Validation of a scoring system to predict recurrence of resected solitary fibrous tumors of the pleura.

BACKGROUND: Solitary fibrous tumors of the pleura (SFTPs) are infrequent neoplasms with no standardized criteria to predict risk of recurrence after curative surgery. The aim of the present study is to validate a recently proposed recurrence score in a large European cohort of patients with SFTP. METHODS: Validation of a previously published scoring system was assessed in a population of 113 patients who underwent complete resection of SFTPs. Patients were scored according to the pleural origin, morphology, size, hypercellularity, presence of necrosis or hemorrhage, and number of mitoses in their SFTPs. Receiver operating characteristic curves were plotted for the score. Time to recurrence analysis was performed using the Kaplan-Meier and Cox proportional hazards methods. RESULTS: After a mean follow-up of 13.2 ± 7.3 years, there were nine recurrences (8.0%). Score performance to predict recurrence was as follows: sensitivity = 78%, specificity = 74%, positive likelihood ratio = 3.0, and negative likelihood ratio = 0.3. A cutoff of 3 points was used to classify 79 patients (69.9%) at low risk and 34 patients (30.1%) at high risk for recurrence. A high-risk classification was significantly associated with more recurrences during follow-up (P = .004), worse overall survival (P = .0008), more extensive lung resections (P = .001), and the use of adjuvant therapies (P = .009). The present score outperformed England's criteria (P = .049) and de Perrot classification (P < .001) when predicting SFTP recurrence. CONCLUSIONS: The proposed scoring system, which combines common clinical and histologic features of resected SFTPs, remains predictive of recurrence in a separate patient population. The simple score may guide the postoperative surveillance of this uncommon tumor.

Subclavian artery resection and reconstruction for thoracic inlet neoplasms.

BACKGROUND: To update the long-term outcomes after subclavian artery (SA) resection and reconstruction during surgery for thoracic inlet (TI) cancer through the anterior transclavicular approach. METHODS: Between 1985 and 2014, 85 patients (60 men and 25 women; mean age, 52 years) underwent en bloc resection of thoracic-inlet non-small cell lung cancer (NSCLC) (n=69), sarcoma (n=11), breast carcinoma (n=3) or thyroid carcinoma (n=2) involving the SA. L-shaped transclavicular cervicothoracotomy was performed, with posterolateral thoracotomy in 18 patients or a posterior midline approach in 15 patients. Resection extended to the chest wall (>2 ribs, n=60), lung (n=76), and spine (n=15). Revascularization was by end-to-end anastomosis (n=48), polytetrafluoroethylene (PTFE) graft interposition (n=28), subclavian-to-common carotid artery transposition (n=8), or grafting of the autologous superficial femoral artery in an anterolateral thigh free flap (n=1). Complete R0 resection was achieved in 75 patients and microscopic R1 resection in 10 patients. Postoperative radiation therapy was given to 51 patients. RESULTS: There were no cases of postoperative death, neurological sequelae, graft infection or occlusion, or limb ischemia. Postoperative morbidity consisted of pneumonia (n=16), phrenic nerve palsy (n=2), recurrent nerve palsy (n=4), bleeding (n=4), acute pulmonary embolism (n=1), cerebrospinal fluid leakage (n=1), chylothorax (n=1), and wound infection (n=2). Five-year survival and disease-free survival rates were 32% and 22%, respectively. Long-term survival was not observed after R1 resection. CONCLUSIONS: Subclavian arteries invaded by TI malignancies can be safely resected and reconstructed through the anterior transclavicular approach, with good long-term survival provided complete R0 resection is achieved.

Subclavian artery resection and reconstruction for thoracic inlet cancer: 25 years of experience.

