Summary Background One of the standard options in the treatment of stage IIIA/N2 non-small-cell lung cancer is neoadjuvant chemotherapy and surgery. We did a randomised trial to investigate whether ...the addition of neoadjuvant radiotherapy improves outcomes. Methods We enrolled patients in 23 centres in Switzerland, Germany and Serbia. Eligible patients had pathologically proven, stage IIIA/N2 non-small-cell lung cancer and were randomly assigned to treatment groups in a 1:1 ratio. Those in the chemoradiotherapy group received three cycles of neoadjuvant chemotherapy (100 mg/m2 cisplatin and 85 mg/m2 docetaxel) followed by radiotherapy with 44 Gy in 22 fractions over 3 weeks, and those in the control group received neoadjuvant chemotherapy alone. All patients were scheduled to undergo surgery. Randomisation was stratified by centre, mediastinal bulk (less than 5 cm vs 5 cm or more), and weight loss (5% or more vs less than 5% in the previous 6 months). The primary endpoint was event-free survival. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00030771. Findings From 2001 to 2012, 232 patients were enrolled, of whom 117 were allocated to the chemoradiotherapy group and 115 to the chemotherapy group. Median event-free survival was similar in the two groups at 12·8 months (95% CI 9·7–22·9) in the chemoradiotherapy group and 11·6 months (8·4–15·2) in the chemotherapy group (p=0·67). Median overall survival was 37·1 months (95% CI 22·6–50·0) with radiotherapy, compared with 26·2 months (19·9–52·1) in the control group. Chemotherapy-related toxic effects were reported in most patients, but 91% of patients completed three cycles of chemotherapy. Radiotherapy-induced grade 3 dysphagia was seen in seven (7%) patients. Three patients died in the control group within 30 days after surgery. Interpretation Radiotherapy did not add any benefit to induction chemotherapy followed by surgery. We suggest that one definitive local treatment modality combined with neoadjuvant chemotherapy is adequate to treat resectable stage IIIA/N2 non-small-cell lung cancer. Funding Swiss State Secretariat for Education, Research and Innovation (SERI), Swiss Cancer League, and Sanofi.
Ex vivo lung perfusion (EVLP) with pharmacological reconditioning may increase donor lung utilization for transplantation (LTx). 3‐Aminobenzamide (3‐AB), an inhibitor of poly(ADP‐ribose) polymerase ...(PARP), reduces ex vivo lung injury in rat lungs damaged by warm ischemia (WI). Here we determined the effects of 3‐AB reconditioning on graft outcome after LTx. Three groups of donor lungs were studied: Control (Ctrl): 1 hour WI + 3 hours cold ischemia (CI) + LTx; EVLP: 1 hour WI + 3 hours EVLP + LTx; EVLP + 3‐AB: 1 hour WI + 3 hours EVLP + 3‐AB (1 mg.mL−1) + LTx. Two hours after LTx, we determined lung graft compliance, edema, histology, neutrophil counts in bronchoalveolar lavage (BAL), mRNA levels of adhesion molecules within the graft, as well as concentrations of interleukin‐6 and 10 (IL‐6, IL‐10) in BAL and plasma. 3‐AB reconditioning during EVLP improved compliance and reduced lung edema, neutrophil infiltration, and the expression of adhesion molecules within the transplanted lungs. 3‐AB also attenuated the IL‐6/IL‐10 ratio in BAL and plasma, supporting an improved balance between pro‐ and anti‐inflammatory mediators. Thus, 3‐AB reconditioning during EVLP of rat lung grafts damaged by WI markedly reduces inflammation, edema, and physiological deterioration after LTx, supporting the use of PARP inhibitors for the rehabilitation of damaged lungs during EVLP.
The pharmacological reconditioning during ex vivo lung perfusion of damaged rat lung grafts, using the poly(ADP‐ribose) polymerase inhibitor 3‐aminobenzamide, reduces inflammation, edema, and physiological deterioration following lung transplantation.
Background
Resection of lung metastases (LM) from colorectal cancer (CRC) is increasingly performed with a curative intent. It is currently not possible to identify those CRC patients who may benefit ...the most from this surgical strategy. The aim of this study was to perform a systematic review of risk factors for survival after lung metastasectomy for CRC.
Methods
We performed a meta-analysis of series published between 2000 and 2011, which focused on surgical management of LM from CRC and included more than 40 patients each. Pooled hazard ratios (HR) were calculated by using random effects model for parameters considered as potential prognostic factors.
Results
Twenty-five studies including a total of 2925 patients were considered in this analysis. Four parameters were associated with poor survival: (1) a short disease-free interval between primary tumor resection and development of LM (HR 1.59, 95 % confidence interval CI 1.27–1.98); (2) multiple LM (HR 2.04, 95 % CI 1.72–2.41); (3) positive hilar and/or mediastinal lymph nodes (HR 1.65, 95 % CI 1.35–2.02); and (4) elevated prethoracotomy carcinoembryonic antigen (HR 1.91, 95 % CI 1.57–2.32). By comparison, a history of resected liver metastases (HR 1.22, 95 % CI 0.91–1.64) did not achieve statistical significance.
