Showing papers in "International Journal of Clinical Oncology in 2016"

PD-1/PD-L1 blockade in cancer treatment: perspectives and issues

Abstract: Recent studies showed that tumor cells ‘edit’ host immunity in several ways to evade immune defenses in the tumor microenvironment. This phenomenon is called “cancer immune escape.” One of the most important components in this system is an immunosuppressive co-signal (immune checkpoint) mediated by the PD-1 receptor and its ligand, PD-L1. PD-1 is mainly expressed on activated T cells, whereas PD-L1 is expressed on several types of tumor cells. Preclinical studies have shown that inhibition of the interaction between PD-1 and PD-L1 enhances the T-cell response and mediates antitumor activity. Several clinical trials of PD-1/PD-L1 signal-blockade agents have exhibited dramatic antitumor efficacy in patients with certain types of solid or hematological malignancies. In this review, we highlight recent clinical trials using anti-PD-1 or anti-PD-L1 antibodies against several types of malignancies, including a trial conducted in our department, and describe the clinical perspectives and issues regarding the PD-1/PD-L1 blockade in cancer treatment.

Tumor angiogenesis--characteristics of tumor endothelial cells.

Abstract: Tumor blood vessels provide nutrition and oxygen to the tumor, resulting in tumor progression. They also act as gatekeepers, inducing tumor metastasis. Thus, targeting tumor blood vessels is an important strategy in cancer therapy. Tumor endothelial cells (TECs), which line the inner layer of blood vessels of the tumor stromal tissue, are the main targets of anti-angiogenic therapy. Because new tumor blood vessels generally sprout from pre-existing vasculature, they have been considered to be the same as normal blood vessels. However, tumor blood vessels demonstrate a markedly abnormal phenotype that includes several important morphological changes. The degree of angiogenesis is determined by the balance between the angiogenic stimulators and inhibitors released by the tumor and host cells. Recent studies have revealed that TECs also exhibit altered characteristics which depend on the tumor microenvironment. Here, we review recent studies on TEC abnormalities and heterogeneity with respect to tumor progression and consider their therapeutic implications.

Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of ovarian cancer including primary peritoneal cancer and fallopian tube cancer

Abstract: The fourth edition of the Japan Society of Gynecologic Oncology guidelines for the treatment of ovarian cancer including primary peritoneal cancer and fallopian tube cancer was published in 2015. The guidelines contain seven chapters and six flow charts. The major changes in this new edition are as follows—(1) the format has been changed from reviews to clinical questions (CQ), and the guidelines for optimal clinical practice in Japan are now shown as 41 CQs and answers; (2) the ‘flow charts’ have been improved and placed near the beginning of the guidelines; (3) the ‘basic points’, including tumor staging, histological classification, surgical procedures, chemotherapy, and palliative care, are described before the chapter; (4) the FIGO surgical staging of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer was revised in 2014 and the guideline has been revised accordingly to take the updated version of this classification into account; (5) the procedures for examination and management of hereditary breast and ovarian cancer are described; (6) information on molecular targeting therapy has been added; (7) guidelines for the treatment of recurrent cancer based on tumor markers alone are described, as well as guidelines for providing hormone replacement therapy after treatment.

Basics of PD-1 in self-tolerance, infection, and cancer immunity

Abstract: Successful cancer treatment requires understanding host immune response against tumor cells. PD-1 belongs to the CD28 superfamily of receptors that work as "checkpoints" of immune activation. PD-1 maintains immune self-tolerance to prevent autoimmunity and controls T-cell reaction during infection to prevent excessive tissue damage. Tumor cells that arise from normal tissue acquire mutations that can be targeted by lymphocytes. Accumulating lines of evidence suggest that tumor cells evade host immune attack by expressing physiological PD-1 ligands and stimulating PD-1 on the lymphocytes. Based on this idea, researchers have successfully demonstrated that systemic administration of monoclonal antibodies that inhibit the binding of PD-1 to the ligands reactivated T cells and augmented the anti-cancer immune response. In this review, I summarize the basics of T-cell biology and its regulation by PD-1 and discuss the current understanding and questions about this multifaceted molecule.

