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Biomedical subjects

G G Kenter

Publications and source records attributed to G G Kenter.

At least 19 recordsLinked to original sources
PubMed2006

The number of pelvic lymph nodes in the quality control and prognosis of radical hysterectomy for the treatment of cervical cancer.

AIMS: To determine if the number of removed lymph nodes in radical hysterectomy with lymphadenectomy (RHL) influences survival of patients with early stage cervical cancer and to analyze the relation of different factors like patient age, tumour size and infiltration depth with the number of nodes examined in node-negative early stage cervical cancer patients. METHODS: Of consecutive patients, who underwent RHL between January 1984 and April 2005, 331 had negative nodes (group A) without adjuvant therapy and 136 had positive nodes (group B). The Kaplan-Meier method and Cox regression model were used to detect statistical significance. Factors associated with excision of nodes were confirmed with linear regression models. RESULTS: The median number of removed nodes was 19 and 18 for group A and group B, respectively. There was no significant relationship between the number of removed nodes and the cancer specific survival (CSS) or disease free survival (DSF) for patients of group A (p=0.625 and p=0.877, respectively). The number of removed nodes in group B was not significantly associated with the CSS (p=0.084) but it was for the DSF (p=0.014). Factors like patient age, tumour size and infiltration depth were not associated with the number of nodes. CONCLUSIONS: No relation was found between the number of negative nodes examined after RHL for the treatment of early stage cervical cancer and CSS or DFS. However, a higher amount of removed lymph nodes leaded to a better DFS for patients with positive nodes. It is suggested that patients with positive nodes benefit from a complete pelvic lymphadenectomy and a sufficient yield of removed nodes.

Adult↗
PubMed2006

Alterations in the p53 pathway and prognosis in advanced ovarian cancer: a multi-factorial analysis of the EORTC Gynaecological Cancer group (study 55865).

PURPOSE: The study was designed to determine independent prognostic variables in suboptimally debulked advanced ovarian cancer patients entered in the randomised phase III study EORTC 55865. EXPERIMENTAL DESIGN: Retrospectively collected paraffin blocks from 169 patients with stages IIb-IV epithelial ovarian cancer, taken at primary debulking surgery, were analysed. All patients were treated with cyclophosphamide and cisplatin (CP), and followed up for a median of 10 years. Expression of p53, bcl-2, P21, Ki-67 and HER-2 status was assessed by immunohistochemistry (IHC). RESULTS: Expression of p21, a downstream effector of the p53 gene, was found to be a favourable prognostic factor for survival (HR 0.58, CI 0.36-0.94, p=0.025) in addition to FIGO stage (HR 1.54, CI 1.08-2.21, p=or<0.02). For progression free survival (PFS), both p21 (HR 0.52) and Ki-67 (HR 0.6) were significant factors. CONCLUSION: P21 overexpression is a positive prognostic factor for survival and PFS in advanced ovarian carcinoma with residual lesions of more than 1 cm.

Adult↗
PubMed2006

The absence of CCL2 expression in cervical carcinoma is associated with increased survival and loss of heterozygosity at 17q11.2.

To determine whether CCL2 mRNA expression is beneficial or detrimental for cervical cancer patients, the association between the expression of this molecule by cervical tumour cells, the number of tumour-associated macrophages, and clinicopathological parameters such as recurrence, relapse-free survival, and overall patient survival was investigated. In cervical cancer samples from 93 untreated cervical cancer patients, the CCL2 mRNA expression level was quantified using RNA in situ hybridization and verified using real-time quantitative RT-PCR. The number of tumour-associated macrophages was determined using immunohistochemistry. Furthermore, the study investigated whether lack of CCL2 expression was due to genetic alterations near the 17q11.2 (CCL2 genomic) region. CCL2 mRNA expression by cervical tumour cells was associated with the number of tumour-associated macrophages (p < 0.001). Lack of CCL2 mRNA expression (15 samples; 16%) was associated with increased cumulative relapse-free survival (log rank test, p = 0.030), increased cumulative overall survival (log rank test, p = 0.024), less post-operative surgery, reduced local and distant recurrence, reduced vascular invasion, and smaller tumour size (<40 mm). The absence of CCL2 mRNA expression corresponded with loss of heterozygosity (LOH) at 17q11.2 in five of six samples. The increased cumulative relapse-free survival and cumulative overall survival of cervical cancer patients lacking tumour cell-associated CCL2 mRNA suggest that the tumour-associated macrophages support tumour progression, presumably by promoting angiogenesis and production of growth factors.

