Lorenzo Gherzi

Introduction: The management of resectable non-small cell lung cancer has long relied on a relatively limited set of determinants, primarily anatomical resectability and pathological stage. Although these parameters remain central to therapeutic planning, accumulating clinical and translational evidence indicates that they do not fully explain variability in outcomes observed after lung cancer surgery. The primary aim of this review is to evaluate whether current evidence supports the need for a novel heuristic framework in resectable NSCLC. Secondary aims are to examine how host-related, clinical, and data-driven factors contribute to prognosis and treatment selection beyond conventional staging systems. Methods: This review integrates evidence from clinical studies, national registries, and translational analyses to examine how these dimensions contribute to prognosis and treatment selection. Results: Over the past two decades, advances in surgical techniques, perioperative management, systemic therapies, and large-scale clinical databases have revealed additional determinants of prognosis beyond tumor burden, including physiological reserve, nutritional condition, systemic inflammatory state, comorbidities, and socioeconomic environment. Developments in multimodal strategies and minimally invasive surgery have reshaped the therapeutic landscape. Data-driven approaches have identified clinically meaningful subgroups not captured by conventional staging systems. Conclusions: A heuristic framework integrating tumor biology, patient characteristics, and treatment context may better reflect the complexity of contemporary thoracic oncology practice.

Introduction: Lung cancer remains the leading cause of cancer mortality worldwide despite advances in treatment. Patient-related factors beyond tumour characteristics may influence prognosis but are seldom integrated into staging or risk stratification. Methods: We analysed data from 59 101 patients with resectable non-small cell lung cancer (NSCLC) in the French nationwide Epithor database. Using an unsupervised machine learning approach, we applied principal component analysis followed by k- means clustering on 13 patient-specific clinical variables excluding tumour or treatment features, to identify distinct patient phenotypes. Survival differences were evaluated with Kaplan-Meier analysis and Cox proportional hazards models. Results: Five distinct patient phenotypes emerged, reflecting differing distributions of sex, age, pulmonary function, comorbidity and performance status. These phenotypes also showed varied distributions of pathological stage and histology, confirming their clinical relevance. Survival outcomes differed significantly between clusters, with 5-year overall survival ranging from 76.6% (95% CI 75.8% to 77.3%) to 53.8% (95% CI 52.9% to 54.6%). Using the lowest-risk cluster (Cluster 0) as reference, crude HRs for mortality were significantly different between clusters: Cluster 1 (HR 1.48 (95% CI 1.42 to 1.54)), Cluster 2 (HR 1.94 (95% CI 1.84 to 2.03)), Cluster 3 (HR 2.45 (95% CI 2.36 to 2.55)) and Cluster 4 (HR 1.95 (95% CI 1.87 to 2.04)). Cluster assignment remained an independent predictor of survival after adjustment for usual confounders (p<0.001). Conclusions: Phenotype-based clustering of non-tumour patient characteristics identifies clinically meaningful subgroups with distinct survival patterns after NSCLC surgery. Incorporating these phenotypes into preoperative evaluation may enhance risk stratification and support personalised treatment strategies alongside traditional tumour staging.

Background: anatomic lung segmentectomies allow accurate resection of pulmonary lesions, maximizing healthy tissue preservation, and reducing unnecessary loss of lung function. In this setting, accurate preoperative planning is crucial. We present our early experience, detailing the successful use of 3D-CT models in tailoring therapeutic strategies for three patients undergoing complex anatomical lung resections due to neoplastic diseases. Case Presentation: (1) 60-year-old male patient with significant pulmonary functional impairment underwent successful right lower lobe bi-segmentectomy (S7–S8) for carcinoid, stage IA1. (2) 65-year-old female patient with previous left lung resection and functional impairment underwent uneventful right upper lobe bi-segmentectomy (S1–S2) for double lung adenocarcinoma, stage IIb. (3) 67-year-old male with previous ipsilateral lung resection underwent left lower lobe segmentectomy (S8) for metastatic colic adenocarcinoma without any complications. Conclusion: 3D-CT imaging, particularly through VP^TM platform, enhances the safety and precision of complex lung segmentectomy, providing a valuable surgical map for improved outcomes.

Background Thoracic endometriosis syndrome gives rise to various clinical and radiological manifestations. We reviewed the records of patients operated for intrathoracic migration of abdominal viscera through a diaphragmatic hernia secondary to thoracic endometriosis. Methods We retrospectively reviewed the single-center prospective collected database of all patients operated for thoracic endometriosis during the twenty years. All cases in which an abdominal organ was found to be herniated into the thoracic cavity were retrieved. Clinical and pathological data are presented and analyzed. Results Twenty women of median age 36 (range 25–58) years were operated for endometriosis-related diaphragmatic hernia. The hernia was diagnosed concomitantly with endometriosis-related pneumothorax in 13 cases and during the exploration of catamenial thoracic pain in seven cases. There were 18 cases on the right side and two cases on the left side. The median diameter of the hernia was 8 cm (2.5–20 cm). In seventeen cases, the hernia was repaired by direct suture, and in three cases a heterologous prosthesis was positioned. At follow-up, two patients had an episode of recurrent pneumothorax. Conclusions Diaphragmatic hernia should be ruled out in the presence of endometriosis-related pneumothorax or catamenial thoracic pain. Surgery is indicated to make a pathological diagnosis, restore anatomy, and prevent recurrence in patients presenting with pneumothorax.