Japanese Society of Clinical Oncology clinical practice guidelines 2010 for antiemesis in oncology: executive summary

Abstract: The purpose of this article is to disseminate the standard of antiemetic therapy for Japanese clinical oncologists. On the basis of the Appraisal of Guidelines for Research and Evaluation II instrument, which reflects evidence-based clinical practice guidelines, a working group of the Japanese Society of Clinical Oncology (JSCO) reviewed clinical practice guidelines for antiemesis and performed a systematic review of evidence-based domestic practice guidelines for antiemetic therapy in Japan. In addition, because health-insurance systems in Japan are different from those in other countries, a consensus was reached regarding standard treatments for chemotherapy that induce nausea and vomiting. Current evidence was collected by use of MEDLINE, from materials from meetings of the American Society of Clinical Oncology National Comprehensive Cancer Network, and from European Society of Medical Oncology/Multinational Association of Supportive Care in Cancer guidelines for antiemesis. Initially, 21 clinical questions (CQ) were selected on the basis of CQs from other guidelines. Patients treated with highly emetic agents should receive a serotonin (5-hydroxytryptamine; 5HT3) receptor antagonist, dexamethasone, and a neurokinin 1 receptor antagonist. For patients with moderate emetic risk, 5HT3 receptor antagonists and dexamethasone were recommended, whereas for those receiving chemotherapy with low emetic risk dexamethasone only is recommended. Patients receiving high-emetic-risk radiation therapy should also receive a 5HT3 receptor antagonist. In this paper the 2010 JSCO clinical practice guidelines for antiemesis are presented in English; they reveal high concordance of Japanese medical circumstances with other antiemetic guidelines that are similarly based on evidence.

Efficacy of aprepitant for the prevention of chemotherapy-induced nausea and vomiting with a moderately emetogenic chemotherapy regimen: a multicenter, placebo-controlled, double-blind, randomized study in patients with gynecologic cancer receiving paclitaxel and carboplatin

Abstract: Substance P contributes to the hypersensitivity reaction (HSR) to paclitaxel in a rat model. Aprepitant acts as an inhibitor of the binding of substance P to the neurokinin-1 receptor and, consequently, may reduce the frequency of paclitaxel-induced HSR. While aprepitant has a prophylactic effect against vomiting caused by high-dose cisplatin, the benefits of aprepitant have not been clearly demonstrated in patients receiving paclitaxel and carboplatin (TC) combination chemotherapy. We conducted a multicenter, placebo-controlled, double-blind, randomized study in Japanese patients with gynecologic cancer who received TC combination chemotherapy. Patients received aprepitant or placebo together with both a 5-HT3 receptor antagonist and dexamethasone prior to chemotherapy. The primary endpoint was the proportion of patients with HSR, and the secondary endpoints were the proportion of patients with “no vomiting”, “no significant nausea”, and complete response, respectively. Of the 324 randomized patients, 297 (151 in the aprepitant group; 146 in the placebo group) were evaluated. The percentage of patients with HSR (9.2 vs. 7.5 %, respectively; P = 0.339) was not significantly different between the groups. The percentage of “no vomiting” patients (78.2 vs. 54.8 %; P < 0.0001), “no significant nausea” patients (85.4 vs. 74.7 %; P = 0.014), and patients showing complete response (61.6 vs. 47.3 %, P = 0.0073) was significantly higher in the aprepitant group than in the placebo group. The administration of aprepitant did not have a prophylactic effect on the HSR but was effective in reducing nausea and vomiting in gynecologic cancer patients receiving TC combination chemotherapy.

The molecular mechanism of human papillomavirus-induced carcinogenesis in head and neck squamous cell carcinoma

Abstract: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Recently, the incidence of oropharyngeal cancer (OPC) has increased markedly in comparison to that of HNSCC, which is associated with the use of tobacco or alcohol or both. This increase has resulted mainly from the global rise in the number of human papillomavirus (HPV)-related oropharyngeal cancers (HPV-OPCs). HPV-OPC has several unique characteristics, including presentation in younger patients, better response rates to treatment, and better prognosis compared to alcohol- and smoking-related HNSCC. HPV infection status is now an independent prognostic factor for survival in patients with OPC. In general, HPV oncoproteins E6 and E7 are the primary viral factors responsible for the initiation and progression of HPV-related cancers via the inactivation of p53 and pRb. However, alterations in additional factors, including genomic instability, HPV DNA integration, and epigenetic alterations, could be equally important for neoplastic transformation and tumor progression. The impact of genomic instability and external environmental factors on the initiation of cervical cancer development through high-risk HPV infection has been well characterized, although less is known about the mechanism underlying HPV-induced carcinogenesis in HNSCC. This review provides an overview of the biology and molecular mechanisms of HPV-related cancers, including a particular focus on several recent studies on the comprehensive characterization of genomic alterations in HPV-associated HNSCC.

