Survival following complete resection of multifocal T4 node-negative NSCLC: a retrospective study.

BACKGROUND: Multifocal NSCLC in the same lobe are staged as T4. This study was designed to assess the impact of multifocal NSCLC in the same lobe on survival in completely resected node-negative patients to determine whether the T4 (stage III B) designation is valid. METHOD: We reviewed our database from October 1987 through 2004 to identify completely resected patients with N0 multifocal (T4) NSCLC. Patients with multifocal pure bronchiolo-alveolar carcinoma were excluded. Thirty-two patients had multifocal NSCLC in the same lobe and were node-negative. RESULTS: Five-year survival rate was 42.4 % for the whole group with a median survival of 48 months. When tumors were staged independently of the satellite nodule/s, patients in stage I A had a 5-year survival rate of 55 % while those in stage I B had a rate of 22 %. CONCLUSION: Patients with N0 multifocal intralobar NSCLC should be upstaged but not to stage IIIB. They should undergo complete surgical resection whenever multiple nodules are detected preoperatively.

Increased prevalence of cardiovascular disease in Type 2 diabetic patients with non-alcoholic fatty liver disease.

AIMS: To estimate the prevalence of cardiovascular disease (CVD) in Type 2 diabetic patients with and without non-alcoholic fatty liver disease (NAFLD), and to assess whether NAFLD is independently related to prevalent CVD. METHODS: We studied 400 Type 2 diabetic patients with NAFLD and 400 diabetic patients without NAFLD who were matched for age and sex. Main outcome measures were prevalent CVD (as ascertained by medical history, physical examination, electrocardiogram and echo-Doppler scanning of carotid and lower limb arteries), NAFLD (by ultrasonography) and presence of the metabolic syndrome (MetS) as defined by the World Health Organization or Adult Treatment Panel III criteria. RESULTS: The prevalences of coronary (23.0 vs. 15.5%), cerebrovascular (17.2 vs. 10.2%) and peripheral (12.8 vs. 7.0%) vascular disease were significantly increased in those with NAFLD as compared with those without NAFLD (P < 0.001), with no differences between sexes. The MetS (by any criteria) and all its individual components were more frequent in NAFLD patients (P < 0.001). In logistic regression analysis, male sex, age, smoking history and MetS were independently related to prevalent CVD, whereas NAFLD was not. CONCLUSIONS: The prevalence of CVD is increased in patients with Type 2 diabetes and NAFLD in association with an increased prevalence of MetS as compared with diabetic patients without NAFLD. Follow-up studies are necessary to determine whether this higher prevalence of CVD among diabetic patients with NAFLD affects long-term mortality.

Non-alcoholic fatty liver disease is associated with carotid artery wall thickness in diet-controlled type 2 diabetic patients.

Non-alcoholic fatty liver disease (NAFLD) is closely associated with several metabolic syndrome (MetS) features. We assessed whether NAFLD is significantly associated with carotid artery intima-media thickness (IMT), as a marker of subclinical atherosclerosis, and whether such association is independent of classical cardiovascular risk factors and MetS features. We studied 100 diet-controlled Type 2 diabetic patients with ultrasonographically diagnosed NAFLD and 100 diabetic patients without NAFLD who were comparable for age and sex. Main outcome measures were carotid IMT (by ultrasonography), classical risk factors, insulin resistance [as estimated by homeostasis model assessment (HOMA)-IR] and MetS (as defined by the Adult Treatment Panel III criteria). NAFLD patients had a markedly greater carotid IMT (1.24 +/- 0.13 vs 0.95 +/- 0.11 mm; p < 0.001) than those without the condition. The MetS and all its clinical traits were more highly prevalent in those with NAFLD (p < 0.001). Adjustment for age, sex, smoking history, diabetes duration, glycosylated hemoglobin, LDL cholesterol, liver enzymes and microalbuminuria did not really affect the significant differences in carotid IMT that were observed between the groups. Further adjustment for the MetS also had little impact, but additional adjustment for HOMA-IR score consistently attenuated any statistical significance (p = 0.28). In multivariate regression analysis, HOMA-IR score along with age and MetS (principally raised blood pressure values) were independently related to carotid IMT, whereas NAFLD was not. In conclusion, these results suggest that among diet-controlled Type 2 diabetic individuals the significant increase of carotid IMT in the presence of NAFLD is largely explained by HOMA-estimated insulin resistance.

