Amedeo Vittorio Bedini

Does Surgery Improve Survival of Patients with Malignant Pleural Mesothelioma?: A Multicenter Retrospective Analysis of 1365 Consecutive Patients

Background: Surgery with pleurectomy/decortication (P/D) or extrapleural pneumonectomy (EPP) can be an option for selected patients with resectable malignant pleural mesothelioma (MPM). The aim of this study was to investigate the impact of surgical treatment on the outcome of patients with MPM. Methods: We retrospectively reviewed data from 1365 consecutive patients with histologically proven MPM, treated from 1982 to 2012 in six Institutions. Patients received chemotherapy alone (n = 172), best supportive care (n = 690), or surgical treatment (n = 503), by either P/D (n = 202) or EPP (n = 301) with or without chemotherapy. Results: After a median follow-up of 6.7 years (range, 1.1–14.8), 230 patients (16.8%) were alive; median survival for patients who received palliative treatment or chemotherapy alone, P/D, and EPP were 11.7 (95% CI, 10.5–12.5), 20.5 (95% CI, 18.2–23.1), and 18.8 (95% CI, 17.2–20.9) months, respectively. The 30-day mortality was 2.6% after P/D and 4.1% after EPP (p = 0.401). According to multivariate analysis (n = 1227), age less than 70, epithelial histology, and chemotherapy were independent favorable prognostic factors. In the subset of 313 patients (25.5%) with all favorable prognostic factors, median survival was 18.6 months after medical therapy alone, 24.6 months after P/D, and 20.9 months after EPP (p = 0.596). Conclusions: Our data suggest that patients with good prognostic factors had a similar survival whether they received medical therapy only, P/D, or EPP. The modest benefit observed after surgery during medical treatment requires further investigation, and a large multicenter, randomized trial, testing P/D after induction chemotherapy versus chemotherapy alone in MPM patients with good prognostic factors, is needed.

Latissimus dorsi reverse flap to substitute the diaphragm after extrapleural pneumonectomy.

BACKGROUND The standard procedure for diaphragm reconstruction after extrapleural pneumonectomy for a malignancy consists of the use of prosthetic patches. Our original technique utilizing the reverse flap of the latissimus dorsi is evaluated. METHODS Once the extrapleural pneumonectomy is performed, the distal portion of the latissimus dorsi, which has been divided with a standard posterolateral thoracotomy at the level of the fifth to sixth rib, is elevated into the chest through the passage obtained by resection of the tenth rib and sutured to the lower pericardium and to the chest wall. Nine patients were evaluated. RESULTS No operative death occurred. No flap-related complication nor infection was postoperatively assessed. Six patients received adjuvant radiotherapy. No late complication was observed. CONCLUSIONS The distal latissimus dorsi can be used for total reconstruction of one hemidiaphragm, ensuring a watertight separation between the pleural and peritoneal cavities and avoiding paradoxical respiratory motion. In our opinion, the technique was easier, faster, and more reliable than the standard procedure employing prosthetic materials. We recommend that the procedure be integrated with the standard technique of extrapleural pneumonectomy.

Prolonged venous infusion of cisplatin and concurrent radiation therapy for lung carcinoma. A feasibility study

Fifty patients with non resectable and/or inoperable bronchogenic carcinoma were entered into a feasibility study of cisplatin (CDDP) given in continuous infusion with concurrent radiation therapy. The radiation therapy regimen consisted of 2 Gy given 5 days a week in the first 3 and last 2 weeks of a 7‐week split course (50 Gy of total dose). The CDDP (daily dose of 4 to 6 mg/m2) was administered to cover the days of radiation treatment by means of a central venous catheter and a portable pump. Less than 1% of predicted duration of infusion was lost due to complications related to venous access and pump. Toxicity was moderate. The overall probability of a locoregional major response (complete + partial) within 1 month after treatment completion was 86%. Twenty‐three patients underwent resection. The 1‐year actuarial probability of survival was 64%. The high response and survival rates warrant further studies on concurrent CDDP continuous infusion and radiation therapy in inoperable lung carcinoma.

cis-Diamminedichloroplatinum(II) given in low-dose continuous infusion with concurrent radiotherapy to patients affected by inoperable lung carcinoma: A pharmacokinetic approach

