What can platinum offer yet in the treatment of PS2 NSCLC patients? A systematic review and meta-analysis.

BACKGROUND: Randomized phase III trials showed interesting, but conflicting results, regarding the treatment of NSCLC, PS2 population. This meta-analysis aims to review all randomized trials comparing platinum-based doublets and single-agents in NSCLC PS2 patients. MATERIALS AND METHODS: Data from all published randomized trials, comparing efficacy and safety of platinum-based doublets to single agents in untreated NSCLC, PS2 patients, were collected. Pooled ORs were calculated for the 1-year Survival-Rate (1y-SR), Overall Response Rate (ORR), and grade 3-4 (G3-4) hematologic toxicities. RESULTS: Six eligible trials (741 patients) were selected. Pooled analysis showed a significant improvement in ORR (OR: 3.243; 95% CI: 1.883-5.583) and 1y-SR (OR: 1.743; 95% CI: 1.203-2.525) in favor of platinum-based doublets. G3-4 hematological toxicities were also more frequent in this group. CONCLUSION: This meta-analysis suggests that platinum-combination regimens are superior to singleagent both in terms of ORR and survival-rate with increase of severe hematological toxicities.

Use of a sealant to prevent prolonged air leaks after lung resection: a prospective randomized study.

BACKGROUND: Pulmonary air leaks are common complications of lung resection and result in prolonged hospital stays and increased costs. The purpose of this study was to investigate whether, compared with standard care, the use of a synthetic polyethylene glycol matrix (CoSeal®) could reduce air leaks detected by means of a digital chest drain system (DigiVent™), in patients undergoing lung resection (sutures and/or staples alone). METHODS: Patients who intraoperatively showed moderate or severe air leaks (evaluated by water submersion tests) were intraoperatively randomized to receive just sutures/staples (control group) or sutures/staples plus CoSeal® (sealant group). Differences among the groups in terms of air leaks, prolonged air leaks, time to chest tube removal, length of hospital stay and related costs were assessed. RESULTS: In total, 216 lung resection patients completed the study. Nineteen patients (18.1%) in the control group and 12 (10.8%) patients in the sealant group experienced postoperative air leaks, while a prolonged air leak was recorded in 11.4% (n=12) of patients in the control group and 2.7% (n=3) of patients in the sealant group. The difference in the incidence of air leaks and prolonged air leaks between the two groups was statistically significant (p=0.0002 and p=0.0013). The mean length of hospital stay was significantly shorter in the sealant group (4 days) than the control group (8 days) (p=0.0001). We also observed lower costs in the sealant group than the control group. CONCLUSION: The use of CoSeal® may decrease the occurrence and severity of postoperative air leaks after lung resection and is associated with shorter hospital stay. TRIAL REGISTRATION: Not registered. The trial was approved by the Institutional Review Board of the IRCCS-CROB Basilicata Regional Cancer Institute, Rionero in Vulture, Italy.

How to distinguish an active air leak from a pleural space effect.

AIM: We aimed to distinguish a pleural space effect from an active air leak, using a digital chest drain system that provided continuous air flow and pleural pressure checks. METHODS: between March 2010 and October 2011, we employed 144 digital drains for 138 thoracic surgical procedures. RESULTS: We observed 18 (12.5%) active air leaks, among which 4 (2.8%) were prolonged air leaks characterized by high differential pleural pressure due to increased mean expiratory pressure (>1 cm H(2)O; p<0.0001), and 3 (2.1%) late air leaks, all long-lasting (p<0.0001), predicted by pressure curve divergence before the air flow appearance. We also reported 25 (17.4%) pleural space effects characterized by a high differential pleural pressure, but mainly due to a lower mean inspiratory pressure (<20 cm H(2)O; p<0.0001), and especially related to surgical pleurodesis procedures (p<0.0003) and wide lung resections (p<0.0002); there was no increasing pneumothorax after provocative clamping. CONCLUSIONS: A digital chest drain system, ensuring continuous air flow and pleural pressure measurement, could clearly identify a pleural space effect, avoiding the frequent misinterpretation of an active air leak, and allowing safe removal of the chest tube at the right time.

