Fine needle aspiration of non-small cell lung cancer: current state and future perspective.

AThe emerging treatment revolution determined by the advent of new targeted therapies requires accurate tumour subtyping as a mandatory step in the clinical workup of patients with non-small cell lung carcinoma (NSCLC). As a result of advanced and inoperable disease or poor performance status, in many patients, minimally invasive procedures must be employed to obtain diagnostic material. Fine needle aspiration (FNA) is a valid and widely employed alternative to either tru-cut or open-sky biopsy. Indeed, cytological specimens are suitable for techniques such as immunocytochemistry, mutation and microRNA analysis, and may present advantages over small biopsies especially if cell blocks are prepared and attention is paid to cytomorphology and pre-analytic management of specimens at the time they are collected. These will allow the adequate stratification of patients into different diagnostic and prognostic classes.

[Improvement of short-term prognosis in patients with refractory heart failure]. / Miglioramento della prognosi a breve termine dei pazienti con scompenso cardiaco refrattario.

BACKGROUND: Prognosis of patients with severe heart failure is poor, despite improved results in medical therapy. Heart transplantation is the only treatment possible in end-stage heart failure. The aim of this study was to evaluate the variation in prognosis over the past six years in the patients admitted to Intensive Care Unit for heart failure in spite of optimal oral therapy. STUDY POPULATION AND METHOD: Between January 1990 and December 1995, 133 patients with heart failure were admitted to the Intensive Care Unit, despite the fact that they were on optimal oral therapy. All patients were in New York Heart Association (NYHA) functional class III to IV and required intravenous administration of sympathomimetic amines, in addition to standard heart failure treatment procedures. Cumulative survival at six months of patients observed between 1990-1992 (group A) was compared with the survival rate of patients observed from 1993 to 1995 (group B). RESULTS: Clinical and haemodynamic parameters were similar in groups A and B, but ACE-inhibitors were used more frequently in group B (75 vs 31% respectively, p < 0.05). During the follow-up period, heart transplantation was indicated in a similar percentage of patients (A 53% vs B 58%). However, mortality on the waiting list (58% group A vs 21% group B; p < 0.05) and the percentage of patients who underwent heart transplantation (41% group A vs 78% group B; p < 0.05) differed. Moreover, all patients in group A and 50% of group B were operated on as "status one" patients. The total six-month mortality rate decreased from 69% before 1992 to 48% thereafter (p < 0.05). CONCLUSION: The short-term prognosis of patients with refractory heart failure improved over time. In the latter period, ACE-inhibitors were used more frequently and the number of heart transplantations was greater. Nevertheless, our results do not allow us to identify the causes of the improved survival rate.

[Coronary angioplasty in acute myocardial infarction]. / Angioplastica coronarica primaria nell'infarto miocardico acuto.

Primary percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction (AMI) allows to obtain a higher reperfusion rate in the culprit vessel than thrombolytic therapy, reducing the incidence of death, non fatal reinfarction and recurrent ischemia. The aim of this study was to test the in-hospital and mid-term results of an early invasive strategy with PTCA in patients with AMI. Thirty-four patients with AMI underwent coronary angiography within 3 hours from the onset of symptoms. Twenty-four patients had anterior AMI and 3 were in cardiogenic shock. Three patients, 1 without significant lesions and 2 with multivessel diffuse coronary disease, were left out of the procedure, and 31 patients underwent PTCA. Twenty-six lesions were total occlusions with TIMI flow 0.A TIMI flow 1 was present in the other 5 vessels. Stent deployment was decided for 16 lesions (52%). Primary success (TIMI flow 3 with mean residual stenosis of 15 +/- 20%) was obtained in 30 patients (97%). In 1 patient recanalization of the anterior descending coronary artery was not possible due to tortuosity of the abdominal and thoracic aorta. At pre-discharge angiography a good result was confirmed in 24/25 patients. After 6 months only 1 patient (3%) underwent a new PTCA for recurrent angina. In conclusion, primary PTCA for AMI within 3 hours of symptom onset allows good in-hospital and mid-term results with a low rate of complications.

Intracoronary stenting for thrombus-containing lesions in the setting of acute ischemic syndromes.

