Complex situations in lung cancer: multifocal disease, oligoprogression and oligorecurrence.

With the emergence of lung cancer screening programmes and newly detected localised and multifocal disease, novel treatment compounds and multimodal treatment approaches, the treatment landscape of non-small cell lung cancer is becoming increasingly complex. In parallel, in-depth molecular analyses and clonality studies are revealing more information about tumorigenesis, potential therapeutical targets and the origin of lesions. All can play an important role in cases with multifocal disease, oligoprogression and oligorecurrence. In multifocal disease, it is essential to understand the relatedness of separate lesions for treatment decisions, because this information distinguishes separate early-stage tumours from locally advanced or metastatic cancer. Clonality studies suggest that a majority of same-histology lesions represent multiple primary tumours. With the current standard of systemic treatment, oligoprogression after an initial treatment response is a common scenario. In this state of induced oligoprogressive disease, local ablative therapy by either surgery or radiotherapy is becoming increasingly important. Another scenario involves the emergence of a limited number of metastases after radical treatment of the primary tumour, referred to as oligorecurrence, for which the use of local ablative therapy holds promise in improving survival. Our review addresses these complex situations in lung cancer by discussing current evidence, knowledge gaps and treatment recommendations.

Genetic profiles of oligometastatic non-small-cell lung cancer and corresponding brain metastases.

OBJECTIVES: In patients with oligometastatic non-small-cell lung cancer (NSCLC), systemic therapy in combination with local ablative treatment of the primary tumour and all metastatic sites is associated with improved prognosis. For patient selection and treatment allocation, further knowledge about the molecular characteristics of the oligometastatic state is necessary. Here, we performed a genetic characterization of primary NSCLC and corresponding brain metastases (BM). METHODS: We retrospectively identified patients with oligometastatic NSCLC and synchronous (<3 months) or metachronous (>3 months) BM who underwent surgical resection of both primary tumour and BM. Mutation profiling of formalin-fixed paraffin-embedded tumour cell blocks was performed by targeted next-generation sequencing using the Oncomine Focus Assay panel. RESULTS: Sequencing was successful in 46 paired samples. An oncogenic alteration was present in 31 primary tumours (67.4%) and 40 BM (86.9%). The alteration of the primary tumours was preserved in the corresponding BM in 29 out of 31 cases (93.5%). The most prevalent oncogenic driver in both primary tumours and BM was a KRAS (Kirsten rat sarcoma viral oncogene) mutation (s = 21). In 16 patients (34.8%), the BM harboured additional oncogenic alterations. The presence of a private genetic alteration in the BM was an independent predictor of shorter overall survival. CONCLUSIONS: In oligometastatic NSCLC, BM retain the main genetic alterations of the primary tumours. Patients may profit from targeted inhibition of mutated KRAS. Additional private genetic alterations in the BM are dismal.

Triple-induction treatment for locally advanced non-small cell lung cancer: a case report of pathological complete response.

BACKGROUND: In patients with resectable stage III non-small cell lung cancer (NSCLC), induction chemoimmunotherapy followed by surgical resection has shown unprecedented rates of pathological response and event-free survival. However, a triple-induction including radiochemotherapy and immunotherapy followed by surgical resection has not been routinely established in clinical practice. CASE PRESENTATION: We report the case of a 47-year-old patient with stage IIIA NSCLC who was treated in a combined concept including induction concurrent radiochemotherapy, followed by 4 cycles of pembrolizumab and subsequent intrapericardial left-sided pneumonectomy. Histological analysis revealed a pathological complete response. CONCLUSIONS: The case demonstrates that the combination of neoadjuvant chemo-, radio- and immunotherapy in advanced NSCLC may lead to a relevant down-staging and may enable a R0-resection of a borderline resectable tumor. However, the combination of four different treatment modalities requires resilience and a good performance status. A triple induction treatment may be a promising option for selected patients with locally advanced NSCLC and good performance status.

Artificial intelligence (AI)-assisted chest computer tomography (CT) insights: a study on intensive care unit (ICU) admittance trends in 78 coronavirus disease 2019 (COVID-19) patients.

