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Japan

Cancer Statistics
Population in 2012: 126.4m
People newly diagnosed with cancer (excluding NMSC) / yr: 703,900
Age-standardised rate, incidence per 100,000 people/yr: 217.1
Risk of getting cancer before age 75:21.8%
People dying from cancer /yr: 378,600
Data from IARC GlobalCan (2012)
Japan: Cancer Organisations and Resources
Japan: Cancer Centres
Journals of Japanese Societies
Latest Research Publications related to Japan

Japan: Cancer Organisations and Resources (12 links)


Japan: Cancer Centres (6 links)


Journals of Japanese Societies (5 links)

See also: Oncology Journals

Latest Research Publications related to Japan

Yanagita T, Kusanagi H
Safety and Effectiveness of Enoxaparin as Venous Thromboembolism Prophylaxis after Gastric Cancer Surgery in Japanese Patients.
Am Surg. 2016; 82(12):1232-1237 [PubMed] Related Publications
Routine prophylaxis for venous thromboembolism (VTE) has been recommended after surgery not only in the West but also in Asia recently. The primary objective of this study was to investigate the safety and effectiveness of enoxaparin as a prophylaxis in patients undergoing distal, proximal, or total gastrectomy (TG) for gastric cancers. A total of 565 patients who underwent gastrectomy for gastric cancer were reviewed retrospectively. About 256 patients received postoperative prophylaxis with enoxaparin (2000 international unit twice daily for at least six days) and compression stockings; these patients were assigned to the enoxaparin group. About 257 patients comprised a historical control group, who used only compression stockings as a thromboprophylaxis. All patients underwent the same rehabilitation programs during the perioperative period. None of the patients developed symptomatic venous thromboembolism in either the enoxaparin group or the control group. The complication rate of bleeding was not significantly different between the two groups. Only one patient who used three antiplatelet agents concomitantly with enoxaparin required reoperation for anastomotic site bleeding. The usage of enoxaparin for venous thromboembolism prophylaxis is safe for Japanese patients after gastrectomy. But, cautious application is still needed especially when used concomitantly with other antiplatelet agents.

Sawada N
Risk and preventive factors for prostate cancer in Japan: The Japan Public Health Center-based prospective (JPHC) study.
J Epidemiol. 2017; 27(1):2-7 [PubMed] Free Access to Full Article Related Publications
The incidence of prostate cancer is much lower in Asian than in Western populations. Lifestyle and dietary habits may play a major role in the etiology of this cancer. Given the possibility that risk factors for prostate cancer differ by disease aggressiveness, and the fact that 5-year relative survival rate of localized prostate cancer is 100%, identifying preventive factors against advanced prostate cancer is an important goal. Using data from the Japan Public Health Center-based Prospective Study, the author elucidates various lifestyle risk factors for prostate cancer among Japanese men. The results show that abstinence from alcohol and tobacco might be important factors in the prevention of advanced prostate cancer. Moreover, the isoflavones and green tea intake in the typical Japanese diet may decrease the risk of localized and advanced prostate cancers, respectively.

Sera T, Kashiwagi S, Takashima T, et al.
Multiple metastatic malignant phyllodes tumor of the breast with tonsillar metastasis: a case report.
BMC Res Notes. 2017; 10(1):55 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Tonsillar metastasis is very rare and accounts for only 0.8% of tonsillar tumors. And phyllodes tumor of the breast with tonsillar metastasis is very rare.
CASE PRESENTATION: A 57-year-old Japanese woman received surgery (partial mastectomy) of malignant phyllodes tumor. Seven months after initial surgery, pharyngeal pain, swelling, and a feeling of dyspnea developed, and tumor was found in the left palatine tonsil. Computed tomography for further evaluation showed a tonsillar lesion with contrast enhancement, and tonsillar metastasis was suspected. The metastatic lung tumors had not progressed. Laryngoscopic biopsy showed a tonsillar metastasis from the malignant phyllodes tumor. Despite the diagnosis of malignant phyllodes tumor with tonsillar and pulmonary metastases, the patient refused further treatment and died about 1 month later.
CONCLUSIONS: A patient with a malignant phyllodes tumor of the breast and tonsillar metastasis was reported, along with a discussion of the relevant literature of this very rare pattern of metastasis.

Jung KJ, Jeon C, Jee SH
The effect of smoking on lung cancer: ethnic differences and the smoking paradox.
Epidemiol Health. 2016; 38:e2016060 [PubMed] Free Access to Full Article Related Publications
The objectives of this review were to determine whether the smoking paradox still exists and to summarize possible explanations for the smoking paradox. Based on published data, we compared the risk of cigarette smoking for lung cancer in Western and Asian countries. We extracted data from the relevant studies about annual tobacco consumption, lung cancer mortality rates according to smoking status from each country, and possible explanations for the smoking paradox. A significantly greater risk of lung cancer death was found among current smokers in Asian countries than among nonsmokers, with relative risks (RRs) of 4.0 to 4.6 for Koreans, 3.7 to 5.1 for Japanese, and 2.4 to 6.5 for Chinese. Although a significantly greater risk of lung cancer was present among current smokers in Asian countries, the RRs in Asian countries were much lower than those reported in Western countries (range, 9.4 to 23.2). Possible explanations for the smoking paradox included epidemiologic characteristics, such as the smoking amount, age at smoking initiation, and the use of filtered or mild tobacco. The smoking paradox definitely exists, but may be explained by major epidemiologic characteristics. Therefore, the smoking paradox should not be interpreted as indicating that tobacco is safer or less harmful for Asians.

