Deniz Koksal

Prognostic factors in malignant pleural mesothelioma: A retrospective study of 60 Turkish patients

AIMnMalignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis. The study aims to examine the effect of certain clinical, laboratory, radiologic, and pathologic characteristics on survival.nnnPATIENTS AND METHODSnSixty patients who had undergone PET/CT evaluation at initial diagnosis were included. We investigated the effect of certain clinical, laboratory, radiologic characteristics, SUVmax of the tumor, and pathological characteristics such as histological subtype, mitotic activity index (MAI), tumor necrosis, and inflammation on survival. The pathological slides of each patient were re-evaluated for MAI, presence of necrosis, and inflammation. The patients were grouped based on number of mitosis as MAI 1:≤ 9, MAI 2:10-19, MAI 3: >19 mitosis.nnnRESULTSnThere were 34 male and 26 female patients with a mean age of 53.6 ± 10.6 years. Mean and median survival time was 14.83 ± 10.75 and 11.95 (min 0.43-max 48.10) months, respectively. Using univariate analysis leukocytosis (P = 0.009), rind-like pleural thickening (P = 0.037), advanced disease stage (P = 0.004), best supportive therapy alone (P = 0.004), SUVmax higher than 8 (P = 0.023), MAI higher than 1 (P = 0.033), and presence of tumor necrosis (P = 0.037) were found as poor prognostic factors. At multivariate analysis, leukocytosis (P = 0.026, HR: 2.27), advanced disease stage (P = 0.021, HR: 2.46), best supportive therapy alone (P = 0.029, HR: 5.12), and MAI higher than 1 (P = 0.01, HR: 3.01) were independently associated with survival, whereas SUVmax of the tumor failed to enter the model (P = 0.07, HR: 1.89).nnnCONCLUSIONnPresence of leukocytosis, advanced disease stages, supportive therapy alone, and higher MAI were found to be negative prognostic factors in patients with MPM.

Diagnostic utility of conventional transbronchial needle aspiration in older patients

BackgroundIn older patients, diagnosis and initial treatment should be considered as soon as possible because of high disease burden and complications. Conventional transbronchial needle aspiration (C-TBNA) is an important and safe method for the diagnosis of mediastinal lesions and staging lung cancer in the general population. We aimed to evaluate the diagnostic utility and complications of C-TBNA procedure in older patients agedxa0≥xa065xa0years.MethodWe retrospectively evaluated C-TBNA results consecutively. Demographic data, clinical, radiological and flexible bronchoscopy (FB) findings, complications during C-TBNA and incidence of diagnostic C-TBNA with the presence of abundant lymphoid cells of polymorphous appearance both in patients agedxa0≥xa065xa0years and in younger patients were determined.ResultsC-TBNA was performed to a total of 317 patients, including 109 older and 208 younger patients attended to our clinic between 2012 and 2016. The mean ages of older and younger patients were 70.3xa0±xa04.6 and 52.5xa0±xa010xa0years, respectively (pxa0<xa00.001). Overall, 75.2% of older and 80.3% of younger patients had diagnostic C-TBNA. The diagnostic utility of C-TBNA did not differ significantly between older and younger patients (pxa0=xa00.297). During C-TBNA, one older patient had a complication of bronchospasm, and four younger patients had complications such as bleeding (nxa0=xa01) and bronchospasm (nxa0=xa03). There was no statistically significant difference between older and younger patients in terms of complications during C-TBNA procedure (pxa0=xa00.49).ConclusionC-TBNA is a safe procedure with similar diagnostic yield in older patients.

Triple test with tumor markers CYFRA 21.1, HE4, and ProGRP might contribute to diagnosis and subtyping of lung cancer

