Alfonso Fiorelli

Methylthioadenosine phosphorylase (MTAP) loss is an emerging biomarker in several human malignancies, mainly due to its frequent co-deletion with CDKN2A on chromosome 9p21. Beyond its diagnostic value, MTAP deficiency has important biological consequences, including metabolic reprogramming, immune microenvironment modulation, and increased dependency on PRMT5-related pathways. This review summarizes the current evidence on MTAP alterations across different tumor types. The role of MTAP immunohistochemistry as a practical surrogate for CDKN2A homozygous deletion is discussed, together with its advantages and interpretative limitations. In addition, the potential predictive relevance of MTAP loss for immunotherapy, antifolate-based treatments, and novel PRMT5-targeted strategies is explored. Overall, MTAP assessment represents a promising tool in modern diagnostic pathology and precision oncology, bridging morphology, molecular alterations, and therapeutic decision-making.

Objectives: Occult visceral pleural invasion (VPI) may upstage cT1N0M0 non-small cell lung cancer (NSCLC) to pT2aN0M0. We compared perioperative and oncological outcomes after segmentectomy and lobectomy in this setting. Methods: This multicentre retrospective study included cT1N0M0 NSCLC patients treated with minimally invasive segmentectomy or lobectomy who were subsequently upstaged to pT2aN0M0 because of VPI. Propensity-score matching (PSM) (1:1) was performed. Perioperative and oncological outcomes were compared. Exploratory and sensitivity analyses evaluated tumours ≤20 mm and patients who did not receive adjuvant therapy. Results: Among 448 patients, 104 underwent segmentectomy and 344 underwent lobectomy. After PSM, 87 matched pairs were analysed. Segmentectomy was associated with shorter operative time, lower postoperative morbidity, and shorter hospital stay. No significant differences were observed in disease-free survival (DFS) (P = .387), overall survival (OS) (P = .075), or cancer-specific survival (CSS) (P = .388). Multivariable analysis identified adjuvant therapy and age as independent predictors of DFS and OS, respectively, whereas the extent of resection was not independently associated with survival. In patients with a preoperative computed tomography (CT) total tumour diameter ≤20 mm, segmentectomy was associated with a higher rate of local recurrence (13.8 vs 2.0%, P = .037) and worse adjusted DFS and OS, despite no significant differences in Kaplan-Meier survival. Conclusions: In patients with cT1N0M0 NSCLC upstaged to pT2aN0M0 because of occult VPI, segmentectomy was associated with lower postoperative morbidity, with no significant differences in oncological outcomes in the overall matched cohort. Exploratory findings in patients with a preoperative CT total tumour diameter ≤20 mm suggest a higher risk of local recurrence and worse adjusted DFS and OS after segmentectomy, warranting further validation.

Background: Mediastinal staging is crucial in patients undergoing lung resection for cancer to plan further adjuvant. Current guidelines recommend resecting at least three mediastinal lymph node stations, including Group7. Herein, we evaluated the role of intraoperative Contrast‐enhanced ultrasound (CEUS) to guide lymph node resection in patients undergoing RATS lobectomy for management of non‐small cell lung cancer. Methods: It was a retrospective study including 24 consecutive patients underwent RATS lobectomy for management lung cancer. The hilar and mediastinal lymph node was firstly evaluated with a CEUS and then resected. A bolus of 2.4 mL SonoVue was injected into the antecubital vein and the perfusion was scanned continuously for at least 3 min. The dynamic image obtained was used to evaluate the mediastinal and hilar lymph nodal and guide the dissection. A radical lymph‐adenectomy was performed in all cases independently from the CEUS results. Results: We evaluated 144 lymph nodes with a CEUS during RATS lobectomy. Histological examination of the lymph nodes showed five lymph nodes metastatic (3.5%); of which 3 (60%) metastatic N1 lymph nodes; 2 (40%) metastatic N2 lymph nodes. Intraoperative CEUS of hilar and mediastinal lymph nodes showed: sensitivity 83%; specificity 98%; PPV, 77%; PNV, 99% and accuracy 94%. Conclusion: Our preliminary results seem to confirm the value of intraoperative CEUS to assess lymph node resection during RATS lobectomy. It may help the lymph node dissection and reduce the risk of intraoperative injury. Future study should confirm our preliminary results and confirm the value of intraoperative CEUS.

