| 1. |
- Bjersand, Kathrine
(författare)
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Predictive and prognostic factors of epithelial ovarian cancer and pseudomyxoma peritonei
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of my thesis was to investigate potential prognostic and predictive factors associated with the tumor cells of epithelial ovarian cancer (EOC) and the gastrointestinal tumor pseudomyxoma peritonei (PMP) to improve and individualize cancer therapy. Both PMP and EOC can develop into peritoneal carcinomatosis (PC), which is characterized by widespread metastasis of cancer tumors in the peritoneal cavity. Major improvements in the management of PC, such as cytoreductive surgery in combination with chemotherapy, have dramatically changed the prognosis.To further optimize and tailor treatment, increased knowledge on tumor biology and pathogenesis is needed. Today’s choice of treatment is mainly based on clinical trials and standard protocols that have not taken individual differences in drug sensitivity into consideration. With ex vivo testing of tumor drug sensitivity, individuals at risk of side effects only (and no treatment benefit) could potentially be identified prior to treatment.Napsin A is an anti-apoptotic protein that promotes platinum resistance by degradation of the cell cycle regulator and tumor suppressor TP53. Immunohistochemical stainings of 131 early EOC tumors in study I showed that expression of Napsin A was associated with expression of the apoptosis regulators p21 and p53 and with histological subtype. Positivity of Napsin A in an epithelial ovarian tumor strengthens the morphological diagnosis of clear cell carcinoma and should be useful in diagnostics. In study II, the relevance of the proteins HRNPM and SLC1A5 as prognostic factors for recurrent disease, survival and impact on clinical or pathological features was evaluated in 123 patients with early EOC. Our results support concomitant positivity of HRMPM and PUMA/p21 in ovarian cancer and indicate that HRNPM may trigger activity in systems of cell cycle regulation and apoptosis. In subgroup analyses of tumors from patients with non-serous EOC histology, expression of SLC1A5 was shown to be a prognostic factor in terms of prolonged disease-free survival. In studies III and VI, we investigated the ex vivo drug sensitivity of tumor cells from EOC and PMP with the 72-h cell viability assay fluorometric microculture cytotoxicity assay (FMCA). The two studies confirm that drug sensitivity varies considerably between tumor samples from patients within the same diagnostic group. In ovarian cancer, ex vivo results show that type I tumors were generally less sensitive to cytotoxic agents than type II tumors. Samples from patients previously exposed to cytotoxic drugs generally tended to be more resistant to most drugs than samples from unexposed patients in both EOC and PMP. This observation is in line with clinical experience and findings supporting that exposure to cytotoxic treatments contribute to development of chemo-resistance mechanisms. In ovarian cancer, resistance to the kinase inhibitors after exposure varied but was less pronounced than that for standard cytotoxic drugs. In PMP patients, ex vivo drug sensitivity provided prognostic information for progression-free survival, and this is in line with earlier findings.
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| 2. |
- Brännström, Mats, 1958, et al.
(författare)
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Uterus transplantation: A Rapidly Expanding Field
- 2018
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 102:4, s. 569-577
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Forskningsöversikt (refereegranskat)abstract
- Uterus transplantation (UTx) has been successfully introduced as a treatment option for women with absolute uterine factor infertility (AUFI). AUFI representing approximately 3% to 5% of the female general population is linked to either congenital uterine agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome), major congenital uterine malformation (hypoplastic uterus, fraction of bicornuate/unicornuate uterus), a surgically absent uterus, or an acquired condition (intrauterine adhesions, leiomyoma) linked to uterine malfunction that causes implantation failure or defect placentation. The world's first clinical uterus transplant was performed in 2000. However, a hysterectomy became necessary shortly after the surgery due to uterine necrosis. In 2011, a group in Turkey reported on a surgically successful deceased donor transplant; however, this procedure has, to date, not resulted in a healthy live birth, the ultimate goal of UTx. Building on an extensive experimental background in various animal models, including primates, the Gothenburg group led by Brannstrom reported on the first delivery of a healthy baby in a recipient of a live donor UTx in 2014. This event did not only show the feasibility of UTx, it also helped defining relevant areas of clinical and basic research. Use of a gestational surrogate carrier, is, at least in theory, an alternative for a woman with AUFI seeking genetic motherhood. However, in the clear majority of countries worldwide, gestational surrogacy is not practiced based on legal, ethical, or religious concerns. Of note, the overwhelming majority of surveyed women in the United Kingdom, a country which permits surrogacy, preferred UTx over gestational surrogacy and adoption. Moreover, randomly selected women of fertile age in Sweden preferred UTx over gestational surrogacy. A recent large survey in Japan with more than 3000 participants revealed that UTx had a twofold higher acceptance rate compared with gestational surrogacy. In a recent US survey exploring the potential of donating vascularized composite allografts, uterus donation achieved the highest priority. Thus, the acceptance of UTx as infertility treatment for women with AUFI is high, although the procedure remains in its infancy. Here, we provide an update of clinical activities, summarize achievements and challenges, and submit areas of research interests.
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| 3. |
- Hjerpe, Elisabet, et al.
(författare)
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Lymph node metastases as only qualifier for stage IV serous ovarian cancer confers longer survival than other sites of distant disease - a Swedish Gynecologic Cancer Group (SweGCG) study.
