Significance of Spread Through Air Spaces and Vascular Invasion in Early-stage Adenocarcinoma Survival: A Comprehensive Clinicopathologic Study of 427 Patients for Precision Management.

Spread through air spaces (STAS) is a novel invasive pattern of lung cancer associated with poor prognosis in non-small cell cancer (NSCLC). We aimed to investigate the incidence of STAS in a surgical series of adenocarcinomas (ADCs) resected in our thoracic surgery unit and to identify the association of STAS with other clinicopathological characteristics. We retrospectively enrolled patients with stage cT1a-cT2b who underwent resection between 2016 and 2022. For each case, a comprehensive pathologic report was accessible which included histotype, mitoses, pleural invasion, fibrosis, tumor infiltrating lymphocytes, necrosis, inflammation, vascular and perineural invasion, as well as STAS. PD-L1 expression was also investigated. A total of 427 patients with ADCs underwent surgery. Regarding overall survival (OS), no significant difference was observed between the STAS positive (STAS+) and STAS negative (STAS-) groups ( P =0.44). However, vascular invasion (VI) was associated with a poorer survival probability ( P =0.018). STAS+/VI+ patients had tendentially worse survival compared with STAS+/VI- ( P =0.089). ADCs with pathologic evidence of immune system (IS) activation (TILs>10% and PD-L1≥1) demonstrated significantly increased OS compared with ADCs with no IS and VI. In terms of recurrence rate, no statistical differences were found between the STAS+ and STAS- samples ( P =0.2). VI was also linked to a significantly elevated risk of recurrence ( P =0.0048). Our study suggests that in resected early-stage ADCs, STAS+ does not seem to influence recurrence or mortality. VI was instead an adverse pathologic prognostic factor for both survival and recurrence, whereas IS seemed to be protective.

Tracheal Tissue Engineering: Principles and State of the Art.

Patients affected by long-segment tracheal defects or stenoses represent an unsolved surgical issue, since they cannot be treated with the conventional surgery of tracheal resection and consequent anastomosis. Hence, different strategies for tracheal replacement have been proposed (synthetic materials, aortic allografts, transplantation, autologous tissue composites, and tissue engineering), each with advantages and drawbacks. Tracheal tissue engineering, on the other hand, aims at recreating a fully functional tracheal substitute, without the need for the patient to receive lifelong immunosuppression or endotracheal stents. Tissue engineering approaches involve the use of a scaffold, stem cells, and humoral signals. This paper reviews the main aspects of tracheal TE, starting from the choice of the scaffold to the type of stem cells that can be used to seed the scaffold, the methods for their culture and expansion, the issue of graft revascularization at the moment of in vivo implantation, and experimental models of tracheal research. Moreover, a critical insight on the state of the art of tracheal tissue engineering is also presented.

Surgery for tracheal and laryngotracheal stenosis: a historical case series.

OBJECTIVES: Benign (laryngo-)tracheal stenosis is a relatively rare pathology and its surgical treatment is performed only at few specialized centres. This study aims to investigate outcomes after (laryngo-)tracheal resection-anastomosis, to explore potential risk factors for postoperative complications and to assess whether, over a 33-year period, there were major changes in surgical indications, techniques or outcomes. METHODS: Retrospective, single-centre review of all consecutive patients who underwent tracheal or laryngo-tracheal resection/anastomosis for benign pathologies from 1990 to 2023. RESULTS: Overall, 211 patients underwent tracheal (149 patients, 70.6%) and laryngo-tracheal (62 patients, 29.4%) resection-anastomosis. Of these, 195 patients (93.8%) were affected by iatrogenic stenosis, while 13 (6.2%) suffered from idiopathic stenosis. The median length of stenosis was 25 mm (interquartile range 1-3, 20-30). The overall morbidity rate was 27.5%, while major morbidity occurred in 10.5% of cases. One patient (0.5%) died in the postoperative period. Glottic oedema (17 patients, 8.1%), granulations (12 patients, 5.7%) and restenosis (10 patients, 4.7%) were the main complications. The only independent risk factor for postoperative complications was the length of the resected airway (P = 0.019). In the latest half of the study period, an older median age was observed, and no patient with idiopathic tracheal stenosis underwent surgery. Postoperative outcomes were comparable between surgical eras. CONCLUSIONS: Surgical treatment of (laryngo-)tracheal stenosis is challenging and should be performed by specialized centres. In our experience, morbidity and mortality rates were satisfactory, and in most cases, patients could breathe without tracheostomy. The length of the stenosis was the most significant risk factor for postoperative complications.

