Norimasa Ito

Sentinel Node Navigation Surgery Using Indocyanine Green in Patients with Lung Cancer

PurposeTo investigate the potential use of sentinel node navigation surgery (SNNS) using indocyanine green (ICG) in lung cancer.MethodsThe subjects were 38 patients with stage cN0 lung cancer. After thoracotomy, we injected 5 ml ICG and 400 U hyaluronidase around the tumor, and identified the stained lymph nodes (LNs) intraoperatively by inspection. Postoperatively, we measured ICG concentrations in the dissected LNs. Lymph nodes with an ICG concentration of more than 1.5 times the mean were defined as sentinel nodes (SNs).ResultsThere were 30 pN0, 6 pN1, and 2 pN2 cancers. The tumor size ranged from 11 to 75 (mean 31 ± 15) mm. Sentinel nodes were identified by inspection in 7 (18.4%) of the 38 patients. Lymphatic mapping with ICG concentration was successful in 38 (100%) of 38. One SN was found in 18 patients and two SNs were found in 20. The SN predicted the status of metastasis of all LNs in 37 (97%) of 38. Metastases were identified in the SN alone in 5 (62.5%) of 8. There was one false negative, caused by a metastatic LN being occupied by tumor cells.ConclusionThese findings support the efficiency of SNNS for clinically node-negative lung cancer.

Prospective Analysis of Oncogenic Driver Mutations and Environmental Factors: Japan Molecular Epidemiology for Lung Cancer Study

PURPOSE Oncogenic driver mutations are critical for lung cancer development and serve as therapeutic targets. However, their associations with environmental factors are not fully understood. We aimed to elucidate the relationship between tumor developmental biology and exposure to environmental factors. PATIENTS AND METHODS This was a prospective, multicenter, molecular epidemiology study. Eligible patients were those with newly diagnosed stages I to IIIB non-small-cell lung cancer (NSCLC) who underwent surgery. The tumors were examined for somatic mutations in 72 cancer-associated genes by targeted deep sequencing, estrogen receptor β (ERβ) expression using immunohistochemical staining, and infection with any of 37 types of human papillomavirus (HPV) using a polymerase chain reaction-based microarray system. Detailed information on patient demographics and environmental factors was obtained from a comprehensive questionnaire. RESULTS From July 2012 to December 2013, 957 patients were enrolled, and molecular analyses were performed on 876 samples (from 441 ever- and 435 never-smokers). Oncogenic driver mutations in P53 and KRAS increased proportionally with smoking status, whereas mutations in EGFR and SMAD4 decreased. KRAS mutations in smokers and SMAD4 mutations were observed more frequently in proportion to body mass index. TP53 and NFE2L2 mutations were observed more frequently in advanced NSCLC stages. As for never-smokers, no environmental factors were significantly associated with mutational changes. EGFR mutations and TP53 mutations were observed more frequently in women and in men, respectively. Mutations in these two genes were also potentially associated with ERβ expression. Only three patients (0.3%) were HPV positive. CONCLUSION The mutational spectrum is associated with smoking, body mass index, and other environmental factors, as well as with ERβ expression. Little association was observed between HPV and NSCLC.

Laparoscopic bilateral partial adrenalectomy for adrenocortical adenomas causing cushing's syndrome : Report of a case

Laparoscopic total adrenalectomy has become a standard technique for small adrenal tumors; however, bilateral adrenalectomy results in postoperative adrenal insufficiency, necessitating lifelong steroid replacement. To preserve adrenocortical function in a 41-year-old woman with bilateral adrenocortical adenoma (BAA) causing Cushings syndrome, we performed laparoscopic bilateral partial adrenalectomy. We based our preoperative diagnosis of bilateral adrenocortical tumors causing Cushings syndrome on the results of endocrinological investigations and imaging findings. Thus, we performed lateral transperitoneal laparoscopic bilateral partial adrenalectomy, preserving the adrenal glands, which were normal. Pathological examination of both tumors confirmed the diagnosis of adrenocortical adenoma. The patient had no postoperative complications, and her adrenocortical function was normal without steroid replacement at her 10-month follow-up. This report shows that Cushings syndrome resulting from bilateral adenomas can be effectively treated by laparoscopic bilateral partial adrenalectomy as a minimally invasive, adrenocortical-preserving operation.

