Effects of abomasal infusion of branched-chain amino acids or branched-chain keto-acids on liver function, inflammation, and oxidative stress in multiparous fresh cows.

Reduced liver function, increased oxidative stress, and inflammation in early lactation negatively impact lactation performance and health of fresh cows. Previous findings from our group demonstrated that branched-chain amino acids (BCAA) infusion improved lactation performance and branched-chain ketoacids (BCKA) infusion decreased liver triglyceride (TG) in fresh cows. The objectives of this study were to determine the effect of BCAA and BCKA on blood and liver biomarkers of liver function, oxidative stress, and inflammation as well as expression of genes regulating inflammation and antioxidant metabolism in the liver. Thirty multiparous Holstein cows were used in a randomized block design receiving continuous abomasal infusion for 21 d after parturition. Treatments (10 cows each) were control (CON), cows abomasally infused with 0.9% saline; BCA, cows abomasally infused with BCAA (67 g valine, 50 g leucine, and 34 g isoleucine); and BCK, cows abomasally infused with BCKA (77 g ketovaline, 57 g ketoleucine, and 39 g ketoisoleucine). All cows were randomly assigned to treatments after parturition and received the same diet throughout the experimental period. Blood was collected at 3, 7, 14, and 21 d postpartum for liver function, oxidative stress, and inflammation biomarker profiling. Liver was also harvested on 7, 14, and 21 d postpartum for quantification of glutathione, protein carbonylation, and expression of genes. ANOVA was conducted for all data using PROC GLIMMIX in SAS. No treatment differences were observed for liver function biomarkers (bilirubin, gamma-glutamyl transferase, and aspartate aminotransferase). Cows receiving BCAA had lower blood NO2- and NO3- concentrations compared with CON. A tendency for lower advanced oxidized protein products was also observed in BCA cows compared with CON. Additionally, on d 7, BCA cows had lower protein carbonylation in the liver compared with CON. In contrast, BCK cows had higher plasma thiol and albumin, as well as liver reduced and total glutathione compared with CON cows. Compared with CON, BCK cows had higher expression glutathione reductase in the liver. Overall, these results suggest favorable alterations in oxidative stress and inflammation status in fresh cows receiving BCAA or BCKA infusion during the first 3 weeks of lactation, which likely contributed to previously-observed changes in lactation performance and liver TG concentrations. Future work is required to evaluate the interrelated metabolism of BCAA and BCKA to better understand their effects on oxidative and immune metabolism.

The role of altered immune function during the dry period in promoting the development of subclinical ketosis in early lactation.

Subclinical ketosis (SCK) may impair white blood cell (WBC) function and thus contribute to the risk of disease postpartum. This preliminary study investigated changes occurring in the immune system before disease onset to elucidate their role in the occurrence of SCK. A group of 13 Holstein dairy cows were housed in tie-stalls and retrospectively divided into 2 groups based on their levels of ß-hydroxybutyrate (BHB) measured in plasma between calving day and 35 d from calving (DFC). Levels of BHB <1.4 mmol/L were found in 7 cows (control cows, CTR group) and levels >1.4 mmol/L were found in 6 cows at ≥1 of 6 time points considered (cows with SCK, KET group). From -48 to 35 DFC, body condition score, body weight, dry matter intake, rumination time, and milk yield were measured, and blood samples were collected regularly to assess the hematochemical profile and test the WBC function by ex vivo challenge assays. Data were submitted for ANOVA testing using a mixed model for repeated measurements that included health status and time and their interactions as fixed effects. Compared with CTR cows, KET cows had more pronounced activation of the immune system (higher plasma concentrations of proinflammatory cytokines, myeloperoxidase, and oxidant species, and greater IFN-γ responses to Mycobacterium avium), higher blood concentrations of γ-glutamyl transferase, and lower plasma concentrations of minerals before calving. Higher levels of nonesterified fatty acids, BHB, and glucose were detected in KET cows than in CTR cows during the dry period. The effect observed during the dry period was associated with a reduced dry matter intake, reduced plasma glucose, and increased fat mobilization (further increases in nonesterified fatty acids and BHB) during early lactation. A reduced milk yield was also detected in KET cows compared with CTR. The KET cows had an accentuated acute-phase response after calving (with greater concentrations of positive acute-phase proteins and lower concentrations of retinol than CTR cows) and impaired liver function (higher blood concentrations of glutamate-oxaloacetate transaminase and bilirubin). The WBC of the KET cows, compared with CTR cows, had a reduced response to an ex vivo stimulation assay, with lower production of proinflammatory cytokines and greater production of lactate. These alterations in the WBC could have been driven by the combined actions of metabolites related to the mobilization of lipids and the occurrence of a transient unresponsive state against stimulation aimed at preventing excessive inflammation. The associations identified here in a small number of cows in one herd should be investigated in larger studies.