Harada Y, Sakai K, Asaka S, Nakayama K
Angioimmunoblastic T-cell Lymphoma Associated with IgA Nephropathy.
Intern Med. 2017; 56(1):85-89 [PubMed] Free Access to Full Article Related Publications
Few cases of IgA nephropathy with angioimmunoblastic T-cell lymphoma (AITL) have been reported. We herein present the case of a 79-year-old Japanese man with AITL and IgA nephropathy. The patient presented with generalized edema, fatigue, and fever. Laboratory investigations revealed polyclonal gammopathy with a high level of IgA, microscopic hematuria, proteinuria, and some other immunological abnormalities. Computed tomography revealed generalized lymphadenopathy. A diagnosis of AITL and IgA nephropathy was made based on inguinal lymph node and renal biopsies. Following chemotherapy for AITL, the patient's edema, microscopic hematuria, and proteinuria were alleviated. These findings indicate that IgA nephropathy may occur in AITL patients.

Ide S, Sakamoto N, Hara S, et al.
Interstitial Lung Disease Induced by Pazopanib Treatment.
Intern Med. 2017; 56(1):79-83 [PubMed] Free Access to Full Article Related Publications
Although pneumothorax has been reported to be a major pulmonary adverse event in patients treated with pazopanib, a multikinase inhibitor, drug-induced interstitial lung disease (DILD) has not been reported. A 74-year-old Japanese man who received pazopanib for the treatment of femoral leiomyosarcoma and lung metastasis presented with dyspnea and fatigue. He had mild interstitial pneumonia when pazopanib treatment was initiated. Chest computed tomography revealed progressive bilateral ground-glass opacity (GGO) and traction bronchiectasis. We diagnosed DILD due to pazopanib. The patient's pazopanib treatment was interrupted and a steroid was administered. The symptoms and GGO were improved with treatment. Physicians should be aware of DILD due to pazopanib in patients with pre-existing interstitial lung disease.

Yamamoto T, Uenishi T, Kaneda K, et al.
Secure, low-cost technique for laparoscopic hepatic resection using the crush-clamp method with a bipolar sealer.
Asian J Endosc Surg. 2017; 10(1):96-99 [PubMed] Related Publications
INTRODUCTION: Laparoscopic hepatectomy is difficult because surgeons must perform the transection using many (four and more) energy devices and without direct manual maneuvers. Here we introduce hepatic transection by the classical method with a few (two or three) energy devices.
MATERIALS AND SURGICAL TECHNIQUE: We performed laparoscopic hepatectomy for 40 patients with hepatic tumor and liver dysfunction. For parenchymal transection, we used bipolar radiofrequency coagulation forceps connected to a voltage-controlled electrosurgical generator and ultrasonic dissector. The demarcation of the liver surface was made by an ultrasonic dissector. Along the demarcation line, the blades of a BiClamp were opened slightly and inserted into the hepatic parenchyma. We clamped slowly, softly, and gradually, and a small amount of hepatic parenchyma was consequently coagulated and fractured. After the crush, the small vessels and intrahepatic bile duct that were sealed were left as atrophic strings, and the strings were divided by an ultrasonic dissector. Large vessels and Glisson's sheaths were left because of the small clamp. Large Glisson's sheaths and hepatic veins were ligated with a titanium clip or autosutures, and cut without bile leakage or bleeding. The mean operation time of the procedure was 196.9 min, mean blood loss was 69.9 mL, and mean postoperative hospitalization was 9.5 days. No blood transfusions were needed. Two cases had perioperative complications-one involving right shoulder pain and the other involving ascites due to liver dysfunction-but there were no serious postoperative complications.
DISCUSSION: The present results appear to demonstrate that this simple and safe method helps decrease intraoperative bleeding and shorten hospital stay.

Fujita H
Anesthesia of Torek's operation: the first successful resection of a cancer in the thoracic esophagus-an abridged translation of an essay in Japanese.
Gen Thorac Cardiovasc Surg. 2017; 65(2):80-84 [PubMed] Related Publications
The first successful resection of a cancer in the thoracic esophagus was performed by Franz Torek around one hundred years ago. Awareness of developments in surgery and the early history can stimulate and foster innovation among surgeons, as well as promote a deeper appreciation of the pioneers of the methods still used today. Here we report the conditions leading to Torek's operation performed in 1913. In the operation, anesthesia was achieved by tracheal insufflation. Ernst Sauerbruch, a surgeon in Germany, first developed a negative-pressure chamber for anesthesia in 1903 and subsequently used this in many open-chest operations. Then in 1909 Samuel Meltzer, a physiologist in New York, proposed ventilation through an intratracheal tube while under anesthesia. Soon afterwards, Sauerbruch gave his chamber to Willey Meyer, a surgeon in the New York German Hospital, who reported Sauerbruch's success in operations in the American journal. The negative-pressure chamber was sent to the Meltzer's laboratory where Meltzer demonstrated that tracheal insufflation was superior to the negative-pressure chamber for open thoracic operations. These findings were conveyed to Meyer and to Franz Torek, a surgeon in the New York German Hospital and a colleague of Meyer, who succeeded in the historical first resection of a cancer in the thoracic esophagus according to Meltzer.

Isaka T, Nakayama H, Yokose T, et al.
Platinum-Based Adjuvant Chemotherapy for Stage II and Stage III Squamous Cell Carcinoma of the Lung.
Ann Thorac Cardiovasc Surg. 2017; 23(1):19-25 [PubMed] Related Publications
INTRODUCTION: The efficacy of platinum-based adjuvant chemotherapy (PBAC) for pathological stage II and stage III squamous cell carcinoma (SCC) of the lung was analyzed retrospectively.
MATERIALS AND METHODS: The prognoses of 94 patients with stage II and stage III SCC with or without PBAC (more than three courses of cisplatin-, carboplatin-, and nedaplatin-based adjuvant chemotherapy) were compared.
RESULTS: The mean observation period was 46.1 months. PBAC was not administered for the following reasons: 39 (55.7%) patients had comorbidities, 25 (35.7%) were older than 75 years, 19 (27.1%) patients underwent surgery before the approval of PBAC, and 3 (4.3%) patients could not continue PBAC (≤2 cycles) because of adverse events. PBAC patients (n = 24) were significantly younger than non-PBAC patients (n = 70; 66.3 vs 69.6 years old, respectively; p = 0.043). Disease-free survival (DFS) did not differ between PBAC and non-PBAC patients (55.0% and 67.1%, respectively; p = 0.266). PBAC patients tended to have worse overall survival (OS) than non-PBAC patients (56.1% and 70.2%, respectively; p = 0.138). PBAC was not prognostic for OS (hazard ratio (HR), 2.11; 95% confidence interval (CI), 0.82%-5.40%; p = 0.120).
CONCLUSION: PBAC did not improve the prognoses of patients with pathological stage II or stage III SCC in the single institution experience.