Biomarkers, Tumor↗
PubMed2005

Survival of patients with ovarian cancer due to a mismatch repair defect.

PURPOSE: Hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome) is characterized by the development of cancer of the colorectum, endometrium and other cancers. Cancer of the ovaries (OC) has frequently been reported in HNPCC. Colorectal cancer associated with HNPCC has a better survival chance compared to sporadic colorectal cancer. It is yet unknown whether patients with OC from HNPCC families (OC-HNPCC) also have a better survival. Therefore, the aim of the study was to compare the survival between patients with OC-HNPCC and a control group. METHODS: A total of 26 patients with OC were identified from the Dutch HNPCC Registry. A control group (52 cases) matched for age, stage and year of diagnosis was derived from the population-based Eindhoven Cancer Registry. Data on treatment were collected for all patients. Kaplan-Meier analysis was used to calculate the crude survival. RESULTS: The mean age at diagnosis of OC-HNPCC was significantly lower than the age of sporadic OC (49.5 vs 60.9 years). Compared to sporadic OC, OC-HNPCC was diagnosed at an earlier stage. The survival rate was not significantly different between patients with OC-HNPCC and the controls with sporadic OC. The cumulative 5-year-survival rates were 64.2 and 58.1% respectively. CONCLUSION: On the basis of our findings, we recommend to treat OC-HNPCC similar to sporadic OC.

Adult↗
PubMed2004

Prognostic difference of surgical treatment of exophytic versus barrel-shaped bulky cervical cancer.

OBJECTIVE: The aim of the study was to evaluate the prognostic significance of tumor geography, defined as exophytic or barrel-shaped growth, in bulky (>4 cm) cervical cancer. METHODS: Four hundred women with cervical cancer, treated by primary radical hysterectomy between January 1984 and November 2000, were followed in a prospective cohort study. Clinical and pathology data were stored in a databank and the clinical protocol was unchanged during the study except for the amendment of additional indications of postoperative radiation in 1997. The assessment of tumor geography was based on pelvic examination at the time of tumor staging or radical hysterectomy or from the pathology report. Survival probabilities were calculated by the Kaplan-Meier method and compared with the log-rank test. RESULTS: The mean age of the patients was 45 years and the mean follow-up duration 48 months. Tumors were of squamous cell type in 291 patients (73%). Lymph node metastases were present in 91 patients (24%) and postoperative radiation was given in 179 patients (45%). In 291 patients, tumor diameter was <4 cm; in 58 patients, the tumor was defined as bulky exophytic and in 51 patients as bulky barrel shaped. There were no differences among these three groups in terms of operating time, blood loss during surgery or complications at 3 or 6 months postoperatively. Bulky exophytic tumors had an identical overall survival as compared to small-diameter (<4 cm) tumors. The overall survival (OS) of bulky barrel-shaped tumors was significantly worse (P < 10(-4)). The same was found for disease-free survival (DFS). CONCLUSION: Bulky exophytic cervical cancer has an identical surgical morbidity, overall and disease-free survival as compared to nonbulky (<4 cm) cervical cancer. In view of these identical characteristics, primary surgical treatment should be considered for patients with bulky exophytic cervical cancer.

Adult↗
PubMed2004

Objective assessment of sexual arousal in women with a history of hysterectomy.

