Koichi Tomoshige

Three-Dimensional Computed Tomography for a Mediastinal Basal Pulmonary Artery

Anatomic variations of the pulmonary artery increase the risks for vessel injury and critical mistakes during pulmonary artery resection. A patient who underwent left lower lobectomy for lung cancer with a mediastinal lingular and basal pulmonary artery that had been detected preoperatively by three-dimensional computed tomography is presented. During thoracoscopic surgery, the mediastinal basal pulmonary arteries were found with careful dissection. The pulmonary arteries were divided, and left lower lobectomy was performed safely. This rare variation of the left pulmonary artery is important to detect before lobectomy to ensure safe surgery. In such cases, three-dimensional computed tomography is necessary.

Germline mutations causing familial lung cancer

Genetic factors are important in lung cancer, but as most lung cancers are sporadic, little is known about inherited genetic factors. We identified a three-generation family with suspected autosomal dominant inherited lung cancer susceptibility. Sixteen individuals in the family had lung cancer. To identify the gene(s) that cause lung cancer in this pedigree, we extracted DNA from the peripheral blood of three individuals and from the blood of one cancer-free control family member and performed whole-exome sequencing. We identified 41 alterations in 40 genes in all affected family members but not in the unaffected member. These were considered candidate mutations for familial lung cancer. Next, to identify somatic mutations and/or inherited alterations in these 40 genes among sporadic lung cancers, we performed exon target enrichment sequencing using 192 samples from sporadic lung cancer patients. We detected somatic ‘candidate’ mutations in multiple sporadic lung cancer samples; MAST1, CENPE, CACNB2 and LCT were the most promising candidate genes. In addition, the MAST1 gene was located in a putative cancer-linked locus in the pedigree. Our data suggest that several genes act as oncogenic drivers in this family, and that MAST1 is most likely to cause lung cancer.

Novel diagnostic procedure for determining metastasis to sentinel lymph nodes in breast cancer using a semi-dry dot-blot method

We developed an easy, quick and cost‐effective detection method for lymph node metastasis called the semi‐dry dot‐blot (SDB) method, which visualizes the presence of cancer cells with washing of sectioned lymph nodes by anti‐pancytokeratin antibody, modifying dot‐blot technology. We evaluated the validity and efficacy of the SDB method for the diagnosis of lymph node metastasis in a clinical setting (Trial 1). To evaluate the validity of the SDB method in clinical specimens, 180 dissected lymph nodes from 29 cases, including breast, gastric and colorectal cancer, were examined. Each lymph node was sliced at the maximum diameter and the sensitivity, specificity and accuracy of the SDB method were determined and compared with the final pathology report. Metastasis was detected in 32 lymph nodes (17.8%), and the sensitivity, specificity and accuracy of the SDB method were 100, 98.0 and 98.3%, respectively (Trial 2). To evaluate the efficacy of the SDB method in sentinel lymph node (SLN) biopsy, 174 SLNs from 100 cases of clinically node‐negative breast cancer were analyzed. Each SLN was longitudinally sliced at 2‐mm intervals and the sensitivity, specificity, accuracy and time required for the SDB method were determined and compared with the intraoperative pathology report. Metastasis was detected in 15 SLNs (8.6%), and the sensitivity, specificity, accuracy and mean required time of the SDB method were 93.3, 96.9, 96.6 and 43.3 min, respectively. The SDB method is a novel and reliable modality for the intraoperative diagnosis of SLN metastasis.

