Lambert-Eaton myasthenic syndrome with primary thymic marginal zone B-cell lymphoma: A case report.

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune paraneoplastic syndrome with proximal muscle weakness, that often complicates small cell lung cancer. It is known that neurological symptoms do not improve with malignancy treatment alone in many LEMS patients, therefore treatment is often difficult. Since Lambert-Eaton myasthenic syndrome is a rare disease with a frequency of about 1/100 that of myasthenia gravis, there are only a few case reports on malignancy complications other than small cell lung cancer. We report a LEMS patient in his 40s who was found to have an anterior mediastinal mass. We performed surgical resection and confirmed the diagnosis of primary thymic marginal zone B-cell lymphoma by pathological diagnosis using immunostaining. Thymectomy and malignant lymphoma treatment with rituximab had no effect on neurological symptoms. The neurological symptoms improved only after we provided comprehensive care with the haematology, neurology, and rehabilitation department.

Postoperative tegafur-uracil for stage I lung adenocarcinoma: first real-world data with an exploratory subgroup analysis.

PURPOSE: The effect of postoperative tegafur-uracil on overall survival (OS) after resection of stage I adenocarcinoma has been shown in clinical trials. The purpose of this study was to investigate whether findings from randomized trials of adjuvant tegafur-uracil are reproducible in a real-world setting. METHODS: A retrospective cohort study was performed using a multi-institutional database that included all patients who underwent complete resection of pathological stage I adenocarcinoma between 2014 and 2016. Survival outcomes for patients managed with and without tegafur-uracil were analyzed using the Kaplan-Meier method and a Cox proportional hazards model for the whole patient cohort and in a selected cohort based on eligibility criteria of a previous randomized trial. Propensity score matching was used to adjust for confounding effects. RESULTS: After propensity score matching, the hazard ratios for OS were 0.57 (95% confidence interval (CI) 0.29-1.14, P = 0.11) in the whole cohort and 0.69 (95% CI 0.32-1.50, P = 0.35) in the selected cohort. CONCLUSIONS: The effects of tegafur-uracil in this retrospective study appear to be consistent with those found in randomized clinical trials. These effects may be maximized in patients aged from 45 to 75 years.

Epidermal growth factor receptor tyrosine kinase inhibitors as first-line treatment for postoperative recurrent EGFR-mutated lung adenocarcinoma: a multi-institutional retrospective study.

OBJECTIVES: The aim of this study was to analyse the long-term survival outcomes and prognostic factors of patients receiving epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as first-line treatment for postoperative recurrent EGFR-mutated lung adenocarcinoma. METHODS: Using a multi-institutional database, we performed a retrospective chart review to identify all patients who had undergone complete resection of stage I-III EGFR-mutated lung adenocarcinoma at 11 acute care hospitals between 2009 and 2016 and had received first-line EGFR-TKI treatment for postoperative recurrence. Adverse events, progression-free survival (PFS) and overall survival (OS) were investigated. Survival outcomes were assessed using Kaplan-Meier analysis. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for PFS and OS. RESULTS: The study sample comprised 154 patients with a median age of 69. The total numbers of events were 101 for PFS and 60 for OS. The median PFS and OS were 26.1 and 55.4 months, respectively. In the multivariable analysis, EGFR ex 21 L858R mutation (HR: 1.71, 95% CI: 1.15-2.55) and shorter disease-free intervals (HR: 0.98, 95% CI: 0.96-0.99) were significantly associated with shorter PFS. Age (HR: 1.03, 95% CI: 1.00-1.07), smoking history (HR: 2.31, 95% CI: 1.35-3.94) and pathological N2 disease at the initial surgery (HR: 2.30, 95% CI: 1.32-4.00) were significantly associated with shorter OS. CONCLUSIONS: First-line EGFR-TKI treatment was generally associated with favourable survival outcomes in patients with postoperative recurrent EGFR-mutated lung adenocarcinoma. EGFR ex 21 L858R mutation may be an important prognostic factor for shorter PFS.

Mediastinal tuberculosis following descending necrotizing mediastinitis: A case report.

