Preoperative chemotherapy in early-stage (stage IB-IIIA) resectable non small cell lung cancer. Is it justified?

Only 20-30% of patients with non small cell lung cancer (NSCLC) present with early-stage disease at the time of diagnosis and may benefit by surgical resection. Five-year survival in early-stage disease varies from 38 to 57% for stage IB and from 13 to 23% for stage IIIA according to the clinical and pathological assessment of the patients. Occult micrometastatic disease already present in many patients with resectable NSCLC at the time of diagnosis and surgical treatment leads to local and distant disease recurrence. Therefore a more systemic approach should be considered in early-stage disease. The role of adjuvant chemotherapy has already been established in this field. Within the past decade attention has been focused on the possible beneficial effects of preoperative chemotherapy considering that patients' compliance to the induction treatment can be very high with eventual eradication of micrometastatic disease and primary tumor downstaging. In this review we present the currently available data on induction chemotherapy followed by surgery in early-stage (stages IB-IIIA) NSCLC with a fundamental question to be answered: is this approach justified in current clinical practice?

Surgery after induction chemoradiotherapy for non small cell lung cancer: when and why.

Stages I and II non small cell lung cancer (NSCLC) are primarily treated by anatomic pulmonary resection. Selected patients with stage IIIB disease are still candidates for surgical treatment. Unfortunately most patients with locally advanced NSCLC don't benefit by surgery alone or even by the combination of chemotherapy and radiotherapy. In order to achieve local and distant disease control, which seems to be the cause of failure of the above mentioned treatments, surgery after induction chemoradiotherapy has been proposed. This approach seems to be the state of the art of therapy for these patients improving survival but with eventual increased risks, especially pulmonary and septic complications. This review of previously published studies indicates the important role of this combined treatment in terms of survival and its risks related either to induction treatment or to surgery.

Carcinoid tumour behind bronchiectasis.

This report describes a female patient with bronchiectasis, presented to our department with recurrent hemoptysis. Bronchoscopy revealed nothing else but blood arising from the upper lobe bronchus. High resolution computing tomography of the lung (HRCT) revealed bronchiectasis of the upper lobe. A right upper lobectomy was performed. Behind bronchiectasis multiple nodular lesions, 5-10 mm were observed. Histological and immunohistochemical examination revealed findings consistent with peripheral typical bronchial carcinoids.

Screening biomaterials with a new in vitro method for potential calcification: porcine aortic valves and bovine pericardium.

Calcification is still a major cause of failure of implantable biomaterials. A fast and reliable in vitro model could contribute to the study of its mechanisms and to testing different anticalcification techniques. In this work, we attempted to investigate the potential calcification of biomaterials using an in vitro model. We purposed to test the ability of this model to screening possible anticalcification efficacy of different biomaterials. Porcine heart valve (PAV) and bovine pericardial (BP) tissues, fixed with glutaraldehyde were immersed into biological mimicking solution, where the pH and the initial concentrations of calcium and phosphoric ions were kept stable by the addition of precipitated ions during calcification. Kinetics of calcification was continuously monitored. The evaluation of biomaterials was carried out by comparing the kinetic rates of formation of calcific deposits. After 24 h, the calcific deposits on PAVs were found to be developed at significant higher rates (ranged from 0.81 x 10(-4)-2.18 x 10(-4)mol/min m2) than on BP (0.19 x 10(-4)-0.52 x 10(-4)mol/min m2) (one-way ANOVA, p < 0.05) depending on the experimental conditions (supersaturation of the solution). Parallel tests for similar biomaterials implanted subcutaneously in animal (rat) model showed after 49 days that significant higher amounts of total minerals deposited on PAV (236.73+/-139.12, 9 animals mg minerals/g dry net tissue) (mean+/-standard deviation) compared with that formed on BP (104.36+/-79.21, #9 mg minerals/g dry net tissue) (ANOVA, p < 0.05). There is evidence that in vitro calcification was correlated well with that of animal model and clinical data.

Recurrent catamenial hemothorax.

