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The physicist Niels Bohr said "How wonderful that we have met with a paradox. Now we have some hope of making progress." Many paradoxical results have no obvious explanation under the standard somatic mutation theory of tumorigenesis including non-genotoxic carcinogens, foreign-body tumorigenesis, tumors lacking the inducing mutation, spontaneous regression of neuroblastoma, epithelial cancer induced by a stromal carcinogen exposure, the link between schistosomiasis and bladder cancer, and experimental reversion of cancer-like alterations to normal tissue. Alternative hypotheses of tumorigenesis provide more plausible explanations. Investigating paradoxical results in tumorigenesis using modern technology guided by various hypotheses of tumorigenesis will likely spur scientific progress and may lead to new strategies for cancer prevention.

ObjectivesThere is sufficient evidence for a causal association of sinonasal epithelial cancers (SNEC) only for exposure to wood and leather dusts, nickel compounds and employment in isopropyl alcohol production. The aim of this study was to assess whether other occupational hazards are associated with the risk of SNEC for the main histologic types, namely adenocarcinoma (AD) and squamous cell carcinoma (SCC).MethodsThe study population included 375 incident SNEC cases collected from 1996 to 2014 (79% of all diagnosed SNEC) throughout the Piedmont region by the regional Sinonasal Cancer Registry, and 408 hospital controls. Exposure to 17 occupational agents was assigned through expert assessment based on interviews to the subjects on jobs held throughout their working life. The relationship of SNEC with ever and cumulative exposure to the hazards was assessed through unconditional logistic regression models adjusted for age, sex, area of residence, smoking habit, year of enrolment and coexposures.ResultsAD was associated with both ever and cumulative exposure to wood dust, leather dust and organic solvents, and with cumulative exposure to textiles dusts. SCC risk was significantly increased by ever exposure to nickel, chromium and welding fumes, as well as by cumulative exposure to welding fumes, arsenic and organic solvents. A mixed group of other histological types was associated with both ever and cumulative exposure to wood dust and textile dusts.ConclusionsThe associations of SNEC with wood dust, leather dust and nickel were confirmed, while some new associations were observed for other hazards, which merit further investigation.

Literary data on the location of the flat epithelium in the cavity of the body of the uterus are very scarce and are limited to only a few articles that interpret the atypical location of the flat epithelium or in inflammatory processes of the uterus, or in cancers of the uterus.Among the works dealing with the question of finding flat epithelium in inflammatory processes of the body of the uterus should be attributed to the work of Zeller, which appeared in 1884.In the number of works treating flat epithelial cancer of the body of the uterus, we have the reports of Piering and Gebhardt.

Demonstrate survival outcomes of stage 3B/3C ovarian–tubal–peritoneal epithelial cancer patients who had metastases on diaphragm. 141 patients who had undergone diaphragm surgery as a part of primary cytoreductive surgery procedures performed for stage 3B and 3C ovarian–tubal–peritoneal epithelial cancers were reviewed retrospectively. Patients who were administered neoadjuvant chemotherapy and patients who were suboptimally cytoreduced were not included to the study. Median follow-up time was 42 months. Median overall survival of the patients who underwent diaphragm full-thickness resection (n = 18) because of tumors infiltrating diaphragm muscle was 40 months. Median overall survival of the patients who did not have a transdiaphragmatic thoracotomy (n = 113) was 77 months. Patients who underwent a willful full-thickness diaphragm resection because of tumors invading diaphragm muscle had significantly shorter survival compared with patients who did not have a transdiaphragmatic thoracotomy (p = 0.033). Seven (38.9%) of the 18 patients who underwent diaphragm full-thickness resection developed a recurrence in thorax. Twelve (9.8%) of the remaining 123 patients developed a recurrence in thorax. Patients who underwent full-thickness diaphragm resection because of tumors infiltrating diaphragm muscle developed recurrence in the thorax more frequently (p = 0.001). Diaphragm muscle involvement is a predictor of thorax recurrences and worse survival outcomes in stage 3B and 3C ovarian–tubal–peritoneal epithelial cancers. Thus, this should be considered when selecting appropriate adjuvant treatment and route of administration (intravenous/intraperitoneal) in patients who had diaphragm implants infiltrating diaphragm muscle.

