The prognostic significance of circulating neuroendocrine markers chromogranin a, pro-gastrin-releasing peptide and neuron-specific enolase in patients with advanced non-small-cell lung cancer.

BACKGROUND: Chromogranin A (CGA), Pro-gastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) are known as immunohistochemical tissue markers closely associated with neuroendocrine differentiation in non-small-cell lung carcinoma (NSCLC). The aim of the present study was to assess the value of serum levels of these markers in predicting response to chemotherapy and survival of patients with unresectable NSCLC. METHODS: The study included 67 patients with advanced NSCLC treated with chemotherapy. Before treatment, serum levels of CGA, ProGRP and NSE were measured with commercial kits. RESULTS: No association was found between serum NSE and age, gender, histology, performance status or extent of the disease. Distribution of serum CGA differed significantly according to gender and histology, with higher levels being found in men (p = 0.01) and in squamous cell carcinoma (p = 0.01). Serum ProGRP levels correlated with disease extent, being higher in patients with metastatic disease (M1) than in those with locoregional disease (M0; p = 0.02). The association of NSE, CGA and ProGRP levels with response to chemotherapy was not significant. While NSE had no impact on survival, the median survival was shorter for patients with elevated serum CGA and longer for patients with high ProGRP levels. Association with survival was significant when the Classification and Regression Tree (CART)-derived or median cutoff points were explored. On inclusion in multivariate Cox models, both CGA and ProGRP retained significance with high levels showing an opposite effect on survival [CART-derived cutoff points: CGA, relative risk (RR) -4.0; p < 0.001, and ProGRP, RR -0.4; p = 0.006, and median cutoff points: CGA, RR -1.8; p = 0.04, and ProGRP, RR -0.5; p = 0.03]. The combined use of CGA, ProGRP and NSE allowed for definition of two sets of patients with significantly different median survival times (25.2 vs. 8.8 months, p = 0.0001). CONCLUSIONS: In the circulation, CGA and Pro-GRP appear to bear important information related to the prognosis for NSCLC patients before chemotherapy. While a high CGA before treatment was found as an unfavorable prognostic determinant, a high ProGRP conferred a survival advantage. The combined use of serum CGA, ProGRP and NSE may supply additional information to prognosis.     

RNASEL mutation screening and association study in Ashkenazi and non-Ashkenazi prostate cancer patients.

Epidemiologic and genetic studies support the considerable effect of heritable factors on prostate tumorigenesis, although to date, no unequivocal susceptibility gene has been identified. The extensive study of RNASEL in prostate cancer patients worldwide has yielded conflicting results. We reevaluated the role of the RNASEL 471delAAAG Ashkenazi founder mutation in 1,642 Ashkenazi patients with prostate, bladder, breast/ovarian, and colon cancers; Ashkenazi controls; and in non-Ashkenazi prostate cancer patients and controls. The entire RNASEL coding sequence was also screened using denaturing high-performance liquid chromatography and multiplex ligation-dependent probe amplification for possible sequence variations or copy number changes in a population of prostate cancer patients. The 471delAAAG mutation was detected in 2.4% of the Ashkenazi prostate cancer patients; in 1.9% of patients with bladder, breast/ovarian, and colon cancers; and in 2.0% of the Ashkenazi controls. Seven additional variants were detected in RNASEL, including a novel potentially pathogenic splice site mutation, IVS5+1delG, although none were associated with increased prostate cancer risk. Multiplex ligation-dependent probe amplification analysis showed two RNASEL gene copies in all 300 prostate cancer patients tested. We estimated that the RNASEL 471delAAAG founder mutation, which was detected in 2% of the Ashkenazi Jews, originated between the 2nd and 5th centuries A.D., compared with the less frequent (1%) BRCA1 185delAG founder mutation, which originated hundreds of years earlier. Taken together, our analysis does not support a role for the RNASEL 471delAAAG Ashkenazi mutation nor for the other alterations detected in RNASEL in prostate cancer risk in Jewish men.     