Abstract The pharmacokinetics of cis-diamminedichloro platinum(II) (cisplatin), given as a continuous infusion with concurrent radiotherapy to patients with locally advanced inoperable non-small-cell lung carcinoma, was investigated in 16 cases. The regimen, repeated for 6 consecutive weeks, consisted of weekly 10-Gy radiotherapy given in five fractions from Monday to Friday, and concurrent 100-h infusion of cisplatin delivered at a daily dose of 4 mg/m2 by a central venous catheter and a portable pump. Throughout the weeks of therapy the platinum levels were determined in plasma and in ultrafiltered plasma by respectively inductively coupled plasma atomic emission spectrometry and inductively coupled plasma mass spectrometry. Mean levels of platinum in plasma ([Pt]tot ) increased from the 1st to the 6th week of infusion, while mean levels of platinum in ultrafiltered plasma ([Pt]uf ), 110 μg/l, showed no marked variation throughout the therapy. [Pt]uf ranged from 16% to 22% of the total Pt. Mean levels of Pt in ultrafiltered plasma were of the same order of magnitude as those found to be active invitro as radiopotentiators. Pt decay levels were measured for 24 h at the end of the 1st and 5th weeks of infusion, allowing the calculation of the Pt half-life and the area under the decay curves. The mean value of the area under the decay curve, plotting [Pt]tot against time (AUC), in the range 0–24 h from the end of the 5th week of infusion, was about twice that from the end of the 1st week; by contrast, the mean AUC values did not vary for the [Pt]uf against time curves. The mean values of the α half-life of Pt in the ultrafiltered plasma were in accordance with those published in the literature; however, an unexpected very long β half-life was found (more than 100 h). Thus it was suggested that Pt species other than free cisplatin were present in the ultrafiltered plasma; such species probably involve metal bound to low-molecular-mass proteins. Throughout the therapy, the toxic effects in all patients were negligible, and 75% of them had an objective locoregional reduction of disease. In only 2 cases was progression of disease observed within the irradiated area. On the basis of these data, it can be concluded that cisplatin at a level of 110 μg/l in the ultrafiltered plasma, in the reported scheme of continuous intravenous infusion, has an enhancing effect on radiation and avoids concentration peaks of platinum not bound to protein.

Reverse flap of distal latissimus dorsi for diaphragm reconstruction in the adult: specification of the technical procedure and report on six cases.

autograft rather than other valve prostheses in children, some specific reasons were present in this special situation. Resection of the aneurysmal aortic root was necessary and the relatively difficult access to the aortic root made the choice of a homograft less preferable in view of the inevitable reoperation. The operation turned out to be straightforward. The anterior placement of the pulmonary trunk made its harvesting easy. Coronary artery problems were not encountered. Transposition may, however, be combined with coronary artery patterns that make harvesting of the pulmonary trunk more difficult, especially a right coronary artery crossing the right ventricular outflow tract. No important mismatch between the diameters of the pulmonary trunk and aortic anulus existed, which further encouraged us to choose the pulmonary autograft for aortic root replacement. In conclusion, the Ross procedure is technically feasible after an arterial switch operation and may be a particularly attractive alternative for this special population. This may be even more true because it is the original aortic valve that is used to replace the insufficient neoaortic valve. R E F E R E N C E S 1. Gittenberger-de Groot AC, Sauer U, Oppenheimer-Dekker A, Quaegebeur JM. Coronary arterial anatomy in transposition of the great arteries: a morphological study. Pediatr Cardiol 1983;4(suppl 1):15-24. 2. Klautz RIM, Ottenkamp J, Quaegebeur JM, Buis-Liem TN, Rohmer J. Anatomic correction for transposition of the great arteries: first follow-up (38 patients). Pediatr Cardiol 1989;10: 1-9. 3. Yamaguchi M, Hosokawa Y, Imai Y, Kurosawa H, Yasui H, Yagihari T, et al. Early and midterm results of the arterial switch operation for transposition of the great arteries in Japan. J Thorac Cardiovasc Surg 1990;100:261-9. 4. Ungerleider RM, Gaynor JW, Israel P, Kanter RJ, Armstrong BE. Report of neoaortic valve replacement in a ten-year-old girl after an arterial switch procedure for transposition. J Thorac Cardiovasc Surg 1992;104:213-5. 5. Serraf A, Roux D, Lacour-Gayet F, Touchot A, Bruniaux J, Sousa-Uva M, et al. Reoperation after arterial switch operation for transposition of the great arteries. J Thorac Cardiovasc Surg 1995;110:892-9.

Extrapericardial solitary fibrous tumour of the pericardium

Solitary fibrous tumour (SFT) occurs most commonly in the pleura and is extremely rare in the pericardium. The authors report a case of a 60-year-old man in whom a large mediastinal mass was accidentally discovered. Computed tomography showed involvement of the left anterosuperior mediastinum with displacement of the trachea, large vessels and oesophagus; histopathological findings after complete resection of the neoplasia demonstrated an SFT of the pericardium, the first reported case with extrapericardial pattern of growth. A review of the literature on SFTs of the pericardium is provided.

