Antifibrotic effects of vitamin D3 on human lung fibroblasts derived from patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. Up to now, no treatment can stop the progression of IPF. Vitamin D3 (VD) reduces experimental lung fibrosis in murine models and depletion of vitamin D3 might be associated with the reduced survival of patients with IPF. In this context, we determined if VD can prevent the pro-fibrotic functions of human lung fibroblasts (HLFs) isolated from patients with IPF. IPF and control HLFs were derived from surgical lung biopsies collected from patients with IPF or with primary lung cancer, respectively. VD (3-100 nM) markedly reduced the basal and PDGF-induced proliferation of HLFs. VD also altered cell cycle by increasing the percentage of IPF HLFs arrested in the G0/G1 phase, and by downregulating the expression of various cell cycle regulatory proteins. In addition, VD barely prevented the TGF-ß1-induced differentiation in HLFs. At 100 nM, VD slightly reduced the expression of the pro-fibrotic marker α-smooth muscle actin, and had no effect on fibronectin and collagen-1 expression. In contrast, 100 nM VD strongly inhibited the aerobic glycolytic metabolism induced by TGF- ß1. Finally, VD reduced both the secretion of lactate, the levels of lactate deshydrogenase mRNA and the activity of intracellular LDH in IPF HLFs. In conclusion, our study shows that VD reduced pro-fibrotic functions of HLFs. These findings suggest that it might be interesting to assess the potential clinical benefits of vitamin D supplementation in patients with IPF, especially on lung function decline.

Anti-fibrotic effects of nintedanib on lung fibroblasts derived from patients with Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs).

The tyrosine kinase inhibitor nintedanib has been recently approved for the treatment of Interstitial Lung Diseases (ILDs) that manifest a progressive fibrosis phenotype other than Idiopathic pulmonary Fibrosis (IPF). Nintedanib reduces the development of lung fibrosis in various animal models resembling features of PF-ILD and in vitro, it inhibits the fibrosing phenotype of human lung fibroblasts (HLFs) isolated from patients with IPF. To get insight on the cellular and molecular mechanisms that drive the clinical efficiency of nintedanib in patients with non-IPF PF-ILD, we investigated its effects on the fibrosing functions of HLFs derived from patients with PF-hypersensitivity pneumonitis (PF-HP, n = 7), PF-sarcoidosis (n = 5) and pleuroparenchymal fibroelastosis (PPFE, n = 4). HLFs were treated with nintedanib (10 nM-1 µM) and then stimulated with PDGF-BB (25-50 ng/ml) or TGF-ß1 (1 ng/ml) for 24-72 h to assess proliferation and migration or differentiation. At nanomolar concentrations, nintedanib reduced the levels of PDGF receptor and ERK1/2 phosphorylation, the proliferation and the migration of PF-HP, PF-sarcoidosis and PPFE HLFs stimulated with PDGF-BB. Moreover, nintedanib also attenuates the myofibroblastic differentiation driven by TGF-ß1 but only when it is used at 1 µM. The drug reduced the phosphorylation of SMAD2/3 and decreased the induction of collagen, fibronectin and α-smooth muscle actin expression induced by TGF-ß1. In conclusion, our results demonstrate that nintedanib counteracts fundamental fibrosing functions of lung fibroblasts derived from patients with PF-HP, PF-sarcoidosis and PPFE, at concentrations previously reported to inhibit control and IPF HLFs. Such effects may contribute to its clinical benefit in patients suffering from these irreversible ILDs.

Medico-economic impact of thoracoscopy versus thoracotomy in lung cancer: multicentre randomised controlled trial (Lungsco01).