Diagnostic value and learning curve of transbronchial needle aspiration in thoracic surgery.

AIM: Transbronchial needle aspiration (TBNA) is particularly indicated in diagnosing mediastinal masses or lymphoadenopathy proximal to the airways. Nowadays TBNA has not been widely accepted among pulmonologist and thoracic surgeons. Since its correct management could reduce patient morbidity we adopted this method. Here is presented an overview of our experience over a 18-months training period. METHODS: Fifty patients underwent TBNA. They presented non diagnosed paratracheal or peribronchial lymphadenopathy or masses of >1 cm. TBNA has been considered in order to spare patients the need for more invasive diagnostic procedures. TBNA has been performed with flexible bronchoscope and 19-gauge or 21-gauge needle. RESULTS: We made diagnosis of disease in 25 of 41 patients whose adequate sampling was obtained. 16 cases showed absence of disease despite criteria for adequacy have been confirmed, 9 cases presented an inadequate specimen. The overall diagnostic yield and sensitivity were 50% and 86%. The overall accuracy was 76%. Considering the last 6 months of the training period diagnostic yield increased from 18.7% to 88.2% (P<0.001),accuracy from 56.2% to 88.2% (P=0.04) and frequency of inadequacy decreased from 43.7% to 11.7% (P=0.046). CONCLUSIONS: TBNA resulted a successful diagnostic tool in selected cases as it is safe and permits to spare patients the need for more invasive procedures. These data revealed that experience is mandatory in order to achieve acceptable RESULTS: We think that an experienced operator should require a training period of approximately 50 procedures to obtain a good technique proficiency.

Position of nuclear medicine modalities in the diagnostic workup of cancer patients: lung cancer.

This review summarizes the current literature and tries to define the status of nuclear medicine in the clinical workup of lung cancer patients. Nuclear medicine procedures and positron emission tomography (PET) with the EMEA-approved radiopharmaceutical fluorodeo-xyglucose (FDG) are indicated for the characterization of lung lesions; the nodal staging of non-small cell lung cancer (NSCLC); the detection of distant metastases; and for the diagnosis of recurrent disease. Recent studies have shown the clinical efficacy of nuclear medicine and especially of FDG-PET in the workup of lung cancer patients and its significant impact on patients' management. Conventional nuclear medicine procedures are established for the pre-therapeutic assessment of pulmonary perfusion and function (lung perfusion and ventilation scintigraphy) and for the detection of bone metastases (skeletal scintigraphy). In studies in thousands of patients, FDG-PET has been proved to be the most accurate non-invasive diagnostic test for the characterization of lung nodules and masses. It can be recommended at least for patients with increased risk at surgery. FDG-PET should be applied in candidates for surgery of lung cancer, as mediastinoscopy may be omitted if PET shows no metastases in the mediastinum, and because FDG-PET avoids futile surgery by a more accurate selection of patients, especially by the detection of unexpected distant metastases. In candidates for thoracic radiotherapy, FDG-PET can help to exclude extrathoracic disease which needs systemic treatment and to better define the target volume for radiation therapy. The time has come for FDG-PET to find its place in new guidelines for the workup of lung cancer patients.

Contribution of three components to individual cancer risk predicting breast cancer risk in Italy.

