The Association of Vacuum-Assisted Closure Therapy with Dynamic Volume Change of a Muscle Flap Transposed in an Empyema Cavity for Chronic Empyema: A Case Report.

A 62-year-old woman with a history of lung resection for lung cancer was admitted to our hospital due to cough, which became progressively more severe. She was diagnosed with chronic empyema with bronchopleural fistula (BPF) of the right upper bronchial stump. Although a pedicled muscle flap was transposed to the empyema cavity, the fistula remained. We used a vacuum-assisted closure system after open-window thoracotomy and observed the cavity reduction with expansion of the transposed muscle flap. We quantitatively evaluated the dynamics of the cavity change using a three-dimensional image analysis system. A reduction of the volume of the muscle flap by prolonged empyema and expansion of the muscle flap was observed immediately after vacuum-assisted management. However, expansion of the right residual lung was not recognized. Pedicled muscle flap transposition followed by vacuum-assisted management after open-window thoracotomy may be effective for treating chronic empyema caused by BPF.

Adenocarcinoma with fetal features invading the right superior sulcus treated with neoadjuvant chemoradiotherapy followed by complete video-assisted thoracoscopic right upper lobectomy: a case report.

BACKGROUND: Fetal adenocarcinoma of the lung is a rare lung neoplasm that accounts for only 0.5% of all primary lung cancers. Because of its rarity, effective treatments for the management of the tumor are poorly understood. We herein report a case of adenocarcinoma with fetal features of the lung with invasion of the right superior sulcus that was treated with neoadjuvant chemoradiotherapy followed by surgical resection. CASE PRESENTATION: A 54-year-old man was referred to a medical institution due to right inner forearm pain. On computed tomography of the chest, a 56-mm mass with invasion of right superior sulcus was discovered. Bronchoscopic biopsy revealed non-small cell lung carcinoma. We performed concurrent chemotherapy (2 cycles of cisplatin and vinorelbine) and thoracic radiation therapy (40 Gy in 20 fractions). As the result of extreme tumor reduction after neoadjuvant chemoradiotherapy, we could perform right upper lobectomy by complete video-assisted thoracoscopic surgery. Since no viable cancer cells were detected from the pathological examination of the resected tissue, the specimen obtained by bronchoscopic biopsy was reexamined by immunohistochemistry. The analysis supported a pathologic diagnosis of adenocarcinoma with fetal features. CONCLUSIONS: We experienced a case of adenocarcinoma with fetal features of the lung in which the patient showed a complete response to neoadjuvant chemoradiotherapy. In addition, the tumor invading the right superior sulcus was completely resected by video-assisted thoracoscopic lobectomy. Neoadjuvant chemoradiotherapy followed by surgery may be also an effective treatment for advanced-stage high-grade fetal adenocarcinoma of the lung, similarly to other subtypes of advanced-stage primary lung cancer.

Programmed Death-ligand 1 Expression With Clone 22C3 in Non-small Cell Lung Cancer: A Single Institution Experience.

BACKGROUND: In recent years, the anti-programmed cell death 1 (PD-1) drug pembrolizumab (Keytruda) was approved for treatment of unresectable advanced non-small cell lung cancer (NSCLC) as first- or second-line therapy depending on the clone 22C3-programmed death-ligand 1 (PD-L1) immunohistochemical expression score by the companion diagnostic assay. We herein evaluated 22C3-PD-L1 expression of NSCLC in a single institution experience and compared it with clinicopathologic features. MATERIALS AND METHODS: We assessed 22C3-PD-L1 expressions of 411 patients with NSCLC from our institution, including in past specimens. Programmed death-ligand 1 immunohistochemistry (IHC) testing was performed using the PD-L1 clone 22C3 pharmDx kit (Agilent Technologies/Dako, Carpinteria, CA, USA). Patients were separated into 3 groups with <1% (no expression), 1% to 49% (low expression), or ⩾50% (high expression) positive tumor cells. RESULTS: In all, 137 patients (33%) did not express PD-L1, 155 (38%) showed low expression, and 119 (29%) demonstrated high expression. Archival samples showed lower PD-L1 expression than that of recent samples, and the ratios of no expression case significantly increased by using paraffin blocks embedded particularly in more than 4 years ago. Programmed death-ligand 1 positivity was significantly associated with male sex, smoking, higher tumor grade, squamous cell carcinoma in histologic type, wild-type EGFR, and ALK rearrangement positive. CONCLUSIONS: The rate of 22C3-PD-L1 expression of NSCLC detected in this study was similar to the frequencies of the previous reports, although the ratio of expression case decreased when using old paraffin blocks.

