[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.

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.

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.

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.

[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.

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.

Combined large-cell neuroendocrine carcinoma and endometrioid adenocarcinoma of the endometrium: A case report and survey of related literature.

Primary large-cell neuroendocrine carcinoma of the endometrium is extremely rare and has a poor prognosis. This report describes a case of combined large-cell neuroendocrine carcinoma and endometrioid adenocarcinoma of the endometrium diagnosed as stage IIIA. The patient underwent surgery and chemotherapy and has been well with no evidence of disease for 20 months. The optimal treatment for this rare tumor has not been established. Considering its rarity and variability, it is difficult to establish an evidence-based therapeutic regimen.

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.

A comparison of thoracic or lumbar patient-controlled epidural analgesia methods after thoracic surgery.

BACKGROUND: We aimed to compare patient-controlled thoracic or lumbar epidural analgesia methods after thoracotomy operations. METHODS: One hundred and twenty patients were prospectively randomized to receive either thoracic epidural analgesia (TEA group) or lumbar epidural analgesia (LEA group). In both groups, epidural catheters were administered. Hemodynamic measurements, visual analog scale scores at rest (VAS-R) and after coughing (VAS-C), analgesic consumption, and side effects were compared at 0, 2, 4, 8, 16, and 24 hours postoperatively. RESULTS: The VAS-R and VAS-C values were lower in the TEA group in comparison to the LEA group at 2, 4, 8, and 16 hours after surgery (for VAS-R, P = 0.001, P = 0.01, P = 0.008, and P = 0.029, respectively; and for VAS-C, P = 0.035, P = 0.023, P = 0.002, and P = 0.037, respectively). Total 24-hour analgesic consumption was different between groups (175 +/- 20 mL versus 185 +/- 31 mL; P = 0.034). The comparison of postoperative complications revealed that the incidence of hypotension (21/57, 36.8% versus 8/63, 12.7%; P = 0.002), bradycardia (9/57, 15.8% versus 2/63, 3.2%; P = 0.017), atelectasis (1/57, 1.8% versus 7/63, 11.1%; P = 0.04), and the need for intensive care unit (ICU) treatment (0/57, 0% versus 5/63, 7.9%; P = 0.03) were lower in the TEA group in comparison to the LEA group. CONCLUSIONS: TEA has beneficial hemostatic effects in comparison to LEA after thoracotomies along with more satisfactory pain relief profile.

Analysis of clinical application of thoracoscopic lobectomy for lung cancer.

BACKGROUND: VATS has been extensively considered as a standard method of pulmonary diagnosis and treatment of benign lung diseases. This study aimed to investigate the safety, efficacy, and feasibility of video-assisted thoracoscopic surgery (VATS) lobectomy compared with conventional lobectomy via open thoracotomy in patients with clinical early stage lung cancer. METHODS: A total of 120 patients with lung cancer underwent VATS lobectomy; another 120 patients with lung cancer underwent conventional lobectomy. The clinical outcomes from these two groups were retrospectively analyzed and compared. RESULTS: The numbers of patients who underwent lobectomy in the left upper lobe, left lower lobe, right upper lobe, right middle lobe, and right lower lobe were 24, 28, 40, 4, and 24 in the VATS group and 38, 20, 30, 7, and 25 in the conventional group, respectively. No statistical differences were observed between the two groups. Likewise, no statistical differences were observed in terms of duration of operation, time for postoperative extubation, complications, length of hospital stay, and number of dissected lymph nodes (VATS group: left, 5.12 ± 1.45, right, 6.84 ± 1.33; conventional group: left, 4.96 ± 1.39 mm, right, 6.91 ± 1.27; P >0.05). CONCLUSION: Anatomical lobectomy was successfully completed by VATS lobectomy for lung cancer; the standard lymph node dissection was also achieved. This procedure also showed advantages in terms of surgical bleeding, duration, postoperative complications, indwelling time of chest tube, and short-term recurrence rate without significant differences from conventional lobectomy.

Combined large cell neuroendocrine carcinoma with giant cell carcinoma of the lungs: a case report.

Combined large cell neuroendocrine carcinoma of the lungs (combined LCNEC) with giant cell carcinoma is extremely rare. A 65-year-old man was found to have an abnormal shadow in his left lung field. Computed tomography revealed a solid, round mass measuring 2.8 × 2.2 cm that was located in the left S9. The patient underwent left lower lobectomy and mediastinal lymph node dissection. Histopathological examination revealed an LCNEC, combined with giant cell carcinoma. The patient received by S-1 (TS-1, an oral fluoropyrimidine) chemotherapy, and he has been disease-free for over 8 months. Combined LCNEC with giant cell carcinoma is an extremely rare tumor with high malignant potential, and thus, multidisciplinary therapy and close follow-up are advised.

Does VMAT for treatment of NSCLC patients increase the risk of pneumonitis compared to IMRT ? - a planning study.