We report the case of an 83-year-old woman with an undiagnosed mediastinal mass and a loculated, symptomatic pericardial effusion, managed by a concomitant robotic pericardial window and tumour biopsy under intraoperative ultrasound guidance, with a final diagnosis of B-cell lymphoma. The patient underwent chemo-immunotherapy; at the 6-month follow-up, an echocardiogram and chest computed tomography showed tumour shrinkage and no effusion recurrence.

Herein, we reported the use of Intraoperative‐Contrast Enhanced Ultrasonography (Io‐CEUS) during Robotic Assisted Thoracic Surgery (RATS) for identification of malignant lung nodule that was missed during previous operation. Pre‐operative CT scan with 3D reconstruction defined the prompt position of the target lesion within S8 segment of right lower lobe and the anatomic landmarks as the distance from interlobar fissure and diaphragm. The lesion was then successfully detected by Io‐CEUS. The different arterial enhancement observed during wash‐in (hyperenhancement) and wash‐out (hypo‐enhancement) phases helped to differentiate the nodule from lung parenchyma. The lesion was resected by mechanical stapler and frozen section analysis diagnosed metastasis from colon carcinoma. Post‐operative course was unremarkable; patient was discharged on post‐operative day 3.

HARMONi-6 trial: a further development in the management of advanced squamous non-small-cell lung cancer

The journal retracts the article titled “AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma”

Herein, we described a redo tracheostomy in a patient with a large mediastinal goitre. A percutaneous dilation tracheostomy was performed under rigid bronchoscopy. Rigid bronchoscopy provided several advantages compared with flexible bronchoscopy. It suctioned significant blood and secretions, secured the airway and ensured adequate ventilation during the entire procedure. Technically, the rigid barrel displacing the trachea anteriorly facilitated the insertion of dilators and the tracheostomy cannula and reduced the risk of airway injury. This strategy was safe and feasible and could turn out to be useful in patients with difficult airways where standard percutaneous dilation tracheostomy is difficult to perform.

Background: Most predictive models for assessing the invasiveness of pure ground-glass nodules (pGGOs) have been developed in Asian populations, which may limit their applicability to Western cohorts. As the detection of pGGOs continues to increase, there is a growing need for reliable, population-specific tools to support preoperative decision-making. Methods: This multicenter retrospective study analyzed patients from the GORDON database who underwent surgical resection for pGGOs < 40 mm between January 2013 and June 2024. Radiologic features were assessed using preoperative high-resolution and contrast-enhanced CT scans. Univariate and multivariable logistic regression analyses were performed to identify independent predictors of invasive adenocarcinoma (IAC). A radiologic nomogram was developed and internally validated using a training (80%) and validation (20%) cohort. Results: A total of 490 pGGOs were included, of which 421 (85.9%) were IAC and 69 (14.1%) noninvasive (Adenocarcinoma in Situ or Minimally Invasive Adenocarcinoma). Upon multivariable analysis, maximum radiologic diameter (adjusted odds ratio [aOR] = 1.09, p = 0.001), spiculated margins (aOR = 3.07, p = 0.006), and unenhanced CT attenuation (aOR = 1.01, p < 0.001) were independent predictors of invasiveness. These variables were incorporated into a nomogram demonstrating good discrimination, with an area under the curve (AUC) of 0.86 (95% CI, 0.81–0.90) in the training cohort and 0.80 (95% CI, 0.70–0.90) in the validation cohort. Conclusions: A radiologic nomogram based on routinely available CT features enables accurate estimation of invasive adenocarcinoma risk in pGGOs. By integrating parameters beyond lesion size, this tool supports personalized management and may improve preoperative decision-making.