Toman J, Von Larson S, Umeno H, et al.
HPV-Positive Oropharyngeal Cancer Via p16 Immunohistochemistry in Japan.
Ann Otol Rhinol Laryngol. 2017; 126(2):152-158 [PubMed] Related Publications
OBJECTIVES: Human papillomavirus (HPV) has emerged as a driving cause of head and neck cancer, but investigations outside the West are limited. A p16 immunohistochemistry is a commonly used biomarker for HPV cancers. We sought to investigate the pathology and rates of HPV head and neck oropharyngeal cancer in Japan via p16 immunohistochemistry at 2 institutions in Japan.
METHODS: Fifty-nine oropharyngeal specimens from 2 university hospitals in Japan were examined for morphology and p16 immunohistochemistry. The rate of p16 positivity was then determined, and the 2 groups were compared for differences in age, smoking history, gender, and stage of presentation and mortality.
RESULTS: The rate of p16 positivity among the oropharyngeal specimens was 29.5%. There were important differences in the pathology compared to morphology usually seen in the US. The patients with p16+ cancer tended to be younger. There was no significant difference in smoking status. Patients with p16+ cancers trended toward better survival.
CONCLUSION: There appears to be a geographical difference in HPV rates of oropharyngeal cancers with persistently lower rates in Asian countries when compared to Western Europe and the US. Conclusions about HPV head and neck squamous cell carcinoma (HNSCC) in Western countries may not be generalizable across the globe at this time.

Nakata B, Tendo M, Okuyama M, et al.
Additional surgical resection after endoscopic mucosal dissection for early gastric cancer: A medium-sized hospital's experience.
Int J Surg. 2016; 36(Pt A):335-341 [PubMed] Related Publications
PURPOSE: In Japan, the majority of early gastric cancers (EGCs) are now treated with endoscopic submucosal dissection (ESD). Patients with non-curative lesions treated by ESD are advised to undergo additional surgical resection (ASR) based on guidelines from the Japan Gastroenterological Endoscopy Society (JGES) and Japanese Gastric Cancer Association (JGCA). However, many studies have demonstrated that residual cancer and lymph node metastasis are only rarely found in ASR specimens. Here we retrospectively analyzed the conditions that could enable the avoidance of unnecessary ASR.
METHODS: The ESD data for 114 absolute indication lesions and 26 lesions of expanded indication lesions were analyzed. The indications and the curability were evaluated according to the JGES/JGCA guidelines.
RESULTS: The rates of non-curative resection and ASR were significantly higher in the expanded indication group compared to the absolute indication group (26.9% and 19.2% vs. 7.9% and 0.9%, respectively). ASR was performed for six patients. Three of their ARS specimens contained neither residual cancer nor lymph node metastasis, and the pathological findings of the preceding ESD specimens deviated slightly from the curative criteria defined by the guidelines. The conditions of the lesions that did not meet the curative criteria were as follows: (1) sm1 invasion of undifferentiated-type lesion <10 mm dia., (2) 21-25 mm dia. mucosal undifferentiated-type lesion, or (3) peacemeal resection with a horizontal margin positive for the mucosal differentiated-type.
CONCLUSIONS: These data suggest that a close follow-up without ASR might be appropriate for patients in the above-mentioned three categories after non-curative ESD for EGC.

Guo CG, Chen YJ, Ren H, et al.
A nomogram for predicting the likelihood of lymph node metastasis in early gastric signet ring cell carcinoma: A single center retrospective analysis with external validation.
Medicine (Baltimore). 2016; 95(46):e5393 [PubMed] Free Access to Full Article Related Publications
Treatment algorithm has not been established for early gastric cancer with signet ring cell carcinoma (SRC), which has a reported low rate of lymph node metastasis (LNM) similar to differentiated cancer. A cohort of 256 patients with early gastric SRC at our center between January 2002 and December 2015 were retrospectively reviewed. Multivariate logistic regression analysis was used to determine the independent factors of LNM. A nomogram for predicting LNM was constructed and internally validated. Additional external validation was performed using the database from Cancer Institute Ariake Hospital in Tokyo (n = 1273). Clinical performance of the model was assessed by decision analysis of curve. The overall LNM incidence was 12.9% (33/256). The multivariate logistic model identified sex, tumor size, and LVI as covariates associated with LNM. Subsequently, a nomogram consisted of sex, tumor size, and depth of invasion was established. The model showed qualified discrimination ability both in internal validation (area under curve, 0.801; 95% confidence interval [CI], 0.729-0.873) and in external dataset (area under curve, 0.707; 95% CI, 0.657-0.758). Based on the nomogram, treatment algorithm for early gastric SRC was proposed to assist clinicians in making better decisions. We developed a nomogram predicting risk of LNM for early gastric SRC, which should be helpful for patient counseling and surgical decision-making.