The evolution of bronchoplasty and broncho-angioplasty as treatments for lung cancer: evaluation of 30 years of data from a single institution

OBJECTIVES The purpose of this study was to evaluate the factors contributing to the outcomes of bronchoplasty for lung cancer by analysing a single institutions data for a 30-year period. METHODS A retrospective review of 213 patients who underwent bronchoplasty for lung cancer between 1980 and 2010 was undertaken. The patients were divided into two groups by the date of surgery: the first period was 1980-95, and the second period was 1996-2010. RESULTS Bronchoplasty and broncho-angioplasty were performed in 100 (75.8%) and 32 (24.2%) patients, respectively, in the first period and 61 (75.3%) and 20 (24.7%) patients, respectively, in the second period. Overall 90-day operative morbidity and mortality rates were 25.8 and 9.8%, respectively, in the first period and 45.7 and 2.5%, respectively, in the second period. Thirty-day mortality rates were 6.8% in the first period and 0% in the second period. Five-year survival was 41.1% (n = 132) in the first period and 61.5% (n = 81) in the second period (P = 0.0003). Comparing bronchoplasty and broncho-angioplasty, the 5-year survival was 45.6 and 26.5%, respectively, in the first period (P = 0.0048) and 60.9 and 62.1%, respectively, in the second period (P = 0. 8131). Using multivariate analysis to identify potential prognostic factors, the type of operation (broncho-angioplasty), postoperative complications and histology (non-squamous cell carcinoma) were significant factors affecting survival in the first period, but none of the factors significantly affected survival in the second period. When the rates of pN2 or N3 histological type disease were compared in each period, the rate of pN2 or N3 disease in non-squamous cell carcinoma was 51.4% in the first period and 45.5% in the second period; both were significantly higher than in squamous cell carcinoma (31.6 and 16.9%, respectively; P = 0. 0365 and 0.0073). CONCLUSIONS The present study suggests that progress in the preoperative staging system and perioperative medical management, as well as surgery, has contributed to current improvements in patients undergoing bronchoplasty and broncho-angioplasty. However, since nodal status in non-squamous cell carcinoma is not precisely evaluated before the operation, the indication for bronchoplasty should be considered carefully.

Intraoperative diagnosis of lymph node metastasis in non-small-cell lung cancer by a semi-dry dot-blot method

OBJECTIVES Sublobar resection procedures, such as segmentectomy and wedge resection, can be used for resectable lung cancer when the cancer is small or the condition of the patient is poor. In such cases, intraoperative lymph node (LN) exploration is necessary to avoid incomplete resection of potential N1 or N2 disease. The semi-dry dot-blotting (SDB) method was developed to detect intraoperative LN metastasis as a quick, cost-effective procedure that does not require special technical expertise. This study examined whether SDB can sufficiently identify LN metastasis in lung cancer patients. METHODS This study prospectively examined 147 LNs from 50 lung cancer patients who underwent surgery at Nagasaki University Hospital between April 2011 and June 2013. The SDB method uses antigen-antibody reactions with anti-pancytokeratin as the primary antibody and detects cancer cells using chromogen. To identify LN metastases, each LN was examined by the SDB method during surgery along with intraoperative pathological diagnosis (ope-Dx) and permanent pathological diagnosis (permanent-Dx). RESULTS Compared with permanent-Dx, SDB offered 94.7% sensitivity, 97.7% specificity and 97.2% accuracy, while ope-Dx exhibited 84.2% sensitivity, 100% specificity and 98.0% accuracy. For 3 cases, micrometastases were detected by the SDB method but not by ope-Dx. Three LNs from lobar stations showed pseudo-positive results by the SDB method because of the presence of alveolar epithelium. CONCLUSIONS The SDB method offers acceptably high accuracy in detecting LN metastasis, especially for mediastinal LNs, and represents a potential alternative for the intraoperative diagnosis of LN metastasis, even in the absence of a pathologist.

A case of primary pulmonary aspergilloma with pneumothorax

30歳男性．胸痛を主訴に近医受診．胸部単純写真にて右気胸，右上肺野結節影を認めた．当院紹介となり胸部CT施行したところ右上葉に嚢胞，および，その内部に径3cm大の球状の充実性成分を認めた．血液検査にてアスペルギルス抗原陽性，β-Dグルカンの上昇を認めた．以上より肺アスペルギローマと診断し胸腔鏡補助下右上葉切除術を施行した．病理では空洞内にアスペルギルス菌糸の増生が認められた．気胸を契機に発見された肺アスペルギローマは稀であるため若干の文献的考察を加え報告する．