Lung cancer: the importance of seeing a respiratory physician.

Patients with lung cancer present to and are managed by a variety of clinicians. In this study the effect of involvement by a respiratory physician on the diagnosis, staging, treatment and survival of a large unselected group of lung cancer patients was investigated. The study population was derived from the Scottish Cancer Registry. A total of 3,855 patients diagnosed during 1995 with lung cancer were studied. The data were validated and supplemented by references to medical records. The study found that a respiratory physician had been involved in the initial management of 2,901 (75.3%) patients. These patients were found more likely to have had the cancer diagnosis confirmed by histological methods and to have received active treatment with surgery, radiotherapy or chemotherapy. Survival, 1 yr after diagnosis was higher in patients who saw a respiratory physician (24.4 versus 11.1%) and benefit was found to have remained 3 yrs after diagnosis (8.1 versus 3.7%). Although the patients who had not seen a respiratory physician were generally older, and had more extensive disease, after correcting for age, stage and other prognostic factors, the relative hazard ratio of death for those not managed by a respiratory physician was 1.44. The data from this study supports the recommendations of recent lung cancer guidelines for the early involvement by a respiratory physician.

Management and survival of patients with lung cancer in Scotland diagnosed in 1995: results of a national population based study.

BACKGROUND: The prognosis of patients with lung cancer in Scotland is poor and not improving. This study was designed to document factors influencing referral, diagnostic evaluation, treatment, and survival in patients with lung cancer. METHODS: Patients diagnosed during 1995 were identified from the Scottish Cancer Registry and their medical records were reviewed. Adequate records were available in 91.2% of all potentially eligible cases. RESULTS: In 1995, patients in Scotland with lung cancer had a high rate of microscopic verification (74.1%) and 75.3% were assessed by a respiratory physician; however, only 56.8% received active treatment (resection 10.7%, radiotherapy 35.8%, chemotherapy 16.1%) and 2.9% participated in a clinical trial. Survival was poor with a median of 3.6 months; 21.1% (95% CI 19.8% to 22.4%) were alive at 1 year and 7.0% (95% CI 6.2% to 7.8%) at 3 years. Management by respiratory physician, oncologist, or thoracic surgeon was an independent predictor of access to potentially curative treatment and better survival. CONCLUSION: This national population based study demonstrates low use of treatment, poor survival, and the influence of process of care on survival. Implementation of evidence-based guidelines will require substantial changes in practice. Increasing the number of patients who receive treatment may improve survival.

Organizing the care of lung cancer patients.

For years lung cancer has been the Cinderella of malignant disease, perceived as being self-inflicted and incurable. The government has put cancer management high on its agenda and is setting targets for clinicians to aim at. This article looks at the changes which are occurring in the way lung cancer is managed.

Oral histoplasmosis: a case report.

We report a case of biopsy-proven histoplasmosis in an 81-year-old man with mouth ulcers. The initial infection was probably contracted whilst he was a prisoner of war in Sumatra, and was reactivated during intercurrent illness with congestive cardiac failure and oral corticosteroid treatment for idiopathic thrombocytopaenic purpura. Of particular note is the latent period of 50 years, and a positive cytoplasmic antineutrophil cytoplasmic antibody (cANCA) titre.

Management of lung cancer in South East Scotland.

BACKGROUND: There are few reports which describe the management of unselected groups of patients with lung cancer. This study was undertaken to audit prospectively the presentation, diagnosis, management, and outcome of patients presenting with lung cancer in South East Scotland. METHODS: Data were recorded on all patients with newly diagnosed lung cancer who presented to a multidisciplinary group of clinicians over a 12 month period. Subsequent follow up data on treatment and survival were collected. RESULTS: Six hundred and twenty two patients were registered, 80% of whom were referred from primary care. There was a considerable variation in the length of history, but the diagnosis was rapidly made after referral (87% within two weeks). In 82% of patients the pathological examination was positive; 70% were treated with palliative intent. Only 36% of patients who underwent surgery had computed tomographic scanning and 55% had sampling of mediastinal nodes. A wide variety of regimens was used for treatment with radiotherapy and chemotherapy, and follow up data were difficult to obtain in these patients. Survival was poor in all patients treated with palliative intent. CONCLUSIONS: This audit confirms the importance of previously noted prognostic factors. Significant variation in referral practice, diagnostic and management evaluation has been shown. The data serve as a useful background for the formation of local management guidelines.