Computer-aided designed 3D-printed polymeric scaffolds for personalized reconstruction of maxillary and mandibular defects: a proof-of-concept study.

PURPOSE: To investigate the potential reconstruction of complex maxillofacial defects using computer-aided design 3D-printed polymeric scaffolds by defining the production process, simulating the surgical procedure, and explore the feasibility and reproducibility of the whole algorithm. METHODS: This a preclinical study to investigate feasibility, reproducibility and efficacy of the reconstruction algorithm proposed. It encompassed 3 phases: (1) scaffold production (CAD and 3D-printing in polylactic acid); (2) surgical simulation on cadaver heads (navigation-guided osteotomies and scaffold fixation); (3) assessment of reconstruction (bone and occlusal morphological conformance, symmetry, and mechanical stress tests). RESULTS: Six cadaver heads were dissected. Six types of defects (3 mandibular and 3 maxillary) with different degree of complexity were tested. In all case the reconstruction algorithm could be successfully completed. Bone morphological conformance was optimal while the occlusal one was slightly higher. Mechanical stress tests were good (mean value, 318.6 and 286.4 N for maxillary and mandibular defects, respectively). CONCLUSIONS: Our reconstructive algorithm was feasible and reproducible in a preclinical setting. Functional and aesthetic outcomes were satisfactory independently of the complexity of the defect.

Human tracheal transplantation: A systematic review of case reports.

BACKGROUND: Patients with long-segment airway stenosis not amenable to conventional surgery may benefit from tracheal transplantation. However, this procedure has been only anecdotally reported, and its indications, techniques, and outcomes have not been extensively reviewed. METHODS: We conducted a systematic Literature search to identify all original articles reporting attempts at tracheal transplantation in humans. RESULTS: Of 699 articles found by the initial search, 11 were included in the systematic review, describing 14 cases of tracheal transplantation. Patients underwent transplantation for benign stenosis in nine cases, and for malignancies in five cases. In 12 cases blood supply to the trachea was provided by wrapping the graft in a vascularized recipient's tissue, while in 2 cases the trachea was directly transplanted as a vascularized composite allograft. The transplantation procedure was aborted before orthotopic transplantation in two patients. Among the remaining 12 patients, there was 1 operative mortality, while 4 patients experienced complications. Immunosuppressants drugs were administered to the majority of patients postoperatively, and only one group of authors attempted their withdrawal, in five patients. At the end of follow-up, all 11 patients surviving the operation were alive, but 2 had a recurrent tracheal stenosis requiring an airway appliance for breathing. CONCLUSION: Human tracheal transplantation is still at an embryonic phase. Studies available in the Literature report different surgical techniques, and information on long-term outcomes is still limited. Future research is needed in order to understand the clinical value of this procedure.

An alternative surgical access for posterior tracheal defects or fistulae situated between the cervical and thoracic region.

Posterior tracheal lesion defects between the cervical and the thoracic region represent a surgical challenge. Cervicotomy or median sternotomy might not allow a satisfactory exposure of the defect, and a history of prior neck surgeries could further complicate the procedure. We propose a high posterior right thoracotomic approach, by which the entire posterior aspect of the trachea is visible, up to the cervical region. We describe our experience with this approach, which is best suited for cases where a non-circumferential repair of the trachea is attempted.

Three-Dimensional Imaging-Guided Lung Anatomic Segmentectomy: A Single-Center Preliminary Experiment.

