Makio Hayama

Experimental study of oversized grafts in a canine living-donor lobar lung transplantation model

BACKGROUND For infants and small children, organ transplantation is limited by the size discrepancy between donor and recipient. To address this problem, the use of over-sized grafts from living-relative donors could potentially expand the donor pool. The aim of this experimental study was to evaluate the effect of oversized grafts on early pulmonary function and to identify an indicator for acceptable size discrepancy. METHODS Fourteen bilateral lobar lung allotransplant operations were performed without cardiopulmonary bypass in weight mismatched pairs of dogs. Animals were divided into 2 groups: Group I (n = 7), donor/recipient lung volume ratio < 2.85; Group II (n = 7), donor/recipient lung volume ratio >2.85. Pulmonary function of the recipient was measured before chest closure, after chest closure, and after the ventilator was removed. RESULTS Pulmonary vascular resistance and airway pressure significantly increased in Group II after chest closure (1493 +/- 195 dynes sec cm(-5) and 14.4 +/- 0.9 mm Hg vs 2784 +/- 140 dynes sec cm(-5) and 23.4 +/- 1.2 mm Hg, p < 0.001). After the ventilator was removed, all recipients in Group I showed PaO2 > 239 mm Hg and PaCO2 < 76 mm Hg, whereas, all recipients in Group II showed PaO2 < 116 mm Hg and PaCO2 > 169 mm Hg. The donor/recipient chest circumference ratio was less than 1.3 in all but 1 dog in Group I. CONCLUSIONS Acceptable, oversized grafts provide adequate pulmonary function, although excessively oversized grafts cause significant impairment in pulmonary function after chest closure. Chest circumference provides useful size-match criteria when oversized grafts are used in this canine experimental model.

In vivo molecular imaging characterizes pulmonary gene expression during experimental lung transplantation.

Experimental gene therapy is a promising strategy to prevent ischemia‐reperfusion (I/R) injury and allograft rejection after lung transplantation, and methods will eventually be needed to characterize pulmonary transgene expression in vivo in humans. Therefore, we studied positron emission tomography (PET) as a means of performing in vivo molecular imaging in rodent models of lung transplantation. Rats were transfected endotracheally with adenovirus encoding a fusion gene of a mutant Herpes simplex virus‐1 thymidine kinase and the green fluorescent protein gene (the former serving as an imaging reporter gene). Twenty‐four hours after transfection, lungs were transplanted in groups representing normal transplantation, I/R injury and acute allograft rejection. Imaging was obtained either 24 h after transplantation to study reperfusion injury or 4 days after transplantation to study graft rejection. After imaging, lungs were excised and analyzed for thymidine kinase activity. Imaging detected transgene expression in transplanted lungs even in the presence of acute rejection or I/R injury. The PET imaging signal correlated with in vitro lung tissue assays of thymidine kinase activity (r2= 0.534). Thus, noninvasive molecular imaging with PET is a feasible, sensitive and quantitative method for characterizing pulmonary transgene expression in experimental lung transplantation.

Clinicopathological characteristics and lymph node metastasis pathway of non-small-cell lung cancer located in the left lingular division

