Surgical therapeutic strategy in non-small-cell bronchial carcinoma

For localized, non-small cell carcinomas (stages I and II) surgery is the treatment of choice because these lesions usually can be excised completely. The choice of the surgical procedure--lobectomy, pneumonectomy, segmental or sleeve resection--depends on the extent of malignant disease and the patients functional status. The procedure of choice is usually that which will encompass all existing disease and provide maximum conservation of normal lung tissue. On occasion, stage III disease may present borderline cases for surgery. Indications are based on existing or imminent complications in advanced locoregional tumor growth. Localized chest-wall or pericardium invasion, superior sulcus tumors, limited mediastinal nodal involvement, and phrenic involvement are not absolute surgical contraindications. Each case must carefully be evaluated and individualised. This kind of tumor management requires sophisticated techniques. The primary aim is to achieve complete tumor resection and to avoid an exploratory thoracotomy or an incomplete surgical resection. The hilar and mediastinal lymph nodes have to be completely resected to ensure a real R0-resection. The presence of distant or extrathoracic metastasis is indicative of inoperability and a surgical procedure is an absolute contraindication. There is no proven place to date for debulking surgical procedures in lung cancer.     

Is preoperative chemotherapy in locally advanced non-small-cell bronchial carcinoma of value?

Although surgeons are able to resect completely locally advanced non-small cell lung cancer with mediastinal lymph node involvement (stage IIIA), the majority of patients succumb from metastatic disease. Therefore, neoadjuvant therapy was introduced in the management of this disease in order to eradicate distant metastases at an early stage. Phase II trials with preoperative chemotherapy in stage IIIA patients have shown that the pathological response (amount of tumour necrosis) and the clearance of mediastinal lymph node correlate with a better survival and is the best predictor for eradication of distant metastases. Indeed, three small randomised phase III studies have demonstrated a survival advantage for preoperative chemotherapy compared to surgery alone. Further studies are required to determine the best neoadjuvant regimen inducing the largest amount of tumour necrosis.     

Chemotherapy of advanced non-small-cell and small-cell bronchial carcinoma with bendamustine--a phase II study

In the palliative treatment of advanced SCLC and NSCLC there is a big need for effective and well tolerable drugs. Bendamustin is an alcylatic agent which had shown activity in the treatment of Non Hodgkin- and Hodgkin-Lymphoma as well as in the treatment of solid tumors like Mamma-Carcinoma and Colorectal-Carcinoma. We treated 21 patients with NSCLC (5 pat. Stad. III b, 16 pat. Stad. IV) and 22 pat. with Extensive Disease SCLC with Bendamustin 70 mg/m2 i.v., day 1-4 (q.28 days). We observed a response rate of 40.9% in the patients with SCLC (9 PR/40.9%), (0 CR) and no response in the patients with NSCLC. Hematologic toxicity in both groups was mild (Leucopenia WHO 1 + 2: 13 pat./30.2%, WHO 3: 2 pat./4.6%; Anemia WHO 1 + 2: 13 pat./30.2%, WHO 3: 1 pat./2.4%; Thrombopenia WHO 1 + 2: 4 pat./9.6%, WHO 3: 1/2.4%). Non Hematologic toxicity consisting of Nausea/Vomiting (WHO 2 + 3:13 pat./30.2%), Diarrhea (WHO 2 + 3:3 pat./7%), Obstipation (WHO 1 + 2: 2 pat./4.6%), Fever (WHO 1 + 2: 9 pat./20.9%) and Alopecia (WHO 1 + 2: 13 pat./31.7%, WHO 3: 1 pat./2.4%) was well tolerable. Cardiac Arrhythmias occurred in 7 pat./16.3% and PNP in 2 pat./4.6%. Treatment had to be stopped in one patient because of an allergic skin reaction. Bendamustin is a well tolerable cytostatic drug with a remarkable activity in advanced SCLC which is comparable to other well known agents in the treatment of this disease. Because of the good toxicity profile a combination with other compounds might be feasible. In advanced NSCLC Bendamustin showed no activity.     

