effective than surgery alone. IMPLICATIONS: This clinical trial strengthens the validity of using perioperative chemotherapy in the management of patients with resectable stage IIIA non-small-cell lung cancer. Further investigation of the perioperative chemotherapy strategy in earlier stage lung cancer is warranted.

Combined modality treatment of extensive small cell lung cancer: a Southwest Oncology Group study.

The Southwest Oncology Group entered 453 patients with extensive small cell carcinoma into a combined modality treatment program, involving a randomized comparison of three different chemotherapy regimens for remission induction, and of maintenance chemotherapy alone versus maintenance treatment with cycles of reinduction added at six and 12 months. In addition, there was systematic comparison of diagnosis by institutional pathologist versus review panel pathologist. No difference was observed among the three different induction arms with respect to the incidence of response to treatment (61%), complete response (16%), or survival duration (median, 31 weeks). Neither overall response rate nor survival are superior to previous results. However, patients who achieved a complete response demonstrated significant survival benefit if they were in the group who received reinduction chemotherapy, as opposed to maintenance alone. This observation may apply most importantly to patients with small cell lung cancer of limited extent, for whom complete response is achieved in a majority. Agreement of institutional and review panel pathologists on the diagnosis of small cell lung cancer was observed in 94% of reviewed cases. A final observation is that the omission of chest irradiation results in a dramatic increase in the incidence of initial relapse at the primary tumor site. This suggests that future studies will need to use better therapy for local control in responding patients.

Gliomatosis peritonei. Report of two cases and review of literature.

Gliomatosis peritonei, a rare complication of solid ovarian teratomas, is a miliary, mature glial implantation on the peritoneum or omentum. Two new cases are reported and 30 previously reported cases are reviewed. Gliomatosis peritonei is thought to be benign in almost all cases and thus deserves no treatment except for confirmatory biopsy. It must be differentiated from teratomatous implants because the latter may imply poor prognosis and require aggressive therapy. The prognostic value of serum alpha-fetoprotein levels in patients with immature ovarian teratoma is not conclusive. The presence of glial fibrillary acidic protein confirms the glial nature of the implants.

Duodenal glucagonoma: a case report.

A case of a primary carcinoid islet cell tumor of the duodenum is reported, demonstrated by histochemistry, electron microscopy, and immunofluorescence to be composed of alpha cells containing glucagon-like material. The patient was found on admission to have hyperglycemia and a diffuse skin rash. Primary duodenal glucagonoma has not been previously reported.

Lung cancer heterogeneity: a blinded and randomized study of 100 consecutive cases.

The heterogeneity of lung carcinomas was recognized in the past, but few previous studies attempted to quantitate this heterogeneity. In the present study 100 consecutive cases of lung carcinoma (65 surgical resections and 35 autopsies) were collected, and either the entire tumor or ten blocks were examined in a blinded and randomized fashion using the revised (1981) WHO classification. At least three of five panelists agreed on the major histologic type present for 94 per cent of the slides. Agreement for the diagnosis of small cell carcinomas (at least four of five observers) was 98 per cent, but only 72 per cent agreement was attained for the subtyping of small cell carcinomas (e.g., oat cell versus intermediate). Only 34 per cent of the cases were homogeneous according to the majority of the panelists. An additional 21 per cent of the cases showed minor (subtype) heterogeneity (e.g., mixtures of acinar and papillary patterns in adenocarcinoma). Forty-five per cent of the cases showed major heterogeneity, i.e., at least one slide from the case showed a major histologic type different from that of the remainder. Seven small cell carcinomas were homogeneous, whereas in eight cases mixtures of small cell and other cell types were seen. In all but one of the cases involving bronchioloalveolar cell patterns, other patterns of adenocarcinoma were present elsewhere in the tumor. In all six cases involving giant cell carcinoma patterns, adenocarcinoma patterns were also present in some sections. Heterogeneity was identified by extensive sampling of the entire tumor and was seldom recognized in biopsy specimens.

Diagnostic and therapeutic challenges following the cytologic diagnosis of in situ carcinoma of the lung.

Clinical challenges associated with the cytologic detection of eight cases of occult pulmonary carcinoma are presented. The pulmonary lesions were successfully localized and resected in three of six cases encountered since the availability of flexible fiberoptic bronchoscopy and selective bronchial brushing. Two of the resected neoplasms were unequivocally in situ, while preoperative radiotherapy precluded accurate pathologic determination of invasiveness in the third. The reported experience with unequivocal in situ bronchogenic carcinoma localized and treated surgically prior to invasion through the basement membrane now totals 17 cases (15 previously reported). Forty-four additional cases (43 previously reported) have been localized and resected following early invasion. From this group totaling 61 occult carcinomas, only two patients (3 percent) are known to have died of pulmonary carcinoma during a followup ranging from 2 to 20 years.

