Giant epiphrenic diverticulum: an unusual case from diagnosis to treatment.

Esophageal diverticulum is a rare disease caused by impairment of esophageal motility. The incidence is not known, due to lack of symptoms in many cases. Surgical treatment is reserved to symptomatic patients. In this case report, we describe a rare case of epiphrenic esophageal diverticulum. A 61-year-old male with silent medical history, suffering severe chest pain had a CT scan showing a large esophageal diverticulum. The patient was referred to our hospital, IRCCS "Casa Sollievo della Sofferenza", to complete pre-operative assessment with a CT scan and a Barium swallowing radiography, giving morphodimensional details of the diverticulum. Based on these findings, the surgeons have chosen the appropriate operative strategy. The surgeons adopted a laparoscopic access, completed with robotic-assisted laparotomy due to the morphology of the diverticulum. Radiological evaluation is crucial in the diagnosis and in the treatment planning of symptomatic patients.

Mixed Pulmonary Adenocarcinoma and Atypical Carcinoid: A Report of Two Cases of a Non-codified Entity With Biological Profile.

Pulmonary carcinoids combined with a non-neuroendocrine component have rarely been described, and this histological subtype is not included as a specific entity in the current World Health Organization classification of pulmonary neoplasms. Here, we described the molecular and histological features of two rare cases of mixed lung neoplasms, composed of atypical carcinoid and adenocarcinoma. The targeted next-generation sequencing analysis covering single nucleotide variations, copy number variations, and transcript fusions in a total of 161 cancer genes of the two different tumor components shows a similar molecular profile of shared and private gene mutations. These findings suggest their monoclonal origin from a transformed stem/progenitor tumor cell, which acquires a divergent differentiation during its development and progression and accumulates novel, specific mutations.

Intraoperative Lung Ultrasound (ILU) for the Assessment of Pulmonary Nodules.

BACKGROUND: The primary aim of this study was to confirm the validity of intraoperative lung ultrasound (ILU) as a safe and effective method of localization for difficult to visualize pulmonary nodules during Video-Assisted Thoracoscopic Surgery (VATS) and open thoracotomy. The secondary aim was to enhance knowledge on the morphological patterns of presentation of pulmonary nodules on direct ultrasound examination. MATERIALS AND METHODS: 131 patients with lung nodule and indication for surgery were enrolled. All patients underwent pre-operative imaging of the chest, including Chest Computed Tomography (CT) and Transthoracic Ultrasound (TUS), and surgical procedures for histological assessment of pulmonary nodules (VATS or open thoracotomy). RESULTS: The identification of 100.00% of lung nodules was allowed by ILU, while the detection rate of digital palpation was 94.66%. It was not possible to associate any specific ILU echostructural pattern to both benign or malignant lesions. However, the actual histological margins of the lesions in the operating samples were corresponding to those visualized at ILU in 125/131 (95.42%) cases. No complications have been reported with ILU employment. CONCLUSIONS: In our experience, ILU performed during both open surgery and VATS demonstrated to be a reliable and safe method for visualization and localization of pulmonary nodules non previously assessed on digital palpation. In addition, ILU showed to allow a clear nodule's margins' definition matching, in most cases, with the actual histological margins.

Aggressive early-stage lung adenocarcinoma is characterized by epithelial cell plasticity with acquirement of stem-like traits and immune evasion phenotype.

Lung adenocarcinoma (LUAD) is the main non-small-cell lung cancer diagnosed in ~40-50% of all lung cancer cases. Despite the improvements in early detection and personalized medicine, even a sizable fraction of patients with early-stage LUAD would experience disease relapses and adverse prognosis. Previous reports indicated the existence of LUAD molecular subtypes characterized by specific gene expression and mutational profiles, and correlating with prognosis. However, the biological and molecular features of such subtypes have not been further explored. Consequently, the mechanisms driving the emergence of aggressive LUAD remained unclear. Here, we adopted a multi-tiered approach ranging from molecular to functional characterization of LUAD and used it on multiple cohorts of patients (for a total of 1227 patients) and LUAD cell lines. We investigated the tumor transcriptome and the mutational and immune gene expression profiles, and we used LUAD cell lines for cancer cell phenotypic screening. We found that loss of lung cell lineage and gain of stem cell-like characteristics, along with mutator and immune evasion phenotypes, explain the aggressive behavior of a specific subset of lung adenocarcinoma that we called C1-LUAD, including early-stage disease. This subset can be identified using a 10-gene prognostic signature. Poor prognosis patients appear to have this specific molecular lung adenocarcinoma subtype which is characterized by peculiar molecular and biological features. Our data support the hypothesis that transformed lung stem/progenitor cells and/or reprogrammed epithelial cells with CSC characteristics are hallmarks of this aggressive disease. Such discoveries suggest alternative, more aggressive, therapeutic strategies for early-stage C1-LUAD.