AIM: The presence of intracoronary thrombus was considered a contraindication for stent deployment. Recently, many investigators have demonstrated that the use of stents for thrombus-laden lesions under both elective and bail-out conditions is effective and safe, even in the setting of acute myocardial infarction (AMI). METHODS AND RESULTS: In this study Palmaz-Schatz stents were implanted to treat suboptimal results and complications of percutaneous transluminal coronary angioplasty (PTCA) in 41 thrombus-containing lesions. Clinical presentation was unstable angina in 24 and AMI in 17 patients. Stents were deployed because of suboptimal result (n = 27), coronary dissection with threatening occlusion (n = 13) or abrupt closure (n = 1). An angiographic successful deployment was obtained in all but one lesions (98%). Four patients (9.8%) suffered from in-hospital complications: three developed a non fatal non-Q wave AMI and one died. There was no need for emergency coronary artery bypass graft surgery, repeat PTCA or blood transfusion for vascular complications. At six-months follow-up one patient (2.6%) developed a non-Q wave AMI and two (5.1%) underwent a repeat coronary angioplasty. CONCLUSIONS: Our experience confirms that adequately dilated Palmaz-Schatz stent might be safe and effective for thrombus-containing lesions in the setting of acute ischemic syndromes.

Troponin T, creatine kinase MB mass, and creatine kinase MB isoform ratio in the detection of myocardial damage during non-surgical coronary revascularization.

The presence of myocardial injury during non-surgical coronary revascularization has been evaluated by means of highly specific and sensitive biochemical markers. Troponin T, creatine kinase-MB isoenzyme mass concentration, and creatine kinase MB2/MB1 isoform ratio have been determined in 80 patients who underwent coronary revascularization with percutaneous transluminal coronary angioplasty (PTCA). Forty-five patients underwent balloon angioplasty, 15 rotational atherectomy, 10 directional atherectomy, and 10 elective coronary stenting. Serum concentration of the evaluated markers did not increase significantly after 57 uncomplicated revascularization procedures, including 15 rotablation procedures, nor after 8 PTCAs complicated by localized coronary type B and C dissections. Significant elevation of all markers above the upper limits of the reference interval (P < 0.05) was detected after occlusion of small side branches (< 0.5 mm diameter) in 5 patients. Creatine kinase MB2/MB1 isoform ratio was the earliest marker to increase. After recanalization of occluded vessels in 8/10 patients with 6-60 days old myocardial infarction only troponin T concentrations increased from a baseline of 0.28 microgram/l to a median peak of 0.80 microgram/l. This increase was statistically not significant (P = 0.12). In conclusion, myocardial damage was not detected following uncomplicated non-surgical revascularization obtained with different techniques. Markers of myocardial injury provide high sensitivity after small side branch occlusion.

[Indications for heart transplant: retrospective evaluation of criteria for selection of candidates]. / Indicazioni al trapianto cardiaco: valutazione retrospettiva dei criteri di selezione dei candidati.

INTRODUCTION: Heart transplantation (HT) is a largerly accepted therapy for patients with refractory congestive heart failure. However, lack of donors imposes a rigorous choice among candidates for transplantation. Aim of this study was to identify retrospectively determinants for the selection of recipients. METHODS: Between december 1985 and december 1993 500 patients were listed for HT at the Department of Cardiovascular Surgery of the Padua University. Among United Network for Organ Sharing (UNOS) status II patients, 42 transplanted (group I) and 38 died waiting for a donor (group II) were chosen. The following parameters were collected at the time of insertion into the waiting list: sex, blood group, diagnosis, age, body surface area, natriemia, renal function, hepatic function, presence of ventricular arrhythmias, use of ACE-inhibitors, cardiac index, mean pulmonary pressure, mean wedge pressure, mean arterial pressure, central venous pressure, pulmonary arteriolar resistances, left ventricular ejection fraction. Also the time on waiting list until a final event (transplantation or death) was considered. RESULTS: Comparing the two groups the diagnosis of dilated cardiomyopathy (59.4% group I vs 36.8% group II; p = 0.04) and ejection fraction (26.4 +/- 9.1% group I vs 22.2 +/- 8.0% group II; p = 0.03) were the only variables statistically different. Multivaried analysis evidenced some parameters as independent predictors for HT. In detail, being listed for HT for more than 6 months lowered the probability to receive a heart to 0.34, while waiting for more than 12 months increased it to 2.64. Mean arterial pressure higher than 75 mmHg increased the probability for HT to 2.87, while an increase in mean pulmonary pressure of 5 mmHg lowered the probability to 0.80. An increase in the cardiac index of 0.5 l/m1/m2 lowered the probability to 0.61. A blood group other than 0 increased the possibility to 3.60, the basal surface area higher than 1.78 m2 lowered it to 0.306 and an ejection fraction higher than 22% increased it to 3.94. CONCLUSIONS: We can conclude that parameters which predict the outcome of patients listed for HT were not only size matching, blood group and waiting time, but also ejection fraction, arterial pressure and diagnosis.

