Alexandros Rodolakis

Management of ureteric injuries during gynecological operations: 10 years experience

OBJECTIVE(S) To present our 10 years experience in the management of ureteric injuries occurring during gynecological surgery. STUDY DESIGN Seventy-six patients had a variety of injuries. In 29 cases, the ureteric damage was diagnosed intraoperatively. Management of early-diagnosed injuries included suturing, ligature removal, end-to-end anastomosis, and reimplantation of the ureter. In 47 cases, the injury was diagnosed postoperatively. Ureteric catheterization was attempted in all cases presenting with obstruction. Catheterization failures were managed with ureterolysis, and reimplantation. Small ureteric fistula were managed with catheterization, and large communications with reimplantation. Two cases with urinomas were treated with surgical evacuation and anastomoses. RESULTS Management of early-diagnosed injuries was relatively easy in most cases. Postoperatively-diagnosed injuries were more difficult to treat. Catheterization failed in 28/44 (65.9%) ureters and surgical re-exploration was necessary. Long-term morbidity was minimal and no relapses occurred. CONCLUSION(S) Early recognition of a ureteric injury is the key to a complications-free repair. Unrecognized injuries cause prolonged morbidity, and their management can be difficult. Treatment of these injuries by experienced teams may minimize long-term consequences.

Recommendations of the Fertility Task Force of the European Society of Gynecologic Oncology about the conservative management of ovarian malignant tumors

In young patients with borderline ovarian tumor a conservative treatment approach does not seem to have a significant impact on survival, and the outcome regarding fertility is good in general. It can be considered even if noninvasive peritoneal implants are discovered at the time of the initial surgery. In contrast, in patients with epithelial ovarian cancer, conservative surgery should be considered only in adequately staged patients, with a stage IA grade 1 (and probably 2) serous, mucinous or an endometrioid tumor, including a careful follow-up. Such an approach could also probably be discussed in stage IC grade 1 disease. In patients with nonepithelial malignant ovarian tumors, conservative surgery is also feasible, particularly in patients with malignant germ cell tumors because of their high chemosensitivity leading to an excellent prognosis in general.

Clinical recommendation radical trachelectomy for fertility preservation in patients with early-stage cervical cancer.

Abstract Radical trachelectomy (RT) is a fertility-sparing procedure with the aim to provide adequate oncological safety to patients with cervical cancer while preserving their fertility. In the current review, indications, development of the procedure, technical aspects, preoperative and postoperative management, and oncological, fertility, and obstetric outcomes are discussed and studied with respect to whether the procedure is performed abdominally or vaginally. Complications of RT, staging, and more conservative alternatives to RT are discussed as well. A systematic MEDLINE search was performed, which yielded 218 articles, of which 75 were selected for further analysis based on the number of patients and the quality of the study. Strict morphologic criteria should be applied to the candidates to maintain oncological safety. When limited to a tumor less than 2 cm in diameter, the overall recurrence rate after vaginal RT is 3% to 6% and the death rate is 2% to 5%. Data on fertility and obstetric outcome are mostly based on the results of patients who underwent vaginal RT. More data are needed to be able to draw the same conclusions for abdominal RT. Fertility seems not to be decreased, but the risk for premature delivery is 2 to 3 times higher compared to women with an intact cervix. In locally advanced cervical tumors with a diameter larger than 2 cm, neoadjuvant chemotherapy followed by RT may be offered after explaining the experimental nature to the patient. In conclusion, RT is an oncologically safe technique in women with early invasive cancer. The rate of term pregnancies still needs improvement. Fertility-preserving treatment of women with tumors larger than 2 cm in diameter can be done by combining neoadjuvant chemotherapy and trachelectomy; however, experience is still limited.

VEGF directly suppresses activation of T cells from ovarian cancer patients and healthy individuals via VEGF receptor Type 2.

The role of vascular endothelial growth factor (VEGF) in tumor angiogenesis is well characterized; nevertheless, it is also a key element in promoting tumor evasion of the immune system by downregulating dendritic cell maturation and thus T cell activation. We sought to investigate the possible direct effect of VEGF on T cell activation and through which type of VEGF receptor (VEGFR) it exerts this effect. Circulating T cells from healthy donors and ovarian cancer patients were expanded in cultures with anti‐CD3 and IL‐2 with or without VEGF for 14 days, and the number of T cells was assessed. Cultured T cells were also tested for their cytotoxic activity in a standard 4‐hr 51Cr‐release assay, and the expression of VEGFRs 1, 2 and 3 was assayed by flow cytometry, immunocytochemistry and Western blotting. To assess the ability of activated T cells to secrete VEGF, levels in culture supernatants were measured by enzyme linked immunosorbent assay. The addition of VEGF in cultures significantly reduced T cell proliferation in a dose‐dependent manner. Protein expression studies demonstrated that CD3+ T cells express VEGFR‐2 on their surface upon activation. Experiments with anti‐VEGFR‐2 antibodies showed that the direct suppressive effect of VEGF on T cell proliferation is mediated by VEGFR‐2. We also showed that VEGF significantly reduced the cytotoxic activity of T cells and that activated T cells secrete VEGF in the culture environment. Overall, our study shows that T cells secret VEGF and expresses VEGFR‐2 upon activation. VEGF directly suppresses T cell activation via VEGF receptor type 2.

