[Superior Vena Cava Syndrome due to Large Cell Neuroendocrine Carcinoma Originated in the Mediastinum].

We report a case of a 53-year-old man with superior vena cava( SVC) syndrome due to large cell neuroendocrine carcinoma (LCNEC) in the mediastinum. His chief complaint was general fatigue. On physical examination, both jugular veins were distended and his face and bilateral upper limbs were swollen. Enhanced chest computed tomography (CT) scan demonstrated a heterogenous tumor of approximately 50 mm in diameter in the middle mediastinum, which infiltrated into the SVC and right atrium, and caused SVC syndrome. Since SVC syndrome developed rapidly, the tumor was resected and the occluded SVC was replaced with a ringed polytetrafluoroethylene graft under cardiopulmonary bypass. After surgery, SVC obstruction was resolved with improvement of the initial symptoms. The patient had an uneventful recovery and was discharged from our hospital. The tumor was diagnosed as LCNEC histologically. He received postoperative adjuvant systemic chemotherapy. Unfortunately, he died of extensive brain and bone metastasis 10 months after the operation. However, we believe that surgical relief from SVC syndrome improved quality of the rest of his life.

Neuroendocrine carcinoma of the endometrium: A very rare gynecologic malignancy.

OBJECTIVE: To investigate the clinicopathologic characteristics, prognostic factors, outcome, and treatment of the neuroendocrine carcinoma (NEC) of the endometrium. MATERIALS AND METHODS: We retrospectively reviewed the clinicopathologic and survival data of 10 patients who underwent surgery for NEC. The patients were collected between 1999 and 2017 from four referral centers in Turkey. RESULTS: The median age of patients was 67 years (range: 34-75 years). The NEC of endometrium consist of 9 cases with small cell carcinoma (SC) NEC (two with mixed histotypes), and one with a large cell (LC) NEC. According to FIGO 2009 criteria, 70 % (7/10) of patients had advanced stage (III and IV) disease. All patients except one underwent surgical staging, eight patients received platinum-based chemotherapy (CTX) and of 6 those were additionally treated with radiotherapy (RT). Four patients died of disease ranging from 2 to 10 months and six were alive 12-72 months with no evidence of disease. In addition, 4 SC NEC cases raised in polypoid features had no evidence of disease from 24 to 72 months. DISCUSSION: NEC of the endometrium is a rare disease with poor prognosis, which frequently diagnosed in advanced stages. The main treatment modality was the administration of platinum-based CTX as an adjuvant to surgery or surgery and RT. Our result suggests that the polypoid feature of the tumor might be one of the best predictors for the prognosis of SC NEC.

Atypical and incomplete pulmonary hypertrophic osteoarthropathy in the left distal femur: a case report.

BACKGROUND: Pulmonary hypertrophic osteoarthropathy (PHO) is a rare paraneoplastic syndrome that mainly occurs in patients with lung cancer. Most symptoms occur symmetrically, and unilateral symptoms without clubbing are infrequent. This report presents the case of a rare atypical symptom that was highly suspected of being PHO. CASE PRESENTATION: A 77-year-old woman with swelling and severe pain in the left femur for 2 months was referred to our hospital. Radiography revealed a remarkably osteogenic thickening and sclerotic lesion in her distal femur. Preliminary diagnoses of malignant bone tumor and hematological tumor were made based on laboratory test results, radiological examination, and clinical manifestation. A needle biopsy was performed, which ruled out the diagnosis of malignant bone tumors. A low-grade bone tumor was still suspected. After that, en bloc resection was performed, followed by replacement of the femur with a mega-prosthesis. Pathological analysis revealed no malignant tumor cells, and immunohistochemical staining for CDK4 and MDM2 yielded negative results. Meanwhile, pulmonary large cell carcinoma was identified on biopsy. Based on published studies, a diagnosis of atypical PHO was made according to clinical and imaging manifestations. CONCLUSIONS: This is an infrequent case of PHO with unilateral symptoms in the left femur. When clinical manifestations and radiological findings are inconsistent with the pathological results, the possibility of benign lesions with malignant clinical manifestations or imaging features should be carefully considered.