The electrodiagnostic examination of psychogenic swallowing disorders

The article discusses the usefulness and technique of investigation of suspected psychogenic dysphagia by surface electromyography (sEMG) of deglutition. Thirty-two patients with suspected psychogenic dysphagia (Group 1) and 40 healthy individuals (Group 2) were involved in the study. The timing, amplitude and graphic patterns of activity of the masseter, submental, infrahyoid and trapezius muscles were examined during voluntary single water swallows (“normal”), and continuous drinking of 100 cc of water. The muscle activity in oral, pharyngeal and initial oesophageal stages of swallowing was measured, and graphic records were evaluated in relation to timing and voltage. Globus hystericus was found in only 14 patients of the Group 1 (43.75%). The main sEMG pattern of psychogenic dysphagia is a lack of any pathologic changes of timing, voltage and graphic patterns of deglutition. In 28% of cases tension of skeletal muscles not involved in deglutition was observed during single swallowing (vs. 0% in controls). Psychogenic/hysteria-conversion dysphagia has no pathologic sEMG patterns associated with deglutition. Skeletal muscle tension during deglutition, being observed in some cases has no connection with the act of swallowing itself. Surface EMG, being non-invasive and non-radiographic, can be used for screening purposes for patients with dysphagia thus avoiding expensive and time-consuming investigation.     

Hemodynamic changes during a new procedure for regional chemotherapy involving occlusion of the thoracic aorta and inferior vena cava

Study Objective: To describe the hemodynamic consequences of a regional chemotherapy procedure involving occlusion of the thoracic aorta and inferior vena cava (IVC) by intraluminal balloons.

Design: Prospective study.

Setting: Operating rooms of an academic hospital.

Patients: 10 patients with inoperable intraabdominal malignancy.

Interventions: After the induction of general anesthesia and the insertion of a pulmonary artery catheter the patients underwent the regional chemotherapy procedure

Measurements and Main Results: Occlusion of the thoracic aorta induced an increase in blood pressure (BP) and systemic vascular resistance (SVR) (41% ± 8% and 80% ± 15% from baseline, respectively), and a 30% ± 7% decrease in cardiac output (CO). After aortic balloon deflation at the end of the procedure, we observed a decrease in BP to baseline values, decrease in SVR (to 62% ± 12% below baseline), and increase in CO (to 80% ± 15% above baseline). Those changes resemble those described during vascular surgery. Isolated occlusion of the IVC before aortic occlusion caused hemodynamic deterioration in only three of 10 patients, suggesting incomplete obstruction or collateral blood flow in others. Occluding the IVC while the aorta was occluded, caused minimal hemodynamic changes.

Conclusions: Independent inflation of the IVC balloon should not be performed routinely because of possible unpredicted hemodynamic instability. Inferior vena cava occlusion should always be performed after complete aortic occlusion, because it is then that it produces negligible hemodynamic consequences. It is possible that a better assessment of IVC occlusion after balloon inflation needs to be done by contrast injection to prevent a possible leak of chemotherapeutic drugs.     

Clinical and physiological aspects of the cortical visual prosthesis

Physiological concepts and experimental evidence indicate the feasibility of developing an effective artificial visual system through direct stimulation of the visual cortex. The technical, medical and physiological aspects are reviewed.     

Envenoming by Cerastes vipera—a report of two cases

Two cases of envenoming by Cerastes vipera are described Both were in snake collectors who were accidentally bitten on the finger while handling the snake. In both cases, local signs included a haemorrhagic bulla with fang marks, swelling and tenderness. These signs were mild in one case and moderately severe in the other, necessitating fasciotomy. No systemic signs were observed. Some coagulation abnormalities were found in both cases. In one, prolonged bleeding from the wound and a shortened euglobulin lysis time may suggest activation of the fibrinolytic mechanism. In the other, prolongation of prothrombin time occurred with no haemorrhagic diathesis. Treatment included fasciotomy in one case and elevation of the affected part and antibiotics in the other. It appears that the clinical course of this snakebite is relatively benign.     

Adverse interaction between capecitabine and warfarin resulting in altered coagulation parameters and bleeding: case report and review of the literature

Capecitabine can interact with warfarin, resulting in altered coagulation parameters and bleeding. Four cases have been reported. We describe a fifth case with life-threatening interaction between these two drugs. A 67-year-old female with metastatic breast cancer developed hemorrhagic blisters, purpura and ecchymoses. She had been well controlled on long-term warfarin (5 mg/day). Capecitabine was initiated 4.5 weeks prior to the bleeding episode. Laboratory work-up revealed an international normalized ratio of 8.56, partial prothrombin time of 61 seconds and prothrombin time of 5.2%. The coagulation parameters gradually normalized within 4 days following vitamin K administration and discontinuation of capecitabine and warfarin. Careful monitoring of coagulation parameters and proper adjustment of the warfarin dose are required in patients taking warfarin and capecitabine concomitantly.