[Synchronous Multiple Thymoma Suggested to be Multi-centric Origin:Report of a Case].

A 57 years-old man was referred to our hospital because of an abnormal shadow in the left hilum on a screening chest X-ray. His physical exam and laboratory data were not notable. Chest computed tomography (CT) showed two nodules one of which is cystic in the anterior mediastinum, and positron emission tomography with 18F-fluoro-2-deoxy-D-glucose showed relatively mild uptake in both tumors. We suspected mucosa associated lymphoid tissue (MALT) lymphoma or multiple thymomas, and performed thoracoscopic thymo-thymectomy. The operative findings showed two separated tumors in the thymus. Histopathological examination revealed that both tumors were type B1 thymomas of 35 mm and 40 mm in size. Since both tumors were encapsulated without continuity, multi-centric origin was suggested.

[Pulmonary Resection for Malignant Tumor after Stereotactic Radiation Therapy].

We describe our experience with 14 patients who underwent surgery for a recurrent malignant lung tumor following stereotactic radiation therapy (SRT). The reasons for selecting SRT were patients'decision in 7 patients, advanced age in 3, reduced lung function in 3, and comorbidity in 1. Eight patients had primary lung cancer and 6 had metastatic lung cancer. Tumor recurrence was diagnosed by chest computed tomography in all patients except for one. The median period from SRT to surgery was 12.2 months. All 14 patients were deemed fit for surgery;5 patients underwent lobectomy, and 9 underwent limited resection. In 13 patients, complete resection was possible. In all 14 patients, lung resection was performed safely, and postoperative course was uneventful. No patients died of cancer during follow-up. Informed consent should be obtained from patients for post-recurrence treatment because tumor recurrence can occur after SRT.

[Chest wall reconstruction after resection of chest wall tumors].

Between 1994 and 2012, chest wall resection and reconstruction were performed 15 patients (16 cases) with primary chest wall tumors, metastatic tumors. and chest wall recurrence of breast carcinoma. In all the patients, reconstruction of the chest wall was performed using layers of polypropylene Marlex mesh sheets. In 9 patients, only Marlex mesh sheets were used. The post-operative course was uneventful, and neither paradoxical respiration nor respiratory failure was observed. In 2 patients, reconstructions of the sternum was performed using a Marlex mesh sandwich. A full thickness chest wall defect was reconstructed using Marlex mesh and a pedicled latissimus dorsi musculocutaneous flap. Chest wall recurrence of breast cancer and primary leiomyosarcoma of the chest wall were observed in 4 and 1 patient, respectively. In conclusion, polypropylene Marlex mesh sheets arranged in a layered form appear to be a stable prosthetic material for chest wall reconstruction.

Significance of preoperative evaluation of modified advanced lung cancer inflammation index for patients with resectable non-small cell lung cancer.

OBJECTIVES: Body composition and systemic inflammation/nutrition have been identified as important clinical factors in cancer patients. The modified advanced lung cancer inflammation index (mALI), which combines body composition and systemic inflammation/nutrition, is defined as appendicular skeletal muscle index × serum albumin/neutrophil-lymphocyte ratio. This retrospective study aimed to investigate associations between preoperative mALI and surgical outcomes in non-small cell lung cancer (NSCLC) patients. METHODS: We examined 665 patients with resectable stage I-III NSCLC who underwent pulmonary resection. Patients were divided into low-mALI (n = 168) and high-mALI (n = 497) based on the lower quartile. Kaplan-Meier curves and Cox regression analysis were used to assess the prognostic value of mALI. We then performed 1:1 propensity score matching (PSM) for high- and low-mALI to further investigate impacts on survival. RESULTS: Overall survival (OS) and recurrence-free survival (RFS) were both significantly poorer in the low-mALI group than in the high-mALI group (58.2% vs. 79.6%, P < 0.001; 48.8% vs. 66.7%, P < 0.001, respectively). Multivariate analysis revealed low-mALI as an independent predictor of OS (hazard ratio [HR], 2.116; 95% confidence interval (CI) 1.458-3.070; P < 0.001) and RFS (HR, 1.634; 95% CI 1.210-2.207; P = 0.001). After PSM, low-mALI remained as an independent predictor of OS (HR, 2.446; 95% CI 1.263-4.738; P = 0.008) and RFS (HR 1.835; 95% CI 1.074-3.137; P = 0.026). CONCLUSION: Preoperative mALI appears to offer an independent predictor of poor surgical outcomes as a simple, routinely available, and inexpensive biomarker in patients with resectable NSCLC.