Endometriosis is a common cause of chronic pelvic pain and infertility affecting women of reproductive age, but the disease in rare conditions may be extragenital so may be present with a variety of symptoms. This is a report of an unusual case of pelvic endometriosis that presented with a recurrent hemothorax.

Donor lung pretreatment with surfactant in experimental transplantation preserves graft hemodynamics and alveolar morphology.

In experimental lung transplantation, the reduction of endogenous surfactant properties occurs after graft preservation and transplant reperfusion. The aim of this study was to evaluate the efficacy of donor lung pretreatment with exogenous surfactant on graft damage after ischemia and reperfusion. Fourteen (control group A, n = 8; study group B, n= 6) young female white pigs (mean weight 27 +/- 3.5 kg) were used in a newly developed autotransplantation model within situcold ischemia. In study group B, before thoracotomy, 1.5 ml/kg surfactant apoprotein-A-free surfactant was administrated into the left main bronchus via flexible bronchoscopy. Belzer UW solution was used for lung preservation. Cold ischemia was achieved for 3 hr with interlobar lung parenchyma temperature at 8 +/- 1.3 degrees C, and central temperature maintained at 37.20 +/- 0.5 degrees C. Animals were sacrificed after 3 hr of graft reperfusion. At the end of reperfusion, pulmonary vascular resistance index (was 447.80 dyn/sec.cm(5).m(2)(+/-66.8) in group A vs 249.51 in group B (P< 0.001) and serum nitric oxide was adequately preserved. The mean alveolar surface area estimated by computerized morphometry was 5280.84 (4991.1) microm(2)(group A) vs 3997.89 (3284.70) microm(2)(group B;P< 0.005). Histology revealed milder macrophage and lymphocyte infiltration in group B at the end of reperfusion. Pretreatment of donor lung with an surfactant apoprotein-A -free surfactant agent appears to be beneficial in terms of maintaining serum NO and reducing hemodynamic disturbances. Furthermore, alveolar histology and stereomorphology are better preserved.

Treatment of postoperative bronchobiliary fistula by nasobiliary drainage.

Bronchobiliary fistula (BBF) is a rare condition. It may present as a complication of echinococcal or amebic liver disease. Management of such a fistula can be very difficult and is often associated with a high rate of morbidity and mortality. We report the case of a 70-year-old woman who presented with a BBF after a one-stage operation for hydatid cysts of the liver and lung that were approached via thoracotomy and transdiaphragmatic incision. The cause of the BBF was an inflammatory collection in the residual liver cavity due to inadequate drainage. This collection eroded the sutured diaphragm, and because of the existing adhesions, it perforated directly into the bronchial system at the area of the previous cystectomy. Initially, endoscopic sphincterotomy was performed to achieve biliary decompression by equalizing intrabiliary and duodenal pressure, but no significant improvement was seen. Subsequently, nasobiliary drainage was instituted by means of an endoscopically inserted, nasobiliary catheter, which further reduced biliary pressure and facilitated biliary flow to the duodenum, as opposed to the fistulous tract. The fistula was successfully closed in a short time. This conservative method reduces the risks of reoperation. Therefore, it should be considered the treatment of choice in the management of bronchobiliary fistula.

Virtual endoscopy in the diagnosis of an adult double tracheal bronchi case.

We report a case of ipsilateral double tracheal bronchi supplying a tracheal lobe in a 42-year-old man, who presented with a 10-year history of recurrent respiratory infections. Diagnosis was established by chest computed tomography (CCT), virtual endoscopy and bronchoscopy. Both bronchi were surgically resected along with the right upper lobe of the lung and the associated tracheal lobe. To our knowledge, this is the first report of ipsilateral double tracheal bronchi in the adult life to be diagnosed and treated on the basis of modern radiological techniques and especially virtual endoscopy findings.

The potential role of bcl-2, bax, and Ki67 expression in thymus of patients with myasthenia gravis, and their correlation with clinicopathologic parameters.

