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Biomedical subjects

M J Matthews

Publications and source records attributed to M J Matthews.

At least 55 records · Page 3Linked to original sources
PubMed1982

Experience of the National Cancer Institute (USA) in the treatment and biology of small cell lung cancer.

This retrospective study deals with 168 patients with small cell lung cancer (SCLC) who were treated at the NCI March 1973 and July 1977 with intensive chemotherapy. Results showed that 12 per cent of all the patients were disease-free for more than 40 months (25% of the limited disease and 3% of the extended stage disease patients which were treated. Complete remission was essential to prolonged survival. The development of a complete remission was favored by a satisfactory initial general condition, localised disease or presence of only one site of metastatic disease. Initial treatment included the following combinations: cyclophosphamide, methotrexate and CCNU. High doses are necessary. However, above a certain level, the toxicity increased without a corresponding increment in activity. Addition of another association without cross-resistance (vincristine-adriamycine-natulan or VP-16 and isophosphamide) may induce a complete remission in cases where only a partial remission was obtained initially. In limited disease, radiotherapy seemed to prolong disease-free survival. This lead the authors to study the use of initial radiotherapy, at the rate of 40 grays in 3 weeks in 15 fractions, at the same time as chemotherapy. The radiotherapist must take certain precautions in the use of this double treatment: reshaped fields and insertion of a spinal cord block above 2 000 rads. In extended disease, thoracic irradiation seemed to be of no benefit. Pilot studies are not underway using intensive chemotherapy with multiple tumor site irradiation and autologous marrow implants 48 per cent of all patients with SCLC will develop cerebral metastatic disease (44% intracranial, 13% leptomeningeal, 9% epidural). At 30 months, 75 percent of those who did not receive prophylactic irradiation developed cerebral disease whereas only 40 per cent of the patients who received a prophylactic dose of 30 grays developed cerebral disease. Inspite of the indisputable but incomplete local benefit of prophylactic brain irradiation, it did not prolong survival. Important biological studies are underway at the NCI. - Cell clone cultures have been established. These were enhanced by the addition of arginine vasopressive (AVP) and bombesine. These two substances may be considered as markers of APUD system and are secreted by the SCLC. Bombesine has been isolated in all the cultures tested. This possible marker was perhaps responsible for the anorexia and cachexia in these patients. - These cultures have allowed for identification of deletion 3p (14-23) chromosome anomalies in all the samples examined. - In vitro chemotherapy studies of these cultures have been carried out. Their correlation with clinical results were encouraging (100% negative p/n; 75% positive p/n). - Lastly, monoclonal AC have been prepared. Inspite of their imperfect specificity and heterogeneity with regard to tumor cells, their potential advantages were considerable.

Antineoplastic Agents↗
PubMed1982

Surgical resection in the management of small cell carcinoma of the lung.

In an attempt to define the role of initial surgical resection in patients with undifferentiated small cell carcinoma of the lung, we reviewed the experience of the Veterans Administration Surgical Oncology Group (VASOG). One hundred forty-eight patients with small cell carcinoma of the lung had undergone a potentially "curative" resection. This represented 4.7% of "curative" resections carried out in four major prospective adjuvant chemotherapy trials. In the early trials (101 patients), 16 patients (15.8%) died within the first 30 postoperative days. These patients have been excluded from the analysis of long-term survival, since in the more recent trials postoperative deaths were excluded prior to randomization. In the 132 patients remaining, the 5 year survival rate by the life-table method was 23.0%. The tumor of each was classified pathologically by the TNM system. Five-year survival rates for each category were as follows: T1 N0 M0 59.9%, T1 N1 M0 31.3%, T2 N0 M0 27.9%, T2 N1 M0 9.0%, and any T3 or N2 3.6%. The effect of postoperative adjuvant chemotherapy was evaluated in each of the trials. No beneficial effect of the adjuvant therapy was noted with a one or two course regimen of either nitrogen mustard or cyclophosphamide, but possible benefit, although not significant, was noted in a prolonged intermittent chemotherapy trial of cyclophosphamide either alone or alternating with methotrexate. In the most recent trial of prolonged intermittent courses of 1-(2-chlorethyl)-3-cyclohexyl-l-nitrosourea (CCNU) and hydroxyurea, a 5 year survival rate of 80.8% was noted in those receiving adjuvant chemotherapy as compared to a 38.1% in the control group. We conclude that resection is definitely indicated in patients with T1 N0 M0 lesions and probably indicated in those with T1 N1 M0 or T2 N0 M0 lesions. Primary surgical resection is contraindicated in patients with any other TNM category.

