Quality-of-life following thoracotomy for lung cancer

Contrary to the issues of perioperative morbidity and survival following surgery for lung cancer, little attention has been given to quality-of-life. To address this, quality-of-life was assessed preoperatively and 1, 3, 6 and 9 months postoperatively in a cohort of 117 consecutive subjects who underwent thoracotomy with a certain or presumptive diagnosis of lung cancer. Those with cancer (n = 91) confirmed at thoracotomy were contrasted to those without (n = 26). Moderate to severe dyspnea, reported in 14% preoperatively, increased to 34% at 1 and 3 months (p < 0.005) but returned to approximately 10% at 6 and 9 months. Similarly, activities of daily living were impaired in 11% preoperatively; this disability increased to 21% at 1 month (p < 0.005), and returned to baseline at 6 and 9 months. Those with cancer compared to those without a postoperative diagnosis of cancer had similar quality-of-life preoperatively but deteriorated more in the postoperative period. This study demonstrates that important deterioration in quality-of-life occurs during the first 3 months postoperatively in those with a final diagnosis of cancer but improvement back to baseline can be expected thereafter.     

Metabolic disposition of antipyrine in patients with lung cancer

The metabolism of antipyrine (10 mg/kg i.v.) was studied in nine patients with cancer of the lung and in a cancer-free control group matched for age, sex, drug intake, and smoking and drinking history. The mean plasma clearance of antipyrine was 0.0475 +/- 0.009 liter/kg/hr in the tumor group and 0.0557 +/- 0.007 liter/kg/hr in the control group (p greater than 0.05). The antipyrine plasma elimination half-life was longer in the group with tumors (9.5 +/- 1.3 hr) compared to the control group (7.7 +/- 1.3 hr), but the difference was not statistically significant (p greater than 0.05). There was no difference between the groups in the excretion of two major antipyrine metabolites, 4-hydroxyantipyrine and N-demethylantipyrine, in a 48-hr urine sample. Thus, the presence of lung cancer in humans does not significantly alter antipyrine elimination.     

Serum levels of interleukin 6 in patients with lung cancer

Serum interleukin 6 (IL-6) levels were measured in 75 patients with lung cancer and in 20 patients with benign lung diseases. IL-6 was detectable in 29 patients with lung cancer (39%), but was not detectable in any of the patients with benign lung diseases. Serum C-reactive protein levels and plasma fibrinogen levels were significantly higher and serum albumin concentration was significantly lower in lung cancer patients with detectable serum IL-6 levels than in those without detectable serum IL-6 levels and in patients with benign lung diseases. On the other hand, no significant difference was observed in blood platelet counts in these three groups. Moreover, serum IL-6 levels were not significantly different in lung cancer patients with or without clinically demonstrated distant metastasis. These results suggest that IL-6 may be a mediator of various reactions including an inflammatory response in lung cancer patients.     

Immunosuppressive effect of radiotherapy on patients with lung cancer

The immunoglobulins A, E, G and M of 25 patients with lung cancer were determined (by radial immunodiffusion) before, during and after radiotherapy. No significant change in any immunoglobulin were noticed overall. In the group with a poor prognosis (survival less than 12 months; 15 patients), there was a significant decrease of IgA and IgM one month after the irradiation. In the group of patients with pulmonary infection (14 patients), the level of IgA, IgG and IgM were lower than in the group without infection throughout the examination period. Cellular immunity measured by the PPD skin test, showed no significant differences between the groups by survival.     

Palliative intubation of esophageal prosthesis in two patients with lung cancer

PURPOSE: Severe eye burns often result in extensive necrosis of the conjunctiva and episcleral tissue. Video fluorescein angiography was performed to reveal the perfusion of the anterior eye segment after severe eye burns. METHODS: A scanning laser ophthalmoscope was used for anterior segment fluorescein angiography in 12 patients (14 eyes) with severe burns grade III-IV and in 7 healthy volunteers. RESULTS: Necrotic tissues occurred as non perfused areas and remained dark throughout the whole angiogram. In general, the borders from healthy to necrotic conjunctival tissue were sharply demarcated. Thus, the extent of scleral and limbal ischemia could be determined exactly. Injured vessels showed hyperfluorescence with late leakage. Damage of the subconjunctival tissue appeared as a deep weak fluorescence in the early angiography and exhibited patchy leakage in the late angiogram. CONCLUSIONS: Anterior segment angiography provides a basis for deciding the extent of surgical debridement of necrotic tissue in the acute phase of the burn. The determination of the extent of limbal and scleral ischemia may give useful information for early plastic-reconstructive procedures.     