Small cell carcinoma of the lung treated with irradiation and chemotherapy. Autopsy confirmation of long-term disease-free survival.

A patient survived clinically disease free for 68 months following combination chemotherapy and radiotherapy for small cell carcinoma of the lung. No evidence of tumor was found at autopsy. To our knowledge, this represents the first documentation by autopsy of a greater than five year disease-free survival following treatment of small cell cancer of the lung.

Myospherulosis--further observations.

Myospherulosis has recently been shown to be composed of altered erythrocytes. Mysopherules have been produced in vivo and in vitro using a petrolatum-based tetracycline antibiotic ointment (Achromycin). In the reported study, myospherules were produced in vitro using either lanolin or petrolatum, the two components of the vehicle of this ointment. Additionally, human fat produced myospherules in vitro.

Pituitary microadenoma and primary lymphoma of brain associated with hypothalamic invasion.

A case of primary histiocytic lymphoma involving the left temporal lobe and hypothalamus is presented. This lesion was associated with a pituitary microadenoma shown immunohistochemically to contain prolactin and with lactational changes in the breasts. The interruption by the neoplasm of neural pathways from cells producing prolactin inhibitory factor in the hypothalamus and increased production of prolactin by the pituitary are suggested as the probable mechanism. The association of lactational changes in the breasts with primary lymphoma of the brain has not been reported.

Pulmonary fibrosis, carcinoma, and ferruginous body counts in amosite asbestos workers. A study of six cases.

The Tyler Asbestos Workers Program is a continuing study of 1,105 former amosite asbestos workers. This report includes a study of six former workers, five of whom died and had autopsies, and one who underwent a lobectomy. Five of these men were exposed to asbestos for three months or less. Four had lung cancer, and one a rectal carcinoma. All were cigarette smokers. Ferruginous (asbestos) body content of the upper and lower lobes of the lungs was quantitated by a digestion technic. Tissue sections from upper and lower lobes were independently quantitated for fibrosis and ferruginous bodies, and chest roentgenograms were examined for interstitial fibrosis. (Control lung tissue was obtained from consecutive autopsies of 52 adults who did not have a known occupational exposure to asbestos.) Relatively low ferruginous body counts (less than 700/g lung tissue) were associated with mild degrees of fibrosis, and higher counts (greater than 10,000/g) with moderate to severe fibrosis. Mild to moderate pulmonary fibrosis could be identified on tissue sections before interstitial changes were detectable by chest roentgenograms.

Chromomycosis. The association of fungal elements and wood splinters.

In two separate specimens received for histopathologic examination, pigmented fungal elements were found within or on embedded wood splinters associated with a foreign-body reaction. The fungus was found to be in direct contact with the surrounding dermis. These findings support the concept of inoculation as a pathogenetic mechanism in cutaneous chromomycosis.

Gaucher's disease involving the maxillary sinuses.

A 46-year-old man with a long history of Gaucher's disease involving the spleen, bone marrow, and multiple bones presented with apparent sinusitis. He had radiologic opacification and histologically documented involvement by Gaucher's disease of the maxillary antra. Bony involvement of the mandible and maxilla has rarely been reported. To the best of our knowledge, this represents the first reported case of paranasal sinus involvement by Gaucher's disease.

Craniofacial duplication (diprosopus) in a twin.

A fused, double-faced (diprosopus), anencephalic monster was born prematurely as one of twins after 30 weeks of gestation. We will describe the autopsy findings and summarize the literature concerning the diprosopus defect. Factors other than fetal environment may contribute to its pathogenesis.

Cutaneous pigmentation.

The color of an individual's skin is an inherited trait, poorly understood in any real genetic sense and likely to remain so in the outbred populace. Pigmentary anomalies are assignable either to hyperpigmentation (melanoderma, ceruloderma) or hypopigmentation (leukoderma). This article briefly reviews such anomalies.

Laryngeal atresia: a detailed histologic study.

Laryngeal atresia is a rare, life-threatening anomaly. A case is reported with histological analysis of the deformity. Although there are different theories of glottic development, all authors agree that the primitive glottis is occluded at one time by an epithelial plug. Laryngeal atresia is felt to represent a lack of recanalization of the embryonic larynx. Laryngeal embryology is reviewed and the various types of laryngeal atresia are compared to the stages of laryngeal development.

Traumatic nodule in surgical scar.

Presented herein is a report on a patient in whom a hyperkeratotic nodule developed in an abdominal surgical scar, ten months after exploratory laparotomy.