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Ovarian cancer

Ovarian cancer. 650-700 nye tilfælde årligt i DK (incl. 150-200 Borderline) Livstidsrisiko - 2% Udgør 30 % af alle gynækologiske cancere Udgør 3,8% af kræft hos kvinder Stiger med alderen 1/3 er yngre end 60 år 90 % epithelial carcinoma.

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Ovarian cancer

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  1. Ovarian cancer • 650-700 nye tilfælde årligt i DK • (incl. 150-200 Borderline) • Livstidsrisiko - 2% • Udgør 30 % af alle • gynækologiske cancere • Udgør 3,8% af kræft hos kvinder • Stiger med alderen • 1/3 er yngre end 60 år • 90 % epithelial carcinoma

  2. Hyppigere i Danmark end i resten af Europa....

  3. Årsager til kræft i æggestokken • Hypoteser • Celleskade ved ægløsningen • Påvirkning fra hormoner i kroppen • Udefra kommende carcinogener

  4. EtiologyRisk factors • Hereditary – 10 % • BRCA I & II prof lap BSO • HNPCC • Reproductive factors • Nulliparity • Infertility • Contraceptive pill • Tidlig menarch – sen menopause • Exogene factors • Talcum • Tubal ligation / hysterectomi

  5. Familiær mamma / ovarie cancer • HBOC • Kromosom 17q og 13q • BRCA1 og BRCA2 • Defekt evne til at reparere DNA

  6. Familiær kræft i tyktarm • HNPCC • Kromosom 2 og 7 • Mismatch repair (MMR) system • hMLH1, hMSH2, hMSH6, and hPMS2 • 45% risiko for kræft i livmoderen • 10 % risiko for kræft i æggestok

  7. Symptomer ved kræft i æggestokken • er oftest svage.... • Øget omfang af maven • Tyngdefornemmelse • Forstoppelse - diarré • Hyppig vandladning • Træthed • Almen sygdomsfølelse

  8. STADIER St IV Yderligere spredning St III Også i øvre del af bughulen St.II Begrænset til underlivet St. I Begrænset til æggestokkene

  9. Stage St I only the ovary (ies) St II pelvic involvement St IIIa Upper abdomen microscopic IIIb Upper abdomen < 2 cm IIIc Upper abdomen > 2 cm or node pos. St IV levermetastases, above diagphragm, groins, bowel

  10. Stadier St IV - 70 % Yderligere spredning St III - 70% Også i øvre del af bughulen St.II - 15 % Begrænset til underlivet St. I - 15 % Begrænset til æggestokkene

  11. Stadier 5-års overlevelse St IV – 10-20 % Yderligere spredning St III - 40 % Også i øvre del af bughulen St.II - 65 % Begrænset til underlivet St. I - 85 % Begrænset til æggestokkene

  12. Prognosis5 year suvival • St I 85% • St II 65% • St III 40 % = 70 % of all o.c. • St IV 10-20 %

  13. Forbedre overlevelse… Danmark…..

  14. Udredning • Gynækologisk undersøgelse • Ultralydscanning • Blodprøver ~ CA-125

  15. Udredning RMI(Risk of Malignancy Index) • Menopause x UL-score x CA-125 • > 200 PAKKEFORLØB

  16. PET - CT

  17. C PET-CT scanningdiss sygdom hjertet nyre blæren Herlev Hospital, klinisk fysiologisk afd.

  18. Behandling • • Operation • • Kemoterapi

  19. Treatment – ovarian cancer • Surgery (RMI< 200: laparoscopy frozen section) • Bilat salpingooopherectomy • Hysterectomy • Omentectomy • Lymphadenectomy • (Appendectomy) NO RECIDUAL TUMOR Maximal debulking bowel, spleen, diagphragm

  20. Kemoterapi To-tre-stof-behandling Carboplatin og taxol, bevazicumab 6/3uger

  21. Neoadjuverende kemoterapi - 3 serier • efterfulgt af operation • Dissimineret sygdom - inoperabel • Høj alder • Comorbiditet

  22. Teknik – lille bækken • Adgang til retroperitoneum • Ureteres frilægges • Uterus fjernes extraperitonealt, • idet vagina åbnes 3-9, ned under peritoneum sv.t fossa Douglasi, så højt på rectum som nødvendigt

