Agathe Seguin-Givelet

Multicentric evaluation of the impact of central tumour location when comparing rates of N1 upstaging in patients undergoing video-assisted and open surgery for clinical Stage I non-small-cell lung cancer

OBJECTIVES Large retrospective series have indicated lower rates of cN0 to pN1 nodal upstaging after video-assisted thoracic surgery (VATS) compared with open resections for Stage I non-small-cell lung cancer (NSCLC). The objective of our multicentre study was to investigate whether the presumed lower rate of N1 upstaging after VATS disappears after correction for central tumour location in a multivariable analysis. METHODS Consecutive patients operated for PET-CT based clinical Stage I NSCLC were selected from prospectively managed surgical databases in 11 European centres. Central tumour location was defined as contact with bronchovascular structures on computer tomography and/or visibility on standard bronchoscopy. RESULTS Eight hundred and ninety-five patients underwent pulmonary resection by VATS (n = 699, 9% conversions) or an open technique (n = 196) in 2014. Incidence of nodal pN1 and pN2 upstaging was 8% and 7% after VATS and 15% and 6% after open surgery, respectively. pN1 was found in 27% of patients with central tumours. Less central tumours were operated on by VATS compared with the open technique (12% vs 28%, P < 0.001). Logistic regression analysis showed that only tumour location had a significant impact on N1 upstaging (OR 6.2, confidence interval 3.6-10.8; P < 0.001) and that the effect of surgical technique (VATS versus open surgery) was no longer significant when accounting for tumour location. CONCLUSIONS A quarter of patients with central clinical Stage I NSCLC was upstaged to pN1 at resection. Central tumour location was the only independent factor associated with N1 upstaging, undermining the evidence for lower N1 upstaging after VATS resections. Studies investigating N1 upstaging after VATS compared with open surgery should be interpreted with caution due to possible selection bias, i.e. relatively more central tumours in the open group with a higher chance of N1 upstaging.

Congenital bronchial atresia in adults: thoracoscopic resection

Congenital bronchial atresia (CBA) is a rare congenital malformation consisting in an interruption of a lobar or-more frequently-of a segmental bronchus. It leads to mucus impaction and hyperinflation of the obstructed lung segment. It causes infectious complications and, in the long term, destruction of the adjacent lung parenchyma. Thus, a surgical resection is usually indicated, even in asymptomatic patients.

Adjuvant Chemotherapy, Retrospective Cohorts, and the Immortal Time Bias

To the Editor: Salazar et al. report a careful retrospective study of patients with T3 NSCLC who have additional tumor nodules in the same lobe that “supports the use of adjuvant chemotherapy in this patient subpopulation.” Actually, the authors find that adjuvant chemotherapy is “associated with improved 3-year overall survival (70% versus 59%, p < 0.001),” a survival advantage that remains significant in a Cox model taking into account “patient, tumor, and treatment factors” (hazard ratio 0.544; p < 0.0001). However,we believe the authors underestimated a bias that could explain at least in part their findings: the immortal time bias. Put simply, it remains uncertain whether some patients survived longer because they received adjuvant chemotherapy, or they could receive chemotherapybecause they lived longer (the “immortals”). In the Methods section, the authors rightly address in part this bias by excluding patients who died within 30 days after their operation because “patients typically must live at least 30 days to be considered for chemotherapy.” However, 30 days is too short a limit for excluding patients who had significant postoperative complications. In large multicenter databases, the operative mortality of lobectomy or bilobectomy—defined as the rate of death before hospital discharge or within 30 days after the index procedure—may reach 5%. But the mortality rate in thoracic surgery grossly doubles between postoperative days (PODs) 30 and 90, and the cause of death within this POD 30 to 90 period is disease progression in only about 10% of patients. Interestingly, the authors seem to identify this issue by noting “an early separation of the survival curves between the two treatment approaches” that could be “the result of a more complicated postoperative course,” which “not only prevented (these patients) from receiving chemotherapy but also threatened their survival in the first several months after their operation.” But they fail to infer that excluding all patients who died before POD 90 instead of POD 30 would have minimized this important bias. Could the authors provide at least some results (e.g., overall survival curves) after such exclusions? In any case, we suggest that similar retrospective studies addressing the same question should use POD 90 as the starting point for survival curves to minimize the immortal time bias. And we certainly concur with Salazar et al.’s prudent conclusion that “additional study is warranted to further characterize the role of adjuvant chemotherapy” in patients with T3 NSCLC with tumor nodules in the same lobe.

Division of the intersegmental plane during thoracoscopic segmentectomy: is stapling an issue?

BACKGROUND Stapling is becoming the method of choice for dividing the intersegmental plane during thoracoscopic segmentectomies. The technique however is controversial as it can impair re-expansion of preserved segments. We have analyzed the morbidity and lung re-expansion on a series of 175 thoracoscopic segmentectomies. METHODS A total of 175 patients underwent a thoracoscopic anatomic segmentectomy. Ten patients were excluded due to conversion into thoracotomy. There were 89 females (54%) and 76 males (46%). Mean age was 63 years (range, 18-83 years). Indications for segmentectomy were as follows: primary lung cancer (n=100, 61%), metastases (n=27, 16%), benign non-infectious lesions (n=20, 12%) and benign infectious lesions (n=18, 11%). The intersegmental plane was divided with an endostapler in all patients. Lung re-expansion assessment included chest roentgenograms at discharge and at one-month consultation. RESULTS The overall complication rate was 17%. There were 0.6% major complications and 16% minor complications. The average duration of drainage was 3 days (range, 1-13 days) and average length of stay was 5.7 days (range, 2-22 days). At discharge and at 1-month follow-up chest radiography, incomplete lung re-expansion was observed in 12 (7.4%) and 4 patients (2.8%) respectively. Patients who underwent upper lobe segmentectomy had significantly more incomplete re-expansion at discharge and at 1-month follow-up. On univariate analysis, mean drainage duration was significantly longer in patients who underwent upper segmentectomy (mean 3.7 days; range, 1-13) than those who underwent lower segmentectomy (mean 2.7 days; range, 1-5). CONCLUSIONS Although stapling of the intersegmental plane most likely slightly impairs lung re-expansion, clinical and radiological consequences are minimal.