Non-alcoholic hepatic steatosis and its relation to increased plasma biomarkers of inflammation and endothelial dysfunction in non-diabetic men. Role of visceral adipose tissue.

AIMS: To compare plasma biomarkers of inflammation and endothelial dysfunction in individuals with and without non-alcoholic hepatic steatosis (HS), and to evaluate whether such differences were mediated by the adverse metabolic pattern, typically found in these subjects. METHODS: HS (by ultrasound and computed tomography), visceral fat (by computed tomography), insulin resistance (by homeostasis model assessment-HOMA), plasma biomarkers of inflammation and endothelial dysfunction (hs-C reactive protein, fibrinogen, von Willebrand factor, plasminogen activator inhibitor-1 activity) were measured in 100 non-smoking, healthy, male volunteers. RESULTS: Plasma hs-CRP, fibrinogen, v-WF and plasminogen activator inhibitor-1 (PAI-1) activity levels were markedly higher (P < 0.01 or less) in subjects with non-alcoholic HS (n = 35) than in those without HS (n = 65). The former also had significantly higher values for body mass index (BMI), visceral fat, diastolic blood pressure, HOMA insulin resistance score, plasma insulin (both fasting and after glucose load), triglycerides, liver enzymes, and lower high-density lipoprotein (HDL)-cholesterol concentration. While the marked differences in these pro-inflammatory biomarkers observed between the groups were little affected by adjustment for age, BMI, blood pressure values, HOMA insulin resistance score, plasma triglyceride and liver enzyme concentrations, they were completely abolished after controlling for visceral fat. Similarly, in multivariate regression analyses, increased visceral fat significantly predicted the pro-inflammatory biomarkers, independently of HS and other potential confounders. CONCLUSIONS: These results indicate that, in non-smoking, non-diabetic men, the significant increase of plasma biomarkers of inflammation and endothelial dysfunction in the presence of non-alcoholic HS is largely mediated by abdominal visceral fat accumulation.

Relationship of non-alcoholic hepatic steatosis to cortisol secretion in diet-controlled Type 2 diabetic patients.

AIMS: To examine the association of non-alcoholic hepatic steatosis (HS) with the activity of the hypothalamo-pituitary-adrenal (HPA) axis in Type 2 diabetic individuals. METHODS: The activity of the HPA axis, as measured by 24-h urinary free cortisol (UFC) excretion and serum cortisol levels after 1.0 mg dexamethasone, was measured in 40 diet-controlled, predominantly overweight, Type 2 diabetic patients with non-alcoholic HS and in 40 diabetic patients without HS who were comparable for age, sex and body mass index (BMI). RESULTS: Subjects with non-alcoholic HS had significantly higher 24-h UFC excretion (191 +/- 4 vs. 102 +/- 3 nmol/24 h; P < 0.001) and post-dexamethasone cortisol concentrations (29.1 +/- 2 vs. 14.4 +/- 1 nmol/l; P < 0.001) than those without HS. Patients with HS had significantly higher values for HOMA insulin resistance score, plasma triglycerides and liver enzymes. Age, sex, BMI, waist-hip ratio (WHR), diabetes duration, HbA1c, LDL-cholesterol and blood pressure values were not different between the groups. The differences in urinary and serum cortisol concentrations between the groups remained significant after adjustment for age, sex, BMI, WHR, HOMA insulin resistance score, plasma triglycerides, HbA1c and liver enzymes. In multiple logistic regression analyses, 24-h UFC or serum cortisol concentrations (P < 0.05 and P = 0.02, respectively), along with age and HOMA insulin resistance, predicted the presence of HS, independently of potential confounders. CONCLUSIONS: These results demonstrate that non-alcoholic HS is closely associated with a subtle, chronic overactivity of the HPA axis in diet-controlled Type 2 diabetic individuals.

Increased plasma markers of inflammation and endothelial dysfunction and their association with microvascular complications in Type 1 diabetic patients without clinically manifest macroangiopathy.