Non-Coding RNAs as Prognostic Biomarkers: A miRNA Signature Specific for Aggressive Early-Stage Lung Adenocarcinomas.

Lung cancer burden can be reduced by adopting primary and secondary prevention strategies such as anti-smoking campaigns and low-dose CT screening for high risk subjects (aged >50 and smokers >30 packs/year). Recent CT screening trials demonstrated a stage-shift towards earlier stage lung cancer and reduction of mortality (~20%). However, a sizable fraction of patients (30-50%) with early stage disease still experience relapse and an adverse prognosis. Thus, the identification of effective prognostic biomarkers in stage I lung cancer is nowadays paramount. Here, we applied a multi-tiered approach relying on coupled RNA-seq and miRNA-seq data analysis of a large cohort of lung cancer patients (TCGA-LUAD, n = 510), which enabled us to identify prognostic miRNA signatures in stage I lung adenocarcinoma. Such signatures showed high accuracy (AUC ranging between 0.79 and 0.85) in scoring aggressive disease. Importantly, using a network-based approach we rewired miRNA-mRNA regulatory networks, identifying a minimal signature of 7 miRNAs, which was validated in a cohort of FFPE lung adenocarcinoma samples (CSS, n = 44) and controls a variety of genes overlapping with cancer relevant pathways. Our results further demonstrate the reliability of miRNA-based biomarkers for lung cancer prognostication and make a step forward to the application of miRNA biomarkers in the clinical routine.

First things first: A late robotic approach to anamnesis, in a patient with a thymus hematoma.

Anterior mediastinal masses are generally asymptomatic until they grow and compress surrounding structures. Chest X-rays only suggest a mediastinal abnormality and contrast-enhanced CT scan and MRI are necessary for a better definition of the lesion. The classification of the anterior mediastinal masses is based on their etiology and it is sometimes a challenge to have an accurate differential diagnosis based only on radiological examinations: therefore, only the histopathological examination makes the correct diagnosis. Surgeons generally agree that symptomatic masses or those with progressive growth should undergo surgical resection. We report a case of an accidental finding of an organized thymic hematoma in a 46-year-old female. At first totally asymptomatic, the hematoma was misdiagnosed for a thymic cyst and resected when it increased in size and compressed surrounding mediastinal structures. A detailed anamnesis highlighted a minor thoracic trauma which turned out to be the cause. Retrosternal hematoma generally grows several months after trauma and initial stabilization; therefore, it is mandatory to include an organized hematoma in the differential diagnosis of the retrosternal neoformations.

Management of Pleural Effusions in the Emergency Department.

BACKGROUND: In symptomatic patients, admitted in emergency department for acute chest pain and dyspnea, who require an urgent treatment, a rapid diagnosis and prompt management of massive pleural effusion or hemothorax can be lifesaving. AIM: The aim of this review was to summarize the current diagnostic and therapeutic approaches for the management of the main types of pleural effusions that physicians can have in an emergency department setting. METHODS: Current literature about the topic was reviewed and critically reported, adding the experience of the authors in the management of pleural effusions in emergency settings. RESULTS: The paper analyzed the main types of pleural effusions that physicians can have to treat. It illustrated the diagnostic steps by the principal radiological instruments, with a particular emphasis to the role of ultrasonography, in facilitating diagnosis and guiding invasive procedures. Then, the principal procedures, like thoracentesis and insertion of small and large bore chest drains, are indicated and illustrated according to the characteristics and the amount of the effusion and patient clinical conditions. CONCLUSION: The emergency physician must have a systematic approach that allows rapid recognition, clinical cause identification and definitive management of potential urgent pleural effusions.