We used data from a multicentre case-control study conducted in Italy between 1991 and 1994 on over 2500 cases of breast cancer and a comparable number of controls, and estimates of breast cancer incidence in Italy to compute individual breast cancer risk for Italian women. The estimated probabilities between age 50 and 80 ranged from approximately 5% (for a woman with no family history and low modifiable risk profile) to about 30% (for a woman with young family history and high modifiable risk) on the basis of various women's baseline characteristics. Expected numbers of breast cancer cases using the present model were compared with those based on the USA Gail model, and with the observed ones in the comparison group of the Italian Tamoxifen Trial. These show a closer agreement between the observed and the expected total numbers of breast cancers than the USA Gail model. Thus, the Gail model can be improved for use in other populations by using estimates of incidence and risk which are more appropriate to the target population.

[Positron emission-computed tomography in diagnosis and staging of lung neoplasms. Personal experience]. / La scintigrafia ad emissione di positroni nella diagnosi e stadiazione del carcinoma polmonare: la nostra esperienza.

BACKGROUND: Positron emission-computed tomography (PET) scans are obtained from the accumulation of a radiotracer in tissues with altered metabolism, such as malignant neoplasms. The authors present their experience with PET, performed in 50 selected patients with lung neoplasms in the 1998-2000 period. METHODS: The indications to PET corresponded to those most frequently reported in the literature, that is: diagnosis in solitary pulmonary nodule 8 patients; mediastinal lymph node staging, 16 patients; re-evaluation after neo-adjuvant therapy, 21 patients; increased markers blood levels in the follow-up of resected patients, 5 cases. Each indication is individually discussed and compared with the data of the literature, especially regarding the role of PET and its relationship with other noninvasive and invasive diagnostic tools. RESULTS: In 47 patients (94%) diagnostic yield was reached. A false positive (acute inflammatory lesion in solitary pulmonary nodule), a false negative (no demonstration of lymphangitic intrathoracic recurrence) and a non-diagnostic result (then pathologically proved non-neoplastic) were recorded. CONCLUSIONS: Thus the authors consider PET extremely useful in the diagnosis and staging of lung neoplasms; the high cost of PET may be compensated for the reduced need for invasive diagnostic tools and, avoiding inappropriate surgical options, with favourable cost-effectiveness.Thus, PET may be indicated in most, if not in all, patients with lung neoplasms.

[Caroli's disease. A case report]. / La malattia di Caroli. Descrizione di un caso clinico.

Personal experience in the treatment of a patient, presenting a pure unilobar Caroli's disease, is described. According on the litterature data, the procedure of choice was the left hepatectomy. The main reason was the high incidence of malignant transformation to cholangiocarcinoma of the cells of the cystic walls. Up to now the follow-up of the patient seems to prove that it was the right indication. Other procedures are discussed.

[Prognostic influence of neoplastic involvement of bronchial stump after anatomical lung resection for NSCLC]. / Influenza prognostica della colonizzazione neoplastica del moncone bronchiale dopo resezione polmonare anatomica per NSCLC.

BACKGROUND: The problem of unexpected neoplastic residual at the bronchial stump after surgery is discussed. Even if the prognostic impact of a macroscopic neoplastic residual at the bronchial stump is well known, the microscopic residual is still uncertain as well as the better therapeutic strategy to face this problem. METHODS: 43 out of 2350 patients operated on for lung cancer in our Institute from 1976 to 1998 had a neoplastic residual bronchial stump; 16 patients underwent a second surgery and are no more included in this study. 27 patients with a mean follow-up of three years were treated without another operation. Radiotherapy was proposed to all these patients and performed only in 20, while 4 patients were treated with polychemotherapy alone. Postoperative stage was IIIa in 17 patients, IIb in 8 and IIa in 2. RESULTS: The three year survival rate is 29% (8 patients still alive, 7 of which disease free); 7 received radiotherapy (35% of the whole patients treated with radiotherapy), only 5 complicated by radiation pneumonia without stopping the treatment, and one only chemotherapy. The survival rate after therapy is the same of patients operated on in the same stage without neoplastic bronchial residual. CONCLUSIONS: The authors are favorable to perform a second look surgery to enlarge bronchial resection in the initial stages and to perform in all cases adjuvant therapy. Attention is given to the meaning of mucosal or extramucosal involvement, to the effectiveness of frozen section examination and the authors' therapeutic suggestions in relationship to stage and histotype are discussed.