BACKGROUND AND AIMnEarly diagnosis and histological subtyping are important issues in the management of patients with lung cancer (LC). The aim of this study is to investigate the diagnostic value of a panel of serum tumor markers in newly diagnosed patients with LC.nnnMETHODSnVenous blood samples were collected from 99 patients with LC (42 adenocarcinoma, 35 squamous, and 22 small cell carcinoma) and 30 patients with benign lung disease. Progastrin releasing peptide (ProGRP), squamous cell carcinoma antigen (SCCAg), cytokeratin 19-fragments (CYFRA 21.1), human epididymis protein 4 (HE4), Chromogranin A (CgA) and neuron specific enolase (NSE) levels were measured. The diagnostic value of the biomarkers was assessed with ROC curve analyses; the area under the curve (AUC) was calculated.nnnRESULTSnSerum CYFRA 21.1, ProGRP, SCCAg, NSE levels were significantly higher in LC patients. While ProGRP levels were higher (pu202f=u202f0.009) in SCLC; CYFRA 21.1 and SCCAg levels were higher in NSCLC (pu202f=u202f0.019 and pu202f=u202f0.001, respectively). The sensitivity and specificity of tumor markers were 72%, 83% for CYFRA 21.1; 70%, 57% for HE4; 18%, 93% for ProGRP; 43%, 77% for SCCAg; 54%, 53% for CgA; 73%, 50% for NSE. CYFRA 21.1 (pu202f<u202f0.001, ru202f=u202f0.394), HE4 (pu202f=u202f0.014, ru202f=u202f0.279) and CgA (pu202f=u202f0.023, ru202f=u202f0.259) levels were positively correlated with tumor stage in NSCLC. CgA levels were significantly higher in extensive stage SCLC (pu202f=u202f0.004). CYFRA 21.1 had the highest diagnostic value for LC (AUCu202f=u202f0.865). When it is combined with HE4, diagnostic value increased (AUCu202f=u202f0.899). ProGRP had the highest diagnostic value (AUCu202f=u202f0.875, pu202f<u202f0.001) for discriminating SCLC from NSCLC.nnnCONCLUSIONnA panel of three tumor markers CYFRA 21.1, HE4 and ProGRP may play a role for discriminating LC from benign lung disease and subtyping as SCLC.

Medical thoracoscopy/pleuroscopy: is it underutilized?

Thoracoscopy is a technique introduced more than 100 years ago. The first reported thoracoscopy is thought to be performed as early as 1866 by an Irish urologist Francis Richard Cruise. He examined the pleural cavity through pleurocutenous fistula of an 11-year-old girl with empyema.[1] However, Hans-Christian Jacobaeus, an internist from Sweden, is regarded to be the father of thoracoscopy, since he introduced the technique together with laparoscopy in 1910 and made it known worldwide by many publications and lectures.[2] Jacobaeus used thoracoscopy for the diagnosis of tuberculous effusions and lysis of adhesions due to tuberculosis in the preantibiotic era of tuberculosis treatment. Jacobaeus operations were applied nearly for 40 years worldwide almost exclusively for this purpose. Between 1950 and 1970, the usage of anti-tuberculosis drugs and a diagnostic yield of 70% with closed pleural needle biopsies decreased the need for thoracoscopy. During the following 20 years (1970–1990), tuberculosis decreased whereas malignancies increased, causing thoracoscopy to become popular again. In 1991, getting inspiration from the experience of abdominal surgeons on minimally invasive surgery, thoracic surgeons introduced ‘surgical thoracoscopy’ or ‘video-assisted thoracic surgery’ (VATS).[3] In 1994, the term ‘medical thoracoscopy’ (MT) was introduced by pulmonologists to better differentiate thoracoscopies performed by interventional pulmonologists and chest surgeons.[4] Some authors support the usage of old term ‘pleuroscopy’ (P) which allows an easier distinction. After the introduction of the semirigid pleuroscope by Olympus Corporation, Tokyo, Japan, the term P became more popular and today both terms are used interchangeably.[5] MT/P is a technique performed by chest physicians in a clean endoscopy suite. It is less invasive than VATS, since it can be performed under local anesthesia and conscious sedation through a single entry. However, VATS is performed by chest surgeons in an operating room, under general anesthesia, selective tube intubation and with multiple entries. VATS is more invasive and more expensive.[3] The main indications of MT/P are diagnosis of undiagnosed exudative pleural effusions and talc pleurodesis of malignant pleural effusions. Currently it is the second most important endoscopic technique in pulmonary medicine after bronchoscopy and considered as an integral part of interventional pulmonology. It is easier to learn thoracoscopy than flexible bronchoscopy if there is sufficient expertise in thoracenthesis and chest tube replacement.[2] Although varying from region to region, the numbers of chest physicians performing MT/P are slightly increasing. The present paper focuses on documenting publications related to MT/P. Its aim is to provide an overview of the nature of publications with regard to the years of publication, publication types, discipline and country of origin. We searched all publications about MT/P published between January 1945 and August 2016, and documented the characteristics of the publications regarding publication types, discipline and country of origin by using Thomson Reuters Web of Knowledge Web of Science software (Thomson Reuters Corporation, New York, NY, USA). Web of Science is the largest abstract and citation database of peerreviewed literature: scientific journals, books, and conference proceedings (http://apps.webofknowledge.com/). ‘Medical Thoracoscopy’ or ‘Pleuroscopy’ were selected as ‘topic’ and ‘all years to present (August, 2016)’ was selected as ‘date range.’ A total of 622 documents were retrieved. Most of the documents (n = 584) were published in 1991–2016, a period in which MT/P was popular again 80 years after the Jacobaeus operations. The distribution of publications among years between 1991 and 2016 is demonstrated in Figure 1. In the last decade there was an increase in the number of publications; the highest number was 58 in 2014. The types and the distributions of publications according to disciplines are depicted in Tables 1 and 2, respectively. The most common type of publication was research articles (n = 425), indicating that the area offers scope for productive research. As expected, the respiratory system was the most common discipline studied in MT/P. The 15 countries which publish the most scientific research into MT/P are given in Table 3. The highest numbers of publications were from USA (n = 161), UK (n = 69) and France (n = 62). Re-evaluating the number of publications by region, the highest number of publications were from Europe (n = 269), USA (n = 161) and Eastern countries (n = 143), respectively. EUROPEAN CLINICAL RESPIRATORY JOURNAL, 2017 VOL. 4, NO. 1, 1270078 http://dx.doi.org/10.1080/20018525.2016.1270078