OBJECTIVE: The potential contribution of psychological and anatomical changes to sexual dysfunction following hysterectomy is not clear. Radical hysterectomy for cervical cancer causes surgical damage to the autonomic nerves which are responsible for the increased vaginal blood flow during sexual arousal. Simple hysterectomy causes more limited nerve disruption. Photoplethysmographic assessment of vaginal pulse amplitude objectively measures vaginal blood flow during sexual arousal. We hypothesised that damage of the autonomic nerves results in a disrupted vaginal blood flow response during sexual stimulation. DESIGN: Between-groups comparison of vaginal pulse amplitude. SETTING: University hospital. SAMPLE: Twelve women with a history of radical hysterectomy, 12 women with a history of simple abdomonal hysterectomy and 17 aged-matched controls. METHODS: Photoplethysmographic assessment of vaginal pulse amplitude during sexual stimulation by erotic films. Self-reported ratings of subjective sexual arousal were collected after each erotic stimulus condition. MAIN OUTCOME MEASURE: Maximum vaginal pulse amplitude. RESULTS: Maximum vaginal pulse amplitude differed between the three groups (P= 0.043). Women with a history of radical hysterectomy had a lower response than controls (P= 0.015). Women in the radical hysterectomy group and controls reported an equally strong subjective arousal. Women with a history of simple hysterectomy showed an intermediate maximum vaginal pulse amplitude. CONCLUSIONS: Radical hysterectomy seems associated with a disturbed vaginal blood flow response during sexual arousal. This cannot be explained solely by uteric extirpation, since it was not observed to the same extent after simple hysterectomy, but might be related to a denervation of the vagina which increases with increasing radicality of surgery.

Adult↗
PubMed2003

[Nerve sparing radical hysterectomy in the case of cervical cancer].

Autonomous pelvic nerves are essential for bladder and rectum function as well as sexuality. These nerves are usually permanent damaged during radical oncological surgery and this results in urological, sexual and proctological morbidity. Japanese surgeons have paved the way for surgical approaches to dissect these nerves during surgery and leave them intact. At the Department of Gynaecology of the Leiden University Medical Center, the Netherlands, a new surgical technique has been developed to spare the autonomous pelvic nerves during radical hysterectomy. In this procedure the lateral parts of the sacro-uterine ligament, through which the N. hypogastricus passes bilaterally, are left intact. The initial results of this nerve-sparing surgical technique during radical hysterectomy seem to be promising. The operation was easy to perform, with almost no extra blood loss and an extra operating time of just 10-15 minutes. Postoperative recovery of the bladder function occurred after a mean period of 9 days.

Female↗
PubMed2003

Nerve sparing radical hysterectomy: latest developments and historical perspective.

Autonomic nerve damage during surgery is thought to play a crucial role in the aetiology of bladder dysfunction, sexual dysfunction and colorectal motility disorders which are seen in patients after radical hysterectomy. In order to prevent these complications, Japanese gynaecologists introduced a surgical technique with preservation of the pelvic autonomic nerves in the 1960s. In the 1980s the first English paper was published. Since then several surgical approaches have been described, i.e. liposuction, electrical stimulation to locate nerves intra-operatively and laparoscopically assisted techniques. Recently, more attention is being paid to the importance of sparing the sympathetic hypogastric nerve. All authors report results on small cohorts of patients. The incidence of urinary dysfunction seems very low after nerve sparing. Sparing the autonomic nerves during radical hysterectomy seems feasible and safe in both Japanese and Western patients. Literature review does not provide strong clues for a compromised radicality and cure due to nerve sparing. Future larger clinical trials will have to decide whether the technique of nerve sparing radical hysterectomy could be implemented as a standard treatment for cervical cancer patients.

Autonomic Pathways↗
PubMed2002

[Recommendations for the management of women with an increased genetic risk of gynaecological cancer].

About 5% of all ovarian-cancer cases are caused by a genetic predisposition, in particular as a component of the autosomal dominant hereditary breast-ovarian-cancer syndrome. This syndrome is usually due to germline mutations in the BRCA1- or BRCA2-gene. Ovarian and endometrial cancer also occur in families with hereditary non-polyposis colorectal cancer (HNPCC). This syndrome is caused by germline mutations in DNA mismatch-repair genes. Women at high risk of gynaecological cancer based upon familial clustering of disease or a demonstrated pathogenic germ-line mutation are candidates for surveillance: annual gynaecological examinations, including vaginal echoscopy and serum carcinoma antigen CA125 testing. Prophylactic surgery in the form of adnexectomy leads to a marked, but not complete, reduction of ovarian-cancer risk in high-risk cases. There is insufficient evidence to advise against the use of oral contraceptives or hormonal substitution after adnexectomy for healthy women with a genetic predisposition to breast cancer. Recommendations for surveillance and prevention should only be given after genetic-risk counselling, based on a detailed family study and DNA-based diagnosis.

