C. Pricopi

Which metastasis management allows long-term survival of synchronous solitary M1b non-small cell lung cancer?

UNLABELLED OBJECTIVES; Patients with extrathoracic synchronous solitary metastasis and non-small cell lung cancer (NSCLC) are rare. The effectiveness of both tumour sites resection is difficult to evaluate because of the high variability among clinical studies. We reviewed our experience regarding the management and prognosis of these patients. METHODS The charts of 4668 patients who underwent lung cancer surgery from 1983 to 2006 were retrospectively reviewed. We analysed the epidemiology, treatment, pathology and prognostic characteristics of those with extrathoracic synchronous solitary metastasis amenable to lung cancer surgery on a curative intend. RESULTS There were 94 patients (sex ratio M/F 3.2/1, mean age 56 years). Surgery included pneumonectomy (n = 27), lobectomy (n = 65) and exploratory thoracotomy (n = 2). Pathology revealed adenocarcinomas (n = 57), squamous cell carcinoma (n = 20), large cell carcinoma (n = 14) and other NSCLC histology (n = 3). Lymphatic extension was N0 (n = 46), N1 (n = 17) and N2 (n = 31). Metastasis involved the brain (n = 57), adrenal gland (n = 12), bone (n = 14), liver (n = 5) and skin (n = 6). Sixty-nine metastases were resected. Five-year survival rate was 16% (median 13 months). Induction therapy, adenocarcinoma, N0 staging and lobectomy were criteria of better prognosis, but metastasis resection was not. CONCLUSIONS These results suggest that extrathoracic synchronous solitary metastasis of pN0 adenocarcinoma may achieve long-term survival in the case of lung resection with or without metastasis resection. This pattern may reflect a specific tumour biology whose solitary metastasis benefits both from surgical or non-surgical treatment.

Is the lymphatic drainage of lung cancer lobe-specific? A surgical appraisal

OBJECTIVES Nowadays, early-stage lung cancers are more frequently encountered. Selective lymph node (LN) dissection based on lobe-specific lymphatic pathway has been proposed. Our aim was to study nodal involvement according to tumour location. METHODS We reviewed 1779 lobectomized patients and analysed their pathological characteristics according to tumour location: Group 1 (G1), right upper lobe; Group 2 (G2), right middle lobe; Group 3 (G3), right lower lobe; Group 4 (G4), left upper division; Group 5 (G5), lingula; Group 6 (G6), left lower lobe. The pN status was recorded for each group to analyse the lymphatic spread of non-small-cell lung cancer (NSCLC) according to tumour location. RESULTS The numbers and proportions of lobectomies in each group were 613 patients in G1 (59.2%), 64 in G2 (6.4%), 359 in G3 (34.6%), 404 in G4 (54.3%), 54 in G5 (7.3%) and 286 in G6 (38.4%). The rates of pN2 involvement were similar, whatever the group was, even when deciphering single- and multistation diseases. on the right side, single-station N2 disease was mainly found in the superior mediastinum (SM) for G1 (95%), and in the inferior for G3 (90%). On the left side, single-station N2 was mainly found in the SM in G4 (94%), and the inferior in G6 (48%). Whatever the side, in case of two-station involvement, both mediastina were concerned in 40% (in G4) to 81% of the case (in G3). Long-term survival rates were different in skip metastasis, single- and multistation involvement, but not between lobes. CONCLUSIONS Tumour location is not a predictor of nodal metastasis pattern. In surgical treatment of NSCLC, complete systematic mediastinal LN dissection remains the only acceptable procedure from an oncological point of view.

Complete thoracoscopic lobectomy for cancer: comparative study of three-dimensional high-definition with two-dimensional high-definition video systems

OBJECTIVES Common video systems for video-assisted thoracic surgery (VATS) provide the surgeon a two-dimensional (2D) image. This study aimed to evaluate performances of a new three-dimensional high definition (3D-HD) system in comparison with a two-dimensional high definition (2D-HD) system when conducting a complete thoracoscopic lobectomy (CTL). METHODS This multi-institutional comparative study trialled two video systems: 2D-HD and 3D-HD video systems used to conduct the same type of CTL. The inclusion criteria were T1N0M0 non-small-cell lung carcinoma (NSCLC) in the left lower lobe and suitable for thoracoscopic resection. The CTL was performed by the same surgeon using either a 3D-HD or 2D-HD system. Eighteen patients with NSCLC were included in the study between January and December 2013: 14 males, 4 females, with a median age of 65.6 years (range: 49-81). The patients were randomized before inclusion into two groups: to undergo surgery with the use of a 2D-HD or 3D-HD system. We compared operating time, the drainage duration, hospital stay and the N upstaging rate from the definitive histology. RESULTS The use of the 3D-HD system significantly reduced the surgical time (by 17%). However, chest-tube drainage, hospital stay, the number of lymph-node stations and upstaging were similar in both groups. CONCLUSIONS The main finding was that 3D-HD system significantly reduced the surgical time needed to complete the lobectomy. Thus, future integration of 3D-HD systems should improve thoracoscopic surgery, and enable more complex resections to be performed. It will also help advance the field of endoscopically assisted surgery.