Effects of surgical stress and nitrous oxide anaesthesia on peri-operative plasma levels of total homocysteine. A randomised, controlled study in general surgery.

Previous studies of patients have shown that anaesthesia with nitrous oxide (N2O) increases the plasma levels of total homocysteine. In a randomised, controlled trial we measured the plasma total homocysteine levels in patients undergoing general surgery before and after anaesthesia with and without N2O. Plasma total homocysteine levels were measured before anaesthesia and 1, 3-5 and 24 h after incision in 24 patients randomly allocated to anaesthesia with N2O (n = 12) and without N2O (n = 12). Total homocysteine levels significantly decreased from 10.4 +/- 2.7 to 8.2 +/- 2.9 micromol x l(-1) in the non-N2O group 24 h after incision (p < 0.02), while they tended to increase slightly in the N2O group from 10.5 +/- 4.5 to 10.9 +/- 4.3 micromol x l(-1) (p > 0.05). Our randomised controlled study indicates that total homocysteine decreases after general surgery in patients in whom anaesthesia is maintained without N2O, but not in patients in whom anaesthesia is maintained with N2O.

Genetic and dietary factors affecting human metabolism of 1,3-butadiene.

The objective of this project was to determine the factors associated with differences in butadiene (BD) inhalation uptake and the rate of metabolism for BD to epoxy butene by monitoring exhaled breath during and after a brief exposure to BD in human volunteers. A total of 133 subjects (equal males and females; four racial groups) provided final data. Volunteers gave informed consent and completed a questionnaire including diet and alcohol use. A venous blood sample was collected for genotyping CYP2E1. Subjects received a 20 min exposure to 2.0 ppm of BD, followed by a 40 min washout period. The total administered dose was 0.6 ppm*h, which is in the range of everyday exposures. Ten, 1 or 2 min exhaled breath samples (five during and five after exposure) were collected using an optimized strategy. BD was determined by GC-FID analysis. Breathing activity (minute ventilation, breath frequency and tidal volume) was measured to estimate alveolar ventilation. After the washout period, 250 mg of chlorzoxazone were administered and urine samples collected for 6 h to measure 2E1 phenotype. The total BD uptake during exposure (inhaled BD minus exhaled) was estimated. A three-compartment PBPK model was fitted to each subject's breath measurements to estimate personal and population model parameters, including in-vivo BD metabolic rate. A hierarchical Bayesian PBPK model was fit by Monte Carlo simulations to estimate model parameters. Regression and ANOVA analyses were performed. Earlier data analysis showed wide ranges for both total uptake BD and metabolic rate. Both varied significantly by sex and age, and showed suggestive differences by race, with Asians having the highest rates. The analyses reported here found no correlation between total BD uptake and metabolic rate. No significant differences were found for oxidation rates by 2E1 genotype or phenotype, but the rates showed trends consistent with reported differences by genotype and phenotype for chlorzoxazone metabolism. No effects on metabolic rate were observed for long-term alcohol consumption, or consumption in the past 24 h. Overall, neither dietary factors nor genetic differences explained much of the wide variability in metabolic rates. Population characteristics, age, sex, and race, were the most important explanatory variables, but a large fraction of the total variability in metabolism remains to be explained.

Sulphuric acid burned women in Bangladesh: a social and medical problem.

In August-September 1998 an Italian medical team, composed of a plastic surgeon, an anaesthesiologist, an infectious diseases specialist and a psychologist, assisted by a local non-government organization (Narripokkho), studied a cohort of Bangladeshi women injured by sulphuric acid. The goals of the mission were: (1) recognition of the magnitude of the phenomenon of acid being intentionally thrown at women; (2) evaluation of the type and severity of burns; (3) preparation of a tentative schedule of surgical treatment of the lesions; (4) organization of local facilities; (5) training of doctors and nurses.

