The Cancer Institute Hospital

Japanese, Japan

The Cancer Institute Hospital

Japanese, Japan
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Inamura K.,The Cancer Institute | Yokouchi Y.,Daiichi Sankyo | Kobayashi M.,The Cancer Institute | Sakakibara R.,The Cancer Institute | And 7 more authors.
Journal of Controlled Release | Year: 2016

Objectives Compared with non-smoking counterparts, smoking-associated lung cancers have a higher mutational load, resulting in the creation of more tumor neoantigens and increased immunogenicity. B7-H3 (also known as CD276) belongs to a family of immune modulators that includes PD-1 and PD-L1 (also known as B7-H1 or CD274). Considering the evidence that PD-L1 inhibitors have been shown to be more effective against lung cancer in smokers, we herein examined the prognostic interaction of tumor B7-H3 expression level with smoking history in lung adenocarcinoma patients. Materials and methods Using tissue microarrays comprising 270 consecutive cases of lung adenocarcinoma, we evaluated tumor B7-H3 expression by immunohistochemistry. We examined the prognostic association between B7-H3 expression levels and smoking history, using Cox proportional hazards regression analysis and the log-rank test. Additionally, we used logistic regression analysis to examine the correlations between B7-H3 expression levels and clinicopathological/molecular features of lung adenocarcinoma. Results The association of B7-H3 expression with survival differed by smoking history (Pinteraction = 0.014); high B7-H3 expression was associated with decreased lung cancer-specific survival in moderate/heavy-smoking patients (smoking index [SI] ≥ 400) (hazard ratio [HR] = 3.07, 95% confidence interval [CI] = 1.74-5.49, P = 0.0001; log-rank: P < 0.0001), but not in non/light-smoking patients (SI < 400) (HR = 1.14, 95% CI = 0.63-1.96, P = 0.64; log-rank: P = 0.64). Interestingly, in moderate/heavy-smoking patients, high B7-H3 expression was associated with decreased survival in stage I cancer (log-rank; P = 0.0005), whereas it showed no significant difference of survival in stage II–IV cancer (P = 0.37). High B7-H3 expression was associated with smokers (univariable odds ratio [OR] = 2.63, 95% CI = 1.51-4.65; P = 0.0005) and independently associated with EGFR wild-type status (multivariable OR = 2.80, 95% CI = 1.38-5.84; P = 0.0042). Conclusions We demonstrated that the prognostic association of B7-H3 expression indeed differed according to smoking history. Our study also showed the significant association of high B7-H3 expression with EGFR wild-type and smoking patients, indicating the potential effectiveness of anti-B7-H3 therapy for EGFR wild-type or smokers’ lung adenocarcinoma. © 2016


Inamura K.,The Cancer Institute Hospital | Yokouchi Y.,Daiichi Sankyo | Kobayashi M.,The Cancer Institute Hospital | Ninomiya H.,The Cancer Institute Hospital | And 8 more authors.
Oncotarget | Year: 2017

TROP2 is a transmembrane glycoprotein that is overexpressed in various cancers. Emerging evidence suggests that TROP2-targeting therapies are efficacious and safe in patients with multiple prior treatments. TROP2 is a promising target for lung cancer treatment; however, little is known regarding the association of TROP2 expression with clinicopathological/molecular features, including prognosis, in lung cancer. We examined consecutive cases of adenocarcinoma, squamous cell carcinoma (SqCC), and high-grade neuroendocrine tumor (HGNET) for the membranous expression of TROP2 using immunohistochemistry. High TROP2 expression was observed in 64% (172/270) of adenocarcinomas, 75% (150/201) of SqCCs, and 18% (21/115) of HGNETs. Intriguingly, the association of TROP2 expression with mortality was dependent on the lung cancer subtype. High TROP2 expression was associated with higher lung cancer-specific mortality in adenocarcinomas [univariable hazard ratio (HR) = 1.60, 95% confidence interval (CI) = 1.07-2.44, P = 0.022)], but not in SqCCs (univariable HR = 0.79, 95% CI = 0.35-1.94, P = 0.79). In HGNETs, high TROP2 expression was associated with lower lung cancer-specific mortality in both univariable and multivariable analyses (multivariable HR = 0.13, 95% CI = 0.020- 0.44, P = 0.0003). Our results suggest a differential role for TROP2 in different lung cancer subtypes.


PubMed | The Cancer Institute Hospital and Yokohama City University
Type: Journal Article | Journal: Journal of thoracic disease | Year: 2017

Dealing with incomplete lung fissures during thoracoscopic surgery is difficult. Our objective was to evaluate the efficacy and safety of a thoracoscopic anterior fissure first technique for dealing with incomplete left lung fissures.One hundred and seventy patients underwent left upper lobectomy or left lower lobectomy between April 2008 and July 2014. Of these, 34 patients underwent surgery using a thoracoscopic anterior fissure first technique for incomplete fissures (group A) and 136 underwent surgery using a conventional thoracoscopic method for unfused fissures (group B). A four-port complete thoracoscopic approach was used in all patients. After completion of the fissure, hilar lymphadenectomy was performed in the conventional manner.There were no significant differences between the two groups in operating time, blood loss, or duration of chest tube drainage. Patients in group A required more staple cartridges than those in group B (mean number of cartridges, 2.4 We found that a thoracoscopic anterior fissure first technique for left lung cancer with an incomplete fissure enabled hilar lymphadenectomy to be performed in the conventional manner without any increase in the prevalence of air leaks, operating time, or duration of chest tube drainage. This technique should be considered for use in left upper lobectomy or left lower lobectomy in patients with an incomplete fissure.