The prognostic value of thrombocytosis in patients with primary lung cancer

The prognostic information provided by platelet counts was studied in 1115 patients with primary lung cancer and in 550 control patients with benign lung disorders. Patient records were retrospectively reviewed regarding histological tumour type, TNM stage, thromboembolic episodes and survival. The prevalence of thrombocytosis (platelet count > 400 x 10(9)/l) in patients with lung cancer was 32.1% vs. 6.4% in controls (p < 0.0001). Platelet counts increased with TNM stage (p < 0.0001). Patients with thrombocytosis had a shorter survival than patients with normal platelet count (p < 0.0001). Thrombocytosis was a predictor of short survival also when adjusted for tumour type, sex, age, and TNM stage (p < 0.001). The platelet count and the frequency of thrombocytosis declined after tumour resection (p < 0.0001). Thrombocytosis was not associated with thromboembolism. In conclusion, thrombocytosis is a clinically significant prognostic indicator regarding survival in patients with primary lung cancer.     

Soluble intercellular adhesion molecule-1 in patients with lung cancer and benign lung diseases

Intercellular adhesion molecule-1 (ICAM-1) expression correlates with tumour progression in patients with malignant melanoma or renal cell carcinoma. To assess the value of soluble ICAM-1 (sICAM-1) for lung cancer patients, sICAM-1 was determined by means of an enzyme-linked immunosorbent assay. Sera from 147 patients with lung cancer, from 75 patients with benign lung diseases and from 108 healthy adults were investigated for sICAM-1 expression. Significant differences in sICAM-1 levels were detected in lung cancer patients (387 +/- 176 ng/ml) and patients with benign lung diseases (365 +/- 110 ng/ml) compared to the group of healthy adults (310 +/- 90 ng/ml). There was no difference in sICAM-1 level among the subtypes of lung cancer. Advanced tumour stages and patients with progressive disease tended to be associated with higher sICAM-1 levels, the site of metastasis being relevant for the level attained. Patients with liver metastasis had the highest sICAM-1 levels (547 +/- 295 ng/ml) compared to patients with cerebral metastasis (317.8 +/- 92.2 ng/ml). An increase of sICAM-1 expression during the progression of the disease coincided with a poorer survival prognosis for the patients compared to patients with stable or falling sICAM-1 levels.     

p53 codon 72 polymorphism in Taiwanese lung cancer patients: association with lung cancer susceptibility and prognosis

Previous studies have indicated that milrinone, a specific type III phosphodiesterase inhibitor, may be able to induce chloride secretion in cystic fibrosis (CF) tissues. We have now assessed the effect of this agent in vivo on the nasal epithelium of CF mutant mice and also in the nose and lungs of human subjects with CF. Wild-type mice showed a small hyperpolarization of the nasal potential difference (PD) in response to milrinone (100 microM, 1.6 +/- 0.6 mV, n = 8, P < 0.05). In contrast, CF mice carrying either the most common human mutation of the gene for the CF transmembrane regulator (CFTR), DeltaF508 (protein mislocalized), or the G551D mutation (protein normally localized) failed to demonstrate this response. Milrinone perfused alone had no significant effect on the baseline nasal PD of human subjects without CF (14.7 +/- 4.0 mV preperfusion; 15.3 +/- 4.6 mV postperfusion), but significantly (P < 0.05) augmented the hyperpolarization induced by a subsequently perfused low-chloride solution (with milrinone, 36.8 +/- 3.0 mV, n = 6; without milrinone, 18.1 +/- 2.2 mV, n = 19). In contrast, in human subjects with CF (n = 6), milrinone alone significantly (P < 0. 05) altered the nasal baseline PD (52.2 +/- 3.3 mV preperfusion; 57. 4 +/- 4.2 mV, postperfusion) but not the subsequent responses to the low-chloride solution (with milrinone, 1.1 +/- 2.2 mV, n = 4; without milrinone, 0.6 +/- 0.5 mV, n = 28) or to isoproterenol (100 microM). In a separate study in subjects (n = 6) with the DeltaF508 mutation, nasal coadministration of milrinone with isoproterenol produced no effect in the presence of amiloride and a low-chloride solution (-0.8 +/- 0.5 mV). This was also the case in the nasal epithelium of CF subjects (n = 4) carrying at least one G551D allele (-0.3 +/- 0.8 mV). Similarly, milrinone did not hyperpolarize the PD of either the tracheal (n = 6) or segmental (n = 6) airways of CF subjects (DeltaF508) when applied topically in vivo in the presence of amiloride, isoproterenol, or adenosine triphosphate (all 100 microM) in a low-chloride solution. These data do not support the use of milrinone to induce chloride secretion in CF airways in vivo.     