Purpose: In this study, we evaluated the significance of parenchymal, hilar, and capsular involvement of the spleen with regard to the overall survival of patients who required a splenectomy during cytoreduction procedures for primary or recurrent cancer. Methods: This study includes data from 287 patients who underwent a splenectomy during optimal cytoreduction in epithelial ovarian, tubal, and peritoneal cancers. Spleen involvement regions were divided into four main groups, and the groups were classified as capsule, hilus, capsule + hilus, and other region involvement (paranchyma ± other(s) involvement site). The overall survivals of these four groups were compared.Results: The mean age of the study group was 57.9 years, and the mean follow-up period of the patients was 43.2 months. The splenic involvement site was most frequently observed as hilus + capsule (42.2% n:121). Splenic parenchymal involvement was present in 27.9% (n: 80) of the patients. The overall survival for patients was 42 months. In the subgroup analysis, the worst overall survival was found in the group with capsule involvement at 33 months.Conclusion: While parenchymal involvement of the spleen was considered to be stage IV according to FIGO staging, we could not detect low overall survival in patients with parenchymal involvement in our study. Our study, which has the largest number in the literature examining the relationship between splenic involvement and overall survival, can provide a remarkable perspective on the relationship between parenchymal involvement of the spleen and prognosis.

Background There is increasing evidence that inflammation-based biomarkers are associated with tumor microenvironment which plays important roles in cancer progression. A high lymphocyte-to-monocyte ratio (LMR), has been suggested to indicate favorable prognoses in various epithelial cancers. We performed a meta-analysis to quantify the prognostic value of LMR in advanced-stage epithelial cancers undergoing various treatment. Methods We searched PubMed, EMBASE, Web of science and Cochrane Library up to July 2018 for relevant studies. We included studies assessing the prognostic impact of pretreatment LMR on clinical outcomes in patients with advanced-stage epithelial cancers. The primary outcome was overall survival (OS) and the secondary outcome was progression free survival (PFS). The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated. Results A total of 8984 patients from 35 studies were included. A high pretreatment LMR was associated with favorable OS (HR = 0.578, 95% CI 0.522–0.641, P

Multiple lines of evidence are indicating that cancer development and malignant progression are not exclusively epithelial cancer cell-autonomous processes but may also depend on crosstalk with the surrounding tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are abundantly represented in the TME and are continuously interacting with cancer cells. CAFs are regulating key mechanisms during progression to metastasis and response to treatment by enhancing cancer cells survival and aggressiveness. The latest advances in CAFs biology are pointing to CAFs-secreted factors as druggable targets and companion tools for cancer diagnosis and prognosis. Especially, extensive research conducted in the recent years has underscored the potential of several cytokines as actionable biomarkers that are currently evaluated in the clinical setting. In this review, we explore the current understanding of CAFs secretome determinants and functions to discuss their clinical implication in oncology.

The recepteur d’origine nantais (RON) receptor tyrosine kinase, belonging to the mesenchymal-to-epithelial transition proto-oncogene family, has been implicated in the pathogenesis of cancers derived from the colon, lung, breast, and pancreas. These findings lay the foundation for targeting RON for cancer treatment. However, development of RON-targeted therapeutics has not gained sufficient attention for the last decade. Although therapeutic monoclonal antibodies (TMABs) targeting RON have been validated in preclinical studies, results from clinical trials have met with limited success. This outcome diminishes pharmaceutical enthusiasm for further development of RON-targeted therapeutics. Recently, antibody–drug conjugates (ADCs) targeting RON have drawn special attention owing to their increased therapeutic activity. The rationale for developing anti-RON ADCs is based on the observation that cancer cells are not sufficiently addicted to RON signaling for survival. Thus, TMAB-mediated inhibition of RON signaling is ineffective for clinical application. In contrast, anti-RON ADCs combine a target-specific antibody with potent cytotoxins for cancer cell killing. This approach not only overcomes the shortcomings in TMAB-targeted therapies but also holds the promise for advancing anti-RON ADCs into clinical trials. In this review, we discuss the latest advancements in the development of anti-RON ADCs for targeted cancer therapy including drug conjugation profile, pharmacokinetic properties, cytotoxic effect in vitro, efficacy in tumor models, and toxicological activities in primates.

In order to compare the clinicopathological characteristics and survival outcomes of patients with ovarian clear cell carcinoma (CCC) to other epithelial cancer types, a total of 27,290 patients were analyzed, including 2,424 patients with CCC (8.9%), 3,505 patients with endometrioid cancer (EC) (12.8%), 2,379 patients with mucinous cancer (MC) (8.7%) and 18,982 patients with serous cancer (SC) (69.6%). Patients with EC had the most favorable prognosis and patients with SC had the poorest prognosis among all epithelial ovarian cancers. Among patients with stage I cancer, patients with CCC had a more favorable prognosis compared with patients with SC, especially after 60 months (landmark analysis results, HR=2.079, P=0.001) and had a poorer prognosis compared with patients with MC [restricted mean survival time (RMST) difference, -3.434 months]. Among patients at stages III and IV, patients with CCC had a poorer prognosis compared with patients with SC (RMST difference in stage III, -7.588 months; RMST difference in stage IV, -15.445 months) and had a more favorable prognosis compared with patients with MC (RMST difference in stage III, 10.850 months; RMST difference in stage IV, 8.430 months). The present results suggested that most patients with CCC exhibited, high grade, an early stage, unilateral status and were of a young age. In general, patients with SC presented the poorest prognosis among all patients with epithelial ovarian cancer and no significant survival difference was found between patients with CCC and MC. However, after adjusting for stage using pairwise comparisons, the prognosis of patients with CCC was found to be more favorable compared with the patients with SC and worse compared with patients with MC at stage I; the results at stage III-IV were opposite and the prognosis of patients with CCC was worse compared with the patients with SC and more favorable compared with the patients with MC.