A review of 250 ten-year survivors after pneumonectomy for non-small-cell lung cancer.

OBJECTIVES During the last decades, pneumonectomy has been increasingly seen as a risky procedure, first reserved for tumours not amenable to lobectomy, and now discouraged even in advanced stages of non-small-cell lung cancer (NSCLC). Our purpose was to assess the long-term survival following pneumonectomy for NSCLC and its prognostic factors. METHODS We set a retrospective study including every patient who underwent a pneumonectomy for NSCLC in 2 French centres from 1981 to 2002. We then described the demographic and pathological characteristics of patients who survived >10 years, and studied the prognostic factors of long-term survival. RESULTS During the study period, 1466 pneumonectomies were performed for NSCLC, including 1121 standard and 345 extended, and accounted for the overall population. Postoperative complications occurred in 396 patients (27%), including 93 deaths (6.3%). Five- and 10-year survival rates were 32 and 19%, respectively. Two-hundred and fifty patients survived >10 years after surgery, and accounted for the study group. The study group included a majority of males (n = 230, 92%), a mean age of 57 ± 9.2 years and a majority of clinical stage IIIA (n = 117, 46.8%). Induction, right-sided pneumonectomy, extended resection and adjuvant therapy were performed in 41 (16.4%), 109 (43.6%), 40 (16%) and 97 patients (38.8%), respectively. Histology revealed a majority of squamous cell carcinoma (n = 181, 72.4%), T2 tumours (n = 117, 36.8%) and N1 disease (n = 105, 42%). In multivariate analysis, factors associated with adverse outcomes included older age, advanced stage, extended resection, non-lethal postoperative complication, adenocarcinoma, lymphatic vessel microinvasion, N1 and N2 disease and R1 and R2 resection. CONCLUSIONS During the last 30 years, pneumonectomy was effectively performed for advanced NSCLC, allowing a 10-year survival rate of 19%. Such results have not been reported with other non-surgical treatments and confirm that pneumonectomy is still an essential weapon in the armamentarium against lung cancer.

Postoperative morbidity and mortality after pneumonectomy: a 30-year experience of 2064 consecutive patients

OBJECTIVES We examined whether the changes in clinical practice with time correlated with the changes in the 90-day mortality following pneumonectomy. METHODS The clinical records of consecutive patients undergoing pneumonectomy in two French centres from 1980 to 2009 were prospectively collected. The 90-day postoperative course was retrospectively studied according to clinical characteristics, underlying diseases, type of surgery and time-period (1980-1989; 1990-1999 or 2000-2009). RESULTS Pneumonectomy was performed in 2064 patients (right n = 948, males n = 1758, mean age 60 ± 10 years). Indications were non-small-cell lung cancer (n = 1805, 87%), mesothelioma (n = 39, 1.8%), other tumours (n = 132, 6.3%) and non-tumour disease (n = 88, 4.2%). The 30- and 90-day mortality were 17.4 and 7.2% in the first decade, 22.3 and 9% in the second decade and 26.4 and 7.3% in the third decade, respectively. In multivariate analysis, older age, right-sided resection, T3-T4 and N2 lung cancer disease were significantly associated with increased overall 90-day mortality, whereas surgery during the last decade was associated with a better outcome when compared with the first decade (RR: 0.63, 95% confidence interval: 0.50-0.80, P = 0.045). When focusing on patients with non-small-cell lung cancer (NSCLC), the 90-day mortality following induction therapy and pneumonectomy decreased from 21.9% in the 1980s to 8.2% in the 2000s (P = 0.038), while such decrease was not found in patients without induction therapy or in patients undergoing a lobectomy. CONCLUSIONS The overall 90-day mortality after pneumonectomy was not significantly modified over the last 30 years, while the 90-day mortality after induction therapy followed by pneumonectomy for NSCLC decreased significantly.