Time course of fenretinide-induced modulation of circulating insulin-like growth factor (IGF)-i, IGF-II and IGFBP-3 in a bladder cancer chemoprevention trial.

The insulin-like growth factor (IGF) system is widely involved in human carcinogenesis. A significant association between high circulating IGF-I concentrations and an increased risk of lung, colon, prostate and pre-menopausal breast cancer has recently been reported. Lowering plasma IGF-I may thus represent an attractive strategy to be pursued for chemopreventive purposes. We have previously shown that the synthetic retinoid fenretinide (4-HPR) lowers plasma IGF-I in pre-menopausal breast cancer patients. We investigated the effect of fenretinide on circulating IGF-I, IGF-II and IGFBP-3 measured at yearly intervals during the 2-year treatment period and one year after treatment discontinuation in a predominantly male population of patients with superficial bladder cancer. Repeated measures analysis, after adjustment for age, body mass index (BMI) and year of study, showed a significant effect of fenretinide on IGF-I levels, which were further lowered after the second year of treatment and only partially recovered after drug discontinuation. Differently from breast cancer patients, the effect of fenretinide was not modified by age. No significant effect was evident on IGFBP-3, IGF-II and the IGF-I+IGF-II/IGFBP-3 molar ratio, expressing the tissue availability of the mitogenic peptides, although IGF-II and the molar ratio were lowered by treatment by an overall mean of 16% and 15%, respectively. Given the increasingly recognized importance of circulating IGFs in the pathogenesis of different solid tumors, our findings strengthen the rationale for studying fenretinide as a chemopreventive agent.

A kinetic binding study to evaluate the pharmacological profile of a specific leukotriene C(4) binding site not coupled to contraction in human lung parenchyma.

We report the identification of a novel pharmacological profile for the leukotriene (LT)C(4) binding site we previously identified in human lung parenchyma (HLP). We used a series of classic cysteinyl-LT (CysLT)(1) receptor antagonists belonging to different chemical classes and the dual CysLT(1)-CysLT(2) antagonist BAY u9773 for both binding and functional studies. Because the presence of (S)-decyl-glutathione interfered with cysteinyl-LT binding, with a kinetic protocol we avoided the use of this compound. By means of heterologous dissociation time courses, we demonstrated that zafirlukast, iralukast, and BAY u9773 selectively competed only for (3)H-LTD(4) binding sites, whereas pobilukast, pranlukast, and CGP 57698 dissociated both (3)H-LTC(4) and (3)H-LTD(4) from their binding sites. Thus, with binding studies, we have been able to identify a pharmacological profile for LTC(4) distinct from that of LTD(4) receptor (CysLT(1)) in HLP. On the contrary, in functional studies, all of the classic antagonists tested were able to revert both LTC(4)- and LTD(4)-induced contractions of isolated HLP strips. Thus, LTD(4) and LTC(4) contract isolated HLP strips through the same CysLT(1) receptor. The results of kinetic binding studies, coupled to a sophisticated data analysis, confirm our hypothesis that HLP membranes contain two cysteinyl-LT high-affinity binding sites with different pharmacological profiles. In functional studies, however, LTD(4)- and LTC(4)-induced contractions are mediated by the same CysLT(1) receptor. In conclusion, the specific LTC(4) high-affinity binding site cannot be classified as one of the officially recognized CysLT receptors, and it is not implicated in LTC(4)-induced HLP strip contractions.

Inter-observer variation in histopathological diagnosis and grading of vulvar intraepithelial neoplasia: results of an European collaborative study.

