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BACKGROUND: Only a small number of studies have explored the clinicopathological features of pulmonary adenocarcinoma (PA) associated with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) false-negative (FN) results. Herein, we investigated the FDG-PET diagnostic performance by stratifying PAs according to International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification. METHODS: From January 2002 to December 2016, all consecutive patients who underwent pulmonary resection for stage I PA at six thoracic surgery institutions were retrospectively reviewed. The diagnostic performance of FDG-PET was analysed according to IASLC/ATS/ERS classification and two validated subclassifications. Univariable and multivariable logistic analysis were used to identify predictors of FDG-PET FN results. RESULTS: Five hundred and fifty (550) patients with stage I PA were included in the analyses. Most of the patients were male (n=354 [64.4%]) and smokers (n=369 [67.1%]). Ninety-seven (n=97 [17.6%]) FN cases were observed at FDG-PET imaging. On multivariable analysis, a lepidic pattern was found to be independently associated with FDG-PET FN results (odds ratio [OR], 3.20; p<0.001), while a solid pattern more commonly presented with a positive finding (OR, 0.40; p=0.066). According to Nakamura's classification, we observed an independent association between lepidic pattern and FDG-PET FN results (OR, 3.17; p<0.001), while solid/micropapillary patterns were independently related with increased FDG uptake (OR, 0.35; p=0.021). According to Yoshizawa's classification, Intermediate-grade tumours were independently correlated with FN FDG-PET results (OR, 2.78; p=0.005). CONCLUSIONS: In our cohort, histopathological features were significantly associated with FDG uptake. In particular, some adenocarcinoma subtypes (mostly Lepidic pattern) have a tendency towards FN FDG-PET findings. The correlation between computed tomography findings, clinical characteristics, and FDG uptake is mandatory, in order to tailor the precise diagnostic and therapeutic pathway for each patient.
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Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/cirurgia , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Masculino , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Estados UnidosRESUMO
Primary mediastinal germ cell tumors are a rare finding, and one third of them are seminomas. Seminomas are found in the anterior mediastinum, whereas they are extremely rare within the posterior compartment. Most clinicians would not consider a primary seminoma in the differential diagnosis of a posterior mediastinal mass, as only two cases have been reported in literature. Here we present the case of a 57-year-old male with a primary seminoma arising in the left posterior mediastinum. He was asymptomatic and the mass was an incidental finding. Positron emission tomography (PET) revealed a small area with an avid tracer uptake. Transthoracic needle aspiration led to a non-diagnostic result. Due to the strong suspect of malignancy, a surgical excision was chosen to obtain a diagnosis. He underwent complete excision, and pathology report demonstrated a mediastinal seminoma. Subsequent further staging did not reveal any other location of the disease. Given the complete excision of the primary tumor, active surveillance was the treatment of choice. The patient is free of disease 48 months after diagnosis.
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Neoplasias do Mediastino , Seminoma , Neoplasias Testiculares , Humanos , Masculino , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/cirurgia , Mediastino/diagnóstico por imagem , Mediastino/patologia , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Seminoma/diagnóstico por imagem , Seminoma/cirurgia , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/cirurgiaRESUMO
AIMS: High mobility group box 1 (HMGB1) is a chromatin structural protein, expressed ubiquitously in the nuclei of mammalian cells. When transported extracellularly, it acts as a tumour suppressor and oncogenic protein. In malignant pleural mesothelioma (MPM), high serum levels of HMGB1 have been related to a poor prognosis. Conversely, the significance of HMGB1 expression in MPM tissues is still unclear. METHODS AND RESULTS: Biopsy samples from 170 patients with MPM were assessed by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to evaluate HMGB1 protein and gene expression. The expression level of HMGB1 protein was scored using a semiquantitative system that sums the intensity (0-3) and the percentage (from 0 to 4) of positively stained cells in nuclei, cytoplasm and in both. The final score was considered as high (>3) or low (<3) expression. Gene expression levels were calculated using the ΔΔCt method. High expression levels of HMGB1 as total (P = 0.0011) and cytoplasmic score (P = 0.0462) were related to a worse disease-specific survival (DSS) in the entire cohort and in the clinicopathological subgroups. No significant correlation was found between HMGB1 gene expression and DSS. CONCLUSIONS: These findings indicate that HMGB1 may be a useful prognostic biomarker in MPM when detected by immunohistochemistry. Conversely, as it is also expressed in normal and reactive mesothelial cells, HMGB1 cannot be considered a diagnostic biomarker in histological samples of mesothelioma.