Study of the expression and function of the tumour-associated antigen CaMBr1 in small cell lung carcinomas

The expression of the epithelial antigen recognised by the MBr1 monoclonal antibody (CaMBr1) was studied on 161 small cell lung carcinoma (SCLC) biopsies. A correlation between the marker expression and the overall survival of the patients was found. To investigate the possible role of CaMBr1 in tumour aggressiveness, the in vivo and in vitro growth capabilities of different SCLC cell lines, in relation to the antigen expression, were analysed. The CaMBr1-positive cell lines displayed a higher growth potential in comparison to CaMBr1-negative cells. The biochemical nature of CaMBr1 was analysed in terms of enzyme sensitivity, molecular weight and comparison with other glycoproteins expressed by SCLC cells. The results indicated the trypsin sensitivity of the molecule, and sialic acid hiding of the CaMBr1 epitope. The increase of MBr1 reactivity after neuraminidase treatment suggests that the CaMBr1 epitope expressed in the SCLC cell line is carried by a sialoglycoprotein.

Determination of platinum in plasma of patients affected by inoperable lung carcinoma treated with radiotherapy and concurrent low-dose continuous infusion ofcis-dichlorodiammine platinum(II)

Platinum microquantities were determined in plasma of patients affected by lung carcinoma during treatment with radiotherapy (RT) and concurrent low-dose continuous infusion ofcis-dichlorodiammineplatinum(II) (CDDP). RT was given at 50 Gy in continuous course; CDDP was continuously infused at 4 mg/m2 daily for 100h/week for 5 weeks, and the infusions were separated by 68h of rest. The percentage of free drug versus total drug in plasma was about 3%. It did not vary with therapy duration and was not significantly different from that found in 5-day continuous infusions at much higher daily doses. Never-theless, maximal values of free Pt in plasma were very low and agreed with the low level of CDDP toxicity encountered on the present administration schedule.

Non-resectable Stage IIIa-b lung carcinoma: a Phase II study on continuous infusion of cisplatin and concurrent radiotherapy (plus adjuvant surgery)

Thirty-eight patients with non-resectable non-small-cell Stage IIIa-b lung cancer were treated in a Phase II study with radiotherapy (50 Gy in a 25-fraction split-course) plus con-current continuous infusion of cisplatin given at a daily dose of 6 mg/m2, with the aim of investigating its radiopotentiation properties. Treatments were given on an outpatient basis by means of a central venous catheter and a portable pump. Adjuvant surgery was undertaken when feasible. Toxicity was mild to moderate. The probability of a partial or complete locoregional response at 4 weeks after treatment completion was 83% (confidence limits at 95%: 13). Eighteen patients were resected. Overall 1-, 2- and 3-year progression-free survival probabilities were 42, 24 and 21%. These figures were 63, 37 and 24% in observed survival curves. Patients with squamous-cell tumors had observed survival rates of 82, 50 and 28% at 1, 2 and 3 years, compared to 42, 19 and 19% in patients with non-squamous histology. The high response and survival rates obtained at a low price according to toxicity require further investigation.

Radiotherapy and concurrent continuous infusion of cisplatin with adjuvant surgery in nonresectable Stage III lung carcinoma: short- and long-term results of a Phase II study.

PURPOSE Cisplatin-enhanced radiotherapy plus adjuvant surgery was evaluated in nonresectable non-small cell lung carcinoma (NSCLC). METHODS AND MATERIALS Doses of 50 Gy (administered in standard fractionation in 5 weeks) were delivered with concurrent cisplatin in continuous infusion (daily dose: 4 mg/m2), to 32 Stage IIIa and 45 Stage IIIb patients enrolled in a Phase II study. Patients without progression underwent surgery. RESULTS Esophagitis (64%), nausea/vomiting (34%), and pulmonary toxicity (14%) were the main side effects. Grade 3 toxicity occurred in 4 instances. A clinical locoregional major response was achieved by 55 patients (there were 10 complete responses). Forty patients underwent surgery, 7 with a nonradical procedure. Seven patients died due to surgery-related complications, which were significantly impacted by right pneumonectomy (71% vs. 6% of the other procedures, p < 0.0001). Eighteen of the 40 surgical patients were assessed to be without viable tumor and 11 with microresidual carcinoma. There were 13 disease-free, 5-year survivors. CONCLUSIONS Toxicity was low but activity high with the chemoradiotherapy. Adjuvant surgery increased the rate of complete responses, but right pneumonectomy had an unacceptable mortality. The role of surgery needs further refinement. Integration of the chemoradiotherapy schedule with cisplatin-based induction chemotherapy is advisable.