OBJECTIVE: To evaluate the inter-observer variability of vulvar intraepithelial neoplasia diagnosis and grading system. DESIGN: Prospective study. SAMPLE: Histological sections of 66 vulvar biopsies. METHODS: Six consultant pathologists working at different European institutions independently reviewed 66 vulvar biopsies. The following variables were investigated: specimen adequacy, gross categorisation into benign or neoplastic changes, presence of atypical cytological pattern, presence of neoplastic architectural pattern, grade of vulvar intraepithelial neoplasia, presence of histopathologic associated findings for human papillomavirus infection. MAIN OUTCOME MEASURES: The degree of inter-observer variation for each histopathologic parameter was assessed by Kappa (kappa) statistics. The frequency and the degree of disagreement were calculated by a symmetrical agreement matrix showing the number paired classifications. RESULTS: A good agreement (overall weighted kappa = 0.65, unweighted kappa = 0.46) was observed for grading vulvar intraepithelial neoplasia. Human papillomavirus infection associated findings and specimen adequacy were the variables with less inter-observer agreement (overall weighted kappa 0.26 and 0.22, respectively). Exact agreement between two pathologists for grade of vulvar intraepithelial neoplasia was observed in 63.6% of paired readings; the rate of paired agreement reached 73.9% considering vulvar intraepithelial neoplasia 2 and 3 as a single class. Conversely, only 5.0% of vulvar intraepithelial neoplasia 1 diagnoses were concordant in paired analysis. CONCLUSIONS: Current terminology offers a reproducible tool in the hands of expert pathologists. While on the diagnosis of 'high grade' vulvar intraepithelial neoplasia (vulvar intraepithelial neoplasia 2 and 3) there is good agreement, the diagnostic category of vulvar intraepithelial neoplasia 1 is not reproducible.

Idarubicinol myelotoxicity: a comparison of in vitro data with clinical outcome in patients treated with high-dose idarubicin.

We evaluated in vitro the toxicity of idarubicin and its active metabolite idarubicinol on haematopoietic progenitors, using human umbilical cord blood and peripheral blood progenitors to obtain dose-response curves. We treated 16 patients with poor prognosis lymphoma in a phase I-II trial of high-dose idarubicin and melphalan and investigated if idarubicinol persisting in patients' plasma at the time of transplantation (day 0), on day +1 and +2 could result in an inhibition of infused progenitors. Colony inhibition was correlated with pharmacokinetic data and with the time of patients' engraftment. Plasma samples obtained before idarubicin treatment demonstrated a colony-stimulating effect, increasing the cloning efficiency by 72%. The inhibitory activity on colony forming unit granulocyte-macrophage (CFU-GM) of patients' plasma collected on the day of transplantation was lower than expected from dose-response curves (21% measured vs 70% expected). The time to patients' WBC and PLT recovery correlated with the amount of CD34+ cells reinfused and, to a lesser extent, with the colony-inhibiting effect of patients' plasma. The correlation between idarubicinol concentration and CFU-GM inhibition was not significant. These data suggest that plasma drug concentration on the day of stem cell reinfusion may overestimate the toxicity of residual anthracyclines to the transplanted cells.

Atrial fibrillation after operation for lung cancer: clinical and prognostic significance.

BACKGROUND: Atrial fibrillation is a common complication of early postoperative period in lung cancer thoracotomy. Its clinical incidence and short- and long-term impact on overall mortality has never been definitely assessed; moreover, it is unclear whether the arrhythmia represents an independent cardiac risk factor. METHODS: We prospectively studied 233 consecutive patients undergoing operation for lung cancer (170 with non-small-cell lung cancer). Postoperative atrial fibrillation incidence was related to different clinical factors possibly involved in its occurrence and to both short- and long-term survival. RESULTS: Atrial fibrillation occurred in 28 patients (12%) (same percentage in non-small-cell lung cancer); a strong relationship was observed between arrhythmia and age, history of hypertension and associated lymph node resection. The mean hospitalization time was 14 +/- 4 days in patients developing atrial fibrillation and 13 +/- 4 days in those who did not (p = not significant). No difference was observed between the two groups with regard to short- or long-term mortality or to long-term atrial fibrillation recurrences, also when considering the entire population and only non-small-cell lung cancer, separately. CONCLUSIONS: At our institution, early atrial fibrillation occurrence after operation for lung cancer does not show any negative impact on short- and long-term mortality or on recurrence rate.

Suppression of telomerase activity as an indicator of drug-induced cytotoxicity against cancer cells: in vitro studies with fresh human tumor samples.