[Solitary metachronous metastasis of the sternum from pancreatic adenocarcinoma]. / Metastasi umica metacrona dello sterno da adenocarcinoma del pancreas.

Sternal metastases from adenocarcinoma of the pancreas are extremely rare, and even more so when solitary. Two years earlier, the patient reported on here, a 67-year-old man with a solitary osteolytic lesion of the sternal manubrium, had undergone a duodeno-cephalopancreatectomy for adenocarcinoma of the pancreas (G2, pY3, pN1) followed by adjuvant radio-chemotherapy. PET/CT scans, in response to the onset of burning pain in the sternal region, revealed a hypermetabolic area only at the level of the manubrium, while MRI showed a bulging manubrium due to the presence of extensive solid pathological tissue towards the right articulations of the ribs. Abnormal tumour markers were: CEA = 12, n.v. 0-4; Ca 15-3 = 512, n.v. 0-51, Ca 19-9 = 8777, n.v. 0-18. A partial sternectomy was performed with en-bloc resection of the hemiclavicles and the anterior tract of the 1st and 2nd ribs bilaterally with a mediastinic lymphadenectomy and repair with a sandwich prosthesis of prolene mesh and methacrylate, protecting the supra-aortic trunks and the anonymous vein with a polytetrafluoroethylene patch. The histological examination revealed secondary adenocarcinoma with 3 mediastinal metastatic lymph nodes. In view of the severe prognosis, a resection with palliative intent was also performed, which, when carried out in specialised centres, presents no contraindications in terms of cost-benefits.

Chemical pleurodesis to improve patients' quality of life in the management of malignant pleural effusions: the 15 year experience of the National Cancer Institute of Milan.

We analyzed chemical pleurodesis role in recurrent neoplastic pleural effusions management, performed by two different techniques: VATS and minimal lateral thoracotomy. We compared the results obtained using the two different procedures, and we also evaluated the two sclerosing agents used (talc and alcohol). From January 1987 to March 2002, we treated 565 patients with malignant pleural effusion: 355 (63%) by VATS and 210 (37%) through mini-thoracotomy all of them underwent chemical pleurodesis: 442 (78%) by means of talc and 123 (22%) by alcohol. Chemical pleurodesis therapeutic success was globally obtained in 436 patients (77%). Dealing with surgical approaches, VATS reduced operating time (33 versus 44 minutes: P < 0.001), mean drainage time (3 versus 5 days: P < 0.001), complications (2% versus 7%: P = 0.006) and mean postoperative course (5 versus 7 days: P < 0.001). Therapeutic success of VATS-treated patients was 81% versus 65% of those undergoing thoracotomy (P < 0.001). We obtained a significantly lower relapse rate in the patients of all the two groups treated with talc versus alcohol (12% versus 35% in VATS group and 25% versus 59% in thoracotomic group). Our data indicate that chemical pleurodesis represents a good palliative treatment of neoplastic pleural effusion. Talc was superior to alcohol as sclerosant agent regardless of the surgical procedure. Comparing the two techniques, VATS should be preferred to minimal thoracotomy. We can suggest talc pleurodesis by VATS as the choice treatment in case of recurrent pleural effusions.

[Iatrogenic hemothorax and unknown spontaneous rupture of the oesophagus, double dramatic disease]. / Emotorace iatrogeno e rottura spontanea misconosciuta dell'esofago, doppio evento drammatico.

