Pseudomyxoma peritonei (PMP) is a rare disease characterized by mucinous peritoneal metastasis (PM). Different loco-regional treatment strategies, i.e. debulking surgery and cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC), have changed the prognosis for these patients. CRS is an aggressive surgical procedure with a long learning curve. PMP exists in different types; how many depends on which classification is used. The aims of this thesis were to investigate the time-frame of PMP development from an isolated appendiceal neoplasm, examine the learning process for CRS, evaluate the differences in treatment outcome between debulking surgery and CRS in combination with HIPEC, to evaluate a more detailed PMP classification and to investigate particularly interesting new cysteine-histidine (PINCH) protein as a prognostic factor for PMP. Retrospectively 26 PMP patients were identified as having had an appendectomy with a neoplasm in the appendix but with no evidence of PM at the appendectomy. They were treated for PMP within a median of 13.1 months (3.8-95.3) after the appendectomy. No difference was seen between the types of PMP regarding the time to a clinically significant development of PMP and how much tumour was found at treatment. CRS is a highly invasive treatment and stabilization in the learning curve was seen after 220±10 procedures. Patients treated with CRS+HIPEC had a better 5-year overall survival (OS) than patients treated with debulking surgery, 74% vs. 40%. CRS increased the rate of complete cytoreduction from 25% in patients treated with debulking surgery to 72%. The new four-grade PMP classification showed very good inter-rater agreement between two independent pathologists and a difference in survival rates was observed between the different grades. A positive PINCH staining was recorded in 83% of the tumours and that was associated with poorer survival.

A carcinogênese epitelial ovariana tem sido foco de estudos científicos em todo o mundo desenvolvido. A angiogênese tumoral ovariana é um processo multifatorial que resulta em vários produtos pró-angiogênicos. Entre eles, o fator de crescimento vascular endotelial (VEGF) é predominante. Os objetivos deste estudo foram relacionar as dosagens do VEGF dos fluidos peritoneais, do plasma periférico e do infundíbulo pélvico aos níveis de citorredução em pacientes operadas de adenocarcinoma epitelial de ovário (CEO); formular um modelo probabilístico de citorredução e utilizar estas dosagens para estimar a probabilidade do desfecho de citorredução. Além disto, foi criada uma nova variável chamada carga de VEGF. Pelo procedimento step-wise a citorredução foi melhor descrita pela carga de VEGF, mas faltou Normalidade aos resíduos, não sendo possível a adequação de um modelo matemático. Porém, a curva ROC, forneceu uma área sob a curva de 0,84, com sensibilidade de 71,4 % e especificidade variando de 69,5 a 73,9%. O ponto de corte ótimo foi 15,52 log de picograma de carga de VEGF. A odds-ratio (OR) calculada para citorredução ótima descrita pela carga de VEGF foi de 11 (IC= 2,59 ; 46,78). No grupo com estágio avançado (III e IV), a OR foi de 6 (IC= 1,15; 31,22). Apesar do pequeno número de casos, esta nova variável pode vir a ser um auxiliar na determinação de situações onde cirurgia citorredutora deixa de ser a pedra fundamental do tratamento primário do CEO e a indução quimioterápica passe a ter o principal papel na citorredução química antes da cirugia nestes casos. / Epithelial ovarian carcinogenesis has been the focus of scientific studies in developed world. The ovarian tumor angiogenesis is a multifactorial process that results in pro-angiogenic products. Among them, vascular endothelial growth factor (VEGF) is predominant. This study aimed to relate VEGF levels in peritoneal fluids, peripheric plasma and pelvic infundibular plasma to debulking levels in patients operated on for epithelial ovarian carcinoma (EOC), formulate a probabilistic model for debulking and use these measurements to estimate the probability of the outcome of debulking. Moreover, it was created a new variable called burden of VEGF. For step-wise procedure, cytoreduction was better described by of burden VEGF, but missed Normality of residuals, so the adequacy of a mathematical model was not possible. Nevertheless, the ROC curve provided an area under the curve of 0.84, with sensitivity of 71.4 % and especificity varying from 69.5 to 73,9%. The optimal cutoff point was 15.52 log of picograms of VEGF burden. An odds-ratio for optimal cytoreduction described by the VEGF burden was 11 (CI= 2.59; 46.78). In the group with advanced stages (III & IV), the OR was 6 (CI= 1.15; 31.22). Apart from the small number of cases, this new variable might help to determine situations where cytoreductive surgery leaves behind the cornerstone of primary treatment of CEO and the chemotherapic induction comes to have main role in chemical cytoreduction prior to surgery in these cases.

A carcinogênese epitelial ovariana tem sido foco de estudos científicos em todo o mundo desenvolvido. A angiogênese tumoral ovariana é um processo multifatorial que resulta em vários produtos pró-angiogênicos. Entre eles, o fator de crescimento vascular endotelial (VEGF) é predominante. Os objetivos deste estudo foram relacionar as dosagens do VEGF dos fluidos peritoneais, do plasma periférico e do infundíbulo pélvico aos níveis de citorredução em pacientes operadas de adenocarcinoma epitelial de ovário (CEO); formular um modelo probabilístico de citorredução e utilizar estas dosagens para estimar a probabilidade do desfecho de citorredução. Além disto, foi criada uma nova variável chamada carga de VEGF. Pelo procedimento step-wise a citorredução foi melhor descrita pela carga de VEGF, mas faltou Normalidade aos resíduos, não sendo possível a adequação de um modelo matemático. Porém, a curva ROC, forneceu uma área sob a curva de 0,84, com sensibilidade de 71,4 % e especificidade variando de 69,5 a 73,9%. O ponto de corte ótimo foi 15,52 log de picograma de carga de VEGF. A odds-ratio (OR) calculada para citorredução ótima descrita pela carga de VEGF foi de 11 (IC= 2,59 ; 46,78). No grupo com estágio avançado (III e IV), a OR foi de 6 (IC= 1,15; 31,22). Apesar do pequeno número de casos, esta nova variável pode vir a ser um auxiliar na determinação de situações onde cirurgia citorredutora deixa de ser a pedra fundamental do tratamento primário do CEO e a indução quimioterápica passe a ter o principal papel na citorredução química antes da cirugia nestes casos. / Epithelial ovarian carcinogenesis has been the focus of scientific studies in developed world. The ovarian tumor angiogenesis is a multifactorial process that results in pro-angiogenic products. Among them, vascular endothelial growth factor (VEGF) is predominant. This study aimed to relate VEGF levels in peritoneal fluids, peripheric plasma and pelvic infundibular plasma to debulking levels in patients operated on for epithelial ovarian carcinoma (EOC), formulate a probabilistic model for debulking and use these measurements to estimate the probability of the outcome of debulking. Moreover, it was created a new variable called burden of VEGF. For step-wise procedure, cytoreduction was better described by of burden VEGF, but missed Normality of residuals, so the adequacy of a mathematical model was not possible. Nevertheless, the ROC curve provided an area under the curve of 0.84, with sensitivity of 71.4 % and especificity varying from 69.5 to 73,9%. The optimal cutoff point was 15.52 log of picograms of VEGF burden. An odds-ratio for optimal cytoreduction described by the VEGF burden was 11 (CI= 2.59; 46.78). In the group with advanced stages (III & IV), the OR was 6 (CI= 1.15; 31.22). Apart from the small number of cases, this new variable might help to determine situations where cytoreductive surgery leaves behind the cornerstone of primary treatment of CEO and the chemotherapic induction comes to have main role in chemical cytoreduction prior to surgery in these cases.