BRCA2 Protein↗
PubMed2002

[The Dutch College of General Practitioners' practice guideline, "Vaginal bleeding"; reaction from a gynaecological perspective].

The Dutch College of General Practitioners' practice guideline 'Vaginal bleeding' is a useful instrument for general practitioners. The changes in the present version are based on recent developments in diagnostic and therapeutic possibilities, such as (hydro-)ultrasonography to diagnose intracavitary abnormalities, progesterone-containing 'intra-uterine devices' (IUDs) and endoscopic techniques for destroying the endometrium. The recommendation to prescribe cyclical progestogens in the case of hypermenorrhoea is not supported by randomised studies. On balance, this guideline provides clear and useful advice for the treatment of abnormal vaginal blood loss.

Female↗
PubMed2001

Tumor diameter and volume assessed by magnetic resonance imaging in the prediction of outcome for invasive cervical cancer.

OBJECTIVE: The aim of this study was to evaluate the predictive value of pretherapeutic magnetic resonance imaging (MRI)-based measurements of tumor diameter and volume with regard to recurrent disease. METHODS: MRI on 0.5- or 1.5-T scanners was performed in 126 consecutive women with invasive carcinoma of the uterine cervix. Initial tumor diameter and volume were determined on T(2)-weighted images; volume was calculated by the standard technique of multiplying the sum of the areas by the slice thickness. Patients were treated by radical surgery, radiotherapy, or a combined approach based on clinical International Federation of Gynecology and Obstetrics (FIGO) stage and individual patient criteria. Clinical data (patient age and FIGO stage), MRI-derived tumor dimensions (diameter and volume), and histological findings (tumor invasion depth and lymph-node involvement) were associated and linked to patient outcome. RESULTS: MRI-based tumor diameter correlated strongly with histological tumor invasion depth and lymph-node status (P < 0.01 and P = 0.01) while tumor volume on MRI was significantly associated only with tumor invasion depth into adjacent tissues (P < 0.01). Univariate analysis demonstrated graphically that MRI-derived tumor diameter and volume and clinical FIGO stage are associated with progression-free survival. Correlation analysis showed a strong association between MRI-derived tumor diameter and volume on MRI (r = 68%, P < 0.01) and also demonstrated a correlation between tumor diameter on MRI and FIGO stage Ib (Ib1 versus Ib2) cervical tumors (r = 46.7%, P < 0.01). CONCLUSION: Tumor diameter and volume, determined by pretreatment MRI examinations, predict progression-free survival for patients with invasive cervical carcinoma. This study demonstrates the value of MRI as an adjunct to clinical evaluation of invasive cervical cancer, providing more complete assessment of morphological risk factors important in patient prognosis and treatment planning.

Adult↗
PubMed2001

Cytokine profile of cervical cancer cells.

OBJECTIVE: In patients with cervical carcinoma, the presence of cytokines produced by T(H)2 cells, and the presence of an eosinophilic inflammatory infiltrate, has been associated with a less effective immune response and tumor progression. In the present study, we have investigated the cytokine profile of cervical carcinoma cells. In addition, we have measured whether differences in cytokine profiles between normal and malignant cervical epithelial cells are present. METHODS: For this purpose we have determined the mRNA expression patterns of 20 relevant cytokines by RT-PCR and Southern blotting in 3 normal primary cervical epithelial cell cultures (NPE) and 10 cervical cancer cell lines (CCCL). RESULTS: TGF-beta(1), IL-4, IL-12p35, and IL-15 were produced by all CCCL and NPE. TNF-alpha, IL-10, IL-5, and RANTES were present in most NPE, but not in any of the CCCL. MCP-1 was expressed in all CCCL but in only one NPE. The presence of the anti-inflammatory cytokine TGF-beta(1) in cervical carcinomas was confirmed by RNA in situ hybridization on tissue sections of carcinomas from which the CCCL originated. CONCLUSIONS: Our results suggest that cervical carcinoma cells produce immunomodulatory cytokines and that cytokine expression patterns change after malignant transformation. The implications of locally produced cytokines by cervical cancer cells are further discussed.