Iatrogenic haemothorax is a dramatic event and generally lethal if not treated appropriately and rapidly. Any thoracic co-morbidity increases the risk of death. Spontaneous rupture of the oesophagus is an equally lethal illness if not treated. We report a case of left haemothorax after a thoracic drain for spontaneous pneumothorax with ipsilateral effusion in a 77-year old male. The patient was operated on 6 hours after admission to hospital. We found a laceration of the left common carotid and an unsuspected rupture of the supradiaphragmatic oesophagus. Repair of the lesions in a single session led to no further complications. The patient was discharged in good condition. We know of only one case in the literature with Boerhaave's syndrome not treated surgically, whereas all the other cases had a negative outcome if surgery was not performed promptly. The non-specific symptoms in our case delayed the correct diagnosis of the spontaneous rupture of the oesophagus. The mortality rate is 31% in the literature even when there is an early diagnosis with well performed surgical reapair. A rapid decision as to the best surgical tactics and sending these patients to referral centres specialising in oesophageal disease are the keys to achieving good results.

The real impact and usefulness of video-assisted thoracoscopic surgery in the diagnosis and therapy of clinical lymphadenopathies of the mediastinum.

BACKGROUND: The aim of this study was to evaluate the impact of video-assisted thoracoscopic surgery (VATS) in the diagnosis and therapy of clinical mediastinal lymphadenopathies. METHODS: In our Institute, from 1995 to 2001, 85 patients underwent VATS biopsy: 55 subjects (group 1) for suspected lung cancer (65%) and 30 (group 2) for unknown nodes enlargement (35%). Lymphonodes were considered suspected if > 1 cm by radiological imaging. We performed 83 thoracoscopic biopsies: 33 in level 5 (39%), 24 in level 6 (29%), 19 in level 7 (22%), and 7 in level 8 (8%). RESULTS: A histological analysis of frozen sections was made in every case. Twenty subjects underwent lung resection in one-time (24%). Histology in group 1 was adenocarcinoma in 28 cases, epidermoid carcinoma in 14, microcytoma in 9, and giant-cell carcinoma in 4. Ten patients were at stage I, 10 at stage II, 33 at stage III, and two at stage IV. Histology of group 2 was lymphoma in 18 cases, sarcoidosis in eight, and focal aspecific hyperplasia in four. CONCLUSION: The usefulness of VATS allowed the pathological assessment of the presumed involved mediastinal lymph nodes in every patient and thus permitted to assure in all the cases the indicated therapeutic treatment.

Cauterization versus fibrin glue for aerostasis in precision resections for secondary lung tumors.

BACKGROUND: Aerostasis control in multiple resections for metastatic pulmonary diseases is a real problem. Long-term air leaks prolong postoperative hospitalization and result in an additional financial burden on the healthcare system. We focused our study on the evaluation of fibrin glue (Tissucol) as an effective means to minimize or prevent air leaks. METHODS: We initiated a case-control study whereby 100 patients underwent precision resections for lung metastases. The subjects were divided into 2 groups, both with 50 patients: group 1 was treated with fibrin glue and group 2 with cauterization. Evaluation parameters consisted of the following: air leak duration, expected complications, drain time, and in-hospital stay. RESULTS: In group 1, air-leak time was 2.68 +/- 1.72 days, versus 7.80 +/- 8.52 for group 2 (P <.001). In group 1, there were 2% complications, whereas in group 2 there were 28% (P <.001). Drain time was 4.54 +/- 1.83 days for group 1 and 9.54 +/- 8.35 for group 2 (P <.001). In-hospital stay was 6.54 +/- 1.83 days for group 1 and 11.54 +/- 8.35 for group 2 (P <.001). CONCLUSIONS: In the group treated with fibrin glue, we observed significant advantages. Our experience shows that the use of fibrin glue can improve aerostasis control in nonanatomical resections with high risk of air leak.

[Complete surgical resection of a huge thoracic mass consisting in a localized fibrous tumor simulating a high-grade malignant neoplasm]. / Asportazione chirurgica completa di una enorme massa toracica riferibile a tumore fibroso localizzato simulante una neoplasia di alto grado di malignità.