Antineoplastic Agents↗
PubMed1982

Skeletal manifestations in cutaneous T-cell lymphomas.

The clinical course of three patients with cutaneous T-cell lymphoma (CTCL) in whom skeletal disease developed is presented and the literature on skeletal involvement in these disorders is reviewed. Three separate types of skeletal manifestations occurred: (1) osteolytic lesions, (2) osteoblastic lesions, and (3) diffuse osteoporosis. Hypercalcemia was present in two cases. Tumor cells from two patients in short-term culture secreted osteoclast-activating factor(s). Both of these patients had pathologic evidence of osteoclast activation in bone sections. Thus, the tumor cells in certain patients with CTCL may derive from a monoclonal proliferation of a T-cell subset capable of producing humoral bone-resorbing factor(s) similar to those demonstrated in cultures of mitogen- and antigen-activated normal lymphocytes. Since skeletal lesions are unusual, it would follow that other T-cell subsets account for pathologic cell proliferation in most patients with CTCL.

Adult↗
PubMed1981

Analysis of a pathology review of patients with lung tumors.

The rates of agreement and patterns of disagreement in the classification of lung tumors were evaluated for a pathology panel review of 476 patients with lung cancer. The panel review consisted of three independent diagnoses made in accordance with the criteria of the Working Party for Therapy of Lung Cancer. At least two of the three pathologists agreed as to the major cell classification in 94% of the patients. In 67% of the evaluations, there was agreement among the three pathologists. Small-cell carcinoma and epidermoid carcinoma were the most consistently evaluated classes, followed by adenocarcinoma and large-cell carcinoma. The poorly differentiated categories provided the greatest source of difficulty in discriminating among major histologic classes. For an initial diagnosis of large-cell carcinoma, 14% of the second classifications were poorly differentiated epidermoid carcinoma, and 20% were poorly differentiated adenocarcinoma. For an initial diagnosis of small-cell carcinoma, 11% of the second independent evaluations classified the carcinoma as other than small-cell. The most likely alternative diagnosis was large-cell carcinoma (5%).

Adenocarcinoma↗
PubMed1981

Prognostic implications of stage of disease and sites of metastases in patients with small cell carcinoma of the lung treated with intensive combination chemotherapy.

The influence of various sites of distant metastases on response and survival was analyzed in 106 consecutive previously untreated patients with small cell carcinoma whose disease was systematically staged. All patients received 6 wk of intensive induction chemotherapy with cyclophosphamide, methotrexate, and lomustine; therapy thereafter varied without differential effects on survival. Staging procedures included physical examination, chest roentgenogram, fiberoptic bronchoscopy, bone marrow and liver biopsies, and radionuclide bone, brain, and liver scans. On the basis of pretreatment staging, 33 patients (31%) had limited disease. In the remaining 73 patients, sites of extensive disease included bone in 40; with bone as the sole site of metastatic disease in 13; liver in 30, with liver as the only site in 5; soft tissues in 25 (only site in 7); bone marrow in 22 (only 2); central nervous system in 9 (only site in 4); opposite lung in 7 (only site in 4). Although patients with limited disease live longer than those with extensive disease (median length of survival, 12 versus 10 months), this difference was not significant. This lack of major impact of traditional stage on survival was explained by the similar survival of patients with limited disease and a single site of extensive disease. Prognosis worsened with increasing number of sites of extensive disease (median survival, 11.5, 10, and 8 months for one, two, and three or more sites, respectively). Metastases to the liver or central nervous system significantly shortened survival, whereas involvement of bone, soft tissues, or bone marrow had little adverse effect. In patients with small cell carcinoma whose disease is thoroughly staged and who are given aggressive chemotherapy, certain sites or a small number of sites of extensive disease may be treated as successfully as limited disease.

Aged↗
PubMed1981

Small cell carcinoma presenting as an extrapulmonary neoplasm: sites of origin and response to chemotherapy.