Assessment of ALK gene rearrangement in lung cancer using a new rapid automated SureFISH (Dako Omnis) assay.

The ALK fluorescence in situ hybridisation (FISH) method is the examination essential for pathological diagnosis and choice of molecular-targeted therapy in ALK-rearranged lung cancer. Here, for detection of ALK gene rearrangement in patients with lung cancer, we evaluated the rapid FISH technology (ALK SureFISH), a newly developed assay for the automated staining platform Dako Omnis, using 21 formalin-fixed paraffin-embedded (FFPE) samples. All cases could be evaluated with the SureFISH method. SureFISH provided excellent quality signals without any background staining. The SureFISH assay was able to offer a rapid turnaround time (approximately 3.5 hours) and was 100% concordant with prior Vysis FISH results in our laboratory.

A Phase II Study of Partial and Subtotal Thymectomy for Thymoma (JART02).

BACKGROUND: We believe the merit of preservation of a part of the thymus following surgery for thymoma. We evaluated the efficacy of partial or subtotal thymectomy for early-stage thymoma in the prospective study. METHODS: The Japanese Association for Research on the Thymus conducted a multiple institutional study of thymectomy for thymoma localized in the thymus without total thymectomy. Patients without autoimmune disease who had an anterior mediastinal tumor that had been clinically diagnosed as an early-stage thymoma were enrolled in the study. Patients who were positive for anti-acetylcholine receptor antibodies were excluded. RESULTS: Sixty-three patients were enrolled preoperatively; 27 patients were judged as being inappropriate based on the other thymic pathologies or tumor invasion. The remaining 36 cases were diagnosed as early-staged thymoma and analyzed. The mean age of the patients was 61 years. The mean maximal tumor diameter in the resected specimens was 3.6 cm. The most common pathological types of thymoma were AB (n = 10) and B1 (n = 10). The Masaoka stages were classified as stage I (n = 22) and II (n = 14). The mean observation period was 63 months. Two patients died due to respiratory dysfunction, which was not related to thymoma. One hundred percent of the patients remained recurrence-free. CONCLUSIONS: This prospective study suggested the efficacy of partial or subtotal thymectomy for early-stage thymoma in patients without any apparent evidence of autoimmune disease. We can preserve a part of the thymus even following surgery for thymoma to prepare the possible second malignancies or diseases in future.

A Case of Solitary Well-Differentiated Papillary Mesothelioma with Invasive Foci in the Pleura.

Well-differentiated papillary mesothelioma (WDPM) is a rare, distinct tumor consisting of mesothelial cells with a papillary architecture, bland cytological features, and a tendency toward superficial spread without invasion. Rare cases with superficial invasion are termed WDPM with invasive foci. We report a case of solitary WDPM with invasive foci in the pleura. A 61-year-old woman presented with a lung adenocarcinoma. A small papillary lesion measuring 29 × 10 × 8 mm was incidentally found in the parietal pleura during a lobectomy for the lung adenocarcinoma. The fibrovascular core of the small papillary lesion was surrounded by a single layer of cuboidal cells with mild to moderate atypia and large nucleoli. Atypical mesothelial cells focally invaded the submesothelial layer. The cells of the papillary lesion were positive for cytokeratins and mesothelial markers. The Ki67 index was <1 %. The lesion did not show p16 loss on fluorescence in situ hybridization. We could not detect atypical mesothelial cells in the specimen from an extrapleural pneumonectomy. WDPM with invasive foci is prone to multifocality; however, our case represents a solitary case in the pleura.