Background: The global coronavirus disease 2019 (COVID-19) pandemic has posed substantial challenges for healthcare systems, notably the increased demand for chest computed tomography (CT) scans, which lack automated analysis. Our study addresses this by utilizing artificial intelligence-supported automated computer analysis to investigate lung involvement distribution and extent in COVID-19 patients. Additionally, we explore the association between lung involvement and intensive care unit (ICU) admission, while also comparing computer analysis performance with expert radiologists' assessments. Methods: A total of 81 patients from an open-source COVID database with confirmed COVID-19 infection were included in the study. Three patients were excluded. Lung involvement was assessed in 78 patients using CT scans, and the extent of infiltration and collapse was quantified across various lung lobes and regions. The associations between lung involvement and ICU admission were analysed. Additionally, the computer analysis of COVID-19 involvement was compared against a human rating provided by radiological experts. Results: The results showed a higher degree of infiltration and collapse in the lower lobes compared to the upper lobes (P<0.05). No significant difference was detected in the COVID-19-related involvement of the left and right lower lobes. The right middle lobe demonstrated lower involvement compared to the right lower lobes (P<0.05). When examining the regions, significantly more COVID-19 involvement was found when comparing the posterior vs. the anterior halves and the lower vs. the upper half of the lungs. Patients, who required ICU admission during their treatment exhibited significantly higher COVID-19 involvement in their lung parenchyma according to computer analysis, compared to patients who remained in general wards. Patients with more than 40% COVID-19 involvement were almost exclusively treated in intensive care. A high correlation was observed between computer detection of COVID-19 affections and the rating by radiological experts. Conclusions: The findings suggest that the extent of lung involvement, particularly in the lower lobes, dorsal lungs, and lower half of the lungs, may be associated with the need for ICU admission in patients with COVID-19. Computer analysis showed a high correlation with expert rating, highlighting its potential utility in clinical settings for assessing lung involvement. This information may help guide clinical decision-making and resource allocation during ongoing or future pandemics. Further studies with larger sample sizes are warranted to validate these findings.

Acoustics of Breath Noises in Human Speech: Descriptive and Three-Dimensional Modeling Approaches.

PURPOSE: Breathing is ubiquitous in speech production, crucial for structuring speech, and a potential diagnostic indicator for respiratory diseases. However, the acoustic characteristics of speech breathing remain underresearched. This work aims to characterize the spectral properties of human inhalation noises in a large speaker sample and explore their potential similarities with speech sounds. Speech sounds are mostly realized with egressive airflow. To account for this, we investigated the effect of airflow direction (inhalation vs. exhalation) on acoustic properties of certain vocal tract (VT) configurations. METHOD: To characterize human inhalation, we describe spectra of breath noises produced by human speakers from two data sets comprising 34 female and 100 male participants. To investigate the effect of airflow direction, three-dimensional-printed VT models of a male and a female speaker with static VT configurations of four vowels and four fricatives were used. An airstream was directed through these VT configurations in both directions, and their spectral consequences were analyzed. RESULTS: For human inhalations, we found spectra with a decreasing slope and several weak peaks below 3 kHz. These peaks show moderate (female) to strong (male) overlap with resonances found for participants inhaling with a VT configuration of a central vowel. Results for the VT models suggest that airflow direction is crucial for spectral properties of sibilants, /ç/, and /i:/, but not the other sounds we investigated. Inhalation noise is most similar to /ə/ where airflow direction does not play a role. CONCLUSIONS: Inhalation is realized on ingressive airflow, and inhalation noises have specific resonance properties that are most similar to /ə/ but occur without phonation. Airflow direction does not play a role in this specific VT configuration, but subglottal resonances may do. For future work, we suggest investigating the articulation of speech breathing and link it to current work on pause postures. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24520585.

From Voxels to Prognosis: AI-Driven Quantitative Chest CT Analysis Forecasts ICU Requirements in 78 COVID-19 Cases.