Measurement of placental alkaline phosphatase activity in benign and malignant pleural effusions.

The usefulness of placental alkaline phosphatase (PLAP) as a diagnostic marker of malignancy was assessed in pleural fluid from 60 patients with effusions. Pleural fluid PLAP activities were measured by an enzyme linked immunoassay (ELISA) using the two monoclonal antibodies H17E2 and H317. Similar values were found in groups of patients with primary bronchial tumours (n = 12), secondary malignancies (n = 23), and "benign" conditions (n = 25). The highest values were found in a small subgroup of patients with metastatic ovarian carcinoma. However, the production of this enzyme by normal lung makes the measurement of PLAP in pleural fluid unhelpful as a diagnostic aid to distinguish "benign" from malignant effusions.

Alveolar atypical hyperplasia in association with primary pulmonary adenocarcinoma: a clinicopathological study of 10 cases.

BACKGROUND: A distinctive cytologically atypical lesion has been found in patients with primary adenocarcinoma of the lung. The aim of this study was to characterise the lesion and assess its role in tumour pathogenesis. METHODS: Lung parenchyma from 175 consecutive resection specimens for primary pulmonary adenocarcinoma were examined. Foci of atypical hyperplasia were identified. Cell proliferation state and expression of S100 and carcinoembryonic antigens were evaluated by immunohistochemistry. Clinical data on cigarette smoking and occupational exposure to carcinogens were abstracted from inpatient case notes. RESULTS: Ten cases (5.7%) with these distinctive cytologically atypical lesions were identified. The lesions showed immunohistochemical evidence of increased cell proliferation and focal carcinoembryonic antigen expression. The associated adenocarcinomas were of peripheral (parenchymal) type. There was an association with cigarette smoking and two of the 10 patients had synchronous carcinomas elsewhere in the lung. CONCLUSION: The clinical and pathological associations of these lesions suggest that they may be important in the histogenesis of primary pulmonary adenocarcinoma.

Characterisation and properties of a small cell lung cancer cell line and xenograft WX322 with marked sensitivity to alpha-interferon.

Controversy exists as to whether interferons usefully influence the growth of epithelial carcinomas. A small cell lung carcinoma (SCLC) cell line, WX322, has been derived which is greater than 1000-fold more sensitive to alpha-interferon (IFN) when grown in agar than other reported SCLC cell lines. The WX322 line has been characterised to prove its epithelial origin and its chemosensitivity compared with that of the NCI-H69 small cell line. The WX322 cell line expresses neuroendocrine and epithelial markers and possesses a morphology consistent with SCLC origin. A concentration of 5 IU ml-1 of IFN produced 50% inhibition of colony formation in agar in the WX322 line, whereas a concentration of greater than 10(5) IU ml-1 was required to produce a comparable effect with the NCI-H69 cell line. In contrast, WX322, possessed similar sensitivity to NCI-H69 cells when exposed to a range of cytotoxic agents. Analysis of the cell cycle indicated that IFN increased the percentage of cells in the G0/G1 phase for the WX322 cell line but increased the percentage in S phase for the NCI-H69 line. Growth of the xenograft, from which the cell line was derived, was also inhibited by IFN at doses greater than 10(5) IU/mouse/day. The WX322 cell line whether grown in agar or as a xenograft shows an unusually high sensitivity to IFN and provides an interesting model for studying mechanisms of IFN cytotoxicity to epithelial cells.

Potentiation of cisplatin by alpha-interferon in advanced non-small cell lung cancer (NSCLC): a phase II study.