Metastatic large cell carcinoma of the lung: A rare cause of acute small bowel obstruction.

Here, we report a case of acute intestinal obstruction as the initial presentation of primary lung cancer in a male patient. Abdominal computed tomography (CT) showed multiple polypoid masses and regional lymphadenopathy with small bowel obstruction. The patient underwent emergency surgery for multiple luminal malignancy with mesenteric masses. According to the various clinicopathological features, the tumor was confirmed to be metastatic large cell carcinoma originating from the lung. Large masses in the left lower lobe of the lung were identified on the chest CT after emergency surgery, and non-small cell lung cancer (NSCLC), not otherwise specified (NOS), was finally diagnosed on biopsy through bronchoscopy.

Application of contrast-enhanced ultrasonography for large cell neuroendocrine carcinoma in the urinary bladder: a case report.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is an uncommon malignant bladder tumor, and the overall prognosis is poor. Contrast-enhanced ultrasound (CEUS) provides a new effective modality for tumor detection and diagnosis. CASE PRESENTATION: A 30-year-old man complained of repeated painless gross haematuria for half a month. Conventional ultrasound demonstrated a hypoechoic solitary lesion with hyperechoic margins measuring 3.4 × 3.1 cm in the anterior wall of the bladder. Superb microvascular imaging (SMI) showed a strong flow signal in the mass. CEUS revealed that the lesion was characterized by hyper-enhancement in the early phase and hypo-enhancement in the late phase. The entire bladder wall was disrupted by homogeneous hyper-enhanced tumor tissue on CEUS. Time-intensity curves (TICs) showed a rapid wash-in with a high maximum signal intensity (SI) and quick wash-out. Finally, partial cystectomy was performed and the pathological examination confirmed the diagnosis of LCNEC with invasion into the whole layer of the bladder wall. CONCLUSION: This case suggested that CEUS was a valuable imaging method to detect and diagnose LCNEC in the bladder, and that CEUS can provide information related to the depth of wall invasion and the microvasculature.

Sequential screening for lung cancer in a high-risk group: randomised controlled trial: LungSEARCH: a randomised controlled trial of Surveillance using sputum and imaging for the EARly detection of lung Cancer in a High-risk group.

BACKGROUND: Low-dose computed tomography (LDCT) screening detects early-stage lung cancer and reduces mortality. We proposed a sequential approach targeted to a high-risk group as a potentially efficient screening strategy. METHODS: LungSEARCH was a national multicentre randomised trial. Current/ex-smokers with mild/moderate chronic obstructive pulmonary disease (COPD) were allocated (1:1) to have 5 years surveillance or not. Screened participants provided annual sputum samples for cytology and cytometry, and if abnormal were offered annual LDCT and autofluorescence bronchoscopy (AFB). Those with normal sputum provided annual samples. The primary end-point was the percentage of lung cancers diagnosed at stage I/II (nonsmall cell) or limited disease (small cell). RESULTS: 1568 participants were randomised during 2007-2011 from 10 UK centres. 85.2% of those screened provided an adequate baseline sputum sample. There were 42 lung cancers among 785 screened individuals and 36 lung cancers among 783 controls. 54.8% (23 out of 42) of screened individuals versus 45.2% (14 out of 31) of controls with known staging were diagnosed with early-stage disease (one-sided p=0.24). Relative risk was 1.21 (95% CI 0.75-1.95) or 0.82 (95% CI 0.52-1.31) for early-stage or advanced cancers, respectively. Overall sensitivity for sputum (in those randomised to surveillance) was low (40.5%) with a cumulative false-positive rate (FPR) of 32.8%. 55% of cancers had normal sputum results throughout. Among sputum-positive individuals who had AFB, sensitivity was 45.5% and cumulative FPR was 39.5%; the corresponding measures for those who had LDCT were 100% and 16.1%, respectively. CONCLUSIONS: Our sequential strategy, using sputum cytology/cytometry to select high-risk individuals for AFB and LDCT, did not lead to a clear stage shift and did not improve the efficiency of lung cancer screening.