Objective: To illustrate trends in sex ratios in epithelial cancer mortality in the EU, USA, and Japan, with a focus on age-specific and cohort patterns. Methods: We obtained certified deaths and resident populations from the World Health Organisation for the period of 1970&ndash, 2014 for the USA, Japan, and the EU for 12 epithelial cancer sites. From these, we calculated both the age-specific and age-standardised male-to-female mortality sex ratios. We applied an age-period-cohort model to the sex ratios in order to disentangle the effects of age, period of death, and birth cohort. Results: Age-standardised mortality sex ratios were found to be unfavourable to males, apart from thyroid cancer. The highest standardised rates were in laryngeal cancer: 7&middot, 7 in the 1970s in the USA, 17&middot, 4 in the 1980s in the EU, and 16&middot, 8 in the 2000s in Japan. Cohort patterns likely to be due to excess smoking (1890 cohort) and drinking (1940 cohort) in men were identified in the USA, and were present but less defined in the EU and Japan for the oral cavity, oesophagus, liver, pancreas, larynx, lung, bladder, and kidney. Conclusion: Mortality sex ratio patterns are partly explained by the differences in exposure to known and avoidable risk factors. These are mostly tobacco, alcohol, and obesity/overweight, as well as other lifestyle-related factors.

Epidermal Growth Factor Receptor (EGFR)-dependent signaling plays a crucial role in epithelial cancer biology, and dictated the development of several targeting agents. The mouse-human chimeric antibody Cetuximab was among the first to be developed. After about two decades of clinical research it has gained a significant place in the management of advanced colorectal and head and neck cancers, whereas its development in non small cell lung cancer (NSCLC) has not led to a place in routine clinical practice, because of marginal clinical benefit despite statistically significant Phase III trials. Recent data from ongoing trials suggest that more careful selection based on molecular markers may identify good responders. Areas covered: In this article, the authors review the literature concerning basic science studies identifying EGFR as a therapeutic target, pharmacological development of Cetuximab, its pharmacodynamics and pharmacokinetics, and clinical trials on Cetuximab in NSCLC, focusing on recent findings on putative predictive biomarkers. Expert opinion: Cetuximab currently has no role in NSCLC treatment outside of research settings. We argue that failure to identify a predictive biomarker early on has hampered its chances to enter routine practice. Although recent research suggests benefit in highly selected patient subsets, its potential impact is severely dampened by lack of regulatory body approval and the emergence of competitors for the same niches.

Nanomedicine is a new approach to fight against cancer by the development of anticancer nanoparticles (NPs) that are of high sensitivity, specificity, and targeting ability to detect cancer cells, such as the ability of Silica NPs in targeting epithelial cancer cells. However, these anticancer NPs require preclinical testing, and zebrafish is a useful animal model for preclinical studies of anticancer NPs. This model affords a large sample size, optical imaging, and easy genetic manipulation that aid in nanomedicine studies. This review summarizes the numerous advantages of the zebrafish animal model for such investigation, various techniques for inducing cancer in zebrafish, and discusses the methods to assess cancer development in the model and to test for the toxicity of the anticancer drugs and NPs. In addition, it summarizes the recent studies that used zebrafish as a model to test the efficacy of several different anticancer NPs in treating cancer.

Background This study aimed to evaluate the current status of secondary debulking surgery (SDS) and tertiary debulking surgery (TDS; performed for recurrence after SDS) and to assess the overall survival after recurrence of Müllerian epithelial cancer in Japan. We also evaluated the data of patients who underwent a fourth debulking surgery (i.e., quaternary debulking surgery (QDS))., Methods We conducted a retrospective study of 164 patients with recurrent Müllerian epithelial cancers (i.e., ovarian, tubal, and peritoneal cancers). The SDS was performed between January 2000 and September 2014 in 20 Japanese hospitals. Clinicopathological data were collected and analyzed., Results Of the 164 patients, 66 patients did not have a recurrence or died after SDS. Ninety-eight patients had a recurrence after SDS. Forty-three of the 98 patients underwent TDS; 55 of the 98 patients did not undergo TDS and were classified into the non-TDS group. The overall survival (OS) after SDS was significantly better in the TDS group than in the non-TDS group. The median OS after SDS was 123 and 42 months in the TDS group and non-TDS group, respectively. Of the 43 patients who received TDS, 11 patients were further treated with QDS. The median OS after SDS was 123 months for patients who underwent QDS., Conclusions This multicenter study on the prognosis of post-SDS is apparently the first report on QDS in Japan. Patients undergoing TDS have a good prognosis, compared to patients in the non-TDS group. Novel drugs are being evaluated; however, debulking surgery remains a necessary treatment for recurrence.