Tuberculosis is a disease that causes latent infection and is sometimes activated by a variety of factors. Descending necrotizing mediastinitis (DNM) is a serious disease caused by spreading oropharyngeal infection. We present a case of mediastinal tuberculosis following mediastinal dissection and antibiotic therapy for DNM. A 62-year-old man was admitted to the hospital with an increasing mass in the right mediastinum during outpatient follow-up after surgical drainage and antibiotic treatment for idiopathic cervical abscess and left DNM caused by oral bacteria. The patient underwent right mediastinal abscess dissection 4 months after the last surgery. As a result of culture tests, no general bacteria but Mycobacterium tuberculosis was detected. Anti-tuberculosis treatment was continued for 9 months, and the patient has progressed without any recurrence of infection. The possibility of relapse of tuberculosis should always be considered in patients with unexplained masses.

Left Lower Lobectomy in a Patient With Absence of Pulmonary Artery Branching Into the Lobe.

Here, we report a case in which we resected non-small cell lung cancer of the left lower lobe and detected an anomaly in the resected lobe. Three-dimensional computed tomography showed more detailed information on this anomaly than the conventional one. Because we recognized the information regarding the anomaly before the operation, we accomplished left lower lobectomy and an uneventful postoperative course. If carcinoma had existed in the other lobe, the intraoperative and postoperative course would have become more serious. Therefore, it is essential to pay attention to the information regarding anatomic abnormality when resecting malignant tumors.

The treatment and survival of patients with postoperative recurrent thymic carcinoma and neuroendocrine carcinoma: a multicenter retrospective study.

PURPOSE: There are few data available on the outcomes of postoperative recurrent thymic carcinoma (TC) and thymic neuroendocrine carcinoma (TNEC). The aim of this study is to evaluate the treatment and survival in patients with recurrent TC and TNEC after undergoing surgical resection. METHODS: A retrospective chart review was performed using our multicenter database to identify patients with a postoperative recurrence of TC and TNEC from 1995 to 2018. The clinicopathological factors were reviewed and the survival outcomes were analyzed. RESULTS: Sixty patients were identified among 152 patients who underwent resection of TC and TNEC. The median follow-up period from the first recurrence was 14.8 months (range 0-144). The 5-year post-recurrence survival was 23% for the whole cohort. According to a univariable analysis, advanced stage [hazard ratio (HR) 2.81, 95% confidence interval (CI) 1.09-9.54], interval between primary surgery and recurrence (HR 0.97, 95% CI 0.95-0.99), any treatment for recurrence (HR: 0.27, 95% CI 0.13-0.58) and chemotherapy for recurrence (HR: 0.46, 95% CI 0.22-0.95) were significant factors related to post-recurrence survival. CONCLUSIONS: Chemotherapy rather than surgery appears to be the mainstay treatment for managing patients with postoperative recurrent TC and TNEC and it may also be considered in multidisciplinary management. Further studies with a larger sample size are required to confirm our findings.

Hemothorax resulting from an initially masked aortic perforation caused by penetration of the sharp edge of a fractured rib: A case report.

INTRODUCTION: There are multiple causes of hemothorax in blunt chest trauma. However, a traumatic hemothorax with an uncertain cause is potentially life-threatening without treatment, because an undetected and hidden great vessel injury can remain unknown. Delayed diagnosis can lead to death. PRESENTATION OF CASE: A 77-year-old man was transferred to a local hospital, after experiencing a 3-m fall. Contrast CT of the chest revealed a left clavicle fracture, multiple left rib fractures and hemopneumothorax, but no obvious signs of great vessel injury, such as aortic injury. His condition was stable, owing to the chest tube thoracostomy with 800 ml blood output and intravenous fluid. The patient was then transferred to our hospital for further treatment. However, his condition rapidly deteriorated in the ambulance on the way to our hospital, and he needed a blood transfusion. On arrival, he was in shock, with his vital signs compromised due to blood loss. Emergency open thoracotomy was performed to explore the bleeding point and stop hemorrhaging. Intraoperative findings revealed sharp edges of the fractured fourth and fifth left ribs to be protruding into the chest cavity toward the descending aorta and causing an aortic pinhole injury. Ruptured aorta was repaired with a pledget-armed sutures and the sharp fractured ribs were resected. The patient was discharged, uneventfully, 35 days after the operation. CONCLUSION: This case suggests that even if great vessel injury is not detected on contrast CT at admission, it should always be considered especially in a hemothorax case with multiple rib fractures.