Ota M, Narumiya K, Kudo K, et al.
Incidence of Esophageal Carcinomas After Surgery for Achalasia: Usefulness of Long-Term and Periodic Follow-up.
Am J Case Rep. 2016; 17:845-849 [PubMed] Free Access to Full Article Related Publications
BACKGROUND Patients with esophageal achalasia are considered to be a high-risk group for esophageal carcinoma, and it has been reported that this cancer often arises at a long interval after surgery for achalasia. However, it is unclear whether esophageal carcinoma is frequent when achalasia has been treated successfully and the patient is without dysphagia. In this study, we reviewed patients with esophageal carcinoma who were detected by regular follow-up after surgical treatment of achalasia.   CASE REPORT Esophageal cancer was detected by periodic upper GI endoscopy in 6 patients. Most of them had early cancers that were treated by endoscopic resection. All 6 patients had undergone surgery for achalasia and the outcome had been rated as excellent or good. Annual follow-up endoscopy was done and the average duration of follow-up until cancer was seen after surgery was 14.3 years (range: 5 to 40 years). Five patients had early cancer. Four cases had multiple lesions.   CONCLUSIONS In conclusion, surgery for achalasia usually improves passage symptoms, but esophageal cancer still arises in some cases and the number of tumors occurring many years later is not negligible. Accordingly, long-term endoscopic follow-up is needed for detection of malignancy at an early stage.

Uemura H, Matsubara N, Kimura G, et al.
Patient preferences for treatment of castration-resistant prostate cancer in Japan: a discrete-choice experiment.
BMC Urol. 2016; 16(1):63 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Up to a fifth of patients diagnosed with prostate cancer (PC) will develop castration-resistant prostate cancer (CRPC), which has been associated with a poor prognosis. The aim of this study was to consider the patient perspective as part of the overall treatment decision-making process for CRPC, given that an alignment between patient preference and prescribing has been shown to benefit patient outcomes. This study examines preferences of patients with CRPC in Japan for treatment features associated with treatments like RA-223, abiraterone, and docetaxel and to examine the extent to which treatment preferences may vary between symptomatic and asymptomatic patients.
METHODS: A two-phase research approach was implemented. In Phase 1, N = 8 patients with CRPC were recruited from a single hospital to complete a qualitative interview to provide feedback on the draft survey. In Phase 2, N = 134 patients with CRPC were recruited from five hospitals to complete a paper survey. The survey included 6 treatment choice questions, each asking patients to choose between two hypothetical treatments for their CRPC. Each treatment alternative was defined by the following attributes: length of overall survival (OS), time to a symptomatic skeletal event (SSE), method of administration, reduction in the risk of bone pain, treatment-associated risk of fatigue and lost work days. A hierarchical Bayesian logistic regression was used to estimate relative preference weights for each attribute level and mean relative importance.
RESULTS: A total of N = 133 patients with CRPC completed the survey and were included in the final analysis. Patients had a mean age of 75.4 years (SD = 7.4) and had been diagnosed with PC a mean of 6.5 years prior (SD = 4.4). Over the attribute levels shown, fatigue (relative importance [RI] = 24.9 %, 95 % CI: 24.7 %, 25.1 %) was the most important attribute, followed by reduction in the risk of bone pain (RI = 23.2 %, 95 % CI: 23.0 %, 23.5 %), and OS (RI = 19.2 %, 95 % CI: 19.0 %, 19.4 %). Although symptomatic patients placed significantly more importance on delaying an SSE (p < .05), no other preference differences were observed.
CONCLUSIONS: CRPC patients were more concerned about reduced quality of life from side effects of treatment rather than extension of survival, which may have implications for shared decision-making between patients and physicians.

Yamamoto-Honda R, Takahashi Y, Yoshida Y, et al.
Body mass index and the risk of cancer incidence in patients with type 2 diabetes in Japan: Results from the National Center Diabetes Database.
J Diabetes Investig. 2016; 7(6):908-914 [PubMed] Free Access to Full Article Related Publications
AIMS/INTRODUCTION: Both type 2 diabetes and obesity increase the risk of some types of cancers, and underlying mechanisms are thought to be, at least in part, common. In the present study, we carried out a retrospective cohort study of the relationship between body mass index (BMI) categories and cancer development in Japanese type 2 diabetic patients.
MATERIALS AND METHODS: A total of 113 incident cancers including 35 cancers whose incidence was reported to be increased by obesity (27 colorectal cancers, two breast cancers in postmenopausal women, one endometrial cancer, four renal cancers and one gallbladder cancer) were identified in 2,334 type 2 diabetic patients (1,616 men and 718 women) over an average observation period of 5.1 years.
RESULTS: In men, there was no significant association between the BMI categories at the start of the observation period and the development of any cancer. In contrast, the incidence of all of the cancers in the women was significantly higher in the group with a BMI of less than 22.0 kg/m(2) (hazard ratio 3.07, 95% CI 1.01-9.36). In either sex, there was no significant relationship between the BMI categories and the development of cancers whose risk is known to be increased by obesity.
CONCLUSIONS: The findings of the present study were limited by the relatively small number of patients in the cohort, which posed a danger of not finding significance. However, the results suggested that obesity did not become an additional risk factor for cancer in Japanese type 2 diabetic patients.

Kitamura H, Takahashi A, Takei F, et al.
Molecular-targeted Therapy and Surgery May Prolong Survival of Renal Cell Carcinoma Patients with Bone Metastasis: A Multi-institutional Retrospective Study in Japan.
Anticancer Res. 2016; 36(10):5531-5536 [PubMed] Related Publications
AIM: To determine prognostic factors for overall survival (OS) in renal cell carcinoma (RCC) patients with bone metastasis in the targeted-therapy era.
PATIENTS AND METHODS: We conducted a retrospective multi-institutional review of the medical records of 149 RCC patients with bone metastasis. Survival was estimated using the Kaplan-Meier method and compared with the log-rank test. Univariate and multivariate Cox proportional hazard regression analyses were performed to identify independent factors associated with OS.
RESULTS: The median OS was 13.4 months. In multivariate analysis, molecular-targeted therapy, nephrectomy and surgery for bone metastasis were independent prognostic factors. Bone-modifying agents (BMAs) were not associated with OS. The median OS of patients receiving molecular-targeted therapy after diagnosis of bone metastasis was significantly better than that of those who did not receive targeted therapy.
CONCLUSION: Molecular-targeted therapy, nephrectomy and surgery for bone metastasis should be considered for RCC patients with metastasis in the bones.