[Anaphylactoid reaction during administration of tissue plasminogen activator (t-PA)]. / Reazione anafilattoide durante somministrazione di attivatore tissutale del plasminogeno (t-PA).

The use of tissue plasminogen activator (t-PA) in the management of acute myocardial infarction, as effective thrombolytic agent, is well established. Thrombolytic therapy, limiting the extent of myocardial necrosis, reduces the infarct-related morbidity and mortality and improves the prognosis in patients with acute myocardial infarction. Thrombolytic agents present various side effects. Allergic reactions may occur with both streptokinase (ST) (or with anistreplase, the equimolecular mixture of streptokinase and human plasminogen); and t-PA. The incidence of allergic reactions associated with the use of t-PA is much lower if compared with other thrombolytic agents. Since t-PA is structurally identical to endogenous t-PA, its administration should not cause anaphylactic reactions. The purpose of this case presentation is to describe the occurrence of an anaphylactoid reaction during infusion of t-PA in a 63 year-old man, admitted to the Cardiac Care Unit (C.C.U.) with diagnosis of acute myocardial infarction.

[Carcinoids in emergency surgery]. / I carcinoidi nell'urgenza chirurgica.

The authors report their experience of three cases of carcinoids of the gastroenteric tract which required emergency surgery. Two patients presented symptoms of acute appendicitis caused by appendicular carcinoid, whereas the third presented an occlusive syndrome due to ileal carcinoid.

Percutaneous transluminal coronary angioplasty in refractory unstable angina pectoris: are new devices useful?

This study was undertaken to assess if the introduction of new angioplasty devices (autoperfusion balloon catheters, stent and atherectomy) could ameliorate early and late results of prompt percutaneous transluminal coronary angioplasty (PTCA) in patients with refractory unstable angina. From January 1993 to June 1995, 59 of 278 patients (14 female, 45 male; mean age: 61 +/- 10 years; range: 38-78) admitted to our Coronary Care Unit with the diagnosis of unstable angina had more than one episode of chest pain at rest with dynamic electrocardiographic ST-T changes and without signs of cardiac necrosis while on medical therapy including oxygen, aspirin, heparin, nitroglycerin and either a beta-blocker or a calcium-antagonist. Coronary angiography was performed within 48 h from the last ischemic attack and a culprilesion technically suitable for PTCA was identified. PTCA was performed in 73 lesions. Elective stent implantation was considered for 16 type B or C lesions in 14 patients. The procedure was initially successful in 52/59 patients (88%), uncomplicated unsuccessful in 4/59 (7%) and complicated in 3/59 (5%). Elective stent insertions were all successful (16/16, 100%). All successfully treated patients were followed up for a mean of 12 +/- 7 months (range: 6-27): 2/52 patients (3.8%) suffered from non-transmural myocardial infarction, 14/52 (26.9%) had a recurrence of angina and 2/52 (3.8%), asymptomatic, had a positive stress test. We conclude that prompt PTCA in refractory unstable angina using 1990s 'state of the art' equipment compares favorably to previous study and that stent delivery might become the elective treatment of complex lesions in this subset of patients.

[Analysis of risk factors in a group of patients referred for heart transplantation for refractory heart failure: multivariate analysis]. / Analisi dei fattori di rischio in un gruppo di soggetti riferiti per trapianto cardiaco a causa di uno scompenso cardiaco refrattario: analisi multivariata.

BACKGROUND: In the absence of evident clinical controindication heart transplantation can be performed in patients with critical degree of cardiac failure. The choice of adequate candidates for transplantation is frequently based on clinical severness but also influenced by factors as body size, blood group and so on. METHODS: To identify the presence of prognostic factors for patients with high risk of death, clinical, hemodynamic and therapeutic features of 70 patients (mean age 44.8 +/- 13.8) with critical cardiac failure (64 patients in IV class N.Y.H.A.) have been reviewed. Most of them were affected by dilated or ischemic cardiomyopathy. RESULTS: All patients were admitted to Cardiac Intensive Care Unit, 13 patients received transplantation, 24 were discharged and 33 died. Univariate analysis evidenced, that in the group of patients who died, sepsis (p = 0.0003), renal (p = 0.04) and liver function impairment (P = 0.007) occurred significantly more frequent. The differentiated use of catecholamines (P = 0.0007) and of vasodilators (P = 0.007), the need of mechanical ventilation (P = 0.0001) and the need of hemodialysis (P = 0.02) resulted significantly higher in the group of dead patients where mean arterial pressure (p = 0.01) and mean systemic resistances (P = 0.04) resulted significantly lower. With multivariate analysis were identified following independent risk factors of death: male sex, infections, mechanical ventilation, differentiated use of vasodilators, mean arterial pressure and mean pressure in pulmonary artery. CONCLUSIONS: As predictive risk factors of death in patients with critical cardiac failure and awaiting transplantation resulted: sex, the presence of infection, mechanical ventilation and differentiated use of vasodilators whereas hemodynamic parameters did not result of important predictive value.

