Bronchioloalveolar adenocarcinoma of lung: monoclonal origin for multifocal disease

In an attempt to understand the histogenesis and molecular pathogenesis of multifocal bronchioloalveolar lung carcinoma (BAC) we studied 28 cases of BAC using a topographic genotyping approach for the presence of K-ras exon 1 mutations and p53 loss of heterozygosity (LOH). This analytical approach demonstrated K-ras exon 1 mutations in 12.5% of solitary BACs, 40% of BACs with microscopic or macroscopic satellite lesions, and 60% of BACs with intrathoracic metastases. In all cases with K-ras mutations, the identical point mutation was present in the primary, satellite, and intrathoracic metastatic lesions. When p53 LOH was demonstrated in the primary lesion, it was also detected in the satellites and intrathoracic metastases. No significant association was noted between the presence of K-ras mutations and p53 LOH. The results strongly support a monoclonal origin of multifocal BACs. Furthermore, the findings support the theories explaining the origin of multifocal BAC by intraalveolar route of spread, intrapulmonary lymphatic spread, or aerosolization leading to implantation at different sites. A trend toward an increased frequency of K-ras mutations and p53 LOH in BACs with satellites or metastases compared to solitary BACs was noted.     

Bronchioloalveolar carcinoma and the air bronchogram sign: a new pathologic explanation

Bronchioloalveolar carcinoma (BAC) is one of the few lung tumors known to demonstrate the air bronchogram sign. Production of this valuable radiologic sign by this tumor has been ascribed to an "alveolar" filling process in which tumor grows along alveolar walls with preservation of the architecture and secretes copious amounts of mucus. Thus, aerated bronchi are surrounded by alveoli that are filled with mucus and tumor. We present a case in which the air bronchogram sign and pulmonary consolidation are associated with a nonsecretory BAC. Alternative mechanisms that may produce the air bronchogram sign in BAC are offered.     

Bronchioloalveolar lung carcinomas: K-ras mutations are constant events in the mucinous subtype

Bronchioloalveolar carcinoma (BAC) is a form of peripheral lung adenocarcinoma growing as a single layer of malignant cells along the walls of terminal airways. The existence of BAC as a separate clinico-pathological entity has been a matter of controversy, mainly because its histogenesis is uncertain and it is not easily distinguishable from conventional lung adenocarcinoma (CLA). Three subtypes of BAC have been described using histological and cytological criteria: mucinous, non-mucinous, and sclerosing. The clinical behaviour of BAC appears to be dependent on the histological subtype. The different morphological patterns and clinical outcome of the subtypes of BAC suggest that their biological behaviour may be different from one another and from CLA. This study has investigated 58 BACs (10 mucinous, 40 non-mucinous, and 8 sclerosing) and 50 control CLAs for mutations at codon 12 of the K-ras oncogene. Twenty-one (36 per cent) BACs and 13 (26 per cent) CLAs showed K-ras mutations. A clear association (P < 0.0001) between K-ras mutations and the mucinous type of BAC was observed: all 10 mucinous tumours examined were scored positive for mutations in the K-ras gene, while only 9 (23 per cent) of the 40 non-mucinous and 2 (25 per cent) of the 8 sclerosing BACs were found to be positive. The frequency of ras mutations in non-mucinous BAC, sclerosing BAC, and CLA was not statistically different. Our data indicate that BACs are a heterogeneous group of lung tumours and that the mucinous form might represent a biological entity separate from both the other two BAC types and CLA.     

Second primary lung carcinoma

Ffity-five patients suffering from second primary lung carcinoma, 10 synchronous and 45 after resection for lung carcinoma (metachronous), have been observed from 1400 resections. The first manifestation of a second carcinoma in this series has always been the appearance of a new shadow in the follow-up radiograph. In our experience, second primary lung carcinoma is a disease affecting only heavy cigarette smokers. Heavy cigarette smokers suffering from squamous-cell carcinoma are at special risk. The results of re-operation, the significance of the time interval between the original operation and the appearance of the second primary carcinoma, and the slow growth rate of some second primaries are briefly discussed. No clear-cut methods exist for distinguishing a second primary from a metastasis from the original carcinoma.     

Gallium-67 scanning for carcinoma of the lung

Gallium-67 citrate scanning was prospectively evaluated in 55 patients who had lung lesions suspected to be primary carcinoma on chest x-ray films and in whom subsequent histologic diagnosis was obtained. Of 47 patients with histologically proved carcinoma of the lung, 44 (94 per cent) had a positive 67Ga scan. No patient with a positive scan had a benign lesion, so that the positive scan accuracy rate was 100 per cent. All 8 patients with a benign lesion and 3 patients with a malignant lesion had negative scans, for a negative scan accurary rate of 72 per cent for benign lesions. These results give statistical validity for the usefulness of the 67Ga scan in diagnosing carcinoma of the lung (p less than 0.001). Tumor cell type had little effect on the sensitivity of 67Ga scan. The 67Ga scan was equally useful in the evaluation of peripheral and central lesions. There was little difference amount T1, T2, and T3 classified lesions in their ability to take up 67Ga. The 67Ga scan was competitive with mediastinoscopy in assessing mediastinal lymph node metastases and provides a noninvasive method of assessing hilar lymph node metastases. There was a good correlation between the clinical staging of patients with lung cancer based on a chest x-ray film and 67Ga scanning and the staging after surgical treatment based on the histology of the resected specimens.     