The radiotherapy of inoperable non-small-cell bronchial carcinoma. A retrospective analysis of 427 cases

BACKGROUND: The influence of tumor and patient characteristics on survival as well as acute normal tissue toxicity was retrospectively analyzed. PATIENTS AND METHODS: 427 patients with inoperable non-small cell lung cancer were retrospectively analyzed. Two thirds received a total dose of at least 70 Gy, and one third was irradiated with 60 to 66 Gy (2.0 to 2.5 Gy per fraction; split-course technique). 92% had a Karnofsky performance index of > or = 80%. Kaplan-Meier survival curves were generated and comparisons were made by the log-rank test. Prognostic factors were adjusted for by a proportional hazards analysis. RESULTS: Five-year survival rates (+/- SE) and the median survival times (95% confidence interval) were 2 +/- 2% and 11.1 months (9.1 ... 14.5) after 60 to 66 Gy; 8 +/- 2% and 14.9 months (13.3 ... 16.5) after 70+ Gy. The difference was significant in univariate (p = 0.0013) and multivariate analysis (p = 0.0006). Tumor stage (p = 0.0029: I + II > III; IIIA > IIIB) and gender (p = 0.0387: female > male patients) reached significance in multivariate analysis. Acute pneumonitis and esophagitis were observed in 11% and 9% of cases. CONCLUSIONS: Inoperable non-small cell lung cancer stage I to IIIA should be treated in a curative intention with total doses of about 70 Gy. This is feasible with acceptable normal tissue toxicity. Stage IIIB patients have a particular bad prognosis and should only be treated palliatively.     

Clubbed fingers and arthralgia as a reversible paraneoplastic syndrome (Pierre-Marie-Bamberger syndrome) in non-small-cell bronchial carcinoma

HISTORY AND CLINICAL FINDINGS: During chemotherapy for a non-small-cell bronchial carcinoma with metastasis to the right femur (previously locally excised), a 34-year-old man suddenly developed severe, lasting joint pain in the ankle, knee, elbow and wrist without signs of increased warmth or swelling of these joints. At the time of diagnosis clubbed fingers had been noted. INVESTIGATIONS: Radiography of the hands showed bilateral periosteal hyperostoses. Computed tomography of the thorax revealed tumor progression. DIAGNOSIS, TREATMENT AND COURSE: The triad of clubbed fingers, periosteal hyperostoses and arthralgia/arthritis with the pulmonary findings established the diagnosis of hypertrophic pulmonary osteoarthritis (HPO; Marie-Bamberger syndrome). Initially there had merely been the signs of the much more frequent incomplete form with only the clubbed fingers, the complete form developing with progression of the disease during chemotherapy, joint pains dominating the symptoms. After right upper lobectomy (primary adenocarcinoma) the joint pains ceased and the finger clubbing regressed. CONCLUSIONS: Only 10% of non-small-cell bronchial carcinomas are associated with HPO. Conversely, such a tumor is found in 90% of HPO of recent onset and should therefore be sought of when searching for the primary tumor. The signs of HPO are reversible if the underlying disease is adequately treated.     

Neoadjuvant combined therapy in stage IIIA if non-small-cell bronchial cancer

BACKGROUND AND OBJECTIVE: The overall prognosis of patients with stage IIIA non-small-cell lung cancer is unfavourable (median survival time 12 months). Tolerance to and efficacity of a multimodal neoadjuvant treatment was assessed in a prospective study. PATIENTS AND METHODS: 25 patients (median age 59 [37-69] years), with histologically confirmed mediastinal lymph node metastases, underwent chemotherapy. Immediately after two cycles with carboplatin/Ifosfamid (dimethoate)/etoposide they received hyperfractionated accelerated radiotherapy (45 Gy; 2 x 1.5 Gy daily) with simultaneous administration of carboplatin and vindesine. This was followed by tumour resection. RESULTS: After conclusion of the neoadjuvant treatment 19 of 25 patients (76%) had a remission. Of the 20 operated patients complete resection (R0) was possible in 17 (85%) and 14 of the 20 patients with resection (70%) had histologically demonstrated marked tumour regression. Critical toxicity consisted of pneumonitis and bronchial stump problems. Median survival time of all patients was 24.8 months and for patients with R0 resection 35.9 months. CONCLUSION: Neoadjuvant multimodal treatment of stage IIIA non-small-cell lung cancer can achieve prolongation in survival time. The place of radiotherapy or radiotherapy with chemotherapy in such a treatment concept will need to be defined in a randomized study.     