Background: The aim of the current study was to investigate the distribution and extent of lung involvement in patients with COVID-19 with AI-supported, automated computer analysis and to assess the relationship between lung involvement and the need for intensive care unit (ICU) admission. A secondary aim was to compare the performance of computer analysis with the judgment of radiological experts. Methods: A total of 81 patients from an open-source COVID database with confirmed COVID-19 infection were included in the study. Three patients were excluded. Lung involvement was assessed in 78 patients using computed tomography (CT) scans, and the extent of infiltration and collapse was quantified across various lung lobes and regions. The associations between lung involvement and ICU admission were analyzed. Additionally, the computer analysis of COVID-19 involvement was compared against a human rating provided by radiological experts. Results: The results showed a higher degree of infiltration and collapse in the lower lobes compared to the upper lobes (p < 0.05) No significant difference was detected in the COVID-19-related involvement of the left and right lower lobes. The right middle lobe demonstrated lower involvement compared to the right lower lobes (p < 0.05). When examining the regions, significantly more COVID-19 involvement was found when comparing the posterior vs. the anterior halves of the lungs and the lower vs. the upper half of the lungs. Patients, who required ICU admission during their treatment exhibited significantly higher COVID-19 involvement in their lung parenchyma according to computer analysis, compared to patients who remained in general wards. Patients with more than 40% COVID-19 involvement were almost exclusively treated in intensive care. A high correlation was observed between computer detection of COVID-19 affections and expert rating by radiological experts. Conclusion: The findings suggest that the extent of lung involvement, particularly in the lower lobes, dorsal lungs, and lower half of the lungs, may be associated with the need for ICU admission in patients with COVID-19. Computer analysis showed a high correlation with expert rating, highlighting its potential utility in clinical settings for assessing lung involvement. This information may help guide clinical decision-making and resource allocation during ongoing or future pandemics. Further studies with larger sample sizes are warranted to validate these findings.

Donor neo-atrial cuff construction after accidental lower lobe vein transection.

BACKGROUND: An inadequate donor left atrial cuff is a rare technical issue after graft procurement for lung transplantation. With regard to the shortage of suitable donor organs for lung transplantation, these organs should be surgically reconstructed to avoid the loss of an organ and a futile intervention in the critically ill recipient. CASE PRESENTATION: We report a case of a 62-year old patient who underwent bilateral sequential lung transplantation for chronic obstructive pulmonary disease. During isolated lung procurement, the right inferior pulmonary vein was circumferentially transsected and separated from the right superior pulmonary and middle lobe veins. Subsequently, a reconstruction of the left atrial cuff with an acellular biological patch was performed to complete the atrium anastomosis. The patient experienced an uneventful postoperative recovery and a follow-up ventilation/perfusion scan showed normal perfusion of the right lower lobe. CONCLUSIONS: This case demonstrates that reconstruction of an inadequate left atrial cuff with a biological patch is feasible and allows for an adequate venous drainage and therefore normal transplant organ function.

Surgical management of lung cancer during the COVID-19 pandemic - a narrative review and single-centre report.

The coronavirus disease 2019 (COVID-19) pandemic has had a severe impact on oncological and thoracic surgical practice worldwide. In many hospitals, the care of COVID-19 patients required a reduction of elective surgery, to avoid viral transmission within the hospital, and to save and preserve personnel and material resources. Cancer patients are more susceptible to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and are at an increased risk of a severe course of disease. In many patients with lung cancer, this risk is further increased owing to comorbidities, older age and a pre-existing lung disease. Surgical resection is an important part of the treatment in patients with early stage or locally advanced non-small cell lung cancer, but the treatment of these patients during the COVID-19 pandemic becomes a challenging balance between the risk of patient exposure to SARS-CoV-2 and the need to provide timely and adequate cancer treatment despite limited hospital capacities. This manuscript aims to provide an overview of the surgical treatment of lung cancer patients during the COVID-19 pandemic including the triage and prioritisation as well as the surgical approach, and our own experience with cancer surgery during the first pandemic wave. We furthermore aim to highlight the risk and potential consequences of delayed lung cancer treatment due to the deferral of surgery, screening appointments and follow-up visits. With much attention being diverted to COVID-19, it is important to retain awareness of cancer patients, maintain oncological surgery and avoid treatment delay during the pandemic.

Patient Selection for Local Aggressive Treatment in Oligometastatic Non-Small Cell Lung Cancer.