OBJECTIVES The purpose of this study is to assess the clinicopathological characteristics of non-small-cell lung cancer (NSCLC) occurring in the left lingular division (LLD) in association with a proposal of the LLD-specific regional lymph node stations. METHODS Medical records of patients, who underwent complete tumour resection with mediastinal lymph node dissection (MLND) for LLD-NSCLC from 2000 to 2009 in multiple institutions, were retrospectively examined. We analysed patient clinicopathological characteristics and obtained the LLD-specific regional lymph node stations, and then the validity of intraoperative navigation in lymphadenectomy for LLD-NSCLC was investigated. RESULTS One hundred and eighty-four LLD-NSCLC patients (97 males and 87 females, and 128 adenocarcinomas and 56 non-adenocarcinomas) were studied. The 5-year overall survival (OS) and disease-free survival (DFS) rates for all LLD-NSCLC patients were 72.9 and 58.3%, respectively. We examined the lymph node metastasis patterns in 42 node-positive tumours. The frequent metastatic lymph node stations were #12u lobar node (n = 22), #5 subaortic node (n = 15) and #11 interlobar node (n = 13) in order. These three node stations were also single metastatic sites in some patients. Metastases to sub-carinal (#7) or inferior mediastinal nodes (#8) were rare. Thus, we assigned the three stations (#5, #11, #12u) as the regional lymph node stations for LLD-NSCLC. If these regional lymph node stations had been examined pathologically during surgery for a total of 160 LLD-NSCLC patients with c-T2N1M0 or lower stage disease, 125 p-N0 and 5 p-N1 patients diagnosed with no metastasis would have been subjected to selective MLND, while 14 p-N1 and all 16 p-N2 patients diagnosed with metastasis would have had complete MLND carried out. As a result, these regional lymph node stations could accurately predict the existence of p-N2 metastasis, and appropriately lead to a selective or complete MLND. CONCLUSIONS An intraoperative pathological examination using our proposed LLD-specific regional lymph node stations may accurately diagnose the status of node metastasis, and appropriately lead to selective or complete MLND in LLD-NSCLC patients with c-T2N1M0 or lower stage disease.

Restrictive ventilatory impairment is associated with poor outcome in patients with cT1aN0M0 peripheral squamous cell carcinoma of the lung

Background Patients with squamous cell carcinoma (SqCC) of the lung sometimes have a comorbid pulmonary disease such as pulmonary emphysema or an interstitial lung disease (ILD), both of which negatively affect patient outcome. The aim of this study was to determine the outcome of patients in a multicenter database who underwent surgery for cT1aN0M0 peripheral SqCC lung cancer. Methods The medical records of a total of 228 eligible patients from seven institutions were reviewed to evaluate the impact of concomitant impaired pulmonary function and other clinicopathological factors on overall survival (OS) and relapse-free survival (RFS). Results Six patients with positive or unclear tumor margins were excluded. Of the 222 remaining study patients, 42 (18.9%) and 97 (43.7%) patients were found to have coexisting restrictive or obstructive ventilatory impairment, respectively. Over a median follow-up period of 30.6 months, the 5-year OS and RFS were 69.0% and 62.6%, respectively. By multivariate analysis, ILDs identified on high-resolution computed tomography (HRCT), pulmonary function test results indicating a restrictive ventilatory impairment, and wedge resection were found to be independent risk factors for poor OS. An increased level of serum squamous cell carcinoma antigen (SCC-Ag) (>1.5 ng/mL) and the same risk factors for poor OS were independent risk factors for recurrence. Among patients who underwent anatomical lung resection (lobectomy and segmentectomy, n=173), a restrictive ventilatory impairment was an independent risk factor for poor OS, and increased serum SCC-Ag level, ILDs on HRCT, and restrictive ventilatory impairment were independent risk factors for poor RFS by multivariate analysis. Factors such as visceral pleural invasion, and lymphatic or vascular invasion were not significantly associated with outcome. Conclusions A restrictive ventilatory impairment negatively affects the outcome of patients with cT1aN0M0 peripheral SqCC lung cancer.

A case of metachronous brain metastases from gastric cancer with no recurrence

症例は75歳の男性で, 急性骨髄性白血病のため当院血液内科で化学療法を受け, 完全寛解状態であった. 今回, 貧血の精査のため行った上部消化管内視鏡検査にて胃体上部に進行胃癌を指摘され, D2郭清を伴う胃全摘術を施行した. 術後1年5か月目に人格変化, 嘔吐がみられ, 頭部MRIを施行したところ, 大脳半球に3個の転移性脳腫瘍を認めた. 胸腹部CT, 腹部超音波検査では転移を認めず, 腫瘍マーカーも正常であった. 白血病再燃による病変も否定できず, 脳腫瘍生検を行った. 病理組織学的診断は中分化型腺癌で, 胃癌の病理組織学的検査所見とも一致しており, 胃癌脳転移と診断した. 脳転移に対し, サイバーナイフを行ったところ, 臨床症状の改善を認め, 通院治療が可能となった. 5か月後, 新たな2個の脳転移に対し, 再度サイバーナイフの施行を要したが, 脳転移発症後1年経過現在, 胸腹部を含め無再発生存中である.