BACKGROUND: The purpose of this study was to evaluate long-term outcomes after subclavian artery resection and reconstruction during surgery for thoracic inlet cancer through the anterior transclavicular approach. METHODS: Between 1985 and 2011, 72 patients (51 men and 21 women; mean age, 51 years) underwent en bloc resection of thoracic inlet non-small cell lung cancer (n=59), sarcoma (n=10), breast carcinoma (n=2) or thyroid carcinoma (n=1) involving the subclavian artery. An L-shaped transclavicular cervicothoracotomy was performed, with posterolateral thoracotomy in 14 patients or a posterior midline approach in 13 patients. Resection extended to the chest wall (more than two ribs, n=53), lung (n=66), and spine (n=13). Revascularization was by end-to-end anastomosis (n=40), polytetrafluoroethylene graft interposition (n=25), subclavian-to-common carotid artery transposition (n=6), or grafting of the autologous superficial femoral artery in an anterolateral thigh free flap (n=1). Complete R0 resection was achieved in 65 patients and microscopic R1 resection in 7 patients. Postoperative radiation therapy was given to 46 patients. RESULTS: There were no cases of postoperative death, neurologic sequelae, graft infection or occlusion, or limb ischemia. Postoperative morbidity consisted of pneumonia (n=16), phrenic nerve palsy (n=2), recurrent nerve palsy (n=2), bleeding (n=3), acute pulmonary embolism (n=1), cerebrospinal fluid leakage (n=1), chylothorax (n=1), and wound infection (n=1). Five-year survival and disease-free survival rates were 28% and 20%, respectively. Long-term survival was not observed after R1 resection. CONCLUSIONS: Subclavian arteries invaded by thoracic inlet malignancies can be safely resected and reconstructed through the anterior transclavicular approach, with good long-term survival provided complete R0 resection is achieved.

IGF-1R targeting increases the antitumor effects of DNA-damaging agents in SCLC model: an opportunity to increase the efficacy of standard therapy.

Insulin-like growth factor receptor-1 (IGF-1R) inhibition could be a relevant therapeutic approach in small cell lung cancer (SCLC) given the importance of an IGF-1R autocrine loop and its role in DNA damage repair processes. We assessed IGF-1R and pAkt protein expression in 83 SCLC human specimens. The efficacy of R1507 (a monoclonal antibody directed against IGF-1R) alone or combined with cisplatin or ionizing radiation (IR) was evaluated in H69, H146, and H526 cells in vitro and in vivo. Innovative genomic and functional approaches were conducted to analyze the molecular behavior under the different treatment conditions. A total of 53% and 37% of human specimens expressed IGF-1R and pAkt, respectively. R1507 showed single-agent activity in H146 and H526 cells but not in H69 cells. R1507 exhibited synergistic effects with both cisplatin and IR in vitro. The triple combination R1507-cisplatin-IR led to a dramatic delay in tumor growth compared with cisplatin-IR in H526 cells. Analyzing the apparent absence of antitumoral effect of R1507 alone in vivo, we observed a transient reduction of IGF-1R staining intensity in vivo, concomitant to the activation of multiple cell surface receptors and intracellular proteins involved in proliferation, angiogenesis, and survival. Finally, we identified that the nucleotide excision repair pathway was mediated after exposure to R1507-CDDP and R1507-IR in vitro and in vivo. In conclusion, adding R1507 to the current standard cisplatin-IR doublet reveals remarkable chemo- and radiosensitizing effects in selected SCLC models and warrants to be investigated in the clinical setting.

Solitary fibrous tumor of the pleura: outcomes of 157 complete resections in a single center.

BACKGROUND: The purpose of this study was to identify factors affecting long-term outcomes after complete resection of solitary fibrous tumors of the pleura (SFTP). METHODS: This was a single-center retrospective study using data from patients operated on from January 1980 to December 2010. RESULTS: Of the 157 patients (72 men, 85 women; median age, 58 years [13-87 years]), 60 (38%) had symptoms. All patients had complete en bloc resection with wedge lung excision (n=122), lobectomy (n=15), bilobectomy (n=3), segmentectomy (n=1), pneumonectomy (n=4), chest wall resection (n=8), diaphragm resection (n=3), or multilevel hemivertebrectomy (n=1). The tumors were pedunculated (n=89) or sessile (n=68). Definitive histologic examination showed benign tumors (bSFTP) in 90 patients (57%) and malignant tumors (mSFTP) in 67 (43%) patients. Compared with the bSFTP group, the mSFTP group had significantly larger tumors (13.4 cm vs 6.4 cm; p<0.0001) and a nonsignificantly higher proportion of symptomatic patients (58% vs 23%). Overall operative mortality and morbidity rates were 0.6% and 5.7%, respectively, with no significant difference between patients with mSFTP and those with bSFTP. The 5-year survival rate was better in patients with bSFTP than in patients with mSFTP (96% vs 68%; p=0.0003). Tumor recurrence was more common in patients with mSFTP than in those with bSFTP (16% vs 2%; p<0.0001) and was associated with decreased survival (p=0.02). Sessile tumors (p=0.05), CD34-negative tumors (p=0.005), and extensive surgical procedures (p=0.04) were significant risk factors for tumor recurrence. CONCLUSIONS: Complete en bloc resection of SFTP provides good long-term survival. Tumor recurrence is the main risk factor for death and may occur in mSFTP despite en bloc resection and requires multimodal treatment and close follow-up.