[Treatment results in pT2, NO1 breast cancer. )A retrospective analysis of 85 cases)]. / Risultati del trattamento del carcinoma mammario pT2, NO-1. (Analisi retrospettiva su 85 casi).

The authors report on 85 T2 breast carcinoma treated from March 1984 to February 1991. The median age was 55.7 years (range: 24-82). The most common type of tumor was infiltrating ductal carcinoma (88.2%). T pathological diameter was in 69 cases < or = 3 cm (81.2%). 47 patients showed pathologically positive axillary nodes (55.3%). Radical mastectomy with total axillary dissection, preferably modified by Patey or Madden (78.8%), was the treatment of choice. Only 5 patients were submitted to conservative surgery (quadrantectomy plus radiotherapy). Mean follow-up time was 42 months. For all considered patients, crude and without evident disease 3 and 5 years actuarial survival was evaluated. Distant metastases were observed in a total of 12/85 patients (14.1%), mainly in N+ with more than 3 nodes (31.5%) three times associated to loco-regional failures. Results at June 1992, as occurrence of first failure from the date of surgery are described. Different therapeutic managements are discussed. Prognosis of T2 breast carcinoma remains still poor. Limited surgery in association with radiotherapy and/or pre- and postoperative chemotherapy in N+ patients with more than 3 nodes or N- patients with high cell proliferation index, seems to be encouraging to T2 cases with a diameter less than 3 cm, when local conditions are suitable for good final aesthetic results.

[Recurrent bacterial endocarditis on mitral and aortic biological prostheses in young drug addicts. The role of transthoracic cardiac echo-Doppler in the diagnosis and assessment of postendocarditis dysfunction]. / Endocardite batterica recidivante su protesi biologiche mitralica ed aortica in giovane tossicodipendente. Ruolo dell'eco-Doppler cardiaco transtoracico nella diagnosi e nella valutazione della disfunzione postendocarditica.

Bioprosthetic infective endocarditis is a very serious complication since both medical and surgical treatment is associated with a high mortality. We describe a case of a young drug addict who presented 3 recurrent episodes of bacterial endocarditis of mitral and aortic bioprosthetic valves, caused by different virulent germs. All 3 episodes were resolved by medical therapy, but the residual aortic bioprosthetic dysfunction was important and the patient died before surgical replacement. Which was not considered an emergency since the patient was asymptomatic, did not present heart failure and left ventricular function was preserved. Color-Doppler echocardiography permitted us to visualize the vegetations and to establish and follow the evolution of residual bioprosthetic dysfunction.

[Abdominal visceral lesions in patients with multiple trauma]. / Le lesioni viscerali addominali nel politraumatizzato.

The paper describes a series of 385 cases of multiple injuries which were treated between 1987 and 1991 at the Emergency Unit of the Fatebenefratelli Hospital in Milan. Special attention was paid to abdominal trauma and visceral injuries in terms of both diagnosis and treatment.

A brief contact of native whole blood with adenosine diphosphate (ADP) promotes the release of the contents of platelet alpha granules but not dense bodies and increases platelet retention to glass bead columns.

We have previously demonstrated that a brief contact of native whole blood with ADP, promotes a dose dependent release of the contents of platelet alpha granules. In the present study we have shown that in our system there is not a parallel release of the contents of platelet dense bodies as measured by the release of serotonin (5 HT). This early and partial platelet activation determines an increase in platelet retention in glass bead columns. After exactly 15 seconds of activation of native whole blood from 6 healthy volunteers with ADP, in fact, there was a significant fall in the platelet count following the flow of native whole blood across glass beads. A significant decrease (from x = 182,000 +/- 13,700 to x = 120,000 +/- 8,00/microliters p less than 0.001) was present when the blood was stimulated with 0.4 microM ADP final concentration. These results suggest that early, partial platelet activation by ADP could facilitate their possible adhesion to a suitable surface exposed along the vascular tree.

[Advantages of a cardiologic ambulatory care facility specifically organized for patients undergoing treatment with oral anticoagulant drugs]. / Vantaggi di un ambulatorio specifico organizzato da cardiologi per pazienti in trattamento con farmaci anticoagulanti orali.