BACKGROUND: Lungsco01 is the first study assessing the real benefits and the medico-economic impact of video-thoracoscopy versus open thoracotomy for non-small cell lung cancer in the French context. METHODS: Two hundred and fifty nine adult patients from 10 French centres were randomised in this prospective multicentre randomised controlled trial, between July 29, 2016, and November 24, 2020. Survival from surgical intervention to day 30 and later was compared with the log-rank test. Total quality-adjusted-life-years (QALYs) were calculated using the EQ-5D-3L®. For medico-economic analyses at 30 days and at 3 months after surgery, resources consumed were valorised (€ 2018) from a hospital perspective. First, since mortality was infrequent and not different between the two arms, cost-minimisation analyses were performed considering only the cost differential. Second, based on complete cases on QALYs, cost-utility analyses were performed taking into account cost and QALY differential. Acceptability curves and the 95% confidence intervals for the incremental ratios were then obtained using the non-parametric bootstrap method (10,000 replications). Sensitivity analyses were performed using multiple imputations with the chained equation method. RESULTS: The average cumulative costs of thoracotomy were lower than those of video-thoracoscopy at 30 days (€9,730 (SD = 3,597) vs. €11,290 (SD = 4,729)) and at 3 months (€9,863 (SD = 3,508) vs. €11,912 (SD = 5,159)). In the cost-utility analyses, the incremental cost-utility ratio was €19,162 per additional QALY gained at 30 days (€36,733 at 3 months). The acceptability curve revealed a 64% probability of efficiency at 30 days for video-thoracoscopy, at a widely-accepted willingness-to-pay threshold of €25,000 (34% at 3 months). Ratios increased after multiple imputations, implying a higher cost for video-thoracoscopy for an additional QALY gain (ratios: €26,015 at 30 days, €42,779 at 3 months). CONCLUSIONS: Given our results, the economic efficiency of video-thoracoscopy at 30 days remains fragile at a willingness-to-pay threshold of €25,000/QALY. The economic efficiency is not established beyond that time horizon. The acceptability curves given will allow decision-makers to judge the probability of efficiency of this technology at other willingness-to-pay thresholds. TRIAL REGISTRATION: NCT02502318.

Impact of robotic-assisted and video-assisted sympathetic nerve reconstruction on quality of life for severe compensatory hyperhidrosis after thoracic sympathectomy.

OBJECTIVES: Severe compensatory hyperhidrosis (CH) is a disabling complication following thoracic sympathectomy. Our study was to establish valid patient selection criteria and determine outcomes of nerve reconstructive surgery. Furthermore, we assessed the clinical feasibility and safety of a robotic-assisted approach compared to video-assisted thoracoscopic surgery. METHODS: Adults with severe CH following bilateral sympathectomy for primary hyperhidrosis were enrolled. We performed 2 questionnaires: the Hyperhidrosis Disease Severity Scale and the Dermatology Life Quality Index before and 6 months after nerve reconstructive surgery. A one-time evaluation of healthy volunteers (controls) was undertaken to validate the quality of life measures. RESULTS: Fourteen patients (mean age 34.1 ± 11.5 years) underwent sympathetic nerve reconstruction. None of the patients had a recurrence of primary hyperhidrosis. Improvement in quality of life was reported in 50% of patients. Both mean Hyperhidrosis Disease Severity Scale and mean Dermatology Life Quality Index were significantly reduced compared to preoperative assessments. In 10 patients, a video-assisted approach and in 4 patients robotic assistance was utilized. There was no significant difference in outcomes between approaches. CONCLUSIONS: Somatic-autonomic nerve reconstructive surgery offers a reversal in the debilitating symptoms in some patients with severe CH. Proper patient selection, preoperative counselling and management of expectation are of paramount importance. Robot-assisted thoracic surgery is an alternative method to conventional video-assisted surgery. Our study provides a practical approach and benchmark for future clinical practice and research.

Upstaged from cT1a-c to pT2a lung cancer, related to visceral pleural invasion patients, after segmentectomy: is it an indication to complete resection to lobectomy?