Background and objectives: VATS segmentectomy has been proven to be effective in the treatment of stage I NSCLC, but its technical complexity remains one of the most challenging aspects for thoracic surgeons. Furthermore, 3D-CT reconstruction images can help in planning and performing surgical procedures. In this paper, we present our personal experience of 11 VATS anatomical resections performed after accurate pre-operative planning with 3D reconstructions. Materials and methods: A 3D virtual model of the lungs, airways, and vasculature was obtained, starting from a 1.25 mm 3-phase contrast CT scan, and the original images were used for the semi-automatic segmentation of the lung parenchyma, airways, and tumor. Results: Six males and five females were included in this study. The median diameter of the pulmonary lesion at the pre-operative chest CT scan was 20 mm. The surgical indication was confirmed in seven patients: in three cases, a lobectomy, instead of a segmentectomy, was needed due to intraoperative findings of nodal metastasis. Meanwhile, only in one case, we performed a lobectomy because of inadequate surgical resection margins. Skin-to-skin operative average time was 142 (IQR 1-3 105-182.5) min. The median post-operative stay was 6 (IQR 1-3 3.5-7) days. The mean value of the closest surgical margin was 13.7 mm. Conclusion: Image-guided reconstructions are a useful tool for surgeons to perform complex resections in order to spare healthy parenchyma and to ensure disease-free margins. Nevertheless, human skill and surgeon experience still remain fundamental for the final decisions regarding the proper resection to perform.

Perioperative outcomes in redo VATS for pulmonary ipsilateral malignancy: A single center experience.

BACKGROUND: The role of video-assisted thoracoscopic surgery for oncological major pulmonary resections is now well established; however, the literature within pulmonary re-operations is still limited. The purpose of this study is to evaluate the safety and efficacy of redo thoracoscopic resections for ipsilateral pulmonary malignancy. METHODS: Data from patients undergoing video-assisted thoracoscopic surgery at the Unit of Thoracic Surgery of Padua were analyzed, comparing the results between the first and second ipsilateral surgery. The retrospective study included patients who underwent 2 thoracoscopic surgeries for oncological reasons between 2015 and 2022. The variables considered included patients' baseline characteristics, pre, intra, and postoperative data. RESULTS: The study enrolled 51 patients undergoing ipsilateral thoracoscopic re-operation. The statistical analysis showed that surgical time (95min vs 115min; p = 0.009), the presence of intrapleural adhesions at second surgery (30 % vs 76 %; p < 0.001), overall pleural fluid output (200 vs 560 ml; p = 0.003), time with pleural drainage (2 vs 3 days; p = 0.027), air leaks duration time (p = 0.004) and post-operative day of discharge (3 vs 4 days; p = 0.043) were significantly higher in the re-operation group. No statistical differences were observed between the 2 groups respect to R0 resection rate (90.2 % vs 89.1 %; p=>0.9) and complications (5.8 % vs 15.6 %; p = 0.11). The conversion rate to open surgery was 11.8 %. CONCLUSION: Although some differences emerged between the first and second intervention, they had minimal impact on the clinical course of the patients. Therefore, thoracoscopic surgery has been shown to be safe and effective in re-operations with satisfying perioperative outcomes. To achieve such results, these procedures should be reserved for experienced surgeons.

Intrathymic Localization of Melanoma: A Brief Report of Two Cases and a Review of the Literature.

Intrathymic localizations of melanoma represent a very rare entity, with fewer than ten cases of intrathymic melanoma described in the literature. Herein, we describe two cases of patients who underwent surgical removal of a thymic mass at our thoracic surgery department between 2015 and 2022. The final pathological examination revealed a malignant melanoma in both cases; we therefore carried out a literature review to identify such rare and similar cases. In the first case, the intrathymic localization of melanoma was the first manifestation of the disease, posing a dilemma regarding the metastatic and primitive nature of the neoplasm. The second case described a thymic metastasis from a known previous cutaneous melanoma, for which the patient had successfully been treated six years earlier. After carefully reviewing the literature, we identified only six cases of verified primary intrathymic melanomas and one case of intrathymic metastasis resulting from melanoma previously described. Pathologists should be aware of the occurrence of this rare entity and mindful of the differential diagnoses. Several tools, including immunostaining of melanocytic markers and molecular investigations, are mandatory for final pathological diagnosis.

Hepatoid Adenocarcinoma of the Lung: A Review of the Most Updated Literature and a Presentation of Three Cases.