Trimodality strategy for treating malignant pleural mesothelioma: results of a feasibility study of induction pemetrexed plus cisplatin followed by extrapleural pneumonectomy and postoperative hemithoracic radiation (Japan Mesothelioma Interest Group 0601 Trial)

Abstract: Purpose We conducted a prospective multi-institutional study to determine the feasibility of trimodality therapy (TMT) comprising induction chemotherapy followed by extrapleural pneumonectomy (EPP) and radiation therapy in Japanese patients with malignant pleural mesothelioma (MPM).

Research misconduct and data fraud in clinical trials: prevalence and causal factors

Abstract: The disclosure of cases of research misconduct in clinical trials, conventionally defined as fabrication, falsification or plagiarism, has been a disturbingly common phenomenon in recent years. Such cases can potentially harm patients enrolled on the trials in question or patients treated based on the results of those trials and can seriously undermine the scientific and public trust in the validity of clinical trial results. Here, I review what is known about the prevalence of research misconduct in general and the contributing or causal factors leading to the misconduct. The evidence on prevalence is unreliable and fraught with definitional problems and with study design issues. Nevertheless, the evidence taken as a whole seems to suggest that cases of the most serious types of misconduct, fabrication and falsification (i.e., data fraud), are relatively rare but that other types of questionable research practices are quite common. There have been many individual, institutional and scientific factors proposed for misconduct but, as is the case with estimates of prevalence, reliable empirical evidence on the strength and relative importance of these factors is lacking. However, it seems clear that the view of misconduct as being simply the result of aberrant or self-delusional personalities likely underestimates the effect of other important factors and inhibits the development of effective prevention strategies.

Sarcopenia, but not visceral fat amount, is a risk factor of postoperative complications after major hepatectomy

Abstract: Major hepatectomy is associated with significant morbidity and mortality rates, particularly in patients aged more than 70 years This study assessed whether physical indicators, such as sarcopenia and visceral fat amount, could predict morbidity and mortality after major hepatectomy The study enrolled 144 patients who underwent curative major hepatectomy Skeletal muscle and visceral fat amount at the third lumbar vertebra (L3) in the inferior direction were quantified using enhanced computed tomography scans The patients were divided into two subgroups, with and without sarcopenia, based on median skeletal muscle mass in men and women (432 cm2/m2 in men; 353 cm2/m2 in women) The study included 108 men and 36 women, with median skeletal muscle tissue of 432 and 353 cm2/m2, respectively The mortality rate was significantly higher in patients with than without sarcopenia [seven cases (97 %), one case (14 %), respectively; P = 0021], whereas liver-related morbidity and mortality rates were similar In patients aged >70 years, the morbidity, liver dysfunction-related morbidity, and mortality rates were significantly higher in patients with than without sarcopenia (P < 005 each) In contrast, surgical outcomes were similar in patients with high and low visceral fat amounts Sarcopenia was a risk factor for postoperative complications after major hepatectomy, particularly in elderly patients

Japan Society of Gynecologic Oncology Guidelines 2013 for the Treatment of Uterine Body Neoplasms

Abstract: The third version of the Japan Society of Gynecologic Oncology guidelines for the treatment of uterine body neoplasms was published in 2013. The guidelines comprise nine chapters and nine algorithms. Each chapter includes a clinical question, recommendations, background, objectives, explanations, and references. This revision was intended to collect up-to-date international evidence. The highlights of this revision are to (1) newly specify costs and conflicts of interest; (2) describe the clinical significance of pelvic lymph node dissection and para-aortic lymphadenectomy, including variant histologic types; (3) describe more clearly the indications for laparoscopic surgery as the standard treatment; (4) provide guidelines for post-treatment hormone replacement therapy; (5) clearly differentiate treatment of advanced or recurrent cancer between the initial treatment and the treatment carried out after the primary operation; (6) collectively describe fertility-sparing therapy for both atypical endometrial hyperplasia and endometrioid adenocarcinoma (corresponding to G1) and newly describe relapse therapy after fertility-preserving treatment; and (7) newly describe the treatment of trophoblastic disease. Overall, the objective of these guidelines is to clearly delineate the standard of care for uterine body neoplasms in Japan with the goal of ensuring a high standard of care for all Japanese women diagnosed with uterine body neoplasms.

