Ability of 18F-FDG Positron Emission Tomography Radiomics and Machine Learning in Predicting KRAS Mutation Status in Therapy-Naive Lung Adenocarcinoma.

OBJECTIVE Considering the essential role of KRAS mutation in NSCLC and the limited experience of PET radiomic features in KRAS mutation, a prediction model was built in our current analysis. Our model aims to evaluate the status of KRAS mutants in lung adenocarcinoma by combining PET radiomics and machine learning. METHOD Patients were retrospectively selected from our database and screened from the NSCLC radiogenomic dataset from TCIA. The dataset was randomly divided into three subgroups. Two open-source software programs, 3D Slicer and Python, were used to segment lung tumours and extract radiomic features from 18F-FDG-PET images. Feature selection was performed by the Mann-Whitney U test, Spearman's rank correlation coefficient, and RFE. Logistic regression was used to build the prediction models. AUCs from ROCs were used to compare the predictive abilities of the models. Calibration plots were obtained to examine the agreements of observed and predictive values in the validation and testing groups. DCA curves were performed to check the clinical impact of the best model. Finally, a nomogram was obtained to present the selected model. RESULTS One hundred and nineteen patients with lung adenocarcinoma were included in our study. The whole group was divided into three datasets: a training set (n = 96), a validation set (n = 11), and a testing set (n = 12). In total, 1781 radiomic features were extracted from PET images. One hundred sixty-three predictive models were established according to each original feature group and their combinations. After model comparison and selection, one model, including wHLH_fo_IR, wHLH_glrlm_SRHGLE, wHLH_glszm_SAHGLE, and smoking habits, was validated with the highest predictive value. The model obtained AUCs of 0.731 (95% CI: 0.619~0.843), 0.750 (95% CI: 0.248~1.000), and 0.750 (95% CI: 0.448~1.000) in the training set, the validation set and the testing set, respectively. Results from calibration plots in validation and testing groups indicated that there was no departure between observed and predictive values in the two datasets (p = 0.377 and 0.861, respectively). CONCLUSIONS Our model combining 18F-FDG-PET radiomics and machine learning indicated a good predictive ability of KRAS status in lung adenocarcinoma. It may be a helpful non-invasive method to screen the KRAS mutation status of heterogenous lung adenocarcinoma before selected biopsy sampling

Minimally Invasive Vacuum-Assisted Closure Therapy With Instillation (Mini-VAC-Instill) for Pleural Empyema

Enthusiasm for minimally invasive thoracic surgery is increasing. Thoracoscopy plays a significant therapeutic role in the fibrinopurulent stage (stage II) of empyema, in which loculated fluid cannot often be adequately drained by chest tube alone. For some debilitated and septic patients, further procedures such as open-window thoracostomy (OWT) with daily wound care or vacuum-assisted closure (VAC) therapy are necessary. In the present article, we propose a new option of minimally invasive VAC therapy including a topical solution of the empyema without open-window thoracostomy (Mini-VAC-instill). Three patients who underwent surgery using this technique are also presented. The discussion is focused on the advantages and disadvantages of the approach

Radical surgical resection of advanced thymoma and thymic carcinoma infiltrating the heart or great vessels with cardiopulmonary bypass support

Background Radical surgical resection of advanced thymic tumors invading either the heart or great vessels facing towards the heart is uncommonly performed because of the potential morbidity and mortality. To achieve a complete tumor resection, the use of cardiolpulmonary bypass (CPB) support might be necessary. Methods Retrospective analysis of the results in six patients, who underwent radical tumor resection with CBP support. Results Mean age was 46 years (27 to 66 years) and five patients were male. Tumor infiltration of the heart or the great vessels was evident in all patients. Five patients underwent induction therapy. Two patients were operated in complete cardioplegic arrest (antegrade cerebral perfusion: n = 1). Arterial cannulation of the ascending aorta (n = 5) or the femoral artery (n = 1) and venous cannulation of the right atrium (n = 4) or the femoral vein (n = 2) were performed. Resection of the left brachiocephalic vein (n = 6), resection of the superior caval vein (n = 2), the ascending aorta (n = 1) and the complete aortic arch with outgoing branches (n = 1) were performed. A macroscopic complete resection (R0/R1) was achieved in five patients, whereas one patient was resected incompletely (R2). In-hospital mortality was 0 %. Three (50 %) patients needed operative revision (hematothorax: n = 2, chylothorax: n = 1). All patients had a complicated postoperative course and developed respiratory insufficiency. Conclusions Locally advanced thymoma/thymic carcinoma invading the heart or great vessels can be treated with radical surgical resection alongside with increased perioperative morbidity. The usage of CBP improves the chance of complete tumor resection in selected patients and might lead to a prolonged survival