Second lung cancers in patients successfully treated for lung cancer

The rate of developing second lung cancers and other aerodigestive tumors in patients who have been treated for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) is approximately 10-fold higher than other adult smokers. The risk of second lung cancers in patients surviving resection of NSCLC is approximately 1% to 2% per year. The series reported show that the patients who develop second NSCLCs tend to have early-stage NSCLC (predominantly stage I and II). The survival of patients after the second resection of lung cancer is similar to that of patients presenting with initial NSCLC. The risk of second lung cancers in patients surviving SCLC is 2% to 14% per patient per year and increases two- to seven-fold with the passage of time from 2 to 10 years. The risk of second lung cancers in patients treated for SCLC appears to be higher than that found in patients with NSCLC who were treated only with surgical resection. In addition, the chances of successful resection of second primary NSCLCs in patients who were treated for SCLC is much less than that for patients with metachronous lung cancers after an initial NSCLC. Patients treated for SCLC who continue to smoke cigarettes increase their rate of developing second lung cancers. The contribution of chest radiation and chemotherapy administration to the risk of developing second lung tumors remain to be defined but may be responsible for some of the increased risk in patients treated for SCLC compared to patients undergoing a surgical resection for NSCLC.     

Cytostatic treatment of patients with advanced non-small cell lung cancer

Complications of patellar resurfacing in total knee arthroplasty have rekindled the interest of many surgeons in patellar retention. In a prospective study 20 randomly selected patients of 40 underwent patellar resurfacing in combination with their total knee arthroplasty. The other 20 patients were left with an unresurfaced patella. Within 24 months of follow-up, the advantages of patellar resurfacing could be seen according to the Knee Society Score. Especially in advanced osteoarthritis of the knee joint, the patients achieved better scores in climbing stairs and in function. The superior functional results are arguments for patellar resurfacing, at least in knees with advanced osteoarthritis.     

State of blood coagulation and capillary permeability in patients with lung cancer

Cinematography was used to biomechanically compare individually selected overground jogging and running velocities with equated treadmill jogging and running by adult males and females. All subjects were regular joggers but not competitive track or cross-country runners. No significant differences were recorded in stride length, stride rate, support time or non-support time for males or females when jogging at velocities of between 3.33 and 4.78 m/s (x = 3.70) or 3.45 and 4.80 m/s (x=3.97) respectively. However, it was demonstrated that at velocities of 4.82 - 6.2 m/s for males (x - 5.41) and 4.85 - 5.76 m/s for females (x = 5.29) significant differences did occur between overground and treadmill running. For both males and females stride length decreased, stride rate increased, and the period of non-support was also significantly less when running on a treadmill as compared to running overground.     

Pulmonary hypertrophic osteoarthropathy and clubbing of fingers in patients with lung cancer

We examined clinical characteristics of patients with primary lung cancer associated with clubbing of the fingers or pulmonary hypertrophic osteoarthropathy. Clubbing was observed in 12.5% of patients with lung cancer. Squamous cell carcinoma was frequently associated with clubbing. Clubbing was found in all clinical stages. PaO2 and PaCO2 were normal in patients with lung cancer, which suggests that neither hypoxemia nor hypercapnia caused the clubbing in these patients. Pulmonary hypertrophic osteoarthropathy was found in three patients with lung cancer (two men and one woman, mean age 49 years). The incidence was 2.9% among lung cancer patients with clubbing, 0.22% in all lung cancer patients, and was apparently lower than those in reports from outside Japan. One of these patients has stage IIIA squamous cell carcinoma, one had stage IV large cell carcinoma, and one had stage IV adenocarcinoma. In all cases bone scans were useful for diagnosis and for following the clinical course.     