A Retrospective Study on Efficacy and Safety of Rivaroxaban and Dalteparin for Long-Term Treatment of Venous Thromboembolism in Patients with Lung Cancer.

BACKGROUND: Standard therapy for cancer-associated venous thromboembolism (VTE) is low-molecular-weight heparin. The use of direct oral anticoagulants for cancer-associated VTE has increased; however, their efficacy and safety in lung cancer patients remain unclear. OBJECTIVES: We examined the efficacy and safety of rivaroxaban compared with dalteparin for cancer-associated VTE in patients with primary lung cancer. METHODS: A single-center retrospective study of 204 patients with primary lung cancer who were prescribed rivaroxaban (n = 131) or dalteparin (n = 73) for VTE was performed. The primary endpoint was a composite event including recurrence and major or clinically relevant nonmajor bleeding. Secondary endpoints included the incidence of recurrence, major and clinically relevant nonmajor bleeding, all-cause mortality, and bleeding or pulmonary embolism-related mortality. RESULTS: The composite event occurred in 38 (29.0) and 12 (16.4%) patients in the rivaroxaban and dalteparin (p = 0.045) groups, respectively. The multivariate Cox proportional hazards model for age, Eastern Cooperative Oncology Group performance score, and bleeding risk factors revealed the rivaroxaban group showed a 1.176-fold composite event risk without statistical significance (0.595-2.324, p = 0.641). There was no statistically significant intergroup difference for the incidence of VTE recurrence (5.3% in the rivaroxaban group versus 2.7% in the dalteparin group, p = 0.495) and major or clinically relevant nonmajor bleeding (23.7% in the rivaroxaban group versus 13.7% in the dalteparin group, p = 0.089). There was no significant difference in the all-cause mortality rate (hazard ratio 0.864, 95% CI 0.624-1.196, p = 0.337). CONCLUSIONS: There was no difference in the safety and efficacy profile of rivaroxaban compared with dalteparin. Therefore, rivaroxaban may be a valuable treatment option for lung cancer-associated VTE.

Cardiovascular disease and survival in non-small cell lung cancer: a multicenter prospective assessment.

PURPOSE: Chronic inflammation contributes to cancer development via multiple mechanisms. We hypothesized that cardiovascular diseases (CVD) are also an independent risk factor for survival in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Prospective multicenter data from 345 consecutive NSCLC patients treated from January 2013 to January 2017 were assessed. Median follow-up for all patients was 13 months (range 3-60 months). There were 109 patients with baseline heart disease (HD 32%), 149 with arterial hypertension (43%), 85 with diabetes mellitus (25%), 129 with hyperlipidemia (37%) and 45 with venous thromboembolism events (VTE 13%). A total of 289 patients (84%) were treated with platinum-based chemotherapy (CT), 300 patients (87%) received thoracic radiation therapy (RT; median radiation dose: 60 Gy [range 12-70]); and 50 (15%) patients underwent surgery. RESULTS: Our cohort consisted of 305 men (88%) and 40 (12%) women, with a median age of 67 years (range 31-88 years). Seventy percent had a Karnofsky performance status (KPS) ≥ 80. Multivariate analyses showed a lower OS and higher risk of distant metastasis in patients with advanced stages (p = 0.05 and p < 0.001, respectively) and HD (HR 1.43, p = 0.019; and HR 1.49, p = 0.025, respectively). Additionally, patients with VTE had lower local control (HR 1.84, p = 0.025), disease-free survival (HR 1.64, p = 0.020) and distant metastasis-free survival (HR 1.73, p = 0.025). CONCLUSIONS: HD and VTE are associated with a higher risk of mortality and distant metastasis in NSCLC patients. Chronic inflammation associated with CVDs could be an additional pathophysiologic factor in the development of distant metastasis.

[Pulmonary Non-tuberculous Mycobacteriosis Complicated with Pulmonary Large Cell Neuroendocrine Carcinoma;Report of a Case].