Blotting, Southern↗
PubMed2000

[Surgical treatment of early stage cervical carcinoma at Leids University Medical Center, 1984-1996: depth of invasion, number and bilaterality of metastatic lymph nodes prognostic for recurrence].

OBJECTIVE: To analyse local tumour parameters of early cervical cancer that might be of prognostic significance for tumour relapse in the pelvis. DESIGN: Retrospective. METHOD: Data were collected from 308 patients who underwent radical hysterectomy and pelvic lymphadenectomy in the years 1984-1996 in the Leiden University Medical Centre, the Netherlands. Treatment policies and operating staff were the same during the study period. The existence of relapse was studied by physical, gynaecological, laboratory and, if indicated, radiological examination. RESULTS: Data on 294 patients were available for analysis. Their mean age was 45 years (range: 21-82). Postoperative radiation treatment was given to 119 patients (40%). Mean follow-up duration was 36 months (range: 1-136). Recurrences had developed in 46 patients (15.6%), 29 of whom had died. The calculated overall 5-year survival rate was 83%; 91% for those with negative and 53% for those with positive pelvic nodes. The calculated recurrence-free-5-year survival rate was 75% for the entire group, 83% for the patients without and 47% for those with lymph node metastases. When more than one lymph node region was affected, 5-year disease free survival was 19% and when lymph node metastasis occurred bilaterally, it was 22%. Multivariate analysis revealed that lymph node involvement (hazard ratio: 4.4), parametrial involvement (5.5), tumour size > 30 mm (4.6) and depth of invasion > 10 mm (5.1) were independent factors of prognostic significance for disease free survival. The current indications for adjuvant treatment might be extended with infiltration depth. The number and the bilaterality, if any, of affected lymph node stations might be indication for additional adjuvant therapy.

Adult↗
PubMed2000

[Good medical care at the borderline of mental incompetence].

A 73-year-old woman with minor intellectual skills had complaints which suggested a vulvar carcinoma. Despite her refusal she was examined and admitted to hospital, on the basis of good professional care. The psychiatrist examined her and judged her incompetent. For the operation of the diagnosed vulvar carcinoma a court ordered representative was obtained. Two months later she underwent radiotherapy to prevent local complications and pain and a few weeks thereafter she died. Because medical decision-making in a doctor-patient relationship is not always possible decision-making power should be assigned to a third party. That forms the basis of proper medical care.

Aged↗
PubMed2000

Prediction of a mismatch repair gene defect by microsatellite instability and immunohistochemical analysis in endometrial tumours from HNPCC patients.

Instability of microsatellite repeat sequences has been observed in colorectal carcinomas and in extracolonic malignancies, predominantly endometrial tumours, occurring in the context of hereditary non-polyposis colorectal cancer (HNPCC). Microsatellite instability (MSI) as a feature of human DNA mismatch repair (MMR)-driven tumourigenesis of the uterine mucosa has been studied primarily in sporadic tumours showing predominantly somatic hypermethylation of MLH1. The present study shows that all endometrial carcinomas (n=12) from carriers of MLH1 and MSH2 germline mutations demonstrate an MSI-high phenotype involving all types of repeat markers, while in endometrial carcinomas from MSH6 mutation carriers, only 36% (4 out of 11) demonstrate an MSI-high phenotype. Interestingly, an MSI-high phenotype was found in endometrial hyperplasias from MSH2 mutation carriers, in contrast to hyperplasias from MLH1 mutation carriers, which exhibited an MSI-stable phenotype. Instability of only mononucleotide repeat markers was found in both endometrial carcinomas and hyperplasias from MSH6 mutation carriers. In 29 out of 31 (94%) endometrial tumour foci, combined MSI and immunohistochemical analysis of MLH1, MSH2, and MSH6 could predict the identified germline mutation. The observation of MSI in endometrial hyperplasia and of altered protein staining for the MMR genes supports the idea that inactivation of MMR genes is an early event in endometrial tumourigenesis. A correlation was found between the variation in the extent and level of MSI and the age of onset of carcinoma, suggesting differences in the rate of tumour progression. A high frequency of MSI in hyperplasias, found only in MSH2 mutation carriers, might indicate a more rapid tumour progression, correlating with an earlier age of onset of carcinoma. The present study indicates that assessment of altered protein staining combined with MSI analysis of endometrial tumours might direct the mutational analysis of MMR genes.