In a Surgical Thoracic Center, two females and a man were unexpectedly diagnosed with hepatoid adenocarcinoma of the lung (HAL) in a single year. HAL is a rare lung cancer with pathological features of hepatocellular carcinoma with no evidence of liver tumor or other primitive sites of neoplasms. As of today, a comprehensive treatment is still not written. We reviewed the most updated literature on HAL, aiming to highlight the proposed treatments available, and comparing them in terms of survival. General hallmarks of HAL are confirmed: it typically affects middle-aged, heavy-smoker males with a median of 5 cm bulky right upper lobe mass. Overall survival remains poor (13 months), with a longer but non-significant survival in females. Treatments are still unsatisfactory today: surgery guarantees a small benefit compared to non-operated HALs, and only N0 patients demonstrated improved survival (p = 0.04) compared to N1, N2, and N3. Even though the histology is fearsome, these are probably the patients who will benefit from upfront surgery. Chemotherapy seemed to behave as surgery, and there is no statistical difference between chemotherapy only, surgery, or adjuvant treatments, even though adjuvant treatments tend to be more successful. New chemotherapies have been reported with notable results in recent years, such as Tyrosine Kinase Inhibitors and monoclonal antibodies. In this complicated picture, new cases are needed to further build shared evidence in terms of diagnosis, treatments, and survival opportunities.

Postoperative hypoxaemic acute respiratory failure after neoadjuvant treatment for lung cancer: radiologic findings and risk factors.

OBJECTIVES: To investigate the rate of hypoxaemic acute respiratory failure (hARF) on patients undergoing surgery for non-small-cell lung cancer (NSCLC) after neoadjuvant chemotherapy, to describe clinical and radiological findings and to explore potential risk factors for this complication. METHODS: Retrospective review of medical records of all patients who underwent surgery for NSCLC after neoadjuvant chemotherapy at a single centre between 2014 and 2021. Computed tomography scans of patients who developed hARF were reviewed by an experienced radiologist to provide a quantitative assessment of radiologic alterations. RESULTS: The final cohort consisted of 211 patients. Major morbidity was 13.3% (28/211) and hARF was the most common major complication (n = 11, 5.2%). Postoperative mortality was 1.9% (4/211) and occurred only in patients who experienced hARF. Most patients who experienced hARF underwent major procedures, including pneumonectomy (n = 3), lobectomy with chest wall resection (n = 3), bronchial or vascular reconstructions (n = 3) and extended or bilateral resections (n = 2). Analysis of computed tomography findings revealed that crazy paving and ground glass were the most common alterations and were more represented in the non-operated lung. Male gender, current smoking status, pathologic stage III-IV and operative time resulted significant risk factors for hARF at univariable analysis (P < 0.05). CONCLUSIONS: hARF is the main cause of major morbidity and mortality after neoadjuvant therapy and surgery for NSCLC and occurs more frequently after complex and lengthier surgical procedures. Overall, our findings suggest that operative time may represent the most important risk factor for hARF.

Anatomical basis of retrograde thoracic veins flow and its implications in complex thoracic wall reconstructive surgery.

PURPOSE: Internal thoracic veins are increasingly used as recipient's vessels in chest wall reconstructive surgery due to their predictable anatomy and to the possibility to make a double venous anastomosis, exploiting the retrograde flow within them. Over the years, retrograde flow had been explained by the absence of valves in internal thoracic veins, which have been found recently instead. Therefore, our aim is to analyze the retrograde flow and its relationship with valves in the internal thoracic veins. METHODS: We evaluated 32 internal thoracic veins of 16 fresh-frozen specimens with undamaged thoracic cages by dynamic analysis focused on retrograde flow assessment through a partial external circulation system obtained cannulating the subclavian veins. Gross anatomical and morphological evaluations about the presence of valves and their pattern were then made. RESULTS: Efficient, partial, and absent retrograde flow was, respectively, found in 17/30, 8/30 and ITVs and 5/30 internal thoracic veins. Following Arnez's classification, 20/32 Type I and 12/32 Type II internal thoracic veins were identified. Valves were observed in 10/16 specimens (62.50%) corresponding to 36.67% of examined veins (11/30). Three valves were found between the 2nd intercostal space and 12 valves in the 3rd intercostal space. 13/15 valves were bicuspid, 2/15 tricuspid. A significant correlation (p < 0.001) between the retrograde flow and the presence of valves in internal thoracic veins was observed. CONCLUSION: Our study suggests a possible influence of the presence and the number of valves in the efficient retrograde flow of the internal thoracic veins, suggesting that, especially for more complex cases, a preoperative or intraoperative evaluation of the chest wall drainage should be recommended.