Solitary fibrous tumour is an infrequent neoplasm generally arising from the parietal and visceral pleura. The diagnosis may be difficult in the presence of a history of malignant disease owing to the different presentations and to radiological findings of evident invasiveness. The authors report the case of a woman with a right giant fibrous solitary tumour of the pleura twenty years after a subcutaneous mastectomy with axillary dissection and radiation therapy for breast cancer. The biopsy diagnosis was consistent with a probable solitary fibrous tumour of the pleura but the discrepancy with the radiological images and the difficult differential diagnosis versus a malignant sarcoma, possibly radio-induced, prompted us to verify the real features of the disease. The patient was submitted to a right anterolateral thoracotomy and partial sternotomy and the giant mass was resected enbloc with the phrenic nerve and diaphragm which proved to be the only structures tightly adhering to the neoplasm. Histological examination confirmed the diagnosis of a solitary fibrous tumour of the pleura. The patient is still alive and disease-free 30 months after the surgical operation. Fibrous solitary tumour is a disease generally characterised by a good prognosis but in particular cases, with unmistakable radiological findings of invasiveness, a precise diagnosis must be obtained in order to choose the most appropriate therapy.

A new proposal of skin-closure system for median sternotomy: usefulness and cosmetic results analysis of MEDIZIP Surgical Zipper in neoplastic immuno-compromised patients.

BACKGROUND AND OBJECTIVES: The authors evaluate the effectiveness and the cosmetic results obtained using the new skin closing system MEDIZIP Surgical Zipper in oncological immuno-compromised patients submitted to median sternotomy. METHODS: In our Institute, from 1999 to 2002, MEDIZIP was used to close the sternal wounds in 45 patients undergoing median sternotomy for bilateral metastasectomy, It took about half a minute (mean time: 32.00 +/- 11.48 sec) to perform the application. To evaluate the cosmetic results, a three-level scale was conceived: level 1: very good, level 2: satisfactory, level 3: inadequate. RESULTS: Overall forty-two 20 cm-long zippers were used, two 25 cm-long and one 30 cm-long. MEDIZIP remained in situ for an average of 9.98 +/- 2.23 days (median: 9 days; range: 8-13 days). The average time taken for inspection was 70.00 +/- 2.48 sec (median: 70, range: 45-130) and the zipper was removed in a few seconds. No wound infections were observed. We classified 39 patients at level 1 (very good, 87%), and 6 at level 2 (satisfactory, 13%). CONCLUSIONS: MEDIZIP can be considered an effective skin-closure system which is easily and quickly handled and assures good cosmetic results with non-invasive removal; it proves particularly useful in pediatric patients and in adults affected by neoplastic diseases and undergoing multiple combined anti-cancer treatments.

[Control of aerostasis in pulmonary metastasectomy by precision resection. Standard technique versus fibrin glue modification]. / Il controllo dell'aerostasi nella metastasectomia polmonare mediante precision resection. Tecnica standard versus modifica mediante colla fibrina.

The control of aerostasis after performing non-anatomical pulmonary resections constitutes a serious problem. The presence of an air leak in the postoperative period requires a prolonged thoracic drainage and consequently a longer hospital stay. The aim of our study was to evaluate the usefulness of fibrin glue and its effectiveness in the prevention of air leaks. At the Department of Thoracic Surgery of the National Cancer Institute of Milan, we conducted a case-control study in 90 patients submitted to metastasectomy for secondary lung cancer, removing multiple small nodules < or = 1.5 cm using the precision resection technique. We divided the patients into two groups, both of 45 subjects: group 1 treated with fibrin glue and group 2 submitted to cauterization of the pulmonary parenchyma. The patient characteristics were well matched for age, type of approach and operation, number of resections performed and type of pathology. The assessment parameters investigated were the duration of the air leak, expected complications, drainage time and length of hospital stay. In group 1 we performed fewer than 5 precision resections in 21 cases, from 5 to 10 in 16, and more than 10 in 8. In group 2 we executed fewer than precision resections in 21 cases, from 5 to 10 in 17, and more than 10 in 7. In group 1 the duration of the air leak was 2.93 +/- 1.91 days as against 6.95 +/- 7.01 days in group 2 (p = 0.000). In group 1 we had one complication (2%) (a long-term air leak lasting > 10 days), while in group 2 we had a long-term air leak in 11 cases (24%) (p = 0.000). Mean thoracic drainage time was 4.22 +/- 1.43 days in group 1, and 8.13 +/- 7.37 in group 2 (p = 0.000). The mean postoperative hospital stay was 6.22 +/- 1.43 days in group 1 compared to 10.13 +/- 7.37 days in group 2 (p = 0.000). In the group of patients treated with fibrin glue we obtained a significant reduction in drainage time, complications and postoperative hospital stay. The results of our experience show that the use of fibrin glue in non-anatomical resections with a high risk of developing air leakage is effective in reducing the expected complications, with a favourable impact also on the quality of life of patients with metasases.

