Takuhiro Ikeda

Difference in Prognostic Significance of Maximum Standardized Uptake Value on [18F]-Fluoro-2-Deoxyglucose Positron Emission Tomography Between Adenocarcinoma and Squamous Cell Carcinoma of the Lung

OBJECTIVE This study evaluates the prognostic significance of [18F]-fluoro-2-deoxyglucose positron emission tomography/computed tomography findings according to histological subtypes in patients with completely resected non-small cell lung cancer. METHODS We examined 176 consecutive patients who had undergone preoperative [18F]-fluoro-2-deoxyglucose-positron emission tomography/computed tomography imaging and curative surgical resection for adenocarcinoma (n = 132) or squamous cell carcinoma (n = 44). Maximum standardized uptake values for the primary lesions in all patients were calculated as the [18F]-fluoro-2-deoxyglucose uptake and the surgical results were analyzed. RESULTS The median values of maximum standardized uptake value for the primary tumors were 2.60 in patients with adenocarcinoma and 6.95 in patients with squamous cell carcinoma (P< 0.001). Analyses of receiver operating characteristic curves identified an optimal maximum standardized uptake value cutoff value to predict recurrence of 3.7 for adenocarcinoma, whereas such an indicator could not be identified for squamous cell carcinoma. Although 2-year disease-free survival rates were 70.2% for maximum standardized uptake value ≤6.95 and 59.3% for maximum standardized uptake value >6.95 (P = 0.83) among patients with squamous cell carcinoma, 2-year disease-free survival rates were 93.9% for maximum standardized uptake value ≤3.7 and 52.4% for maximum standardized uptake value >3.7 (P < 0.0001) among those with adenocarcinoma, and notably, 100 and 57.2%, respectively, in patients with Stage I adenocarcinoma (P < 0.0001). On the basis of the multivariate Cox analyses of patients with adenocarcinoma, maximum standardized uptake value (P = 0.008) was a significantly independent factor for disease-free survival as well as nodal metastasis (P = 0.001). CONCLUSIONS Maximum standardized uptake value of the primary tumor was a powerful prognostic determinant for patients with adenocarcinoma, but not with squamous cell carcinoma of the lung.

Radical hybrid video-assisted thoracic segmentectomy: long-term results of minimally invasive anatomical sublobar resection for treating lung cancer

We analysed the results of radical segmentectomy achieved through a hybrid video-assisted thoracic surgery (VATS) approach that used both direct vision and television monitor visualization at a median follow-up of over 5 years. Between April 2004 and October 2010, 102 consecutive patients able to tolerate lobectomy to treat clinical T1N0M0 non-small cell lung cancer (NSCLC) underwent hybrid VATS segmentectomy in which we used electrocautery without a stapler to divide the intersegmental plane detected by selective jet ventilation in addition to the path of the intersegmental veins. Curative resection was achieved in all patients. The median surgical duration and blood loss during the surgery were 129 min (range, 60-275 min) and 50 ml (range, 10-350 ml), respectively. The complication rate was 9.8% (10/102) with the most frequent being prolonged air leak, and there was no case of in-hospital death or 30-day mortality post procedure. Five and seven patients developed locoregional and distant recurrences, respectively. The overall and disease-free 5-year survival rates were 89.8% and 84.7%, respectively. Radical hybrid VATS segmentectomy including atypical resection of (sub)segments is a useful option for clinical stage-I NSCLC. The exact identification of anatomical intersegmental plane followed by dissection using electrocautery is critical from oncological and functional perspectives.

Prognostic impact of the primary tumor location based on the hilar structures in non-small cell lung cancer with mediastinal lymph node metastasis

The status of mediastinal lymph node metastasis is one of the main factors determining the treatment strategy for non-small cell lung cancer (NSCLC), but the primary tumor location is not considered crucial in the tumor-node-metastasis (TMN) classification at present. The aim of this study was to estimate the prognostic value of the primary tumor location on the basis of the hilar structures in NSCLC with mediastinal lymph node metastasis. We retrospectively reviewed the cases of 337 consecutive patients who underwent surgical resection for NSCLC between 1995 and 2004, divided the pN2 NSCLC cases (n=40) into central- and peripheral-type tumors according to the distance of the primary tumor from the first branch of the extrapulmonary bronchus, and compared the surgical outcomes between these tumor groups. Eighteen and twenty-two cases were classified as central- and peripheral-type tumors, respectively. The 5-year survival rate was significantly better for patients with central-type tumors than peripheral-type tumors (51.5% vs. 21.2%, P=0.034). The location-specific prognostic tendency was noted irrespective of the presence (n=13) or absence of skip metastasis. In a multivariate Cox analysis of the N2 NSCLC cases, the primary tumor location was a significant (P=0.026) prognostic factor for overall survival. In conclusion, evaluation of the primary tumor location based on the hilar structures is useful to predict the prognosis in N2 NSCLC.

