Intratumoral Treatment with Chemotherapy and Immunotherapy for NSCLC with EBUS-TBNA 19G.

Introduction: Immunotherapy is being used for the past five years either as first line or second line treatment with great results. Chemotherapy and radiotherapy have been also used as combination to immunotherapy to further enhance this type of treatment. Intratumoral treatment has been previously proposed as a treatment option for certain non-small cell lung cancer patients. Patients and Methods: We recruited in total seventy four patients with non-small cell lung cancer in their second line treatment who received only chemotherapy in their first line treatment with programmed death-ligand-1 ≤ 50. Only adenocarcinoma or squamous cell carcinoma, and all negative for epidermal growth factor receptor, anaplastic lymphoma kinase, proto-oncogene tyrosine-protein kinase-1 and proto-oncogene B-Raf. Data were first examined with descriptive statistics choosing frequencies for categorical variables and histograms for the continuous ones. Twenty five received only intravenous immunotherapy and forty-nine intravenous cisplatin with immunotherapy. Data were first examined with descriptive statistics choosing frequencies for categorical variables and histograms for the continuous ones. Results: The relationships between changes of performance status and disease progression were examined via a single correspondence analysis. The two-dimensional scores (coordinates) derived from the correspondence analysis were then regressed against the predictors to form distinct splits and nodes obtaining quantitative results. The best fit is usually achieved by lowering exhaustively the AICc criterion and looking in parallel the change of R2 expecting improvements more than 5%. both types of therapy are capable of producing best ameliorative effects, when either the programmed death-ligand-1 expression or parenchymal site in joint with low pack years are present in the sampling data. Conclusions: Intratumoral treatment combination with cisplatin plus immunotherapy indifferent of nivolumab or pembrolizumab combination is an effective choice. In specific for those with endobronchial lesions. Moreover; patients with programmed death-ligand-1 ≥ 50 had their performance status and disease progression improved over the eight month observation.

Bronchogenic cyst or lung cancer. Only biopsy can tell.

Bronchogenic cysts are rare congenital malformations which derive from primitive ventral foregut. They are usually observed in intrathoracically. A fifty year old male was admitted for the investigation of a three month chest pain. Computed tomography scan of the thorax revealed a lesion around the esophagus and left stem bronchus. Endobronchial ultrasound with convex probe and a 19G needle biopsy revealed a bronchogenic cystic which was removed with video assisted thoracic surgery. Initial radiologic assessment although was thought to be lung cancer because of the smoking habit it turned out to be benignancy. EBUS-TBNAB with 10G needle is safe and absolutely necessary for these lesions, as they take large samples.

Pleurodesis and Immunotherapy in NSCLC; Medical Thoracoscopy or VATS?

Introduction: Immunotherapy is a treatment option for non-small cell lung cancer advanced disease. However; immunotherapy in several patients induces orogonitis and effusion in different cavities. It is up to the treating physician to understand whether there is effusion due to adverse effect or disease progression. Pleurodesis in both cases might be a solution for recurrent pleura effusion. Patients and Methods: Three hundred and thirty seven non-small cell lung cancer patients with adenocarcinoma and pleura effusion during first line immunotherapy treatment underwent medical thoracoscopy or Video assisted thoracic surgery (VATS) for pleurodesis with talk poudrage. Uniportal medical thoracoscopy was performed under general with dual channel endotracheal tube in one hundred and eleven patients. Video assisted thoracic surgery was performed in one hundred and eighty seven patients and conversion from medical to VATS procedure was done to thirty nine patients. All patients had stage IV disease with pleura involvement and were under first line pembrolizumab treatment with 200mg (PD-L1 ≥ 50%). Results: The quantitative parameters of the study (expression, PY and cycle) were converted to an ordinal scale to facilitate the performance of statistical analysis. All parameters were examined as dependent against the parameter technique acting as independent to detect potential relationships. The results of multi Y versus X relationship revealed no statistically significant effect (p>0.05) of the three levels of technique against any response considered. Thus we can infer, quite safely, that the innovative operation (level 0) does not differ from the other two conventional methods (levels 2 and 3) through all parameters entered in the model. There was no significant difference between the different pleurodesis techniques. Discussion: Immunotherapy is known to induce in a number of patients pleura effusion and pericarditis. However; pleurodesis is efficient when the appropriate method is performed to every patient. Careful assessment in a case by case manner has to be performed for each patient before any procedure is performed.