Successful video-thoracoscopic drainage for descending necrotizing mediastinitis

Descending necrotizing mediastinitis (DNM) is a rare but severe disease with a high mortality rate. We report a case of a 77-year-old woman with DNM who was treated using video-thoracoscopic drainage and a Blake drain. She was admitted to our hospital with a 3-day history of a sore throat. Computed tomography (CT) revealed a peritonsillar abscess descending into the anterior and posterior mediastinum below the carina. She was diagnosed with DNM, and emergency surgery was performed. The mediastinal abscess was drained via video-thoracoscopy, and a 24F Blake drain was inserted into the mediastinum. Following mediastinal drainage, cervical drainage was performed for treatment of the retropharyngeal abscess. The outcome of videothoracoscopic mediastinal drainage was satisfactory, and no further invasive treatment was required. We believe that video-thoracoscopic mediastinal drainage is an effective, minimally invasive treatment for DNM with subcarinal spread. Blake drains are useful for mediastinal drainage.

Dissociation Between T Helper Type 1 and Type 2 Differentiation and Cytokine Production in Tumor-Infiltrating Lymphocytes in Patients with Lung Cancer

Abstract We recently reported the balance of T helper type 1 (Th1) cells and type 2 (Th2) cells in patients with lung carcinomas. This study was conducted to investigate their activity and role in tumors, which remain unclear. We determined the population of lymphocytes with intracellular interferon (IFN)-γ or interleukin (IL)-4 by flow cytometry, and investigated cytokine production using enzyme-linked immunosorbent assay (ELISA) in 22 patients with non-small cell lung cancer. The IFN-γ-positive subset showed a significant increase in the number of tumor-infiltrating lymphocytes (TIL) compared with the peripheral blood lymphocytes (PBL) (PBL, 13.8% ± 1.5%; TIL, 34.3% ± 3.4%; P < 0.001), and the IL-4 positive subset showed reverse results (PBL, 3.7% ± 0.6%; TIL, 2.1% ± 0.3%; P = 0.037). However, TIL did not produce more IFN-γ than PBL. The results of intracellular IFN-γ analysis and the production of IFN-γ in PBL and TIL were significantly correlated (PBL: n = 22, r = 0.50, P = 0.025; TIL: n = 22, r = 0.44, P = 0.022). The dissociation between Th1 differentiation and IFN-γ production in TIL was one of the host factors influencing the immune anergy against tumors.

Cisplatin-based chemotherapy followed by surgery for malignant nonseminomatous germ cell tumor of mediastinum: one institution’s experience

ObjectiveThe objective of this study was to evaluate the efficacy and safety of cisplatin-based chemotherapy followed by surgery for patients with a malignant nonseminomatous germ cell tumor (NSGCT) of the mediastinum.MethodsTen patients with malignant NSGCTs received cisplatin-based induction chemotherapy and then underwent surgery. The clinicopathological characteristics of these 10 patients were examined retrospectively.ResultsA partial response to induction chemotherapy was noted in eight patients and no response in two. The induction chemotherapy was tolerated well by all the patients. Each patient underwent complete surgical resection of the residual tumor following chemotherapy. A yolk sac tumor was detected in one patient and malignant teratoma along with a yolk sac tumor in one patient postoperatively. The overall survival of the 10 patients was 67% at 60 months of follow-up. The survival rate at 60 months was poorer for the patients whose resected specimens exhibited the presence of viable cells than for those whose specimens were free of viable cells.ConclusionPostchemotherapy surgical resection of the residual tumor plays an integral role in the management of patients with NSGCT. The presence of viable tumor cells in the resected specimens is associated with poor survival.

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.

Preoperative Identification of Anomalous Drainage Vein for Posterior Segment of Right Upper Lobe

A 62-year-old man had a small nodule in the right upper lobe, which was diagnosed as adenocarcinoma by transbronchial biopsy analysis. Preoperative three-dimensional (3D) angiography with contrastenhanced images obtained using multi detector-row computed tomography (CT) revealed a 3-mm diameter vein for the posterior segment of the right upper lobe running posterior to the right hilum that drained directly to the left atrium, and independent of both the superior and inferior pulmonary veins (Fig 1, arrows). A corresponding small vessel located dorsal to the right bronchus intermedius was seen in axial CT sections. We performed a thoracoscopic right upper lobectomy along with mediastinal lymph node dissection. Intraop-

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.