Pulmonary metastases from epithelial tumours: late results of surgical treatment.

OBJECTIVE: Development of distant metastases is one of the primary characteristics of malignant tumours. During the last decades, lung metastasectomy has been progressively accepted as a therapeutic option in oncology patients. The present paper aims to evaluate the long-term results and factors influencing prognosis in patients submitted to lung resection for metastases from extrapulmonary epithelial tumours. METHODS: We retrospectively analysed data of 202 patients undergoing 207 procedures of lung metastasectomy between January 1980 and December 2003. Factors that may influence long-term prognosis such as completeness of resection, histology of the tumour, disease-free interval, number of resected lesions, involvement of hilar or mediastinal lymph nodes, systemic treatments were investigated. RESULTS: Complete resection was carried out in 169 patients (83.7%). The more frequent lung resection was sublobar in 67.6% of cases, but rarely in selected patients bilobectomy or pneumonectomy has been carried out too. Perioperative morbidity and mortality were 7.7% and 0.9%. Mean disease-free interval was 49+/-48 months. Mean follow-up was 33+/-31 months, 5-year and 10-year survival rates for completely resected patients were 43% and 17%, respectively. By univariate and multivariate analyses, completeness of resection, disease-free interval of 36 months or more, and single resected metastasis were found to be significant prognostic factors. CONCLUSIONS: Resection of epithelial lung metastases allows an acceptable prognostic result in appropriately selected patients with very low perioperative morbidity and mortality. Factors such as high disease-free interval, single metastasis and completeness of resection are demonstrated and confirmed to be significantly associated with long-term survival.     

The ultraviolet derivative spectrophotometric determination of neutral liposome-entrapped beta-lactam antibiotics

A simple, non-invasive spectrophotometric assay to measure the concentration of some beta-lactam antibiotics in turbid solutions containing liposomes was carried out. Since zero-order spectra gave strong interference because of sample turbidity, derivative spectrophotometry was used to enhance the spectral details. Derivative spectra showed bands in the ultraviolet region due to the presence of the cephalosporin and penicillin beta-lactams. A linear relationship between derivative amplitudes and antibiotic concentration was found when antibiotic-containing liposome solutions were measured. A saturative trend in the liposome-encapsulation was observed. The antibiotic entrapment was lowered by increasing the cholesterol-phospholipid ratio in the mixture used for liposome preparation. After treatment of antibiotic-loaded liposomes with beta-lactamase, a hydrolytic enzyme specific for beta-lactams, the remaining antibiotic concentration decreased significantly, showing that some of the antibiotic was retained on the outer surface of the vesicles.     

Prevention of venous thrombosis and thrombophlebitis in long-haul flights with pycnogenol.

The aim of this study was to evaluate the occurrence of deep venous thrombosis (DVT) and superficial vein thrombosis (SVT) and its prophylaxis with an oral anti-edema and antithrombotic agent (Pycnogenol, Horphag, Research Management SA, Geneva, Switzerland) in long-haul flights, in subjects at moderate to high-risk of DVT and SVT. The study pre-included 244 pre-selected subjects; 211 were included (33 were excluded for several reasons due to logistic problems) and 198 completed the study; 13 subjects were lost for follow-up at the end of the flight, all for non-medical problems (i.e., for difficult connections). All subjects were scanned within 90 minutes before the flight and within 2 hours after disembarking. Subjects were supplemented with 100 mg Pycnogenol per capsule. Treatment subjects received two capsules between 2 and 3 hours before flights with 250 mL of water; two capsules were taken 6 hours later with 250 mL of water and one capsule the next day. The control group received comparable placebo at the same intervals. The flight duration was on average 8 hours and 15 minutes (SD 55 min) (range, 7.45-12.33). In the control group there were five thrombotic events (one DVT and four superficial thromboses) while only nonthrombotic, localized phlebitis was observed in the Pycnogenol group (5.15% vs. no events; p<0.025). The ITT (intention to treat) analysis detects 13 failures in the control group (eight lost to follow up + five thrombotic events) of 105 subjects (12.4%) vs. five failures (4.7%; all lost, no thrombotic events) in the treatment group (p<0.025). No unwanted effects were observed. In conclusion, this study indicates that Pycnogenol treatment was effective in decreasing the number of thrombotic events (DVT and SVT) in moderate-to-high risk subjects, during long-haul flights.     

Prognostic factors in surgically resected N2 non-small cell lung cancer: the importance of patterns of mediastinal lymph nodes metastases.