Acute massıve pulmonary embolism assocıated wıth olanzapıne

ABSTRACT Treatment with low‐potency anti‐psychotic agents is an important risk factor in the development of pulmonary embolism (PE). We report a case of 74 years old female patient receiving olanzapine for psychotic depression admitted to the emergency service with the complaints of chest pain and shortness of breath. She had tachypnea, hypotension and tachycardia. Arterial blood gas analysis showed hypoxemia‐hypocapnia and D‐dimer level was high. Computed tomographic pulmonary angiography (CTPA) demonstrated pulmonary embolism in both main pulmonary arteries, through lobar and segmental branches. Tissue plasminogen activator (t‐PA) was administered in intensive care unit. As the only possible risk factor for PE was olanzapine, olanzapine treatment was terminated with pyschiatry consultation. During the 12‐month follow‐up of the patient; malignancy was not observed. Diagnosis and prevention of PE are the important goals to reduce morbidity and mortality in subjects receiving olanzapine.

Definitive chemoradiotherapy in Stage III nonsmall cell lung cancer: Turkey experience

AIMnConcurrent chemoradiotherapy (CRT) is the standard therapy for patients with unresectable Stage III nonsmall cell lung cancer (NSCLC). The aim of this study was to assess the efficacy and safety of concurrent CRT in unresectable Stage III NSCLC in Turkey.nnnPATIENTS AND METHODSnThe study included 82 patients with histologically proven unresectable Stage III NSCLC, Eastern Cooperative Oncology Group performance status 0-1, who received concurrent CRT in two different referral centers. Treatment consisted of two cycles of cisplatin at 50 mg/m 2 on days 1, 8, 29, and 36 and etoposide 50 mg/m 2 between days 1 and 5, 29-33 and concurrent radiotherapy administered once daily, 1.8-2.0 Gy per fraction, at a total dose of 60-66 Gy.nnnRESULTSnThe stages of the patients were Stage IIIA in 39 (47.5%) and IIIB in 43 (52.5%) patients. Complete and partial responses were achieved in 15 (18.2%) and 31 (37.8%) of the patients, respectively. Twenty-eight (34.2%) patients had stable disease and 8 (9.8) had progressive disease. Forty-one (50%) patients recurred during follow-up. The primary site of recurrence was as distant metastasis in 19 (23.2%) patients. Median overall survival (OS) was 20 months (95% confidence interval; 12.9-27.09 months), 3 and 4 years survivals were 27.9% and 20.9%, respectively. Median progression-free survival (PFS) was 9 months, 3 and 4 years PFSs were 20.1% and 16.1%. Myelosuppression was the most common toxicity. In 15 (19.2%) patients grade 2-3 lung toxicity and in seven (8.5%) patients grade 2-3 dysphagia were reported.nnnCONCLUSIONnConcurrent CRT with cisplatin and etoposide schedule is a well-tolerated regimen with acceptable toxicity profile and survival rates in patients with unresectable Stage IIIA/IIIB NSCLC. Median survival and OS results were consistent with the literature.