  23. Pelvis

  24. Teknik – øvre abdomen • Incisionen forlænges • Ligamentum falciforme deles • Leveren mobiliseres • Peritoneum på diagphragma reseceres skarpt • Omentectomi • Colonresektion, splenectomi, ect

  25. Extensivt kirurgisk indgreb omfattende Lille bækken: En bloc resektion af genitalia interna, peritoneum og tarmsegment, med primær tarmanastomose eller stomi, blære- og ureterresektion. Øvre abdomen: Omentectomi, operation på diaphragma (peritoneal resektion eller argon beaming), splenectomi, resektion cauda pancreatis, yderligere tarmresektion Operationsvarighed 4-8 timer

  26. Case • 39-årig kvinde • UL: bilat , multicyst ovarietumorer, hhv 6 og 4 cm • CA-125 = 63 • Hvad gør vi ?

  27. Udredning RMI(Risk of Malignancy Index) • Menopause x UL-score x CA-125 • UL malignitetskriterier : > Bilokulær , Solide områder, Bilateral ,Excrescenser , Ascites, + Extra-ovariel sygdom

  28. Udredning RMI(Risk of Malignancy Index) • Menopause x UL-score x CA-125 • 1 x 3 x 63= 189 dvs < 200

  29. Udredning RMI(Risk of Malignancy Index) • Menopause x UL-score x CA-125 • < 200 Laparoskopi • USO til frys

  30. Case • 46 årig præmenopausal kvinde • UL: multilokulær tumor, ve adnex • PET-CT: mulig carcinose i lille bækken + øvre abd • CA-125 = 841 • Hvad gør vi ?

  31. Åben laparoskopi ved avanceret ovariecancer • Be-/afkræfte diagnosen – 2/3 vs 1/3 • Vurdere operabilitet – 90 %, • Tilrettelægge/udnytte operationstid mere rationelt • Planlægge evt gastrokirurgisk assistence • Ingen neg effekt på prognosen

  32. Open laparoscopy in advanced ovarian cancer • Open laparoscopy - the best technique to • evaluate operability, • plan operating time of debulking surgery • make a histological diagnosis, • exclude other primary tumors (or benign disease) • refer patients to a tertiary center

  33. Other studies on laparoscopy to judge operability • Fagotti et al (Gyn Oncol 2005): Optimal reduction in 90% of the patients jugded to be operable. • Deffieux et al (Int J Gyn Cancer 2006). 10/11 patients thought to be resectable were resected to no residual tumor. • Angioli et al (Gyn Oncol 2006): Optimal reduction (R0) in 96% of the patients jugded to be operable (i.e. n = 53/87 or 61%).

  34. Open Laparoscopy in stage III and IV ovarian carcinoma (n=228,1995 - 2002)Vergote et al Int J Gynecol Cancer 2005 15:776-9 • 55 patients (32%) with suspect ovarian mass in combination with omental cake and/or ascites have no ovarian carcinoma stage III or IV (metastases from other primaries, stage I-II, benign, ..) • 90% of the patients with advanced ovarian carcinoma (n = 173) judged to be operable were optimally debulked. • In 71 patients the port sites were completelyexcised at the time of debulking.

  35. Åben laparoskopi ved advanceret ovariecancer • Længdeincision (3 cm) under umbilicus • Fascie og peritoneum åbnes • Sikre sig fri adgang • Trokar med stump spids, ballon på peritonealsiden, skumkrave på hudsiden

  36. Laparoscopy to judge operability Definitions for inoperability: • Extended visceral peritoneal disease • Extended small bowel involvement • Large involvement of upper abdomen (diaphragm, liver, porta) • Heavily bleeding tumors Sammenholdes med PET-CT

  37. Indications for neoadjuvant chemotherapy 1. Tumors larger than 2 cm around the superior mesenteric artery or around the porta hepatis, or 2. Intrahepatic (multiple) metastases or several extraabdominal metastases (excluding resectable inguinal or supraclavicular lymph nodes) larger than 2 cm , or 3. Poor general condition (e.g. > 80 years) making a “maximal surgical effort” to no residual tumor impossible, or 4. Extensive serosal invasion (e.g. plaques) of the intestines necesitating bowel resections of > 1.5 m

  38. Case • C ovarii st IIIC, makroradikal operation 2012 • Adjuv kemoterapi (carbo/tax) • 9 mdr kontrol: velbefindende • CA-125= 86 Hvad gør vi ?

