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BACKGROUND An accurate diagnosis of cancer of Müllerian origin is required before the initiation of treatment. An overlap in clinical presentation and cytological, histological, or imaging studies with other nongynecological tumors does occur. Therefore, immunocytochemistry markers are used to determine tumor origin. Human epididymis protein 4 (HE4) is overexpressed in tissue of epithelial ovarian cancer (EOC). It has shown to be a sensitive and specific serum marker for EOC and to be of value for the differentiation between EOC and ovarian metastases of gastrointestinal origin. The objective of the current study was to evaluate HE4 immunocytochemistry in malignant ascites for differentiation between cancer of Müllerian origin, including EOC, and adenocarcinomas of the gastrointestinal tract. METHODS Cytological specimens of 115 different adenocarcinomas (45 EOCs, 46 cases of gastric cancer, and 24 cases of colorectal cancer) were stained for HE4, paired box 8 (PAX8), and other specific markers. RESULTS 91% of the ascites samples from patients with EOC stained for both HE4 and PAX8. The 4 samples without HE4 staining were a clear cell carcinoma, a low-grade serous adenocarcinoma, an undifferentiated adenocarcinoma, and a neuroendocrine carcinoma. All high-grade serous adenocarcinomas (n = 37, 100%) stained with HE4, compared with 94% that stained positively for PAX8. In cases of gastric or colorectal cancer, 25% and 21% of cases, respectively, stained positive for HE4. No PAX8 staining was observed in colorectal or gastric adenocarcinomas. CONCLUSIONS HE4 staining in ascites is feasible and appears to have a high sensitivity for high-grade serous ovarian cancer. HE4 is a useful addition to the current panel of immunocytochemistry markers for the diagnosis of EOC and for differentiation with gastrointestinal adenocarcinomas. Cancer Cytopathol 2017;125:197-204. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Introduction: There is ongoing discussion about the primary treatment of women with bulky early-stage cervical cancer. Because of the high number of patients who need adjuvant (chemo)radiotherapy after initial surgical treatment, some state that primary (chemo)radiotherapy should be the treatment of choice to prevent morbidity. The aim of our study is to assess the results of radical surgery for women with bulky early-stage cervical cancer in terms of recurrence patterns and survival.Materials and Methods: We conducted a retrospective cohort study. We included 129 women who underwent a radical hysterectomy with pelvic lymphadenectomy for stage IB2/IIA2 cervical cancer between 1984 and June 2010. Disease-specific survival was measured using a Kaplan-Meier method and univariate and multivariate regression analyses were performed to determine prognostic factors associated with survival. A literature search was performed to analyze our data in the context of findings from the literature.Results: Five-year disease-specific survival was 84%. Fifty percent of the women received adjuvant treatment. The pelvic recurrence rate was 8%. With our multivariate analysis we found that histology, tumor diameter, and parametrial involvement were independently associated with disease-specific survival. Our literature search showed wide diversity in rates of adjuvant treatment after initial surgery as well as for survival and recurrence rates.Conclusions: In the context of current knowledge about survival and side effects of various treatments for bulky early-stage cervical cancer, radical surgery is a good treatment option in these patients. Depending on the type of surgery used, adjuvant radiotherapy can be minimized. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to retrospectively determine the objective response rate to hormone therapy (HT) for patients with a measurable adult granulosa cell tumor (GCT) of the ovary in a consecutive series of patients.Material and Methods: All patients with an adult GCT who were treated with HT [steroidal progestins, selective estrogen receptor modulators, aromatase inhibitors and gonadotropin-releasing hormone agonists] within three referral hospitals were identified and their records were screened for HT administration. The main outcome measure was the objective response rate to HT.Results: We identified 127 patients with an adult GCT, of whom 81 (64%) had a recurrence. Twenty-five of these patients (20%) were treated with hormones, of whom 22 had measurable