Prognostic factors in patients with uterine carcinosarcoma: a multi-institutional retrospective study from the Japanese Gynecologic Oncology Group

Abstract: Uterine carcinosarcomas (UCSs) are rare and aggressive tumors. The prognostic factors are not sufficiently known. We performed a multi-institutional, retrospective study of women with stage I–IV UCS, diagnosed between 2007 and 2012. Data obtained from medical records included demographic, clinicopathological, treatment, and outcome information. A total of 486 patients (median age 65 years) were identified—224 (46 %) were stage I, 32 (7 %) were stage II, 139 (28 %) were stage III, and 91 (19 %) were stage IV. Among them, 277 (57 %) had disease recurrence. Median disease-free survival (DFS) was 16.4 months [95 % confidence interval (CI) 15.7–27.2], and median overall survival (OS) was 72.0 months (95 % CI 43.0–not reached). In total, 454 (94 %) patients received adjuvant treatment, and 440 (91 %) received adjuvant chemotherapy. In multivariate analysis, stage III–IV disease, CA-125 level, and lymphovascular space invasion (LVSI) were significantly associated with shorter median DFS. Stage III–IV disease, performance status 2–4, ≥50 % myometrial invasion depth, and postsurgical residual tumor size >1 cm were significantly associated with shorter median OS. Conversely, pelvic lymph node lymphadenectomy was associated with improved DFS and OS. Stage, performance status, CA-125 level, LVSI, and myometrial invasion were associated with poor prognoses. Pelvic lymphadenectomy was associated with improved survival, and may be necessary for the surgical management of UCS.

Implication of programmed cell death ligand 1 expression in tumor recurrence and prognosis in rectal cancer with neoadjuvant chemoradiotherapy.

Abstract: Programmed cell death ligand 1 (PD-L1) regulates immune responses through interaction with its receptor. PD-L1 is not only a predictor of poor prognosis but also a new therapeutic target in several malignancies. Neoadjuvant chemoradiotherapy (CRT) is an effective tool for local control of rectal cancer, but the disease recurrence rate remains high. The aim of this study was to retrospectively evaluate the correlation between PD-L1 expression and clinicopathological variables in rectal cancer after neoadjuvant CRT. A total of 90 rectal cancer patients who underwent neoadjuvant CRT were enrolled in this study. We evaluated PD-L1 expression using immunohistochemistry. Moreover, we investigated the correlation between PD-L1 expression and tumor-infiltrating T cells, and between CD8- and Foxp3-positive cells. Patients with high PD-L1 expression more frequently had vascular invasion and tumor recurrence compared to patients with low PD-L1 expression (P = 0.0225 and P = 0.0051). High PD-L1 expression was significantly associated with poor recurrence-free and overall survival (P = 0.0027 and P = 0.0357). Multivariate analysis revealed lymph node metastasis and high PD-L1 expression as independent risk factors for tumor recurrence (P = 0.0102 and P = 0.0374). Numbers of infiltrating CD8-positive cells in patients with high PD-L1 expression were significantly lower than in patients with low PD-L1 expression (P = 0.0322). Our data suggest that inhibition of PD-L1 may be a new immunotherapeutic strategy to reduce tumor recurrence and improve prognosis in patients with rectal cancer after neoadjuvant CRT.

Prognostic value of glucosylceramide synthase and P-glycoprotein expression in oral cavity cancer.