One-fourth of all patients with metastatic non-small cell lung cancer presents with a limited number of metastases and relatively low systemic tumor burden. This oligometastatic state with limited systemic tumor burden may be associated with remarkably improved overall and progression-free survival if both primary tumor and metastases are treated radically combined with systemic therapy. This local aggressive therapy (LAT) requires a multidisciplinary approach including medical oncologists, radiation therapists, and thoracic surgeons. A surgical resection of the often advanced primary tumor should be part of the radical treatment whenever feasible. However, patient selection, timing, and a correct treatment allocation for LAT appear to be essential. In this review, we aimed to summarize and discuss the current evidence on patient selection criteria such as characteristics of the primary tumor and metastases, response to neoadjuvant or first-line treatment, molecular characteristics, mediastinal lymph node involvement, and other factors for LAT in oligometastatic NSCLC.

Primary Lung Cancer Organoids for Personalized Medicine-Are They Ready for Clinical Use?

Despite many developments in recent years, non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. Therefore, additional research, aiming to further elucidate the underlying molecular mechanisms of malignant transformation and development of therapy resistance, as well as the identification of additional novel therapeutic avenues, is crucial. For this purpose, reliable in vitro models are indispensable, as they allow for quick identification of suspected oncogenic drivers or evaluation of novel therapeutic strategies in a timely and cost-effective fashion. However, standard two-dimensional cell culture systems, the most frequently used in vitro model, are usually not truly representative of the situation in a patient as these models lack the tumor heterogeneity, the surrounding tumor microenvironment and the three-dimensional complexity of a tumor in vitro. For this reason, 3D cell culture systems, in particular organoids generated from normal non-malignant cells or tumor cell-based organoids (tumoroids), have in recent years gained much attention as alternative in vitro model systems that more closely resemble the actual primary tumor. In this review, we provide an overview of the available literature in the field of NSCLC organoids, which might still be in its infancy, but is gaining momentum.

Pediatric lung transplantation as standard of care.

For infants, children, and adolescents with progressive advanced lung disease, lung transplantation represents the ultimate therapy option. Fortunately, outcomes after pediatric lung transplantation have improved in recent years now producing good long-term outcomes, no less than comparable to adult lung transplantation. The field of pediatric lung transplantation has rapidly advanced; thus, this review aims to update on important issues such as transplant referral and assessment, and extra-corporal life support as "bridge to transplantation". In view of the ongoing lack of donor organs limiting the success of pediatric lung transplantation, donor acceptability criteria and surgical options of lung allograft size reduction are discussed. Post-transplant, immunosuppression is vital for prevention of allograft rejection; however, evidence-based data on immunosuppression are scarce. Drug-related side effects are frequent, close therapeutic drug monitoring is highly advised with an individually tailored patient approach. Chronic lung allograft dysfunction (CLAD) remains the Achilles' heel of pediatric lung transplant limiting its long-term success. Unfortunately, therapy options for CLAD are still restricted. The last option for progressive CLAD would be consideration for lung re-transplant; however, numbers of pediatric patients undergoing lung re-transplantation are very small and its success depends highly on the optimal selection of the most suitable candidate.

Blood consumption in total arterial coronary artery bypass grafting.

BACKGROUND: Accumulating evidence consistently demonstrates that blood transfusion in cardiac surgery is related to decreased short- and long-term survival. We aimed to evaluate periprocedural blood loss and transfusion rates in elective, isolated total arterial coronary artery bypass grafting (CABG) using exclusively skeletonized bilateral internal mammary arteries (IMAs). METHODS: We identified 1011 consecutive patients with coronary artery disease who underwent CABG between 1/2007 and 12/2014. Of them, 595 patients who presented preoperative hemoglobin levels >9md/dl and underwent elective, isolated CABG for multi-vessel coronary artery disease were included in the study population. 419 patients (70.4%) received total arterial CABG using skeletonized bilateral IMAs, in 176 patients (29.6%) mixed CABG (single IMA & saphenous vein) was performed. Propensity score adjustment using 16 variables was applied to control for treatment effect. RESULTS: In patients undergoing total arterial CABG, heterologous blood transfusion could be avoided in 87.8% of all cases. Propensity score adjusted results showed a significantly lower incidence of erythrocyte concentrate transfusion in patients undergoing total arterial CABG compared to mixed CABG (odds ratio 2.74, 95% confidence interval 1.38-5.43, P = 0.004). There were no statistically significant differences in the rates of thrombocyte concentrate (P = 0.39) and fresh frozen plasma transfusions (P = 0.07). CONCLUSIONS: In this study, patients who underwent elective, isolated total arterial CABG using exclusively skeletonized bilateral IMAs showed reduced transfusion rates of erythrocyte concentrates compared to mixed CABG using a combination of single IMA and saphenous vein grafts. No evidence for a higher incidence of complications was found with a total arterial approach.