OBJECTIVE: The aim of this study was to evaluate bcl-2, bax (apoptotic-oncoproteins), and Ki67 (cell proliferation-marker) expression in thymus of patients with myasthenia gravis (MG) and to determine the potential correlation with clinicopathologic parameters. METHODS: The study was done on 38 patients (16 males, 22 females; mean age 38+/-10 years) with MG who underwent modified maximal thymectomy (MMT). Clinical staging (Osserman classification) included stage I in three, IIA in 19, IIB in 13 and III in three. Microscopic examination of thymus showed thymic hyperplasia in 19, atrophy in eight, thymoma in nine and thymic carcinoma in two. On paraffin sections, the streptavidin-biotin technique, using antibodies to bcl-2, bax, and Ki67, was employed, and in situ hybridization with digoxigenin-labeled probes to bcl-2 and bax was performed. In addition, the apoptotic body index (ABI) was assessed via the TUNEL method. Staining results were correlated with clinicopathologic parameters. RESULTS: Bcl-2 expression was higher in hyperplasia and thymoma cases, compared to thymic carcinomas (P<0.001). Higher expression in carcinomas, compared to hyperplasia and thymomas, was observed for bax (P<0.001), Ki67 (P<0.001) and ABI (P<0.001). Statistical analysis demonstrated: (A) positive correlation of bax+ cells with MG stage (P<0.001), ABI and %Ki67+ cells with MG stage (P<0.001, respectively), %Ki67+ and %bax+ cells with ABI (P<0.05); and (B) reverse correlation between %bcl-2+ cells and MG stage (P<0.05). CONCLUSIONS: In patients with MG who underwent MMT, bcl-2, bax, and Ki67 expression correlates positively or reversibly with the microscopic findings of thymus. Increased apoptosis and proliferation accompany advanced disease stage and possible worse prognosis.

Blood use in lung resection for carcinoma: perioperative elective anaemia does not compromise the early outcome.

OBJECTIVE: Blood transfusion may adversely affect the prognosis following surgery for non-small cell lung carcinoma (NSCLC). Conventionally by most thoracic surgeons, a perioperative haemoglobin (Hb) less than 10 g/dl has been considered a transfusion trigger. In this prospective trial we have (a) evaluated the overall blood transfusion requirements and factors associated with an increased need for transfusion and (b) in a subsequent subset of patients, tested the hypothesis that elective anaemia after major lung resection may be safely tolerated in the early postoperative period. METHODS: A total of 198 (M/F 179/10, mean age 61.2, range 32--85 years) patients suffering from NSCLC were submitted to pneumonectomy (n = 89), bilobectomy (n = 19) and lobectomy (n = 90). A rather strict protocol was used as a transfusion strategy. The transfusion requirements were analyzed and seven parameters (gender, age > 65, preoperative Hb < 11.5 g/dl, chest wall resection, history of previous thoracotomy, pneumonectomy and total blood loss) were statistically evaluated by univariate and logistic regression analysis. Subsequently, according to the perioperative Hb level during the first 48 h, patients were divided into group A (n = 49, Hb = 8.5--10) and group B (n = 149, Hb > 10) with a view to estimate the risks of elective perioperative anaemia. Groups were comparable in terms of age, sex, type of operation performed, preoperative Hb, creatinine level, FEV1, arterial blood gases and history of heart disease. RESULTS: The overall transfusion rate was 16%. Univariate analysis revealed that preoperative Hb < 11.5 g/dl (P < 0.01) and total blood loss (P < 0.0001) were associated with increased need for transfusion, but only the total blood loss was identified as an independent variable in multivariate analysis. Statistical analysis between groups A and B showed no significant difference regarding postoperative morbidity and mortality: atelectasis (3 vs. 6), chest infection (2 vs. 9), sputum retention requiring bronchoscopy (5 vs. 12), admission to intensive care unit (5 vs. 7), ARDS (0 vs. 3), postoperative hospital stay (7.7 +/- 2.6 vs. 9.1 +/- 3.8 days) and deaths (1 vs. 3). CONCLUSIONS: The use of a strict transfusion strategy could help in reducing overall blood transfusion. Furthermore, a perioperative Hb of 8.5--10 g/dl could be considered safe in elective lung resections for carcinoma.