Laparoscopic Treatment of Ovarian Dermoid Cysts: Eleven Years' Experience

STUDY OBJECTIVE To compare laparoscopic and open approaches in the management of benign ovarian teratomas (dermoid cysts) with regard to operative outcome, complications, and postoperative follow-up. Factors that predispose to rupture of dermoid cysts during laparoscopic removal and rates of adhesion formation in women with and without cyst rupture during laparoscopic surgery also were considered. DESIGN Review of cases of women with dermoid cysts who underwent cystectomy either by laparoscopy or laparotomy in our department from 1992 through 2002 (Canadian Task Force classification III). SETTING The Infertility and Operative Laparoscopy units of the First Department of Obstetrics and Gynecology of the University of Athens, Alexandra Maternity Hospital, Athens, Greece. PATIENTS Two hundred twenty-two women with an ovarian mass requiring surgical management. Of these, 187 women with benign cystic teratomas underwent laparoscopic cystectomy, and 35 underwent cystectomy by laparotomy. INTERVENTIONS Cystectomy either by laparoscopy or laparotomy. MEASUREMENTS AND MAIN RESULTS Potential benefits of operative laparoscopy include reduced blood loss, less postoperative pain, shorter hospital stay, fast recovery, and an excellent cosmetic result. CONCLUSION Laparoscopy should be considered the method of choice for the removal of benign ovarian cystic teratomas as it offers the advantages of fewer postoperative adhesions, reduced pain, shorter hospital stay, and better cosmetic result. It should be performed by surgeons with considerable experience in advanced laparoscopic surgery.

USE OF MISOPROSTOL FOR THE TERMINATION OF SECOND TRIMESTER PREGNANCIES

Abstract Surgical termination of pregnancy is of high risk for the woman’s health and safe medical ways are required. The use of prostaglandins may substantially reduce this risk. The efficacy and safety of misoprostol as a medication for the termination of the second trimester pregnancies were studied. During a 15-month period ninety-eight healthy pregnant women (13–24 weeks) wishing to terminate their pregnancy due to medical reasons participated voluntarily in this study. Misoprostol was administered 400 µg per os and 400 µg vaginally. Dose was repeated every 6 hours until adequate contractions and cervical ripening were achieved. Outcome measures included successful termination rates, mean expulsion time and side effects of the medication. The efficacy of the method was as high as 91.8% (90/98 cases 95%, CI 86–97%). Mean expulsion time was 10.2 h (range 3–23.4 h) for primigravida and 9.2 h (range 2.5–22.2 h) for multigravida. In 9 cases (9.2%) placenta remnants and in 8 (8.2%) placenta retention were found. Most common side effect was shivering in 17.3% of cases, vomiting and nausea (10.2%), headache and dizziness (7.1%), abdominal pain (79.6%), while diarrhea was noticed in 4.1%. The high efficacy and low incidence of side effects make misoprostol a useful alternative method for medical termination of second trimester pregnancies.

European Society of Gynecological Oncology Task Force for Fertility Preservation: Clinical Recommendations for Fertility-Sparing Management in Young Endometrial Cancer Patients.

Abstract Endometrial cancer (EC) in young women of reproductive age is a relatively rare diagnosis. However, since in the modern era women delay their childbearing for a variety of social reasons, more and more women in the near future will be nulliparous and have a diagnosis of EC at the same time. Hence, a more conservative approach of EC is desirable to preserve fertility of these women, without compromising their survival. Recently, the number of studies reporting encouraging results on fertility-sparing management of EC with high dose of progestins is increasing. It seems that preserving the uterus and the ovaries in a carefully selected patient with EC confers only a very small risk combined with an enormous benefit. Selection of women suitable for such a conservative approach, as well as method of treatment, follow-up, recurrence, obstetric outcomes, and survival rates are very important parameters when consulting women with EC wishing to preserve their fertility. In this article, we try to elucidate all the previously mentioned aspects and formulate clinical recommendations, based on published data, about the most proper approach and consultation of these patients.