Pulmonary infections in lung cancer patients at diagnosis

We carried out a prospective study involving 96 consecutive lung cancer patients at diagnosis, in order to determine through quantitative cultures of the bronchoalveolar lavage (BAL) fluid, the prevalence of pulmonary infections; we also evaluated the relationship between a patient's performance status, immunocompetence, lung cancer stage, histotype and the occurrence of respiratory infections. The patients (81 males, 15 females) had a mean age of 64 +/- 9 years. Of these, 62 were smokers, 30 were ex-smokers and four had never smoked. Sixty-seven patients had a prior history of chronic bronchitis. A total of 42 micro-organisms were cultured from the BAL fluids of 33 patients (34.3%). Fifty percent of these micro-organisms were gram-negative, 33.3% were gram-positive and the remaining 16.7% were other micro-organisms. The bacilli most often isolated were the Haemophilus species, accounting for 38.8% of all gram-negative bacilli. The most frequently isolated gram-positive pathogen was the Staphylococcus aureus. We have not found a significant relationship between the presence of a respiratory infection and the different cell types separately analyzed, nor with SCLC and NSCLC patient groups, nor with the stage of the disease. The performance status, the immunoregulatory ratio and the lymphocyte subsets were not significantly different in patients with or without a pulmonary infection. We think that the identification of a definite etiologic agent is of great importance for a rational anti-microbial treatment of pulmonary infections.     

Current approaches to the use of radiotherapy in patients with non-small-cell lung cancer

Interactions of specific amino acid residues of the carboxyl-terminal domain of MetRS with the CAU anticodon of tRNAMet assure accurate and efficient aminoacylation. The substitution of one such residue, Trp461 by Phe, impairs the binding of cognate tRNA, but enhances the binding of noncognate tRNAs, particularly those containing G at the wobble position. However, the enhanced binding of noncognate tRNAs is not accompanied by the increased aminoacylation of these tRNAs. A genetic screening procedure was designed to isolate methionyl-tRNA synthetase mutants which were able to aminoacylate a GGU (threonine) anticodon derivative of tRNAfMet. One such mutant, obtained from W461F MetRS, had an Ile29 to Thr substitution in helix A located in the amino-terminal dinucleotide-fold domain that forms the site for amino acid activation. Analysis of the catalytic properties of the I29T/W461F enzyme indicates that the mutation in helix A of the dinucleotide-fold domain affects kcat for aminoacylation of tRNAs having a GGU threonine anticodon. Interactions with cognate tRNAfMet (CAU), as well as with methionine and ATP were not affected by the Ile29 to Thr substitution. We conclude that the I29T substitution leads to a slight adjustment of the alignment of the CCA stem of noncognate tRNAs (GGU) in the catalytic domain of the enzyme, reflected in the increase in kcat, which also allows mischarging in vivo. A function of Ile29 is therefore to minimize the mischarging of tRNAThr (GGU) by methionyl-tRNA synthetase. The methods described here provide useful tools for examining the mechanisms of tRNA selection by aminoacyl-tRNA synthetases.     

Effects of gemcitabine on renal function in patients with non-small cell lung cancer

Gemcitabine is a novel fluorine-substituted cytarabine (Ara-C) analogue with activity against a range of solid tumours. Besides dose-limiting haematological toxicity, renal side-effects were observed from phase I and II studies concerning elevations of serum creatinine, proteinuria and erythrocyturia. The aim of this study was to investigate the effect of gemcitabine on renal function in 11 untreated patients with non-small cell lung cancer (NSCLC). Gemcitabine was given as weekly infusions of 1250 mg/m2 for 3 weeks, followed by 1 week rest. This comprised one cycle (maximum of six cycles). The glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured simultaneously with a constant infusion of 125I-iothalamate and 131I-hippuran, respectively. Tubular damage was monitored by excretion of tubular enzymes (lactic dehydrogenase (LDH), alkaline phosphatase (ALP), gamma-glutamyltransferase (GT) and beta 2-microglobulin); glomerular damage was monitored by excretion of albumin in the urine. In 9 patients, the effect of the first infusion was evaluated. After the first infusion of gemcitabine, no change was observed in renal function. After two, three, and six cycles of treatment, no significant changes in GFR and ERPF were noticed in 9 evaluable patients. However, in 3 patients, a decrease in GFR of > 10% was observed after multiple cycles. In one of them this was accompanied with albuminuria (360 mg/24 h) and erythrocyturia. There were no significant changes in urinary excretion of tubular enzymes or albumin. In conclusion, we did not observe acute renal toxicity with gemcitabine. No significant cumulative effects of gemcitabine on renal function could be detected, although 3 patients, treated with multiple cycles of gemcitabine, showed a moderate decrease in renal function. Glomerular damage might play a role in the development of renal function loss.     