AIMS: To evaluate whether plasma biomarkers of inflammation and endothelial dysfunction differed in Type 1 diabetic patients as compared with those in non-diabetic subjects, and to examine the association of these biomarkers with early stages of microvascular complications. METHODS: Plasma biomarkers of inflammation [fibrinogen, hs-C-reactive protein (hs-CRP)] and endothelial dysfunction [von Willebrand factor (v-WF), intercellular adhesion molecule-1, plasminogen activator inhibitor-1 (PAI-1) activity] were measured in 88 non-smoking young patients with Type 1 diabetes without clinical macrovascular disease and in 40 healthy controls. RESULTS: Plasma levels of hs-CRP, fibrinogen, v-WF, soluble intracellular adhesion molecule-1 (sICAM-1) and PAI-1 activity were markedly higher (P < 0.01 or less) in Type 1 diabetic patients than in healthy controls; these results were essentially unchanged when healthy controls were compared with patients without complications. After stratification by microvascular complication status, plasma biomarkers of inflammation and endothelial dysfunction were significantly increased in those with more advanced disease compared with those with early complications or without complications, respectively. However, while the significant differences in these biomarkers were little affected by adjustment for sex, age, BMI and blood pressure values, they were totally abolished after additional adjustment for diabetes duration and glycaemic control. CONCLUSIONS: These results indicate that in Type 1 diabetes there is a subclinical, chronic inflammation which is, at least partly, independent of clinically manifest macro- and microvascular complications, smoking or other traditional cardiovascular risk factors; this subclinical inflammation is closely correlated to the magnitude and duration of hyperglycaemia.

Completion pneumonectomy for non-small cell lung cancer: experience with 59 cases.

OBJECTIVE: The objective of this study was to assess the results of completion pneumonectomy performed for non-small cell lung cancer, classified as second primary or recurrence/metastasis. METHODS: From 1982 to 2000, 59 patients underwent completion pneumonectomy for lung cancer, classified second primary or recurrence/metastasis according to a modified form of Martini's criteria, after a mean interval from first resection of 60 months for second primary lung cancers and 19 months for recurrences/metastases. RESULTS: Operative mortality was 3.4% and complications occurred in 30% of patients. Five-year survival rate for completely resected patients was 25% (median 20 months). No significant difference in long-term survival was detected between second primary and recurrent tumors; survival was not adversely affected by a resection interval of less than 2 years or less than 12 months. CONCLUSIONS: Completion pneumonectomy for non-small cell lung cancer is a safe surgical procedure in experienced hands; long-term survival is acceptable and the best results are obtained for stage I lung cancer. Distinction between second primary lung cancer and recurrence failed to demonstrate a prognostic value.

Sleeve lobectomy for non-small cell lung cancer and carcinoids: results in 160 cases.

OBJECTIVE: To assess operative mortality (OM), morbidity and long-term results of sleeve lobectomies performed for non-small cell lung cancer (NSCLC) and carcinoids during a 35-year period. METHODS: A retrospective review of patients who underwent a sleeve lobectomy for NSCLC and carcinoids was undertaken, univariate and multivariate analyses of factors influencing early mortality in NSCLC were performed and for this purpose the series was split into an early and a contemporary phase, the Kaplan-Meier method was used to calculate the cumulative survival rate, and statistical significance was calculated with the log-rank test. Causes of death were evaluated in relation to the stage of the disease. RESULTS: OM for NSCLC was 14.6% in the early phase and 6% in the contemporary one; late stenosis occurred in 7.7% of NSCLC patients in the early phase and in 2% in the contemporary one. No OM or late stenosis occurred in carcinoid patients. Three, 5 and 10-year survival rates excluding carcinoids were 77, 62 and 31% for stage I(A-B), 45, 34 and 27% for stage II(A-B), 33, 22 and 0% for stage III(A-B). The 10-year survival rate for carcinoids was 100%. There was no significant difference in long-term survival between stages II and III, while the difference between stage I and stages II and III was significant (P<0.001). When survival was analyzed in relation to nodal status, 3, 5 and 10-year survival rates were 71, 57 and 33% for N0 disease, 42, 33 and 22% for N1 disease, and 34 and 19% with the last observation at 82 months of 19% for N2 disease; there was no significant difference in survival between N1 and N2 disease. A second primary lung cancer occurred in six patients (3.7%) who underwent resection. Late mortality was not related to cancer in most stage I patients while in stages II and III patients it was related to local and distant recurrences. CONCLUSIONS: Sleeve lobectomy is a valid alternative to pneumonectomy: careful patient selection and surgical technique make it possible to achieve a mortality rate comparable to or lower than that for pneumonectomy along with a better quality of life. In addition, it allows further lung resection, if necessary.

