Mitsuhito Kaji

Long-term benefits for the quality of life after video-assisted thoracoscopic lobectomy in patients with lung cancer.

Quality of life (QOL) after video-assisted thoracic surgical (VATS) lobectomy remains to be defined. Forty-four consecutive patients with clinical stage I lung cancer underwent lobectomy by the VATS approach (n = 22 patients) or thoracotomy approach (n = 22 patients). Acute pain was quantitated by postoperative narcotic requirements and the need for epidural anesthesia. Long-term QOL was assessed by questioning patients about the presence of chronic chest pain, ongoing limitations in arm or shoulder function, time until return to preoperative activity, and satisfaction with the operation. Patients who underwent VATS lobectomy had significant decreases in both acute and chronic chest pain and time until return to preoperative activity. Patients also had more confidence regarding wound size and their overall impression of the operation. In this series, VATS lobectomy was associated with long-term benefits for the QOL in patients with lung cancer. However, the exact role of this approach should be defined by carefully-designed controlled trials studying long-term survival.

Overexpression of CDC20 predicts poor prognosis in primary non-small cell lung cancer patients

This study examined the expression of CDC20 in human non‐small cell lung cancer (NSCLC), explored its clinicopathological significance, and evaluated as a potential prognostic marker.

Overexpression of KIF23 predicts clinical outcome in primary lung cancer patients.

OBJECTIVE High-level expression of kinesin family member 23 (KIF23), a member of microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division, has been observed in a variety of human malignancies. The aims of the present study were to observe the expression of KIF23 in lung cancer, examine the role of KIF23 in lung cancer cell growth and/or survival by small interfering RNA experiments, and explore its clinicopathologic significance and evaluate KIF23 expression as a prognostic marker. MATERIALS AND METHODS Quantitative reverse transcription-polymerase chain reaction analysis was performed to detect the expression of KIF23 mRNA using metastatic lymph nodes from patients with advanced lung cancer obtained by endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA) and primary lung tumors through surgical sample. The role of KIF23 in cancer cell growth was examined by small interfering RNA experiments. A total of 339 lung cancers were analyzed immunohistochemically on tissue microarrays to examine the expression of KIF23 protein and its clinicopathologic significance. RESULTS KIF23 transcript was found to be overexpressed in the great majority of metastatic lymph nodes from advanced lung cancers and primary lung tumors. Inhibiting KIF23 expression effectively suppressed lung cancer cell growth. High-level KIF23 expression was observed in 67.8% of the 339 cases. Lung adenocarcinoma patients with tumors displaying a high-level of KIF23 expression was also identified as an independent prognostic factor by multivariate analysis (P=0.0064). CONCLUSION KIF23 not only provides additional prognostic information for surgical treatment of lung cancer, but may also be a novel therapeutic target for these patients.

Overexpression of KIAA0101 predicts poor prognosis in primary lung cancer patients

High expression of KIAA0101 (p15(PAF)/OEATC-1) which contains a proliferating cell nuclear antigen (PCNA)-binding motif, a key factor in DNA repair and/or apoptosis and cell cycle regulation, has been observed in a variety of human malignancies. The aim of this study was to observe the expression of KIAA0101 in human non-small-cell lung cancer (NSCLC), explore its clinicopathological significance and evaluate KIAA0101 expression as a potential prognostic marker. KIAA0101 transcript was found to be overexpressed in the great majority of lung cancers by semi-quantitative RT-PCR. A total of 357 NSCLCs were analyzed immunohistochemically on tissue microarrays. High-level KIAA0101 expression was observed in 33.9% (121 of 357 cases), and correlated with male gender (P<0.0001), tumor progression (pT status) (P=0.0008), lymph node metastasis (pN status) (P=0.0003), non-adenocarcinoma histological classification (P<0.0001), and smoking history (P<0.0001), but not with patient age or pleural invasion. Patients with tumors displaying high-level KIAA0101 expression showed significantly shorter survival (P<0.0001, log-rank test). Similarly, gender, pT status, pN status, pleural invasion, histological classification, and smoking history were significant prognostic markers in univariate Cox survival analysis. Importantly, high-level KIAA0101 expression was also identified as an independent prognostic factor by multivariate analysis (P=0.0320). These results provide additional information for determining postoperative adjuvant treatment of NSCLC.

Solitary capillary hemangioma of the lung : report of 2 resected cases detected by high-resolution CT

We report 2 cases of capillary hemangioma, each presenting as a solitary nodule in the peripheral lung. Both of the patients were asymptomatic with a small solitary nodule that had revealed by computed tomography. In both cases, the nodule was resected surgically under a clinical diagnosis of early lung cancer. Macroscopically, each lesion was ill defined and irregular in shape with a dark brown cut surface. Microscopically, the alveolar septa in both nodules were thickened by accumulations of numerous thin-walled capillary vessels, which characteristically extended along, or infiltrated, each septum. We diagnosed these lesions as “solitary capillary hemangioma” of the peripheral lung. Tumors or tumorlike lesions of capillary vessels in the lung are rare. Among them, pulmonary capillary hemangiomatosis (PCH) has been described as multiple nodules in the lung parenchyma or bronchovascular walls, comprised of infiltrating thin-walled capillary blood vessels. Moreover, PCH-like foci have been found in a retrospective study of autopsy cases. However, the presented cases should be differentiated from PCH in terms of their clinical setting such as history of hypertension or veno-occlusive disease and multiplicity of the lesion. This is a rare case series of solitary capillary hemangioma discovered incidentally during life, and the lesions were difficult to differentiate radiologically from early lung cancer. After the recent advances in imaging diagnosis for early detection of peripheral lung cancer, these lesions are important to bear in mind for differential diagnosis of bronchioloalveolar carcinoma.