Lung Cancer Invading the Pericardium: Quantum of Lymph Nodes

BACKGROUND Lung cancer may invade the pericardium (T3) and the intrapericardial pulmonary veins and left atrium (T4). Our purpose was to analyze the characteristics of this invading process in search of the reasons explaining its poor prognosis. METHODS The clinical records of 4,668 patients who underwent surgery for lung cancer between January 1983 and December 2006 in two thoracic surgery centers were retrospectively reviewed. The epidemiology, pathology, and prognostic characteristics of the tumors invading the pericardium alone (T3) or with pulmonary veins and atrium (T4) were analyzed and compared with all other tumors. RESULTS There were 75 male and 16 female patients, with 85 pneumonectomies and 6 lobectomies that proved R0 in 59.3% of patients, and contained 69 squamous cell cancers, 11 adenocarcinomas, and 13 miscellaneous tumors; 12 were N0 (13.2%), 31 were N1 (34.1%), and 48 were N2 (52.8%). Pericardium alone was invaded in 32 patients (35.2%), and with pulmonary vein and atrium in 34 (37.3%) and 25 (27.5%), respectively. Patient characteristics were similar in each group. Five-year and 10-year survival rates were 15.1% and 10.4%, respectively. Frequency of pneumonectomy, R1-2 resection, and N1-2 involvement were significantly more important compared with noninvading tumors (p < 10(-6)). CONCLUSIONS Reports on T3 and T4 cancer with pericardial involvement are few, but also stress that pulmonary vein and left atrium invasion does not worsen the prognosis more than pericardial invasion alone. The rich pericardial lymph drainage might enhance the spread of tumor cells, explaining excessively high N1-N2 rates and pericardial invasion-related poor prognosis.

Diaphragm pacing: the state of the art

Diaphragm pacing (DP) is an orphan surgical procedure that may be proposed in strictly selected ventilator-dependent patients to get an active diaphragm contraction. The goal is to wean from mechanical ventilation (MV) and restore permanent efficient breathing. The two validated indications, despite the lack of randomised control trials, concern patients with high-level spinal cord injuries (SCI) and central hypoventilation syndromes (CHS). To date, two different techniques exist. The first, intrathoracic diaphragm pacing (IT-DP), based on a radiofrequency method, in which the electrodes are directly placed around the phrenic nerve. The second, intraperitoneal diaphragm pacing (IP-DP) uses intradiaphragmatic electrodes implanted through laparoscopy. In both techniques, the phrenic nerves must be intact and diaphragm reconditioning is always required after implantation. No perioperative mortality has been reported and ventilator-weaning rate is about 72% to 96% in both techniques. Improvement of quality of life, by restoring a more physiological breathing, has been almost constant in patients that could be weaned. Failure or delay in recovery of effective diaphragm contractions could be due to irreversible amyotrophy or chest wall damage. Recent works have evaluated the interest of IP-DP in amyotrophic lateral sclerosis (ALS). After some short series were reported in the literature, the only multicentric randomized study including 74 ALS patients was prematurely stopped because of excessive mortality in paced patients. Then, another trial analysed the place of IP-DP in peripheral diaphragm dysfunction but, given the multiple biases, the published results cannot validate that indication. Reviewing all available literature as in our experience, shows that DP is an effective method to wean selected patients dependent on ventilator and improve their daily life. Other potential indications will have to be evaluated by randomised control trials.

Lung transplantation in childhood and adolescence: unicentric 14-year experience with sex matching as the main prognosticator.

OBJECTIVES Lung transplantation (LTx) is an accepted therapy for selected infants, children and adolescents with end-stage lung and pulmonary vascular disease. It remains a challenge for a selected group of patients. In 2011, the number of paediatric lung transplantations (PLTxs) worldwide was 107. In France, a total of 131 PLTxs have been performed since 2000 (data from ABM: Agence de biomédecine), 65 of which were conducted at our institution. METHODS All patients under 18 (4.8-17.11) years of age matching inclusion and exclusion criteria, who underwent LTx at our institution were included in this study (n = 58). We analysed the outcomes of these patients in terms of survival rates, controlling for indications for transplantations and surgical procedures. Secondary outcomes were analysis of surgical and medical complications and identification of prognostic factors in the field of LTx in these categories of ages. RESULTS The 30-day mortality rate was 10%. Kaplan-Meier survival rates at 1 month, 1, 3, 5 and 10 years were 90, 81, 66, 60 and 57%, respectively; the median survival was 91 months. Reduced-size transplantation was performed in 33% of double-lung transplantation (DLTx) patients without negatively impacting survival. In our series, female sex, the presence of a sex mismatching and, in particular, the occurrence of a male donor to a female recipient (F/M group) have been poor prognostic factors after PLTx. CONCLUSIONS The overall survival after PLTx was encouraging (57% at 10 years). A PLTx should be offered to the small number of patients with end-stage pulmonary disease. The limited number of paediatric donor organs can be overcome by using reduced-size organs without a survival disadvantage to the patients. In our series, male sex and sex matching seemed to be positive predictive prognostic factors after PLTx but further studies are required to confirm these results and to also clarify the role of age of donor, time of cold ischaemia and body mass index in PLTx.