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Biomarcadores Tumorais/análise , Proteína HMGB1/biossíntese , Neoplasias Pulmonares/patologia , Mesotelioma/patologia , Neoplasias Pleurais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Proteína HMGB1/análise , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Mesotelioma/mortalidade , Mesotelioma Maligno , Pessoa de Meia-Idade , Neoplasias Pleurais/mortalidade , PrognósticoRESUMO
We report a case of extralobar pulmonary sequestration (ELS) in a young woman, presenting with right recurring massive pleural effusion. The patient initially underwent a diagnostic Video Assisted Thoracic Surgery (VATS) for a suspected diffuse malignancy. After the aspiration of the pleural effusion we observed a highly vascularised cystic mass, with its origin from the right lower lobe. As we tried to retract the right lower lobe, the mass broke with massive bleeding requiring emergency right lateral thoracotomy. The mass was succesfully excised, resembling an extra-lobar pulmonary sequestration. The patient was discharged on post-operative day 5.
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Sequestro Broncopulmonar/patologia , Sequestro Broncopulmonar/cirurgia , Derrame Pleural Maligno/patologia , Derrame Pleural Maligno/cirurgia , Cirurgia Torácica Vídeoassistida , Adulto , Feminino , HumanosRESUMO
Liposarcomas are rare entities and those located in the neck and mediastinum are exceptional. We report the case of a 58 year-old Caucasian male who presented with dysphonia, mild dysphagia to solids, dyspnoea at exertion and cough due to a giant mass of the neck originating from the deep cervical space at C6 vertebral level spreading into the posterior mediastinum. The lesion, that was associated with a right vocal cord palsy, caused severe lateral displacement of the trachea and oesophagus. The case has been managed by complete surgical resection through a combined cervical and thoracic approach associated with a tracheostomy due to the risk of bilateral recurrent nerve dysfunction at the end of the intervention. The tumour was diagnosed as a encapsulated low-grade liposarcoma. Six months after surgery the tracheostomy was closed. At 24 months clinical and radiological follow-up the patient is doing well and disease free.
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Neoplasias de Cabeça e Pescoço , Lipossarcoma , Neoplasias do Mediastino , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Lipossarcoma/diagnóstico por imagem , Lipossarcoma/cirurgia , Masculino , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/secundário , Neoplasias do Mediastino/cirurgia , Pessoa de Meia-Idade , RadiografiaRESUMO
Background: Despite greater appreciation for the importance of frailty in surgical patients, due to improved understanding that frailty is often linked to poor outcomes, the optimal method of assessment remains unknown. In this study, we sought to evaluate the prevalence of frailty in patients considered for elective thoracic surgery and to test the ability of several frailty measurements to predict postoperative outcomes. Methods: Patients included were candidates for major elective thoracic surgery. Preoperative assessment of frailty included the Fried frailty phenotype, the Edmonton Frail Scale (EFS), the modified frailty index (mFI), the Clinical Frailty Scale (CFS), and additional components of frailty. Outcome data include days with chest drain, length of hospital stay, and postoperative adverse events. Results: According to the Fried frailty phenotype, 53% of 94 patients included were prefrail or frail. A significant association between frailty and postoperative complications was found (odds ratio 7.65; P=0.001). No association between CFS, mFI, EFS, and complications was observed. The Frailty Phenotype seemed the most accurate in predicting postoperative complications, with an area under the curve (AUC) of 0.77. Twenty-seven percent of patients meet the criteria for depression according to the Geriatric Depression Scale and they showed a higher risk of postoperative complications (OR 2.47; P=0.03). A lower psoas muscle index was associated with a higher risk of complications (OR 3.40; P=0.04). Conclusions: According to our results, the Fried frailty phenotype seems the most accurate tool to test frailty in patients undergoing thoracic resections. Surgeons should be aware that, although these aspects are not routinely tested, they are potential targets to improve clinical outcomes. Studies on additional interventions specifically targeting frail people in the setting of elective thoracic surgery are required.