We successfully synthesized the antitumor agent 1-methoxydiazofluorene via an artificial intelligence (AI)-proposed design. The pivotal biphenyl scaffold of 1-methoxydiazofluorene was constructed by applying Pd(OAc)2-catalyzed cycloaromatization, a method developed by our group. AI-proposed functional group conversion of the biphenyl intermediate provided 9-diazo-1-methoxy-9H-fluorene, which inhibits the proliferation of HeLa cells, was achieved in reasonable chemical yield. In addition, various diazofluorenes were synthesized using the above protocol and their antitumor effects were evaluated. As a result, several novel diazofluorenes, which have a stronger cytotoxic activity than cisplatin against various human epithelial cancer cells, were found.

e15043 Background: The presence of circulating tumor cells (CTC) in the vascular system is a tell-tale signature of metastasis in epithelial origin cancers including lung, breast, colorectal and head and neck cancers. Noteworthy, about 90% of cancer deaths are due to the progression of metastasis. Yet, cancer therapy is focussed on inhibiting tumour growth and there is a paucity of options that target metastasis. We demonstrate the POP ‘device’ that removes circulating tumour cells (CTC) from a patient’s blood to reduce the metastatic progression and improve overall survival. Methods: We designed, multi-component glass beads enriched antibody EpCAM conjugate substrates as POP blood fluidic device. We characterized the substrate and accounted for the biocompatibility using whole blood of healthy volunteers. We evaluated, the acute toxicity of substrates using rat (Wistar Albino) whole blood (CPCSEA registration number: 941/PO/Re/S/06/CPCSEA; 31/07/2019) and further studied major histopathological tissues for any toxicity. Finally, we evaluated 06 cancer patients whole blood (1.5 mL) for capturing and for the elimination of CTCs. The captured cells were immuno-stained, and the optimal fluorescence acquisition intensity was critically quantified in accounting CK18 protein over-expression. Results: The multi-component antibody EpCAM based substrate exhibited efficient CTC capture ability with a mean capture efficiency ranging from 40% to 100 % when compared to the OncoDiscover CTC test approved by CDSCO/ drug controller general of India (DCGI). Furthermore, the substrate indicated high biocompatibility primarily exhibited by the absence of haemolysis on whole human blood. Additionally, the preliminary animal experiments in rats showed a 100% survival rate and negligible toxicity to major organs. Conclusions: Removal of circulating tumor cells as a therapeutics is highly implicated in improving the overall survival of epithelial cancer patients.

The tumor-stroma ratio (TSR) has been reported as a strong, independent prognostic parameter in colon cancer as well as in other epithelial cancer types, and may be implemented to routine pathology diagnostics. The TSR is an easy technique, based on routine hematoxylin and eosin stained histological sections, estimating the amount of stroma present in the primary tumor. It links tumors with high stromal content to poor prognosis. The analysis time is less than 2 min with a low inter-observer variation. Scoring of the TSR has been validated in a number of independent international studies. In this manuscript, we provide a detailed technical description of estimating the TSR in colon cancer, including examples, pitfalls, and recommendations. Electronic supplementary material The online version of this article (10.1007/s00428-018-2408-z) contains supplementary material, which is available to authorized users.

Probe-based confocal laser endomicroscopy (pCLE) is an emerging tool for epithelial cancer diagnosis, which enables in-vivo microscopic imaging during endoscopic procedures and facilitates the development of automatic recognition algorithms to identify the status of tissues. In this paper, we propose a transfer recurrent feature learning framework for classification tasks on pCLE videos. At the first stage, the discriminative feature of single pCLE frame is learned via generative adversarial networks based on both pCLE and histology modalities. At the second stage, we use recurrent neural networks to handle the varying length and irregular shape of pCLE mosaics taking the frame-based features as input. The experiments on real pCLE data sets demonstrate that our approach outperforms, with statistical significance, state-of-the-art approaches. A binary classification accuracy of 84.1% has been achieved.

This chapter addresses several important aspects of ovarian cancer prevention. One pertains to the risk factors and efforts at early detection, critically reviewing the data on screening tests for ovarian cancer. Another addresses the role of the fallopian tube, a topic that has been at the center of efforts to reduce the risk of high-grade serous cancer via both risk reduction salpingo-oophorectomy and opportunistic salpingectomy. The role of the pathologist is first and foremost by more careful scrutinizing of the fallopian tube using the Sectioning and Extensively Examining the FIMbraited End (SEE-FIM) protocol, which has allowed all pathologists to participate in this paradigm shift to the oviduct as a potential source and target of prevention. Both supporting data and caveats are presented on this compelling issue that continues to evolve and the various entities that deserve attention as either potential premalignant lesions or their mimics are illustrated.