Hisashige A.,The Institute of Healthcare Technology Assessment | Sasako M.,Hyogo College of Medicine | Nakajima T.,The Cancer Institute Hospital
BMC Cancer | Year: 2013

Background: The effectiveness of specific regimens of adjuvant therapy for gastric cancer has not been verified by large clinical trials. Recently, several large trials attempted to verify the effectiveness of adjuvant therapy. The Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer in Japan, a randomized controlled trial of adjuvant S-1 therapy for resected gastric cancer, demonstrated significant improvement in overall and relapse-free survival, compared to surgery alone. To evaluate value for money of S-1 therapy, cost-effective analysis was carried out.Methods: The analysis was carried out from a payer's perspective. As an economic measure, cost per quality-adjusted life-year (QALY) gained was estimated. Overall survival was estimated by the Kaplan-Meier method, up to 5-year observation. Beyond this period, it was simulated by the modified Boag model. Utility score is derived from interviews with sampled patients using a time trade-off method. Costs were estimated from trial data during observation, while in the period beyond observation they were estimated using simulation results. To explore uncertainty of the results, qualitative and stochastic sensitivity analyses were done.Results: Adjuvant S-1 therapy gained 1.24 QALYs per patient and increased costs by $3,722 per patient for over lifetime (3% discount rate for both effect and costs). The incremental cost-effectiveness ratio (95% confidence intervals) for over lifetime was estimated to be $3,016 ($1,441, $8,840) per QALY. The sensitivity analyses showed the robustness of these results.Conclusion: Adjuvant S-1 therapy for curatively resected gastric cancer is likely cost-effective. This therapy can be accepted for wide use in Japan. © 2013 Hisashige et al.; licensee BioMed Central Ltd.


Osako T.,The Cancer Institute | Osako T.,The Cancer Institute Hospital | Takeuchi K.,The Cancer Institute | Horii R.,The Cancer Institute Hospital | And 2 more authors.
Histopathology | Year: 2013

Aims: Secretory carcinoma (SC) is a rare histological type of breast cancer, and ETV6-NTRK3 gene fusion is highly specific to it. The differential diagnoses of SC include acinic cell carcinoma (ACCA) and cystic hypersecretory carcinoma (CHC), as well as invasive ductal carcinoma (IDC). For patients with these rare but distinctive histological subtypes, SC and its histopathological mimics should be differentiated from each other. However, differential markers have not yet been assessed systematically, and we aimed to identify and evaluate novel and existing markers. Methods and results: We reviewed 19 cases diagnosed initially as SC using integrated diagnostic techniques, including morphology, immunohistochemistry and molecular pathology, and validated promising markers in 445 breast cancers. We reclassified 19 formerly diagnosed 'SCs' into nine SCs, three ACCAs, three CHCs, three IDCs and one microglandular adenosis. We confirmed that ETV6-NTRK3 gene rearrangement and amylase positivity are good diagnostic markers for SC and ACCA, respectively. Vacuolar staining for adipophilin, positivity for α-lactalbumin and negativity for ETV6 rearrangement are diagnostic markers for CHC. Conclusions: In this study, we propose a panel of four markers (ETV6 rearrangement, amylase, α-lactalbumin and adipophilin) for distinguishing SC, ACCA, CHC and IDC. This simple but robust panel will serve pathologists well as a practical guide for reaching an appropriate diagnosis. © 2013 John Wiley & Sons Ltd.


Kabeya M.,The Cancer Institute | Kabeya M.,Niigata University | Furuta R.,The Cancer Institute | Kawabata K.,The Cancer Institute Hospital | And 2 more authors.
Cancer Science | Year: 2012

The carcinogenetic role of human papillomavirus (HPV) in mobile tongue cancer remains unclear because of conflicting results reported in the literature. This disparity is likely to be due to variations in the samples and methods used. Furthermore, despite a tendency for increased prevalence of mobile tongue cancer in young adults, only a few reports specifically in young patients have been published. In the present study on 32 patients, including six in their 20s, we genotyped the prevalence of HPV using a highly sensitive detection tool in fresh-frozen samples from surgical specimens and a novel detection device with electrochemical DNA chip and loop-mediated isothermal amplification. In addition, we confirmed HPV prevalence by in situ hybridization and immunohistochemistry for the p16 INK4a protein, regarded as a biomarker of HPV-associated cancers. The frequency of 13 genotypes of high-risk HPV was 0/32 (0%), which was further confirmed by in situ hybridization. Overexpression of p16 INK4a protein was observed in six of the 32 patients (19%), with four (67%) also overexpressing p53. Because there is usually a lack of p53 overexpression in HPV-associated cancer, it is unlikely that p16 INK4a protein overexpression is correlated with HPV infection. Consequently, it is unlikely that HPV infection plays an important role in mobile tongue carcinogenesis, in particular in young adults. In addition, our data suggest that the overexpression of p16 INK4a protein is not an appropriate biomarker for HPV association in mobile tongue carcinogenesis. © 2011 Japanese Cancer Association.