Potential Prognostic Role of SPARC Methylation in Non-Small-Cell Lung Cancer.

The silencing of SPARC (secreted protein acid and rich in cysteine) gene through methylation of its promoter region represents a common event in many solid tumors and it is frequently associated with tumor progression and an aggressive clinical outcome. Anyhow, the data concerning the epigenetic mechanism of SPARC deregulation and its prognostic value in lung cancer are still incomplete. We explored the aberrant methylation of SPARC and its effects in 4 non-small cell lung cancer (NSCLC) cell lines and 59 NSCLC tissues and correlated the methylation levels with clinical-pathological features and disease outcome of patients. In 3 out of 4 tumor cell lines high SPARC methylation levels were observed. An inverse correlation between the epigenetic silencing and SPARC expression was confirmed by 5-Aza-2'-deoxycytidine ((5-Aza-CdR) treatment that also significantly induced a reduction in cell viability, proliferation and tumor cell migration. In tissues, the DNA methylation levels of the SPARC gene were significantly lower in paired non-neoplastic lungs (NLs) and normal lungs distant from tumor (NLDTs) than in NSCLCs (p = 0.002 and p = 0.0034 respectively). A promoter hypermethylation was detected in 68% of squamous cell carcinoma (SqCCs, 17/25) and 56% of adenocarcinoma (ADCs, 19/34), with SqCC showing the highest levels of methylation. Higher SPARC methylation levels were significantly associated with higher mortality risk both in all NSCLCs early stage patients (Hazard Ratio, HR = 1.97; 95% Confidence Interval, CI: 1.32-2.93; p = 0.001) and in those with SqCC (HR = 2.96; 95% CI: 1.43-6.12; p = 0.003). Promoter methylation of SPARC gene should represent an interesting prognostic biomarker in NSCLC, with potential application in the squamous early-stage context. Further research in this setting on larger independent cohorts of lung patients with different histologies and stages of disease are warranted.

Early nasal high-flow versus Venturi mask oxygen therapy after lung resection: a randomized trial.

BACKGROUND: Data on high-flow nasal oxygen after thoracic surgery are limited and confined to the comparison with low-flow oxygen. Different from low-flow oxygen, Venturi masks provide higher gas flow at a predetermined fraction of inspired oxygen (FiO2). We conducted a randomized trial to determine whether preemptive high-flow nasal oxygen reduces the incidence of postoperative hypoxemia after lung resection, as compared to Venturi mask oxygen therapy. METHODS: In this single-center, randomized trial conducted in a teaching hospital in Italy, consecutive adult patients undergoing thoracotomic lung resection, who were not on long-term oxygen therapy, were randomly assigned to receive high-flow nasal or Venturi mask oxygen after extubation continuously for two postoperative days. The primary outcome was the incidence of postoperative hypoxemia (i.e., ratio of the partial pressure of arterial oxygen to FiO2 (PaO2/FiO2) lower than 300 mmHg) within four postoperative days. RESULTS: Between September 2015 and April 2018, 96 patients were enrolled; 95 patients were analyzed (47 in high-flow group and 48 in Venturi mask group). In both groups, 38 patients (81% in the high-flow group and 79% in the Venturi mask group) developed postoperative hypoxemia, with an unadjusted odds ratio (OR) for the high-flow group of 1.11 [95% confidence interval (CI) 0.41-3] (p = 0.84). No inter-group differences were found in the degree of dyspnea nor in the proportion of patients needing oxygen therapy after treatment discontinuation (OR 1.34 [95% CI 0.60-3]), experiencing pulmonary complications (OR 1.29 [95% CI 0.51-3.25]) or requiring ventilatory support (OR 0.67 [95% CI 0.11-4.18]). Post hoc analyses revealed that PaO2/FiO2 during the study was not different between groups (p = 0.92), but patients receiving high-flow nasal oxygen had lower arterial pressure of carbon dioxide, with a mean inter-group difference of 2 mmHg [95% CI 0.5-3.4] (p = 0.009), and were burdened by a lower risk of postoperative hypercapnia (adjusted OR 0.18 [95% CI 0.06-0.54], p = 0.002). CONCLUSIONS: When compared to Venturi mask after thoracotomic lung resection, preemptive high-flow nasal oxygen did not reduce the incidence of postoperative hypoxemia nor improved other analyzed outcomes. Further adequately powered investigations in this setting are warranted to establish whether high-flow nasal oxygen may yield clinical benefit on carbon dioxide clearance. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02544477 . Registered 9 September 2015.