Kato H, Furuya Y, Miyazawa Y, et al.
Consequences of an Early PSA Response to Enzalutamide Treatment for Japanese Patients with Metastatic Castration-resistant Prostate Cancer.
Anticancer Res. 2016; 36(11):6141-6149 [PubMed] Related Publications
BACKGROUND/AIM: Recent studies have shown that an early prostate-specific antigen (PSA) response to androgen receptor (AR)-targeting agents in metastatic castration-resistant prostate cancer (mCRPC) is associated with a better prognosis. We analyzed early PSA response to enzalutamide and oncological outcomes to study their prognostic significance in the Japanese population.
PATIENTS AND METHODS: Fifty-one patients with mCRPC (26 of pre-docetaxel and 25 of post-docetaxel status) were treated with enzalutamide. The PSA progression-free survival (PFS), radiographic PFS (rPFS) and overall survival (OS) were assessed. The association of rPFS and OS in patients with an early PSA response at 4 weeks after commencement of enzalutamide was studied.
RESULTS: Early PSA responses were significantly associated with a longer rPFS (median of 47.9 vs. 20.1 weeks, p<0.001, in patients exhibiting a 50% PSA response; median of 40.9 vs. 20.1 weeks, p=0.016, in patients exhibiting a 30% PSA response). OS was also significantly associated with an early PSA response (p=0.002 for patients exhibiting a 50% PSA response, p=0.003 for patients exhibiting a 30% PSA response). Multivariate analysis showed that the predictors of a 50% PSA response were an interval to mCRPC and a docetaxel treatment history, while the predictor of a 30% PSA response was a docetaxel treatment history. Furthermore, a 50% PSA response was independently prognostic of rPFS.
CONCLUSION: An early PSA response to enzalutamide was significantly associated with a longer rPFS and OS. This information will aid in the management of patients treated with enzalutamide.

Endo Y, Dong Y, Kondo N, et al.
HER2 mutation status in Japanese HER2-positive breast cancer patients.
Breast Cancer. 2016; 23(6):902-907 [PubMed] Related Publications
BACKGROUND: Human epidermal growth factor receptor 2 (HER2) gene amplification/overexpression is a major therapeutic target in breast cancer, and has been introduced as a predictive biomarker to identify patients who may benefit from therapy with anti-HER2 agents. HER2 somatic mutations have been reported, and these may influence the effect of HER2-targeted drugs.
METHODS: Here, we sought HER2 mutations in a group of 135 Japanese breast cancer patients with HER2-positive tumors. We analyzed HER2 mutations by direct Sanger sequencing of two major areas, the extracellular domain at position 309-310 and the kinase domain between 755 and 781.
RESULTS: Two patients with the HER2 somatic mutation S310F in the extracellular domain were found in this series. One patient with the S310F mutation had a node-negative invasive ductal carcinoma classified as HER2 2+ by the HercepTest and fluorescence in situ hybridization (FISH) positive, and which was estrogen receptor (ER)-negative and progesterone receptor (PgR)-negative. Another patient with the S310F mutation had an apocrine carcinoma with seven lymph nodes positive for metastasis, classified as HER2 3+ by the HercepTest, but which was FISH-negative, as well as ER-negative and PgR-negative. Both patients had received adjuvant single-agent trastuzumab therapy, and had no local recurrence or distant metastasis for five and three years after surgery, respectively.
CONCLUSIONS: Our data show that HER2 mutations are rare in HER2-positive Japanese breast cancer patients. The two mutations found in this study were identical, S310F. We suggest that in vitro experiments to determine whether the S310F mutation could be involved in resistance to anti-HER2 drugs are worthwhile in future.

Nose T, Otani Y, Asahi S, et al.
A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using interstitial brachytherapy: clinical results with a median follow-up of 26 months.
Breast Cancer. 2016; 23(6):861-868 [PubMed] Related Publications
BACKGROUND: A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using interstitial brachytherapy was performed. The first clinical results were reported with a median follow-up of 26 months.
PATIENTS AND METHODS: Forty-six female breast cancer patients with positive hormone receptors and tumors ≤3 cm, pN0M0, completed the protocol treatment. After breast-conserving surgery and histological confirmation of negative surgical margins and pN0, brachytherapy applicators were implanted either postoperatively (n = 45) or intraoperatively (n = 1). High-dose-rate brachytherapy of 36 Gy/6 fractions was delivered. All clinical data were prospectively collected using case report forms and the Common Terminology Criteria for Adverse Events ver.3.0.
RESULTS: At the median follow-up of 26 months, no breast cancer recurrence of any type was observed. Sequelae ≥G2 were dermatitis (G2, 7 %), fibrosis (G2, 11 %; G3, 4 %), fracture (G2, 2 %), pain (G2, 7 %; G3, 2 %), and soft tissue necrosis (G2, 6 %). Cosmetic outcomes evaluated by excellent/good scores were 100 % at pre-therapy (n = 46), 94 % at 12 months (n = 46), and 81 % at 24 months (n = 36), respectively.
CONCLUSIONS: Disease control and sequelae were satisfactory due to the strict eligibility and protocol-defined treatment parameters. The cosmetic outcomes were comparable to those of previous Japanese breast-conserving therapy series.