Clinical factors affecting the survival of patients diagnosed with non-small cell lung cancer and metastatic malignant pleural effusion, treated with hyperthermic intrathoracic chemotherapy or chemical talc pleurodesis: a monocentric, prospective, randomized trial.

BACKGROUND: There is a plethora of treatment algorithms for managing patients with malignant pleural effusions (MPEs), sharing many common points and principles. Our study aims to compare hyperthermic intrapleural chemotherapy (HITHOC) and talc pleurodesis (TALC), as treatment options for patients with non-small cell lung cancer (NSCLC) and metastatic MPE. METHODS: This prospective, randomized trial was conducted at a single thoracic surgery center, the "Theagenio" Cancer Institute, in Greece, under the identification code NCT01409551 and was completed. All 40 patients enrolled were adults with histologically proven metastatic, unilateral, MPE caused by NSCLC. Exclusion criteria included patients >80 years, trapped lung, and major comorbidities. Patients were randomly and equally assigned 1:1 to either HITHOC (group A) or TALC (group B) by video assisted thoracic surgery (VATS). The primary outcome was the median overall survival (OS) from trial intervention to death, while secondary outcome was the identification of clinical factors affecting the survival. RESULTS: The patients were followed up for 45 months. The OS of the full group was 8 months (95% CI: 7.046-8.954). Participants who underwent HITHOC had an OS of 8 months (95% CI: 7.141-8.859), whereas the participants of TALC had an OS of 9 months (95% CI: 7.546-10.454), with no significant difference between groups. Among fifty-four factors that were tested for their effects on survival, only TNM stage and creatinine values both preoperatively and 7 days postoperatively could be regarded as risk-factors for survival. Other recorded parameters, which had significant variance between the two groups, were urea levels, C-reactive protein, white blood cells and total in hospital length of stay (LOS). CONCLUSIONS: Both HITHOC and TALC are equally effective and safe therapeutic options in treating patients with MPE and NSCLC with acceptable survival. The study revealed independent clinical risk factors influencing survival, which could be utilized as starting points for larger clinical studies. KEYWORDS: Pleurodesis; pleural effusion; malignant; carcinoma; non-small cell lung; hyperthermia.

Malignant peripheral nerve sheath tumor (MPNST) arising from angiosarcoma: a rare case report.

PURPOSE: An extremely rare case of divergent differentiation of a cutaneous angiosarcoma to a malignant peripheral nerve sheath tumor (MPNST) is presented. METHODS: A 62-year-old male patient presented with an angiosarcoma of the left buccal region, which was excised with wide surgical margins. Four months after the operation, the tumor recurred locally as a MPNST. The recurrent tumor was treated with surgical excision followed by postoperative radiotherapy. Four years later, the patient presented with solitary lung metastasis. The patient underwent upper right lobectomy. RESULTS: The patient is alive and disease-free 2 years after the lobectomy and 6 years after initial presentation. CONCLUSIONS: Divergent differentiation of an angiosarcoma to a neurosarcoma supports the theory that cells of the neural crest capable of differentiating both to neuroectoderm and to mesenchyme give origin to these tumors.

Endobronchial ultrasound convex probe for lymphoma, sarcoidosis, lung cancer and other thoracic entities. A case series.