El cáncer mamario se observa tanto en la multípara como en la nulípara y la ausencia de relaciones sexuales no constituye hecho protector contra este cáncer. En lo que se refiere al sexo, como ustedes saben muy bien, es cáncer dominante en la mujer y las estadísticas nos señalan como cifra promedio la de 1 % en el hombre. El factor edad nos hace invadir momentáneamente lo que se refiere a la estructura tumoral, marcándose que el cáncer epitelial es predominante después de los cuarenta años y el conjuntivo antes de esa edad; sin embargo, cada día estamos viendo mayor número de cánceres epiteliales en personas entre 30 y 40 años.

T-cells targeting shared oncogenic mutations can induce durable tumor regression in epithelial cancer patients. These T-cells can be detected in tumor-infiltrating lymphocytes, but whether such cells can be detected in the peripheral blood of patients with common metastatic epithelial cancer is unknown. Using a highly sensitive in vitro stimulation and enrichment of peripheral memory T-cells from six metastatic cancer patients, we identified and isolated memory T-cells targeting the mutated KRASG12D and KRASG12V variants, in three patients. In an additional two metastatic colon cancer patients, we detected CD8+ neoantigen-specific cells targeting the unique mutated SMAD5 and MUC4 proteins. Therefore, memory T-cells targeting KRAS and neoantigens can be detected in the peripheral blood of epithelial cancer patients and can potentially be used for the development of effective personalized T-cell-based cancer immunotherapy across multiple patients. Citation Format: Gal Cafri, Rami Yossef, Anna Pasetto, Drew Deniger, Jared J. Gartner, Todd Prickett, Paul F. Robbins, Steven A. Rosenberg. Memory T-cells targeting unique and shared oncogenic mutations detected in peripheral blood of epithelial cancer patients [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A175.

To identify the appropriate management we review the current literature on the diagnostic and different surgical procedures to which the patients affected by Sertoli-Leyding cell tumors (SLCTs) were submitted. Through the description of a case report we also propose an interdisciplinary diagnostic approach and a laparoscopic surgical staging, with a long-term follow-up. The analysis shows that pelvic ultrasound is primary diagnostic procedure, and only 36% of publications clearly describe to have performed more specific investigation. The hormone assessment is performed in the presence of specific endocrine symptoms. Laparoscopic approach is chosen by a few surgeon. Laparotomic surgery is preferred based in not recent recommendations for ovarian cancer treatment, although it is demonstrated the efficacy and safety of laparoscopy in the treatment of ovarian epithelial tumors. Different steps that are usually used for oncological ovarian cancer staging are not always performed. Conservative and fertility sparing surgery is commonly accepted, and even preferred due to the young age of patients. In the surgical treatment of SLCTs is necessary to adopt common guidelines, and evenly define the steps that the patient should be submitted. If are observed epithelial cancer oncological principles, laparoscopic surgery should be the approach of choice for these patients.

NUT midline carcinoma is a rare epithelial cancer characterized by a simple karyotype with a single abnormality: the translocation t(15;19)(q14;p13.1). In this way it resembles fusion gene-driven leukemias, sarcomas, and a small subset of other carcinomas. These tumors occur throughout life and in most cases are accompanied by distant metastases at the time of diagnosis. There is so far no effective treatment for NUT midline carcinoma; therefore, the international, Web-based NMC Registry (www.nmcregistry.org) was recently established for this cancer. The registry provides access to treatment guidelines based on the experiences of oncologists, and gives patients the opportunity to participate in clinical trials. He were present two case reports, and a review of the definition, clinicopathologic features, genetics, pathogenesis, diagnostic criteria and therapeutic treatment of this aggressive tumor.

Endogenous FLIM images are being acquired in vivo from patients undergoing tissue biopsy of oral lesions. Preliminary results from 20 patients strongly suggest the potential of endogenous FLIM for detecting oral pre-cancer/cancer from benign conditions.

Urachal carcinoma (UrC) is a rare but highly malignant epithelial cancer and commonly found in the urachal remnant which connects the dome of the bladder to the umbilicus via the ligamentum commune. Because of the specificity of the tumor location and its rarity, the diagnosis of UrC is often difficult. Although surgery is the treatment of choice for UrC, it still has a high incidence of local recurrence and distant metastasis and there are few modestly standard chemotherapy regimens for these patients (response rate 30-40%). Thus, the treatment of local recurrence and distant metastasis of UrC following surgery has been a challenge. We review the clinical diagnosis and therapy of UrC and factors related to its prognosis.