Non-intubated video-assisted pulmonary metastasectomy: a narrative literature review Lorenzo Gherzi, Michele Ferrari, Alessandro Pardolesi

Background: Telemedicine, and particularly video-consulting, has rapidly accelerated since the coronavirus disease 2019 (COVID-19) pandemic outbreak. The role of e-healthcare for the management of patients with lung diseases is evolving. We report the results of the initial experience of the SmartDoc Project, a telemedicine program activated in a cancer center (Istituto Nazionale Tumori) at the epicenter of the COVID-19 pandemic onset in Italy. Method: The SmartDoc project was established to guarantee continuity of healthcare services for patients with lung cancer during the COVID-19 pandemic crisis. The project was promoted within the National Health System to create a regulatory framework to authorize and reimburse telemedicine in its care delivery for all patients. At the end of the virtual meeting, patients were asked to answer an online survey. Results: From June 19 to December 1, 2020, 83 patients participated in the SmartDoc project and received a teleconsultation. The majority of patients were older than 65 years. Among the 83 televisits, 14 (16.9%) were new visits, 2 (2.4%) second opinions, 4 (4.8%) 30-day postsurgery controls, and 63 (75.9%) long-term follow-up visits. A “complete satisfaction” score (5 out of 5 points) was reported in 70.59% of all the respondents; most patients (76.5%) preferred video-consulting and defined it as better than or comparable to an in-person visit. Conclusion: The favorable initial results of this study suggest that telemedicine should continue beyond the pandemic crisis and should be embedded in a more efficient and accessible healthcare system.

Despite the promising results achieved so far in long-term survival after lung transplantation (LuTx), airway complications (ACs) still arise in the post-operative period. Early diagnosis and prompt treatment of ACs play a critical role in preventing their onset. Specifically, large bronchi ischemia has been recognized as a triggering factor for ACs. Autofluorescence bronchoscopy, which was first introduced for early cancer diagnosis, displays ischemic mucosae as red spots, while normal vascularized mucosae appear in green. The aim of this study is to investigate whether a significant correlation exists between ACs and the red/green (RG) ratio detected on scheduled autofluorescence bronchoscopy up to 1 year after LuTx. This prospective, observational, single-center cohort study initially considered patients who underwent LuTx between July 2014 and February 2016. All patients underwent concomitant white-light and autofluorescence bronchoscopy at baseline (immediately after LuTx), on POD7, POD14, POD21, POD28, POD45, 3 months, 6 months, and 1 year after LuTx. An autofluorescence image of the first bronchial carina distal to the anastomosis was captured and analyzed using histograms for red and green pixels; the R/G ratio was then recorded. Potential ACs were classified according according to the presence of a white-light following the MDS (macroscopic aspect, diameter and suture) criteria. The authors assessed the association between the R/G ratio and the ACs occurrence using a generalized estimating equations model. Thirty-one patients met the inclusion criteria and were therefore selected. Out of a total of 53 bronchial anastomoses, 8 developed complications (late bronchial stenosis), with an average onset time of 201 days after LuTx. ACs showed a similar baseline covariate value when compared to anastomoses that involved no complication. Generalized estimating equations regression indicated a clear association over time between the R/G ratio and the rise of complications (p = 0.023). The authors observed a significant correlation between post-anastomotic stenosis and the delayed decrease of the R/G ratio. Preliminary outcomes suggest that autofluorescence bronchoscopy may be an effective and manageable diagnostic tool, proving complementary to other instruments for early diagnosis of ACs after LuTx. Further research is needed to confirm and detail preliminary findings.

Minimally invasive lung segmentectomy is being more commonly performed, although the rule of sublobar resection as definitive management of non-small cell lung cancer (NSCLC) is still under debate. To date, anatomical segmentectomy should be considered a valid option for the treatment of patients with ground-glass opacity and small-sized early-stage NSCLC, not larger than 2 cm. The safety and feasibility of robotic pulmonary segmentectomy have been widely demonstrated, with comparable results in terms of perioperative morbidity and long-term outcomes compared to video-assisted thoracoscopic approach. Differently from other minimally invasive technique, Robotic platform could be integrated with new upcoming technology such as advanced three-dimensional (3D) images model and multimodal surgical navigation system. These integrated multimodal systems should improve surgical procedure from preoperative planning to intraoperative assistance.

Chest wall resection and reconstruction by composite prosthesis for locally recurrent breast carcinoma