Endobronchial ultrasound endoscopy is a state of the art diagnostic endoscopic procedure for the thorax. Firstly it was designed mainly for the staging of lung cancer and of course for the diagnosis of suspicious findings in large central airways. The main limitation of the equipment is the diameter of the instrument and therefore it can only be guided through large airways. However; the diameter of the working channel also provides a large tissue sample nowadays with the 19G biopsy needle. We will provide our experience with the 22G needle of the endobronchial convex-probe in several medical situations of the thorax.

Immunotherapy "Shock" a case series of PD-L1 100% and pembrolizumab first-line treatment.

In this decade a "bloom" of novel therapies has been observed for non-small cell lung cancer. We have new tools for the diagnosis of lung cancer and also we can re-biospy easier than before in different lesions and obtain tissue samples in order to investigate whether a patient can receive new targeted therapies. Immunotherapy has been well established previously for other forms of cancer, and nowadays it is also available for lung cancer. There are two immunotherapies for now nivolumab and pembrolizumab which can be administered as second line treatment, the second can also be administered as first-line if there is a programmed death-ligand 1 ≥50% expression.

Increased Δ133p53 mRNA in lung carcinoma corresponds with reduction of p21 expression.

Modification of p53 expression levels and its principle apoptosis and cell cycle regulatory partners, mouse double minute 2 homolog (MDM­2) and p21, has been previously reported in various types of cancer. In the current study, the expression of Δ133p53 isoforms was investigated in lung carcinomas with respect to the expression of the aforementioned genes. The expression of p53 full­length transcript and Δ133p53 isoforms α, ß and γ transcripts, MDM­2 and p21 transcripts were determined by reverse transcription­quantitative polymerase chain reaction, in total RNA isolated from 17 lung carcinoma specimens and 17 corresponding adjacent non­cancerous tissues. RNA expression analysis was performed according to the Pfaffl equation and Rest tool using ß­actin as a reference gene. Detection of the above proteins was additionally performed by western blotting. Significant overexpression of the Δ133p53 mRNAs was observed in cancerous as compared with adjacent non­cancerous tissues (3.94­fold), whereas full­length p53 and MDM­2 expression exhibited a smaller, however significant, increase. The expression of the p21 transcript was significantly reduced in cancerous specimens. Δ133p53 and p21 expression levels varied in parallel, however were not significantly correlated. p53 full­length protein expression observed by western blot analysis strongly varied from the Δ133p53 isoforms, however MDM­2 protein isoforms were not detectable and p21 protein was more abundant in non­cancerous tissues. In conclusion, Δ133p53 mRNA levels is suggested as a potentially useful marker of malignancy in lung cancer. The absence of Δ133p53 protein in lung carcinomas, which overexpress Δ133p53 transcripts, may indicate the role of the latter in post­transcriptional regulation through RNA interference in the cell cycle and apoptosis.

Burnout syndrome and job satisfaction in Greek residents: exploring differences between trainees inside and outside the country.

BACKGROUND: The purpose of this study is to investigate the levels of burnout among Greek residents, highlighting potential differences between those practicing at home and abroad, as well as to investigate correlations with demographic, individual and labor factors. METHODS: The research was conducted on a sample of 131 residents, using an anonymous questionnaire which included demographic, individual and labor characteristics, Maslach's Burnout Inventory, questions regarding job and life satisfaction levels, working conditions and the impacts of the economic recession. RESULTS: Fifty two point seven percent of the sample were training in the Greek National Health Service (N.H.S.), 27.5% in Germany and 19.8% in the United Kingdom. One out of three residents in the Greek system showed high levels of burnout in all three dimensions of the syndrome, while 51.1%, 72.2% and 30.8% of the Greek, British and German team, respectively, appeared burnt out simultaneously in two dimensions. Levels of job and life satisfactions ranged on average, while workload appeared heavy. CONCLUSIONS: The occurrence of burnout was associated with gender, specialty, employment characteristics (working hours, autonomy, support etc.), proneness to accidents, country, job satisfaction and quality of life, but was not associated with age or marital status. No correlation was found with susceptibility to medical errors.

Coincidence of thymoma and breast cancer and in a 56-year-old female patient.