Gold standard for sternectomies and plastic reconstructions after resections for primary or secondary sternal neoplasms.

BACKGROUND: Between January 1980 and December 1999, 88 patients underwent the surgical resection of sternal tumors: 30 primary malignant tumors, 28 local relapses or metastases from breast carcinomas, 16 other types of tumor, and 14 radionecroses. METHODS: The sternectomies were total in 8 cases, subtotal in 32, and partial in 48. Prosthetic materials covered by flaps of myocutaneous or muscle tissue were used in 55 patients, prosthetic material alone in 13, myocutaneous or muscle flaps alone in 5, and other techniques in the remaining 15. The resection was radical in 78 cases and palliative in the other 10. RESULTS: Forty-eight of the subjects who underwent radical surgery were alive and disease free at the end of the follow-up period. The expected 10-year survival of the patients treated for primary tumors is approximately 85% (Kaplan-Meier), and that of the patients with relapsing breast carcinomas is the same as after 5 years (41.8%). CONCLUSIONS: In our experience, the treatment of neoplasms by means of a broad sternal resection followed by a reconstruction based on the use of prosthetic materials is an effective and safe solution that considerably improves the quality of life and makes it possible to perform curative broad radical resections in the case of primary sternal resections.

Liposomal amphotericin B (AmBisome): efficacy and safety of low-dose therapy in pulmonary fungal infections.

A prospective study of the treatment of fungal infections with low-dose AmBisome enrolled 36 of 52 patients with thoracic malignancies who developed pulmonary fungal infections in the National Cancer Centre, Milan, over a 3.5 year period. Thirty-three high-risk patients had received standard prophylaxis with iv fluconazole. In these patients, symptoms indicating deep mycosis were detected after 7-9 days of primary prophylactic therapy. Another three patients, not treated with fluconazole, showed similar symptoms. Bronchoalveolar lavage, blood culture and/or CT scan of chest diagnosed invasive aspergillosis in 29 patients and deep invasive Candida infection in seven. AmBisome was given at 1-2.2 mg/kg/day i.v. for 10 days to avoid or decrease toxicity normally induced by amphotericin B. The fungal infection was eradicated in all 36 patients. Negative cultures were obtained after 5 or 6 days of antifungal treatment. No adverse reactions attributed to AmBisome were detected. After a follow up of 5-48 months, 30 patients were still alive. Six patients had died, two due to adult respiratory distress syndrome and four due to progression of cancer. No mycotic relapses or reinfections were detected during follow up. In a subset of critically ill patients with thoracic malignancies, the administration of low-dose liposomal amphotericin B (AmBisome) resulted in complete eradication of pulmonary Aspergillus and Candida infections, and was remarkably well tolerated.

Primary malignant mucosal melanoma of the esophagus: a case report

O melanma maligno primário é uma rara lesäo que só compreende cerca de 0,1% das neoplasias malignas primárias de esôfago. O tumor é polipóide, pedunculado, e algumas vezes ulcerado. Os sintomas se assemelham aos de portadores de carcinomas de células escamosas, tomando-se importante o diagnóstico diferencial pré-operatório. A ressecçäo cirúrgiuca é o tratamento de escolha. Radioterapia intracavitária pode ser uma forma útil de tratamento em pacientes selecionados. Relatamos o caso de um homem de 67 anos, portador de melanoma maligno primário de esôfago, que sobreviveu ainda cinco meses após submeter-se à esofagectomia