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OBJECTIVES: Robotic thymectomy has been suggested and considered technically feasible for thymic tumours. However, because of small-sample series and the lack of data on long-term results, controversies still exist on surgical and oncological results with this approach. We performed a large national multicentre study sought to evaluate the early and long-term outcomes after robot-assisted thoracoscopic thymectomy in thymic epithelial tumours. METHODS: All patients with thymic epithelial tumours operated through a robotic thoracoscopic approach between 2002 and 2022 from 15 Italian centres were enrolled. Demographic characteristics, clinical, intraoperative, postoperative, pathological and follow-up data were retrospectively collected and reviewed. RESULTS: There were 669 patients (307 men and 362 women), 312 (46.6%) of whom had associated myasthenia gravis. Complete thymectomy was performed in 657 (98%) cases and in 57 (8.5%) patients resection of other structures was necessary, with a R0 resection in all but 9 patients (98.6%). Twenty-three patients (3.4%) needed open conversion, but no perioperative mortality occurred. Fifty-one patients (7.7%) had postoperative complications. The median diameter of tumour resected was 4 cm (interquartile range 3-5.5 cm), and Masaoka stage was stage I in 39.8% of patients, stage II in 56.1%, stage III in 3.5% and stage IV in 0.6%. Thymoma was observed in 90.2% of patients while thymic carcinoma occurred in 2.8% of cases. At the end of the follow-up, only 2 patients died for tumour-related causes. Five- and ten-year recurrence rates were 7.4% and 8.3%, respectively. CONCLUSIONS: Through the largest collection of robotic thymectomy for thymic epithelial tumours we demonstrated that robot-enhanced thoracoscopic thymectomy is a technically sound and safe procedure with a low complication rate and optimal oncological outcomes.
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Procedimentos Cirúrgicos Robóticos , Timectomia , Neoplasias do Timo , Humanos , Timectomia/métodos , Neoplasias do Timo/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Estudos Retrospectivos , Idoso , Adulto , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Itália/epidemiologia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Epiteliais e Glandulares/patologia , Adulto JovemRESUMO
Lung cancer is still the leading cause of cancer-related death worldwide. Interest is growing towards early detection and advances in liquid biopsy to isolate circulating tumor cells (CTCs). This pilot study aimed to detect epithelial CTCs in the peripheral blood of early-stage non-small cell lung cancer (NSCLC) patients. We used Smart BioSurface® (SBS) slide, a nanoparticle-coated slide able to immobilize viable nucleated cellular fraction without pre-selection and preserve cell integrity. Forty patients undergoing lung resection for NSCLC were included; they were divided into two groups according to CTC value, with a cut-off of three CTCs/mL. All patients were positive for CTCs. The mean CTC value was 4.7(± 5.8 S.D.) per ml/blood. In one patient, next generation sequencing (NGS) analysis of CTCs revealed v-raf murine sarcoma viral oncogene homolog B(BRAF) V600E mutation, which has also been identified in tissue biopsy. CTCs count affected neither overall survival (OS, p = 0.74) nor progression-free survival (p = 0.829). Multivariable analysis confirmed age (p = 0.020) and pNodal-stage (p = 0.028) as negative predictors of OS. Preliminary results of this pilot study suggest the capability of this method in detecting CTCs in all early-stage NSCLC patients. NGS on single cell, identified as CTC by immunofluorescence staining, is a powerful tool for investigating the molecular landscape of cancer, with the aim of personalized therapies.
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BACKGROUND: Air leak is the major factor that influences the permanence of the chest tube and the in-hospital length of stay (LOS) among patients undergoing lung resections. The aim of this study was to determine whether the use of digital chest drain systems, compared with traditional ones, reduced the duration of chest drainage and postoperative in-hospital LOS in patients undergoing video-assisted thoracoscopic (VATS) lobectomy. METHODS: The study was a prospective, randomized, multicenter trial. Patients undergoing VATS lobectomy were randomized in 2 groups, receiving a digital drain system or a traditional one and managed accordingly to the protocol. RESULTS: Among 503 patients who fulfilled inclusion criteria and were randomized, 38 dropped out after randomization. Finally, 465 patients were analyzed, of whom 204 used the digital device and 261 the traditional one. In the digital group, there was a significantly shorter median chest tube duration of 3 postoperative days (interquartile range [IQR], 2-4 days) vs 4 postoperative days (IQR, 3-4 days; P = .001) and postoperative in-hospital LOS of 4 days (IQR, 3-6 days) vs 5 days (IQR, 4-6 days; P = .035). Analysis of predictors for increased duration of air leaks showed a relationship with male sex (P = .039), forced expiratory volume in 1 second percentage (P = .004), forced vital capacity percentage (P = .03), and presence of air leaks at the end of surgery (P = .001). CONCLUSIONS: In patients undergoing VATS lobectomy, the use of a digital drainage system allows an earlier removal of the chest drain compared with the traditional system, leading to a shorter in-hospital LOS.