A 64-year-old man with pulmonary non-tuberculous mycobacteriosis(pulmonary NTM) who had been treated by antituberculous chemotherapy, developed a new nodule of 8 mm in size in the segment 3 of the right upper lobe. The cavity of 4.0 cm in size in the segment 1+2 of the left upper lobe due to Mycobacterium avium infection was preexisted. Radiologically, new nodule of the right lung was suspected to be lung cancer. Left upper lobe apical trisegmentectomy was performed at first. Three months later, enlarging of the right lung nodule with increased fluoro-2-deoxy-D-glucose(FDG) activity was noted, and the diagnosis of lung cancer was made by transbronchial lung biopsy(TBLB). Then, right upper lobectomy with systematic nodal dissection were performed.

Lung Cancer: Clinical Presentation and Diagnosis.

In the absence of screening, most patients with lung cancer are not diagnosed until later stages, when the prognosis is poor. The most common symptoms are cough and dyspnea, but the most specific symptom is hemoptysis. Digital clubbing, though rare, is highly predictive of lung cancer. Symptoms can be caused by the local tumor, intrathoracic spread, distant metastases, or paraneoplastic syndromes. Clinicians should suspect lung cancer in symptomatic patients with risk factors. The initial study should be chest x-ray, but if results are negative and suspicion remains, the clinician should obtain a computed tomography scan with contrast. The diagnostic evaluation for suspected lung cancer includes tissue diagnosis, staging, and determination of functional capacity, which are completed simultaneously. Tissue samples should be obtained using the least invasive method possible. Management is based on the individual tumor histology, molecular testing results, staging, and performance status. The management plan is determined by a multidisciplinary team consisting of a pulmonology subspecialist, medical oncology subspecialist, radiation oncology subspecialist, and thoracic surgeon. The family physician should remain involved with the patient to ensure that patient priorities are supported and, if necessary, to arrange for end-of-life care.

In Vivo Adaptive Optics Ophthalmoscopy Correlated with Histopathologic Results in Cancer-Associated Retinopathy.

PURPOSE: To demonstrate the validity of adaptive optics scanning laser ophthalmoscopy (AOSLO) imaging of the retina in human disease based on clinicopathologic correlation in a patient with cancer-associated retinopathy (CAR). DESIGN: Case report. PARTICIPANT: Sixty-four-year-old man with CAR. METHODS: Fundus photography, electroretinography, visual field testing, fundus autofluorescent imaging, spectral-domain OCT scans, AOSLO, and histopathologic analysis were performed. MAIN OUTCOME MEASURE: Comparison of AOSLO with histopathologic results. RESULTS: Changes in photoreceptor morphologic features were correlated highly between AOSLO and histopathologic results. CONCLUSIONS: We present a unique case where a patient with a rare and fatal disease, CAR, underwent AOSLO imaging during the course of the disease, and then shortly thereafter, postmortem histopathologic analysis of the eyes was carried out. This is the first report of use of AOSLO to elucidate further the retinal changes that occur in CAR and the first study to demonstrate correlation of AOSLO with histopathologic results in any human disease.

Ectopic ACTH-producing large cell neuroendocrine Pancoast tumour presenting as Horner syndrome.

We present an interesting case where a patient is presented with a droopy left eyelid (as part of Horner syndrome) and Cushingoid features which were a result of a Pancoast tumour (apical lung tumour in superior pulmonary sulcus) involving the left lung. This tumour was secreting ectopic adrenocorticotropic hormone (ACTH), a paraneoplastic endocrine phenomenon, which resulted in Cushing syndrome symptomatology. Though most ectopic ACTH-producing lung cancers are either small cell or carcinoid tumours, this was in fact a large cell neuroendocrine cancer (LCNEC). Patient underwent surgical resection and adjuvant/neoadjuvant chemotherapy with radiation; however, he succumbed to LCNEC given aggressive nature of the disease.

A case of anti-nuclear matrix protein 2 antibody positive myopathy associated with lung cancer.