Significance of preoperative evaluation of skeletal muscle index and immune-nutritional status for patients with early-stage non-small cell lung cancer.

OBJECTIVES: Sarcopenia involves several mechanisms, including age-related changes, nutritional deficiencies, and inflammation, and is associated with unfavorable clinical outcomes. However, the significance of skeletal muscle index (SMI) and immune-nutritional status for patients with early-stage non-small cell lung cancer (NSCLC) remains unclear. This retrospective study was performed to investigate associations between preoperative SMI based on computed tomography (CT) at the L1 level and immune-nutritional status, and whether these factors correlated with surgical outcomes. METHODS: We retrospectively investigated 386 patients with stage I-II NSCLC who underwent curative anatomical pulmonary resection. SMI was assessed on CT at the L1 level and patients were divided into low-SMI (n = 97) and high-SMI (n = 289) groups. We examined the significance of SMI for postoperative outcomes and evaluated correlations between SMI and clinical characteristics, including immune-nutritional status. RESULTS: Low SMI was significantly associated with body mass index and geriatric nutritional risk index. Five-year overall survival rate was significantly lower in the low-SMI group (66.0%) than in the high-SMI group (82.2%, P = 0.004). Multivariate analysis revealed SMI (hazard ratio [HR] 1.850; 95% confidence interval [CI] 1.091-3.135; P = 0.022) and prognostic nutritional index (PNI) (HR 2.031; 95% CI 1.231-3.352; P = 0.006) as independent predictors of overall survival. Low SMI correlated significantly with postoperative complications (P = 0.024). CONCLUSIONS: Low preoperative SMI based on CT at the L1 level appears associated with poor prognosis and postoperative complications among patients with early-stage NSCLC. PNI is also an independent prognostic factor for surgical outcomes.

Surgical outcomes of ipsilateral metachronous second primary lung cancer.

OBJECTIVES: The optimal surgical approach for metachronous second primary lung cancer (MSPLC), especially ipsilateral MSPLC, remains unclear. This study aimed to review postoperative complications and examine surgical outcomes based on the extent of resection after surgery for ipsilateral MSPLC. METHODS: Clinical data from 61 consecutive patients who underwent pulmonary resection for ipsilateral MSPLC according to the Martini-Melamed criteria between January 2005 and December 2017 in 3 institutes were retrospectively reviewed. RESULTS: Postoperative complications were identified in 12 patients (19.7%). Regarding the combination of initial and second surgery, intraoperative bleeding was significantly greater in patients with anatomic-anatomic resection than in others (P < 0.001). Operation time was significantly longer in patients with anatomic-anatomic resection than in others (P < 0.001). However, postoperative complications showed no significant differences based on the combination of surgeries. Five-year overall survival rates in patients with anatomic resection and wedge resection after second surgery were 75.8% and 75.8%, respectively (P = 0.738), and 5-year recurrence-free survival rates were 54.2% and 67.6%, respectively (P = 0.368). Cox multivariate analysis identified ever-smoker status (P = 0.029), poor performance status (P = 0.011) and tumour size >20 mm (P = 0.001) as independent predictors of poor overall survival, while ever-smoker status (P = 0.040) and tumour size >20 mm (P = 0.007) were considered independent predictors of poor recurrence-free survival. CONCLUSIONS: Regarding postoperative and long-term outcomes for patients with ipsilateral MSPLC, surgical intervention is safe and offers good long-term survival. Wedge resection is an acceptable provided tumours ≤2 cm and ground-glass opacity-predominant as a second surgery for early-stage ipsilateral MSPLC.

[Surgical treatment for metachronous lung cancer].

We performed a retrospective review of 45 consecutive patients with metachronous multiple primary lung cancer who underwent resection between 1990 and 2009. Surgical treatment of the 1st tumor consisted of 39 lobectomies and 3 segmentectomies, and 3 wedge resections. The 2nd tumor was removed by means of a lobectomy in 9 patients, a segmentectomy in 17 patients, a wedge resection in 19 patients. No postoperative mortality was observed. Histologic classification was similar in 86.4% of patients and different in 13.6%. Postoperative stage of the 2nd tumor was IA in 31 patients, IB in 7, IIA in 1, IIIA in 3, IIIB in 3. Median follow-up was 48.4 months after 2nd operation. The 5-year survival rate was 90.8% after 1st operation and 85.6% after 2nd operation. The 5-year survival rate in patients with p-stage IA was 96.4%. Patients with metachronous lung cancer could have a favorable outcome. Thus we need careful follow-up of the patients after treatment on the 1st lung cancer, and moreover an aggressive surgical treatment is recommended as long as their performance state or residual pulmonary function allows.

