Primary fallopian tube cancer

Primary fallopian tube cancer (PFTC) is a rare and aggressive gynecologic malignancyand it accounts for less than 5% of all genital female cancers according to the SwedishCancer Registry. In a retrospective study we have analysed histopathological, clinical,biological and prognostic factors among patients with PFTC. 128 cases of PFTC treatedbetween 1923 and 1991 were histopathologically reviewed and retrospectively stagedaccording to the new FIGO staging system. Seventy-four percent were found to be instage Ia-IIa, compared to 36% in stage Ia-IIa among ovarian cancer cases treatedat Radiumhemmet in 1958 to 1973. In stage Ia a 5-year actuarial survival of 70.1%was demonstrated. Forty-five percent were nulliparous and the mean age at diagnosiswas 56 years. Twenty-two per cent were suffering from salpingitis and the infertilityrate was 25%. Among the 14 variables studied in the clinical and pathological reviewand tested in the multivariate analysis the first in rank were the stage (p=0.001)and grade of differentiation of the tumors (p=0.070). Treatment modalities changedduring the studied period. Thirty-three per cent of patients underwent surgery withtotal abdominal hysterectomy and bilateral salpingo oophorectomy. Patients receivingchemotherapy had superior survival rates (p=0.0006) and patients with cisplatinum-containingchemotherapy did better than those without. In this thesis, attempts have been made to further characterize the malignancypotential of the PFTC by biological prognostic factors. The patients in the matenalwere divided into two groups according to survival time and the interval was chosenin order to get a maximal contrast with regard to survival at a minimal cost - short-timesurvivors < 2years and long-time survivors > 8 years. We have evaluated theDNA ploidy content, proliferative activity (MIB-I), p53 overexpression combined ornot with the downstream product p21/WAF-I, and tumor angiogenesis (F8) in correlationto clinical outcome. Furthermore, we studied the frequences of p53 mutations in PFTCand in their corresponding metastases/recurrences as well as the influence of p53on therapeutic effect and clinical course in individual cases with careful clinicalfollow-up. All PFTCs showed aneuploid DNA distribution patterns. The following investigated biological markers (DNA, MIB-I, P53, p21/WAF-I, F8)could not discriminate between short- and long-time survivors. A tendency to increasedfrequency of mutations (combined p53 and p21/WAF-I) was found among short-time survivorsin stage I as well as in stage IV. Increasing MIB-I correlated to poor survival in a multivariate analysis of stageI cases. MMMT showed aneuploid DNA content patterns. MIB-I, p53, WAF-I, and F8did not allow discrimination between short- and long-time survivors. A comparison of SSCP and CDGE suggests that CDGE is superior as a TP53 genemutation detection method. In spite of the limited number of cases investigated, our data indicate thatp53 immunoreactivity and TP53 mutation analysis is not correlated to tumor progression,survival and response to treatment. CGH analysis indicates that PFTC is a genomically highly unstable type of malignancyand 3 q gain/ amplification is the major event. The frequent 3q-gains observed inHPV infected cervical carcinoma do not appear to be related to the insertion of virusDNA since all PFTC cases studied were found to be exclusively HPV negative. In conclusion, this study has confirmed that PFTC is an aggressive gynecologicmalignancy which showed a high number of chromosomal aberrations comprising all chromosomesand without connection to HPV infection. This is in agreement with the high frequency(100%) of DNA aneuploid cases. None of the biological markers investigated was foundto be of principal value in predicting the clinical outcome of PFTC. Only the clinicalstage was found to be significantly related to patient survival. Key words: primary fallopian tube cancer, prognosis, symtoms, treatment, staging,DNA ploidy, cell proliferation, tumor angiogenesis, p53, p21/WAF I expression, HPV,CGH, PCR/SSCP, CDGE ISBN 91 -628-2742-

Preoperative MR staging of cervical carcinoma: are oblique and contrast-enhanced sequences necessary?

Background As the choice of treatment in patients with cervical carcinoma depends on cancer stage at diagnosis, accurate staging is essential. Purpose To compare three different combinations of magnetic resonance (MR) sequences for preoperative staging. Material and Methods Fifty-seven consecutive patients with biopsy proven cervical carcinoma underwent MR imaging (MRI) staging followed by primary surgical treatment. Thirty-two of 57 patients had had a cone biopsy prior to MRI. Three MR pulse sequence combinations were retrospectively reviewed by two experienced radiologists. The first imaging protocol consisted of pre-contrast sagittal and transverse images (protocol A), the second protocol included additionally oblique high-resolution T2-weighted (T2W) MR images of the cervix (protocol A+B), and the third included also contrast-enhanced sequences (protocol A+B+C). The imaging findings in the three steps (A, A+B, A+B+C) were recorded. The TNM stage was used for comparison between preoperative imaging and histopathology. Histopathology, together with surgical findings, served as gold standard. Results In 4/57 (7%) patients, the MR assessment of tumor stage (mrT) was altered when oblique sequences were added to the standard two plane imaging protocol (A+B). The mrT stage was altered in 1/57 (2%) patient when contrast-enhanced sequences were added to standard and oblique sequences (protocol A+B+C). The correlation between visible tumor on MRI and presence of tumor in the resected specimen did not change by adding oblique or contrast-enhanced images. Conclusion It is not necessary to perform oblique and contrast-enhanced sequences in small cervical carcinomas, i.e. without parametrial invasion. To avoid erroneous interpretation, information on previous cone biopsy is essential