OBJECTIVES: Segmentectomy may be indicated for T1a-cN0 non-small-cell lung cancer. However, several patients are upstaged pT2a at final pathological examination due to visceral pleural invasion (VPI). As resection is usually not completed to lobectomy, this may raise issue of potential worse prognosis. The aim of this study is to compare prognosis of VPI upstaged cT1N0 patients operated on by segmentectomy or lobectomy. METHODS: Data of patients from 3 centres were analysed. This was a retrospective study, of patients operated on from April 2007 to December 2019. Survival and recurrence were assessed by Kaplan-Meier method and cox regression analysis. RESULTS: Lobectomy and segmentectomy were performed in 191 (75.4%) and in 62 (24.5%) patients, respectively. No difference in 5-year disease-free survival rate between lobectomy (70%) and segmentectomy (64.7%) was observed. There was no difference in loco-regional recurrence, nor in ipsilateral pleural recurrence. The distant recurrence rate was higher (P = 0.027) in the segmentectomy group. Five-year overall survival rate was similar for both lobectomy (73%) and segmentectomy (75.8%) groups. After propensity score matching, there was no difference in 5-year disease-free survival rate (P = 0.27) between lobectomy (85%) and segmentectomy (66.9%), and in 5-year overall survival rate (P = 0.42) between the 2 groups (lobectomy 76.3% vs segmentectomy 80.1%). Segmentectomy was not impacting neither recurrence, nor survival. CONCLUSIONS: Detection of VPI (pT2a upstage) in patients who underwent segmentectomy for cT1a-c non-small-cell lung cancer does not seem to be an indication to extend resection to lobectomy.

Recurrence-Free Survival in Early and Locally Advanced Large Cell Neuroendocrine Carcinoma of the Lung after Complete Tumor Resection.

BACKGROUND: Large Cell Neuroendocrine Carcinoma (LCNEC) is a rare subtype of lung cancer with poor clinical outcomes. Data on recurrence-free survival (RFS) in early and locally advanced pure LCNEC after complete resection (R0) are lacking. This study aims to evaluate clinical outcomes in this subgroup of patients and to identify potential prognostic markers. METHODS: Retrospective multicenter study including patients with pure LCNEC stage I-III and R0 resection. Clinicopathological characteristics, RFS, and disease-specific survival (DSS) were evaluated. Univariate and multivariate analyses were performed. RESULTS: 39 patients (M:F = 26:13), with a median age of 64 years (44-83), were included. Lobectomy (69.2%), bilobectomy (5.1%), pneumonectomy (18%), and wedge resection (7.7%) were performed mostly associated with lymphadenectomy. Adjuvant therapy included platinum-based chemotherapy and/or radiotherapy in 58.9% of cases. After a median follow-up of 44 (4-169) months, the median RFS was 39 months with 1-, 2- and 5-year RFS rates of 60.0%, 54.6%, and 44.9%, respectively. Median DSS was 72 months with a 1-, 2- and 5-year rate of 86.8, 75.9, and 57.4%, respectively. At multivariate analysis, age (cut-off 65 years old) and pN status were independent prognostic factors for both RFS (HR = 4.19, 95%CI = 1.46-12.07, p = 0.008 and HR = 13.56, 95%CI 2.45-74.89, p = 0.003, respectively) and DSS (HR = 9.30, 95%CI 2.23-38.83, p = 0.002 and HR = 11.88, 95%CI 2.28-61.84, p = 0.003, respectively). CONCLUSION: After R0 resection of LCNEC, half of the patients recurred mostly within the first two years of follow-up. Age and lymph node metastasis could help to stratify patients for adjuvant therapy.

Soluble CD163 is produced by monocyte-derived and alveolar macrophages, and is not associated with the severity of idiopathic pulmonary fibrosis.