Abstract: Glucosylceramide synthase (GCS) and P-glycoprotein (P-gp) overexpression are associated with multidrug resistance in several human cancers. This study investigated the prognostic value of GCS and P-gp in oral cavity squamous cell carcinoma (OSCC). The association between GCS and P-gp overexpression and clinical outcomes was assessed in 186 human clinical specimens of primary tumors obtained from curative surgery. Immunohistochemistry staining results were scored as high or low for GCS, and positive or negative for P-gp. Univariate and multivariate analyses using the Cox proportional hazards model were conducted to assess the significance of differences in recurrence or survival outcomes between variables. GCS overexpression was observed in 128 (68.8 %) patients and P-gp overexpression in 43 (23.1 %) patients. High GCS expression was significantly correlated with P-gp immunopositivity (P = 0.005). GCS and P-gp overexpression was significantly correlated with cervical nodal metastasis (P < 0.05). Univariate analyses showed that tumor lymphovascular invasion, positive neck lymph nodes, advanced overall TNM stage, high GCS expression, and P-gp immunopositivity were associated with poor locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) (P < 0.05). Multivariate analyses showed that lymphovascular invasion, nodal positivity, and P-gp overexpression remained independent prognostic variables for LRC, DFS, and OS, and that GCS expression was an independent predictor of LRC and DFS (P < 0.05). GCS and P-gp expression is associated with poor prognosis, suggesting suitability as novel biomarkers in OSCC.

Colorectal cancer in young patients: is it a distinct clinical entity?

Abstract: Background The incidence of colorectal cancer in young patients is increasing. It remains unclear if the disease has unique features in this age group.

Quantitative analysis of the BRAF V600E mutation in circulating tumor-derived DNA in melanoma patients using competitive allele-specific TaqMan PCR

Abstract: BRAF V600E is a common mutation in melanoma, and BRAF inhibitors are effective in treating of BRAF mutation-positive melanoma. DNA carrying this mutation is released from melanoma cells into the circulation. As such, circulating tumor-derived DNA (ctDNA) in peripheral blood represents a novel biomarker for evaluating tumor features in cancer patients. However, ctDNA is present in the peripheral blood at very low levels, which makes the detection of specific mutations in this DNA a challenge. Competitive allele-specific TaqMan PCR (castPCR), a straightforward commercially available assay, is a sensitive technique for quantitating a small amount of DNA. The level of BRAF V600E ctDNA was quantified by castPCR in 26 consecutive plasma samples from six melanoma patients. The castPCR assay was performed using a mixture of BRAF V600E DNA and BRAF wild DNA and found to be able to detect BRAF V600E at a fractional abundance of ≥0.5 % in 2- to 10-ng samples of genomic DNA. Cell-free DNA was then extracted from peripheral blood samples collected from six patients with melanoma harboring the BRAF V600E mutation. BRAF V600E ctDNA was detected in three patients, at a fractional abundance of between 1.28 and 58.0 % of total BRAF cell-free DNA. The abundance of BRAF V600E ctDNA correlated with tumor burden, as determined by computed tomography imaging. In two cases, an increase in the level of BRAF V600E ctDNA preceded exacerbation of clinical symptoms. The castPCR assay can detect and quantitate small amounts of BRAF V600E ctDNA in samples containing large amounts of BRAF wild cell-free DNA. Thus, we suggest that the castPCR assay is suitable for monitoring ctDNA in the plasma of melanoma patients.

A population-based study on the associations between chronic periodontitis and the risk of cancer

Abstract: To date, the associations between chronic periodontitis (CP) and cancer lack large-scale population-based epidemiological evidence This study aimed to investigate the subsequent risk for cancers among subjects with CP This study cohort included 40,140 subjects with CP and 40,140 subjects who were matched for a comparison cohort We individually tracked each patient for a 5-year period following their index date to identify those who had received a diagnosis of cancer The incidence rate of cancer during the 5-year follow-up period was 1480 (95 % CI 1428–1534) per 1,000 person-years in subjects with CP Cox proportional hazards regression revealed that the hazard ratio of cancer during the 5-year follow-up period for subjects with CP was 123 (95 % CI 120–127) compared to that of the comparison cohort We observed an increased risk for the subsequent development of a number of cancers among subjects with CP

Efficacy and safety of febuxostat for prevention of tumor lysis syndrome in patients with malignant tumors receiving chemotherapy: a phase III, randomized, multi-center trial comparing febuxostat and allopurinol.

Abstract: Background Control of serum uric acid (sUA) levels is very important during chemotherapy in patients with malignant tumors, as the risks of tumor lysis syndrome (TLS) and renal events are increased with increasing levels of sUA. We investigated the efficacy and safety of febuxostat, a potent non-purine xanthine oxidase inhibitor, compared with allopurinol for prevention of hyperuricemia in patients with malignant tumors, including solid tumors, receiving chemotherapy in Japan.