Adult↗
PubMed2000

Can initial serum cyfra 21-1, SCC antigen, and TPA levels in squamous cell cervical cancer predict lymph node metastases or prognosis?

OBJECTIVE: The aim of this study was to determine whether lymph node metastases or prognosis can be predicted by initial serum Cyfra 21-1, tissue polypeptide antigen (TPA), and squamous cell carcinoma antigen (SCC-Ag) levels in squamous cell cervical cancer. METHODS: Pretreatment serum levels of 92 patients were correlated with clinicopathologic parameters and prognostic data. The clinical performance of the tests was evaluated by their receiver operating characteristic curves. The prognostic power of the variables was assessed using Cox regression analysis. RESULTS: Serum levels of each marker were significantly related to tumor stage, size, and depth of infiltration. The clinical performance of each marker in predicting lymph node metastases or parametrial involvement was poor. In the stepwise Cox regression analysis, regarding patients with early stage cervical cancer (stage Ib/IIa, n = 63), tumor size (P = 0.0005) was the only independent prognostic factor for disease-free interval. Lymph node status (P = 0.0014), tumor size (P = 0.004), and parametrial involvement (P = 0.025) were independent risk factors for survival. Considering all patients with stages Ia through IVb disease, tumor size (P = 0.0001) and TPA level (P = 0. 026) were independent risk factors for disease-free interval, whereas tumor size (P = 0.0001) and parametrial involvement (P = 0. 0002) were risk factors for survival. CONCLUSIONS: Pretreatment Cyfra 21-1, TPA, and SCC-Ag levels were strongly related to tumor burden, but insufficiently reliable for identifying patients at risk of the presence of lymph node metastases or parametrial involvement. Serum levels of each marker showed no independent prognostic value in early stage cervical cancer.

Adult↗
PubMed2000

The long learning curve of gynaecological cancer surgery: an argument for centralisation.

OBJECTIVE: To study the development of surgical performance of an unchanging surgical team over 13 years. DESIGN: Prospective, observational study. SETTING: A university hospital, The Netherlands. PARTICIPANTS: Three hundred and eight women who underwent surgical treatment for early cervical cancer. INTERVENTIONS: Radical hysterectomy and pelvic lymphadenectomy between 1 January 1984 and 31 December 1996. RESULTS: The surgical procedure and indication for treatment remained unchanged during the study period. This applied also to the surgical team. The women's age increased significantly during the study years, as was the case with the number of nodes removed. The depth of infiltration by the tumour increased steadily throughout the study, but this failed to reach statistical significance. The distribution of FIGO stages, percentage of positive lymph nodes, radicality of the surgical margins and post-operative morbidity remained the same. Overall, the five year survival rate was 83%; for women with negative nodes 91%, and for women with positive nodes 53%. Survival tended to improve during the course of the study, but this was not statistically significant. Blood loss during surgery decreased consistently during the whole study period, from a mean of 1,515 mL at the beginning of the study to a mean of 1,071 mL at the end (P < 0.0001). The operating time also diminished significantly by 8 minutes per year (P < 0.0001). In 1985 the average operating time was 270 minutes, compared with 187 minutes in 1996. CONCLUSIONS: These findings indicate that it takes a long time to acquire skill in the surgical treatment of early cervical cancer. Centralisation of relatively infrequent operations for cancer should be encouraged.

Adult↗