- 2018
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Ingår i: Acta oncologica (Stockholm, Sweden). - : TAYLOR & FRANCIS LTD. - 1651-226X .- 0284-186X. ; 57:3, s. 331-337
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Tidskriftsartikel (refereegranskat)abstract
- The International Federation of Gynecology and Obstetrics (FIGO) ovarian cancer staging system includes no sub-stage for lymph nodes (LN) as only distant disease manifestation. We explore the prognostic implication of LN as only stage IV classifier in serous ovarian cancer.This is a nation-wide, population-based study on 551 women with serous stage IV cancers diagnosed between 2009-2014. We compare overall survival (OS) in women with LN as only distant metastatic site to those with pleural metastases only and to patients with other/multiple stage IV manifestations. Cox regression models were used for uni- and multivariable estimations.Of 551stage IV cases, distant metastatic site was registered in 433. Median OS for women with LN (n=51) was 41.4 months, compared to 25.2 and 26.8 months for patients with pleural (n=195) or other/multiple (n=187) distant metastases (p=.0007). The corresponding five-year survival rates were 32, 11 and 22%, respectively. Multivariable analyzes confirmed shorter survival for women with pleural (HR 2.99, p=.001) or other/multiple distant sites (HR 2.67, p=.007), as compared to LN cases. LN only patients lived 9.1 months longer after primary than after interval surgery, but this difference was not significant (p=.245).Women with stage IV serous ovarian cancer having lymph nodes as only distant metastatic site live longer than other stage IV patients.
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| 4. |
- Lindfors, Anna, et al.
(författare)
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Robotic vs Open Surgery for Endometrial Cancer in Elderly Patients: Surgical Outcome, Survival, and Cost Analysis.
- 2018
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Ingår i: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. - 1525-1438. ; 28:4, s. 692-699
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to compare robotic and open surgery in elderly women diagnosed as having endometrial cancer, in terms of costs, survival, surgical outcome, and operating time.Women 70 years or older undergoing open and robotic surgery for endometrial cancers were included consecutively before and after the introduction of robotic surgery at a tertiary center. Costs were calculated using the case-costing system, cost per patient, including the first 30 postoperative days. Relative and overall survival outcomes were obtained from the Swedish National Cancer Registry and analyzed using the Kaplan-Meier method. Surgical outcomes including operating and anesthesia times, estimated blood loss, hospital stay, and intraoperative and postoperative complications were reviewed.In all, 137 and 141 women 70 years or older were identified to have undergone open and robotic surgery, respectively. The groups showed similar body mass index, comorbidities, and tumor characteristics. No statistically significant differences were seen in costs (robotic &OV0556;11,874 vs open &OV0556;11,521, P = 0.463) or 5-year survival outcomes (robotic 94% [95% confidence interval {CI}, 84-105] vs open 87% [95% CI, 78-98], P = 0.529). Robotic surgery was associated with significantly lower estimated blood loss (P < 0.001) and shorter hospital stay (P < 0.001) but longer anesthesia time (186 vs 174 minutes; P < 0.05) and operating theater time (205 vs 190 minutes; P < 0.05). There were no significant differences in intraoperative complications, but robotic surgery resulted in fewer postoperative Clavien-Dindo grade II complications.Elderly women can safely undergo robotic surgery for endometrial cancer and could be offered this technique to the same extent as younger patients. They may benefit from shorter hospital stay, decreased blood loss, and postoperative complications, without resulting in higher costs to the health care system or jeopardizing their survival.
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| 5. |
- Rosenberg, P., et al.
(författare)
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Data quality in the Swedish Quality Register of Gynecologic Cancer - a Swedish Gynecologic Cancer Group (SweGCG) study
- 2018
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 57:3, s. 346-353
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of this study is to evaluate the quality of data on endometrial (EC) and ovarian, fallopian tube, peritoneal, abdominal or pelvic cancers (OC) registered in the Swedish Quality Register of Gynecologic Cancer (SQRGC).Method: A random sample of 500 patients was identified in the SQRGC and their medical charts were reviewed for re-abstraction of 31 selected core variables by an independent validator. The data in the SQRGC and the re-abstracted data were compared. The data were collected from 25 hospitals evenly distributed throughout Sweden. The main outcomes were comparability, timeliness, completeness and validity. Coverage was compared with the National Cancer Register (NCR). Timeliness was defined as the speed of registration i.e. when patients were registered in the SQRGC relative to date of diagnosis. Internationally accepted coding systems for stage, grading and histologic type were used ensuring a high degree of comparability. Correlations were estimated using Pearson's correlation coefficient and Cohens kappa coefficient.Results: The completeness was 95%. The timeliness was 88-91% within 12 months of diagnosis. The median degree of agreement between re-abstracted data and data in the SQRGC was 82.1%, with a median kappa value of 0.73 for ordinate variables and a median Pearson's correlation coefficient of 0.96. The agreements for the type of surgery were 76% (95% CI 70-81%; kappa 0.49) and type of primary treatment 90% (95% CI 87-94%; kappa 0.85) in OC and in EC 88% (95% CI 84-93%; kappa 0.84). The agreements for the FIGO stage were in OC and EC 74% (95% CI 68-80%; kappa 0.69) and 87% (95% CI 82-91%; kappa 0.79), respectively.Conclusions: The data in the Swedish Quality Register for Gynecologic Cancer are of adequate quality in order to be used as a basis for research and to evaluate possible differences in treatment, lead times and treatment results.
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