Intraoperative Contrast-Enhanced Ultrasonography (Io-CEUS) in Minimally Invasive Thoracic Surgery for Characterization of Pulmonary Tumours: A Clinical Feasibility Study.

BACKGROUND: The intraoperative detection of solitary pulmonary nodules (SPNs) continues to be a major challenge, especially in minimally invasive video-assisted thoracic surgery (VATS). The location, size, and intraoperative frozen section result of SPNs are decisive regarding the extent of lung resection. This feasibility study investigates the technical applicability of intraoperative contrast-enhanced ultrasonography (Io-CEUS) in minimally invasive thoracic surgery. METHODS: In this prospective, monocentric clinical feasibility study, n = 30 patients who underwent Io-CEUS during elective minimally invasive lung resection for SPNs between October 2021 and February 2023. The primary endpoint was the technical feasibility of Io-CEUS during VATS. Secondary endpoints were defined as the detection and characterization of SPNs. RESULTS: In all patients (female, n = 13; mean age, 63 ± 8.6 years) Io-CEUS could be performed without problems during VATS. All SPNs were detected by Io-CEUS (100%). SPNs had a mean size of 2.2 cm (0.5-4.5 cm) and a mean distance to the lung surface of 2.0 cm (0-6.4 cm). B-mode, colour-coded Doppler sonography, and contrast-enhanced ultrasound were used to characterize all tumours intraoperatively. Significant differences were found, especially in vascularization as well as in contrast agent behaviour, depending on the tumour entity. After successful lung resection, a pathologic examination confirmed the presence of lung carcinomas (n = 17), lung metastases (n = 10), and benign lung tumours (n = 3). CONCLUSIONS: The technical feasibility of Io-CEUS was confirmed in VATS before resection regarding the detection of suspicious SPNs. In particular, the use of Doppler sonography and contrast agent kinetics revealed intraoperative specific aspects depending on the tumour entity. Further studies on Io-CEUS and the application of an endoscopic probe for VATS will follow.

Assessment of concentration and penetration depth of cisplatin in human lung tissue after decortication and hyperthermic exposure.

BACKGROUND: Hyperthermic perfusion of the pleural cavity with cisplatin after pleurectomy/decortication is an additional therapeutic option to reduce local relapse of malignant pleural tumours. Although there are data on the clinical effect, only little is known about the local impact on human lung tissue by cisplatin. The objective of this experimental study is to evaluate both the concentration and the penetration depth of cisplatin in human lung tissue after normothermic and hyperthermic exposure under ex-vivo-in-vitro conditions. METHODS: This study was approved by the local ethics committee. In total, 46 patients underwent elective lobectomy and wedge resections were taken from the resected lobes. A decortication of the visceral pleura was performed under ex-vivo conditions, and the tissue samples were incubated with cisplatin (c =0.05 mg/mL) at 37, 42 or 45 °C for 60 minutes. Then the mass concentration of platinum was measured with flameless atomic absorption spectroscopy and then converted into cisplatin concentration. In addition, the current data were compared with previous data of our working group (42 °C, without decortication). RESULTS: The overall maximum penetration depth was 7.5 mm due to limitations of our methods. The functional maximum penetration depth did not vary with temperature (P=0.243) but by decortication (P<0.001). The cisplatin concentration decreased with increasing penetration depth (P<0.001). An increase of temperature showed no effect on the cisplatin concentration in decorticated tissue samples (P=0.985). However, decortication at 42 °C significantly increased the cisplatin concentration in comparison to not decorticated tissue samples (P=0.005). CONCLUSIONS: Decortication of the visceral pleura increases the cisplatin concentration in the lung tissue. Therefore, it possibly reduces the likelihood of a local relapse. An increase of temperature did not show any effect.

Evaluation of treatment options for postoperative and spontaneous chylothorax in adults.