Expression of 5-fluorouracil-related enzymes in lung cancer: ELISA characterizes enzyme activity and messenger RNA expression.

The enzymes thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT) are involved in the metabolism of the anticancer drug 5-fluorouracil (FU). Expression of TS, DPD and OPRT in cancer tissue has been reported to be associated with sensitivity and/or resistance to 5-FU therapy. However, the role of TS, DPD and OPRT expression in lung cancer has not been fully established. Furthermore, among several measuring methods, it is not clear which method effectively predicts the response to 5-FU therapy. The aim of this study was to analyze the expression of 5-FU-related enzymes using enzyme-linked immunosorbent assay (ELISA) and to examine the correlation of ELISA and the results obtained using different measuring methods such as reverse transcript polymerase chain reaction (RT-PCR), immunohistochemistry, and enzymatic activity. Lung cancer specimens were obtained from 134 patients who underwent curative resection for lung cancer. As a pilot study, enzyme expression of 11 samples was measured using 4 different methods for DPD: RT-PCR, immunohistochemistry, enzymatic activity and ELISA. The relationships between pairs of results were compared, and then enzyme protein expression was measured using ELISA in 119 patients with adenocarcinoma. Of the 4 independent methods, the highest correlation was observed between protein expression measured by ELISA and enzyme activity. The correlation of gene expression and ELISA was also significant. The protein level in stage I adenocarcinoma measured using ELISA was 13.0+/-24.8 ng/mg protein for TS, 362.2+/-264.3 ng/mg protein for DPD and 4.5+/-2.0 ng/mg protein for OPRT. The predictive value of the enzymes for prognosis and the effectiveness of 5-FU was not determined as few recurrences were observed during the short follow-up period. In conclusion, ELISA is a simple and reliable method to measure key enzymes related to 5-FU therapy.

Superior vena cava reconstruction via a posterolateral thoracotomy without venous occlusion for locally advanced lung cancer: report of a case.

We performed a right upper lobectomy with prosthetic replacement of the superior vena cava (SVC) through a posterolateral thoracotomy in a 65-year-old man undergoing complete resection of a locally advanced non-small-cell lung cancer with invasion of the SVC. Instead of using a vascular shunt, the right atrium and a right brachiocephalic vein (BCV) were anastomosed using a ringed polytetrafluoroethylene (PTFE) graft. During the anastomosis, vascular flow was maintained through the left BCV. By using this technique, SVC resection and reconstruction during lung cancer surgery can be safely performed through a posterolateral thoracotomy without blood flow interruption.

Absence of gene mutations in KIT-positive thymic epithelial tumors.

BACKGROUND: Overexpression of KIT, a tyrosine kinase receptor protein encoded by the proto-oncogene c-kit, is observed in human neoplasms such as gastrointestinal stromal tumors (GISTs), myeloproliferative disorders, melanoma and seminoma. In patients with GIST, overexpression of mutated KIT within the tumor is predictive of response to molecular targeted therapy using imatinib. However, the role of KIT expression in thymic carcinoma is not fully understood. METHODS: Thymic epithelial tumors from 37 patients (17 thymic carcinomas and 20 thymomas) were examined. Immunohistochemical staining with anti-KIT polyclonal antibody and anti-CD5 was performed. Mutation analyses in the juxtamembrane domains, exons 9 and 11, and in the tyrosine kinase domains, exons 13 and 17, were undertaken using polymerase chain reaction (PCR) and direct DNA sequencing in KIT-positive samples. RESULTS: KIT- and CD5-positive staining was observed only in thymic carcinoma. Percentage of positive staining was 100% in squamous cell carcinoma, with no positive staining in other histologies, including atypical carcinoid. Mutation analysis of the KIT gene was performed in 11 squamous cell carcinomas, 1 adenocarcinoma and 1 adenosquamous cell carcinoma. None of the tested samples showed mutations in any of the four exons. CONCLUSIONS: Squamous cell carcinoma of the thymus frequently expressed KIT and CD5 proteins, whereas other tumors did not. Unlike GIST, overexpression of KIT does not necessarily indicate gene mutation in thymic carcinoma. KIT and CD5 appear useful for evaluating and subtyping thymic epithelial tumors.

Primary mediastinal lymph node malignancy with features suggestive of dendritic cell sarcoma.