Treatment results and prognostic factors for advanced squamous cell carcinoma of the head and neck treated with salvage surgery after concurrent chemoradiotherapy

Abstract: For primary organ preservation, concurrent chemoradiotherapy (CCRT) is performed for advanced squamous cell carcinoma of the head and neck (SCCHN). In this organ-preservation setting with CCRT, surgery is reserved as a salvage treatment in cases of locoregional failure after CCRT. The purpose of the study was to review our experience with salvage surgery after CCRT for patients with SCCHN and to evaluate the effectiveness and prognostic factors affecting survival. The records of patients with stage II-IVB SCC of the larynx, oropharynx, or hypopharynx treated with salvage surgery after CCRT between 1998 and 2012 were reviewed. A total of 645 patients with previously untreated, resectable SCC of the larynx, oropharynx, or hypopharynx received CCRT. Salvage surgery was performed for 78 of 225 patients with residual or recurrent tumors. The 5-year overall survival (OS) and disease-specific survival rates for patients who received salvage surgery were 61.0 and 65.5 %, respectively. Stage IV, poorly differentiated, synchronous double cancer, and surgical complications were significant predictors of unfavorable OS on multivariate analysis. Postoperative complications were observed in 30 patients (38.5 %). Salvage surgery is the best therapeutic option for failure after CCRT for SCCHN because of its good survival rate, although a high surgical complication rate is seen. Patients with initial stage IV tumors, poorly differentiated SCC, or synchronous double cancer are considered for further adjuvant treatment.

Clinical features and treatment strategy for HPV-related oropharyngeal cancer

Abstract: Among head and neck squamous cell carcinoma (HNSCC), the incidence of oropharyngeal SCC (OPSCC) is increasing in contrast to carcinoma with origin in other subsites. Human papillomavirus (HPV) is now recognized as a significant risk factor of the carcinogenesis of OPSCC. The HPV-related OPSCC patients tend to be relatively young, less exposed to tobacco and alcohol, and have a relatively high socioeconomic status and education level, which is distinct from HPV-unrelated classical OPSCC. The neck metastases tend to be aggressive and cystic. The better response to treatment resulting in improved prognosis of HPV-related OPSCC led to reconsidering the clinical staging and treatment approaches. Clinical trials of treatment deintensification to reduce the acute and late toxicity without compromising efficacy have been conducted. This review of HPV-related OPSCC focuses on current and generally accepted facts regarding the biology, epidemiology, and therapeutic strategy of this new disease entity.

Stromal markers AKR1C1 and AKR1C2 are prognostic factors in primary human breast cancer

Abstract: Stromal fibroblasts influence tumor growth and progression. We evaluated two aldo–keto reductases, AKR1C1 and AKR1C2, in stromal fibroblasts and carcinoma cells as prognostic factors in primary human breast cancer. They are involved in intratumoral progesterone metabolism. Immunohistochemistry was performed on tissue microarrays from 504 core biopsies from breast cancer patients. Primary endpoints were disease-free (DFS) and overall (OS) survival. AKR1C1 and AKR1C2 expression in fibroblasts and tumor cells correlated with favorable tumor characteristics, such as small tumor size and negative nodal status. In univariate analysis, AKR1C1 expression in carcinoma cells correlated positively with DFS und OS; AKR1C2 expression in both fibroblasts and tumor cells also showed a positive correlation with DFS and OS. In multivariate analysis, AKR1C1 expression in carcinoma cells was an independent prognostic marker. It can be assumed that our observations are due to the independent regulatory function of AKR1C1/2 in progesterone metabolism and therefore provide a basis for new hormone-based therapy options for breast cancer patients, independent of classic hormone receptor status.

Tumor hypoxia: a new PET imaging biomarker in clinical oncology

Abstract: Tumor hypoxia is associated with tumor progression and resistance to various treatments. Noninvasive imaging using positron emission tomography (PET) and F-18-labeled fluoromisonidazole (FMISO) was recently introduced in order to define and quantify tumor hypoxia. The FMISO uptake was closely correlated with pimonidazole immunohistochemistry and hypoxia-inducible factor 1 expression in basic studies. Tumor hypoxia in head and neck cancers and other tumors in a clinical setting may also indicate resistance to radiation and/or chemotherapy. Hypoxic imaging may thus play a new and important role for suitable radiation planning, including dose escalation and dose reduction based on the image findings. Such radiation-dose painting based on the findings of hypoxia may require high-performance PET imaging to provide high target-to-background ratio images and an optimal quantitative parameter to define the hypoxic region. A multicenter prospective study using data from a large number of patients is also warranted to test the clinical value of hypoxic imaging.