Postoperative prognosis in patients with non-small cell lung cancer with synchronous ipsilateral intrapulmonary metastasis

BACKGROUND: Non-small cell lung cancer with intrapulmonary metastasis (PM) was recently reclassified according to the revision of the TNM classification. To determine whether the new staging system is appropriate, we analyzed the postoperative prognosis of patients with synchronously detected and resected PM lesions. METHODS: Of 509 patients with non-small cell lung cancer who underwent surgical resection, 42 patients were revealed to have synchronous and ipsilateral PM. Their survival was compared with that of matched stage groups (without PM) by Kaplan-Meier test and log rank test. RESULTS: Two patients who were classified as stage I survived 40 and 30 months after operation, respectively. One patient was determined to be stage II, and survived 100 months postoperatively. Thirty-eight patients were classified as stage IIIA/IIIB (19 each) (90.5% of all cases with PM). There was no significant difference between 3- and 5-year survival rates of the PM stage IIIA group (34.2% and 34.2%) and those of the other IIIA (144 patients; 37.9% and 31.6%). Survival rates of such stage IIIA subgroups as PM, T3 and N2, were comparable. No significant differences were observed between the 3- and 5-year survival rates of the PM stage IIIB (16.6/16.6%) and those of the other stage IIIB (45 cases; 11.7% and 0.0%). The survival rates of such stage IIIB subgroups as PM, T4 and N3 were also similar. CONCLUSIONS: The new staging system for patients with synchronous resectable PM appears to be reasonable regarding survival. Most cases of PM are categorized as locally advanced disease; however, stage IIIA/IIIB cases have become a more heterogeneous population.     

The results of treatment in 100 patients with limited-stage small cell lung cancer

Strain differences in midgut basal lamina thickness, assessed by measurement in transmission electron micrographs, and disseminated infection rates of dengue-1 virus were compared among three laboratory strains of Aedes albopictus (Skuse). Mean basal lamina thickness for the New Orleans and Houston strains were significantly greater than those for the Oahu strain, which exhibits a higher disseminated infection rate than the former two. Although basal lamina thickness among the F1 progeny of reciprocal crosses of the Oahu and Houston strains were intermediate between the parental strains, they were too variable to be useful as markers in genetic studies. Measurements of basal laminae among individuals of the New Orleans strain, with disseminated or nondisseminated infections, failed to demonstrate a role for basal lamina thickness as a modulator of dengue-1 virus dissemination across the midgut epithelium of Ae. albopictus.     

Paclitaxel in combination chemotherapy with radiotherapy in patients with unresectable stage III non-small-cell lung cancer

PURPOSE: The addition of combination chemotherapy to standard radiation therapy has improved treatment for locally unresectable non-small-cell lung cancer. In this phase II study, we evaluated the toxicity and efficacy of a novel chemotherapy regimen that included paclitaxel, cisplatin, and etoposide plus concurrent radiation therapy in this group of patients. PATIENTS AND METHODS: Thirty-three patients with previously untreated, unresectable stage III non-small-cell lung cancer (stage IIIA, 11 patients; stage IIIB, 22 patients) initially received two courses of chemotherapy, which included paclitaxel 135 mg/m2 by 1-hour infusion on day 1, cisplatin 60 mg/m/ intravenously (i.v.) on day 2, and etoposide 100 mg/m2 i.v. on days 1, 2 and 3. On week 6, radiation therapy (60 Gy in 30 fractions) was initiated in conjunction with two additional courses of chemotherapy: paclitaxel 135 mg/m2 i.v. by 1-hour infusion on day 1, cisplatin 5 mg/m2 i.v. on days 2- to 10, and etoposide 25 mg/m2 on days 1 to 10. RESULTS: This combined modality program was feasible and well tolerated by most patients. During the two courses of induction chemotherapy, grade 3 or 4 myelosuppression occurred in only six patients (18%). Esophagitis was common during combined modality therapy (grade 3, 10 patients; grade 4 five patients). Forty-two percent of patients had partial response after two courses of induction therapy, and 82% of patients had an objective response at completion of therapy. Twelve patients (36%) had a complete response. Nineteen patients remain progression-free at a median of 8 months; the median survival time has not been reached. CONCLUSION: This paclitaxel-containing combined modality therapy is feasible and highly active in patients with inoperable stage III lung cancer. Esophagitis is the most common severe toxicity with this program. Further studies with paclitaxel-containing combination regimens in patients with stage III non-small-cell lung cancer are indicated.