Unilateral antibiotic-induced acute eosinophilic pneumonia on the operative side after surgery for primary lung cancer: a case report.

BACKGROUND: Acute eosinophilic pneumonia (AEP) is a rare idiopathic lung disease characterized by pulmonary eosinophilia. The epidemiology of AEP remains understudied; however, past reports have reported that AEP can be caused by an allergic reaction to medications, such as antibiotics or inhaled antigens, such as tobacco smoke. AEP usually occurs bilaterally. However, we encountered an unusual case of antibiotic-induced eosinophilic pneumonia showing unilateral consolidation just on the operative side, which was initially diagnosed as postoperative bacterial pneumonia and treated with antibiotic therapy. The prescribed antibiotics paradoxically provoked AEP and worsened the patient's condition. Here, we report this antibiotic-induced AEP case showing unilateral consolidation only on the operative side which could be triggered by surgery for primary lung cancer. CASE PRESENTATION: A 74-year-old man underwent right upper lobectomy for lung adenocarcinoma. On postoperative day (POD) 9, an interstitial shadow appeared in the right lower lung field of the chest radiographs, along with a fever of 38.5 °C, dyspnea needing oxygen supplementation, and increased purulent sputum production, suggesting postoperative bacterial pneumonia. Despite administration of the broad-spectrum antibiotic, meropenem, the fever did not improve, and pulmonary opacity gradually worsened. Blood analysis showed increased peripheral eosinophils at 1182/mm3. The meropenem treatment was discontinued and bronchoscopy was performed for further evaluation, and the bronchoalveolar lavage fluid assessment showed a remarkable increase in the eosinophil population (51%). The drug lymphocyte stimulation test (DLST) for meropenem was positive. We diagnosed the patient with antibiotic-induced unilateral AEP, after which corticosteroid treatment was initiated. The patient subsequently improved and the infiltration in the right lower lung field completely disappeared. The patient was discharged on POD 43 without oxygen supplementation and is doing well without tumor recurrence 16 months after the surgery. CONCLUSIONS: Unilateral drug-induced AEP is rare. Nonetheless, it should be recognized as a differential diagnosis of postoperative pneumonia even in cases of a unilateral radiographic infiltration, because the lung operation itself could trigger this type of AEP.

Low incidence of and mortality from a second malignancy after resection of thymic carcinoma†.

OBJECTIVES: Previous studies have suggested that a second malignancy often develops after resection of thymoma; however, it remains unknown whether this is applicable to thymic carcinoma. METHODS: A retrospective chart review was performed based on our multi-institutional database of resected thymic epithelial tumours between 1991 and 2016. A second malignancy was defined as newly diagnosed after thymic tumour resection. The cumulative incidence of and related death from a second malignancy after thymic and neuroendocrine carcinoma resections were estimated using a competing risk model and were compared to those of patients undergoing a thymoma resection. RESULTS: Two hundred and thirty-eight patients were identified (thymic carcinoma 59; thymoma 179). A second malignancy developed in 1 patient (1.7%) with thymic carcinoma and in 17 patients (9.5%) with thymoma. Deaths from second malignancies were noted in 7 patients with thymoma. There was a tendency towards a lower cumulative incidence of and a lower cumulative death from a second malignancy after thymic carcinoma resection (P = 0.139 and P = 0.20, respectively) than after thymoma resection. The cumulative incidence of a second malignancy in patients with thymic carcinoma was 2.8% at 5 years and at 10 years (8.0% at 5 years and 11.8% at 10 years in patients with thymoma). CONCLUSIONS: After resection of thymic and thymic neuroendocrine carcinoma, the probability of developing a second malignancy, as well as mortality from a second malignancy, is very low. A prospective study with a larger sample size is required to validate our results.