Primary Marginal Zone Lymphoma in the Posterior Mediastinum with Pleural Involvement.

We herein report a case of primary marginal zone lymphoma (MZL) of the posterior mediastinum in an 84-year-old woman. Computed tomography of the chest showed a posterior mediastinal mass in the right thoracic paravertebral region with right pleural effusion. Pathological findings of a surgical biopsy from the posterior mediastinum, along with immunohistochemical and flow cytometric results, indicated MZL. The patient was treated with chemotherapy and radiation therapy for the mediastinal lesion and achieved complete remission. A relapse occurred 3 months after the initial treatment regimen. However, a second relapse has not occurred more than 2 years after second-line chemotherapy. This is the first case of MZL originating in the posterior mediastinum.

A case of long-term survival after multimodal local treatments of intramedullary spinal cord metastasis of squamous cell lung cancer.

Intramedullary spinal cord metastasis of non-small cell lung cancer is rare, and it has a short prognosis. We report a 53-year-old man diagnosed with cT4N0M0, stage IIIA squamous cell lung cancer. Ten months after left pneumonectomy (pT4N0M0), an intramedullary spinal cord tumor developed at the axis level. The intramedullary spinal cord tumor was resected, and he was diagnosed with metastatic squamous cell lung cancer. Radiotherapies and another tumor resection were conducted, as he had a good performance status and the discrete lesion was associated with the risk of brain stem compression. Multimodal local treatments for intramedullary spinal cord metastasis caused the tumor to shrink, and he lived for 25 months after the spinal metastasis occurred.

The Outcomes of a Limited Resection for Non-Small Cell Lung Cancer Based on Differences in Pathology.

OBJECTIVE: A precise preoperative diagnosis of in situ or minimally invasive carcinoma may identify patients who can be treated by limited resection. Although some clinical trials of limited resection for lung cancer have started, it will take a long time before the results will be published. We have already reported a large-scale study of limited resection. We herein report the data for a subclass analysis according to differences in pathology. METHODS: Data from multiple institutions were collected on 1710 patients who had undergone limited resection (segmentectomy or wedge resection) for cT1N0M0 non-small cell carcinoma. The disease-free survival (DFS) and recurrence-free proportion (RFP) were analyzed. Small cell carcinomas and carcinoid tumors were excluded from this analysis. Adenocarcinomas were sub-classified into four groups using two factors, the ratio of consolidation to the tumor diameter (C/T) and the tumor diameter alone. RESULTS: The median patient age was 64 (20-75) years old. The mean maximal diameter of the tumors was 1.5 ± 0.5 cm. The DFS and RFP at 5 years based on the pathology were 92.2 and 94.7 % in adenocarcinoma (n = 1575), 76.3 and 82.4 % in squamous cell carcinoma (SqCC) (n = 100), and 73.6 and 75.9 % in patients with other tumors (n = 35). The prognosis of adenocarcinoma in both groups A (C/T ≤0.25 and tumor diameter ≤2.0 cm) and B (C/T ≤0.25 and tumor diameter >2.0 cm) was good. In SqCC, only segmentectomy was a favorable prognostic factor. In the groups with other pathologies, large cell carcinomas were worse in prognosis (the both DFS and RFP: 46.3 %). CONCLUSION: Knowing the pathological diagnosis is important to determine the indications for limited resection. Measurement of the tumor diameter and C/T was useful to determine the indications for limited resection for adenocarcinoma. Limited resection for adenocarcinomas is similar with a larger resection, while the technique should be performed with caution in squamous cell carcinoma and other pathologies.

Early and late recurrence after intentional limited resection for cT1aN0M0, non-small cell lung cancer: from a multi-institutional, retrospective analysis in Japan.