Fibrinogen/thrombin-based collagen fleece (TachoComb®) promotes regeneration in pulmonary arterial injury

OBJECTIVES To repair unexpected damage of the pulmonary artery (PA) during thoracic surgery, fibrinogen/thrombin-based collagen fleece (TachoComb(®) [TC]) can be applied as a haemostatic material. The progression of vessel restoration with TC has not been elucidated. In this study, we investigate details of the healing process with TC after PA injury using a canine model. METHODS Left thoracotomy was performed on female beagles under general anaesthesia. PA injury was induced and repaired using TC. Repair sites were histologically evaluated 2, 4 and 8 weeks after surgery (n = 3 in each group). RESULTS Haemostasis of PA injury was achieved promptly after TC application. After surgery, no bleeding was found in the thoracic cavity, and no repair sites revealed stenosis, thrombi or false aneurism formation. Two weeks after surgery, inflammatory cells had infiltrated around the vascular defect, and vascular endothelium had regenerated on the innermost surface of TC applied to the defect. At Week 4, elastic and smooth muscle fibres had begun to extend into the defect between the endothelial layer and collagen fleece. By Week 8, elastic fibres and smooth muscle had completely regenerated in the medial layer. The adventitial layer had also fully regenerated. CONCLUSIONS Haemostasis of injured PA using TC was safe and reliable. TC provided a mechanical scaffold on which vascular regeneration occurred. Three layers reconstructed in the PA defect were identical to those in normal structures.

Non-small-cell lung cancer prognosis using carcinoembryonic antigen levels in pleural lavage fluid

OBJECTIVES The study aimed to evaluate the prognostic significance of carcinoembryonic antigen levels in pleural lavage fluid (p-CEA) in patients with completely resected non-small-cell lung cancer (NSCLC). METHODS We examined 72 patients who underwent curative surgical resections. Pleural lavage fluid was collected at thoracotomy before lung resection. Pleural lavage cytology and p-CEA were determined. The relationships between p-CEA and clinicopathological factors were analysed. RESULTS Four patients (5.6%) had positive pleural lavage cytologies. The median p-CEA was 65.2 ng/g protein (range, 0-7331.7). p-CEA was significantly correlated with pleural invasion and CEA levels in serum (s-CEA). Receiver operating characteristic curve analysis identified an optimal cut-off of 38 ng/g protein for p-CEA for predicting recurrence [area under the curve (AUC) = 0.669; sensitivity = 91.7%; specificity = 43.7%; 95% confidence interval (CI) = 0.541-0.796; P = 0.020], whereas this could not be identified for s-CEA (AUC = 0.535; 95% CI = 0.392-0.678; P = 0.629). With a mean follow-up period of 57.5 months, 5-year disease-free survival (DFS) rates were 86.5% for p-CEA ≤ 38 ng/g protein and 47.7% for p-CEA >38 ng/g protein (P = 0.0013). Even for patients with Stage I lung cancer, 5-year DFS rates were 88.2 and 53.8%, respectively (P = 0.017). Multivariate Cox analysis revealed that p-CEA was a significant independent factor for DFS and overall survival. CONCLUSIONS Intraoperative p-CEA may be a more powerful prognostic determinant than s-CEA for patients with NSCLC.

Splenic hamartoma associated with thrombocytopenia: A case report

Highlights • Few cases of splenic hamartomas associated with thrombocytopenia have been reported.• Imaging findings in splenic hamartomas are non-specific, variable, and making definitive preoperative diagnosis difficult.• Surgery is necessary for diagnosis when malignancy cannot be ruled out.• Surgery may also improve symptoms of hypersplenism, including thrombocytopenia.

Adoptive Immunotherapy of Cancer Using Autologous Lymphocytes

Adoptive immunotherapy (AIT) of cancer using lymphocytes is a highly promising modality for eradicating cancer. The AIT strategy is less dependently of cancer-associated immune dysfunction, which exists in tumor-bearing host. The cloning of interleukin-2 (IL-2) has facilitated to manipulate and to propagate effector cells. Lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TILs) were introduced into clinical trials for cancer treatment and demonstrated, to some extents, objective tumor responses. Identification of tumor antigens and understanding of antigen presentation and recognition machinery has permitted to stimulate HLA-restricted antigen-specific lymphocytes with dendritic cells (DCs) and tumor antigens, including peptide, tumor lysate, tumor fusion, and tumor RNA. HLA-un-restricted effector cells, including NKT cells and γδT cells, have also been promising to investigate. It is the most important to define and establish a suitable culture system that can permit adequate expansion of effector lymphocytes with sufficient activities that can persist in vivo. It must also be of importance to conduct scientific clinical trials for establishing effective AIT applications. I believe, the time is coming soon when the AIT can provide clinical benefits for patients with advanced cancer in the world.

Functional inactivation of CD4+CD25high regulatory T cells using low dose human/mouse chimeric anti-CD25 monoclonal antibody enhanced lymphokine-activated killer cells activity

Functional modulation of regulatory T cells (T-regs) is one possible approach to cancer immunotherapy. In this study, we investigated whether low-dose basiliximab, a chimeric anti-CD25 monoclonal antibody, could suppress the T-regs function not by depletion but by inactivation, and increase immune responses. Peripheral blood mononuclear cells from healthy donors and patients with malignancy were collected. We tried T-regs inactivation using various concentrations of basiliximab before induction of lymphokine-activated killer (LAK) cells. We measured cell proliferation, lymphocyte phenotype, intracellular T-regs maker, and Th1/2 cytokines production. Our results showed that the optimal concentration of basiliximab for specifically down-modulating only T-regs was 0.001 μg/ ml. The reduction of Th-2 cytokine secretion with concomitant APC induction without suppressing cell proliferation offers the promise of a novel adoptive immunotherapy to cancer patients.