We present a case of a 56-year-old female, with a familial history of breast, lung and brain cancer, which revealed a breast tumor, located in the upper outer quadrant of the left breast. During the routinely staging examinations, a 15 cm intrathoracic tumor was found in the upper left mediastinum, penetrating the pericardium and a smaller tumor, in the left side of parietal pleura. Core biopsies from both lesions, revealed a lobular carcinoma of the breast classic type, grade II (e-cadherin-, ER+, PR+, Her-2-, Ki-67 10%) and a B3 thymoma (CK19+, CD5+) penetrating the pericardium and the left lung. A synchronous removal of both tumors was scheduled, including median sternotomy and left intrapericardial pneumonectomy, followed by a modified radical left mastectomy and a sentinel lymph node biopsy. The postoperative course was uneventful. This case advocates that thymoma patients appear to have a predisposition towards developing additional neoplasms, as breast carcinoma. Clinicians should be aware of the increased incidence of extrathymic cancers, occurring in thymoma patients.

Successful surgical treatment of a complicated esophageal perforation, by use of primary closure and lung parenchyma reinforcement.

Esophageal perforation (EP) is a medical condition which demands urgent confrontation with significant complications. The cause of the perforation may be common, spontaneous or iatrogenic, with conservative or surgical therapeutic strategy, which is needed in the majority of incidents, depending on the characteristics of the lesion. We report a case of a 68-year-old man, with the existence of an ulcerative lesion 31 cm approximately from the dental barrier, and a coexistent stenosis, diagnosed through esophagogastroduodenoscopy, which evolved to an extensive purulent necrotic mediastinitis, diagnosed through a thorax CT scan after the patient began to complain of asphyxiation during eating. A right posterolateral thoracotomy was performed along with intensive wide spectrum antibiotic therapy. Primary closure of the perforation as well as pulmonary tenting was used with satisfactory results. There was no evidence of leakage after a 12-month "follow-up" period. The early diagnosis of an EP combined with immediate surgical procedure and frequent "follow-up" of the patient, eliminate the risks for the patient's life and ensure a satisfactory outcome.

Percutaneous tracheostomy-beware of the thyroidea-ima artery.

Percutaneous tracheostomy is a minimally invasive operation performed in patients, in order to provide an air passage through the windpipe. A rare cause of severe bleeding during such operation is the injury of the thyroidea-ima artery. This case report presents a patient with hemorrhage after thyroidea-ima injury during percutaneous dilatational tracheostomy. Surgeons should always be aware of such anatomic variation, in order to prevent urgent sternotomy.

A patient with situs inversus totalis and lung cancer-a rare combination.

Situs inversus totalis (SIT) is a rare clinical entity which is characterized by a complete reverse anatomy of the thoracic cage and abdomen. There are a few reports of patients with SIT and lung cancer. The number of the cases that have been treated surgically is also very small. We report a case of an 80 years old patient who underwent left lower lobectomy after staging with uniportal video-assisted thoracoscopic surgery (VATS) and mediastinoscopy.

Screening of Pleural Mesotheliomas for DNA-damage Repair Players by Digital Gene Expression Analysis Can Enhance Clinical Management of Patients Receiving Platin-Based Chemotherapy.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare, predominantly asbestos-related and biologically highly aggressive tumour leading to a dismal prognosis. Multimodality therapy consisting of platinum-based chemotherapy is the treatment of choice. The reasons for the rather poor efficacy of platinum compounds remain largely unknown. MATERIAL AND METHODS: For this exploratory mRNA study, 24 FFPE tumour specimens were screened by digital gene expression analysis. Based on data from preliminary experiments and recent literature, a total of 366 mRNAs were investigated using a Custom CodeSet from NanoString. All statistical analyses were calculated with the R i386 statistical programming environment. RESULTS: CDC25A and PARP1 gene expression were correlated with lymph node spread, BRCA1 and TP73 expression levels with higher IMIG stage. NTHL1 and XRCC3 expression was associated with TNM stage. CHECK1 as well as XRCC2 expression levels were correlated with tumour progression in the overall cohort of patients. CDKN2A and MLH1 gene expression influenced overall survival in this collective. In the adjuvant treated cohort only, CDKN2A, CHEK1 as well as ERCC1 were significantly associated with overall survival. Furthermore, TP73 expression was associated with progression in this subgroup. CONCLUSION: DNA-damage response plays a crucial role in response to platin-based chemotherapeutic regimes. In particular, CHEK1, XRCC2 and TP73 are strongly associated with tumour progression. ERCC1, MLH1, CDKN2A and most promising CHEK1 are prognostic markers for OS in MPM. TP73, CDKN2A, CHEK1 and ERCC1 seem to be also predictive markers in adjuvant treated MPMs. After a prospective validation, these markers may improve clinical and pathological practice, finally leading to a patients' benefit by an enhanced clinical management.