Bronchial carcinoid of an accessory tracheal bronchus.

We present a rare case of bronchial carcinoid tumor arising in an accessory right tracheal bronchus and involving the associated tracheal lobe in a 48-year-old man, who presented with a history of recurrent respiratory infections and recent onset of hemoptysis. Diagnosis was established on preoperative bronchoscopy and biopsy. The tumor was completely removed by right upper lobectomy with the tracheal bronchus resected flush to its origin from the right lower tracheal wall. Final histology revealed a typical carcinoid tumor.

Non-invasive estimation of pulmonary arterial hypertension in chronic obstructive pulmonary disease.

The feasibility and reliability of the combination of several noninvasive methods using a multivariate method of analysis to predict pulmonary artery hypertension (PAH) is evaluated in 20 patients with chronic obstructive pulmonary disease. These methods comprised arterial blood gases (Pao2, Paco2), pulmonary functional parameters (FEV1), echo-Doppler parameters (tricuspid regurgitation jets, acceleration time on pulmonary valve), computed tomography measurements (transhilar distance, hilar thoracic index, and measurement of the descending branch of the right pulmonary artery to the lower lobe). A multiple stepwise regression analysis (including one Doppler parameter, two parameters of arterial blood gases, and one functional parameter) revealed a coefficient of determination (R2) equal to 0.954 for mean pulmonary artery pressure (MPAP) with a standard error of estimate (S.E.E.) of 5.25 mmHg. A stepwise regression analysis including computed tomography and radiographic parameters revealed an R2 equal to 0.970 for PAP with a S.E.E. of 4.26 mmHg. Logistical regression analysis classified correctly 80% of patients with PAH using noninvasive methods such as the diameter of the main pulmonary artery and the diameter of the left pulmonary arterial branch calculated by computed tomography. Not only the presence of PAH but also the level of MPAP can be estimated by the combination of multiple stepwise and logistical regression analyses.

Long-term results of reoperations for recurrent angina with internal mammary artery versus saphenous vein grafts.

OBJECTIVE: To evaluate the long term results of coronary reoperations for recurrent angina with internal mammary (thoracic) arteries versus vein grafts. DESIGN: Inception cohort of 103 patients with a mean follow up of 7.1 years (range 1.0-11.6). SETTING: Regional cardiothoracic centre. PATIENTS: Among 103 consecutive patients, mean (SD) age 61.8 (9.7) years, who were reoperated for recurrent angina between January 1982 and December 1991, 53 patients had unilateral or bilateral internal mammary artery (IMA) grafting supplemented or not with saphenous vein (SV) grafts (group A), and 50 patients underwent reoperative coronary surgery using SV grafts only (group B). The two groups were comparable in terms of demographic and clinicopathological data. MEASUREMENTS AND RESULTS: Operative mortality was 5.6% (95% confidence interval 4.6 to 6.6) for group A, and 10% (8.2 to 11.8) for group B (p > 0.05). Probability of freedom from new recurrence of angina was 86% at 5 and 10 years in group A, compared with 56% and 25% respectively in group B (p = 0.005). Freedom from cardiac events was estimated to be 81% at 5 and 10 years in group A, v 52% and 20% for group B, respectively. Actuarial survival was 95% v 93% at 3 years, 95% v 85% at 5 years, and 88% v 71% at 10 years after reoperation (p > 0.05). CONCLUSIONS: The long term results of IMA are superior to SV grafts in terms of freedom from new recurrence of angina and other cardiac events. The IMA is thus the conduit of choice in coronary revascularisation.

Neuronal cell death in the ischemic spinal cord: the effect of methylprednisolone.