disease at the start of their treatment, i.e. a tumor of more than 1 cm in diameter as seen on imaging, either as a recurrence or as residual disease. The pooled objective response rate, defined as the proportion of patients whose best overall response to hormone therapy was either complete response or partial response to HT, was 18% (4/22) (95% confidence interval 6-41%). In one patient (4.5%) a complete response and in three (14%) a partial response was described. Fourteen patients (64%) had stable disease and in four patients (18%) disease was progressive.Conclusions: Although several case reports described good responses to HT in patients with a GCT, we found a response in only four of 22 patients in this relatively large consecutive series of patients. [ABSTRACT FROM AUTHOR]

Although complete debulking surgery for epithelial ovarian cancer (EOC) is more often achieved with interval debulking surgery (IDS) following neoadjuvant chemotherapy (NACT), randomized evidence shows no long-term survival benefit compared to complete primary debulking surgery (PDS). We performed an observational cohort study of patients treated with debulking surgery for advanced EOC to evaluate the prognostic value of residual disease after debulking surgery. All patients treated between 1998 and 2010 in three Dutch referral gynaecological oncology centres were included. The prognostic value of residual disease after surgery for disease specific survival was assessed using Cox-regression analyses. In total, 462 patients underwent NACT-IDS and 227 PDS. Macroscopic residual disease after debulking surgery was an independent prognostic factor for survival in both treatment modalities. Yet, residual tumour less than one centimetre at IDS was associated with a survival benefit of five months compared to leaving residual tumour more than one centimetre, whereas this benefit was not seen after PDS. Leaving residual tumour at IDS is a poor prognostic sign as it is after PDS. The specific prognostic value of residual tumour seems to depend on the clinical setting, as minimal instead of gross residual tumour is associated with improved survival after IDS, but not after PDS. [ABSTRACT FROM AUTHOR]

Objective Many women treated for cervical cancer (CC) report sexual complaints and sexual distress. It is important to assess these women's and their partners' sexual healthcare needs. This study aims to (a) investigate the prevalence of psychosexual healthcare needs and help-seeking behaviour among CC survivors, (b) identify the association between psychosocial variables and help-seeking intentions among CC survivors and (c) assess survivors' and partners' preferences regarding psychosexual healthcare services. Methods A multicentre cross-sectional questionnaire study was conducted in a cohort of women with a history of CC ( n = 343, mean age = 48.7), and their partners ( n = 154, mean age = 50.8). Questions concerned professional healthcare needs, help-seeking behaviour, help-seeking intentions and preferences regarding sexual healthcare services. Furthermore, the questionnaire assessed social cognitive variables related to help-seeking intentions. Data were analysed with multivariate linear regression analyses with future help-seeking intention as an outcome variable. Results About 51% of the women reported a need for information and/or professional help, although only 35% of these women had initiated a conversation with a professional about sexuality. Women considering sexual functioning important, expecting relief from seeking help, perceiving social support to seek help and having positive beliefs about the quality of professional psychosexual support had higher help-seeking intentions. Women who were embarrassed to discuss sexual issues with a professional were less likely to seek help. Most participants would appreciate receiving information about sexuality and CC. Conclusions Many CC survivors have psychosexual healthcare needs, although few seek professional help. Women and their partners should be facilitated in accessing sexual healthcare services. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective To determine if female partners of patients with penile cancer have more cervical lesions and neoplasia than would be expected from population-based data., Patients and Methods We included all consecutive patients with primary penile carcinoma in the period 2004-2010., Results of Dutch cervical cancer screening were used to consider (pre)malignant cervical lesions in female partners of patients with penile cancer., Results In all, 206 women were included., Gynaecological information was available in 195 women: Papanicolaou test ( PAP) smears were normal were in 129 partners, 10 smears were abnormal (5.1%, 95% confidence interval 2.5-9.2)., PAP2 was found in five, PAP3a in two, PAP3b in two women and PAP4 in one woman., Colposcopy in two women with PAP3b showed cervical intraepithelial neoplasia grade 3 in both., This prevalence was not different from baseline results in the general Dutch population., Conclusion Female partners of patients with penile cancer did not show more premalignant cervical lesions than in the general population. [ABSTRACT FROM AUTHOR]

A detailed analyses of HPV-specific immunity was performed in a large group of patients with HPV-induced cervical cancer (CxCa) in relation to HLA-types and prognostic factors. Patients were HLA-typed and HPV16/18-specific T-cell immunity was assessed by proliferation assay and cytometric bead array using freshly isolated PBMC and by phenotypic analysis of HPV-specific T cells. The results were analyzed in relation to known disease-related HLA-types (DR7, DR13, DR15/DQ06), invasion-depth and size of tumor, lymph node (LN) status and disease free survival. In total 119 HLA-typed patients with CxCa were analyzed. Patients expressing the HLA-DR13 haplotype were underrepresented as compared to the Dutch population ( p = 0.014), whereas HLA-DR7 was overrepresented in patients with HPV16+ CxCa ( p = 0.006). In 29 of 94 patients (31%) from whom blood could be tested, a proliferative response to HPV16/18 was detected, which was associated with increased numbers of HPV-specific CD4+CD25+ (activated) T cells ( p = 0.03) and HPV-specific CD4+CD25+FoxP3-positive T cells ( p = 0.04). The presence of both FoxP3-positive and negative HPV-specific CD4+CD25+ T cells was significantly correlated ( p = 0.01). Interestingly, the detection of HPV-specific proliferation was associated with invasion depth ( p = 0.020) but not with HLA type, tumor size nor LN status. Moreover, the detection of HPV-specific immunity was associated with an improved disease free survival ( p = 0.04) in patients with deeply infiltrating tumors. In conclusion, HPV-specific proliferative T-cell response, comprising higher percentages of HPV-specific CD25+ and CD25+FoxP3-positive CD4+T cells, are more frequently detected in patients with deep infiltrating CxCa tumors and associated with an improved survival. [ABSTRACT FROM AUTHOR]

We have tested the safety and feasibility of a synthetic long peptide-based HPV16-specific skin test to detect cellular immune responses to HPV16 E2, E6 and E7 in vivo. Women with cervical neoplasia ( n = 11) and healthy individuals ( n = 19) were intradermally challenged with 8 different pools of HPV16 E2, E6 and E7 peptides. The skin test was safe as the injections were perceived as mildly painful and no adverse events were observed. The majority of skin reactions appeared significantly earlier in HPV16+ patients (<8 days) than in healthy subjects (8-25 days). The development of late skin reactions in healthy subjects was associated with the appearance of circulating HPV16-specific T cells and the infiltration of both HPV16-specific CD4+ Th1/Th2 and CD8+ T cells into the skin. These data show that the intradermal injection of pools of HPV16 synthetic long peptides is safe and results in the migration of HPV16-specific T cells into the skin as well as in an increase in the number of circulating HPV16-specific T cells. The use of this test to measure HPV16-specific immunity is currently tested in a low resource setting for the measurement of spontaneously induced T-cell responses as well as in our HPV16 vaccination trials for the detection of vaccine-induced immunity. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV)-induced malignancies are frequently infiltrated by lymphocytes. To comprehend the contribution of HPV-specific T cells in this anti-tumor response we developed a method that allowed the analysis of the presence and specificity of cervix-infiltrating and draining lymph node resident T cells in a group of 74 patients with cervical malignancies, 54 of which were induced by HPV16 or HPV18. We detected the presence of HPV16 or HPV18-specific T cells in at least 23 of the 54 HPV-16 or -18 positive patients, and not in the 20 controls. Detailed studies resulted in the identification of 17 novel CD4+ and CD8+ T cell epitopes and their HLA-restriction elements, and also revealed that the HPV-specific immune response was aimed at both E6 and E7 and showed no preferential recognition of immunodominant regions. Unexpectedly, the vast majority of the CD4+ T cell epitopes were presented in the context of the less abundantly expressed HLA-DQ and HLA-DP molecules. Since the identified T cell epitopes constitute physiological targets in the immune response to HPV16 and HPV18 positive tumors they will be valuable for detailed studies on the interactions between the tumor and the immune system. This is crucial for the optimization of cancer immunotherapy in patients with pre-existing tumor-immunity. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background. Autonomic nerve damage plays a crucial role in the etiology of bladder dysfunction, sexual dysfunction, and colorectal motility disorders that occur after radical hysterectomy. We investigated the extent and nature of nerve damage in conventional and nerve-sparing radical hysterectomy. Methods. Macroscopical disruption of nerves was assessed through anatomical dissection after conventional and nerve-sparing surgery on five fixed and one fresh cadaver. Immunohistochemical analysis of surgical margins was performed to confirm nerve damage using a general nerve marker (S100) and a sympathetic nerve marker (anti-tyrosine hydroxylase) within sections of biopsies. Results. Macroscopical dissection showed that in the conventional procedure, transsection of the uterosacral ligaments resulted in disruption of the major part of the hypogastric nerve. After nerve-sparing surgery, only the medial branches of the hypogastric nerve appeared disrupted. Division of the cardinal ligaments in the conventional procedure identified the inferior hypogastric plexus running into the most posterior border of the surgical margin. The anterior part of the plexus was disrupted. Dissection of the nerves after the nerve-sparing procedure showed that this anterior part of the plexus was not involved in the surgical dissection line. Dissection of the vesicouterine ligament disrupted only small nerves on the medial border of the inferior hypogastric plexus in both techniques. Microscopical evaluation of the surgical margins confirmed the macroscopical findings. Conclusion. Conventional radical hysterectomy results in disruption of a substantial part of the pelvic autonomic nerves. The nerve-sparing modification leads to macroscopic reduction in nerve disruption which is substantiated by microscopical evaluation of surgical margins. [ABSTRACT FROM AUTHOR]

Background. In the present study we report on the results of a retrospective study on the effect on survival of the pelvic lymphadenectomy in a group of 294 patients with stage Ia2-IIa cervical carcinoma treated by radical hysterectomy from 1984 through 1996 at the Leiden University Medical Center. Methods. Lymphadenectomy was called ‘complete’ when lymph node bearing tissue had been removed from 5 or 6 lymph node stations and ‘not-complete’ when this was the case in 1–4 stations. Results. A radical hysterectomy was carried out in 294 patients. In 63 patients positive lymph nodes were found. Patients with positive nodes showed poorer 5 year survival: 64.5% compared to 90% in patients with negative nodes. In the univariate analysis the following factors were found to affect the presence of node metastases in a statistically significant way: age, tumor size, depth of infiltration, vaso-invasion, surgical margins, parametrial infiltration, stage and place of referral. In 63 patients with positive nodes, a complete lymphadenectomy was carried out in 23 patients, and in 40 patients the procedure was incomplete. All 63 patients were treated by adjuvant radiation therapy; those with complete lymphadenectomy had significantly less recurrences (25%) compared to those with incomplete lymphadenectomy (56%): the relative risk (RR) was 2.9 (95% ci: 1.3–6.7), p=0.012. After adjustment for other prognostic factors including tumor size, depth of infiltration and parametrial involvement, the complete lymphadenectomy showed an independent effect on disease free survival: RR=3.2 (95% ci:1.3–7.7), p=0.011. Prognostic factors were not significantly different for patients with complete or incomplete lymphadenectomy. Conclusions. From the results of this study, although retrospective and non randomized, it can be concluded that to complete removal of lymph nodes in combination with radical hysterectomy seems to have a beneficial effect... [ABSTRACT FROM AUTHOR]