Watanabe Y, Iwamura A, Shimada YJ, et al.
Transforming Growth Factor-β1 as a Predictor for the Development of Hepatocellular Carcinoma: A Nested Case-Controlled Study.
EBioMedicine. 2016; 12:68-71 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Transforming growth factor-β1 (TGF-β1) reportedly acts as a tumor suppressor in tumorigenesis. However, little is known as to how TGF-β1 concentrations change prior to the development of hepatocellular carcinoma (HCC) in humans. We examined the association between the serum TGF-β1 concentrations and death from HCC to determine whether the serum TGF-β1 can be a predictor of incident HCC.
METHODS: We conducted a nested case-controlled study of participants in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. We used a conditional logistic regression analysis to estimate the adjusted relative risks (aRRs) of death from HCC according to the serum TGF-β1 concentrations among 1940 participants including 83 patients with HCC and 1857 controls matched for age, sex, and hepatitis C virus (HCV)-antibody seropositivity.
FINDINGS: When serum TGF-β1 was modelled as a continuous variable, the aRR of death from HCC associated with a decrement of 7.9ng/mL (one standard deviation) in the serum TGF-β1 concentrations was 2.3 (95% CI 1.7-3.0, P<0.001) for all the subjects. The area under the receiver operating characteristic curve for the serum TGF-β1 concentrations was 0.78 (P<0.05).
INTERPRETATION: Our finding suggests that TGF-β1 serves as a predictor for HCC.

Matsuda S, Takeuchi H, Kawakubo H, et al.
Current Advancement in Multidisciplinary Treatment for Resectable cStage II/III Esophageal Squamous Cell Carcinoma in Japan.
Ann Thorac Cardiovasc Surg. 2016; 22(5):275-283 [PubMed] Free Access to Full Article Related Publications
Multidisciplinary treatment comprising surgery, chemotherapy, and radiotherapy for resectable esophageal squamous cell carcinoma (ESCC) is widely used with improved prognosis. Transthoracic esophagectomy (TTE) with extended lymph node (LN) dissection, known as three field LN dissection, has been recommended for ESCC using open thoracotomy or the thoracoscopic approach. The Japan Clinical Oncology Group (JCOG) trial (JCOG1409) is investigating the patients' long term survival using the thoracoscopic approach that has been shown to reduce the incidence of postoperative respiratory complication. For perioperative treatment, neoadjuvant chemotherapy using cisplatin plus 5-fluorouracil (5-FU), has been accepted as the standard of care in Japan based on the JCOG9907 trial. In Western countries, neoadjuvant chemoradiotherapy was shown to prolong overall survival for esophageal cancer, including ESCC. Although surgery has been recognized as an initial curative treatment for esophageal cancer, definitive chemoradiotherapy is an alternative treatment for patients who are unable to undergo thoracotomy or who decline to undergo surgery. This article reviews multidisciplinary treatment advances for ESCC. However, current standard treatments are country dependent and the ongoing trial may help standardize ESCC treatment across various societies.

Arizumi T, Ueshima K, Iwanishi M, et al.
Validation of Kinki Criteria, a Modified Substaging System, in Patients with Intermediate Stage Hepatocellular Carcinoma.
Dig Dis. 2016; 34(6):671-678 [PubMed] Related Publications
BACKGROUND: The standard treatment option that is available for patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) is transarterial chemoembolization (TACE). However, the condition of the patients with BCLC stage B disease is heterogeneous showing different tumor statuses and Child-Pugh scores; treatment strategies other than TACE are frequently employed for the patients in this stage. Based on the subclassification system proposed by Bolondi et al. [Semin Liver Dis 2012;32:348-359], we developed the Kinki criteria focusing on a substaging for BCLC stage B disease, which is simpler and should be more suitable in actual clinical setting in Japan. In this study, we evaluated the performance of Kinki criteria.
SUMMARY: This study included 1,633 HCC patients who received first-line treatment at the Kindai University Hospital. Patients were classified into subgroups based on the Kinki criteria and the survival time was estimated for each group. There were 156 (33.3%) patients in subclass B1, 278 (59.3%) in B2, and 35 (7.4%) in B3. The median overall survival times and 95% CI for BCLC B subclasses B1, B2, and B3 were 4.3 years (3.7-4.9), 2.9 years (2.2-3.4), and 1.1 years (0.5-1.8), respectively (p < 0.001). Key Messages: Classification of HCC patients in BCLC stage B based on the Kinki criteria showed statistically significant differences in survival, indicating the performance of Kinki criteria, which takes Child-Pugh score and tumor status into account for determining treatment options for HCC in BCLC stage B.

Ohya E, Mizutani M, Sakaguchi H, Sekine T
Diffuse Large B-cell Lymphoma during Corticosteroid Therapy for TAFRO Syndrome.
Intern Med. 2016; 55(19):2861-2867 [PubMed] Free Access to Full Article Related Publications
Thrombocytopenia, anasarca, myelofibrosis, renal dysfunction and organomegaly (TAFRO) syndrome is a variant of Castleman's disease recently identified in Japan. A 73-year-old man was diagnosed with TAFRO syndrome according to clinical findings, and his symptoms improved after corticosteroid therapy. Ten months later, lymphadenopathy worsened during tapering of corticosteroids. Histological findings of abdominal lymph nodes showed diffuse large B-cell lymphoma. After 6 cycles of R-CHOP therapy, he has remained in sustained complete remission. This is a rare case of the development of malignant lymphoma during the treatment of TAFRO syndrome, which suggests an association between diffuse large B-cell lymphoma and TAFRO syndrome.

