Bevacizumab and arterial hypertension or proteinuria: management

Bevacizumab is a monoclonal antibody against vascular endothelial growth factor that is currently validated for treatment and has shown survival benefit in various cancers, particularly non-small cell lung cancer. However, a very specific toxicity profile has been observed with bevacizumab. This article presents data from the literature concerning hypertension and proteinuria, and provides recommendations for the management of these toxicities.     

EGFR inhibitors in non-small cell lung cancer: more than yesterday (but less than tomorrow)

Molecular targeted agents represent a major breakthrough in the treatment of non-small cell lung cancer. Among these agents, Epidermal Growth Factor Receptor (EGFR) inhibitors are probably the more important so far. Whether inhibition is obtained by targeting the tyrosine kinase of the receptor (gefitinib or erlotinib) or by using a monoclonal antibody (cetuximab), the place of these treatments will increase in the next years. This article details the role of EGFR in lung carcinogenesis and the main therapeutic approaches used to inhibit EGFR activity. The results of the major clinical trials evaluating these agents are also discussed.     

Contribution of immunohistochemistry to the management of lung cancer: from morphology to diagnosis and treatment

Immunohistochemistry (IHC) has become an indispensable tool in pathology. For proper interpretation, results must be read with knowledge of the diagnostic, clinical, and morphological circumstances. We detail here the contribution of IHC to the classification of lung cancer: small-cell lung cancer and other neuroendocrine tumors, basaloid carcinoma, large-cell carcinoma. Using IHC techniques, pathologists can now determine with certainty that an intrathoracic adenocarcinoma is primary or secondary. The distinction is less clear for large-cell carcinoma or squamous-cell carcinoma, or for tumors with a pleural or mediastinal presentation. IHC is also useful as a diagnostic aid for rare entities: carcinomas with an unusual morphology (alpha-fetoproetin secretors or beta-HCG secretors), melanomas, lymphomas, sarcomas. By demonstrating the presence of carcinomatous cells within the neighboring structures (pleura) or lymph nodes, IHC contributes to lung cancer staging, particularly when there are few of these elements morphologically difficult to distinguish. Finally, IHC contributes to prognosis (proliferation markers, differentiation markers) or prediction of therapeutic response (chemotherapy or targeted therapies). IHC studies may also be requested in a forensic setting, for example to demonstrate that the lung cancer observed in a patient exposed to asbestosis is primary. In light of these different situations, a wide panel of antibodies is required. Other morphological techniques such as hybridization in situ or molecular biology techniques will further complete the histological diagnosis in the future.     

Pleomorphic carcinoma of the lung: a case report

Pleomorphic carcinoma is a rare malignancy belonging to the family of nonsmall cell lung cancers. A 40-year-old man, a smoker, was hospitalized for thoracic pain and dry cough with a deteriorating general condition. The imaging showed a "drop ball" of both lungs. The pathological evidence was obtained by lung biopsy under scanographic control. The presence of supraclavicular and abdominal nodes classified the tumour as stage IV. The patient received six cycles of first-line chemotherapy associating cisplatin and vinorelbine. However, the disease continued to progress and distant metastases were observed. The patient died 6 months after the diagnosis. Pleomorphic carcinoma is identified by purely histological criteria: the concomitant presence of malignant epithelial and homologous sarcomatoid spindle-cell components. Like the other nonsmall cell lung cancers, the treatment is primarily surgical, and the invasive nature of this tumour makes it very difficult. Pleomorphic carcinoma has a poorer prognosis than conventional nonsmall cell lung cancers despite surgery, irradiation and chemotherapy, because relapse occurs early.     

Ethambutol dosage for the treatment of children: literature review and recommendations.