  39. Early treatment of relapsed ovarian cancer based on CA125 level alone versus delayed treatment based on conventional clinical indicators Results of the randomized MRC OV05 and EORTC 55955 trials Gordon Rustin (Mount Vernon Cancer Centre) and Maria van der Burg On behalf of all OV05 and 55955 Collaborators 31st May 2009

  40. 1.00 0.75 Proportion alive not started second-line chemotherapy 0.50 0.25 0.00 0 3 6 9 12 15 18 21 24 Months since randomisation Number at risk Early 265 23 16 14 11 11 10 10 9 264 177 116 91 69 56 49 42 33 Delayed Time from randomisation to second-line chemotherapy Median (months) Early 0.8 Delayed 5.6 HR=0.29 (95% CI 0.24, 0.35) p<0.00001

  41. 1.00 0.75 Proportion surviving 0.50 0.25 0.00 0 6 12 18 24 30 36 42 48 54 60 Months since randomisation Number at risk Early 265 247 211 165 131 94 72 51 38 31 22 Delayed 264 236 203 167 129 103 69 53 38 31 19 Overall Survival HR=1.00 (95%CI 0.82-1.22) p=0.98 Abs diff at 2 years= 0.1% (95% CI diff= -6.8, 6.3%) Early Delayed

  42. Conclusions • In early treatment arm based on rise in CA125 • Second-line chemotherapy started a median of 4.8 months earlier • Third-line chemotherapy started a median of 4.6 months earlier • This early treatment did not improve overall survival • HR=1.00, 95% CI 0.82-1.22, p=0.98 • Absolute difference at 2 years 0.1% (95%CI -6.8, 6.3%) • Early chemotherapy does not improve Qol

  43. HOT scientific topics • Ovarian cancer • Difference among countries • Lymphadenectomy • Extensive surgery • Neoadjuvant chemotharapy • Recurrence – surgery

  44. HOT scientific topics • Ovarian cancer • Difference among countries • Lymphadenectomy • Extensive surgery • Neoadjuvant chemotharapy • Recurrence – surgery

  45. Benchmarking study • Modul 1: Basis-benchmarking på grundlag af eksisterende data • Modul 2: Patienters opmærksomhed på egen sundhedstilstand, herunder patienters kultur og opfattelser • Modul 3: Almen praksis’ kultur, opfattelser og ageren • Modul 4: Årsager til forsinkelser i diagnosticeringen • Modul 5: Behandlingskvalitet

  46. Cancer survival in Australia, Canada, Denmark, Norway,Sweden, and the UK, 1995–2007 (the International CancerBenchmarking Partnership): an analysis of population-basedcancer registry data Lancet 2011; 377: 127–38 Interpretation Up-to-date survival trends show increases but persistent differences between countries. Trends in cancer incidence and mortality are broadly consistent with these trends in survival. Data quality and changes in classification are not likely explanations. The patterns are consistent with later diagnosis or differences in treatment, particularly in Denmark and the UK, and in patients aged 65 years and older.

  47. Stage at diagnosis and ovarian cancer survival: Evidence from the InternationalCancer Benchmarking Partnership, Gynecologic OncologyData from population-based cancer registries in Australia, Canada, Denmark, Norway, and the UK were analysed for 20,073 women diagnosed with ovarian cancer during 2004–07. Results. One-year survival was 69% in the UK, 72% in Denmark and 74–75% elsewhere. In Denmark, 74% of patients were diagnosed with FIGO stages III–IV disease, compared to 60–70% elsewhere. International differences in survival were evident at each stage of disease; women in the UK had lower survival than in the other four countries for patients with FIGO stages III–IV disease (61.4% vs. 65.8–74.4%). International differences were widest for older women and for those with advanced stage or with no stage data

  48. DGCG

  49. HOT scientific topics • Ovarian cancer • Difference among countries • Lymphadenectomy • Extensive surgery • Neoadjuvant chemotharapy • Recurrence – surgery

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