The soluble form of the membrane hemoglobin scavenger receptor CD163 (sCD163), released by shedding, is a strong marker for macrophage activation. Serum sCD163 levels rise in several acute inflammatory states and some fibrosing diseases. Monocyte-derived macrophages (MoDM) differentiated by macrophage colony-stimulating factor (M-MoDM) contribute to the pathophysiology of idiopathic pulmonary fibrosis (IPF), an irreversible and rapidly fatal interstitial lung disease. Since M-MoDM express high membrane CD163 levels, we thus postulated that sCD163 could be a relevant biomarker for macrophage activation in IPF. We found that M-MoDM constitutively released higher amounts of sCD163 (49.5 ± 24.5 ng/ml) than monocytes (0.45 ± 0.32 ng/ml) or MoDM differentiated with granulocyte macrophage-stimulating factor (2.24 ± 0.98 ng/ml). The basal production of sCD163 by M-MoDM was increased following stimulation with lipopolysaccharide (123.4 ± 54.9 ng/ml) or ATP (168.9 ± 41.8 ng/ml). The sCD163 release was controlled by metalloproteases but not through ADAM17 activation. Moreover, CD163-positive macrophages and sCD163 were detected in pulmonary tissues and alveolar fluids of Caucasian patients with IPF, respectively. IPF alveolar macrophages constitutively secreted sCD163 amounts (67.6 ± 44.6 ng/µg RNA) which were significantly higher than those released by alveolar macrophages isolated from controls (19.2 ± 7.6 ng/µg RNA) or patients with other interstitial lung disease (31.5 ± 16.6 ng/µg RNA). However, the concentrations of sCD163 in blood serum collected from 155 patients with IPF did not correlate with the severity of their disease. In conclusion, our results show that M-MoDM constituted a pertinent model to study the regulation of sCD163 production. Yet, serum sCD163 values could not provide a prognostic biomarker for IPF in our cohort.

Arsenic trioxide inhibits the functions of lung fibroblasts derived from patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal interstitial lung disease. Currently, no treatment can block or reverse the development of lung fibrosis in patients suffering from IPF. Recent studies indicate that arsenic trioxide (ATO), a safe, effective anti-cancer pro-oxidant drug, prevents the differentiation of normal human lung fibroblasts (NHLFs) in vitro and reduces experimental pulmonary fibrosis in vivo. In this context, we investigated the anti-fibrotic effects of ATO on the main fibrosis functions of human lung fibroblasts (HLFs) isolated from patients with IPF. IPF and non-IPF (control) HLFs were incubated with 0.01-1 µM ATO and stimulated with pro-fibrotic factors (PDGF-BB or TGF-ß1). We measured their rates of proliferation, migration and differentiation and the cell stress response triggered by ATO. ATO did not affect cell viability but strongly inhibited the proliferation and migration of PDGF-BB-stimulated IPF and control HLFs. ATO also prevented myofibroblastic differentiation, as assessed by the expression of α-smooth muscle actin (α-SMA) and collagen-1, and the phosphorylation of SMAD2/3 in TGF-ß1-stimulated HLFs. These antifibrotic effects were associated with increased expression of the transcription factor NRF2 and its target genes NQO1 and HMOX1. Genetic silencing of NRF2 inhibited the ATO-induced cell stress response but did not prevent the ATO-dependent inhibition of α-SMA expression in TGF-ß1-stimulated HLFs. The results demonstrate that ATO, at concentrations similar to exposure in blood plasma of ATO-treated cancer patients, counteracted pro-fibrotic activities of HLFs from IPF patients. We propose to consider ATO for clinical exploration to define the therapeutic potential in patients with IPF.

The illusion of a chest wall tumor: a case-report of sternal tuberculosis.

The incidence rate of tuberculosis in developed countries is low. The most common presentation of this disease is its pulmonary form but with the increasing use of immunosuppressive drugs, extra-pulmonary tuberculosis is re-emerging. Nevertheless, sternal bone involvement is uncommon. We report the case of an eighty-three-year-old man who presented a painful sternal mass which progressed towards cutaneous ulceration. The first diagnostic hypothesis was neoplasia. The pathological and microbiological diagnosis of tuberculosis was achieved after surgical biopsy. The patient received treatment against tuberculosis for nine months enabling recovery without surgery. This case illustrates the importance of having a diagnosis prior to any kind of treatment facing any voluminous parietal thoracic lesions.  This diagnosis is made possible by surgical samples and interdisciplinary teamwork. This case underlines that tuberculosis remains a differential diagnosis that must be evoked in case of unusual bone mass.

A rare case of Neuhauser syndrome associated with a Kommerell diverticulum.

Neuhauser syndrome is a rare vascular anomaly characterized by the esophagus and trachea circling via the ligamentum arteriosum and right aortic arch. Kommerell's diverticulum have the same characteristic by an outpouch at the onset of an aberrant left subclavian artery worsening this compression. The association between these pathologies is very rare and the operative strategy is unclear. We describe a case with the association with a computed tomography scanner aortic reconstruction and a repair's operative strategy.