Telomerase is a ribonucleoprotein complex with reverse-transcriptase activity responsible for telomere reconstitution. High telomerase activity was found in cancer cells, but not in differentiated homologous nonmalignant tissues. We demonstrated previously that the disappearance of telomerase activity is a reliable marker of tumor cell killing in human cancer cell lines. We have investigated the possibility of evaluating chemosensitivity of neoplastic cells of different origin [ovary, lung, breast, gastrointestinal, skin (melanoma)] obtained from cancer patients, by measuring residual telomerase activity after drug treatment in vitro. Using the classical telomeric repeat amplification protocol ("TRAP") assay based on polymerase chain reaction, we examined telomerase activity of untreated or drug-treated tumor cell suspensions, derived from the processing of surgical specimens. Feasibility and reproducibility of the assay were evaluated according to various parameters, including drug concentration, time of in vitro culture, and type of tumor. The results indicated that the assay is highly sensitive and reproducible, and can be performed using surgical specimens in a reasonable percentage of cases, ranging from 40% (breast cancer) to 100% (ovarian cancer). Moreover, the assay provides comparable results using a wide range of tumor cells, and the presence of normal cells does not interfere with the results. Prolonged tumor cell culture is not required because the assay can be completed within 24 to 72 hours after sample collection. In conclusion, the present investigation provides the technical bases for future studies to evaluate whether this assay would be able to predict patient's response to antitumor agents.

Intraoperative ultrasound during thoracoscopic procedures for solitary pulmonary nodules.

BACKGROUND: Traditional nonoperative diagnostic approaches to the solitary pulmonary nodule (bronchoscopy and percutaneous needle biopsy) can be inconclusive. Video-assisted thoracic surgery (VATS) provides a minimally invasive way to diagnose and treat these nodules. We evaluated the use of a dedicated intraoperative ultrasound probe as an aid in localization of small pulmonary nodules during VATS. METHODS: An intraoperative ultrasound examination during a thoracoscopic procedure was performed on 18 patients to localize deep pulmonary nodules less than 20 mm in diameter without a definitive diagnosis by preoperative imaging techniques. RESULTS: In the 18 patients, all nodules were successfully identified by intraoperative ultrasound. A definitive pathologic diagnosis was obtained from thoracoscopic biopsy or resection. The final diagnoses were primary lung cancer in 5 patients, metastatic lesions in 4 patients, hamartoma or chondroma in 4, granuloma in 3, and interstitial fibrosis in 2 patients. CONCLUSIONS: In our experience, intraoperative ultrasound can safely and effectively localize invisible or nonpalpable pulmonary nodules at the time of thoracoscopy. This may help surgeons perform minimally invasive lung resections with clear surgical margins.

A controlled study of postoperative radiotherapy for patients with completely resected nonsmall cell lung carcinoma. Groupe d'Etude et de Traitement des Cancers Bronchiques.

BACKGROUND: Postoperative radiotherapy is commonly used to treat patients with completely resected nonsmall cell lung carcinoma, but its effect on overall survival has not been established. METHODS: After undergoing complete surgical resection, 728 patients with non-small cell lung carcinoma (221 Stage I, 180 Stage II, and 327 Stage III) were randomized to receive either postoperative radiotherapy at a total dose of 60 gray or observation only . The main end point was overall survival. RESULTS: At the reference date, 218 of 355 patients in the control group had died and 262 of 373 in the radiotherapy group had died. Five-year overall survival was 43% for the control group and 30% for the radiotherapy group (P = 0.002, log rank test; relative risk [RR]: 1.33; 95% confidence interval [CI]: 1.11-1.59). This result was not modified by adjustment for potential prognostic factors. The excess mortality rate for the radiotherapy group was due to an excess of intercurrent deaths (P = 0.0001; RR: 3.47; the 5-year intercurrent death rate was 8% for the control group and 31% for the radiotherapy group). Radiotherapy had no significant effect on local recurrence (RR: 0.85; 95% CI: 0.64-1.14) and no effect on metastasis (RR: 1.06; 95% CI: 0.85-1.31). The rate of non-cancer-related death increased with the dose per fraction delivered.