OBJECTIVES: In 2015, we reported the outcomes of patients undergoing intentional limited resection (ILR) for non-small-cell lung cancer (NSCLC) from a retrospective, multi-institutional large database in Japan. Here, we analyse the clinicopathological characteristics of the patients extracted from this database with late recurrence and compare them with those with early recurrence. METHODS: Of 1538 patients in the database with cT1aN0M0 NSCLC, 92 (6%) had recurrence. In this study, early recurrence was defined as recurrence within 5 years and late recurrence as recurrence beyond 5 years after surgery. We compared the clinicopathological characteristics and post-recurrence survival (PRS) between patients with early and late recurrence. RESULTS: Of the 92 patients with recurrence, 21 (23%) had late recurrence. Compared with the early recurrence group, there were significantly more adenocarcinomas and local recurrences in the late recurrence group (P = 0.04 for both). The 3- and 5-year PRS rates were 53 and 24%, respectively, and the median PRS period was 38 months. There were no significant differences in the PRS curves between patients with early and late recurrence (P = 0.12). Only 3 patients (0.2%) had recurrence more than 10 years after ILR. Of the 21 late-recurrence patients, 17 (81%) had tumours with a consolidation/tumour ratio (CTR) >0.25. CONCLUSIONS: Late recurrence occurred in 21 (23%) of 92 patients with recurrence after ILR for cT1aN0M0 NSCLC. Late recurrence was more likely to involve adenocarcinoma and local recurrence. It is thus considered reasonable to follow patients with a CTR >0.25 for 10 years after ILR.

Molecular analysis of human papillomavirus in never-smokers with non-small cell lung cancer.

The causes of lung cancer in never-smokers remain unclear. The potential contribution of human papillomavirus (HPV) to the carcinogenesis of non-small cell lung cancer (NSCLC) has been reported. In 2008, a prospective registry of never-smokers with NSCLC was established at the Kinki-Chuo Chest Medical Center, Sakai, Osaka, Japan. Never-smokers with NSCLC were consecutively enrolled onto the registry. Of these patients, 114 with large tumor specimens, the majority of which were surgical tissues, were selected. In total, 23 of the most clinically relevant HPV types were assayed using polymerase chain reaction amplification of the viral genome. Following exclusion of samples with suboptimal quality, DNA was extracted from 96 formalin-fixed paraffin-embedded samples. These 96 cases consisted of 82 females (85.4%) and 14 males (14.6%), with a median age of 67 years (range, 29-83). Almost all cases (93.8%) were of the adenocarcinoma histological subtype. Despite confirmation of the quality and amount of DNA, HPV type 6 was detected in only one case (1.1%). Furthermore, no other samples examined were positive for any other HPV types. The results therefore suggest that HPV does not play a major role as the driving oncogenic event in never-smokers with NSCLC.

Small calcifying fibrous pseudotumor of the heart confined to the epicardium.

A calcifying fibrous pseudotumor (CFPT) is a rare benign lesion that often presents in the upper and lower extremities of children and young adults. In the present report, we describe a case of a small CFPT arising from the epicardium (visceral pericardium) in a 32-year-old woman. The tumor presented as a 25-mm polypoid mass protruding into the pericardial cavity, without extending into the myocardium. A complete resection was performed, and the patient has not experienced any relapse for more than 2 years. On histological examination, the lesion contained densely hyalinized collagen with psammomatous and dystrophic calcifications, as well as patchy chronic inflammatory infiltrate. The localization in the epicardium with no involvement of the myocardium was confirmed by the elastic stain. Amyloid was negative by the Congo red stain. On immunohistochemical analysis, the lesional cells indicated diffuse positive staining for vimentin and factor XIIIa and focal positive staining for CD34, but did not indicate positive staining for other pertinent antigens such as cytokeratins, calretinin, desmin, α-smooth muscle actin, ALK, and estrogen and progesterone receptors as well as IgG4 in plasma cells. To our knowledge, only three cases of CFPT in the heart have been reported in the literature, all of which developed in young females as a large mass involving the epicardium; the lesion also extended to the parietal pericardium in two cases. Moreover, all cases presented with few symptoms, despite the large lesion. In the present case, the CFPT developed also in a young woman, but the lesion was much smaller than those previously published and was localized in the visceral serous membrane of the heart. The findings of this case suggest a potential preferable site of origin of CFPTs of the heart.