Elevated plasma levels of soluble receptors of TNF-alpha and their association with smoking and microvascular complications in young adults with type 1 diabetes.

The purposes of this study were 1) to compare soluble tumor necrosis factor-alpha receptors, which are thought to reflect the degree of TNF-alpha activation, in nondiabetic subjects and type 1 diabetic patients, and 2) to evaluate the effects of smoking and microvascular complications on soluble tumor necrosis factor-alpha receptor levels in type 1 diabetic individuals. Plasma soluble tumor necrosis factor-alpha receptor levels (R1 and R2) were measured in 50 young type 1 diabetic patients without clinical macroangiopathy and in a matched group of 20 healthy volunteers. When diabetic patients were grouped according to smoking and microvascular complication status, the groups of patients had similar values of age, sex, body mass index, blood pressure, lipids, creatinine, and glycometabolic control. Nevertheless, soluble tumor necrosis factor-alpha receptor-R1 levels but not R2 levels, were markedly elevated (P < 0.05 or less) in complicated vs. uncomplicated (2.40 +/- 0.3 vs. 1.80 +/- 0.1 ng/ml) patients and in smokers vs. nonsmokers (2.66 +/- 0.4 vs. 1.76 +/- 0.1 ng/ml). In a two-factor ANOVA, both smoking (P < 0.01) and microvascular complications (P < 0.05) were independent predictors of soluble tumor necrosis factor-alpha receptor-R1. Soluble tumor necrosis factor-alpha receptor levels of diabetic patients who did not smoke or without complications were similar to those of healthy controls. In conclusion, smoking and microvascular complications seem to exert an additive and deleterious impact on TNF-alpha activation, as reflected by levels of soluble tumor necrosis factor-alpha receptors, in young adults with type 1 diabetes.

Early hilar lung cancer--clinical aspects and long term survival. Identification of a subgroup of stage IA patients with more favorable prognosis.

Twenty-nine patients out of 2018 operated on for a non-small-cell lung cancer from 1987 to February 1998 met the criteria proposed by the Japan Lung Cancer Society (JLCS) for the definition of early hilar lung cancer (EHLC). Twenty-six patients were symptomatic and 20 had a radiologically visible lesion. All cancers were located and diagnosed by bronchoscopy and all patients were resected. At histology, all tumors were squamous in nature. The five-year cumulative survival rate was 96%--a second primary lung cancer (2nd Pr.) developed in 4 patients (13.8%). The definition of EHLC proposed by the JLCS allows the selection of a subgroup of stage I patients with a very good prognosis. Nevertheless, a close follow-up is mandatory because more than 10% of these patients develop a 2nd Pr.

[Lung resection after pneumonectomy for bronchogenic carcinoma]. / Resezioni polmonari dopo pneumonectomia per carcinoma broncogeno.

METHODS: Four patients who previously underwent pneumonectomy for lung cancer, underwent a new contralateral resection for a metachronous cancer. Functional evaluation of these patients was not different from the standard one and included ECG, spirometry, blood gas analysis and a careful clinical evaluation. A femoro-femoral bypass was used in 2 patients to work on a collapsed lung, High Frequency Jet Ventilation was used in 1 while the last patient was hyperoxygenated and then ventilation was discontinued for the time required for the resections. RESULTS: Each method was free of complications. Operative mortality was nil. Two patients are alive free of disease at 66 and 14 months, two died for metastatic disease at 4 (N2 paratracheal nodes) and 12 months. CONCLUSIONS: Patients with a single lung should not be denied a further resection on contralateral lung. A routine evaluation of cardiopulmonary function may be sufficient but a more sophisticated evaluation including exercise oxygen consumption test, cardiac catheterization, lung perfusion scan, should be used when there is some doubt on the possibility of the patients to sustain the resection. Due to the high operative risk of this kind of patients mediastinoscopy should be performed even if preoperative CT scan of the chest shows minimally enlarged mediastinal nodes.