Value and limits of surgery in stage IIIB non-small-cell bronchial cancers

Storage of radon-producing material in two silos and two waste pits is one of the major environmental and occupational issues at a former uranium production facility, now a Superfund site. In addition, up to 100 metric tons of thorium is stored on the northeast side of the site. Concentrations of radium up to 17,600 Bq g(-1) (477,000 pCi g(-1)) or higher for silos and up to 45 Bq g(-1) (1,200 pCi g(-1)) for waste pits have been reported. This study was conducted to identify factors and climatic conditions that contribute to higher radon levels and to assess workers' exposure at the site. Data covering a 12-mo period were compiled from monitoring hourly real-time radon levels at indoor (within 3 buildings) and outdoor (at 14 on-site and 2 off-site monitoring stations) locations and from hourly site-specific meteorological information. The ranges of radon levels were as follows: 1.8-3,655 Bq m(-3) (0.05-98.8 pCi L(-1)) outdoor on-site, 3.7-329 Bq m(-3) (0.1-8.9 pCi L(-1)) outdoor off-site, and 1.8-111 Bq m(-3) (0.05-3.0 pCi L(-1)) indoor on-site. Only radon levels in the vicinity of the storage silos were significantly higher than levels off-site. Radon concentrations showed diurnal variations, with maximum levels occurring in the early morning and minimum levels in the afternoon. Seasonal variation was also observed, with radon levels higher during the summer through early fall and lower during the late winter through spring. Wind speed, relative humidity, and wind direction appeared to be the most significant predictors of radon concentration. The estimated radon dose to workers, calculated by using exposure models and annual average levels of radon in the work area, was below recommended exposure limits. These results suggest that the emission control methods at this site have been effective in maintaining environmental radon contamination and workers' exposure at acceptable levels.     

Successful multimodal therapy of a locally advanced non-small-cell bronchial cancer

HISTORY AND CLINICAL FINDINGS: A chest radiogram, performed on a 60-year-old man with unproductive cough for 3 months, showed a space-occupying lesion in the right upper lobe, and breath sounds were diminished in this area. He had been a heavy smoker. His general condition and nutritional state were good. INVESTIGATIONS: Computed tomography, skeletal scintigraphy, bronchoscopy with biopsy and mediastinoscopy established the diagnosis of a locally advanced non-small-cell bronchial carcinoma (stage IIIB or T2N3M0). TREATMENT AND COURSE: Combined adjuvant treatment was begun in the hope of improving the median survival time of 8 months predicted for this tumour stage. After two cycles of a combined chemotherapy scheme (ifosfamide, carboplatin, etoposide) he received hyperfractionated-accelerated radiotherapy (total dose 45 Gy; 1.5 Gy twice daily) together with carboplatin and vindesine. This was followed by a right upper lobectomy with lymphadenectomy. Full remission was confirmed in both the resected specimen and the lymph nodes. The patients remains free of tumour 30 months after the diagnosis. CONCLUSION: Neoadjuvant treatment can significantly improve the prognosis of non-small-cell bronchial carcinoma in stage III. Such patients should therefore be treated according to the appropriate study protocol, if possible.     

Cerebral metastasis in bronchial carcinoma

A prospective study of 61 consecutive cases of bronchial carcinoma was done to detect cerebral metastasis and study their clinical presentations. Computerised tomography (CT Scan) was utilised as a screening procedure in 36 cases along with electroencephalography to detect cerebral secondaries. Of the cases studied with CT Scan and autopsy, 55% had brain secondaries. 18% of these cases had silent cerebral secondaries. 30% of the 61 cases studied has signs and symptoms referable to brain secondaries. An interesting clinical presentation was a dysequilibrium which in many of them was an extreme truncal ataxia, confining them helplessly to bed and relieved to some extent by a shunt operation.     