Intraoperative flow profiles of arterial and venous bypass grafts to the left coronary territory.

OBJECTIVES: The different mechanical and vasodilatory properties of arteries and veins may influence their flow profiles when used for coronary artery bypass grafting (CABG). This may be of significance when assessing the cut-off values for adequate flow. However, conduit-related flow differences are less examined. METHODS: In a study of 268 patients, transit time flowmetry parameters of 336 arterial and 170 venous conduits all grafted to the left coronary territory were compared. With transit time flowmetry, the mean graft flow (MGF), pulsatility index, percentage of diastolic filling and percentage of backwards flow were measured. Conduit-related differences were further compared according to on- or off-pump CABG (ONCABG versus OPCABG) surgery. RESULTS: Overall MGF and pulsatility index were comparable between arterial and venous grafts, but in arterial grafts, MGF was higher during ONCABG than during OPCABG (49.1 ± 35.3 ml/min vs 38.8 ± 26.6 ml/min; P = 0.003). Percentage of diastolic filling was higher in arterial grafts than in venous grafts (overall 71.0 ± 7.9% vs 63.7 ± 11.1%; ONCABG 69.9 ± 7.1% vs 63.9 ± 10.4%; OPCABG 71.9 ± 8.3% vs 63.4 ± 12.2%; all P < 0.001). Furthermore, percentage of backwards flow was higher in arterial grafts than in venous grafts in the overall (2.3 ± 3.2% vs 1.7 ± 3.2%, P = 0.002) and in the ONCABG (2.3 ± 3.2% vs 1.3 ± 2.5%, P < 0.001) cohorts. In venous grafts, percentage of backwards flow was lower during ONCABG versus OPCABG (1.3 ± 2.5% vs 2.6 ± 3.9%, P = 0.016). CONCLUSIONS: No statistically significant difference was observed for MGF and pulsatility index between arterial and venous conduits. However, arterial grafts have significantly higher diastolic filling and backwards flow than venous grafts. Furthermore, arterial grafts have a significantly higher MGF in ONCABG versus OPCABG.

Fracture of a Transcatheter Atrial Septal Defect Occluder Device Causing Mitral Valve Perforation.

Transcatheter atrial septal defect (ASD) device closure has gained increasing popularity over the past decades due to shorter hospital stay and the absence of skin scars. However, concern about the seriousness of device-related complications is accumulating. We report a case of device fracture in a young asymptomatic woman almost 4 years after percutaneous secundum ASD closure, resulting in mitral valve perforation. Subsequently, elective surgical removal of the device and mitral valve reconstruction was performed. This case demonstrates that complications from transcatheter ASD closure may even occur late after implantation.

Intraoperative Bypass Graft Flow Measurement With Transit Time Flowmetry: A Clinical Assessment.

