PARP inhibition: A promising therapeutic target in ovarian cancer.

Ovarian cancer is burdened by the highest mortality rate among gynecological cancers. Gold standard is represented by the association of platinum-taxane -based chemotherapy and radical surgery. Despite several adjustments occurred in cytotoxic drug in last decades, most patients continue to relapse, and no significant enhancement has been reached in the overall survival. The development of drug resistance and the recurrence of disease have prompted the investigations of other targets that can be used in the treatment of ovarian cancers. Among such targets, polyadenosine diphosphate-ribose polymerase (PARP) represents a novel way to target specific patways involved in tumor growth. PARP accelerates the reaction of the polyADP-ribosylation of proteins implicated in DNA repair. PARP inhibitors have shown activity in cancers with BRCA mutations, with other deficient DNA repair genes or signaling pathways that modulate DNA repair, or in association with DNA damaging agents not involved in DNA repair dysfunction. A number of inhibitors for PARP has been developed, and such drugs are under investigation in clinical trials to identify their impact in the treatment of ovarian cancers. This review aims to summarize the recent researches and clinical progress on PARP inhibitors as novel target agents in ovarian cancer.

[Radical trachelectomy with lymphadenectomy]. / La trachelectomia radicale con linfoadenectomia.

Radical trachelectomy was described for the first time by Dargent in 1987 as an alternative to the traditional radical hysterectomy; it led to a changed procedure in therapy for early cervical cancer in young women who want to preserve their fertility. With this technique it is possible to remove the uterine cervix and parametrius and at the same time preserve the upper part of the cervical canal and uterus. Only a low-risk subset of young patients with early cancer of the cervix are considered eligible for this treatment; to select them histological and clinical staging of the lesion are the most important criteria. We describe the cases of three patients treated with radical trachelectomy between June 1997 and March 1998 in our Institute, reporting in detail the surgical procedure and the results.

[The creation of a neovagina with laparoscopic technique]. / Creazione di una neovagina con tecnica laparoscopica.

Vaginal agenesis is sometimes found isolated but more frequently as a part of a malformative syndrome, such as the Rokitansky-Küster-Hauser or the Morris syndrome. In our department the technique of choice for surgical creation of a neovagina is that described by Vecchietti. A pelviscopic approach for this technique has recently been described. Two cases of vaginal atresia are described; one with Rokitansky-Küster-Hauser and the other with Morris syndrome, in which the laparoscopic technique was attempted. Due to the aetiopathogenetic and anatomical differences of the two syndromes, the laparoscopic technique resulted easy in the first case but very difficult in the Morris syndrome case, needing laparotomic conversion. We therefore believe that in choosing the surgical approach, a decisive issue is the type of malformation. Indeed in the Morris syndrome, the contiguity between rectum and bladder makes the laparoscopic technique more difficult.

[Deep venous thrombosis in pregnancy: diagnostic difficulties and therapeutic indications. Discussion of a clinical case]. / La trombosi venosa profonda in gravidanza: difficoltà diagnostiche e indirizzi terapeutici. Discussione di un caso clinico.

Pregnancy is a risk factor for deep and superficial venous thrombosis because of hemodynamic changes and modifications of the coagulation and fibrinolitic systems. In case of a patient suffering from a congenital or acquired thrombophilia, risk of severe and recurrent thrombosis becomes much higher, with the possibility of a life threatening complication as pulmonary embolism. Recently a number of congenital thombophilic syndromes have been described, in particular congenital hereditary deficit of coagulation inhibitors. Among the acquired pathologies, the antiphospholipid syndrome has been recently object of studies. Diagnostic and therapeutic options are still controversial. The authors present a case of recurrent deep vein thrombosis in pregnancy treated with positioning of a caval filter for the prophylaxis of pulmonary embolism. Diagnostic difficulties are discussed, as the patient presented with low levels of the coagulation inhibitor protein S, and also circulating antibodies anticardiolipin.

Complications in the surgical treatment of carcinoma of the endometrium.

The authors report their experience in medical and surgical complications after surgical treatment of endometrial carcinoma, from January 1976 to December 1992, 301 cases of adenocarcinoma were operated by abdominal or vaginal route. From 1980 onwards abdominal route was the most frequent (radical hysterectomy with bilateral adnexectomy Rutledge type II-III with pelvic and/or aortic lymphadenectomy). No lesion occurred either during surgery or later, in the urinary or intestinal apparatus or to the great abdomino-pelvic vessels. The only medical complication observed was one episode of cerebral ictus three days after operation. Two cases of adynamic ileus and five of ventral hernia occurred.

Considerations on the prognostic significance of bone marrow micrometastases in breast cancer.

Research of bone marrow micrometastases in patients with breast cancer was proposed as a prognostic factor in order to detect those patients at high risk for early recurrence. The Authors present a review of current literature and describe the different methods used, with particular regard to monoclonal antibodies. The biological significance and prognostic value of the presence of bone marrow micrometastases in clinically Mo patients with breast cancer are discussed.

Ovarian cysts in the postmenopause: is a conservative treatment feasible?

The incidence of epithelial ovarian cancer reaches a peak between the ages of 50 and 59 years. Therefore any ovarian enlargement in the postmenopause has been treated up to now with prompt surgical exploration. Recently the reliability of ultrasound has allowed a conservative management of small unilocular ovarian cysts even in the postmenopause. The Authors report here their experience on benign masses in postmenopausal women, and discuss the feasibility of ultrasound-guided aspiration of small, anechoic adnexal cysts.