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Drenagem , Pneumonectomia , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento , Pneumonectomia/métodos , Drenagem/métodos , Tubos Torácicos , Tempo de Internação , Eletrônica , Cirurgia Torácica Vídeoassistida/métodosRESUMO
The aim of this study was to assess the impact of BMI on perioperative outcomes in patients undergoing VATS lobectomy or segmentectomy. Data from 5088 patients undergoing VATS lobectomy or segmentectomy, included in the VATS Group Italian Registry, were collected. BMI (kg/m2) was categorized according to the WHO classes: underweight, normal, overweight, obese. The effects of BMI on outcomes (complications, 30-days mortality, DFS and OS) were evaluated with a linear regression model, and with a logistic regression model for binary endpoints. In overweight and obese patients, operative time increased with BMI value. Operating room time increased by 5.54 minutes (S.E. = 1.57) in overweight patients, and 33.12 minutes (S.E. = 10.26) in obese patients (P < 0.001). Compared to the other BMI classes, overweight patients were at the lowest risk of pulmonary, acute cardiac, surgical, major, and overall postoperative complications. In the overweight range, a BMI increase from 25 to 29.9 did not significantly affect the length of stay, nor the risk of any complications, except for renal complications (OR: 1.55; 95% CI: 1.07-2.24; P = 0.03), and it reduced the risk of prolonged air leak (OR: 0.8; 95% CI: 0.71-0.90; P < 0.001). 30-days mortality is higher in the underweight group compared to the others. We did not find any significant difference in DFS and OS. According to our results, obesity increases operating room time for VATS major lung resection. Overweight patients are at the lowest risk of pulmonary, acute cardiac, surgical, major, and overall postoperative complications following VATS resections. The risk of most postoperative complications progressively increases as the BMI deviates from the point at the lowest risk, towards both extremes of BMI values. Thirty days mortality is higher in the underweight group, with no differences in DFS and OS.
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Sobrepeso , Magreza , Humanos , Sobrepeso/complicações , Índice de Massa Corporal , Magreza/complicações , Pneumonectomia/efeitos adversos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Resultado do Tratamento , Obesidade/complicações , Complicações Pós-Operatórias/etiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Despite the use of robotics becoming increasingly popular among thoracic surgeons worldwide, there remains debate over the best robotic approach for lung resections. In this paper, we delineated the main port placement strategies and discussed their advantages and disadvantages. METHODS: A PubMed literature review was performed using key phrases such as "robotic lobectomy technique", "RATS lobectomy", and "port placement robotic lobectomy". After the final review, 22 articles were included as references, of which 10 described common robotic port mapping techniques. RESULTS: Several port strategies for robot-assisted pulmonary lobectomies have been proposed and described in the literature, each showing its own limitations and advantages. CONCLUSIONS: New robotic surgeons may choose their port strategy according to personal preference and previous surgical experience, especially regarding open or VATS resections. Robust data comparing different port placements in robotic surgery are lacking. Further research should be directed toward comparisons of clinical outcomes with different robotic approaches.
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INTRODUCTION: Malignant pleural mesothelioma (MPM) is a tumour associated with asbestos exposure. Approximately, 10% of patients with MPM carry a germline pathogenic variant (PV), mostly in DNA repair genes, suggesting the occurrence of inherited predispositions. AIM: This article aimed to 1) search for new predisposing genes and assess the prevalence of PVs in DNA repair genes, by next-generation sequencing (NGS) analysis of germline DNA from 113 unselected patients with MPM and 2) evaluate whether these patients could be sensitive to tailored treatments. METHODS: NGS was performed using a custom panel of 107 cancer-predisposing genes. To investigate the response to selected drugs in conditions of DNA repair insufficiency, we created a three-dimensional-MPM cell model that had a defect in ataxia telangiectasia mutated (ATM), the master regulator of DNA repair. RESULTS: We identified PVs in approximately 7% of patients with MPM (8/113) and a new PV in BAP1 in a further patient with familial MPM. Most of these PVs were in genes involved or supposedly involved in DNA repair (BRCA1, BRIP1, CHEK2, SLX4, FLCN and BAP1). In vitro studies showed apoptosis induction in ATM-silenced/inhibited MPM spheroids treated with an enhancer of zeste homologue 2 inhibitor (tazemetostat). CONCLUSIONS: Overall these data suggest that patients with MPM and DNA repair insufficiency may benefit from this treatment, which induces synthetic lethality.
