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Women who carry a BRCA mutation have a greatly increased risk for serous ovarian carcinoma and tubal carcinoma. Since preventative ovarian screening is not effective, these women are advised to undergo prophylactic bilateral salpingo-oophorectomy (pBSO) around the age of 40 years. Following pBSO, hormone replacement therapy is advisable up to the age of 45-50 years, with the exception of those women with a history of breast cancer. The advice for women with a familial history of ovarian carcinoma but without the BRCA mutation is less clear. Based on data from the literature, we suggest considering pBSO only in women with at least two first or second degree family members with epithelial ovarian carcinoma. pBSO is not indicated in women from families without a BRCA mutation who have no family members, or just one family member, with epithelial ovarian carcinoma. In these families the lifetime risk for ovarian cancer is considered to be well below 10%.

To determine the current situation regarding the epidemic of clear cell adenocarcinoma of the vagina and the uterine cervix (CCAC) in relation to the exposure in utero to diethylstilbestrol (DES).Descriptive.Patients with CCAC of the uterine cervix or vagina born after 1946 and diagnosed in the period 1969-2005, were identified through the Nationwide network and registry of histo- and cytopathology in the Netherlands and from 2003 onwards through the Netherlands Cancer Registry. Exposure data and clinical data were obtained by means of questionnaires and medical records. The histology slides of tumours were reviewed. For the patients who did not provide consent, only the date of diagnosis and age at diagnosis were known (n = 10).Up to 2005, 144 CCAC patients were registered. Age at diagnosis varied from 8-54 years (mean: 28 years). In the years 1981-2000, the number of new diagnoses in 4 successive 5-year periods was fairly stable (n=26-30) but it was considerably lower in 2001-2005 (n=13). Of the patients whose history of intrauterine exposure to DES was known, 62% had been exposed (76/122). The mean age at diagnosis was 24 years for exposed patients compared to 32 years for non-exposed patients. The 10-year survival rate was 78% (95% CI: 68-87) for exposed and 69% (95% CI: 56-82) for non-exposed patients.Since 2000, the incidence of CCAC of the vagina and cervix has decreased markedly compared to the situation in the 1980s and 1990 s. In particular, the number of patients with CCAC exposed in utero to DES has decreased. Whether this decrease shall continue over the coming years remains to be seen.

An unassigned and prominent resonance in the region from delta 2.0-2.1 ppm has frequently been found in the in vivo MR spectra of cancer patients. We demonstrated the presence of this resonance with in vivo MRS in the cyst fluid of a patient with an ovarian tumor. (1)H-NMRS on the aspirated cyst fluid of this patient confirmed the observation. A complex of resonances was observed between 2.0 and 2.1 ppm. It was also present in 11 additional ovarian cyst fluid samples randomly chosen from our biobank. The resonance complex was significantly more prominent in samples from mucinous tumors than in samples from other histological subtypes. A macromolecule (10 kDa) was found responsible for this complex of resonances. A correlation spectroscopy (COSY) experiment revealed cross peaks of two different types of bound sialic acid suggesting that N-glycans from glycoproteins and/or glycolipids cause this resonance complex. In the literature, plasma alpha-1 acid glycoprotein (AGP), known for its high content of N-linked glycans, has been suggested to contribute to the delta 2.0-2.1 spectral region. The AGP cyst fluid concentration did not correlate significantly with the peak height of the delta 2.0-2.1 resonance complex in our study. AGP may be partly responsible for the resonance complex but other N-acetylated glycoproteins and/or glycolipids also contribute. After deproteinization of the cyst fluid, N-acetyl-L-aspartic acid (NAA) was found to contribute significantly to the signal in this spectral region in three of the 12 samples. GC-MS independently confirmed the presence of NAA in high concentration in the three samples, which all derived from benign serous tumors. We conclude that both NAA and N-acetyl groups from glycoproteins and/or glycolipids may contribute to the delta 2.0-2.1 ppm resonance complex in ovarian cyst fluid. This spectral region seems to contain resonances from biomarkers that provide relevant clinical information on the type of ovarian tumor.

Sister Mary Joseph nodule is one of the less well-known signs of intra-abdominal metastatic disease. The primary tumor site is nearly always detected because of specific morphologic and immunohistochemical features of the umbilical tumor. We describe a case of a 74-year-old woman with a Sister Mary Joseph nodule, which appeared most likely to be metastatic from a primary serous papillary ovarian carcinoma based on the histologic examination and the immunohistochemical analysis. Despite an extensive workup, no primary tumor could be detected and therefore we ultimately diagnosed the tumor as an extraovarian carcinoma with primary site at the umbilicus. After a literature search we concluded that a primary adenocarcinoma of the umbilicus is extremely rare and to our knowledge has never been described with both morphologic and immunohistochemical features of a serous ovarian carcinoma.

The alpha(v)beta(3) integrin is expressed on proliferating endothelial cells such as those present in growing tumors, as well as on tumor cells of various origin. Tumor-induced angiogenesis can be blocked in vivo by antagonizing the alpha(v)beta(3) integrin with small peptides containing the Arg-Gly-Asp (RGD) amino acid sequence. This tripeptidic sequence, naturally present in extracellular matrix proteins, is the primary binding site of the alpha(v)beta(3) integrin. Because of selective expression of alpha(v)beta(3) integrin in tumors, radiolabeled RGD peptides are attractive candidates for alpha(v)beta(3) integrin targeting in tumors. We studied the in vivo behavior of the radiolabeled dimeric RGD peptide E-[c(RGDfK)](2) in the NIH:OVCAR-3 s.c. ovarian carcinoma xenograft model in BALB/c nude mice. Conjugation of the 1,4,7,10-tetraazadodecane-N,N',N",N"'-tetraacetic acid (DOTA) and hydrazinonicotinamide (HYNIC) chelators enabled efficient radiolabeling with (111)In/(90)Y and (99m)Tc, respectively. The radiolabeled peptide was rapidly excreted renally. Uptake in nontarget organs such as liver and spleen was considerable. Tumor uptake peaked at 7.5% injected dose (ID)/g ((111)In-DOTA-E-[c(RGDfK)](2)) or 6.0%ID/g ((99m)Tc-HYNIC-E-[c(RGDfK)](2)) at 2 and 1 h postinjection, respectively. Integrin alpha(v)beta(3) receptor binding specificity was demonstrated by reduced tumor uptake after injection of the scrambled control peptide (111)In-DOTA-E-[c(RDKfD)](2) (0.28%ID/g at 2 h p.i.) and after coinjection of excess nonradioactive (115)In-DOTA-E-[c(RGDfK)](2) (0.22%ID/g at 2 h p.i.). A single injection of (90)Y-DOTA-E-[c(RGDfK)](2) at the maximum-tolerated dose (37 MBq) in mice with small s.c. tumors caused a significant growth delay as compared with mice treated with 37 MBq (90)Y-labeled scrambled peptide or untreated mice (median survival of 54 versus 33.5 versus 19 days, respectively). In conclusion, the radiolabeled RGD peptides (111)In-DOTA-E-[c(RGDfK)](2) and (99m)Tc-HYNIC-E-[c(RGDfK)](2) demonstrated high and specific tumor uptake in a human tumor xenograft. Injection of (90)Y-DOTA-E-[c(RGDfK)](2) induced a significant delay in tumor growth. Potentially, these peptides can be used for peptide receptor radionuclide imaging as well as therapy.