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.

Imaging of the skin with 20-MHz US.

PURPOSE: The authors clinically evaluated a new high-frequency ultrasound (US) scanner to determine the value of US for dermatologic applications. MATERIALS AND METHODS: A 20-MHz US scanner was used to visualize normal skin at eight sites in 10 healthy volunteers and to evaluate 200 skin lesions (45 malignant, 155 benign). RESULTS: In normal skin, the dermis was markedly echogenic and sharply demarcated from hypoechoic subcutaneous fat. The epidermis was not resolved except on the palm and sole. Only three superficial lesions were not identified with US; evaluation of another three was limited by shadowing. Thickness of the lesions visualized was 0.2-26.0 mm (mean, 1.9 mm +/- 2.6). Most lesions (77%) were hypoechoic, 9% were anechoic, 12% had mixed echogenicity, and 2% were isoechoic or hyperechoic. CONCLUSION: The diagnostic role of high-frequency US appears limited. It did not help differentiate benign from malignant lesions, but it did enable accurate delineation of deep margins of lesions and allowed noninvasive measurement of thickness. These features may help in the preoperative evaluation of skin tumors and in monitoring the response to therapy for certain inflammatory conditions.

Pagetoid dyskeratosis: a selective keratinocytic response.

Pale cells that resemble those of Paget's disease have been found within apparently normal epidermis in a variety of benign papules. Although they have been considered an artifact, they show characteristic premature keratinization. In contrast to other dyskeratotic processes they mature into orthokeratotic squamae. The histopathologic, ultrastructural and immunocytochemical features of these cells are illustrated, and the differential diagnosis is reviewed.

Carcinosarcoma of the skin.

A 91-year-old patient with an extraskeletal osteosarcoma (characterized by atypical mesenchymal cells with ossification) of the forehead associated with a basal cell carcinoma is reported. Both osteoid and basal cell carcinoma nests were found embedded in a stroma containing markedly atypical cells. The 2 previously reported carcinosarcomas of the skin are reviewed.

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.

Lung cancer heterogeneity. Prognostic implications.

Although histologic heterogeneity of lung cancer is well recognized, little information is available related to possible effects of this heterogeneity on prognosis. We collected 100 consecutive lung cancer cases, including 35 autopsies and 65 surgical resections, which were extensively sampled (average, ten blocks per case) and analyzed for histologic heterogeneity. Slides were randomized and classified by five pathologists using the 1981 World Health Organization (WHO) classification scheme. Five-year follow-up data were obtained for the surgical cases, and detailed information on staging and survival from time of diagnosis was available in 91 cases. Survival time was analyzed with respect to the patient's age, sex, stage, predominant histologic pattern, and presence or absence of major heterogeneity. The latter is defined as the presence on at least one slide of a major histologic pattern different from that of the remaining slides for that case. The only statistically significant predictor of survival was tumor stage (P less than 0.0001). Heterogeneous tumors appeared to have a worse survival, but this did not reach statistical significance. There was no relationship between survival and predominant histologic pattern (cell type), sex, or age.

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.

Torre's syndrome: exacerbation of cutaneous manifestations with immunosuppression.

Torre's syndrome is characterized by the association of sebaceous neoplasms and keratoacanthomas with visceral malignancies. We report on a patient in whom the cutaneous manifestations of Torre's syndrome dramatically increased following immunosuppression.

Hansen's disease following lymphoma.

We report two instances of Hansen's disease as a complication of lymphoma. Although patients with leprosy may be at risk for the development of neoplasia, the converse has only rarely been reported. Nonetheless, granulomatous lesions in patients with lymphoreticular malignancy should suggest appropriate studies to rule out Hansen's disease, as illustrated by the cases detailed herein.

Caripito itch: dermatitis from contact with Hylesia moths.

Caripito itch, a pruritic dermatosis rarely seen in the United States, is caused by contact with moths of the genus Hylesia--specifically, with urticating abdominal hairs of the adult female moth. The purpose of this study was to investigate an outbreak of Caripito itch that occurred in thirty-four of thirty-five crew members of a British oil tanker who were exposed to Hylesia moths at the port of Caripito, Venezuela. Methods of investigation included general history and physical examination of all crew members, complete inspection of the ship, transparent-tape slide preparations from involved skin, cutaneous histopathologic studies, and entomologic examination of the moths. The patients had a typical papulourticarial eruption, primarily on exposed surfaces. Although Hylesia moths do not occur in the United States, primary care physicians and dermatologists, especially those located in port cities, should be aware of cutaneous lepidopterism caused by Hylesia moths.

Livedo reticularis due to multiple cholesterol emboli.

Three patients with advanced atherosclerotic vascular disease developed multiple cholesterol emboli. The clinical presentation typically includes livedo reticularis of the lower part of the body and purple toes. Small areas of necrosis and ulceration may be present distally, despite palpable pulses. Muscular and abdominal pain, as well as alterations in renal function, may also occur. Cutaneous biopsy reveals characteristic cholesterol clefts within atheromatous debris filling small, deep arterial lumen. Pathophysiologic mechanisms are discussed.

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.

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.

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.

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.

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.

Pulmonary asbestos body counts and electron probe analysis of asbestos body cores in patients with mesothelioma: a study of 25 cases.

Malignant mesotheliomas of the pleura and peritoneum are well-recognized risks of asbestos exposure. We determined the asbestos body content of the lungs from 24 cases of malignant mesothelioma (19 pleural, five peritoneal) and compared such to the content of lungs from 50 consecutive adult autopsies and four cases of overt asbestosis using a Clorox-digestion concentration technique. The cores of 90 asbestos bodies were examined by energy dispersive x-ray analysis and compared with similar data from 120 standard asbestos fibers and 20 fiberglass fibers. The malignant mesothelioma patients had asbestos body counts intermediate between those of the general population and those of patients with asbestosis, although some of the mesothelioma cases overlapped with the general population. These latter cases often lacked an identifiable occupational exposure to asbestos. EDXA studies demonstrated an amphibole core in 88 of the 90 asbestos bodies (amosite or crocidolite in 80 of 88, anthophyllite or tremolite in eight of 88), and chrysotile in two instances.