Survival outcomes after minimally invasive thymectomy for early-stage thymic carcinoma.

Minimally invasive surgery (MIS) has occasionally been used for selected patients with thymoma, but there is little information on the MIS approach for thymic carcinoma. The aim of this study was to evaluate survival outcomes after MIS for early-stage (Masaoka stage I-II) thymic carcinoma and thymic neuroendocrine carcinoma. A retrospective chart review of the cases recorded in our multi-institutional database was performed to identify patients who underwent resection for thymic carcinoma between 1995 and 2017. MIS thymectomy was performed in 17 cases (VATS, n = 14; RATS, n = 3. male, 41%; median age, 72 years). The median follow-up period was 32.7 (range 7.4-106) months. The five-year overall survival and relapse-free survival rates were 84.4% and 77.8%, respectively. The present study demonstrated encouraging preliminary results regarding MIS for the treatment of early-stage thymic carcinoma and thymic neuroendocrine carcinoma. Further studies with a larger sample size are required to evaluate the indications for this surgery.

Pulmonary artery sarcoma resected via median sternotomy with thoracoscopic assistance.

Median sternotomy is frequently selected for the resection of pulmonary artery tumor, and pneumonectomy is performed for complete resection. However, it is difficult to see the inferior pulmonary vein and transect it safely via median sternotomy, so additional thoracotomy is often required and this is highly invasive. In the present case, we employed thoracoscopy (which we routinely use for VATS lobectomy) to transect the inferior pulmonary vein via median sternotomy without additional intercostal thoracotomy. This method has advantages for patients undergoing pneumonectomy via median sternotomy.

[Clear Cell Tumor of the Lung Showing Gradual Growth for 6 years].

Clear cell tumor of the lung (CCTL) is a rare benign tumor that originates from the lung. We report a case of CCTL which had grown for 6 years. The patient was a 25-year-old woman and her chest roentgenogram detected a well-circumscribed coin-like shadow in the left lower lung field. Its size was 30 mm in diameter at consultation, and retrospectively we recognized a nodule of 13 mm in diameter in the same location on the health checkup roentgenogram 6 years before. The growth of the tumor suggested the possibility of malignancy, and the tumor was surgically resected by partial resection of the lung. Post operative course was uneventful. The tumor was clearly separated from pulmonary parenchyma, and was immunohistochemically diagnosed as CCTL.

[Multiple lung metastases from cutaneous adenoid cystic carcinoma resected 21 years before].

A 79-year-old woman whose cutaneous tumor had been resected 21 years and 12 years (local recurrence)before pathologically confirmed as primary cutaneous adenoid cystic carcinoma (ACC), was referred to our hospital for the abnormal shadow on chest X-ray. Chest computed tomography (CT)revealed 3 nodules in the peripheral field of both lungs, which were diagnosed by echo-guided needle biopsy as metastasis from the cutaneous ACC, and were completely resected at 5 months intervals. Any recurrences have not been detected for 2 years after the lung resection. In primary cutaneous ACC, not only complete resection with adequate margin but long-term follow up is recommended.

A novel surgical approach to refractory hepatic hydrothorax.

Hepatic hydrothorax is defined as the presence of a pleural effusion in a patient with liver cirrhosis in the absence of cardiopulmonary disease, and it is a devastating complication impairing quality of life in the end stage of liver disease. The management of the effusion is challenging, and chest tube drainage can sometimes cause more serious complications by removing massive amounts of protein-rich fluid. Though the most plausible mechanism is the influx of ascites to the pleural cavity through a small diaphragmatic defect, the defect often cannot be found. Hepatic hydrothorax could be controlled by repairing an invisible defect of the diaphragm. With pneumoperitoneum after intraperitoneal administration of indocyanine green, the defect, clearly dyed green, appeared on the diaphragm. This novel combination technique could be useful for ensuring the surgical repair of an invisible diaphragmatic defect.