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Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Reparo do DNA/genética , Células Germinativas/patologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mesotelioma/tratamento farmacológico , Mesotelioma/genética , Mesotelioma/patologia , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/genética , Neoplasias Pleurais/patologiaRESUMO
Malignant pleural mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Early therapeutic interventions could improve patient outcomes. We aimed to identify a pattern of microRNAs (miRNAs) as potential early non-invasive markers of MPM. In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition cohort, we screened the whole miRNome in serum extracellular vesicles (EVs) of preclinical MPM cases. In a subgroup of 20 preclinical samples collected five years prior MPM diagnosis, we observed an upregulation of miR-11400 (fold change (FC) = 2.6, adjusted p-value = 0.01), miR-148a-3p (FC = 1.5, p-value = 0.001), and miR-409-3p (FC = 1.5, p-value = 0.04) relative to matched controls. The 3-miRNA panel showed a good classification capacity with an area under the receiver operating characteristic curve (AUC) of 0.81 (specificity = 0.75, sensitivity = 0.70). The diagnostic ability of the model was also evaluated in an independent retrospective cohort, yielding a higher predictive power (AUC = 0.86). A signature of EV miRNA can be detected up to five years before MPM; moreover, the identified miRNAs could provide functional insights into the molecular changes related to the late carcinogenic process, preceding MPM development.
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Germline mutations in the tumor suppressor gene BRCA1-associated protein-1 (BAP1) lead to BAP1 tumor predisposition syndrome (BAP1-TPDS), characterized by high susceptibility to several tumor types, chiefly melanoma, mesothelioma, renal cell carcinoma, and basal cell carcinoma. Here, we present the results of our ten-year experience in the molecular diagnosis of BAP1-TPDS, along with a clinical update and cascade genetic testing of previously reported BAP1-TPDS patients and their relatives. Specifically, we sequenced germline DNA samples from 101 individuals with suspected BAP1-TPDS and validated pathogenic variants (PVs) by assessing BAP1 somatic loss in matching tumor specimens. Overall, we identified seven patients (7/101, 6.9%) carrying six different germline BAP1 PVs, including one novel variant. Consistently, cascade testing revealed a total of seven BAP1 PV carriers. In addition, we explored the mutational burden of BAP1-TPDS tumors by targeted next-generation sequencing. Lastly, we found that certain tumors present in PV carriers retain a wild-type BAP1 allele, suggesting a sporadic origin of these tumors or a functional role of heterozygous BAP1 in neoplastic development. Altogether, our findings have important clinical implications for therapeutic response of BAP1-TPDS patients.
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Background: Persistent air leak and the management of intraoperative blood loss are common threats in thoracic surgical practice. The availability of new procedures, technology and materials is constantly evolving topical hemostats and surgical sealants must be added to this toolkit. Topical hemostats and surgical sealants differ according to their chemical nature and physical characteristics, to their origin and mechanism of action, regulatory/registration and vigilance paths. A Delphi consensus was set to highlight the different points of view on the use of topical haemostatic products and sealants among the members of Italian Society of thoracic surgery. Methods: The board was formed by a group of five Italian experts; in the first phase after a careful review of the scientific literature and two rounds, the board finally generated 16 consensus statements for testing across a wider audience. During the second phase, the statements were collated into a questionnaire, which was electronically sent to a panel of 46 Italian surgeons, experts in the field. Results: Out of 46 Italian surgeons, 33 (72%) panel members responded to the Delphi questionnaire. All the items reached a positive consensus, with elevated levels of agreement, as demonstrated by the presence of a 100% consensus for nine items. For the remaining 7 statements the minimum level of consent was 88% (29 participants approved the statement and 4 disagreed) and the maximum was 97% (32 participants approved the statement and 1 was in disagreement). Conclusions: The present Delphi analysis shows that air leak and intraoperative bleeding are clinical problems well known among thoracic surgeons. Nevertheless, the aim of the scientific societies and of the group of experts is to execute the education activities in the surgery community. This Delphi survey suggest the need of wider and updated scientific information about technical and registration characteristics of most recent technologic solutions, such as the of topical hemostats and surgical sealants to provide healthcare and administrative staff with the opportunity to work and interact through a common and shared language and eventually to guarantee minimal requirements of assistance.