The goal of the current study was to determine the efficacy of oral docetaxel in combination with cyclosporine in the treatment of canine epithelial cancer. Requirements for eligibility were histological confirmation of epithelial neoplasia, measurable disease, no chemotherapy treatment within 2 weeks, and a life expectancy of ≥ 3 months. Fifty-one dogs were enrolled. All dogs received 1.625 mg kg(-1) of docetaxel with 5 mg kg(-1) of cyclosporine (DT/CSA) by gavage. Ten dogs had progressive disease at 2 weeks, one dog died, and one dog was withdrawn from the study. Thirty-nine dogs were given a second dose of DT/CSA, three each receiving a third or fourth dose. Eight dogs had a dose reduction (1.5 mg kg(-1)) and six dogs had treatment delays primarily for gastrointestinal toxicity. The overall response rate was 16.7% (8/48 had a partial response there were no complete responses). The highest response rate was seen in dogs with oral squamous cell carcinoma (50%; 6/12).

Many ovarian carcinomas are presumed to arise within ovarian cortical inclusion cysts (CICs). This study examined the frequency of ovarian CICs in relation to epidemiologic risk factors in women with BRCA1 and BRCA2 (BRCA+) mutations.BRCA+ women who underwent risk-reducing bilateral salpingo-oophorectomy were studied (n=74). Fifteen demographic variables (e.g., age at time of surgery, age at first birth, age at menopause, body mass index (BMI), gravidity) from a review of the medical records and three pathologic variables (cystic and atretic follicles, corpora lutea) were recorded. Statistical associations were made using T-test or Chi Square analysis and logistic regression analysis for p-trend.Women whose ovaries contained 7 for more CICs were older at first birth (p=0.034), surgery (p=0.059), menopause (p=0.046) and had a higher BMI (p=0.034) than those with7 CICs. Regression analysis revealed a significant association between CICs and increasing BMI (p=0.01).CICs correlate with greater body mass index, similar to low-grade serous and endometrioid tumors and in contrast to high-grade serous carcinoma and its putative precursor in the fallopian tube. A model is presented for ovarian and tubal pathways to pelvic cancer that are linked to different microscopic precursors with distinct epidemiologic correlates.

Monocytes are a common source for generating dendritic cells (DCs). The aim of the present study was to evaluate the efficiency of a platform for monocyte collection and enrichment in a clinical setting. The platform was based on the combination of two semiautomated devices; the Cobe Spectra Auto PBSC for mononuclear cells (MNC) collection followed by counterflow elutriation for monocyte enrichment (Gambro BCT Elutra). Twenty-four patients with various types of epithelial cancer participated in the study. MNC collections were first performed as large volume leukapheresis (LVL). Subsequently, MNC products were processed with an elutriation system for monocyte isolation. LVL resulted in the collection of MNC at a median of 8.1 × 109 cells, containing of 31.4% monocytes. A similar efficacy was also shown in patients with lower peripheral blood counts. Elutriation of the MNC product with the Cobe Elutra device resulted in the enrichment of monocytes at a median of 2.7 × 109 cells, with a recovery of 80.2% and a purity of 90.7%. These monocytes were then successfully developed into DCs for clinical therapy after in vitro manipulation. These data suggest that the combination of the Cobe Spectra Auto PBSC and the Gambro BCT Elutra is an effective platform for monocyte enrichment in clinical practice according to GCP standards and GMP guidelines, and can be easily implemented in the clinical routine under current DC protocols. J. Clin. Apheresis, 2008. © 2008 Wiley-Liss, Inc.

The role of serous tumors of low malignant potential (LMP) in the development of invasive epithelial cancer of the ovary is debatable. This review summarizes the current clinical, genetic, and genomic evidence for the existence of a continuum comprising both LMP serous tumors and low-grade serous ovarian carcinomas.

Meeting abstracts EnAd is a potent, chimeric Ad11p/Ad3 adenovirus with selective oncolytic activity against a range of epithelial cancer cells. Ongoing clinical studies have shown that i.v. dosed EnAd infects and selectively replicates in tumor cells, producing detectable levels of viral protein

Early detection would double the five-year survival rate of oral epithelial cancer patient. An overview of our current efforts towards developing multimodal optical imaging approaches for early detection of oral epithelial cancer will be presented. Article not available.

Non-urothelial bladder cancers include squamous cell carcinoma, adenocarcinoma and the non-epithelial bladder tumours (NEBT).