Complex pleural empyema can be safely treated with vacuum-assisted closure

<p>Abstract</p> <p>Objective</p> <p>For patients with postoperative pleural empyema, open window thoracostomy (OWT) is often necessary to prevent sepsis. Vacuum-assisted closure (VAC) is a well-known therapeutic option in wound treatment. The efficacy and safety of intrathoracal VAC therapy, especially in patients with pleural empyema with bronchial stump insufficiency or remain lung, has not yet been investigated.</p> <p>Methods</p> <p>Between October 2009 and July 2010, eight consecutive patients (mean age of 66.1 years) with multimorbidity received an OWT with VAC for the treatment of postoperative or recurrent pleural empyema. Two of them had a bronchial stump insufficiency (BPF).</p> <p>Results</p> <p>VAC therapy ensured local control of the empyema and control of sepsis. The continuous suction up to 125 mm Hg cleaned the wound and thoracic cavity and supported the rapid healing. Additionally, installation of a stable vacuum was possible in the two patients with BPF. The smaller bronchus stump fistula closed spontaneously due to the VAC therapy, but the larger remained open.</p> <p>The direct contact of the VAC sponge did not create any air leak or bleeding from the lung or the mediastinal structures. The VAC therapy allowed a better re-expansion of remaining lung.</p> <p>One patient died in the late postoperative period (day 47 p.o.) of multiorgan failure. In three cases, VAC therapy was continued in an outpatient service, and in four patients, the OWT was treated with conventional wound care. After a mean time of three months, the chest wall was closed in five of seven cases. However, two patients rejected the closure of the OWT. After a follow-up at 7.7 months, neither recurrent pleural empyema nor BPF was observed.</p> <p>Conclusion</p> <p>VAC therapy was effective and safe in the treatment of complicated pleural empyema. The presence of smaller bronchial stump fistula and of residual lung tissue are not a contraindication for VAC therapy.</p

Immune Architecture of Colorectal Lung Metastases and Implications for Patient Survival

Background: Pulmonary metastases occur in 10-20% of patients with colorectal cancer and significantly influence long-term survival. In this study, the immunological architecture of colorectal lung in comparison to liver metastases and its impact on patient survival were examined. Methods: Specimens of patients with colorectal lung and liver metastases were stained for HE, CD4, CD8, CD20, CD68 and CD45RO. Besides histomorphological evaluation, immunohistochemical stainings were analyzed for the respective cell numbers separately for tumor area, infiltrative margin and distant lung or liver stroma. These findings were correlated with clinical data and patient outcome. Results: In colorectal lung (n = 69) in comparison to liver (n = 222) metastases, the immunological focus is located in the tumor region. A high CD4(+) cell infiltration of this area is associated with prolonged survival of patients after resection of colorectal lung metastases [103 +/- 33 (high) vs. 37 +/- 6 months (low); p = 0.0246]. Patients who were treated with preoperative chemotherapy did not show differences in immune infiltrates compared to chemotherapy-naive patients. Conclusion: Colorectal lung and liver metastases showed a distinct immunological architecture. A dense cell infiltration of colorectal lung metastases by CD4(+) cells was related to prolonged patient survival. Preoperative chemotherapy did not influence cellular immune infiltrates. (C) 2016 S. Karger AG, Base

Disseminated cancer cells detected by immunocytology in lymph nodes of NSCLC patients are highly prognostic and undergo parallel molecular evolution

In melanoma, immunocytology (IC) after sentinel lymph node disaggregation not only enables better quantification of disseminated cancer cells (DCCs) than routine histopathology (HP) but also provides a unique opportunity to detect, isolate, and analyse these earliest harbingers of metachronous metastasis. Here, we explored lymph node IC in non-small cell lung cancer (NSCLC). For 122 NSCLC patients, 220 lymph nodes (LNs) were split in half and prepared for IC and HP. When both methods were compared, IC identified 22% positive patients as opposed to 4.5% by HP, revealing a much higher sensitivity of IC (p < 0.001). Assessment of all available 2,952 LNs of the same patients by HP uncovered additional patients escaping detection of lymphatic tumour spread by IC alone, consistent with the concept of skip metastasis. A combined lymph node status of IC and complete HP on a larger cohort of patients outperformed all risk factors in multivariable analysis for prognosis (p < 0.001; RR = 2.290; CI 1.407–3.728). Moreover, isolation of DCCs and single-cell molecular characterization revealed that (1) LN-DCCs differ from primary tumours in terms of copy number alterations and selected mutations and (2) critical alterations are acquired during colony formation within LNs. We conclude that LN-IC in NSCLC patients when combined with HP improves diagnostic precision, has the potential to reduce total workload, and facilitates molecular characterization of lymphatically spread cancer cells, which may become key for the selection and development of novel systemic therapies. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Chirurgische Therapie von Pseudotumoren der Lunge

Introduction Pseudotumour of the lung is a collective term for various subentities. Some subgroups are considered to be intermediary malignant tumours. A pseudotumour is a rare condition, which makes it difficult to estimate its incidence and prevalence. Methods Retrospective analysis of all surgically treated patients between 2008 and 2015 diagnosed with a pseudotumour of the lung. The primary endpoint of this study was to estimate the rates of local recurrence and metastasis. Secondary endpoints were to determine the nomenclature, medical history, treatment, and the perioperative course. Results Out of 27 patients (10 females and 17 males) with a median age of 58 years, 19 patients (70%) had an inflammatory pseudotumour (IPT), and four patients (15%) had an inflammatory myofibroblastoma (IMT). Two patients had a pneumocytoma/histiocytoma. A preoperative pulmonary infection was present in 12 (44%) patients. The average tumour size was 2.1 cm (0.8-5.3 cm), with the lower pulmonary lobes being mostly affected (52%). One enucleation, 20 atypical wedge resections and six anatomical resections were performed. This was done in a minimally invasive procedure (VATS) in 48% of cases (13/27). R0 resection was achieved in 93% of cases (25/27). Complications occurred in seven (26%) patients. The difference between the duration of hospital stay (mean duration 8 days) after open resection and VATS was minimal (8.8 vs. 7.2 days). Patients were followed up over a period of 4 years, during which time only one patient developed a tumour recurrence, which led to the patient's death, although she had had a R0 resection of an IMT. Conclusions The treatment of choice for pseudotumours of the lung is R0 resection, preferably with VATS. Most patients have a benign course of disease, although relapses are possible in some cases, especially in IMT. Follow-up monitoring is necessary for IMT. The application of a uniform nomenclature and classification would be a sensible approach