Myasthenia gravis associated with small-cell carcinoma of the lung

A 49-year-old man complained of a 3-month history of progressive generalized muscle weakness. He was diagnosed as having small-cell lung carcinoma at the same time. He received an intravenous injection of edrophonium chloride with remarkable improvement of muscle strength. Electromyographic studies revealed a compound muscle action potential that decreased after repetitive stimulation. These findings were considered representative of myasthenia gravis (MG), and inconsistent with Eaton-Lambert syndrome. The appearance of MG with small-cell lung carcinoma seems to be very rare, but possible.     

Radical irradiation with the split-course technique in carcinoma of the lung

The possible advantages of a split-course of irradiation in the treatment of patients with locally advanced and/or inoperable carcinoma of the lung were explored in over 200 cases. The patients were separated into two groups with different prognostic factors: Group A, patients with well-differentiated tumors confined to the lung and mediastinum; and Group B, cases with anaplastic tumors and/or supraclavicular metastases, bone erosion, or superior venal caval syndrome. The treatment consisted of 5500-6000 rads tumor dose in 20 to 24 fractions over a period of 7 to 8 weeks with a rest interval of 2 to 4 weeks in the middle. The 3- and 5-year survival figures, 19% and 16%, respectively, in Group A cases, along with the excellent tolerance, suggest that the split-course approach has definite advantages.     

Extramedullary hematopoiesis mimicking metastatic lung carcinoma

Extramedullary hematopoiesis is a rare condition defined as the appearance of hematopoietic elements outside of the bone marrow, which occurs primarily in patients with chronic myeloproliferative disorders or congenital hemolytic anemias. We report a patient who presented with a left lower lobe lung carcinoma and right paravertebral and left pleural masses, initially thought most consistent radiographically with inoperable metastatic disease, until biopsies of the paravertebral and pleural masses established the presence of extramedullary hematopoiesis. The left lower lobe neoplasm was subsequently resected uneventfully.     

Extrinsic compression of the pulmonary artery by non-microcytic lung carcinoma

A patient with a remitting non-microcytic pulmonary carcinoma was subjected to Doppler-echocardiography. The detection of a pericardial effusion with compression of the pulmonary artery due to an extrinsic mass indicated that the disease was progressing. The Doppler technique was used to evaluate the degree of arterial stenosis by determining the pressure gradient caused by it (49 mmHg) and to calculate the right ventricle pressure (75 mmHg). Tumor infiltration of mediastinal structures was posteriorly confirmed by computed tomography.     

Large cell carcinoma of the lung metastatic to nuchal muscle

An attempt to achieve problem-based examining by the structured assessment of presentations is described. Students can choose to participate in the scheme in teams and then elect to use their awarded mark instead of part of the formal examination assessment. The element of choice of the study or examination method is seen as being a valuable element of the scheme. The scheme can be introduced without radical revision of existing curricula or substantial investment of staff time, and meets some of the expressed desires of the UK General Medical Council in terms of the introduction of novel methods of assessment.     

Muscle metastasis in a patient with epidermoid carcinoma of the lung

Diagnosis of vertically acquired human immunodeficiency virus (HIV) infection is often difficult because of transplacentally acquired maternal antibodies. The polymerase chain reaction (PCR) test is commercially available and has high sensitivity and specificity. To evaluate the usefulness of PCR testing in the early diagnosis of perinatally acquired HIV infection, we reviewed records of 122 children having follow-up in the Northeast Florida Pediatric AIDS Program. Seventy-two children were excluded for various reasons. Of the remaining 50 children, 37 had PCR testing. In 5 children, the initial PCR test was done at > 18 months of age. Results of PCR testing were positive in 8 of 13 (62%) at birth, 12 of 18 (67%) by 1 month of age, 18 of 23 (78%) by 2 months of age, and 20 of 24 (83%) by 3 months of age. In 24 of 27 (85%), results were positive by the time the children reached 4 months of age. Our data suggest that the PCR test is a useful tool for early diagnosis of vertically transmitted HIV infection.     

Operative management of adrenal metastases from lung carcinoma

Most surgeons consider patients with solitary adrenal metastasis from a primary lung carcinoma incurable and avoid excision of both the adrenal and primary lung tumors. However, several cases of successful surgical management of these patients recently have been reported. We reviewed 12 surgically treated patients with isolated adrenal and lung disease and identified 2 survivors of greater than fifteen years (17%) and 4 additional patients who are still alive following combined resection (34%). This survival rate, albeit in a selected population, represents an improvement over the natural history of nine months' survival. We suggest that if after six to twelve months of following patients with lung cancer and isolated adrenal metastasis no other evidence of spread of disease is evident, the tumor biology may be favorable and resection of both adrenal and lung lesions is reasonable.     