Right tracheal sleeve pneumonectomy for complex pulmonary aspergilloma in a patient with diffuse large B-cell lymphoma.

Tracheal sleeve pneumonectomy consists of en bloc resection of the lung, main bronchus plus a section of the carina and its subsequent anastomosis with the remaining main-stem bronchus. We present the unique case of a 56-year-old patient, who underwent tracheal sleeve pneumonectomy for a complex pulmonary aspergilloma invading almost the entire right lung up to the carina.

Resection of the internal carotid artery in selected patients affected by cancer of the skull base.

Invasion of the internal carotid artery (ICA) has been historically considered a criterion of non-resectability of skull base cancer (SBC). Patients affected by SBC who underwent surgery including resection of ICA at two tertiary institutions were included. Demographics, oncologic, and surgical information, complications, and survival outcomes were retrospectively reviewed. Survival outcomes were calculated. Ten patients were included. Three surgical approaches (transnasal endoscopic, transorbital, and transpetrosal) were employed to resect the invaded/abutted tract(s) of the ICA. All patients underwent ICA temporary balloon occlusion test. In two patients, an extracranial-to-intracranial arterial bypass was harvested. Major neuromorbidity was observed in two patients. Perioperative mortality of the series was 10.0%. Mean overall survival was 27.2 months, with 2-year overall and progression-free survival rate of 88.9%. ICA resection is feasible as part of the ablation performed for very advanced SBCs. Survival outcomes are acceptable in adequately selected patients.

Development of a cadaveric head and neck cancer model and three-dimensional analysis of margins in surgical navigation-aided ablations.

INTRODUCTION: The adequacy of the surgical resection is the main controllable variable that is in the hands of the surgical team. There exists an unmet need to increase the rate of negative margins, particularly in cancers invading the craniofacial area. The study aimed 1) at developing a gross tumor model to be utilized for research, educational, and training purposes and 2) establishing the 3-dimensional relationship between the outer surface of the surgical specimen and tumor surface and test the effect of guiding ablations on cadavers with surgical navigation (SN). MATERIAL AND METHODS: Seven cadaver heads were employed to create 24 craniofacial tumor models. Simulation of tumor resections was performed by 8 surgeons. Fourteen and 10 resections were performed with and without SN-guidance, respectively. Gross specimens underwent computed tomography and 3-dimensional analysis through dedicated software. Task load was assessed through a validated questionnaire. Tumor model reliability was studied based on visual analogue scale rate by surgeons and radiologists. RESULTS: SN reduced the rate of margin involvement, particularly by decreasing the percentage of the gross specimen outer surface involvement in areas uncovered by normal bony structures. The workload of SN-aided ablations was found to be medium-to-somewhat-high. Tumor model reliability was deemed satisfactory except for the extension to bony structures. CONCLUSIONS: A gross tumor model for head and neck cancers involving the craniofacial area was developed and resulted satisfactorily reliable from both a surgical and radiologic standpoint. SN reduced the rate of margin involvement, particularly by improving delineation of bone-uncovered areas.

Additive Manufacturing for Personalized Skull Base Reconstruction in Endoscopic Transclival Surgery: A Proof-of-Concept Study.