Thromboembolic Events in Malignant Pleural Mesothelioma.

Aim: Malignant pleural mesothelioma (MPM) increases the risk of thromboembolic events (TEEs). In this retrospective study, we aimed to determine the rate of TEEs in MPM and investigate its relationship with the presence of thrombocytosis, the disease stage, and the tumor histopathology. Methods: The study included 178 patients who were histopathologically diagnosed as MPM between the years January 2008 and June 2014. Results: The mean age was 58.7 ± 11.8 years, and the median follow-up time was 8 months. Seventy-one patients (39.9%) had thrombocytosis (>350 × 103/mL). In total, 14 (7.9%) TEEs were identified: 6 (3.4%) pulmonary thromboembolism, 6 (3.4%) deep venous thrombosis, and 2 (1.1%) myocardial infarctions. Although 5 (2.8%) of the TEEs preceded the diagnosis of MPM, 1 (0.6%) occurred simultaneously with the diagnosis of MPM and 8 (4.5%) followed the diagnosis of MPM. Thromboembolic event rates were not statistically different based on the presence of thrombocytosis (P = .51), disease stage (P = .14), and histopathology (P = .38). Conclusion: The rate of TEEs was 7.9%. Presence of thrombocytosis, disease stage, and histopathology did not affect the incidence of TEEs.

Primary diffuse pleural rhabdomyosarcoma in an adult patient

Rhabdomyosarcoma is an aggressive malignant tumor of childhood, originating from immature cells that are destinated to form striated skeletal muscle. It usually arises in the head and neck or the extremities. Primary diffuse pleural rhabdomyosarcoma is exceptionally rare. Herein we report a case of primary diffuse pleural rhabdomyosarcoma in a 48-year-old man. The diagnosis was confimed by percutaneous pleural biopsy. Chemotherapy (cisplatin, ifosfamide, adriamycin, vincristine) was initiated due to the large volume of the tumor. After 3 months, computed tomography of the thorax showed stable radiological findings.

Recovery of pulmonary and skin lesions of sarcoidosis after thymectomy.

Objective and importance: Sarcoidosis is a multisystem inflammatory disorder of unknown etiology. It is characterized by the presence of noncaseating granulomas and an inflammatory process in which T lymphocytes, especially type-1 helper T (Th1) cells, macrophages and different cytokines are involved. Different studies have shown the importance of genetic background in addition to environmental exposure in explaining different clinical phenotypes and disease outcome. In addition, potential auto antigens that might lead to the disease have been identified. Clinical presentation: Here, we present a 53-year-old female patient presenting with subcutaneous nodules and mediastinal hilar lymphadenopathies refractory for corticosteroid treatment. Computed tomography of the thorax revealed a soft-tissue lesion in the thymus location. Intervention: The lesions due to sarcoidosis resolved after thymectomy. Conclusion: The remission of skin and pulmonary sarcoidosis only after thymectomy does potentially indicate the critical role that the thymus might play in the pathogenesis of this disease in a certain group of patients.

Lymph Node/Tumor SUVmax Ratio Can Predict Metastasis to Mediastinal Lymph Nodes in Lung Cancer Patients

To the Editor: We were interested to read the article by Evison et al. published in the January 2015 issue of Journal of Thoracic Oncology. We appreciated the idea of proposing a risk stratification model for negative lymph nodes by endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) in lung cancer patients. The proposed model increased the negative predictive value of EBUSTBNA from 91% to approximately 99%. We believe that this model can help to discriminate patients that may directly proceed to curative treatment after a negative EBUS-TBNA. On the basis of this model, an EBUS-TBNA negative lymph node needs no further evaluation if the lymph node maximum standardized uptake value (SUVmax) is lower than 4, the SUVmax ratio between lymph node and primary tumor (LN/T SUVmax) is lower than 0.4, and the lymph node has homogeneous echogenecity during ultrasonographic assessment. In the absence of distant metastasis, proper staging of mediastinum is of great importance for identification of patients who are candidates for radical curative therapies. Although positron emission tomography/computed tomography (PET/CT) can never replace pathological staging, it is regarded as the most accurate imaging modality for nodal staging. However, there are a significant number of false positivity (underlying inflammatory processes, such as immune reaction because of presence of tumor, obstructive Reply to: “Lymph Node/Tumor SUVmax Ratio Can Predict Metastasis to Mediastinal Lymph Nodes in Lung Cancer Patients”