Extended operation for T4 lung carcinoma

PURPOSE: The study objective was to determine an "optimal" individual pressure support (PS) level for beginning weaning with PS ventilation in patients with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Eleven COPD patients intubated and ventilated for acute respiratory failure and judged ready for weaning were studied. The technique consisted of lowering the PS level from a point that was characteristic for each patient and measurable under controlled mechanical ventilation, after setting the ventilator as recommended for COPD patients judged ready for weaning, that is, peak inflation pressure (PIP). This determination was based mainly on exploring the diaphragm with an electromyographic technique by defining the optimal PS level as the lowest PS level associated with no EMG evidence of diaphragmatic stress. Diaphragmatic electromyographic activity (diEMG) was recorded by a bipolar esophageal electrode (Disa-Denmark), and the high-frequency electrical component/low-frequency ratio (H/L) was calculated. The reference H/L was determined during a few spontaneous ventilatory cycles. Muscle stress was defined as a greater than 20% reduction in H/L compared with the reference value. RESULTS: Optimal PS levels ranged from 4 to 24 cm H2O with a mean of 14+/-6 cm H2O. Two patients with optimal PS level at 4 cm H2O did not require weaning and were quickly extubated. For the nine other patients, optimal PS levels were found to be 70% of PIP; in none was it necessary during weaning to use PS levels higher than individual optimal PS levels. CONCLUSIONS: Optimal PS level established with diEMG monitoring seems to be a useful index for beginning weaning in the PS ventilation mode in COPD patients. The hypothesis of beginning weaning with a PS level equal to 70% of PIP needs to be tested.     

Photodynamic therapy for early stage squamous cell carcinoma of the lung

We studied 9 patients with bilateral vertebral artery occlusion (BVAO). BVAO was confirmed using angiography in order to clarify its clinical feature, mechanism, and long term prognosis. Three patients showed bilateral intra-cranial occlusion, 3 bilateral extra-cranial occlusion, and 3 intra and extra-cranial occlusion. The basilar artery was fed by the posterior communicating artery in 8 out of 9 patients. In one of the 8, reconstitution of the thyrocervical artery was seen. We divided the patients into 4 groups according to MRI findings, as follows: Group 1 with no abnormal finding on MRI (N = 2); Group 2 with deep pontine infarcts and non-territorial small cerebellar infarcts (N = 2); Group 3 with extended pontine infarcts (N = 3); and Group 4 with cerebellar cortical artery infarcts, deep pontine infarcts, and non-territorial small cerebellar infarcts (N = 2). Transient episodes were seen in all patients, 8 patients out of 9 had vertigo/dizziness, 3 tinnitus, 2 diplopia, 2 headache, 2 numbness, and 1 hearing disturbance. These episodes preceded a final attack or complete stroke 2 days to 5 months, and those who had a longer period of episodes in the preceding term tended to have less severe deficits. Six of the patients had vertebro-basiler symptoms after being in the upright position, including all the patients in Groups 2 and 4, which had cerebellar border zone/terminal zone infarcts. These results indicate that the hemodynamic mechanism plays an important role in BVAO. The prognosis was not always grave. Four of the patients could walk independently, 2 could walk with a cane, and 3 were bed ridden (2 of which died). Long-term follow-up data (a mean of 5 years) were obtained in all patients. In the patients who could walk, one had asymptomatic cerebellar infarcts, and one had TIAs frequently. Patients with BVAO often also have TIAs and/or preceding episode and show cerebellar border zone/terminal zone infarcts. This research strongly suggests that hemodynamic mechanism might play an important role in BVAO, and that paying attention to border zone infarction in MRI and transient episodes can lead to earlier diagnosis and treatment.     

Multidisciplinary approach to potentially curable non-small cell carcinoma of the lung

The management of patients with non-small-cell lung cancer (NSCLC) is still evolving. Newer third-generation chemotherapy (paclitaxel [Taxol]-based; vinorelbine [Navelbine]/ cisplatin [Platinol]) is more effective than second-generation cisplatin-based chemotherapy for patients with stage IIIB and IV disease. The combined use of cisplatin-based chemotherapy with sequential or concurrent radiation therapy has improved the survival of patients with unresectable stage IIIA disease. Neoadjuvant cisplatin-based chemotherapy has improved the survival of patients with resectable stage IIIA disease compared to surgery alone. Combined-modality therapy is a fertile area of innovative clinical investigations for the majority of stage III resectable and potentially curable NSCLC patients, as well as those with locally advanced unresectable stage III disease. We expect therapy to substantially improve over the next few years. Cooperative groups should move quickly to incorporate third-generation chemotherapy into large randomized trials in order to redefine the standard of therapy for patients with this disease.