OBJECTIVE: Patients with non-small cell lung cancer (NSCLC) with metastases to ipsilateral mediastinal lymph nodes (N2) are an heterogeneous group of patients as regard to prognosis and treatment. Indication and timing of surgery remain controversial. The present study investigates the prognostic factors, in order to identify homogenous subgroups of patients. METHODS: Histologically proven N2-NSCLC patients, who underwent a complete surgical resection were retrospectively reviewed. Clinical and pathological features were reported and analyzed, and survival study was performed. RESULTS: One hundred eighty-three patients were analyzed. Overall 1.3 and 5 years survival rates were, respectively, 70, 35 and 20%, with a median survival time of 24 months. Univariate analysis showed a significant better prognosis for: incidental N2 respect to clinical N2 (5-years 35.4 vs 17.4%); single level lymph node involvement respect to multiple levels (5-years 23.8 vs 14.7%); metastases to superior mediastinal or aortic nodes respect to lower mediastinal nodes (5-years 32 and 24.3 vs 16.3%); right upper lobe tumors with superior mediastinal nodes and left upper lobe tumors with aortic nodes respect to lower lobes tumors with lower mediastinal nodes (5-years 31.8 and 26.9 vs 15.7%). Skip metastases had not a significant survival advantage respect to continuous lymphatic spread. N2 clinical status, the number of levels involved and the two specific patterns of lymphatic spread resulted significant prognostic factors at multivariate analysis. CONCLUSIONS: Clinical N2 status, number of lymph nodes levels involved and specific patterns of lymphatic spread identify homogenous subgroups of patients that can be proposed for different therapeutic strategies.     

Resection and radical lymphadenectomy for lung cancer: prognostic significance of lymphatic metastases

From 1979 to 1987, 1103 thoracotomies were performed in patients with lung cancer: 824 (74.7%) radical resections, 141 (12.7%) palliative resections and 138 (12.5%) exploratory thoracotomies. Among the 965 patients who underwent resection, 539 patients were N0, 190 patients N1 and 236 patients N2. Among patients with N1 disease we observed more frequent hilar metastases in the more advanced tumors (p less than 0.05). In 84 out of the 232 N2 patients (36.2%; 13.4% of all patients) a skipping of all pulmonary sites was observed. The most commonly invaded mediastinal levels were the paratracheal nodes on the right and the aortic nodes on the left, followed by the subcarinal nodes. The greater the neoplastic involvement of pulmonary nodal sites, the higher the percentage of patients with N2 disease and the number of mediastinal levels with tumor cells (p less than 0.05). The 5-year survival rate is 60% for N0, 46% for N1 and 23% for N2 disease. There is no significant difference in survival between N2 and N1 + N2 patients. Metastatic involvement of both upper and lower mediastinal levels carries a poorer prognosis compared to involvement of one compartment only (p less than 0.02). Patients with findings of mediastinal metastatic involvement should be selected: studies on lymphatic metastases are useful to better establish surgical indications for N2 patients.     

Effects of long-term acetyl-L-carnitine administration in rats--II: Protection against the disrupting effect of stress on the acquisition of appetitive behavior.

Long-term acetyl-L-carnitine (ALCAR) administration prevents the development of escape deficit produced by acute exposure to unavoidable stress. However, it does not revert the escape deficit sustained by chronic stress exposure. Rats exposed to chronic stress show a low dopamine (DA) output in the nucleus accumbens shell (NAcS) and do not acquire an appetitive behavior sustained by the earning of vanilla sugar (VS) made contingent on the choice of one of the two divergent arms of a Y-maze (VS-sustained appetitive behavior, VAB), while control rats consistently do. The present study shows that ALCAR treatment in rats exposed to a 7-day stress protocol prevented a decrease in DA output in the NAcS and medial prefrontal cortex (mPFC) of rats, and that it strengthened the DA response to VS consummation in the same two areas. Moreover, rats treated with long-term ALCAR or exposed to chronic stress while treated with ALCAR acquired VAB as efficiently as control rats. Moreover, VAB acquisition in stressed rats treated with ALCAR coincided with the reversal of the deficits in escape and in dopaminergic transmission in the NAcS. Thus, repeated ALCAR treatment preserved the DA response to VS in chronically stressed rats and this effect appeared to be predictive of the rat's competence to acquire VAB.     

Glycosaminoglycan Supplementation Promotes Nerve Regeneration and Muscle Reinnervation

This study shows that treatment of rats with exogenous glycosaminoglycans stimulates peripheral nerve regeneration, increases the abundance of mRNAs for myelin proteins and promotes muscle reinnervation. After the sciatic nerve had been crushed the number of regenerating axons in the distal stump was markedly and highly significantly increased by glycosaminoglycan treatment throughout the experimental period. The increased number of axons was correlated with increased axon and fibre (axon + myelin) diameter. The abundance of mRNAs for P_o protein and myelin basic protein of regenerating nerves was also affected by treatment with glycosaminoglycans. The increase in mRNA was also observed in the contralateral unlesioned nerve. Such a phenomenon did not occur in saline-treated rats. Glycosaminoglycan treatment markedly increased the number of muscle fibres reinnervated and accelerated the restoration of muscle twitch tension elicited by nerve stimulation. The effect was particularly evident during the early stages (16 and 21 days after nerve crush) of muscle reinnervation.     

Factors controlling the selectivity and efficiency of tumour damage in photodynamic therapy

The scope and potential of the photodynamic therapy of tumors can be enhanced through an adequate control of the factors which improve the selectivity of tumour targeting by the systemically injected photosensitizer and increase the efficiency of photosensitized tumour damage. Promising results are obtained by using hydrophobic photosensitizers which can be specifically transported and released to the tumour by serum lipoproteins, especially low-density lipoproteins. The photosensitizer molecule should possess those structural features which induce a high probability of photoactivation by 700–800 nm light, as well as a high yield of long-lived triplet state. The use of liposome-delivered Zn-phthalocyanine as a second generation phototherapeutic agent for tumours is proposed.