OBJECTIVES: Both postoperative and spontaneous chylothorax remain therapeutic challenges without recommendations for a standardized treatment approach. Regardless of its aetiology, patients with chylothorax experience prolonged hospitalization and suffer from the associated complications or the invasive therapy administered. METHODS: We conducted a retrospective, observational review of adult patients with chylothorax treated between January 2010 and September 2019. The primary end point was successful management with sustained cessation and/or controlled chylous output. Therapy duration, inpatient stay and the incidence of complications were evaluated as secondary end points. RESULTS: Of the 36 patients included (22 men; median age 63 years), 24 patients (67%) suffered from a postoperative accumulation of chylous fluid in the pleural space; in the remaining 12 (33%) patients, chylothoraces occurred spontaneously. Initial conservative treatment was successful in 42% (n = 15); in the other 20 cases (56%) additional invasive therapeutic strategies were followed. A complicated course requiring more than 1 treatment was seen in 54% (n = 13) of the postoperative and in 58% (n = 7) of the spontaneous cases. The median length of hospitalization was significantly longer in the postoperative group (37.5 vs 15.5 days; P = 0.016). Serious complications were observed only in the postoperative group (P = 0.28). There were no in-hospital deaths. CONCLUSIONS: Basic treatment of both postoperative and spontaneous chylothorax should include dietary measures in all patients. Additional sclerosing radiotherapy and interventional or surgical therapy are often necessary. The choice of therapeutic approach should be indicated, depending on the aetiology and development of the chylothorax. Early, multimodal treatment is recommended.

Video-assisted pulmonary metastectomy is equivalent to thoracotomy regarding resection status and survival.

BACKGROUND: Surgical resection of pulmonary metastases leads to prolonged survival if strictly indicated. Usually, thoracotomy with manual palpation of the entire lung with lymph node dissection or sampling is performed. The aim of this study was to evaluate the role of video-assisted thoracoscopic surgery (VATS) in pulmonary metastectomy with curative intent. METHODS: In this study, all patients with suspected pulmonary metastasis (n = 483) who visited the Center for Thoracic Surgery in Regensburg, between January 2009 and December 2017 were analysed retrospectively. RESULTS: A total of 251 patients underwent metastectomy with curative intent. VATS was performed in 63 (25.1%) patients, 54 (85.7%) of whom had a solitary metastasis. Wedge resection was the most performed procedure in patients treated with VATS (82.5%, n = 52) and thoracotomy (72.3%, n = 136). Postoperative revisions were necessary in nine patients (4.8%), and one patient died of pulmonary embolism after thoracotomy (0.5%). Patients were discharged significantly faster after VATS than after thoracotomy (p < 0.001). Complete (R0) resection was achieved in 89% of patients. The median recurrence-free survival was 11 months (95% confidence interval 7.9-14.1). During follow-up, eight (12.7%) patients in the VATS group and 42 (22.3%) patients in the thoracotomy group experienced recurrence (p = 0.98). The median overall survival was 61 months (95% confidence interval 46.1-75.9), and there was no significant difference with regard to the surgical method used (p = 0.34). CONCLUSIONS: VATS metastasectomy can be considered in patients with a solitary lung metastasis. An open surgical approach with palpation of the lung showed no advantage in terms of surgical outcome or survival.

Clopidogrel improves endothelial function and NO bioavailability by sensitizing adenylyl cyclase in rats with congestive heart failure.

Clopidogrel treatment in patients with coronary artery disease not only inhibits platelet activation but also improves endothelial function and nitric oxide (NO) bioavailability. Congestive heart failure (CHF) is associated with endothelial dysfunction and increased platelet activation. In rats with CHF following myocardial infarction (MI), we investigated whether treatment with clopidogrel modifies endothelial function. Eight weeks after coronary artery ligation, rats with CHF were randomized to placebo or the P2Y(12) receptor antagonist clopidogrel (5 mg/kg twice daily, given by gavage) for another 2 weeks. Afterwards, endothelial function was assessed in isolated aortic rings in organ bath experiments. Acetylcholine-induced, endothelium-dependent, nitric oxide-mediated vasorelaxation was significantly attenuated in CHF rats compared to sham-operated animals, and was significantly improved by treatment with clopidogrel. Adenosine-induced vasorelaxation via adenylyl cyclase stimulation was attenuated in CHF and significantly improved by clopidogrel. Increased vasoconstriction to phenylephrine was observed in CHF, particularly evident under cyclooxygenase inhibition, but prevented by clopidogrel treatment. Vasoconstriction by the P2Y(12) activator 2MeS-ADP was increased in CHF. Clopidogrel-treated CHF animals displayed enhanced phosphorylation of AKT and eNOS. In conclusion, clopidogrel improved endothelial function and NO bioavailability in heart failure. During CHF, sensitivity to P2Y(12) signaling was increased leading to impaired adenylyl cyclase-mediated signaling. Chronic P2Y(12)-blockade with clopidogrel improved adenylyl cyclase-mediated signaling including increased AKT- and eNOS-phosphorylation contributing to improved NO-mediated vasorelaxation.