Fast-track rehabilitation following video-assisted pulmonary sublobar wedge resection: A prospective randomized study.

BACKGROUND: Postoperative morbidity and inhospital length of stay are considered major determinants of total health care expenditure associated with thoracic operations. The aim of this study was to prospectively evaluate the role of video-assisted thoracic surgery (VATS) compared to mini-muscle-sparing thoracotomy in facilitating early recovery and hospital discharge after pulmonary sublobar wedge resections. PATIENTS AND METHODS: A total number of 120 patients undergoing elective pulmonary sublobar wedge resection were randomly assigned to VATS (n = 60) or mini-muscle-sparing thoracotomy (n = 60). The primary endpoint was time to hospital discharge. Postoperative complications, cardiopulmonary morbidity and 30-day mortality served as secondary endpoints. RESULTS: Patients' baseline demographic and clinical data did not differ among study arms as well as the number of pulmonary segments resected and the morphology of the nodular lesions. Total hospital stay was significantly shorter in patients assigned to the thoracoscopic technique as opposed to those who were operated using the mini-muscle-sparing thoracotomy approach (4 ± 0.6 versus 4.4 ± 0.6 days respectively, P = 0.006). Multivariate analysis revealed that VATS approach was inversely associated with longer inhospital stay whereas the number of resected segments was positively associated with an increased duration of hospitalization. Patients in the VATS group were less likely to develop atelectasis (≥1 lobe) compared to those who underwent thoracotomy (0% versus 6.7% respectively, P = 0.042). Kaplan-Meier analysis revealed similar 30-day mortality rates in both study arms (Log-rank P = 0.560). CONCLUSION: VATS was associated with shorter duration of hospitalization positively affecting the patients' quality of life and satisfaction. Significant suppression of the total cost of recovery after thoracoscopic pulmonary resections is expected.

Prognostic factors for long term survival in patients with advanced non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) represents 85% of all lung cancers. It is estimated that 60% of patients with NSCLC at time of diagnosis have advanced disease. The aim of this study was to investigate clinical and demographic prognostic factors of long term survival in patients with unresectable NSCLC. METHODS: We retrospectively reviewed data of 1,156 patients with NSCLC stage IIIB or IV who survived more than 60 days from the time of diagnosis and treated from August 1987 until March 2013 in the Oncology Department of Pulmonary Clinic of the General Hospital Papanikolaou. Initially univariate analysis using the log-rank test was conducted and then multivariate analysis using the proportional hazards model of Cox. Also Kaplan Meier curves were used to describe the distribution of survival times of patients. The level of significance was set at 0.05. RESULTS: The mean age at diagnosis was 62 years. About 11.9% of patients were women and 88.1% were male. The majority of cases were adenocarcinomas (42.2%), followed squamous (33%) and finally the large cell (6%). Unlike men, most common histological type among women was adenocarcinoma rather than squamous (63% vs. 10.9%). In univariate analysis statistically significant factors in the progression free survival (PFS) and overall survival (OS) were: weight loss ≥5%, histological type, line 1 drugs, line 1 combination, line 1 cycles and radio lung. Specifically radio lung gives clear survival benefit in the PFS and OS in stage IIIB (P=0.002) and IV (P<0.001). On the other hand, the number of distant metastases in stage IV patients did not affect OS, neither PFS. In addition patients who received platinum and taxane had better PFS (P=0.001) and OS (P<0.001) than those who received platinum without taxane. Also the third drug administration proved futile, since survival (682.06±34.9) (P=0.023) and PFS (434.93±26.93) (P=0.012) of patients who received less than three drugs was significantly larger. Finally, large cell carcinoma recorded the shortest OS and PFS compared with adenocarcinoma (P=0.043 and P=0.016 respectively) and squamous cell carcinoma (P=0.021 and P=0.004 respectively). In multivariate analysis the same predictors were statistically significant except for line 1 drugs. CONCLUSIONS: This study confirms the increased incidence of adenocarcinoma in women than in men and the aggressiveness of large cell carcinoma. It also underlines the vitality of factors such as weight loss, radio lung and doublet platinum-based. On the other hand, it excludes significant factors such as gender, age and smoking.