Intrapleural use of urokinase and DNase in pleural infections managed with repeated thoracentesis: A comparative cohort study.

INTRODUCTION: Evacuation of infected fluid in pleural infections is essential. To date, the use of an intrapleural fibrinolytic agent such as urokinase and DNase has not yet been assessed in infections managed by repeated therapeutic thoracentesis (RTT). METHODS: We performed a retrospective comparative study of two successive cohorts of consecutive patients with pleural infections from 2001 to 2018. Between 2001 and 2010, patients had RTT with intrapleural urokinase (RTT-U). After 2011, patients received intrapleural urokinase and DNase with RTT (RTT-UD). Data were collected through a standardized questionnaire. RESULTS: One hundred and thirty-three patients were included: 93 were men and the mean age was 59 years (standard deviation 17.2). Eighty-one patients were treated with a combination of intrapleural urokinase and DNase, and 52 were treated with intrapleural urokinase only. In the RTT-UD, RTT failure occurred in 14 patients (17%) compared to 10 (19%) in the RTT-U group (P = 0.82). There was no difference between the two groups in intensive care unit admission, surgical referrals or in-hospital mortality. RTT-UD was associated with faster time to apyrexia (aOR = 0.51, 95%CI [0.37-0.72]), a reduced length of hospital stay (aOR = 0.61, 95%CI [0.52-0.73]) and a higher volume of total pleural fluid retrieved (aOR = 1.38, 95%CI [1.02-1.88]). Complications were rare with only one hemothorax in the RTT-UD group and no pneumothorax requiring drainage in either group. CONCLUSION: Compared to urokinase only, intrapleural use of urokinase and DNase in RTT was associated with quicker defervescence, shorter hospital stay and increased volumes of pleural fluid drained. Randomized controlled trials evaluating urokinase and DNase with RTT technique would be required to confirm these results.

Thoracic splenosis: Case report of a symptomatic case.

Thoracic splenosis is the autotransplantation of splenic tissue in the left thoracic cavity as a result of a splenic injury. This rare pathology is usually asymptomatic and may be discovered on incidental imaging, but the diagnosis often requires invasive procedures such as surgery in order to eliminate a neoplasic origin. We report a rare symptomatic case of a 39-year-old man presenting with chest pain and multiple nodules revealed on a computed tomography scan. The patient underwent a surgical exploration and the pathological studies concluded to a thoracic splenosis. Indeed, the previous medical history of the patient revealed a left thoraco-abdominal traumatism during childhood. The aim of this paper is to emphasize that the diagnosis can now be performed using only imaging techniques such as technetium-99 sulfur colloid or labelled heat-denatured red blood cell scintigraphy to avoid unnecessary invasive procedures including thoracotomy.

TNF-α and IL-10 Control CXCL13 Expression in Human Macrophages.

The chemokine CXCL13 controls the normal organization of secondary lymphoid tissues and the neogenesis of ectopic lymphoid structures in nonlymphoid organs, particularly the lungs. The progression and severity of idiopathic pulmonary fibrosis (IPF), a fatal and irreversible interstitial lung disease, is predicted by the circulating blood concentrations of CXCL13. Although CXCL13 is produced by pulmonary tissues, it has not been determined which cells are involved. This study examines CXCL13 production by lung tissue macrophages from patients with IPF and the signaling pathways controlling CXCL13 gene expression in human alveolar macrophages (AM) and monocyte-derived macrophages (MoDM). CXCL13 is found in CD68- and CD206-positive AM from patients with IPF, and the CXCL13 gene is induced in these macrophages and MoDM when they are stimulated with LPS. We found that TNF-α and IL-10 control optimal CXCL13 gene expression in MoDM and possibly in AM by activating the NF-κB and JAK/STAT pathways, respectively. We also found that blood TNF-α and CXCL13 concentrations are significantly correlated in patients with IPF, suggesting that TNF-α contributes to CXCL13 production in humans. In conclusion, the results of this study demonstrate that AM from patients with IPF produces CXCL13 and that the NF-κB and JAK/STAT pathways are required to induce the expression of this major chemokine.