Survival of 1737 lobectomy-tolerable patients who underwent limited resection for cStage IA non-small-cell lung cancer.

OBJECTIVES: A precise preoperative diagnosis of 'very early' lung carcinoma may identify patients who can undergo curative surgery with limited resections. METHODS: Data from a multi-institutional project were collected on 1737 patients who had undergone limited resections (segmentectomy or wedge resection) for T1N0M0 non-small-cell carcinomas. As it was expected, this study was predominantly including ground glass nodules. Computed tomography was used to obtain the ratio of consolidation to the maximal tumour diameter to determine invasive potential of the tumours. Overall and disease-free survivals and recurrence-free proportions were analysed. RESULTS: Median age was 64 years. Mean maximal diameter of the tumours was 1.4±0.5 cm. Overall and recurrence-free survivals after limited lung resection were 94.0 and 91.1% at 5 years, respectively. Recurrence-free proportions were 93.7% at 5 years. Unfavourable prognostic factors in overall survival were lymph node metastasis, interstitial pneumonia, male gender, older age, comorbidities (cardiac disease, diabetes etc.) and consolidation/tumour ratio (C/T)≤0.25. C/T≤0.25 predicted good outcomes especially in cT1aN0M0 disease. In a subclass analysis of cT1N0M0 squamous cell carcinomas, wedge resection was the only unfavourable prognostic factor in both overall and disease-free survivals. CONCLUSIONS: If the patient was 75 years old or younger and was judged fit for lobectomy, limited resection for cStage I non-small-cell lung cancer (NSCLC) showed excellent outcomes and was not inferior to the reported results of lobectomy for small-sized NSCLC. The carcinomas with C/T≤0.25 rarely recur and are especially good candidates for limited resection.

[Treatment strategy for thymoma and thymic carcinoma].

Thymoma and thymic carcinoma are neoplasms originating from the epithelial cells of the thymus. Although these tumors should be treated according to the pathological diagnosis and the stage, they have distinct characteristics in the clinical behaviors, and therefore, should be treated separately. The standard treatment strategy has not been established because of the rarity of these tumors, but the recent accumulation of experiences provided some insights into therapeutic method for these tumors. In thymoma, Masaoka staging and completeness of surgical resection are important factors to determine the therapeutic method. Stage I and II thymomas are often good candidates for less invasive approach by endoscopic surgery. Highly invasive stage III thymoma, especially with involvement of the great vessel, is supposed to be treated with preoperative chemotherapy. Postoperative adjuvant therapy after complete resection has not been shown to have significant effect. Stage IVA thymoma patients with pleural dissemination sometimes achieve long-term survival after resection, and even subtotal resection has some value. In thymic carcinomas, patients often appear with advanced stage, and multimodality treatment is more frequently recommended than thymomas. Histological grade of aggressiveness is also an important factor for prognosis. Further study is still required for establishment of the universal approach to these tumors including TNM classification.

Lymphatic and venous malformation or "lymphangiohemangioma" of the anterior mediastinum: case report and literature review.

Lymphatic and venous malformations (LVM) are tumor-like lesions combining dysplastic lymphatic and venous vessel structures. They are rarely found in the mediastinum. We present a case of mediastinal LVM, with review of the literature. An asymptomatic 60-yearold man presented for evaluation of an anterior mediastinal mass. On chest computed tomography (CT), the mass demonstrated contrast enhancement and its 7-mm vein draining directly into the left brachiocephalic vein. The tumor was resected completely using video-assisted thoracoscopic surgery. The surgical specimen revealed combined features of venous and lymphatic dysplasia, and was diagnosed it as LVM, so-called mediastinal lymphangiohemangioma. Management plans based on precise imaging studies using magnetic resonance imaging and multi-detector-row CT phlebography could be helpful in guiding both preoperative diagnosis and subsequent treatment decisions for mediastinal LVM.

Radiation-induced osteosarcoma 17 years after mediastinal irradiation following surgical removal of thymoma.