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BACKGROUND: To evaluate epidermal growth factor receptor (EGFR) phenotypic expression and related gene status in malignant pleural mesothelioma (MPM) and to correlate the results with patients' prognosis. METHOD: Eighty-three cases of MPM specimens were submitted to immunohistochemical (IHC) staining to evaluate the expression of EGFR protein; positive cases were submitted to fluorescence in situ hybridization (FISH) to investigate the gene status. Results were correlated with clinico-pathological characteristics and long-term survival. RESULTS: Thirty-eight cases (46%) demonstrated a positive IHC reaction [30/57 (52%) epithelial and 8/20 (40%) biphasic whereas sarcomatous MPM were negative]. No association was recorded between EGFR IHC positive staining and age, gender, or asbestos exposure. Three out of 38 (8%) cases submitted to FISH were positive revealing gene amplification or polysomy. Mean follow-up was 15.4 months (range 2-44). Epithelial subtype only was confirmed to affect prognosis (2-years survival rate 40 vs. 18% for non-epithelial subtype, P = 0.042). When epithelial MPM patients were considered, IHC EGFR positive staining was demonstrated to be a negative prognostic factor (2-years survival rate 26 vs. 60% for IHC EGFR negative staining; P = 0.026). CONCLUSIONS: EGFR overexpression is identified by IHC in 52% of epithelial MPM and is demonstrated to be a factor negatively affecting prognosis. Phenotypic overexpression seems not to be related to gene status alteration.
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Receptores ErbB/genética , Mesotelioma/genética , Derrame Pleural Maligno/genética , Neoplasias Pleurais/genética , Idoso , Receptores ErbB/metabolismo , Feminino , Seguimentos , Amplificação de Genes , Dosagem de Genes , Humanos , Técnicas Imunoenzimáticas , Hibridização in Situ Fluorescente , Masculino , Mesotelioma/metabolismo , Mesotelioma/patologia , Mutação/genética , Derrame Pleural Maligno/metabolismo , Derrame Pleural Maligno/patologia , Neoplasias Pleurais/metabolismo , Neoplasias Pleurais/patologia , Prognóstico , Taxa de SobrevidaRESUMO
Malignant pleural mesothelioma (MPM) is often associated with a poor prognosis and options for the treatment of this disease are few. To date, the important role of the immune microenvironment in modifying the disease natural history is well established. The programmed cell death pathway (PD-1/PD-L1) limits the T lymphocyte activation in peripheral tissues when an inflammatory response occurs, and controls the tumour immune escape. PD-L1 is broadly expressed in several malignant tumours and associated with poor clinical outcomes. Thus, the aim of our study is to investigate the potential role of PD-L1 expression in MPM prognosis. Biopsy samples from 198 patients diagnosed with MPM were examined by immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) to evaluate PD-L1 protein and gene expression. For PD-L1 protein expression we consider at least 5% membranous staining as positive. Gene expression levels were calculated with ΔΔCt method. Positive expression of PD-L1 by IHC was correlated with worse overall survival (OS; p=0.0225) in MPM patients. PD-L1 positive status was correlated with worse OS in the subgroup of patients with ECOG score <2 (p=0.0004, n=129) and these data were confirmed by multivariate analysis. No significant correlation was found between PD-L1 gene expression and OS. Our results show that PD-L1 evaluated by IHC assay may be a prognostic biomarker for MPM patients with good performance status.