A 56-year-old man underwent preoperative chest computed tomography to further evaluate a well defined mass in the middle lobe with subcarinal lymph node swelling. There was no pathological diagnosis established by either bronchoscopic biopsy specimens or computed tomography-guided percutaneous needle biopsy. The middle lobe and mediastinal lymph nodes were excised, then postoperative radiotherapy (60 Gy) was administered to the mediastinum. Results of histological and immunohistochemical study showed that the lung mass consisted of completely necrotic tissue and that the subcarinal lymph node was involved by malignant cells suggestive of dendritic cell sarcoma. Primary dendritic cell sarcoma of the mediastinal lymph node is extremely rare. Dendritic cell sarcoma is a neoplasm of reticular dendritic origin and includes both follicular dendritic cell sarcoma and interdigitating reticulum (or dendritic) cell sarcoma. These rare neoplasms may pose difficulty in pathologic diagnosis and treatment. Although our patient died of hepatic rupture due to dendritic cell sarcoma or gastric cancer metastases one year after surgery, complete surgical resection with or without postoperative radiotherapy may be an acceptable therapeutic option for localized dendritic cell sarcoma.

Long-term results and predictors of survival after surgical resection of patients with lung cancer and interstitial lung diseases.

OBJECTIVES: Patients with interstitial lung diseases have a poor prognosis and are at increased risk of developing lung cancer. We evaluated the survival and predictors of survival after surgical resection in lung cancers in patients with interstitial lung diseases. METHODS: We retrospectively analyzed data from 1763 patients with non-small cell lung cancer with a clinical diagnosis of interstitial lung disease who underwent pulmonary resection between 2000 and 2009 at 61 Japanese institutions. RESULTS: Male patients (90.4%) and smokers (93.8%) were in the majority. The overall 5-year survival was 40%. The 5-year survivals were 59%, 42%, 43%, 29%, 25%, 17%, and 16% for patients with stage Ia, Ib, IIa, IIb, IIIa, IIIb, and IV, respectively. Patients with stage IA had a 5-year survival of 33.2%, 61.0%, and 68.4% in the wedge resection, segmentectomy, and lobectomy groups, respectively (log-rank test, P = .0038). The leading cause of death was cancer recurrence (50.2%), followed by respiratory failure (26.8%). Wedge resection reduced mortality due to respiratory failure when compared with that of lobectomy (P = .022). Multivariable analysis revealed that the type of surgical procedure, predicted percent vital capacity, and tumor locations were independent predictors for survival. The 5-year survival was 20% for patients with stage Ia with a predicted percent vital capacity of 80% or less, and 64.3% for patients with a predicted percent vital capacity greater than 80% (log-rank test, P < .0001). CONCLUSIONS: In these patients, there are competing risks of death. Wedge resection reduced death caused by respiratory failure but resulted in poorer long-term prognosis than lobectomy. For patients with poor predictors of survival, such as predicted percent vital capacity of 80% or less, surgical resection should be limited.

Primary thymic adenocarcinoma coexisting with type AB thymoma: a rare case with long-term survival.

Thymic carcinoma is a rare tumor. The most common histological subtype is squamous cell carcinoma, and only a few cases of thymic adenocarcinoma have been reported. A case of papillary adenocarcinoma of thymic origin that coexisted with type AB thymoma as a separate nodule is presented herein. The patient was found to have an abnormal mediastinal shadow on chest X-ray. A computed tomography scan revealed a round, 6.5-cm-diameter mass in the right anterior mediastinum. The preoperative diagnosis was thymoma, and thymothymectomy was performed. On pathological examination, two tumors, which were diagnosed as papillary adenocarcinoma and type AB thymoma, respectively, were present in the thymus without any connection with each other. The patient has been alive without any signs of recurrence for 11 years after surgery. We diagnosed the adenocarcinoma in this case was a primary thymic carcinoma.

Large bronchial granular cell tumor.

We report a 20-year-old woman who underwent complete resection of a granular cell tumor (GCT). On chest computed tomography (CT) scan, a mass with a maximum diameter of 36 mm at the lower bronchus with atelectasis of the right lower lobe was noted. Bronchoscopic examination revealed a whitish mass in the truncus intermedius, and the middle and lower bronchus were unable to be seen. A cytopathological examination of the mass revealed GCT. A right middle and lower lobectomy was performed via a posterolateral thoracotomy. Microscopically, the tumor was composed of polygonal cells with oxyphilic granular cytoplasm and small ovoid nuclei. The cytoplasm of the neoplastic cells was positive for S-100 protein and neuron-specific enolase. The patient's postoperative course was uneventful, and she was asymptomatic after 4 months. A large bronchial GCT is rare, which is why we report this case.

Results of surgical treatment for small (2 cm or under) adenocarcinomas of the lung.