[Thymoma, aplastic anemia, hypogammaglobulinemia and malignant pulmonary neoplasm: a case report]. / Timoma, anemia aplastica, ipogammaglobulinemia e neoplasia polmonare maligna: presentazione di un caso.

A 67 year old man presented with non-invasive thymoma, associated aplastic anemia and important hypogammaglobulinemia; the postoperative course has been characterized, three months later, by thrombocytopenia (kept under control with steroid therapy) and, two years later, by squamous lung cancer, not susceptible of surgical treatment. The patient died five years after operation because of progression of the lung cancer. Anemia improved only partially after operation; there where no effects on hypogammaglobulinemia. Thymoma has been reported in literature in 50% of patients with aplastic anemia, 7-13% of adult patients with hypogammaglobulinemia is affected by thymoma, in 21% of patients that presented with thymoma other tumors have been discovered through clinical history.

[Diagnosis and treatment of traumatic diaphragmatic hernia with delayed presentation]. / Diagnosi e trattamento dell'ernia traumatica del diaframma a tardiva presentazione.

AIM: To evaluate the clinical picture, diagnostic techniques and most appropriate treatment in traumatic diaphragmatic hernia with delayed presentation on the basis of personal experience and in the light of other published studies. EXPERIMENTAL DESIGN: Review of cases treated. SETTING: Patients treated in University General Surgery wards. PATIENTS: Those patients in whom diagnosis was made some time after trauma and after the acute event were selected from a group of patients with traumatic diaphragmatic hernia. SURGERY: All patients underwent surgery to reduce hernia and repair the diaphragmatic lesion. MEASUREMENTS: All clinical findings were examined together with the tests performed and the type of treatment carried out. RESULTS: The diagnosis was made between 3 months and 3 years after the injury. Three patients presented manifest symptoms of high intestinal occlusion on entry. Radiological alterations were present in standard chest X-rays in all patients and digestive tract contrast radiography was positive for the diagnosis of hernia in 3 out of 4 cases in which it was performed; a preoperative diagnosis of hernia was obtained in 4 cases. Patients were operated using a thoracotomy (3 cases) or combined laparothoracotomy access (2 cases); the diaphragmatic lesion, localised in all cases in the cupula of the left hemidiaphragm, was repaired using separate sutures in non-reabsorbable material without the use of grafts. One patient died postoperatively owing to septic complications. CONCLUSIONS: traumatic diaphragmatic hernia with delayed presentation involves severe complications that increase morbidity and operating mortality.

Intimal-medial thickness of the carotid artery in nondiabetic and NIDDM patients. Relationship with insulin resistance.

OBJECTIVE: The aim of this study was 1) to compare intimal-medial thickness (IMT) of the carotid artery in nondiabetic and NIDDM patients and 2) to evaluate the association of this early marker of atherosclerosis with several cardiovascular risk factors, including plasma insulin and insulin resistance. RESEARCH DESIGN AND METHODS: A total of 58 nondiabetic and 56 NIDDM patients, randomly selected among those attending the outpatient Diabetes Clinic or the Clinic for Internal Medicine were examined. BMI, waist-to-hip ratio (WHR), blood pressure, glycohemoglobin (HbA1c), and fasting concentrations of plasma glucose, serum lipids (total and HDL cholesterol, triglycerides), and serum insulin were measured. Insulin resistance was assessed by computing glucose disappearance rate from plasma after intravenous insulin injection (Kitt). IMT of the carotid artery was measured by ultrasonography. RESULTS: IMT was significantly higher in diabetic patients, and the difference remained highly significant after adjusting for sex, age, BMI, WHR, presence of hypertension and dyslipidemia, and smoking status (1.39 vs. 1.24 mm, common SD 0.12, P < 0.001). Univariate regression analyses showed that IMT was negatively correlated with Kitt in either nondiabetic (r = -0.348, P < 0.01) or diabetic patients (r = -0.492, P < 0.001). However, multiple regression analyses showed that IMT was independently associated with age and WHR in nondiabetic subjects, whereas in diabetic patients, IMT was independently predicted by Kitt and hypertension. These two variables explained approximately 62% and approximately 35% of the variability of IMT in nondiabetic and diabetic patients, respectively. Plasma insulin was not independently associated with IMT in either groups. CONCLUSIONS: These results indicate that 1) diabetes is characterized by a greater thickness of the carotid artery independently of other established risk factor of atherosclerosis, 2) early atherosclerosis is independently associated with insulin resistance in diabetic but not in nondiabetic patients, 3) central adiposity is an independent predictor of IMT in nondiabetic individuals.