BACKGROUND: Cell death occurs by either necrosis or apoptosis. The role of apoptosis in the neuronal degeneration after ischemia remains to be defined. We studied (1) the nature of neuronal death and (2) the neuroprotective action of methylprednisolone in a rat model of spinal cord ischemia. METHODS: Spinal cord ischemia was induced in adult Long-Evans rats by occluding the aortic arch for 14 minutes and simultaneously equilibrating the femoral artery pressure to the atmospheric pressure. Twenty rats were subjected to ischemia without treatment and another twenty to ischemia after treatment with methylprednisolone (30 mg/kg, 4 hours before ischemia). The animals were sacrificed and the lumbar spinal cords were examined on postoperative days 1 and 2. RESULTS: On day 1, neurons with morphology indicative of apoptosis were present in the gray matter. Their numbers increased from the ventral to the dorsal location. There were significantly fewer apoptotic neurons in the dorsal horn of the methylprednisolone-treated animals. DNA obtained from the spinal cord of untreated rats on days 1 and 2 showed laddering after electrophoresis, a feature of apoptosis. Pretreatment with methylprednisolone inhibited the development of DNA laddering. Methylprednisolone treatment was not associated with significantly improved neurologic function in the postoperative period. CONCLUSIONS: Apoptotic neuronal death occurs in the rat spinal cord after transient ischemia and is attenuated by pretreatment with methylprednisolone.

Reoperations on the aortic root and ascending aorta.

BACKGROUND: Reoperations on the aortic root and the ascending aorta are being performed with increasing frequency and remain a challenging problem. METHODS: Eighty-one patients (age range, 14 to 78 years) underwent reoperations on the aortic root or the ascending aorta during a 14.5-year interval ending October 1996. The previous operations were aortic valve procedure (28%), coronary artery bypass grafting (25%), aortic root replacement (24%), ascending aortic replacement (19%), and miscellaneous (5%). Twenty-two patients (27%) had had two or more previous operations. The principal indications for reoperation were true or false aneurysm (35%), acute or chronic dissection (28%), and malfunction of an aortic valve substitute (27%). The reoperations performed were aortic root replacement (composite graft, allograft, or autograft) in 48 patients and graft replacement of the ascending aorta in 33 patients. Concomitant procedures included aortic arch replacement in 43 patients (55%) and coronary artery bypass grafting in 33 patients (41%). RESULTS: The 30-day mortality rate was 8.6% (7 patients). It was 8.3% for aortic root replacement and 9.1% for ascending aorta replacement (p > 0.05). Using stepwise multivariate logistic regression analysis of 23 variables, preoperative functional class III/IV (p = 0.047) and duration of cardiopulmonary bypass (p = 0.007) were significant independent predictors of early death. The mean duration of follow-up was 3.6 years. The 1-year, 5-year, and 10-year survival rates were 89%, 81%, and 69%, respectively. Freedom from reoperation on the heart or ascending aorta was 98%, 92%, and 69%, respectively. Reoperation for false aneurysm (p = 0.050) and the presence of coexisting coronary artery disease requiring bypass grafting (p = 0.010) were the only significant predictors of late mortality. CONCLUSIONS: Reoperations on the aortic root and the ascending aorta can be accomplished with acceptable early mortality and satisfactory long-term results. More frequent resection of the aneurysmal or dissected segments of the ascending aorta and aortic root at the initial operation may reduce the need for subsequent reoperation.

Late survival and predictors of recurrent angina after coronary artery reoperation.

Although coronary artery reoperations are now well established, there is limited information concerning factors predisposing to further recurrent angina after a successful second bypass operation. We have retrospectively evaluated the late (10-year) results, and identified predictors associated with poor long-term outcome, of fifty-seven consecutive patients, mean age 54.8 (SD = 9.7) years, range 43 to 67 years, reoperated on for recurrent angina (RA) between January 1980 and May 1988. Twenty-four factors possibly influencing the probability of further recurrence of angina (FRA) were evaluated, comparing operative survivors who developed FRA with those who remained symptom-free during a complete follow-up study period ranging from 35 to 134 months. Reoperative mortality was 8.7% [95% confidence limits (95% CL) 6.7 to 11%]. Survival analysis (Kaplan-Meier) revealed 94% at 3 (95% CL +/- 7%), 90% at 5 (95% CL +/- 8%) and 83% at 10 years (95% CL +/- 12%). Probability of freedom from FRA was 88%, 73%, and 56% at 1, 5, and 10 years, respectively. Using univariate analysis, female sex (p < 0.05), time between 1st operation and RA (p < 0.005), family history of ischaemic heart disease (IHD) (p < 0.01), obesity (p < 0.001), time between 1st and 2nd operation (p < 0.001), and the non-use of internal mammary artery at reoperation (p < 0.0001) were associated with increased incidence of FRA. Independent risk-factors, by multivariate analysis (Cox's proportional hazards), were: family history of IHD (p = 0.006), triple-vessel disease (p = 0.024), obesity (p = 0.052), and time interval-between 1st and 2nd operation (p = 0.046). We conclude that reoperative surgery results in satisfactory long-term survival and angina-free interval. Patients with a short time interval between reoperations, family history of IHD, obesity, triple-vessel disease, and non-use of internal mammary artery at reoperation are at higher risk of developing further recurrent angina, and, therefore, more likely to require a subsequent revascularisation procedure.