BACKGROUND: Guidelines advocate transit time flowmetry (TTFM) for intraoperative graft patency verification during coronary artery bypass graft surgery (CABG), but studies on accuracy and precision of the TTFM technique are few. In an observational study of CABG patients, we analyzed covariation of left internal mammary artery (LIMA) blood flow with TTFM and free flow measurements. METHODS: Covariation of TTFM and free blood flows was evaluated in 60 patients undergoing CABG using the LIMA as one of the conduits. With LIMA flow measurements routinely performed before and after vasodilation, results are based on 120 paired intraoperative measurements. RESULTS: As demonstrated by a combined approach of regression and Bland-Altman analysis for the two flow situations, TTFM was higher than free flow in 64% of measurements, with an overestimation by TTFM of 7.1% ± 16.3% in the overall cohort (prevasodilation), statistically carried by measurements with 4-mm probes (overestimation by 13.3% ± 15.4%, both p < 0.01). In a multiregression analysis, oversizing of the TTFM probe (odds ratio 9.56, 95% confidence interval: 2.03 to 45.10, p = 0.004) and high flows (odds ratio 1.02, 95% confidence interval: 1.01 to 1.04, p < 0.001) were independent determinants of flow overestimation by TTFM, although in the Bland-Altman analysis no systematic overestimation was seen in the postvasodilation situation. In a receiver-operating characteristics analysis, optimal cutoff value as determined from Youden's index for assuming flow overestimation was 68 mL/min. CONCLUSIONS: Overall, with slight overall overestimation of 7.1%, TTFM is an accurate indicator of LIMA blood flow during CABG, with a clinically acceptable precision. Overestimation may be expected with flows greater than 68 mL/min, but most importantly, in situations with oversized TTFM probes.

Influence of coronary territory on flow profiles of saphenous vein grafts.

BACKGROUND: Differing perfusion of the left and right ventricular coronary territory may influence flow-profiles of saphenous vein grafts (SVGs). We compared flow parameters, measured by transit-time flowmetry (TTFM), in left- and right-sided SVGs during coronary artery by-pass grafting (CABG). METHODS: Routine TTFM measurements were obtained in 167 SVGs to the left territory (55%) and 134 SVGs to the right territory (total of 301 SVGs in 207 patients). The four standard TTFM parameters, [mean graft flow (MGF), pulsatility index (PI), percentage diastolic filling (%DF), and percentage backward flow (%BF)] were compared. Differences in flow parameters were also examined according to surgical technique (on- vs. off-pump). RESULTS: No significant difference between coronary territories was found for MGF, PI and %BF. However, a higher %DF was noted in left-sided SVGs in the overall cohort as well as in the on-pump (both p < 0.001) and the off-pump cohorts (p = 0.07). Further, a significantly higher %BF was found in SVGs performed off-pump to the left territory (1.2 ± 2.5 vs. 2.3 ± 3.0, p = 0.023). In a multivariate regression analysis, anastomosing a SVG to the left territory was weakly associated with higher PI (OR = 0.36, p = 0.026) and strongly associated with higher %DF (OR = 5.1, p < 0.001). No significant association was found for MGF, PI, %DF or %BF in either the on-pump nor the off-pump cohorts. CONCLUSIONS: Although statistically significant, the established differences in TTFM parameters between left- and right-sided vein grafts were small and unlikely to be of clinical relevance.

Influence of external stenting on venous graft flow parameters in coronary artery bypass grafting: a randomized study.

OBJECTIVES: Long-term patency of saphenous vein grafts (SVGs) remains a concern after coronary artery bypass grafting. Interventions to overcome this problem include monitoring intraoperative flow profile and, more recently, external stenting of SVGs. It is not known to what extent external stenting changes the perioperative flow characteristics of SVGs. The aim of this study was to assess whether the presence of an external stent affects perioperative graft flow parameters as evaluated by transit time flowmetry. METHODS: Thirty-five patients were included from 1 centre participating in a multicentre, randomized clinical trial of external stenting of SVGs. Patients were eligible if scheduled for on-pump multivessel coronary artery bypass grafting including planned SVGs to both the right and the left coronary territories. Each patient received external stenting of a single SVG randomly allocated intraoperatively to either coronary territory. The primary end-points were mean graft flow, pulsatility index, percentage of diastolic filling and percentage of backward flow in stented versus non-stented SVGs. RESULTS: External stenting was performed in 17 SVGs supplying the left territory (20 non-stented SVGs for control) and in 18 SVGs supplying the right territory (18 non-stented SVGs for control). No significant difference was found in flow parameters between stented and non-stented SVGs in the overall group or between pre-defined groups of SVGs supplying the right and left territories, respectively. CONCLUSIONS: External stenting of SVGs do not affect intraoperative flow parameters significantly. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02511834.