Does extended pancreaticoduodenectomy increase operative morbidity and mortality vs. standard pancreaticoduodenectomy?

The poor prognosis of pancreatic carcinoma after resection is related to distant metastases and local recurrence that is characterized by a strong tendency to infiltrate the retroperitoneal tissue and spread along the neural plexuses and lymph nodes. Thorough clearance of these tissues around the celiac and mesenteric axes, aorta, and inferior vena cava from the diaphragm to the inferior mesenteric artery (extended pancreaticoduodenectomy may lower the rate of local recurrence, but the procedure has been criticized for its higher morbidity and mortality. Our aim was to compare extended pancreaticoduodenectomy (EPD) with standard pancreaticoduodenectomy (SPD) in terms of postoperative morbidity and mortality. Data from 47 patients who underwent either EPD (n=24) or SPD (n=23) between November 1992 and October 1995 were retrospectively analyzed. Preoperative laboratory findings, operative risk (according to the American Society of Anesthesiologists classification), type of operation (classic Whipple vs. pylorus-preserving Whipple), operative time, intraoperative blood and plasma transfusion, postoperative morbidity and mortality, and postoperative hospital stay were scrutinized. The results showed that all of the parameters considered were similar in the EPD and SPD groups (intraoperative blood transfusion 800+/-490 ml vs. 700+/-586 ml, postoperative mortality 0% vs. 4.3%, overall morbidity 45.8% vs. 47.8%, surgical morbidity 37.5% vs. 34.7%, and postoperative hospital stay 16+/-8.1 days vs. 17+/-13.1 days. These two groups differed only in the operative time, which was significantly longer for EPD than for SPD (360+/-68.9 minutes vs. 330=66.9 minutes, P=0.02). Although the operative time is increased with EPD, there does not appear to be an increase in intraoperative complications, postoperative morbidity and mortality, or postoperative hospital stay with this procedure. However, definitive confirmation of these results can only be provided by a prospective randomized study.

Lung resection on single residual lung after pneumonectomy for bronchogenic carcinoma.

Seven patients who had undergone a pneumonectomy for lung cancer developed a second tumor in the remaining lung after a mean time of 28.5 months and underwent a further resection. Preoperative evaluation was based on standard functional tests and on the "stair climbing test". Three patients were operated on using an extracorporeal oxygenator to work on a collapsed lung, three using standard anesthesiologic techniques, and one using high-frequency jet ventilation. There was no operative mortality. Complications occurred in two patients, requiring a temporary tracheostomy in one case. No patient required home oxygen supplementation. Four patients died of metastatic disease after 4, 8, 10, and 12 months, while two patients are alive and free of disease after 83 and 9 months, one is alive and free of symptoms but with a local recurrence after 29 months. Lung resection for bronchogenic carcinoma on a single lung can be safely performed provided that careful clinical judgment is used; long-term survival can be achieved with the resection of the new tumor.

Left pneumonectomy for a second primary tumor after right upper lobectomy for superior sulcus tumor.

We report on a patient who underwent a left pneumonectomy for a second primary lung cancer after a right upper lobectomy and upper chest wall resection for a superior sulcus tumor. Although the postoperative course was complicated by sputum retention which required a temporary tracheostomy the outcome was good and the patient is now living without supplementary oxygen supply. Left pneumonectomy may be considered in patients with previous contralateral lobectomy when the preoperative evaluation of the patient shows an acceptable predicted postoperative pulmonary function. A long-term cure and a good quality of life must, however, be offered.