What are the best indicators to assess malnutrition in idiopathic pulmonary fibrosis patients? A cross-sectional study in a referral center.

OBJECTIVES: Little is known about the indicators to assess malnutrition in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to determine the following: 1) the prevalence of malnutrition in IPF patients; 2) the nutritional indicators predictive of low fat-free mass (FFM) as measured by bioimpedance analysis; 3) the IPF patients' characteristics associated with low FFM. METHODS: The IPF patients were consecutively recruited in a referral center for rare pulmonary diseases. Malnutrition was defined as a fat-free mass index (FFMI) = FFM (kg) / (height [m]2) <17 (men) or <15 (women). Nutritional assessment included body mass index (BMI), mid-arm circumference (MAC), triceps skinfold thickness, analogue food intake scale, and serum albumin and transthyretin. The primary endpoint was FFMI. Area under the receiver operating characteristic curve (AUC) assessed low FFMI prediction from nutritional indicators. Multivariable logistic regression determined variables associated with low FFMI. RESULTS: Eighty-one patients were consecutively recruited. Low FFMI prevalence was 28% (23 of 81). BMI AUC was 0.91 (95% confidence interval [CI], 0.84‒0.97) and MAC AUC was 0.85 (0.76‒0.94). Multivariable analysis associated BMI (odds ratio [OR] 0.26 [95% CI, 0.12-0.54], P = 0.0003), male sex (OR 0.02 [0.00-0.33], P = 0.005), and smoking (OR 0.10 [0.01-0.75], P = 0.024) with a lower risk of malnutrition. CONCLUSIONS: Malnutrition occurred in nearly one-third of IPF patients. Malnutrition screening should become systematic based on BMI and MAC, which are good clinical indicators of low FFMI. We propose a practical approach to screen malnutrition in IPF patients.

Optimized radiotherapy to improve clinical outcomes for locally advanced lung cancer.

BACKGROUND: We aimed to evaluate the toxicity, loco-regional control (LRC) and overall survival (OS) associated with accelerated intensity-modulated radiotherapy (IMRT) for locally advanced lung cancer. METHODS: Seventy-three patients were consecutively treated with IMRT from November 2011 to August 2016. A total dose of 66 Gy was delivered using two different schedules of radiotherapy: simultaneous modulated accelerated radiotherapy (SMART) (30 × 2.2 Gy, across 6 weeks) with or without chemotherapy, or moderate hypofractionated radiotherapy (HRT) (24 × 2.75 Gy, across 4 weeks) in patients unfit to receive concomitant chemotherapy. Data on esophageal and pulmonary toxicities, LRC and OS were prospectively collected. RESULTS: The median follow-up duration was 44 months. Severe pneumonitis and esophagitis (grade 3-4) were observed in 7% and 1% of patients respectively, with only one case of grade 4 (pneumonitis). Overall, the 1-year and 2-year LRCs were 76% [95 confidence interval (CI)%: 66-87%] and 62% [95 CI%: 49-77%] respectively. The 1 and 2-year OS rates were 72% [95% CI: 63-83%] and 54% [95 CI%: 43-68%] respectively. None parameters were correlated with LRC or OS. In particular, no difference was observed between patients treated with SMART and H-RT (p = 0.26 and 0.6 respectively), with a 1-year LRC of 74% [95 CI%: 62-86%] for SMART and 91% [95 CI%: 74-100%] for H-RT. No significant differences were observed in the toxicity rates associated with each of the RT schedules. CONCLUSIONS: Accelerated IMRT for locally advanced lung cancer is associated with low toxicities and high LRC. Moderate hypofractionated RT, by decreasing the total treatment time, may be promising in improving clinical outcomes.

Natural History of Localized and Locally Advanced Atypical Lung Carcinoids after Complete Resection: A Joined French-Italian Retrospective Multicenter Study.