Management of non resectable malignant esophageal stricture and fistula.

OBJECTIVE: The palliation of dysphagia caused by esophageal carcinoma and other inoperable tumours obstructing the esophagus presents a challenge for the thoracic surgeon, in particularly when associated with fistula (F). In a prospective study over the last 5 years, we have evaluated the effectiveness of different approaches and types of prostheses to solve the above problem. METHOD: Thirty three patients (mean age: 63.5 years, range 42-76, M/F:24/9) with inoperable tumours obstructing the esophagus underwent intubation and/or palliative surgery according to the following protocol: (1) Preoperative esophagography; (2) endoscopy and biopsy; (3) dilatation and insertion of prosthesis usually under general anaesthesia; and (4) re-evaluation the following day, in 30 days and as required thereafter. Prosthesis used were: Atkinson 3, Wilson-Cook (plain) 12, Wilson-Cook (cuffed) 4, Strecker (metallic self-expandable) 13. The patients were divided in three groups according to the extension of the disease: group A (n = 19) plain malignant strictures, group B (n = 5) strictures with respiratory Fs, group C (n = 9) strictures with mediastinal or pleural Fs. RESULTS: All patients of group A had successful palliation irrespectively of prosthesis used and site of obstruction. One patient required two stents. There was no death and 50% survival at 6 months was 70%. In group B, a cuffed prosthesis successfully closed two bronchoesophageal Fs, while three patients underwent retrosternal bypass surgery. There was one death on the 26th postoperative day. In group C, one Strecker, two plain Wilson-Cook and two cuffed Wilson-Cook stents, although initially succeeded, in due course, failed to block the Fs in five patients who subsequently underwent bypass surgery with one death. With four patients both leak and dysphagia were significantly improved with the use of self-expandable stents therefore, not requiring surgery. Overall, there were two deaths but no failure in palliating dysphagia. Longer survival was 20 months. Patients with fistulae had poorer prognosis as compared to those suffering from plain malignant stricture (P = 0.01). CONCLUSIONS: Plain malignant inoperable oesophageal strictures can be successfully palliated with intubation. Complicated with fistula strictures, however, are difficult to manage and have a poor prognosis. Due to the fact that bypass surgery is associated with an increased mortality, it should be kept for those with late stent failures and fistula recurrences.

Advanced non-small cell lung cancer chemotherapy: a randomized trial of two active regimens (MVP and PE).

The treatment of advanced or metastatic NSCLC remains a controversial issue and cisplatin-based combination chemotherapy is by far the most common treatment. Two of these cisplatin-based standard combinations, MVP and PE, were compared in this study in order to evaluate their response rates and survival times. Eighty-five previously untreated NSCLC patients were randomly selected to receive either MVP or PE and 72 of these patients were eligible for evaluation for response rate and survival. Response rates for MVP were: CR 11%, PR 35%, SD 19% and PD 35% and for PE: CR 0%, PR 26%, SD 22% and PD 52%. The median survival time was 9.7 months for MVP and 6.9 months for PE. Both schedules were well tolerated. The administration of MVP in advanced NSCLC resulted in superior response rates and survival times over those produced by PE.