Visceral pleura and pN involvement in lung cancer

Adachi et al. [1] studied visceral pleural involvement (VPI) in 639 patients collected from 9 hospitals and reported that VPI was present as PL1 (tumour invading beyond the elastic layer but not exposed on the visceral pleura) in 135 patients and PL2 (tumour invading and exposed on the visceral surface but not involving adjacent anatomical structures) in 42. They compared them with the 462 other PL0 (tumour within the lung parenchyma not reaching the elastic layer) patients. The 5-year survival rate differed significantly between PL0 (75.9%) and PL1 patients (63.6%), but not between PL1 and PL2 (54.1%). Those differences persisted in 502 pN0 patients (96 PL1, 27 PL2) and in 69 pN1 (18 PL1, 12 PL2), but were not significant in the latter. The pN2 patients (44 PL0, 21 PL1 and 3 PL2) represented 10.4% in the study. On multivariate analysis, VPI was an independent predictor of survival. When reviewing a similar VPI population from a two-hospital database [2], we found 1687 PL0, 255 PL1 and 180 PL2 patients with 5-year survival rates of 61.2, 60.3 and 41.9%, respectively (P = 0.000034), but no difference in survival between PL0 and PL1 patients. The difference existed in pN0 patients but not in case of pN involvement. The pN involvement was similar in PL1 and PL0 patients (pN1 12.2%, pN2 18.4% and pN1 16.8%, pN2 19.1%, respectively), but more important in PL2 (pN1 18.9% and pN2 28.3%). On multivariate analysis, VPI was not a predictor of survival. The results of Adachi et al. [1] lead them to suggest that the presence rather than the extent of VPI had an impact on survival in patients with pN0 and pN1, which does not correspond with our findings. These differences between their work and ours may be due to the weak statistical power of their study, which was relatively small as they suggested, but also probably to the selection of their population. Clinical N2 patients might have undergone induction therapy and be excluded from the study. In such a case, studying the role of VPI in pN involvement without including clinical N2 that could benefit from a curative surgery might have biased the results. The pleura effectively plays an important role in lung cancer dissemination. Its involvement affects pN but to a greater extent in pN2 than in pN1 patients [2].

Facteurs pronostiques cliniques et paracliniques dans la chirurgie du cancer du poumon non à petites cellules

INTRODUCTION Lung cancer prognosis is mainly based on the TNM, histology and molecular biology. Our aim was to analyze the prognostic value of certain clinical and paraclinical variables. PATIENTS AND METHODS We studied among 6105 patients operated on, divided during 3 time-periods (1979 to 2010), the following prognostic factors: type of surgery, pTNM, histology, age, sex, smoking history, clinical presentation, and paraclinical variables. RESULTS Postoperative mortality was 4% (243/6105), rate of complications was 23.3% (1424/6105). The 5-year overall survival was 43.2% and 10-year was 27%. Best survival was observed after complete resection (R0) (P<10(-6)), lobectomy (P<10(-6)), lymph node dissection (P=0.0006), early pTNM stages (P<10(-6)), absence of a solid component in adenocarcinoma. Other pejorative factors were: male gender (P=10(-5)), age (P=0.0000002), comorbidity (P=0.016), history of cancer (P<10(-5)), postoperative complications (P=0.0018), FEV lower than 80% (P=0.0000025), time-periods (P<10(-6)). All these factors were confirmed by multivariate analysis, except gender. Smoking was not poor prognostic factor in univariate analysis (P=0.09) but became significant in the multivariate one (P=0.013). CONCLUSION Medical and human factors, and the general physiological state, play an important role in prognosis after surgery. We do not know their exact meaning and, like studies on chemotherapy, they justify special research.