Studies in experimental human lung cancer models have suggested that interferon may enhance significantly the response to some cytotoxic drugs. We have performed a phase II study of cisplatin (100 mg/m2 q.21 or 28 days) and alpha-2 interferon (3 or 5 MU three times weekly) in 68 patients with advanced non-small cell lung cancer and good performance status. As toxicity was acceptable, the dose of interferon and schedule of cisplatin were increased at the midpoint of the study. 46% (11/24) of patients with squamous carcinoma responded and an overall partial response rate of 30% was attained in 60 evaluable patients. There was no potentiation of haematological, renal or neurological toxicity but nausea and vomiting were severe. These results suggest that the combination has activity in this usually refractory disease.

Measurement of glutathione S-transferase pi isoenzyme in plasma, a possible marker for adenocarcinoma of the lung.

Using a specific radioimmunoassay, we measured glutathione S-transferase (GST; EC 2.5.1.18) pi isoenzyme in the plasma of 29 patients diagnosed as having carcinoma of the bronchus. Concentrations of the enzyme were significantly higher (P less than 0.01) than those measured in a control group of 16 patients with respiratory disorders other than malignancy. Although, overall, only 19 (66%) of patients with cancer of the bronchus had increased concentrations of GST pi in plasma, eight of the nine (89%) patients diagnosed as having adenocarcinoma had above-normal concentrations of GST pi. To obviate spuriously high results for GST pi concentrations caused by platelet release, we assayed blood samples collected in "Thrombotect" tubes, which contain inhibitors of platelet activation.

Activity of a new nitrosourea (TCNU) in human lung cancer xenografts.

The activity of a new nitrosourea (TCNU) based on the endogenous amino acid taurine was assessed in three human lung cancer xenografts growing in immunodeficient mice. Moderate activity (specific growth delays of 0.63 and 1.13 compared with controls) was seen in two non-small cell tumours after a single oral administration of 20 mg-1kg. This dose was curative in a small cell xenograft. By using high performance liquid chromatography it was possible to detect parent drug in the tumours as well as the plasma and tissues after oral administration of TCNU. Drug sensitivity was correlated inversely with the amount of the DNA repair enzyme 0(6)-methylguanine-DNA methyltransferase assayed from extracts of the tumour cells but not with the levels of parent drug within the tumour. This compound appears to have unique pharmacokinetic properties compared with other chloroethylnitrosoureas.

Augmentation of cytotoxicity of chemotherapy by human alpha-interferons in human non-small cell lung cancer xenografts.

Three human non-small lung cancer xenograft lines were used to study the activity of combinations of cytotoxic drugs with human alpha-interferons (IFNs). Statistically significant potentiation of cis-platinum (CDDP) and cyclophosphamide (CY) given weekly in a low dose was seen when human lymphoblastoid interferon (IFN-alpha nl) (2 X 10(5) mu/mouse/day) was administered simultaneously. The median tumor doubling times for CDDP in the three tumors (35, 22, and 29 days) increased to 52, 51, and 41 days when IFN-alpha nl was added. A similar though less marked effect was seen with CY (median doubling time increased from 21.5, 19.5, and 27 days to 32, 27, and 35 days with the addition of IFN-alpha nl). IFN-alpha nl alone at this dosage was shown to have some cytotoxic activity. Similar potentiation of CDDP and ifosfamide was seen in two tumors when human recombinant alpha-2 interferon was added at a lower dose (2 X 10(4) mu/mouse/day). Median doubling times for CDDP increased from 17 and 14 days to 27 and 18.5 days with the addition of human recombinant alpha-2 interferon, whereas for ifosfamide they increased from 11.5 and 14 days to 15 and 16 days. Human recombinant alpha-2 interferon in this dose had no effect as a single agent.

Human tumour xenografts growing in immunodeficient mice: a useful model for assessing chemotherapeutic agents in bronchial carcinoma.

Xenografts from eight human bronchial carcinomas have been established in CBA/Lac mice rendered immunodeficient by neonatal thymectomy followed three weeks later by whole body irradiation (7.35 Gy (735 rads)) after a priming dose of cytosine arabinoside. Growth rates of individual tumour lines remain constant and the histological and chromosomal characteristics of the original tumour are maintained through multiple serial passages over many months. With specific growth delay as the principal end point this system may be used to assess the response of histologically different lung tumours to chemotherapeutic agents.