Cost of Preventing, Managing, and Treating Human Papillomavirus (HPV)-Related Diseases in Sweden before the Introduction of Quadrivalent HPV Vaccination

<div><p>Objective</p><p>Costs associated with HPV-related diseases such as cervical dysplasia, cervical cancer, and genital warts have not been evaluated in Sweden. These costs must be estimated in order to determine the potential savings if these diseases were eradicated and to assess the combined cost-effectiveness of HPV vaccination and cervical cancer screening. The present study aimed to estimate prevention, management, and treatment costs associated with cervical dysplasia, cervical cancer, and genital warts from a societal perspective in Sweden in 2009, 1 year before the quadrivalent HPV vaccination program was implemented.</p><p>Methods and Materials</p><p>Data from the Swedish cervical cancer screening program was used to calculate the costs associated with prevention (cytological cervical cancer screening), management (colposcopy and biopsy following inadequate/abnormal cytological results), and treatment of CIN. Swedish official statistics were used to estimate treatment costs associated with cervical cancer. Published epidemiological data were used to estimate the number of incident, recurrent, and persistent cases of genital warts; a clinical expert panel assessed management and treatment procedures. Estimated visits, procedures, and use of medications were used to calculate the annual cost associated with genital warts.</p><p>Results</p><p>From a societal perspective, total estimated costs associated with cervical cancer and genital warts in 2009 were €106.6 million, of which €81.4 million (76%) were direct medical costs. Costs associated with prevention, management, and treatment of CIN were €74 million; screening and management costs for women with normal and inadequate cytology alone accounted for 76% of this sum. The treatment costs associated with incident and prevalent cervical cancer and palliative care were €23 million. Estimated costs for incident, recurrent and persistent cases of genital warts were €9.8 million.</p><p>Conclusion</p><p>Prevention, management, and treatment costs associated with cervical dysplasia, cervical cancer, and genital warts are substantial. Defining these costs is important for future cost-effectiveness analyses of the quadrivalent HPV vaccination program in Sweden.</p></div

Unit cost of resources expressed in 2009 Euros (€).

<p>^a) Indirect productivity-related costs are estimated based on travel time to and from care site, wait time and visit time [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0139062#pone.0139062.ref020" target="_blank">20</a>], treatment, and follow-up or sick leave due to cervical cancer [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0139062#pone.0139062.ref021" target="_blank">21</a>].</p><p>^b) KPP [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0139062#pone.0139062.ref032" target="_blank">32</a>].</p><p>^c) KPP 2009.</p><p>^d) Total cost including staging, treatment, and follow up [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0139062#pone.0139062.ref021" target="_blank">21</a>].</p><p>^e) Costs included procedure and pharmacological treatment at home and hospice care retrieved from the palliative care unit and advanced home care unit, Långbro Park, Stockholm County Council. Average cost per day of care at home was based on calculations from a previous Swedish report on advanced care at home in Sweden [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0139062#pone.0139062.ref025" target="_blank">25</a>].</p><p>^f) KPP 2009, clinical expert panel.</p><p>^g) The Dental and Pharmaceutical Benefits Agency (available in English at <a href="http://www.tlv.se" target="_blank">http://www.tlv.se</a>)</p><p>CIN: cervical intraepithelial neoplasia; LEEP: loop electrode excision procedure; KPP: cost per patient</p><p>Unit cost of resources expressed in 2009 Euros (€).</p

Cost of treating genital warts in Sweden, expressed in 2009 Euros (€).

<p>Cost of treating genital warts in Sweden, expressed in 2009 Euros (€).</p

Number and mean percentage of patients undergoing different treatment procedures for genital warts based on estimates from the clinical expert panel.

<p>Number and mean percentage of patients undergoing different treatment procedures for genital warts based on estimates from the clinical expert panel.</p

Annual cost of prevention, management, and treatment of CIN and cervical cancer in Sweden, expressed in 2009 Euros (€).

<p>N = number of women</p><p>^a) Cases were multiplied by the number of follow up-procedures according to recommendations after treatment as previously described in detail [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0139062#pone.0139062.ref021" target="_blank">21</a>].</p><p>^b) Average cost of LEEP and other procedure included 1 follow-up procedure according to current national guidelines (available at <a href="http://www.sfog.se" target="_blank">http://www.sfog.se</a>).</p><p>CIN: cervical intraepithelial neoplasia; LEEP: loop electrode excision procedure</p><p>Annual cost of prevention, management, and treatment of CIN and cervical cancer in Sweden, expressed in 2009 Euros (€).</p