Hepatocellular carcinoma outcomes based on indicated treatment strategy

Hepatocellular carcinoma (HCC) in Western populations historically has been associated with poor survival. In this study, we conducted a 7-year retrospective analysis of patients evaluated at our institution with HCC to determine the effects of newer treatment strategies on outcome. During the period of study, 117 patients [86 (74%) male; mean age, 59 years (range, 16-85)] were evaluated with treatment as follows: surgical resection in 22 (19%), chemoembolization with or without systemic chemotherapy in 40 (35%), systemic treatment alone in 16 (13%), orthotopic liver transplantation in 8 (7%), and supportive care only in 31 (26%). Sixty-nine patients (59%) had documented cirrhosis, with hepatitis C being the most common cause in 27 of 69 (39%). In patients receiving no treatment, median survival was just under 3 months, with only two 1-year survivors. Patients with orthotopic liver transplantation had 1-, 2-, and 3-year survival rates of 87, 87, and 58 per cent compared with 69, 52, and 43 per cent in surgically resected patients. Survival after chemoembolization was 35, 20, and 11 per cent at 1, 2, and 3 years, whereas survival after systemic chemotherapy was 30 and 15 per cent at 1 and 2 years, respectively. One-year survival was improved in noncirrhotic patients compared with cirrhotics (47% vs 29%; P < 0.05) but was no different in patients younger than 55 years compared with older patients (38% vs 38%). When possible, surgical treatment strategies offer superior survival.     

Integrated treatment of the inoperable bronchial carcinoma (author's transl)

The inoperable bronchial carcinoma tends to early formation of metastases. If the tumor responds well to different cytostatic drugs, chemotherapy is absolutely necessary. In this case, combined therapy has better results than monotherapy. We use chemotherapy prior to radiotherapy in order to prevent hematogenic extension of the disease and to ameliorate the receptiveness of the primary tumor. In order to avoid local recurrence it is necessary to submit the primary tumor and the mediastinum to radiotherapy. A focal dose of 3000 rd within three weeks is considered to be sufficient. This dose generally does not cause severe myelosuppression, so that the chemotherapy can be continued. A report is given on the provisional results of different chemotherapeutic combinations. Further studies, however, are absolutely necessary in order to be in a position to give recommendations of common validity.     

Therapeutic possibilities of surgical treatment of patients with non-small-cell lung carcinoma and adrenal metastasis

Reports on successful surgical treatment of patients with non-small lung carcinoma and adrenal metastasis are infrequent. For this reason the Authors believe interesting to report a case of a patient with non-small lung cancer and single adrenal metastasis who underwent lung superior lobectomy and, after chemotherapy, adrenalectomy. A relapse was observed one year later in the lumbar region and the patient was reoperated undergoing removal of the recurrence associated to splenectomy and pancreas tail resection; thereafter the patient was treated with local radiotherapy. Forty-one months after the first operation the patient is well and disease free.     

The role of bronchial arteriography and therapeutic embolization in hemoptysis

A case is presented which demonstrates the value of bronchial arteriographic studies in localizing and treating hemoptysis. The patient was bleeding from an old post-tuberculous bulla and for several reasons was not a candidate for surgery. Bronchial arteriographic studies demonstrated both hypervascularity in the region of the cavity and also a mycotic aneurysm of a bronchial artery. After therapeutic embolization with gelatin (Gelfoam), the hypervascularity and aneurysm were no longer opacified. Active bleeding abruptly ceased and, except for a single mild recurrence, has not recurred during the three months since therapeutic embolization. The major theoretic risk of bronchial arteriographic study and therapeutic embolization is spinal injury. It is believed that permanent injury can almost be avoided, providing proper technique is used.