Keidai Ishikawa

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 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.

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.

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.

Optimal predictive value of preoperative serum carcinoembryonic antigen for surgical outcomes in stage I non‐small cell lung cancer: Differences according to histology and smoking status

The cutoff value of preoperative serum carcinoembryonic antigen (CEA) levels has not been investigated using appropriate subgroup analyses for non‐small cell lung carcinoma (NSCLC). This study was undertaken to determine whether the most predictive preoperative CEA level for risk of recurrence differs according to histological type, and how smoking status influences predictive values in Stage I NSCLC.

A Case of Castleman's Disease with Myasthenia Gravis

A rare case of Castlemans disease with myasthenia gravis is reported. A 55-year-old woman with bilateral ptosis, speech impairment, and severe dyspnea had been previously diagnosed with myasthenia gravis. Computed tomography showed a 5 cm × 3 cm paratracheal mass in the mediastinum, thought to be an ectopic thymoma. Two days after surgical resection, the patient suddenly developed dyspnea. Postoperative myasthenic crisis was diagnosed, and plasmapheresis was performed. Her general condition improved, and her subsequent course was uneventful. The final pathological diagnosis was mediastinal solitary Castlemans disease, hyaline vascular type. Castlemans disease with myasthenia gravis is especially rare. One of the serious complications is postoperative myasthenic crisis. For patients with myasthenia gravis, the rate of postoperative myasthenic crisis seems significantly higher in Castlemans disease patients than in patients with thymic epithelial tumors. Castlemans disease with myasthenia gravis is discussed along with a review of the literature.

Spontaneous pneumothorax in a patient with dendriform pulmonary ossification: report of a case.

We report herein the rare case of a patient with dendriform pulmonary ossification (DPO) who developed spontaneous pneumothorax. A 33-year-old male with a history of bronchial asthma presented with pneumothorax of the left lung. An intraoperative inspection revealed no findings of bullae in the entire left lung, but inflammatory pleural changes were identified on the interlobular surface of the left lower lobe. In addition, hard, twig-like configurations were clearly palpable in the subpleural parenchyma and were resected. A histological examination showed acicular bone formations containing myeloid tissue and marrow fat in the lung. DPO was thus diagnosed, and the bony spines were considered to have caused a rupture of the elastic fiber layer of the visceral pleura. DPO may thus have been directly responsible for the pneumothorax in this case.

The CD40-CD154 interaction would correlate with proliferation and immune escape in pancreatic ductal adenocarcinoma

CD40 and CD154 are associated with lymphocyte signaling pathways and they are also expressed in some malignant neoplasms, but the significance in pancreatic cancer is unknown.

Method for the validation of immunohistochemical staining using SCID mouse xenografts: Expression of CD40 and CD154 in human non-small cell lung cancer

This report proposes a concept for the standardization of immunohistochemical evaluation. Immunohistochemical staining has several problems associated with the sensitivity of the technical process and standardization of the assessment of potent staining. We provided data focusing on this concept through immunostaining for CD154 in non-small cell lung cancer (NSCLC). We used two types of anti-CD154 antibody as primary antibodies in immunohistochemical staining, as previously reported. Western blot analysis confirmed strong CD154 expression in the cultured cell line PC10, but not in LK2. We also assessed CD154 expression in SCID mouse xenografts of these cell lines. SCID xenograft data on western blot analysis were consistent with those of cultured cell lines. These xenografts could thus be used as positive or negative tissue controls for CD154 immunostaining. Primary antibodies should therefore be confirmed as recognizing target lesions, while control tissue specimens should be objectively confirmed as having target products using another experimental method. Our method would allow results to be unified at more than one laboratory and could act as an objective control assessment method in immunohistochemistry.

Reduced port video-assisted thoracoscopic surgery using a needle scope for lung and mediastinal lesions

OBJECTIVES There are many recent and minimally invasive surgical innovations, yet there has been little evaluation of the limitations of such techniques, particularly those related to video-assisted thoracoscopic surgery. The aims of this study were to determine the usefulness and limitations of video-assisted thoracoscopic surgery using one-port access and needle scope and to evaluate the feasibility of this procedure based on our institutional experience. METHODS This retrospective study involved 127 patients who underwent video-assisted thoracoscopic surgery using the one-window and puncture method at our institute from 1997 to 2011. One hundred patients underwent surgical treatment and 27 underwent diagnostic procedures. If there was one lesion present with only mild adhesion that did not require lymph node dissection, we decided to opt for the one-direction approach that provisionally indicates the one-window and puncture method. We compared the conversion and success groups for factors like age, sex, laterality of surgery, objective of surgery, target organ and surgery location. RESULTS Of 127 cases, 115 (91%) successfully underwent the one-window and puncture procedure. Twelve cases (9%) were converted to the two-window method or thoracotomy. Compared with those targeting the lung, patients with mediastinal lesions demonstrated a higher tendency for conversion (P<0.05). However, age (P=0.89), sex (P=0.46), laterality of surgery (P=0.34) and purpose of surgery (P=0.68) did not show any significant differences between the groups. CONCLUSIONS For lung and mediastinal diseases, video-assisted thoracoscopic surgery with the one-window and puncture method can be performed at any location (upper, middle and lower lobe of lung and anterior, middle and posterior of the mediastinum) under limited indications that include the possibility of one-way resection, mild adhesion and no requirement of lymph node dissection. Under provisional criteria, the procedure may be feasible.