Local anaesthetic thoracoscopy for intractable pneumothorax in a high-risk patient.

The management of high-operative-risk patients with a pneumothorax is complicated. The case of a 79-year old man with an intractable secondary pneumothorax, who had taken oral steroids to control asthma, is presented. Since the patient could not tolerate general anaesthesia because of poor cardiac function, thoracoscopic surgery was performed under local anaesthesia. A successful lung fistula closure was achieved and the continuous air leakage disappeared immediately after the surgery.

D2-40-positive lymphatic vessel density is a poor prognostic factor in squamous cell carcinoma of the lung.

BACKGROUND: Experimental studies have revealed that D2-40 is useful in identifying the presence of lymphatic invasion in various malignant neoplasms, but the clinical significance remains unclear. The purpose of this study is to assess the clinical significance of D2-40 status in completely resected non-small cell lung cancer. METHODS: A total of 215 consecutive patients with resected pathological stage I-IIIA non-small cell lung cancer were reviewed. Expression of D2-40 in tumor cells and in endothelial cells was examined immunohistochemically, and D2-40-positive lymphatic vessel density (LVD) at the tumor periphery were quantitatively evaluated. RESULTS: D2-40 expression on tumor cells was positive in 55 (25.6%) of 215 patients, and the incidence was significantly higher in squamous cell carcinoma (SCC) patients than in adenocarcinoma patients (48.8% vs. 8.6%, P < .001). D2-40 was also seen on lymphatic vessels in tumor tissues, and the mean number of D2-40-LVD was significantly decreased along with differentiation of tumor cells (P = .038). For all histologic types of tumors, there was no difference in the postoperative survival between higher D2-40-LVD patients and lower D2-40-LVD patients. For SCC, however, lower D2-40-LVD patients showed a significantly better survival than higher D2-40-LVD patients (5-year survival rates, 52.9% vs. 78.9%, P = .040), which was confirmed by a multivariate analyses (P = .048). CONCLUSIONS: D2-40 expression on tumor cells was more frequently seen in SCC than in adenocarcinoma of the lung. In addition, D2-40 expression on lymphatic vessels in tumor tissues was a statistically significant prognostic factor in SCC.

Perimembrane Aurora-A expression is a significant prognostic factor in correlation with proliferative activity in non-small-cell lung cancer (NSCLC).

PURPOSE: Aurora-A, also known as STK15/BTAK, is a member of the protein serine/threonine kinase family, and experimental studies have revealed that Aurora-A plays critical roles in cell mitosis and in carcinogenesis. However, no clinical studies on Aurora-A expression in non-small-cell lung cancer (NSCLC) have been reported. Thus, the present study was conducted to assess the clinical significance of Aurora-A status. EXPERIMENTAL DESIGN: A total of 189 consecutive patients with resected pathologic (p-)stage I-IIIA, NSCLC were retrospectively reviewed, and immunohistochemical staining was used to detect Aurora-A expression. RESULTS: Aurora-A expression was negative in 31 patients (16.4%); among Aurora-A positive patients, 124 patients showed pure diffuse cytoplasmic Aurora-A expression and the other 34 patients showed perimembrane Aurora-A expression. Perimembrane Aurora-A tumors showed the highest proliferative index (PI) (mean PIs for negative, diffuse cytoplasmic, and perimembrane tumors: 49.2, 41.7, and 63.5, respectively; P < .001). Five-year survival rates of Aurora-A negative, diffuse cytoplasmic, and perimembrane patients were 67.8%, 66.7%, and 47.6%, respectively, showing the poorest postoperative survival in perimembrane patients (P = .033). Subset analyses revealed that perimembrane Aurora-A expression was a significant factor to predict a poor prognosis in squamous cell carcinoma patients, not in adenocarcinoma patients. A multivariate analysis confirmed that perimembrane Aurora-A expression was an independent and significant factor to predict a poor prognosis. CONCLUSIONS: Perimembrane Aurora-A status was a significant factor to predict a poor prognosis in correlation with enhanced proliferative activity in NSCLC.