Angiolymphatic invasion exerts a strong impact on surgical outcomes for stage I lung adenocarcinoma, but not non-adenocarcinoma.

Angiolymphatic invasion (ALI), representing lymphatic invasion (Ly) and intratumoral vascular invasion (V), is considered to be a useful prognostic factor for pathological stage I non-small cell lung carcinoma (NSCLC). However, the types of tumor for which prognoses are most influenced by ALI positivity have not previously been discussed, nor has the question of whether these findings should influence postoperative therapeutic decision-making after complete resection. The present study investigated 195 cases of stage I NSCLC treated by potentially curative surgical resection of the primary tumor and systematic lymphadenectomy. ALI-positive (ALI(+)) results were found in 31.8% of tumors, and 5.1% exhibited both Ly(+) and V(+). Five-year recurrence-free survival was significantly lower in ALI(+) cases (50.6%) than in ALI(-) cases (85.9%; p<0.0001, log-rank test). In particular, 5-year recurrence-free survival rate was only 10.0% for Ly(+)V(+) cases. ALI(+) correlated with high age, male sex, tumor size (>2.0 cm), elevated preoperative serum carcinoembryonic antigen level (≥5.0 ng/mL), high maximum standard uptake value (SUVmax) on (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) (≥5.0), pleural invasion, and histological classification of non-adenocarcinoma (ADC). According to histopathological subset analyses, ALI(+) was associated with shorter recurrence-free survival than ALI(-) only among ADC patients (p<0.0001, log-rank test), and not among non-ADC patients (p=0.7710). High preoperative serum CEA level, high SUVmax on FDG-PET, pleural invasion, Ly(+), and V(+) were significant risk factors for recurrence in univariate Cox survival analysis among stage I ADC patients. Importantly, Ly(+) and V(+) were identified as independent risk factors for recurrence by multivariate analysis. Histopathological detection of ALI as a risk factor for recurrence should be considered for inclusion in the staging criteria and as additional information for determining postoperative adjuvant treatment of stage I NSCLC, particularly among ADC patients, but not among non-ADC patients.

Lymphokine-activated killer cytotoxicity against pancreas adenocarcinoma cell lines and vascular endothelial cells.

Eight pancreas carcinoma cell lines of duct cell origin (PCI‐6, 10, 19, 24, 35, 43, 55, and 64) were established. Using one of these lines, PCI‐24, human umbilical vein endothelial cells (HUVEC), and several recombinant cytokines, conditions and specificity of antl‐PCI LAK induction were Investigated, with the focus on a search for lymphokine‐activated killer (LAK) activity that differentiates neoplastic (PCI) from non‐neoplastic (HUVEC) cells. Interferon‐γ (IFN‐γ), IFN‐α, IL‐4, 11–6, and IL‐7, but not tumor necrosis factor‐α (TNF‐α) or IL‐1β, induced a weak LAK activity against PCI‐24, whereas IL‐2‐induced (1000U/mL) LAK exhibited a far more potent cytotoxicity. When these cytokines were added at the suboptimal dose IL‐2 (100U/mL), no significant augmentation in LAK activity was induced. Staphylococcal protein A (SpA) induced LAK activity as potent as that seen with IL‐2 (1000 U/mL). Both IL‐2‐induced and SpA‐induced LAK had a potent, dose‐dependent cytotoxicity against HUVEC. HUVEC inhibited both IL‐2– and SpA‐induced LAK cytotoxicity against PCI‐24 to almost the same extent as seen with PCI‐24. Thus, two potent LAK‐inducers did not generate LAK activity that differentiates neoplastic from non‐neoplastic cells. Thus, in vitro cytotoxicity of LAK agalnst non‐neoplastic endothelial cells is unavoidable when handling cytokines in LAK induction.

Up‐regulation of CD40 with juxtacrine activity in human nonsmall lung cancer cells correlates with poor prognosis

CD40 and its ligand, CD154, play a regulatory role in several signaling pathways among lymphocytes. Recently, it was reported that CD40 is expressed in several malignant tumors. However, the clinical impact of CD40 expression in nonsmall cell lung cancer has not been studied widely.

Successful Resection of a Recurrent Mediastinal Liposarcoma Invading the Pericardium: Report of a Case

Primary liposarcoma of the mediastinum is rare, but cases of recurrence have been reported in the English literature. We successfully resected a recurrent pericardial liposarcoma, detected 5 years after the initial resection of a liposarcoma of the anterior mediastinum invading the pericardium. Routine follow-up computed tomography showed the recurrence and suggested invasion of the pericardial cavity, which was supported by the findings of transesophageal ultrasonography. As cine-magnetic resonance imaging suggested that the tumor was resectable, an operation was performed. Histopathology confirmed the diagnosis of recurrent liposarcoma and showed clear surgical margins.

Necrotizing Sarcoid Granulomatosis Presenting with Elevated Serum Soluble Interleukin-2 Receptor Levels

A 52-year-old woman presented with a one-week history of low-grade fever and dyspnea. A CT scan showed multiple pulmonary nodules with cavitation, as well as bilateral pleural thickenings with effusions. A specimen resected by video-assisted thoracoscopic surgery showed multiple confluent granulomas with central necrosis and granulomatous vasculitis. These findings were consistent with necrotizing sarcoid granulomatosis. An elevated serum soluble interleukin-2 receptor level became normal following clinical and radiological improvement. This indicates that the serum soluble interleukin-2 receptor can be a useful marker for the clinical management of necrotizing sarcoid granulomatosis.