Radiation-induced osteosarcoma is a rare complication after irradiation of primary malignancies. In the chest wall, it is usually secondary to radiotherapy for breast cancer or lymphoma. We report a rare case of radiation-induced osteosarcoma of the sternum after mediastinal irradiation of a thymoma. A 49-year-old woman presented with a sternal tumor 17 years after surgery plus mediastinal irradiation (50 Gy) for a stage III thymoma. On biopsy, this second tumor was diagnosed as a radiation-induced osteosarcoma. Systemic survey revealed additional metastatic spread to vertebrae and pelvis. Despite intensive combination chemotherapy that initially stabilized her disease, the patient died 2 years after the diagnosis was made. Because thymoma patients receiving mediastinal irradiation are thus at additional risk of radiation-induced secondary malignancy, long-term follow-up is advisable.

Efficacy of intra-operative unilateral diaphragm plication for patients undergoing unilateral phrenicotomy during extended surgery.

OBJECTIVE: Diaphragm plication is used to improve lung function and respiratory insufficiency in patients suffering from diaphragm paralysis. We assessed the efficacy of intra-operative unilateral diaphragm plication for prevention of postoperative pulmonary complications in patients, who underwent a phrenicotomy due to extended surgical intervention. METHODS: Intra-operative unilateral diaphragm plication was performed in 13 patients, who underwent a unilateral phrenicotomy during an extended thoracic operation. Six patients had lung cancer, six had a mediastinal tumour and one had a mesothelioma. We retrospectively observed the postoperative clinical courses in the perioperative period and lung function results at 1 year after operation. The postoperative lung function was compared with the predicted postoperative lung function. In addition, we observed clinical symptoms and radiological findings of the follow-up period. RESULTS: Ten (77%) of the cases revealed no postoperative complications, while three (23%) had pulmonary complications and two (15%) required prolonged mechanical ventilation. Diaphragm paralysis was not shown clinically and radiologically during the follow-up period. Postoperative lung function was similar to predicted postoperative lung function. CONCLUSION: Unilateral diaphragm plication in a patient undergoing a unilateral phrenicotomy during an extended thoracic operation is effective to prevent postoperative pulmonary complications and to preserve postoperative lung function.

Local IL-17 production and a decrease in peripheral blood regulatory T cells in an animal model of bronchiolitis obliterans.

BACKGROUND: Recently, it has been reported that Th17 contributes to allograft rejection after transplantation. We investigated the alteration of Th17 and regulatory T cells (Treg) distribution in an animal model of bronchiolitis obliterans following ectopic tracheal transplantation model. METHODS: Tracheal grafts from B6 mice transplanted into subcutaneous sites of C3H mice. Allografts were histologically evaluated, and expressions of CD4, CD8, CD25, CD28, CD127, CD152 and Foxp3, and intracellular interleukin (IL)-4, -6, -17, and interferon-gamma, in peripheral blood lymphocytes were analyzed. Tracheal graft IL-6 and -17 mRNA expression was assessed using a quantitative reverse-transcriptase polymerase chain reaction. All the data in allogenic transplantation was compared with those in isograft controls. In addition, the effect of IL-6 neutralization on the allograft was evaluated with histopathology and the IL-17 mRNA expression. RESULTS: Treg was significantly lower in peripheral blood of allogenic mice, whereas no significant difference in Th17 in the CD4 T-cell population was observed after allogenic or isogenic transplantation. Locoregional histologic examination revealed the presence of IL-6-producing lymphocytes and endothelium in the allograft, and the luminal obliteration by fibroblast proliferation. Both IL-6 and IL-17 mRNA levels were elevated in the allograft. Severity of tracheal obliteration and IL-17 mRNA level was significantly suppressed in the IL-6 neutralized allografts. CONCLUSIONS: After allograft in a mouse bronchiolitis obliterans model, IL-17 production increases locally without an alteration in peripheral blood Th17 cells, whereas peripheral Tregs decreases. Th17 cells, which can be regulated by IL-6 stimulation, may play a role in posttransplantation rejection of the allograft.