Epithelioid haemangioendothelioma of the superior vena cava.

Primary calcified tumours of major central veins are extremely rare. Epithelioid haemangioendotheliomas (EHs) are malignant tumours of vascular origin with very limited reports in the literature. The aetiology is unknown. Immunohistochemically, tumours are often positive for at least one endothelial marker. We present a unique presentation of an EA in the superior vena cava.

Minimal residual disease in solid neoplasia: New frontier or red-herring?

Despite recent advances in prevention, screening, molecular characterization, and treatment, cancer evolution is still associated with late local, regional, or metastastic recurrence, even in early stages. Residual tumor cells can persist locally as cancer stem cells, in the blood flow as circulating tumor cells, and in distant organs as disseminated tumor cells or micrometastasis, defining three faces of minimal residual disease. Definition, preclinical models and clinical implications of these patterns will be detailed, with emphasis on overlaps and therapeutic implications, to determine whether minimal residual disease is only an old concept currently revisited, or a major shift in cancer paradigm.

Bioluminescent orthotopic mouse models of human localized non-small cell lung cancer: feasibility and identification of circulating tumour cells.

BACKGROUND: Preclinical models of non-small cell lung cancer (NSCLC) require better clinical relevance to study disease mechanisms and innovative therapeutics. We sought to compare and refine bioluminescent orthotopic mouse models of human localized NSCLC. METHODS: Athymic nude mice underwent subcutaneous injection (group 1-SC, n = 15, control), percutaneous orthotopic injection (group 2-POI, n = 30), surgical orthotopic implantation of subcutaneously grown tumours (group 3-SOI, n = 25), or transpleural orthotopic injection (group 4-TOI, n = 30) of A549-luciferase cells. Bioluminescent in vivo imaging was then performed weekly. Circulating tumour cells (CTCs) were searched using Cellsearch® system in SC and TOI models. RESULTS: Group 2-POI was associated with unexpected direct pleural spreading of the cellular solution in 53% of the cases, forbidding further evaluation of any localized lung tumour. Group 3-SOI was characterized by high perioperative mortality, initially localized lung tumours, and local evolution. Group 4-TOI was associated with low perioperative mortality, initially localized lung tumours, loco regional extension, and distant metastasis. CTCs were detected in 83% of nude mice bearing subcutaneous or orthotopic NSCLC tumours. CONCLUSIONS: Transpleural orthotopic injection of A549-luc cells in nude mouse lung induces localized tumour, followed by lymphatic extension and specific mortality, and allowed the first time identification of CTCs in a NSCLC mice model.

Early severe digestive complications after lung transplantation.

OBJECTIVE: This study aimed to describe and to analyze early severe digestive complications (ESDC) after lung transplantation (LT) in our center. METHODS: A retrospective study included 351 patients, who underwent LT without cardiopulmonary bypass (CPB) at our center between March 1988 and December 2009. There were 86 double LTs and 265 single LTs. ESDCs were defined as complications (1) occurring during the first 30 days after transplantation or during initial hospitalization if longer; (2) involving the gastrointestinal tract; and (3) jeopardizing survival or requiring invasive therapeutic procedure. Patients' characteristics, associated risk factors, and influence of ESDC on early outcome have been analyzed. RESULTS: During the first 30 days after LT or initial hospitalization if longer, 26 ESDCs occurred in 26 patients (rate 7.4%, sex ratio M/F 66%, mean age 56 ± 6 years). This included 10 acute cholecystitis (38%), four angiocholitis (15%), three perforated gastroduodenal ulcers (11%), three digestive perforations (11%), two intestinal occlusions (8%), two mesenteric ischemia (8%), and two acute pancreatitis (8%). ESDC occurred after a mean postoperative follow-up of 14 days (5-46), required emergency surgical treatment in 20 cases (77%), significantly prolonged the mean duration of hospitalization (96 days with ESDC vs 55 days without ESDC, p < 0.0001), and was responsible for death in five cases (19%). Surgical treatment included cholecystectomy (n = 11), bowel resection (n = 3), ulcer surgery (n = 2), subtotal colectomy (n = 2), Hartmann procedure (n = 1), and open coelioscopy (n = 1). Age and bilateral LT were found to be significant risk factors for ESDC in both uni- and multivariate analyses. CONCLUSION: ESDC occurred in 7.4% of patients after LT without CPB, and was responsible for longer in-hospital stay. Relevant risk factors included older age and bilateral LT, interfering with current debate regarding recipients' selection and procedure's choice.