A 46-Year-Old Woman With an Uncommon Case of Massive Pneumothorax.

A 46-year-old woman arrived at our ED for the worsening of a thoracic pain localized in the left interscapulo-vertebral region that she had been commenting on for the past few days. Anamnestic data were collected; vital parameters, blood tests, and ECG were normal.

Lymph node upstaging for non-small cell lung cancer after uniportal video-assisted thoracoscopy.

BACKGROUND: Radical lymph node dissection (LND) plays a major role in the treatment of non-small cell lung cancer (NSCLC). This study presents the analysis of the results after uniportal video-assisted thoracoscopy (VATS) lymphadenectomy during anatomical lung resections for NSCLC, focusing on pathological nodal upstaging. Any possible risk factor affecting nodal upstaging was also investigated. METHODS: The prospectively collected clinical data of 136 patients undergone uniportal VATS anatomical lung resections, from June 2012 to September 2017, were reviewed. In particular, all details inherent the clinical and pathological node stage and any possible risk factor affecting nodal upstaging were analyzed. RESULTS: The patient population consisted of 90 males and 46 females; their mean age was 67.42±10.64 years. The mean number of lymph nodes retrieved during uniportal VATS lymphadenectomy was 20.14±10.73 (7.27±5.90 and 12.60±7.96 in N1 and N2 stations, respectively). The incidence of nodal upstaging was 13.3% (18 cases). In particular there was a N0-1 upstaging in 10 cases (7.4%), a N1-2 upstaging in 3 (2.2%) and a N0-2 in 4 (3%). The ROC analysis showed that the resection of 18 lymph nodes was the best predictor of a general upstaging with an AUC-ROC of 0.595, while the resection of 7 hilar lymph nodes was the best predictor of N1 upstaging (AUC-ROC: 0.554) and 11 mediastinal nodes was the best predictor of N2 upstaging (AUC-ROC: 0.671). The number of positive lymph nodes of stations 5-6 (OR: 2.035, 95% CI: 1.082-3.826, P=0.027) and stations 2-3-4 (OR: 6.198, 95% CI: 1.580-24.321, P=0.009) were confirmed to be the only independent risk factors for N2 upstaging by multivariate analysis. CONCLUSIONS: According to our experience, uniportal VATS allows a safe and effective radical lymphadenectomy, with a satisfactory pathological nodal upstaging, comparable to other minimally invasive techniques.

Uniportal video-assisted thoracoscopy major lung resections after neoadjuvant chemotherapy.

BACKGROUND: The combination of neoadjuvant chemotherapy and surgery in lung cancer therapy is well established. The role of uniportal video assisted thoracoscopy (VATS) is still not described in literature. This study presents the preliminary short-term results of uniportal VATS after neoadjuvant therapy in our series. METHODS: The prospectively collected data of 154 patients after uniportal VATS anatomical lung resection (18 patients after neoadjuvant chemotherapy and 136 surgeries alone) were retrospectively reviewed. The perioperative results and follow-up of patients after neoadjuvant therapy were analyzed and compared to those after surgery alone. RESULTS: The mean age of population was 67.51±10.63 years. The mean operative time was overlapping in both groups: 248.97±118.17 min in surgery group and 287.17±94.13 min in chemotherapy + surgery group (P=0.190), with no difference in terms of types of anatomical lung resections performed and number of lymph nodes retrieved. The intraoperative mortality was null in both groups. The incidence of all complications was the same in both groups and no correlations was found with any possible risk factor evaluated (age, gender, comorbidities, type of resection, histology, etc.). Among minor complications, the incidence of parenchymal fistula was significantly higher in the 18 patients underwent chemotherapy (22.2% vs. 5.1% respectively, P=0.013). The overall survival of the series was 93% at 1 year follow-up and 88% at 5-year. The 1- and 2-year survival in only surgery group was 94% and 89% respectively vs. 85% and 85% in Chemotherapy + surgery, without any significant difference (P=0.324). CONCLUSIONS: According to our experience, uniportal VATS after neoadjuvant therapy is feasible and quite safe. The oncological results and postoperative complications are comparable to those of other techniques. Uniportal VATS can be performed even for complicated cases in experienced centers.