3046 Background: Recent genomic and bioinformatic technological advances have made it possible to dissect the immune response to personalized neoantigens encoded by tumor-specific mutations.However, rapid and efficient identification of neoantigens is still fraught with difficulty, and a systematic evaluation of personalized neoantigens based immunotherapy in advanced refractory epithelial tumors is lacking. Methods: Tumor and ctDNA samples from 16 advanced epithelial cancer patients were underwent mutational profiling by cancer-associated genes panel. Neoantigens identification were performed by two strategies: As classic mode, somatic mutations were subjected to in silico analysis to predict potential high-affinity epitopes and mutated peptides were denovo synthesized; Hotspot mutations were matched to our customized driver mutation-derived neoantigens peptide library. Candidate neoepitopes were identified. Approximately 108 neoantigen loaded DC vaccine and 1010 bulk T cells composed of 109 neoantigen reactive CD8+T cells were generated for personlized immunotherapy. Results: Among the sequenced patients, 3 of 4 patients who utilized the classic mode and 6 of 12 patients who performed customized neoantigens library have successfully identified 1~2 neoantigens recognized by autologous T cells, respectively. Subsequently, a total number of 6 patients received immunotherapy targeting personalized neoantigen. To date, one patient with metastatic thymoma is achieving a complete and durable response beyond 9 months. In addition, immune related partial response was observed in another advanced pancreatic cancer patient. The remaining 4 patients achieved prolonged stabilization of disease with median PFS of 8.6 months. Conclusions: Our costomized neoantigens library can provide a novel approach for neoantigens screening in advanced epithelial cancer patients. Besides, targeted sequencing is sufficient for somatic variant and neoantigen identification. The combination of two strategies can accelerate the neoantigen-based translational immunotherapy research into the paradigm of precision medicine.

Malignant tumors harbor genetic alterations. Recently, adoptive T cell therapies have taken advantage of this: T cells specific for mutations in tumors are infused into patients to generate an antitumor immune response. Although therapeutic benefit has been seen for melanomas, effectiveness against more common epithelial tumors is unclear. Using whole-exome sequencing, Tran et al . identified tumor-infiltrating CD4+ T cells specific for a mutated antigen expressed by a tumor from a patient with metastatic cholangiocarcinoma. Infusion of this patient with an expanded-population, mutation-specific T cell resulted in tumor regression and stabilization of disease. E. Tran, S. Turcotte, A. Gros, P. F. Robbins, Y.-C. Lu, M. E. Dudley, J. R. Wunderlich, R. P. Somerville, K. Hogan, C. S. Hinrichs, M. R. Parkhurst, J. C. Yang, S. A. Rosenberg, Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science 344 , 641–645 (2014). [Abstract][Full Text]

This two-arm, randomised, multicentre, openlabel, phase IIIb study investigated the safety and efficacy of a 3-h catumaxomab infusion with/without prednisolone premedication to reduce catumaxomab-related adverse events. Patients with malignant ascites due to epithelial cancer received four 3-h intraperitoneal catumaxomab infusions with/without intravenous prednisolone (25 mg) premedication before each infusion. The primary safety endpoint was a composite safety score calculated from the incidence and intensity of the most frequent catumaxomab-related adverse events (pyrexia, nausea, vomiting and abdominal pain). Puncture-free survival (PuFS) was a coprimary endpoint. Time to next puncture (TTPu) and overall survival (OS) were secondary endpoints. Prednisolone premedication did not result in a significant reduction in the main catumaxomab-related adverse events. The mean composite safety score was comparable in both arms (catumaxomab plus prednisolone, 4.1; catumaxomab, 3.8; p = 0.383). Median PuFS (30 vs. 37 days) and TTPu (78 vs. 102 days) were shorter in the catumaxomab plus prednisolone arm than in the catumaxomab arm, but the differences were not statistically significant (p = 0.402 and 0.599, respectively). Median OS was longer in the catumaxomab plus prednisolone arm than in the catumaxomab arm (124 vs. 86 days), but the difference was not statistically significant (p = 0.186). The superiority of catumaxomab plus prednisolone versus catumaxomab alone could not be proven for the primary endpoint. Prednisolone did not result in a significant reduction in the main catumaxomab-related adverse events. The study confirms the safety and efficacy of catumaxomab administered as four 3-h intraperitoneal infusions for the treatment of malignant ascites. © Springer Science+Business Media 2014.

Background: The reliability of a new screening test for epithelial cancer of the urinary tract was evaluated and the results were compared with those obtained employing urinary cytology in routine use. Methods: The subjects consisted of 187 cases selected randomly from among the patients who attended Toho University Ohashi Hospital during a period of 1 year from January 1998. The values for urine basic fetoprotein (BFP) and polyamine and urinary cytology were examined. Results: Urine BFP is considered useful for screening and monitoring urinary tract epithelial cancer as is urinary cytology. Urine BFP showed a statistically significant difference (P < 0.05) for G1 compared with urinary cytology and a significantly high level compared with urinary cytology as to the positive rate in the low stage group (P < 0.05). The positive rate of urine BFP was high in patients with urinary tract infection. Conclusion: Determining urine BFP, when combined with urinary cytology, is considered very useful for diagnosing patients with urinary tract epithelial cancer. This study suggests the possibility of urine BFP being superior to urinary cytology for screening early cancer and also as an indicator for observations on the clinical course.