Conclusions
Clinical variables associated with prolonged survival after surgery for LM in CRC patients include prolonged disease-free interval between primary tumor and metastatic spread, normal prethoracotomy carcinoembryonic antigen, absence of thoracic node involvement, and a single pulmonary lesion.
•Some Colorectal cancer (CRC) patients may benefit from a curative Lung Metastasis resection.•There is no single success criterion, but surgical management demonstrates steady ...progress.•Stratification of patients and selection bias impact the conclusions.•Surgical management (including repeat surgery) may prolong life or cure some CRC patients.•Instances of long-term disease-free survival remain exceptional.
Colorectal cancer (CRC) is a frequently occurring disease, yet diagnosed at a local stage in only 40% of cases. Lung metastases (LM) appear in 5–15% of patients and, left untreated, carry a very poor prognosis. Some CRC patients may benefit from a potentially curative LM resection, but success and benefit are difficult to predict. We discuss prognostic factors of survival after lung metastasectomy in CRC patients under several scenarios (with/ without prior liver metastases; repetitive pulmonary resections).
We reviewed all studies (2005–2015) about pulmonary metastases surgical management with curative intent in CRC patients, with a minimum threshold on the number of patients reported (without prior liver metastases: n ≥ 100; with prior resection of liver metastases: n ≥ 50; repetitive thoracic surgery: n ≥ 30).
The picture of the prognostic factors of survival is nuanced: surgical management demonstrates clear successes and steady progress, yet there is no single success criterion; stratification of patients and selection bias impact the conclusions. Surgical management of liver and lung metastases may prolong life or cure CRC patients, provided the lesions are fully resected and patients carefully selected. Repeat lung metastasectomy is a safe approach to treat patients in selected cases.
In conclusion, there is no standard for surgical management in CRC patients with pulmonary metastases. Patients with isolated unilateral lung metastasis with normal CEA level and no lymph node involvement benefit the most from surgery. Most series report good results in highly selected patients, but instances of long-term disease-free survival remain exceptional.
Video-assisted thoracic surgery (VATS) is currently performed to diagnose and treat solitary pulmonary nodules (SPN). However, the intra-operative identification of deep nodules can be challenging ...with VATS as the lung is difficult to palpate. The aim of the study was to report the utility and the results of pre-operative computed tomography (CT)-guided hook wire localization of SPN.
All records of the patients undergoing CT-guided hook wire localization prior to VATS resection for SPN between 2002 and 2013 were reviewed. The efficacy in localizing the nodule, hook wire complications, necessity to convert VATS to thoracotomy and the histology of SPN are reported.
One hundred eighty-one patients (90 females, mean age 63 y, range 28-82 y) underwent 187 pulmonary resections after CT-guided hook wire localization. The mean SPN diameter was 10.3 mm (range: 4-29 mm). The mean distance of the lesion from the pleural surface was 11.6 mm (range: 0-45 mm). The mean time interval from hook wire insertion to VATS resection was 224 min (range 54-622 min). Hook wire complications included pneumothorax requiring chest tube drainage in 4 patients (2.1%) and mild parenchymal haemorrhage in 11 (5.9%) patients. Migration of the hook wire occurred in 7 patients (3.7%) although it did not affect the success of VATS resection (nodule location guided by the lung puncture site). Three patients underwent additional wedge resection by VATS during the same procedure because no lesion was identified in the surgical specimen. Conversion thoracotomy was required in 13 patients (7 %) for centrally localized lesions (6 patients) and pleural adhesions (7 patients). The mean operative time was 60 min (range 18-135 min). Pathological examination revealed a malignant lesion in 107 patients (59 %). The diagnostic yield was 98.3 %.
VATS resection for SPN after CT-guided hook wire localization for SPN is safe and allows for proper diagnosis with a low thoracotomy conversion rate.
Background
Due to the underlying diseases and the need for immunosuppression, patients after lung transplantation are particularly at risk for gastrointestinal (GI) complications that may negatively ...influence long-term outcome. The present study assessed the incidences and impact of GI complications after lung transplantation and aimed to identify risk factors.
Methods
Retrospective analysis of all 227 consecutively performed single- and double-lung transplantations at the University hospitals of Lausanne and Geneva was performed between January 1993 and December 2010. Logistic regressions were used to test the effect of potentially influencing variables on the binary outcomes overall, severe, and surgery-requiring complications, followed by a multiple logistic regression model.