Eight (4%) of 203 consecutive prospectively staged and treated patients with small cell carcinoma (SCC) had no evidence of pulmonary or mediastinal tumor on chest roentgenogram or at fiberoptic bronchoscopy at the time of diagnosis. There were two distinct clinical presentations in these SCC patients with exclusively extrapulmonary tumors. Four had discrete localized extrapulmonary neoplasms, presumably originating in these sites. In the other 4 cases with either regional or widely metastatic disease, no obvious primary tumor could be documented in the lungs or elsewhere. One complete and two partial responses to chemotherapy (duration 6 to greater than 11 mo) occurred in 6 evaluable patients. Two remaining patients were inevaluable for response because they received adjuvant chemotherapy after irradiation or excision of the primary tumor and are free of disease at 15 and 28 months. Results document two clinicopathologic entities of extrapulmonary SCC, more firmly establish that it can be responsive to chemotherapy, and encourage systemic therapy as part of initial treatment planning.

Aged↗
PubMed1980

Smoking abstinence and small cell lung cancer survival. An association.

The prognostic implications of cigarette smoking were investigated in 112 patients with small cell lung cancer. Twenty had stopped smoking permanently before diagnosis (NS-Prior), 35 had stopped at diagnosis (NS-Dx), and 57 patients continued smoking (S). Therapies included chemotherapy alone or with radiation therapy, with or without thymosin fraction V. The survival difference among the three groups was statistically significant. The NS-Prior patients had the best survival, followed by NS-Dx patients and finally S patients. No S patient has survived, disease free, more than 96 weeks, while three NS-Prior and three NS-Dx patients are disease free 103 to 220 weeks after start of treatment. Thymosin, 60 mg/sq m, yielded survival benefits for the S group only. Continuation of smoking during the treatment of small cell lung cancer was associated with a poor prognosis, while discontinuation of smoking, even at diagnosis, may have beneficial effects on survival.

Carcinoma, Small Cell↗
PubMed1980

Hepatic involvement in the cutaneous T-cell lymphomas: results of percutaneous biopsy and peritoneoscopy.

Forty-three patients with cutaneous T-cell lymphomas (mycosis fungoides and the Sezary syndrome) underwent routine staging procedures to assess extent of disease prior to therapy. Evaluation of the liver included physical examination, liver function tests, 99mTc-liver-spleen scans, percutaneous liver biopsy, and peritoneoscopy with multiple liver biopsies. Seven patients (16%) had biopsy-documented hepatic lymphoma, histologically defined as focal aggregates of atypical convoluted lymphocytes in portal zones or hepatic lobules. The liver was the most frequently involved visceral site. Involvement of peripheral blood, leukocytosis, and generalized erythroderma were significantly associated with hepatic lymphoma. Biopsy examination was the only accurate method of detecting hepatic involvement, and peritoneoscopy with multiple biopsies appeared to be more sensitive than a single percutaneous biopsy, since the yield of positive biopsies increased from three to seven. In order to better understand the natural history of the cutaneous T-cell lymphomas and the relation of hepatic involvement to survival, histologic evaluation of the liver in patients with the cutaneous lymphomas should be carried out prior to therapy.

Adult↗
PubMed1980

Evaluation of response to chemotherapy with fiberoptic bronchoscopy in non-small cell lung cancer.

Fiberoptic bronchoscopy was performed before and during administration of chemotherapy in 32 patients with unresectable non-small cell carconoma of the lung. Pretreatment findings varied with the histologic cell type. Direct visual and/or pathologic evidence of cancer was obtained in 11 of 11 patients with epidermoid, in 5 of 7 with large cell, and in 9 of 14 with adenocarcinoma. In 5 of the 32 patients, intrathoracic tumor was documented at bronchoscopy but not by chest x-ray. During chemotherapy, one of five episodes of response and eight of 21 episodes of chest tumor progression were detected solely by bronchoscopy, while in an additional two objective responses and six progressions, bronchoscopic and radiographic findings simultaneously improved or deteriorated. The likelihood of documenting disease progression by bronchoscopy also depended upon the histologic type of cancer. Enlarging chest tumor found solely by chest x-ray occurred exclusively in patients with large cell carcinoma and adenocarcinoma. During chemotherapeutic treatment of our pateints, addition of serial bronchoscopic examinations to standard means of assessing tumor response frequently allowed the earlier discontinuation of an ineffective drug regimen.