Matsusaka S.,The Cancer Institute Hospital
Nihon rinsho. Japanese journal of clinical medicine | Year: 2012

Cancer therapies are changing from general chemotherapeutic agents to drugs that target specific proteins and signaling pathways. Target therapies, which attack specific cancer cells without harming normal cells, have the potential to treat cancers with fewer side effects than conventional therapies. This article reviews mechanisms of resistance to targeted agents, including genetic resistance, bypass track resistance, and defect growth arrest/apoptosis. Secondary mutations reduce the biologic effects of inhibiting the driver oncoprotein. Interaction and cross signaling from targeting receptor to other growth factor receptors may potentially contribute to therapeutic resistance. They explain why solid tumors develop resistance to target therapies in a highly reproducible fashion.


Motoi N.,The Cancer Institute Hospital | Ishikawa Y.,The Cancer Institute Hospital
Diagnostic Histopathology | Year: 2014

Salivary gland-type tumours of the lung, which include adenoid cystic carcinoma and mucoepidermoid carcinoma, are rare entities. Histologically, they show morphologies that are similar to those of salivary gland origin. For classification purposes, the terminology applied to tumours of salivary gland origin is also applied to their pulmonary counterparts. Of these types of tumours, adenoid cystic carcinoma is the most common followed by mucoepidermoid carcinoma. Epithelial-myoepithelial carcinoma and pleomorphic adenoma are uncommon. The possibility of metastasis from the salivary glands is important to exclude through careful examination of patients' medical history because low-grade salivary cancers can metastasize after long latencies. A gene rearrangement analysis is helpful in making a definitive diagnosis, particularly in cases with an unusual morphology. Molecular-based classification may be useful to understand the nature of morphologically varied tumours. The immunohistochemical profile of the tumours is also a valuable tool for an accurate diagnosis in difficult cases. © 2014 Elsevier Ltd.


PubMed | The Cancer Institute Hospital
Type: Journal Article | Journal: Journal of thoracic disease | Year: 2017

Identification of the exact location of small peripheral pulmonary nodules during thoracoscopic wedge resection (TWR) is crucial. We describe a new method of computed tomography (CT)-guided marking without puncturing the visceral pleura (VP) for minimally palpable pulmonary nodules.Preoperative CT scans were performed 1 day before TWR with the patient in the lateral decubitus position. Under CT guidance, we marked the skin over the pulmonary nodule. During TS, an indwelling catheter was inserted perpendicular to the marked skin surface and put a mark with gentian violet (Pyoktanin blueBetween October 2012 and April 2016, we performed CT-guided marking in 54 patients (24 males and 30 females, median age 65 years). Cases included 39 primary lung cancers, 10 metastatic lung tumors, and 5 benign tumors. The mean diameter of the nodules was 10 mm (range, 3-26 mm), and the mean distance of the nodule from the VP was 4 mm (range, 0-17 mm). The mean time of intraoperative marking was 3.5 min (range, 1-4.5 min). The mean distance from the nodule to the marking point was 7.0 mm (range, 0-30 mm). We were able to identify the location of the nodule using this procedure in 53 patients (98%). Hematoma of the chest wall after marking was observed in one patient. There were no other complications.This marking technique is a simple, economic, and effective procedure to locate small peripheral pulmonary nodules during TWR.


PubMed | The Cancer Institute Hospital
Type: Journal Article | Journal: Molecular and clinical oncology | Year: 2016

The local renin-angiotensin system promotes angiogenesis and vascular proliferation via expression of vascular endothelial growth factor or epidermal growth factor receptor. We hypothesized that angiotensin II type-1 receptor blockers (ARBs) in combination with bevacizumab (Bev) may improve clinical outcomes in patients with metastatic colorectal cancer (mCRC). A total of 181 patients with histopathologically confirmed mCRC treated with first-line oxaliplatin-based chemotherapy in combination with Bev were enrolled between June, 2007 and September, 2010. The patients were divided into two groups based on the presence or absence of treatment with ARBs prior to the initiation of second-line chemotherapy. Kaplan-Meier analysis and Cox proportional hazard modeling were used in the statistical analysis. The median progression-free survival (PFS) in patients undergoing second-line chemotherapy in combination with Bev and ARBs (n=56) vs. those treated in the absence of ARBs (n=33) was 8.3 vs. 5.7 months, respectively [hazard ratio (HR)=0.57, 95% confidence interval (CI): 0.35-0.94, P=0.028]. The median overall survival (OS) was 26.5 vs. 15.2 months, respectively (HR=0.47, 95% CI: 0.25-0.88, P=0.019). In the multivariate analysis, the use of ARBs was independently associated with prolongation of OS and PFS. In conclusion, the use of ARBs prolonged survival in mCRC patients.

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