The ratio of membrane-bound form Flt-1 mRNA to VEGF mRNA correlates with tumor angiogenesis and prognosis in non-small cell lung cancer.

Fms-like tyrosine kinase 1 (Flt-1), a receptor for vascular endothelial growth factor (VEGF), have two isoforms: membrane-bound form (mFlt-1) and soluble form. In the present study, we quantitatively evaluated expression level of mFlt-1 mRNA and VEGF mRNA in non-small cell lung cancer, and demonstrated the clinical significance of the ratio of mFlt-1 mRNA to VEGF mRNA (mFlt-1/VEGF). High mFlt-1/VEGF tumor showed a significantly lower microvessel density (P=0.004), and patients with high mFlt-1/VEGF tumor had a significantly favorable survival (P=0.037). Thus, the ratio of mFlt-1 mRNA to VEGF mRNA was inversely correlated with tumor angiogenesis, and was a significant prognostic factor.

Influence of epidermal growth factor receptor (EGFR) gene mutations on the expression of EGFR, phosphoryl-Akt, and phosphoryl-MAPK, and on the prognosis of patients with non-small cell lung cancer.

BACKGROUND AND OBJECTIVES: In this paper we examined the influence of epidermal growth factor receptor (EGFR) gene mutations on EGFR expression, downstream mediators, and survival in patients with non-small cell lung cancer (NSCLC). METHODS: We retrospectively analyzed the tumors of 53 patients with completely resected pathological stage I-IIIA NSCLC for the presence of EGFR gene mutations, the expression of EGFR mRNA and protein, phosphoryl-Akt, and phosphoryl-mitogen-activated protein kinase (MAPK) using immunostaining, and patients' prognosis. RESULTS: EGFR mutations were associated with elevations in EGFR mRNA (P = 0.004) and protein (P = 0.029) expression, but not with the expression of phosphoryl-Akt or phosphoryl-MAPK. The 5-year survival rate for all patients who exhibited an EGFR mutation was similar to those who were free of such mutations (71% vs. 56%, P = 0.252). However, the 5-year survival rate of patients with either a stage I adenocarcinoma or large cell carcinoma who had an EGFR mutation was significantly greater than for those who did not have such a mutation (92% vs. 57%, P = 0.037). CONCLUSIONS: EGFR gene mutations were significantly associated with higher EGFR expression, but not with p-Akt or p-MAPK status. In early stage NSCLC, the presence of an EGFR gene mutation bode well for the patient's prognosis.

Maspin expression and its clinical significance in non-small cell lung cancer.

BACKGROUND: Maspin is a member of the serpin (serine protease inhibitor) superfamily, and its exact function in the development and progression of malignant tumors remains controversial, though some experimental studies have revealed potential tumor-suppressor activities. In addition, there have been only a few clinical studies on maspin expression in malignant tumors including non-small cell lung cancer (NSCLC). The purpose of this study was to assess maspin expression and its clinical significance in NSCLC. METHODS: A total of 210 consecutive patients with completely resected pathological (p-) stage I-IIIA NSCLC were retrospectively reviewed. Maspin expression along with intratumoral microvessel density, proliferative activity, and p53 status were evaluated immunohistochemically. The incidence of apoptotic cell death was also evaluated. RESULTS: The incidence of strong maspin expression was significantly higher in lung squamous cell carcinoma (56/76, 73.7%; P < .001) than in other histological types. The incidence of aberrant expression of p53 was significantly higher in maspin-strong than in maspin-weak tumors (56.2% and 35.8%, respectively; P = .005). There was no difference in prognosis according to maspin status for all patients. However, for squamous cell carcinoma patients, univariate analysis showed that enhanced maspin expression was a significant factor in predicting a favorable prognosis (5-year survival rates, 70.1% for maspin-strong tumors and 41.5% for maspin-weak tumors; P = .014), which was confirmed in a multivariate analysis (hazard ratio = .475, 95% confidence interval .241-.936; P = .032). CONCLUSIONS: Enhanced maspin expression was a significant and independent factor in predicting a favorable prognosis in lung squamous cell carcinoma.