Anti-PD-L1/PD-1 immune therapies in ovarian cancer: basic mechanism and future clinical application.

Abstract: Tumor immune therapy, especially anti-programmed cell death ligand-1/programmed cell death-1 (PD-L1/PD-1) treatment, is currently the focus of substantial attention. Ovarian cancer is the leading cause of mortality from gynecological malignancies, and novel treatment modalities, including immune therapy, are needed. However, a basic understanding of tumor immunity associated with the PD-L1/PD-1 signal has only recently emerged. In this review, we first discuss the importance of local tumor immunity, which affects the clinical outcome of ovarian cancer. We subsequently provide an overview of the basic findings regarding how the PD-L1/PD-1 signal influences local tumor immunity in ovarian cancer. Finally, we discuss what is needed to apply immune therapy in future clinical medicine.

Prognostic value of hematological parameters in patients undergoing esophagectomy for esophageal squamous cell carcinoma.

Abstract: Background It is now widely recognized that outcomes in cancer patients are not determined by their tumor characteristics alone. In this study, we retrospectively analyzed the clinical data of esophageal cancer patients to evaluate the impact of red blood cell distribution width (RDW), platelet distribution width (PDW), and mean platelet volume (MPV) on cancer-specific survival (CSS).

Microdissection testicular sperm extraction in Japanese patients with persistent azoospermia after chemotherapy

Abstract: Combinations of surgery, radiation therapy, and chemotherapy can achieve high remission rates in patients with cancer, but these treatments can have damaging effects on spermatogenesis. In particular, cytotoxic chemotherapy may lead to irreversible spermatogenic dysfunction. Microdissection testicular sperm extraction (micro-TESE) is the only method that can address infertility in cancer survivors with persistent postchemotherapy azoospermia. We included 66 Japanese patients with postchemotherapy azoospermia who underwent micro-TESE for sperm retrieval in this analysis. Age, oncology data, hormone profiles, and outcomes of micro-TESE and subsequent intracytoplasmic sperm injections (ICSIs) were reviewed. The common disease in our patients was testicular cancer (21 patients), followed by acute lymphoblastic leukemia and Hodgkin’s lymphoma (nine patients). In this cohort of 66 patients, sperm was successfully retrieved in 31 patients (47 %), and clinical pregnancy occurred in 23 cases (35 %). The live birth rate was 27 %. No significant differences in sperm retrieval, clinical pregnancy, and live birth rates were seen between testicular cancer, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, or sarcoma cases. Multiple logistic regression analysis showed that the chance of retrieving sperm during micro-TESE could not be predicted by any variable. Cryopreservation of sperm should be offered before any gonadotoxic chemotherapy takes place. However, micro-TESE and subsequent ICSI could be effective treatment options for patients with persistent postchemotherapy azoospermia whose sperm were not frozen before therapy. Our results suggest that micro-TESE-ICSI could benefit 27 % of such Japanese patients.

KAP1 is overexpressed in hepatocellular carcinoma and its clinical significance

Abstract: The transcriptional regulator in embryonic development, KAP1, has been proved could promote cell proliferation and metastatic progression in a variety of human cancers. However, the role of KAP1 in hepatocellular carcinoma (HCC) remains unclear. The purpose of this study is to investigate the relationship of KAP1 expression with the progression and prognosis of HCC. We measured the expression level of KAP1 in both human hepatoma cell lines and HCC tissues obtained from HCC patients by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot. Furthermore, the effect of KAP1 expression on hepatoma cell proliferation was investigated through KAP1 knock-down strategy. Besides that, the correlation between KAP1 expression and HCC progression was analyzed. KAP1 overexpression was proved broadly existed in the human hepatoma cell lines. Furthermore, down-regulate the expression of KAP1 by specific siRNA could inhibit cell proliferation which was partly originated from the activation of p53 mediated signal pathway. Moreover, comparisons between the cancer tissues and noncancerous tissues proved the expression level of KAP1 was significant higher in tumor tissues obtained from HCC patients. In addition, KAP1 overexpression was significantly correlated with tumor size and tumor stage and also a predictor for poor prognosis of HCC patients. Our results presented here demonstrate that KAP1 plays an important role in HCC and could be regarded as a valuable biomarker for tumor diagnosis and prognosis prediction, as well as a potential target for the treatment of HCC.