Myositis-specific autoantibodies (MSAs) are associated with myositis. Anti-nuclear matrix protein 2 (NXP-2) antibody was recently identified as a major MSA and was observed mostly in juvenile dermatomyositis. We report the case of a 44-year-old man who presented with myopathy with anti-NXP-2 antibody and large cell carcinoma of the lung. He was hospitalized because of myalgia and edema of limbs. Neurological examination revealed mild proximal-dominant weakness in all four extremities, and laboratory studies showed elevated creatine kinase level (6,432 IU/l). Needle electromyography showed myogenic patterns. MRI of the lower limbs demonstrated inflammatory lesions in the thighs. Biopsied specimen from the left quadriceps femoris muscle showed mild mononuclear inflammatory infiltrate surrounding muscle fibres but no fiber necrosis. He was diagnosed with myopathy based on neurological examinations and clinical symptoms. His chest X-ray and CT showed tumor shadow on the right upper lung field, but CT didn't indicate the findings of interstitial lung disease. This was surgically removed, and a histological diagnosis of non-small cell lung cancer was suspected. He was also treated with definitive chemoradiotherapy before and after operation. His symptoms of myopathy promptly remitted with the preoperative chemotherapy. His serum analysis was positive for the anti-NXP-2. Further investigation and experience of MSAs are necessary to evaluate the therapeutic strategy against cancer-associated myopathy/myositis.

Large-cell lung cancer originating from tracheal bronchus - A rare case.

Tracheal bronchus is a rarely seen congenital anomaly generally originating from the right lateral wall of the trachea and approximately 2 cm above the carina. It was firstly defined by Sandifort in 1785 and its frequency of incidence in normal population changes between 0.1% and 2%. There are two types called ''Supernumerary'' and ''Displaced''. It is a rarely seen kind of tracheal anomaly although fairly well defined. The cases accompanied by lung cancer are seen more rarely. Nine cases of this association were reported in literature and tracheal bronchus-lung cancer association whose pathological result is undifferentiated large-cell carcinoma has not been stated so far. We present a 75 years old male patient as possibly the first case having tracheal bronchus and large-cell carcinoma association in literature.

The Effect on Cognition of Mitochondrial Respiratory System Proteins in Peripheral Blood Mononuclear Cells in the Course of Lung Cancer.

Peripheral blood mononuclear cells (PBMC) represent an easily available population of cells for the studies on remote effects of lung cancer. NADH dehydrogenase (ubiquinone) Fe-S protein-1 (Ndufs1), a marker of mitochondrial complex I, and mitochondrially encoded cytochrome c oxidase 1 (MTCO1), a marker of complex IV, may participate in cognitive decline during the course of lung cancer. In this study, Ndufs1 and MTCO1 expression in PBMC was evaluated by means of ELISA in 80 lung cancer patients. Mini-Mental State Examination (MMSE) were conducted Trail Making Tests (TMT-A and TMT-B) at baseline and after the 6 months' follow-up. Autoantibodies were identified by means of indirect immunofluorescence and line blot. We found that enhanced levels of Ndufs1 in PBMC were related to impaired cognitive performance; TMT-A of 13.6 ± 3.1 s and TMT-B of 162.5 ± 46.4 s compared with 8.6 ± 4.5 s (p = 0.003) and 124.8 ± 51.8 s (p < 0.05), respectively, in the case of low Ndufs-1 levels. The Ndufs1 expression at baseline was associated with MMSE - τb (Kendall's tau-b) = -0.31; p = 0.024; TMT-A - τb = 0.30; p = 0.001), and TMT-B - τb = 0.199; p = 0.012) after the 6 months' follow-up. Higher MTCO1 expression was accompanied by worse TMT-A results than in case of inhibited MTCO1; 11.1 ± 5.8 s vs. 8.5 ± 4.1 s; respectively; p = 0.048. MTCO1 expression was correlated with TMT-A results (τb = 0.17; p = 0.034) at baseline. We conclude that stimulation of PBMC mitochondrial function in lung cancer patients is associated with cognitive impairment. Mitochondrial dysfunction in PBMC may reflect cytotoxicity responsible for neurological deficits.