Adenocarcinoma↗
PubMed1980

Possible role of prolactin and pineal prolactin-regulating substances in pineal-mediated gonadal atrophy in hamsters.

Homoplastic anterior pituitaries were transplanted beneath the renal capsule of adult male, Syrian golden hamsters and the effects studied on the gonadal and accessory organ atrophy following bilateral optic enucleation or placement in reduced (L/D = 10/14 h) photoperiods. In all cases, control hamsters, bearing kidney fragments transplanted beneath their renal capsules, showed gonadal atrophy and reduced blood levels of prolactin and LH at 8--10 weeks following light deprivation. On the other hand, hamsters, bearing three or four homoplastic pituitary grafts, showed complete maintenance of gonadal and accessory weights as well as normal or supranormal serum prolactin levels. Prolactin, but not LH, levels were maintained in hypophysectomized male hamsters bearing pituitary homografts. These results point out the significant role played by prolactin, and possibly that of pineal prolactin-regulating factors, in pineal-mediated gonadal atrophy.

Animals↗
PubMed1980

Prospective staging evaluation of patients with cutaneous T-cell lymphomas. Demonstration of a high frequency of extracutaneous dissemination.

A prospective pretreatment staging evaluation was done on 49 consecutive patients with mycosis fungoides or the Sézary syndrome to study patterns of disease spread and prognostic factors. Routine staging procedures included complete blood count, blood chemistries, chest roentgenogram, lymphangiogram, radionuclide scans, bone marrow aspiration and biopsy, liver biopsy, and lymph node biopsy. Special evaluations included cytogenetic analysis, electron microscopy, and T-cell cytology. Extracutaneous lymphoma was documented by light microscopy in 51% of patients and by the three special procedures in 88%. Extracutaneous lymphoma was most frequent in blood and lymph nodes; 18% of patients had visceral involvement. Patients with generalized erythroderma had a higher frequency of extracutaneous disease than did patients with cutaneous plaques and tumors by both light microscopy and special studies. Survival was directly related to the type of skin involvement and the presence or absence of extracutaneous disease. Systemic dissemination of cutaneous T-cell lymphoma is frequent, generally asymptomatic, and develops early via the circulation. These findings may explain why cutaneous therapies are associated with a high frequency of relapse.

Adult↗
PubMed1980

Influence of histologic subtype of small cell carcinoma of the lung on clinical presentation, response to therapy, and survival.

Patients with small cell carcinoma of the lung (SCCL) were histologically subtyped according to the Working Party for Therapy of Lung Cancer classification and were treated with combination chemotherapy. Of the 103 patients studied, 54 had the lymphocyte-like (oat cell) subtype, 41 had the intermediate cell subtype, and 8 had a mixture of the two. No significant difference in initial performance status, extent of disease, chemotherapeutic response rate, or survival (median, 10.2 mo) was noted among the histologic subtypes. When the histologic subtype of the primary biopsy tissue was compared with the subtype of other pathology specimens from the same patient, concordance of subtype was present in 74% of the patients. In the remaining 26%, two or three histologic subtypes were present. This study demonstrates no clinically significant differences among the various histologic subtypes of SCCL in patients extensively staged and treated with aggressive cytotoxic therapy. Because of this and because concurrent biopsy tissues from multiple sites in the same patient may vary in subtype, we conclude that prognostic or therapeutic decisions should not be based on SCCL subtype.

Carcinoma, Small Cell↗
PubMed1979

Thymosin fraction V and intensive combination chemotherapy. Prolonging the survival of patients with small-cell lung cancer.

Patients with small-cell bronchogenic carcinoma who received intensive remission-induction chemotherapy randomly received either thymosin fraction V, 60 mg/sq m or 20 mg/sq m twice weekly, or no thymosin treatment during the initial six weeks of chemotherapy. Chemotherapy was then continued for two years. Thymosin administration did not increase the complete response rate. Patients receiving thymosin, 60 mg/sq m, had significantly prolonged survival times relative to the other treatment groups. This benefit was due to prolonged relapse-free survival in complete responders to treatment. The mechanism by which thymosin increased survival duration is unclear but may relate to restoration of immune deficits due to disease or treatment.

Antineoplastic Agents↗