BACKGROUND: The natural history and the best modality of follow-up of atypical lung carcinoids (AC) remain ill defined. The aim of this study was to analyze recurrence-free survival (RFS) after complete resection (R0) of stage I-III pulmonary AC. Secondary objectives were prognostic parameters, the location of recurrences, and the modality of follow-up. METHODS: A retrospective review of 540 charts of AC patients treated between 1998 and 2008 at 10 French and Italian centers with experience in lung neuroendocrine tumor management was undertaken. The exclusion criteria were MEN1-related tumor, history of another cancer, referral after tumor relapse, and being lost to follow-up. A central pathological review was performed in each country. RESULTS: Sixty-two patients were included. After a median follow-up time of 91 months (mean 85, range 6-165), 35% of the patients experienced recurrence: 16% were regional recurrences and 19% were distant metastases. Median RFS was not reached. The 1-, 3-, and 5-year RFS rate was 90, 79, and 68%, respectively. In univariate analysis, lymph node involvement (p = 0.0001), stage (p = 0.0001), mitotic count (p = 0.004), and type of surgery (p = 0.043) were significantly associated with RFS. In multivariate analysis, lymph node involvement was significantly associated with RFS (HR 95% CI: 0.000-0.151; p = 0.004). During follow-up, somatostatin receptor scintigraphy, fibroscopy, and abdominal examination results were available for 22, 12, and 25 patients, respectively. The median time interval for imaging follow-up was 10 months. CONCLUSIONS: After complete resection of AC, recurrences were observed mostly within the first 5 years of follow-up, within bronchi, mediastinal nodes, the liver, and bones. In R0 patients, lymph node involvement could help to stratify follow-up intervals. Suboptimal imaging is evidenced.

Combined thoracic and hepatobiliary surgery for iatrogenic bronchobiliary fistula.

Bronchobiliary fistula is a rare pathology mainly caused by hepatic tumors, bile duct obstruction, or hepatic hydatid disease. A 70-year-old man developed a bronchobiliary fistula after biliary stenting. After failure of conservative treatment including endoscopic retrograde biliary drainage, he underwent a combined operation with a two-level approach. Both a thoracotomy and laparotomy were performed, allowing pulmonary resection, diaphragmatic repair, and bile duct reconstruction during the same operation. Postoperative follow-up at one year showed optimal healing of the fistula.

Small pulmonary nodule localization with cone beam computed tomography during video-assisted thoracic surgery: a feasibility study.

OBJECTIVES: To describe a non-invasive guidance procedure, using intraoperative cone beam computed tomography (CBCT) and augmented fluoroscopy to guide lung resection during video-assisted thoracic surgery (VATS). METHODS: Patients with solitary or multiple lung nodules between 5 and 20 mm in size were included. Under general anaesthesia, a moderate pneumothorax allowing the CBCT acquisition was first performed. Then a segmentation of the lesion was performed on a 3D reconstruction. A projection of this 3D reconstruction was then integrated into the digital workspace and automatically registered into the fluoroscopic images, creating an augmented fluoroscopy. The procedure was continued under classic video-thoracoscopic vision taking account of the augmented fluoroscopy to locate the targeted nodule. RESULTS: Eight patients were included (mean age 61 ± 11.7 years): 7 patients had an isolated lesion and 1 patient had two lesions (mean size 13.2 ± 5.1 mm). Their mean depth to the pleura was 21.4 ± 10.7 mm. Four patients underwent a wedge resection associated with lymph node resection. Two patients had an initial wedge resection followed by a complementary lobectomy associated with lymph node resection (primary lung tumour). One patient had a wedge resection in the upper lobe and a lobectomy of the inferior lobe associated with lymph node resection. One patient underwent a conversion and a bilobectomy due to vascular injury. The mean global operating time was 100.6 ± 36.7 min. All the nodules have been identified on the CBCT acquisitions. The segmentation of the lesion has been performed in all cases. We have been able to detect all the nodules and to successfully perform the resection in all cases owing to the augmented fluoroscopy. The mean fluoroscopic time was 134.2 ± 55.0 s. The mean imaging time, between the incision and the final nodule localization, was 11.8 ± 3.8 min. CONCLUSIONS: This paper is the first describing a clinical application of CBCT performed during thoracic surgery. Associated with augmented reality, it offers a significant progress in VATS resection of subpalpable lung nodules. This preliminary experience highlights the potential of the proposed CBCT approach to improve the perception of targeted small tumours during VATS.