Results
Final analysis included 205 patients for the purpose of the present study, and 22 patients were excluded due to re-transplantation, multiorgan transplantation, or incomplete datasets. GI complications were observed in 127 patients (62 %). Gastro-esophageal reflux disease was the most commonly observed complication (22.9 %), followed by inflammatory or infectious colitis (20.5 %) and gastroparesis (10.7 %). Major GI complications (Dindo/Clavien III–V) were observed in 83 (40.5 %) patients and were fatal in 4 patients (2.0 %). Multivariate analysis identified double-lung transplantation (
p
= 0.012) and early (1993–1998) transplantation period (
p
= 0.008) as independent risk factors for developing major GI complications. Forty-three (21 %) patients required surgery such as colectomy, cholecystectomy, and fundoplication in 6.8, 6.3, and 3.9 % of the patients, respectively. Multivariate analysis identified Charlson comorbidity index of ≥3 as an independent risk factor for developing GI complications requiring surgery (
p
= 0.015).
Conclusion
GI complications after lung transplantation are common. Outcome was rather encouraging in the setting of our transplant center.
Background
Pulmonary metastasectomy is increasingly performed in selected patients by video-assisted thoracic surgery (VATS) on the base of thin-slice high-resolution CT-Scan (HRCT). This study ...determines the overall survival and ipsilateral recurrence rate and of patients undergoing after VATS lung metastasectomy.
Patients and method
Retrospective single institution study of all patients who underwent VATS pulmonary metastasectomy on the base of HRCT with curative intent between 2005 and 2014.
Results
Seventy-seven patients (41 males, 36 females) underwent VATS pulmonary metastasectomy for solitary (
n
= 63) or multiple (
n
= 14) lung metastases in the context of colorectal carcinoma (
n
= 26), sarcoma (
n
= 17), melanoma (
n
= 16), or other primaries (
n
= 18). Nine patients had bilateral lung metastases and underwent synchronous (
n
= 4) or sequential (
n
= 5) VATS resections. Preoperative CT-guided hook wire localization of the lesions was performed in 65 patients (84 %). The postoperative mortality and morbidity rates were 0 and 5.2 %, respectively. During a mean follow-up time of 24 months (range 1–120 months), tumor progression occurred in 46 patients. Twenty-three patients (30 %) had pulmonary recurrence only, of them, eight patients (10 %) in the operated lungs. Seven of eight patients with recurrence in the operated lungs underwent a second metastasectomy by VATS (
n
= 5) or thoracotomy (
n
= 2). The overall 5-year survival rate was 54 % and without difference between patients without tumor recurrence and those with pulmonary recurrence treated by re-metastasectomy.
Conclusion
Ipsilateral recurrence remains low after VATS pulmonary metastasectomy guided by preoperative HRCT and can be efficiently treated by re-metastasectomy.
Damaged lung grafts obtained after circulatory death (DCD lungs) and warm ischemia may be at high risk of reperfusion injury after transplantation. Such lungs could be pharmacologically reconditioned ...using ex-vivo lung perfusion (EVLP). Since acute inflammation related to the activation of nuclear factor kappaB (NF-κB) is instrumental in lung reperfusion injury, we hypothesized that DCD lungs might be treated during EVLP by pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. Rat lungs exposed to 1h warm ischemia and 2 h cold ischemia were subjected to EVLP during 4h, in absence (CTRL group, N = 6) or in presence of PDTC (2.5g/L, PDTC group, N = 6). Static pulmonary compliance (SPC), peak airway pressure (PAWP), pulmonary vascular resistance (PVR), and oxygenation capacity were determined during EVLP. After EVLP, we measured the weight gain of the heart-lung block (edema), and the concentration of LDH (cell damage), proteins (permeability edema) and of the cytokines IL-6, TNF-α and CINC-1 in bronchoalveolar lavage (BAL), and we evaluated NF-κB activation by the degree of phosphorylation and degradation of its inhibitor IκBα in lung tissue. In CTRL, we found significant NF-κB activation, lung edema, and a massive release of LDH, proteins and cytokines. SPC significantly decreased, PAWP and PVR increased, while oxygenation tended to decrease. Treatment with PDTC during EVLP inhibited NF-κB activation, did not influence LDH release, but markedly reduced lung edema and protein concentration in BAL, suppressed TNFα and IL-6 release, and abrogated the changes in SPC, PAWP and PVR, with unchanged oxygenation. In conclusion, suppression of innate immune activation during EVLP using the NF-κB inhibitor PDTC promotes significant improvement of damaged rat DCD lungs. Future studies will determine if such rehabilitated lungs are suitable for in vivo transplantation.
Abstract Video-assisted thoracoscopic surgery (VATS) is currently a routinely performed procedure for the management of early non small cell lung cancer. The oncological results of VATS in terms of ...local recurrence and overall survival are equivalent or superior to those of conventional thoracotomy with lower morbidity and hospital stay. In the field of pulmonary metastasectomy, current guidelines support a thoracotomy approach in order to properly palpate the lung and detect nodules too small to be identified on standard radiological examinations (typically less than 5 mm in diameter). However, the oncological and clinical significance of these millimetric nodules is not known. This has led some thoracic surgeons to rethink the approach of solitary pulmonary metastasectomy: because of improvements in thin slice helical CT-scans, some support a VATS approach for solitary pulmonary nodules without formal bimanual palpation and suggest this allows equivalent oncological results and decreased surgical morbidity.
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