In patients with artificial heart valve prosthesis oral anticoagulants reduce but not eliminate the thromboembolic complications however, they do increase the risk of bleeding. In the present study, the incidence of thromboembolic and hemorrhagic complications in two homogeneous groups of patients with artificial heart valves on long term oral anticoagulant treatment has been evaluated. Group A (99 patients; total follow-up = 309 years) were resident in the Triveneto regions and received a questionnaire while group B (104 patients; total follow-up = 370 years) were referred to our department's centre for the control of oral anticoagulant treatment. Both groups were kept at a therapeutic range of 20-30% in terms of prothrombin activity. The incidence of thromboembolic and hemorrhagic complications is expressed as the number of episodes per 100 patient/years. Thromboembolic episodes were 2.6 (1.3 fatal) in group A while they were 1.08 (0.27 fatal) in group B; the reduction of fatal thromboembolic events was statistically significant (p less than 0.05). Hemorrhagic episodes were 1.9 (0.63 fatal) in group A while they were 0.81 (0 fatal) in group B. We concluded that an organized control of oral anticoagulant treatment in patients with artificial heart valves is advantageous as it significantly reduces fatal thromboembolism. Moreover, it could reduce the incidence of total thromboembolic and hemorrhagic episodes by more than 50%.

The optimal therapeutic range for oral anticoagulant treatment as suggested by fibrinopeptide A (FpA) levels in patients with heart valve prostheses.

Fibrinopeptide A is a good marker of in vivo thrombin formation. The aim of oral anticoagulants (OA) is to lower in vivo thrombin formation. We therefore assessed FpA levels on several occasions in 38 patients receiving OA for artificial heart valve prostheses and in 20 patients receiving OA for biological heart valve prostheses. The mean FpA level, 1.82 ng ml-1 (SEM 0.14, n = 176), in patients with artificial valves was significantly higher than the mean, 1.02 ng ml-1 (SEM 0.4), obtained in 41 healthy subjects (P = 0.01). FpA mean value for biological valves was 1.41 ng ml-1 (SEM 0.14, n = 76), which was not significantly higher than controls (P = 0.08). A decrease in FpA levels, for both artificial and biological heart valve prostheses, was associated with a parallel increase in the intensity of anticoagulation. When considering FpA values obtained in the optimal therapeutic range for oral anticoagulant treatment, (International Normalized Ratio [INR] between 3 and 4.5), the mean level for artificial valves, 1.87 ng ml-1 (SEM 0.18, n = 102), was significantly higher than the mean value, 1.25 ng ml-1 (SEM 0.16, n = 55), obtained for biological valves. From a biological point of view, this indicates that artificial valves should be kept at a higher intensity of anticoagulation.

Adenosine diphosphate (ADP)-induced alpha-granules release from platelets of native whole blood is reduced by ticlopidine but not by aspirin or dipyridamole.

A brief contact between native whole blood and ADP promotes a dose-dependent release of platelet alpha-granules without a fall in the platelet number. We assessed the "ex vivo" effect of three widely used antiplatelet drugs, aspirin dipyridamole and ticlopidine, on this system. Aspirin (a single 800 mg dose) and dipyridamole (300 mg/die for four days) had no effect, while ticlopidine (500 mg/die for four days) significantly reduced the alpha-granules release for an ADP stimulation of 0.4 (p less than 0.02), 1.2 (p less than 0.01) and 2 microM (p less than 0.01). No drug, however, completely inhibits this early stage of platelet activation. The platelet release of alpha-granules may be related to platelet shape change of the light transmission aggregometer and may be important "in vivo" by enhancing platelet adhesiveness and by liberating the platelet-derived growth factor.

[Emergency surgical treatment of spontaneous internal fistulas of the digestive tract]. / Trattamento chirurgico d'urgenza delle fistole interne spontanee del tubo digerente.

The Authors report 16 cases of gastrointestinal fistulas which have been observed during the last 5 years in the Emergency Surgery Division of Milan's Fatebenefratelli Hospital. We have considered only the cases of fistulas between two hollow abdominal organs and which have occurred spontaneously, following local pathology (cholelithiasis, neoplasms, abscesses etc.) and not from iatrogenic causes. Of these 16 patients, all surgically treated, 9 were female and 7 male, their age ranging from 24 to 77 years (average: 58 years). The medium post-operative period was of 11 days; the overall mortality was of 2 patients (12,5 per cent). These, having presented at surgery a serious stercoraceous peritonitis, died of septic shock.