Uniportal video-assisted thoracic surgery Roman experience-a report of the first 16-month Roman experience.

BACKGROUND: The acceptance of uniportal video-assisted thoracic surgery (U-VATS) for thoracic procedures has been growing worldwide. This study reports one of the widest Italian U-VATS experiences. METHODS: The prospectively collected data of 237 patients underwent a U-VATS procedure, between May 2016 and September 2017, were retrospectively reviewed. A wide range of procedures, like major and minor lung resections, esophageal surgery, pleural and mediastinal one, was performed. The main aim of the study was evaluating general outcomes in terms of safety and effectiveness, and analyzing short-term results of U-VATS approach. RESULTS: The mean age of population was 59.93±16.03 years. In 208 cases (85.3%) a U-VATS lung resection was performed, in 10 cases (4.1%) an esophagectomy or an esophageal diverticulectomy, in 15 (6.1%) a mediastinal procedure and in 11 (4.5%) a toilette for pleural empyema or removal of pleural lesions. The chest tube duration was 4.24±3.73 days and the postoperative hospital stay was 4.62±4.59 days. The intraoperative and thirty-day mortality were null. Mean level of pain in I postoperative day was 2.30±1.26 on VAS scale and the mean duration was of 1.54±1.21 days. In 93% of cases there was a resolution of pain after chest tube removal. Furthermore, the average level of cosmetic satisfaction was 2.73±0.49 (measured on a 0-3 scale). CONCLUSIONS: According to our experience, U-VATS seems to be a safe and practicable mini-invasive technique, above all for surgeons who already have thoracoscopy experience or made proper training attending multilevel courses, hands-on conferences and wet-labs.

Uniportal video-assisted thoracic surgery in the treatment of pleural empyema.

BACKGROUND: The efficacy of video-assisted thoracic surgery (VATS) in the treatment of pleural empyema has recently been proven. Till today, very few works evaluated the role of uniportal-VATS (U-VATS) approach in the treatment of pleural empyema even if it currently represents the most innovative and less invasive thoracoscopic approach. We report our experience with U-VATS in the treatment of pleural empyema. METHODS: A retrospective bicentric analysis of 35 consecutive patients who underwent surgical treatment of stage II and stage III pleural empyema was performed, from January 2015 to May 2017. RESULTS: The mean age of patients was 57.26±18.29 years and 54.3% of them were males. In 85.7% of the cases, empyema was related to a complicated parapneumonic effusion; in only 5 cases it was a post-surgical consequence. All patients were treated with broad-spectrum antibiotics and subsequent target therapy for 14.62±21.76 days prior to operation and 23 patients needed the placement of a chest tube. Twenty patients (57.1%) presented with stage III, 11 patients (31.4%) stage II and 4 patients (11.4%) stage I empyema. Complete debridement and decortication were obtained in all patients through U-VATS approach and no conversion or further access was needed for any reason. No major complication was recorded. Only 2 cases of trapped lung were not responsive to surgical treatment. At a mean follow-up of 247.42±306.29 days, 33 patients (94.3%) were alive with no recurrence, 2 patients died for causes unrelated to the operation. CONCLUSIONS: According to our experience, we consider U-VATS as an adequate procedure in the treatment of "stages II and III" empyemas when the necessary surgical expertise has been achieved. Indeed, U-VATS permits an easier performance and complete debridement and decortication, with a very low risk for conversion and excellent postoperative outcomes in terms of less pain, fast recovery and cosmetic results.