Gain of 3q26: A genetic marker in low-grade squamous intraepithelial lesions (LSIL) of the uterine cervix

OBJECTIVE Physicians have few resources for determining which LSIL will progress to HSIL or regress. Recently the chromosome 3q26 region was found to be amplified in patients with cervical cancer. The frequency of this 3q gain increased with severity of dysplasia. The primary objective of this study was to evaluate an automated FISH assay for detection of 3q gain in liquid cytology samples as a potential tool for risk stratification and triaging. METHODS Slides prepared from 257 liquid cytology specimens (97 Negative, 135 LSIL 25 HSIL) were hybridized with a single-copy probe for the chromosome 3q26 region and a probe for the centromeric alpha-repeat sequence of chromosome 7, using standard FISH methods. Using automated analysis, the total number of nuclei and the number of nuclei with >2 signals for 3q26 were determined, using a 20x objective. The nuclei were rank ordered based on number of 3q26 FISH signals. The 800 nuclei with the highest number of signals were scored using both FISH probes and nuclei with increased numbers of 3q signals were enumerated. RESULTS AND CONCLUSIONS Analysis of 257 specimens demonstrated that a fully automated FISH scoring system can detect 3q gain in liquid cytology samples. A fully automated method for determination of 3q gain in liquid cytology may be the assay necessary to implement routine testing. Additional studies to validate the utility of this technology are needed.

Prognostic evaluation of tumour type and other histopathological characteristics in advanced epithelial ovarian cancer, treated with surgery and paclitaxel/carboplatin chemotherapy: Cell type is the most useful prognostic factor

AIM Ovarian carcinomas have been classified into types I and II according to the hypothesised mode of carcinogenesis and molecular characteristics. The prognostic significance of this classification has not been studied. PATIENTS AND METHODS Five hundred and sixty-eight patients with histologically confirmed, ovarian, fallopian tube or peritoneal carcinomas, international federation of gynecology and obstetrics (FIGO) stages IIC-IV, treated with paclitaxel/platinum following cytoreductive surgery, were included in this analysis. Type I included low-grade serous, mucinous, endometrioid and clear-cell and type II high-grade serous, unspecified adenocarcinomas and undifferentiated carcinomas. RESULTS Median overall survival (OS) was 49 months for type I versus 45 for type II (p=0.576). In contrast to type II, there was considerable prognostic heterogeneity among the subtypes included in type I. Cox regression analysis showed that cell-type classification: low-grade serous, mucinous, endometrioid, clear-cell, type II (high-grade serous, unspecified adenocarcinomas, undifferentiated carcinoma) was an independent predictor of survival (respective median OS 121 versus 15 versus 64 versus 29 versus 45 months, p=0.003). On the contrary, histopathological subtype or tumour type (I versus II) did not offer additional prognostic information. CONCLUSION The proposed model of ovarian tumourigenesis does not reflect tumour behaviour in advanced disease. Tumour-cell type is the most relevant histopathological prognostic factor in advanced ovarian cancer treated with platinum/paclitaxel.

Fertility preserving management in gynecologic cancer patients: the need for centralization.

Abstract Preservation of fertility has became a very important issue in gynecologic oncology. It is a result of both the increasing incidence of gynecologic cancer in young patients and the increasing age at first pregnancy. Today, in a young patient with a gynecologic cancer, preservation of fertility is possible and depends primarily on the extent and type of cancer. The clinical importance of an appropriate management of young patients with gynecologic cancer has lead the ESGO Task Force for Fertility Preservation in Gynecologic Cancer to conduct a survey with the aim of exploring the numbers and eligibility of gynecologic cancer patients for fertility-sparing treatment in selected gynecologic oncology centers across Europe. A questionnaire designed to allow adequate insight into the number of patient eligible for fertility-sparing treatment and the resulting treatment was sent to 20 ESGO-accredited centers. The data were collected retrospectively for the year 2007. The reply was received from 14 gynecologic oncology centers, and those surveys were included for analysis. The small numbers of patients eligible for conservative management (14-15 per year/median number in ESGO-accredited centers) and even the smaller number of those who actually receive fertility-sparing treatment (<10) raise the question of quality of care for these patients. These low numbers support the concept of centralization for fertility-sparing management to improve the quality of patients care. Since carrying out the survey on fertility-sparing management in ESGO-accredited gynecologic oncology centers in Europe, the ESGO Task Force for Fertility Preservation in Gynecologic Cancer has proposed a protocol for referrals to centralized units that have developed specific expertise. Optimal management for young patients with gynecologic cancer should include a clear decision-making process, an adequate counseling about the future oncological and obstetrical risks, the appropriate management, and a careful follow-up within a multidisciplinary setting.