The currently recommended daily dose of ethambutol (EMB) for the treatment of tuberculosis (TB) in children varies from a maximum daily dose of 15 mg/kg body weight daily (without a range) to 15-20 mg/kg and 20 mg/ kg (range 15-25 mg/kg). Published evidence relating to the dosage, toxicity and pharmacokinetics of EMB in children and adults is reviewed and a dose of EMB for use in childhood is recommended. Using key words 'ethambutol', 'childhood', 'TB', 'pharmacokinetics', 'bioavailability' and 'toxicity', Medline searches were conducted; cross-references were sought from original papers, books and conference proceedings dating from 1961. When English summaries were available, data were extracted from papers in languages other than English. EMB has a dose-related efficacy best seen when given to adults alone or with a single other drug. Together with isoniazid (INH), a dose of 15 mg/kg EMB gave better results than 6 mg/kg, and 25 mg/kg better than 15 mg/kg. The occurrence of ocular toxicity was also dose-related; >40% of adults developed toxicity at doses of >50 mg/ kg, and 0-3% at a dose of 15 mg/kg/daily. Peak serum EMB concentrations increase in relation to dose, but are significantly lower in children receiving the same dosage. In only 2 of 3811 children (0.05%) receiving EMB doses of 15-30 mg/kg was EMB stopped due to possible ocular toxicity; children of all ages can be given EMB in daily doses of 20 mg/kg (range 15-25 mg/kg) and three times weekly intermittent doses of 30 mg/kg body weight without undue concern.     

Platelet-inhibitor drugs before and after coronary artery bypass surgery and coronary angioplasty: the basis of their use, data from animal studies, clinical trial data, and current recommendations

The pathogenesis of aortocoronary vein-graft occlusion appears to be similar to the development of atherosclerosis, except that it is more accelerated, especially during the first postoperative year. Initiation of platelet-inhibitor therapy before operation is important especially in patients at high risk of bypass graft occlusion because platelet deposition starts during operation and initiates the process of occlusion. The largest and only placebo-controlled trial to start therapy before operation showed that dipyridamole (Persantine) plus aspirin markedly reduced occlusion (compared with placebo) in both high- and low-risk subgroups both early and at a median of 1 year after operation. Arterial balloon angioplasty often causes severe arterial wall injury, which is a potent stimulus for immediate platelet-thrombus deposition and is probably the main contributing factor in the process of restenosis. Animal studies suggest the potential value of antithrombotic therapy starting the day before the angioplasty procedure, but results from placebo-controlled trials in humans are needed before optimal therapy can be established.     

Tumor interaction with hemostasis: the rationale for the use of platelet inhibitors and anticoagulants in the treatment of cancer

Clinical and experimental observations have firmly established the concept of a two-way interaction between malignancy and the hemostatic system. On the one hand, certain tumors can activate platelets and the coagulation mechanism in vivo, on the other, a convincing case has been made for the involvement of platelets and fibrin in tumor growth and metastasis. A large number of clinical and experimental studies have been conducted in order to test the efficacy of platelet inhibitors and anticoagulants as adjuvants in the treatment of cancer. Antiplatelet drugs gave variable results, depending on the drug and the tumor system tested. Prostaglandin synthetic pathways by both the host and tumor seem to be an important determinant in the response to platelet function inhibitors. Of the various anticoagulants tested, the coumarin derivatives gave somewhat consistent antitumor effect in certain human and experimental cancer. The antitumor effect of oral anticoagulants does not appear to be a primary drug effect and seems related to their role as vitamin K antagonists. It should be emphasized that although the antitumor potential of antithrombotic agents is a subject of keen interest at the present, their use in treating human cancer is still controversial.     

The risks of screening: data from the Nottingham randomised controlled trial of faecal occult blood screening for colorectal cancer

AIMS: To determine the harm that ensues from faecal occult blood (FOB) screening for colorectal cancer. METHODS: 150 251 people were randomly allocated either to receive biennial Haemoccult FOB tests (n =75 253) or not to be contacted (n=74 998). Study group patients returning positive tests were offered colonic investigation; 1774 underwent complete investigation of the colon. RESULTS: There was no significant difference in the stage at presentation of interval versus control group cancers. Survival in the interval cancer group was significantly prolonged compared with the control group. Sensitivity for colonoscopy or flexible sigmoidoscopy and double contrast barium enema (DCBE) was 96.7%. There were no complications of DCBE but seven (0.5%) complications of colonoscopy, of which six required surgical intervention. There were no colonoscopy related deaths. No patients without colorectal cancer died within 30 days of colonic investigation. Five patients died within 30 days of surgery for screen detected colorectal neoplasia and a further two died without having surgery. Six patients died after 30 days but within two years of surgery for screen detected benign adenomas or stage A cancers; in all cases the cause of death was not related to colorectal cancer. CONCLUSIONS: There was investigation related morbidity but no mortality and little to support overdiagnosis bias. The group returning falsely negative tests had a better outcome compared with the whole control group. There is a negative side to any screening programme but mortality reduction in this and other trials suggests that a national programme of colorectal cancer screening should be given consideration.