Pathological complete response in a patient with pleural mesothelioma treated with immunotherapy: a case report.

The role of immunotherapy in the multimodal treatment for pleural mesothelioma (PM) is still under investigation, particularly in the preoperative setting. Pathological complete response (pCR) has been previously described after chemotherapy and immunotherapy; however, there is no prior experience reported with immunotherapy alone before surgery. We report the case of a 58-year-old male with biphasic PM treated with immunotherapy, resulting in a major clinical partial response. Following a multidisciplinary evaluation between thoracic surgeons, medical oncologists, pathologists, radiologists and radiation oncologists, the patient underwent surgery with radical intent through a right extended pleurectomy/decortication (eP/D). Histopathological examination of the specimen confirmed a pathological Complete Response (pCR). This case supports the feasibility and potential efficacy of combining preoperative immunotherapy with surgery in the management of advanced PM.

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.

Impact of a standardized protocol for chest tube management after VATS pulmonary resections on post-operative outcomes and complications.

Chest tube management represents a major issue after lung surgery as no protocol is widely accepted and tube management is generally based on local or personal habits. Aim of this study is to evaluate the impact of a standardized protocol for chest tube management after pulmonary resections on the post-operative outcomes. We performed a single center retrospective analysis of all adult patients undergoing thoracoscopic pulmonary resection from January 2020 to December 2021. Starting from January 2021 a standardized protocol of chest tube management was applied after all procedures. Patients were divided into two groups according to the chest tube management strategy. he two groups had similar pre-operative characteristics and the extent of lung resection was comparable. Intervention group had significantly shorter time to chest tube removal (median 1 vs 3 days, p < 0.001) and post-operative length of stay (median 3 vs 4 days, p < 0.001). Despite earlier chest tube removal, there was not an increased incidence of post-removal complications. On multivariable analysis, the new chest drain management strategy was an independent predictor of earlier chest tube removal. A standardized protocol of chest tube management allows for an earlier chest tube removal and a shorter hospital stay, without an increase in post-operative complications.

Development and In Vitro/In Vivo Comparative Characterization of Cryopreserved and Decellularized Tracheal Grafts.

Tracheal reconstruction represents a challenge when primary anastomosis is not feasible. Within this scenario, the study aim was to develop a new pig-derived decellularized trachea (DecellT) to be compared with the cryopreserved counterpart (CryoT) for a close predictive analysis. Tracheal segments underwent decellularization by a physical + enzymatic + chemical method (12 cycles); in parallel, cryopreserved samples were also prepared. Once decellularized (histology/DNA quantification), the two groups were characterized for Alpha-Gal epitopes/structural proteins (immunohistochemistry/histology/biochemical assays/second harmonic generation microscopy)/ultrastructure (Scanning Electron Microscopy (SEM))/mechanical behaviour. Cytotoxicity absence was assessed in vitro (extract-test assay/direct seeding, HM1SV40 cell line) while biocompatibility was verified in BALB/c mice, followed by histological/immunohistochemical analyses and SEM (14 days). Decellularization effectively removed Alpha-Gal epitopes; cartilage histoarchitecture was retained in both groups, showing chondrocytes only in the CryoT. Cryopreservation maintained few respiratory epithelium sparse cilia, not detectable in DecellT. Focusing on ECM, preserved structural/ultrastructural organization and collagen content were observed in the cartilage of both; conversely, the GAGs were significantly reduced in DecellT, as confirmed by mechanical study results. No cytotoxicity was highlighted by CryoT/DecellT in vitro, as they were also corroborated by a biocompatibility assay. Despite some limitations (cells presence/GAGs reduction), CryoT/DecellT are both appealing options, which warrant further investigation in comparative in vivo studies.

Preclinical and clinical orthotopic transplantation of decellularized/engineered tracheal scaffolds: A systematic literature review.

Severe tracheal injuries that cannot be managed by mobilization and end-to-end anastomosis represent an unmet clinical need and an urgent challenge to face in surgical practice; within this scenario, decellularized scaffolds (eventually bioengineered) are currently a tempting option among tissue engineered substitutes. The success of a decellularized trachea is expression of a balanced approach in cells removal while preserving the extracellular matrix (ECM) architecture/mechanical properties. Revising the literature, many Authors report about different methods for acellular tracheal ECMs development; however, only few of them verified the devices effectiveness by an orthotopic implant in animal models of disease. To support translational medicine in this field, here we provide a systematic review on studies recurring to decellularized/bioengineered tracheas implantation. After describing the specific methodological aspects, orthotopic implant results are verified. Furtherly, the only three clinical cases of compassionate use of tissue engineered tracheas are reported with a focus on outcomes.

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.

The Impact of New Treatments on Short- and MID-Term Outcomes in Bilateral Lung Transplant: A Propensity Score Study.

BACKGROUND: Despite many efforts to improve organ preservation and recipient survival, overall lung transplant (LT) mortality is still high. We aimed to investigate the impact of 'prophylactic' veno-arterial extracorporeal membrane oxygenation (VA ECMO) and tacrolimus on 72-h primary graft dysfunction (PGD) and 30-day acute cellular rejection, respectively. METHODS: All consecutive LT patients admitted to the Intensive Care Unit of the Padua University Hospital (February, 2016-2022) were screened. Only adult patients undergoing first bilateral LT and not requiring cardio-pulmonary bypass, invasive mechanical ventilation, and/or ECMO before LT, were included. A propensity score weighting analysis was employed to account for the non-random allocation of the subjects to different treatments. RESULTS: A total of 128 LT recipients were enrolled. Compared to the 'off-pump'-group (n.47, 37%), 'prophylactic' VA ECMO (n.51,40%) recorded similar 72-h PGD values, perioperative blood products and lower acute kidney dysfunction. Compared with cyclosporine (n.86, 67%), tacrolimus (n.42, 33%) recorded a lower risk of 30-day cellular rejection, kidney dysfunction, and bacteria isolation. CONCLUSIONS: 'Prophylactic' VA ECMO recorded 72-h PGD values comparable to the 'off-pump'-group; while tacrolimus showed a lower incidence of 30-day acute cellular rejection.