Expression of LLT1 and its receptor CD161 in lung cancer is associated with better clinical outcome

ABSTRACT Co-stimulatory and inhibitory receptors expressed by immune cells in the tumor microenvironment modulate the immune response and cancer progression. Their expression and regulation are still not fully characterized and a better understanding of these mechanisms is needed to improve current immunotherapies. Our previous work has identified a novel ligand/receptor pair, LLT1/CD161, that modulates immune responses. Here, we extensively characterize its expression in non-small cell lung cancer (NSCLC). We show that LLT1 expression is restricted to germinal center (GC) B cells within tertiary lymphoid structures (TLS), representing a new hallmark of the presence of active TLS in the tumor microenvironment. CD161-expressing immune cells are found at the vicinity of these structures, with a global enrichment of NSCLC tumors in CD161+ CD4+ and CD8+ T cells as compared to normal distant lung and peripheral blood. CD161+ CD4+ T cells are more activated and produce Th1-cytokines at a higher frequency than their matched CD161-negative counterparts. Interestingly, CD161+ CD4+ T cells highly express OX40 co-stimulatory receptor, less frequently 4-1BB, and display an activated but not completely exhausted PD-1-positive Tim-3-negative phenotype. Finally, a meta-analysis revealed a positive association of CLEC2D (coding for LLT1) and KLRB1 (coding for CD161) gene expression with favorable outcome in NSCLC, independently of the size of T and B cell infiltrates. These data are consistent with a positive impact of LLT1/CD161 on NSCLC patient survival, and make CD161-expressing CD4+ T cells ideal candidates for efficient anti-tumor recall responses.

Adult pulmonary intralobar sequestrations: changes in the surgical management

Background Until now, the traditional procedure to treat intralobar pulmonary sequestration (ILS) in adults has been a lobectomy performed by open chest surgery. We have reviewed our data to determine whether the surgical management of these lesions has evolved over the last years. Methods We retrospectively reviewed the records of patients who were operated on for an ILS by either posterolateral thoracotomy (PLT group), or by thoracoscopy (TS group) between 2000 and 2016. Results Eighteen patients were operated on for a ILS during this period. Before 2011, all resections were performed by thoracotomy (n=6) and after 2011 the approach was either a thoracotomy (n=5) or a thoracoscopy (n=7). There was one conversion because of dense pleural adhesions and this patient was integrated in the PLT group for further analysis. ILS presented more frequently on the left side (n=12, 66.7%) than on the right one (n=6, 33.3%) and exclusively in the lower lobes. All the PLT group patients underwent a lobectomy. In the TS group, five patients underwent a sublobar resection (2 segmentectomies S9+10, 1 basilar segmentectomy and 2 atypical resections). There was no mortality. In the PLT group, 5 patients (45%) had complications versus one patient (14%) in the TS group. The mean hospital stay was 7.4 days in the PLT group versus 5.4 days in the TS group. Conclusions These data confirm that ILS can be safely treated by a sublobar resection that should be performed, whenever possible, without opening the chest.

Anatomical variations and pitfalls to know during thoracoscopic segmentectomies

The rate of sublobar resection (SLR) for early-stage non-small cell lung carcinoma (NSCLC) is increasing, mainly because of a growing rate of early-stage lung carcinomas and ground-glass opacities. More and more SLRs are now performed by a thoracoscopic, a video-assisted or a robotically-assisted approach. Although surgeons are performing pulmonary segmentectomies for years, they need a better understanding of anatomy when using a closed chest approach, because vision is more limited and they cannot stretch and expose the parenchyma and broncho-vascular elements. In this article, we will describe most of the significant anatomical variations we have encountered during a consecutive series of 390 full thoracoscopic segmentectomies, either at surgery or preoperatively by studying the 3-dimensional (3D) modelisation.

Planning and marking for thoracoscopic anatomical segmentectomies

Although sublobar resection (SLR) for treating non-small cell lung carcinoma (NSCLC) is still controversial, thoracoscopic segmentectomy is rising. Performing it by closed chest surgery is complex as it means confirming the location of the lesion, identifying vascular and bronchial structures, preserving venous drainage of adjacent segments, severing the intersegmental plane and ensuring an oncological safety margin with no manual palpation and different landmarks. Accurate planning is mandatory. We discuss in this article the interest of 3D reconstruction and mapping technics to enhance safety and reliability of these procedures.

Early and delayed post-pneumonectomy empyemas: Microbiology, management and prognosis

Post‐pneumonectomy empyema (PPE) is the most severe complication of pneumonectomy. Microbiology and its impact on management and prognosis have rarely been reported

Technical means to improve image quality during thoracoscopic procedures

Although high definition imaging systems are now available in the operating room (OR), the displayed image quality during video-assisted procedures is often poor. This is due to several factors such as inappropriate angle of vision, instable endoscope, lens soiling and fogging. The aim of this article is to provide information about some technical and technological means that make it possible to keep a perfect picture all along a thoracoscopic procedure.