PURPOSE: The objectives of this study were to identify the clinicopathologic characteristics and prognostic factors of small (2 cm or less in diameter) adenocarcinomas, and furthermore to assess the acceptability of performing a limited pulmonary resection in such patients. METHODS: We retrospectively reviewed 523 cases of cT1N0M0 peripheral adenocarcinoma measuring 2 cm or less on diagnostic images treated by a complete resection between 1991 and 2004. RESULTS: The overall 5-year survival rate of the patients with small adenocarcinomas was 83.6%. Univariate and multivariate analyses identified an older age, male sex, wedge resection, advanced stage, and Noguchi classification of C, D, E, or F as independent prognostic factors that adversely affected overall survival. However, there were no significant differences in the survival according to surgical procedure in the patients whose tumors had a maximum diameter of 1.0 cm or less or in Noguchi type A and B cases. CONCLUSIONS: Age, sex, surgical procedure, p-stage, and Noguchi classification were independent prognostic factors for survival in patients with small adenocarcinomas. A segmentectomy is therefore considered to be an acceptable alternative to a lobectomy for adenocarcinomas of 2 cm or less in diameter. A wedge resection may be acceptable for tumors measuring 1 cm or less in diameter or Noguchi type A and B tumors.

Segmentectomy for multiple adenocarcinoma presenting as ground-glass opacities after lung cancer surgery.

During follow-up of patients after primary lung cancer resections, small nodules or ground-glass opacities (GGOs) are sometimes detected on chest computed tomography. We report a case with multiple GGOs that were noted after primary lung cancer resection. A 76-year-old woman, who had undergone right upper lobectomy, middle lobe partial resection, and mediastinal lymph node dissection 3 years earlier, was admitted owing to five GGOs in the right lower lobe that had been increasing in size or density. A right S6+10 segmentectomy was performed. On histology, one adenocarcinoma and four bronchioloalveolar carcinomas (BACs), as well as two additional BACs that had not been detected preoperatively, were identified. No complications occurred postoperatively. Three years 4 months later, no tumor recurrence or new lesions have been found. Given the high possibility of malignancy, the appearance of new GGOs in patients with a history of lung cancer requires appropriate investigation.

Ross procedure for aortic insufficiency due to doubly committed subarterial ventricular septal defect in adults.

A 52-year-old female, with aortic insufficiency due to doubly committed subarterial ventricular septal defect (VSD) underwent a successful surgical repair by the Ross procedure. Preoperatively, she developed congestive heart failure because of less compliance to oral medication, raising concerns regarding life-threatening thromboembolism if she undergoes mechanical valve replacement. Despite the pulmonary autograft being defective, there were no difficulties in completing the surgery. The defect of pulmonary autograft and the VSD was closed by an expanded polytetrafluoroethylene patch. She tolerated the procedure well and now enjoys improved quality of life. We present a discussion of the indication of Ross procedure in the rare presentation of congenital heart disease, as well as several issues raised in this case.

Ruptured aneurysm of the subclavian artery in a patient with von Recklinghausen's disease.

A vascular manifestation of von Recklinghausen's disease is rare, but may be fatal if it is disrupted. A 39-year-old male with von Recklinghausen's disease presented with a large and tender bruise extending from his left neck to his left shoulder and arm. Computerized axial tomography revealed a ruptured aneurysm of the left subclavian artery. The patient underwent emergency surgery to exclude the aneurysm, and cross-over bypass grafting of both subclavian arteries was performed. We present a brief review of vascular maintestation of von Recklinghausen's disease, as well as a discussion regarding the strategy for treating this rare presentation.

Chromosome binding site of latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus is essential for persistent episome maintenance and is functionally replaced by histone H1.

Latency-associated nuclear antigen 1 (LANA1) of Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus 8) persistently maintains a plasmid containing the KSHV latent origin of replication (oriP) as a closed circular episome in dividing cells. In this study, we investigated the involvement of chromosome binding activity of LANA1 in persistent episome maintenance. Deletion of the N-terminal 22 amino acids of LANA1 (DeltaN-LANA) inhibited the interaction with mitotic chromosomes in a human cell line, and the mutant concomitantly lost activity for the long-term episome maintenance of a plasmid containing viral oriP in a human B-cell line. However, a chimera of DeltaN-LANA with histone H1, a cellular chromosome component protein, rescued the association with mitotic chromosomes as well as the long-term episome maintenance of the oriP-containing plasmid. Our results suggest that tethering of KSHV episomes to mitotic chromosomes by LANA1 is crucial in mediating the long-term maintenance of viral episomes in dividing cells.