Sarcopenia as a Predictor of Short- and Long-Term Outcomes in Patients Surgically Treated for Malignant Pleural Mesothelioma.

Surgery for malignant pleural mesothelioma (MPM) should be reserved only for patients who have a good performance status. Sarcopenia, a well-known predictor of poor outcomes after surgery, is still underinvestigated in MPM. The aim of this study is to evaluate the role of sarcopenia as a predictor of short-and long-term outcomes in patients surgically treated for MPM. In our analysis, we included patients treated with a cytoreductive intent in a multimodality setting, with both pre- and post-operative CT scans without contrast available. We excluded those in whom a complete macroscopic resection was not achieved. Overall, 86 patients were enrolled. Sarcopenia was assessed by measuring the mean muscular density of the bilateral paravertebral muscles (T12 level) on pre-and post-operative CTs; a threshold value of 30 Hounsfield Units (HU) was identified. Sarcopenia was found pre-operatively in 57 (66%) patients and post-operatively in 61 (74%). Post-operative sarcopenic patients had a lower 3-year overall survival (OS) than those who were non-sarcopenic (34.9% vs. 57.6% p = 0.03). Pre-operative sarcopenia was significantly associated with a higher frequency of post-operative complications (65% vs. 41%, p = 0.04). The evaluation of sarcopenia, through a non-invasive method, would help to better select patients submitted to surgery for MPM in a multimodality setting.

Tracheal resection and anastomosis for squamous cell carcinoma.

Tracheal malignant tumors are uncommon lesions. The rarity of this condition may generate uncertainties in the diagnosis and treatment. For this reason especially, the surgical treatment should be performed only in centers with a high expertise in tracheal surgery. If the involved tracheal tract is less than 4-5 cm and the tumor is localized, the treatment of choice is based on a segmental tracheal resection with an end-to-end anastomosis. In this video tutorial, we describe how we perform tracheal resection with an end-to-end anastomosis in a patient with a squamous cell carcinoma.

Computed Tomography and Spirometry Can Predict Unresectability in Malignant Pleural Mesothelioma.

Preoperative identification of unresectable pleural mesothelioma could spare unnecessary surgical intervention and accelerate the initiation of medical treatments. The aim of this study is to determine predictors of unresectability, testing our impression that the contraction of the ipsilateral hemithorax is often associated with exploratory thoracotomy. Between 1994 and 2020, 291 patients undergoing intended macroscopic complete resection for mesothelioma after chemotherapy were retrospectively investigated. Eligible patients (n = 58) presented a preoperative 3 mm slice-thickness chest computed tomography without pleural effusion or hydropneumothorax. Lung volumes (segmented using a semi-automated method), modified-Response Evaluation Criteria in Solid Tumors (RECIST) measurements, and spirometries were collected after chemotherapy. Multivariable analysis was performed to determine the predictors of unresectability. An unresectable disease was found at the time of operation in 25.9% cases. By multivariable analysis, the total lung capacity (p = 0.03) and the disease burden (p = 0.02) were found to be predictors of unresectability; cut-off values were <77.5% and >120.5 mm, respectively. Lung volumes were not confirmed to be associated with unresectability at multivariable analysis, probably due to the correlation with the disease burden (p < 0.001; r = -0.4). Our study suggests that disease burden and total lung capacity could predict MPM unresectability, helping surgeons in recommending surgery or not in a multimodality setting.

Relapse Patterns and Tailored Treatment Strategies for Malignant Pleural Mesothelioma Recurrence after Multimodality Therapy.

To date, there have been no established therapies for recurrent malignant pleural mesothelioma (MPM) after multimodality treatment. Aims of this retrospective study are to analyze the recurrence pattern, its treatment and to identify the predictors of best oncological outcomes for relapsed MPM, comparing extrapleural pneumonectomy (EPP) vs. pleurectomy/decortication (PD). Study population: 94 patients with recurrence of MPM after multimodality treatment underwent macroscopic complete resection (52.1% with EPP and 47.9% with PD) between July 1994 and February 2020. Distant spread was the most frequent pattern of recurrence (71.3%), mostly in the EPP group, while the PD group showed a higher local-only failure rate. Post-recurrence treatment was administered in 86.2%, whereas best supportive care was administered in 13.8%. Median post-recurrence survival (PRS) was 12 months (EPP 14 vs. PD 8 months, p = 0.4338). At multivariate analysis, predictors of best PRS were epithelial histology (p = 0.026, HR 0.491, IC95% 0.263-0.916), local failure (p = 0.027, HR 0.707, IC95% 0.521-0.961), DFS ≥ 12 months (p = 0.006, HR 0.298, IC95% 0.137-0.812) and post-recurrence medical treatment (p = 0.046, HR 0.101, IC95% 0.897-0.936). The type of surgical intervention seems not to influence the PRS if patients are fit enough to face post-recurrence treatments. In patients with a prolonged disease-free interval, in the case of recurrence the most appropriate treatment seems to be the systemic medical therapy, even in the case of local-only relapse.