Kumondai M, Hosono H, Orikasa K, et al.
CYP2A13 Genetic Polymorphisms in Relation to the Risk of Bladder Cancer in Japanese Smokers.
Biol Pharm Bull. 2016; 39(10):1683-1686 [PubMed] Related Publications
Tobacco-specific nitrosamines including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosonornicotine (NNN), which can be activated by the metabolic enzyme CYP2A13, are potent procarcinogens. Smoking plays a role in carcinogenesis in the human bladder, which expresses CYP2A13 at a relatively high level. Numerous genetic polymorphisms of CYP2A13 causing amino acid substitution might reduce CYP2A13 metabolic activity toward NNK and NNN, resulting in decreased susceptibility to bladder cancer. The aim of this study was to reveal any association between bladder cancer development and CYP2A13 genetic polymorphisms in Japanese smokers. The CYP2A13 genotype of each subject (163 bladder cancer patients and 161 controls) was determined by next-generation sequencing (NGS) of the full CYP2A13 gene. All samples were genotyped for five CYP2A13 variant alleles (CYP2A13*2, *3, *4, *6, *7). Based on biological logistic regression, the odds ratio (95% confidence interval) for the CYP2A13*1/*2 genotype was 0.34 (0.17-0.69). Thus, CYP2A13 genetic polymorphisms might play important roles in the development of bladder cancer in Japanese smokers.

Nasirden A, Saito T, Fukumura Y, et al.
In Japanese patients with papillary thyroid carcinoma, TERT promoter mutation is associated with poor prognosis, in contrast to BRAF (V600E) mutation.
Virchows Arch. 2016; 469(6):687-696 [PubMed] Related Publications
The prognostic value of BRAF (V600E) and TERT promoter mutation in papillary thyroid carcinoma (PTC) is controversial. We examined alterations in BRAF (V600E) and TERT promoter by PCR-direct sequencing in PTC of 144 Japanese patients. Alternative lengthening of telomeres was examined as another mechanism of telomere maintenance by immunohistochemical staining for ATRX and DAXX. Of the clinicopathological characteristics, regional lymph node metastasis, extra-thyroid extension, multifocality/intrathyroidal spread, and advanced stage (III/V) were associated with shorter disease-free survival rate (DFSR). TERT promoter mutation was found in eight patients (6 %), and this was significantly associated with total thyroidectomy, multifocality/intrathyroidal spread, lymph node metastasis and advanced stage. The BRAF (V600E) mutation was found in 53 patients (38.2 %) but was not associated with any clinicopathological factors. TERT mutations were not correlated with BRAF (V600E) mutation status. TERT mutation-positive tumors (TERT+) showed lower DFSR than BRAF (V600E) -mutation-positive tumors (BRAF (V600E) +), and TERT+/BRAF (V600E) + tumors showed lower DFSR than BRAF (V600E) + tumors. No cases showed loss of ATRX/DAXX expression by immunohistochemistry. TERT promoter mutations showed a lower prevalence in our series and appeared to be associated with aggressive behavior. In PTCs, telomerase activation by TERT promoter mutation might be more important than alternative lengthening of telomeres.

Hiyama E, Hishiki T, Watanabe K, et al.
Resectability and tumor response after preoperative chemotherapy in hepatoblastoma treated by the Japanese Study Group for Pediatric Liver Tumor (JPLT)-2 protocol.
J Pediatr Surg. 2016; 51(12):2053-2057 [PubMed] Related Publications
BACKGROUND/PURPOSE: We aimed to clarify whether surgical resectability and tumor response after preoperative chemotherapy (preCTx) represented prognostic factors for patients with hepatoblastoma (HBL) in the JPLT-2 study (1999-2012).
METHODS: Patients (N=342) with HBL who underwent preCTx were eligible. PRETEXT, CHIC risk stratification (standard [SR], intermediate [IR] and high risk [HR]) at diagnosis, POST-TEXT, and tumor resectability were evaluated by imaging. Tumor response was classified into responders (CR or PR) and nonresponders (NC or PD) according to RECIST criteria.
RESULTS: There were 7 PRETEXT I, 106 II, 143 III, and 86 IV, including 71 metastatic HBLs. In POST-TEXT, 12 PRETEXT II, 42 III, and 58 IV were down-staged. The 5-year EFS/OS rates of 198 SR, 73 IR, and 71 HR-HBLs were 82/94%, 49/64%, and 28/34%, respectively. In 198 SR, 154 of 160 responders and 24 of 38 nonresponders survived event-free (P<0.01). In 73 IR, 12 of 24 whose tumors remained unresectable experienced recurrence, 9 of whom were nonresponders (P<0.01). In 71 HR, chemoresponders and tumor resectability after preCTx correlated with favorable outcomes (P<0.05).
CONCLUSIONS: Evaluation of response and tumor resectability after preCTx is useful for predicting prognosis in HBLs. To improve outcomes, we should reconsider surgical procedures according to resectability and chemoresponsiveness.
LEVEL OF EVIDENCE: Level II.

Sugiyama Y, Sasaki H, Komatsu K, et al.
A Multi-Institutional Feasibility Study on the Use of Automated Screening Systems for Quality Control Rescreening of Cervical Cytology.
Acta Cytol. 2016; 60(5):451-457 [PubMed] Related Publications
OBJECTIVE: To evaluate the efficacy of the automated screening system FocalPoint for cervical cytology quality control (QC) rescreening. False-negative rates (FNRs) were evaluated by a multi-institutional retrospective study.
STUDY DESIGN: Cervical cytology slides that had already been reported as negative for intraepithelial lesion or malignancy (NILM) were chosen arbitrarily for FocalPoint rescreening. Slides stratified into the highest 15% probability of being abnormal were rescreened by a cytotechnologist. The slides that were abnormal were reevaluated by a cytopathologist to be false negatives.
RESULTS: Rescreening of 12,000 slides, i.e. 9,000 conventional slides and 3,000 liquid-based cytology (LBC) slides, was performed; 9,826 (7,393 conventional and 2,433 LBC) were satisfactory for FocalPoint (2,174 were determined unsatisfactory) and those within the highest 15% of probability (1,496, i.e. 1,123 conventional and 373 LBC) were rescreened. As a result, 117 (96 conventional and 21 LBC) were determined as abnormal (other than NILM) and the FNR was 1.19%. Among these 117 slides, 40 (35 conventional and 5 LBC) were determined as high-grade squamous intraepithelial lesion and greater (HSIL+).
CONCLUSION: Of 117 (1.19%) abnormal slides detected, 40 (0.41%) were determined to be HSIL+. This result suggests that FocalPoint is effective for QC rescreening of cervical cytology.