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Antígeno B7-H1/metabolismo , Mesotelioma Maligno/diagnóstico , Neoplasias Pleurais/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Biomarcadores/metabolismo , Estudos de Coortes , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Itália , Masculino , Mesotelioma Maligno/metabolismo , Mesotelioma Maligno/patologia , Pessoa de Meia-Idade , Neoplasias Pleurais/metabolismo , Neoplasias Pleurais/patologia , Prognóstico , Estudos RetrospectivosRESUMO
Sarcopenia is a skeletal muscle disorder characterized by reduced muscle mass, strength, and performance. Muscle ultrasound can be helpful in assessing muscle mass, quality, and architecture, and thus possibly useful for diagnosing or screening sarcopenia. The objective of this study was to evaluate the reliability of ultrasound assessment of tibialis anterior muscle in sarcopenia diagnosis. We included subjects undergoing total or partial hip replacement, comparing measures with a healthy control group. We measured the following parameters: tibialis anterior muscle thickness, echogenicity, architecture, stiffness, skeletal muscle index (SMI), hand grip strength, and sarcopenia related quality of life evaluated through the SarQoL questionnaire. We included 33 participants with a mean age of 54.97 ± 23.91 years. In the study group we found reduced tibialis anterior muscle thickness compared to the healthy control group (19.49 ± 4.92 vs. 28.94 ± 3.63 mm, p < 0.05) with significant correlation with SarQoL values (r = 0.80, p < 0.05), dynamometer hand strength (r = 0.72, p < 0.05) and SMI (r = 0.76, p < 0.05). Moreover, we found reduced stiffness (32.21 ± 12.31 vs. 27.07 ± 8.04 Kpa, p < 0.05). AUC measures of ROC curves were 0.89 predicting reduced muscle strength, and 0.97 predicting reduced SMI for tibialis anterior muscle thickness, while they were 0.73 and 0.85, respectively, for muscle stiffness. Our findings showed that ultrasound assessment of tibialis anterior muscle might be considered a reliable measurement tool to evaluate sarcopenia.
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BACKGROUND: Bronchial reconstruction is one of the most challenging procedures for thoracic surgeons. This study aimed to report the surgical techniques and clinical outcomes of bronchoplastic and sleeve resection for central lung cancer and summarize our center's experience of this challenging procedure over the past 8 years. METHODS: Between January 2013 and April 2021, 54 patients underwent a sleeve resection or a lobectomy with bronchoplasty, including 11 patients who received video-assisted thoracoscopic surgery (VATS) bronchial sleeve resection (4 via the uniportal approach and 7 via the biportal approach). Perioperative parameters and surgical short-term patient outcomes were analyzed to evaluate the safety and feasibility of this surgical procedure. RESULTS: The average operative time and blood loss were 247.8±73.1 (range, 126-455) minutes and 300.4±321.8 (range, 50-1,500) mL, respectively. The mean postoperative length of stay was 10.5±5.8 (range, 4-29) days. Eleven patients underwent additional pulmonary angioplasty or sleeve resection. For patients who underwent biportal VATS sleeve lobectomy, the median operative time was 255 (interquartile range, 179-360) minutes, the median blood loss was 200 (interquartile range, 100-600) mL, and the median postoperative hospital stay was 5 (interquartile range, 5-8) days. For patients who underwent uniportal VATS sleeve lobectomy, the median operative time was 288 (interquartile range, 241.5-343) minutes, the median blood loss was 75 (interquartile range, 50-100) mL, and the median postoperative hospital stay was 5 (interquartile range, 4.5-5.5) days. No anastomosis-related complications or perioperative mortality was observed. CONCLUSIONS: Both bronchoplastic resection and sleeve resection are safe and feasible procedures. Uniportal thoracoscopic sleeve lobectomy can be performed by skilled surgeons with satisfactory short-term outcomes, although it is surgically complicated.
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Boosting antitumor immunity has emerged as a powerful strategy in cancer treatment. While releasing T-cell brakes has received most attention, tumor recognition by T cells is a pre-requisite. Radiotherapy and certain cytotoxic drugs induce the release of damage-associated molecular patterns, which promote tumor antigen cross-presentation and T-cell priming. Antibodies against the "do not eat me" signal CD47 cause macrophage phagocytosis of live tumor cells and drive the emergence of antitumor T cells. Here we show that CXCR4 activation, so far associated only with tumor progression and metastasis, also flags tumor cells to immune recognition. Both CXCL12, the natural CXCR4 ligand, and BoxA, a fragment of HMGB1, promote the release of DAMPs and the internalization of CD47, leading to protective antitumor immunity. We designate as Immunogenic Surrender the process by which CXCR4 turns in tumor cells to macrophages, thereby subjecting a rapidly growing tissue to immunological scrutiny. Importantly, while CXCL12 promotes tumor cell proliferation, BoxA reduces it, and might be exploited for the treatment of malignant mesothelioma and a variety of other tumors.