The flavonoids, a group of more than 4,000 polyphenolic antioxidants, are potential cancer preventive components of fruits and vegetables. Catechins, one of the 6 major groups of flavonoids, are present in high concentrations in tea as well. Our objective was to evaluate the association between intake of catechins and incidence of epithelial cancers with data from the Zutphen Elderly Study, a prospective cohort study among 728 men aged 65-84 years in 1985. The average catechin intake at baseline was 72 mg/day (range, 0-355 mg/day). After 10 years of follow-up, 96 incident epithelial cancers were recorded, including 42 cases of lung cancer. After multivariate adjustment, catechin intake was not associated with epithelial cancer (risk ratio [RR] from lowest to highest tertile: 1.00, 0.75, 0.94; p for trend: 0.82), or lung cancer (RR from lowest to highest tertile: 1.00, 0.72, 0.92; p for trend: 0.80). Catechins not from tea were borderline significantly inversely associated with lung cancer incidence (RR and 95% confidence interval [CI] for a 7.5-mg increase in intake: 0.66, 0.42-1.05), whereas catechins from tea were not. Catechins from apple, the major source of non-tea catechins, were also related to lung cancer incidence (RR and 95% CI for a 7.5-mg catechin increase: 0.67, 0.38-1.17). Because tea, the major catechin source in this population, was not associated with cancer risk, it seems unlikely that catechins are responsible for the observed inverse trend between non-tea catechins and lung cancer incidence. However, differences in bioavailability of the various catechins may play a role; effects on individual cancer sites cannot be excluded and merit further investigation.

Transitional cell carcinoma (TCC) of the ovary is a rare and recently recognized subtype of ovarian surface epithelial cancer. We present a case that presented with metastatic cervical lymph nodes which is an extremely rare presentation of an ovarian carcinoma.

Malignant neoplasms arising in the upper aerodigestive tract (encompassing the oral cavity, pharynx, esophagus, larynx, and lung) are among the most common cancers in the United States and worldwide, accounting for nearly one third of all malignancies. These cancers are often fatal despite combined

Simultaneous endogenous fluorescence lifetime imaging (FLIM) and optical coherence tomography (OCT) of a hamster cheek-pouch model of oral epithelial cancer allowed discriminating in-vivo benign and malignant lesions with sensitivity and specificity >90%.

Trends in the incidence of non-epithelial cancers are particularly likely to reflect environmental carcinogens, since these malignancies are not commonly the targets of screening efforts, and have generally not been closely associated with life style factors such as cigarette smoking and diet. We used data from nation-wide cancer registries in Denmark, Finland, and Sweden to examine trends in non-epithelial cancers over the period I96 I - 1990. Linear regression analysis of age-standardized rates, and age-period-cohort models were fit to assess the temporal patterns within each country. Within each of the 3 countries, there was a similarly increasing incidence of both hematological malignancies and nervous systemlbonelsoft-tissue neoplasms. The increases were smallest in children and adolescents (ages 0-14), moderate among young and middle aged adults (ages 15-64), and most pronounced among the elderly (ages 65+). Age-period-cohort modeling suggested that the dominant factor in the increases were birth cohort effects. It is not clear what factors underlie this increase in incidence; it seems most likely that increases both in diagnostic efficiency and in exposure to environmental carcinogens play a role. o 1996 U‘iley-Liss, Inc.

The incidence of ovarian cancer is gradually rising in Japan. There are approximately 8,000 cases annually. There were 4,006 deaths from this disease in 1996 and 4,467 in 2005 [1]. The main reason for the increasing incidence in Japan is believed to be changes in the lifestyle of Japanese women. As in Western countries, childbearing now occurs later in life and the number of pregnancies per woman is decreasing. Moreover, oral contraceptives are not as popular in Japan as in Western countries. Although ovarian cancers are classified into various histological subtypes, most are common epithelial carcinoma. Germ cell, stromal, and borderline tumors are fairly rare. Therefore, this counterpoint focuses on common epithelial cancer.

Improved molecular-based detection of early epithelial cancer creates an oupportunity for selective pharmacologic agents to arrest the development of emerging cancers. Developing a successful prevention approach to cancer control could eventually lead to a significant decline in cancer mortality rates; progress depends on the amount of resources committed to this area. Most major prevention trials are federally supported due to their size, duration, and cost. Much of the initial developmental cost for advanced cancer treatment agents was supported by the pharmaceutical industry. Developing a cancer treatment agent is perceived as more clearly defined and achievable than for prevention agents. Preliminary discussions with representatives of the pharmaceutical and biotech industry have identified a number of barriers to chemoprevention product development. Researchers agree that a number of promising agents are being passed over for expeditious development due to the uncertainty associated with chemoprevention drug development. The major factors affecting this circumstance are considered, including cost of clinical trials, absence of a positive model, and inability to project liability exposure. Similar problems were encountered in the area of childhood vaccine development. Insights from that process may have applicability to prevention drug development. Resolving these problems now can have a significant effect on the rate of progress in this promising new approach to cancer control.