Nakaji Y, Oki E, Nakanishi R, et al.
Prognostic value of BRAF V600E mutation and microsatellite instability in Japanese patients with sporadic colorectal cancer.
J Cancer Res Clin Oncol. 2017; 143(1):151-160 [PubMed] Related Publications
PURPOSE: In colorectal cancer (CRC), the BRAF V600E mutation is an important biomarker for poor prognosis, while high microsatellite instability (MSI-H) indicates good prognosis. Using a commercial BRAF V600E-specific antibody, we investigated the BRAF V600E mutation according to immunohistochemistry (IHC) and the MSI status in Japanese patients with CRC.
METHODS: In this retrospective study, tissue samples from 472 Japanese patients with CRC, stratified for MSI, were analyzed to determine the prognostic value of BRAF V600E, as assessed using IHC. Mutations in 254 patients were evaluated using the direct sequencing method to check for concordance.
RESULTS: The frequency of MSI-H was 9.3 % (44/472), and BRAF V600E mutation was detected immunohistochemically in 8.7 % patients (41/472). The sensitivity and specificity for detection of BRAF V600E mutations by IHC were 100 % (17/17) and 98.7 % (234/237), respectively. BRAF V600E mutations were significantly correlated with the anatomical tumor site (P = 0.0035), histological type (P < 0.0001), and MSI status (P < 0.0001). Consistent with other published series, patients with BRAF V600E mutation exhibited a significantly shorter overall survival (hazard ratio = 1.500, P = 0.0432). In particular, the microsatellite stable/BRAF mutation group had inferior prognosis compared with the MSI-H/BRAF wild-type group (hazard ratio = 2.621, P = 0.0004).
CONCLUSIONS: IHC using a BRAF V600E-specific antibody was useful for diagnosis and concurred with direct sequencing results. CRC cases could be stratified by combining BRAF V600E mutation and MSI status as a prognostic factor in Japanese patients.

Kaida H, Azuma K, Kawahara A, et al.
The correlation between FDG uptake and biological molecular markers in pancreatic cancer patients.
Eur J Radiol. 2016; 85(10):1804-10 [PubMed] Related Publications
PURPOSE: We examined whether fluorine-18 fluorodeoxyglucose (FDG) uptake is related to the mammalian target of rapamycin (mTOR) signal pathway and its related proteins in pancreatic cancer patients.
METHODS: We retrospectively studied 53 pancreatic cancer patients who underwent FDG positron emission tomography (PET) or FDG PET/CT, and complete curative surgical resection. The SUV max, the tumor to nontumor activity of pancreas [T/N (P)] ratio and the T/N of liver [T/N (L)] ratio were calculated. The expressions of glucose transporter-1(Glut-1) and mTOR pathway proteins in pancreas cell lines were examined by immune blots. Excised tumor tissue was analyzed by immunohistochemistry using monoclonal antibodies for Glut-1, epidermal growth factor receptor (EGFR), mTOR, p70S6kinase (p70S6) and S6 ribosomal protein (S6).
RESULTS: The expressions of Glut-1, EGFR and p70S6 were significantly correlated with the SUV max, T/N (P) ratio and T/N (L) ratio. The expressions of mTOR and S6 were not correlated with all parameters. The expression of Glut-1 was positively correlated with the expressions of EGFR and p70S6, but not with mTOR or S6. S6 was positively correlated with p70S6.
CONCLUSIONS: Glut-1, EGFR and p70S6 expressions are associated with the FDG uptake mechanism of pancreatic cancer. FDG uptake may predict the levels of EGFR and p70S6 expressions, and FDG uptake reflects glucose metabolism and cancer progression.

Adachi Y, Nojima M, Mori M, et al.
Insulin-like growth factor-related components and the risk of liver cancer in a nested case-control study.
Tumour Biol. 2016; 37(11):15125-15132 [PubMed] Related Publications
Insulin-like growth factor-1 (IGF1) is a potent mitogen. IGF-binding protein-3 (IGFBP3) binds and inhibits IGF1. High circulating IGF1 levels and low IGFBP3 levels are associated with increased risk of several cancers. We examined relationships between serum levels of these factors and hepatoma risk in a case-control study nested in a prospective cohort study (the Japan Collaborative Cohort Study (JACC Study)). A baseline survey was conducted from 1988 to 1990, and 39,242 subjects donated blood samples. Participants diagnosed with hepatoma by 1997 were considered cases for nested case-control studies. Ninety-one cases and 263 sex- and age-matched controls were analyzed. A conditional logistic model was used to estimate odds ratios (ORs) for the incidence of hepatoma associated with serum IGF1 and IGFBP3 levels. Neither IGF1 nor the molar ratio of IGF1/IGFBP3 was correlated with hepatoma risk. After adjustment for hepatitis viral infection, body mass index, smoking, and alcohol intake, a higher molar difference of (IGFBP3 - IGF1) was associated with a decreased hepatoma risk more than IGFBP3 alone (p for trend <0.001 and = 0.003, respectively). People in the highest quartile had a lower risk (OR = 0.098; 95 % confidence interval = 0.026-0.368). In subgroup analyses of males and females, the molar difference was associated with a decreased hepatoma risk (p for trend <0.05). In non-elderly individuals, the difference was inversely correlated with the incidence of hepatoma (p for trend <0.01). The molar difference of (IGFBP3 - IGF1) may be inversely associated with the incidence of hepatoma.

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