BACKGROUND: Endoscopic transnasal transclival intradural surgery is limited by a high postoperative cerebrospinal fluid leak rate. The aim of this study was to investigate the role of three-dimensional printing to create a personalized, rigid scaffold for clival reconstruction. METHODS: Two different types of clivectomy were performed in 5 specimens with the aid of neuronavigation, and 11 clival reconstructions were simulated. They were repaired with polylactide, three-dimensional-printed scaffolds that were manually designed in a computer-aided environment based either on the real or on the predicted defect. Scaffolds were printed with a fused filament fabrication technique and different offsets. They were positioned and fixed either following the gasket seal technique or with screws. Postdissection radiological evaluation of scaffold position was performed in all cases. In 3 specimens, the cerebrospinal fluid leak pressure point was measured immediately after reconstruction. RESULTS: The production process took approximately 30 hours. The designed scaffolds were satisfactory when no offset was added. Wings were added during the design to allow for screw positioning, but broke in 30% of cases. Radiological assessment documented maximal accuracy of scaffold positioning when the scaffold was created on the real defect; accuracy was satisfactory when the predicted clivectomy was performed under neuronavigation guidance. The cerebrospinal fluid leak pressure point was significantly higher when the scaffold was fixed with screws compared with the gasket technique. CONCLUSIONS: In this preclinical setting, additive manufacturing allows the creation of customized scaffolds that are effective in reconstructing even large and geometrically complex clival defects.

Step-by-Step Cadaver Dissection and Surgical Technique for Compartmental Tongue and Floor of Mouth Resection.

BACKGROUND: The aim of oral cancer surgery is tumor removal within clear margins of healthy tissue: the latter definition in the literature, however, may vary between 1 and 2 cm, and should be intended in the three dimensions, which further complicates its precise measurement. Moreover, the biological behavior of tongue and floor of mouth cancer can be unpredictable and often eludes the previously mentioned safe surgical margins concept due to the complexity of tongue anatomy, the intricated arrangements of its intrinsic and extrinsic muscle fibers, and the presence of rich neurovascular and lymphatic networks within it. These structures may act as specific pathways of loco-regional tumor spread, allowing the neoplasm to escape beyond its visible macroscopic boundaries. Based on this concept, in the past two decades, compartmental surgery (CS) for treatment of oral tongue and floor of mouth cancer was proposed as an alternative to more traditional transoral resections. METHODS: The authors performed three anatomical dissections on fresh-frozen cadaver heads that were injected with red and blue-stained silicon. All procedures were documented by photographs taken with a professional reflex digital camera. RESULTS: One of these step-by-step cadaver dissections is herein reported, detailing the pivotal points of CS with the aim to share this procedure at benefit of the youngest surgeons. CONCLUSIONS: We herein present the CS step-by-step technique to highlight its potential in improving loco-regional control by checking all possible routes of tumor spread. Correct identification of the anatomical space between tumor and nodes (T-N tract), spatial relationships of extrinsic tongue muscles, as well as neurovascular bundles of the floor of mouth, are depicted to improve knowledge of this complex anatomical area.

Endoscopic-assisted multi-portal compartmental resection of the masticatory space in oral cancer: Anatomical study and preliminary clinical experience.

OBJECTIVES: To present an anatomical cadaver dissection study and our preliminary surgical experience with endoscopic-assisted multi-portal compartmental resection of the masticatory space (MS) in locally advanced oral squamous cell carcinoma (OSCC) of the retromolar area. MATERIALS AND METHODS: Two fresh-frozen cadaver heads were dissected in the Laboratory of Anatomy to define the surgical steps of an endoscopic-assisted multi-portal compartmental approach to the MS. After this preclinical anatomical study, patients affected by locally advanced OSCC originating from the retromolar area with extension to the MS were prospectively enrolled and operated at two Italian referral centers for head and neck cancer between October 2019 and May 2020. RESULTS: Surgical technique of endoscopic-assisted multi-portal compartmental resection of the MS was preclinically defined step by step in 3 phases: transnasal, transoral/trancervical, and multi-portal. Compartmental resection of the MS was successfully completed in all specimens (4 MSs dissected). The surgical technique was subsequently applied in 3 patients affected by primary OSCC of the retromolar area, providing satisfactory results in terms of negative resection margins and local control. CONCLUSIONS: Multi-portal compartmental resection of the MS combining the transnasal and transoral/transcervical corridors is technically feasible. Such an approach to the MS in locally advanced OSCC provides different angles of incidence to the target and full control of tumor margins.