Video-assisted thoracic surgery reduces early postoperative stress. A single-institutional prospective randomized study.

BACKGROUND: Video-assisted thoracic surgery (VATS) has been shown to effectively reduce postoperative pain, enhance mobilization of the patients, shorten in-hospital length of stay, and minimize postoperative morbidity rates. The aim of this prospective study is to evaluate neuroendocrine and respiratory parameters as stress markers in cancer patients who underwent lung wedge resections, using both mini muscle-sparing thoracotomy and VATS approach. METHODS: The patients were randomly allocated into two groups: Group A (n=30) involved patients who were operated on using the VATS approach, while in group B (n=30), the mini muscle-sparing thoracotomy approach was used. Neuroendocrine and biological variables assessed included blood glucose levels, C-reactive protein (CRP) levels, cortisol, epinephrine, and adrenocorticotropic hormone (ACTH) levels. Arterial oxygen (PaO2) and carbon dioxide (PaCO2) partial pressure were also evaluated. All parameters were measured at the following time points: 24 hours preoperatively (T1), 4 hours (T2), 24 hours (T3), 48 hours (T4), and 72 hours (T5), after the procedure. RESULTS: PaO2 levels were significantly higher 4 and 24 hours postoperatively in group A vs group B, respectively (T2: 94.3 vs 77.9 mmHg, P=0.015, T3: 96.4 vs 88.7 mmHg, P=0.034). Blood glucose (T2: 148 vs 163 mg/dL, P=0.045, T3: 133 vs 159 mg/dL, P=0.009) and CRP values (T2: 1.6 vs 2.5 mg/dL, P=0.024, T3: 1.5 vs 2.1 mg/dL, P=0.044) were found increased in both groups 4 and 24 hours after the procedure. However, their levels were significantly lower in the VATS group of patients. ACTH and cortisol values were elevated immediately after the operation and became normal after 48 hours in both groups, without significant difference. Postoperative epinephrine levels measured in group A vs group B, respectively, (T2: 78.9 vs 115.6 ng/L, P=0.007, T3: 83.4 vs 122.5 ng/L, P=0.012, T4: 67.4 vs 102.6 ng/L, P=0.021). The levels were significantly higher in group B. CONCLUSION: This study confirmed that minimally invasive thoracic surgery, by means of VATS, significantly reduces the acute-phase response and surgical stress, while enables better postoperative oxygenation.

Single sternal metastasis due to malignant melanoma with unexpected long-term survival: a case report.

Metastases from melanoma have a very poor prognosis for the patient. Single metastatic lesions in the sternum due to melanoma are extremely rare. A rare case of a presternal mass in a 56-year-old patient who had undergone excision for malignant melanoma is presented. Review of the patient's history and surgical resection of a single metastatic soft tissue lesion offer the best chance of long-term survival.