Putative risk factors for postoperative pneumonia which affects poor prognosis in patients with gastric cancer

Abstract: Several recent studies identified that postoperative infectious complications contribute to recurrence and poor outcome in patients with gastric cancer. This study was designed to investigate the prognostic impact of postoperative pneumonia, and to identify the putative risk factors for its occurrence. We retrospectively analyzed 1,415 consecutive patients who underwent curative gastrectomy for gastric cancer between 1997 and 2013. A total of 31 (2.2 %) patients developed postoperative pneumonia (Clavien–Dindo classification ≥II). Patients with postoperative pneumonia showed a significantly poorer prognosis than patients without (P < 0.001). Concerning the occurrence of postoperative pneumonia, univariate and multivariate analyses identified older age (≥65 years; P = 0.010; odds ratio [OR] 3.59), lower nutritious status (albumin <3 0; P = 0.029; OR 4.51), advanced stage (pStage ≥II; P = 0.045; OR 2.35), concurrent hypertension (P = 0.042; OR 2.21) and total gastrectomy (P = 0.026; OR 2.42) as independent risk factors. Postoperative pneumonia was shown to be associated with long-term poor outcome in patients with gastric cancer. Care should be taken for patients with clinical factors such as older age, lower nutritional status, advanced stage, concurrent hypertension, and total gastrectomy.

Comparison of clinical and functional outcome between surgical treatment and carbon ion radiotherapy for pelvic chondrosarcoma

Abstract: Background As there are no reports of studies in patients with pelvic chondrosarcoma treated with carbon ion radiotherapy (CIRT), the aim of this study was to evaluate the applicability of CIRT for patients with chondrosarcoma of the pelvis.

A retrospective analysis on the utility and complications of upper arm ports in 433 cases at a single institute

Abstract: Background We have employed upper arm central venous ports (UACVPs) since 2006 for long-term intravenous chemotherapy (CTx) or fluid supplementation. We evaluated the long-term availability of CVPs implanted in the upper arm to determine whether UACVPs could be one of the treatment options besides chest CVPs in terms of CVP-related complications.

Feasibility of laparoscopic total proctocolectomy with ileal pouch–anal anastomosis and total colectomy with ileorectal anastomosis for familial adenomatous polyposis: results of a nationwide multicenter study

Abstract: Data supporting the safety and feasibility of laparoscopic total proctocolectomy with ileal pouch–anal anastomosis (TPC-IPAA) and total colectomy with ileorectal anastomosis (TC-IRA) for patients with familial adenomatous polyposis (FAP) are limited. The aim of this study was to clarify the feasibility and morbidity of laparoscopic TPC-IPAA and TC-IRA for patients with FAP, using a large Japanese multicenter dataset. Data on 256 patients with FAP who underwent TPC-IPAA (n = 171) or TC-IRA (n = 85) at 23 institutions between the years 2000 and 2012 were collected. Short- and long-term clinical outcomes were compared between laparoscopic and open approaches for each procedure. Among the 256 patients with FAP, a total of 126 patients underwent laparoscopic surgery, consisting of 74 laparoscopic TPC-IPAAs and 52 laparoscopic TC-IRAs. The proportion of the FAP patients who underwent laparoscopic surgery increased during the study period, reaching 79 % of all TPC-IPAAs and 82 % of all TC-IRAs in the final two years covered by the data. In both TPC-IPAA and TC-IRA, the laparoscopic approach was associated with a longer operative duration but a similarly low postoperative morbidity and comparably adequate anal function compared with the open approach. The overall survival and the incidence of desmoid tumor were also comparable between the laparoscopic and open approaches in both procedures. Laparoscopic TPC-IPAA and TC-IRA are both feasible options—with low rates of morbidity, good functional outcomes, and excellent overall survival rates—in patients with FAP. Since the data indicate that laparoscopic TPC-IPAA and TC-IRA are feasible, they also support the recent increase in laparoscopic surgery for patients with FAP in Japan.