BACKGROUND: Volumetric modulated arc therapy (VMAT) for treatment of non-small cell lung cancer (NSCLC) patients potentially changes the risk of radiation-induced pneumonitis (RP) compared to intensity modulated radiation therapy (IMRT) if the dose to the healthy lung is changed significantly. In this study, clinical IMRT plans were used as starting point for VMAT optimization and differences in risk estimates of RP between the two plan types were evaluated. MATERIAL AND METHODS: Fifteen NSCLC patients prescribed 66 Gy in 2 Gy fractions were planned with IMRT and subsequently with single arc VMAT. Dose metrics were evaluated for target and lung together with population averaged dose volume histograms. The risk of RP was calculated using normal tissue complication probability (NTCP) models. Finally, applicability of the plans was tested through delivery on an Elekta accelerator. RESULTS: When changing from IMRT to VMAT only modest differences were observed in the dose to the lung and target volume. On average, fractions of lung irradiated to doses between 18 Gy and 48 Gy were statistically significant reduced using VMAT compared to IMRT. For the fraction of lung receiving more than 20 Gy the reduction was 1.2% percentage points: (range -0.6 -2.6%). The evaluated toxicity were smaller with VMAT compared to IMRT, however only modest differences were observed in the NTCP values. The plans were delivered without any problems. The average beam on time with VMAT was 83 s. This was a reduction of 141 s (ranging from 37 s to 216 s) compared to IMRT. CONCLUSIONS: Using IMRT as reference for the VMAT optimization it was possible to implement VMAT in the clinic with no increase in estimated risk of RP. Thus, toxicity is not expected to be a hindrance to using VMAT and will profit from the shorter delivery time with VMAT compared to IMRT.

Acute small bowel obstruction: a rare initial presentation for the metastasis of the large-cell carcinoma of the lung.

We present one case with symptom of paroxysmal abdominal pain for over 20 days. Abdominal computerized tomography (CT) scan revealed intestinal obstruction and a mass of 6.0 cm × 6.0 cm in size located at the left adrenal. Chest CT scan showed a lobulated mass of 2.7 cm × 2.7 cm in size at the upper left lung. Core needle biopsy of the lung mass confirmed the diagnosis of large cell carcinoma. The patient underwent an emergency abdominal laparotomy and received a chemotherapy regimen that consisted of pemetrexed and cisplatin postoperatively. In addition, we made a review of the literature of the occurrence, diagnosis and outcome of this manifestation.

[Lung cancer incidentally detected at the treatment of pneumothorax ; report of two cases].

We report 2 cases of lung cancer incidentally detected following pneumothorax. Case 1:A 40-year-old man complaining of dyspnea was admitted with right pneumothorax. Chest computed tomography (CT) after chest drainage showed a cavitary nodule with pleural indentations in the right lower lobe. It was indicated at surgery that pneumothorax was caused by perforation of the tumor into the pleural cavity. Right lower lobectomy was performed because the pathological diagnosis of the nodule was a large cell carcinoma. The final histopathological diagnosis was stage II A (pT2aN1M0). The patient died of recurrence 14 months after surgery. Case 2:A 47-year-old man who admitted with right pneumothorax was found to have a nodule with pleural indentations closely a bulla at the apex of the right lung by chest CT after chest drainage. Pneumothorax was indicated to be caused by rupture of the bulla at surgery. Right upper lobectomy was performed because the pathological diagnosis of the nodule was a squamous carcinoma. The final histopathological diagnosis was stage I A (pT1bN0M0). The patient is alive at 2 years after the operation without recurrence. Lung cancer detected following pneumothorax which was caused by perforation of the tumor is generally considered to have poor prognosis. Whereas, prognosis of lung cancer incidentally detected following pneumothorax depends on its staging.

Large cell neuroendocrine carcinoma of the ampulla of vater with adenocarcinoma and squamous cell carcinoma components.

A 73-year-old woman visited our hospital complaining of general fatigue and jaundice. Laboratory tests revealed an elevated total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and γ-glutamyltransferase. Computed tomography and magnetic resonance imaging demonstrated a mass lesion at the ampulla of Vater with dilatation of the common bile duct and main pancreatic duct. Percutaneous transhepatic cholangiography revealed dilatation of the bile duct and a negative filling defect due to the tumor. Pancreatoduodenectomy was performed. The specimen included an ulcerated firm tumor of the papilla Vater. The surface of the ampulla consisted of well-differentiated papillary adenocarcinoma, whereas the deep layer, such as submucosal or muscular layer, contained large cell neuroendocrine carcinoma and squamous cell carcinoma. Immunohistochemistry revealed that the large cell neuroendocrine carcinoma component was positive for chromogranin A, synaptophysin and CD56. The patient died from multiple liver and bone metastases 13 months after surgery. This is a very rare case of a large cell neuroendocrine carcinoma accompanied by adenocarcinoma and squamous cell carcinoma components.