Diffusion-weighted imaging of solid or predominantly solid gynaecological adnexial masses: is it useful in the differential diagnosis?

OBJECTIVES: This study investigated whether diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) values provide specific information that allows the diagnosis of solid or predominantly solid gynaecological adnexial lesions, especially whether they can discriminate benign and malignant lesions. METHODS: DWI was performed in 37 patients with histologically proven solid or predominantly solid adnexial lesions (22 malignant and 15 benign neoplasms). The lesions in our data set were divided into two groups, all adnexial lesions or lesions of ovarian origin, for evaluation. The areas of the highest signal intensity on DWI (b = 800 s mm(-2)) and the lowest ADC values within the lesions were evaluated. RESULTS: On DWI, high signal intensity was observed more often in malignant than in benign lesions (p<0.0001). There was no significant difference between the ADC values of the malignant and benign lesions in either the adnexial (0.88±0.16 vs 0.84±0.42; p = 0.96) or the ovarian (0.85±0.14 vs 1.05±0.2; p = 0.133) lesions. When signal intensities on DWI were compared, however, malignant lesions had higher values than the benign lesions in both the adnexial (0.69±0.21 vs 0.29±0.13; p<0.0001) and the ovarian lesions (0.75±0.14 vs 0.37±0.24; p = 0.003). CONCLUSION: On DWI, high signal intensity was observed more frequently with the malignant lesions.

Groin recurrence following stage IA squamous cell carcinoma of the vulva with negative nodes on superficial inguinal lymphadenectomy.

PURPOSE OF INVESTIGATION: Stage IA vulvar cancer with a depth of stromal invasion less than 1 mm is generally managed by wide local excision alone since there is less than 1% risk of lymph node involvement. CASE: A 62-year-old patient was admitted to a university hospital with a suspicious vulvar lesion. RESULTS: We present the first case of inguinal node and a possible contralateral pubic ramus recurrence following bilateral superficial inguinal lymphadenectomy and wide local resection for Stage 1A vulvar cancer. CONCLUSION: There is no evidence that extended radical surgery provides a better overall survival or reduces recurrence rate in Stage 1A vulvar carcinomas. Conservative vulvar resection and sentinel node dissection seem to be a rational choice. Nevertheless the disease may recur in the inguinal areas and frequently be lethal, therefore close surveillance and early attempts to treat the recurrent disease before infection and inflammation ensues should be the aim of current treatment strategies.

Evaluation of serum levels of interleukin-10, interleukin-11 and leukemia inhibitory factor in differentiation of eutopic and tubal ectopic pregnancies.

PURPOSE OF STUDY: To investigate whether serum levels of leukemia inhibitory factor (LIF), interleukin 10 (IL-10) and interleukin 11 (IL-11) are different in reference to the site of implantation. METHODS: Seventeen patients with laparoscopic diagnoses of tubal ectopic pregnancy (EP) and 19 patients with intrauterine pregnancy delivering healthy term neonates (IUP) were prospectively evaluated for LIF, IL-10 and IL-11 levels. The data were compared by using the Student's t-test, chi-square test, Kruskal-Wallis and the Mann-Whitney U test with Bonferroni's correction (p < 0.05) as appropriate. RESULTS: A statistically significant difference was observed in serum LIF levels between the EP and IUP groups (p = 0.002). Ranges of LIF were 15-300 and 70-1200 ng/ml for the IUP and EP groups, respectively. There were no significant differences between groups in terms of IL-10 and IL-11 levels. CONCLUSION: LIF, but not IL-10 or IL-11, levels may be increased in early tubal ectopic pregnancies when compared to normal intrauterine pregnancies.

Factors affecting recurrence and disease-free survival in granulosa cell tumors of the ovary.

PURPOSE OF INVESTIGATION: To determine risk factors for prognosis and recurrence in ovarian adult-type granulosa cell tumor (GCT). METHODS: A retrospective review of GCT cases treated at our university hospital between 1991-2006. RESULTS: Of 39 patients with GCT, 82% had Stage I disease. The median follow-up period was 71 months. There were 12 cases of recurrence (30.8%) and seven of them had died of disease. The pelvis and liver were the most common sites of recurrence (8 and 3 patients, respectively). Interestingly lymph node recurrence was encountered in two patients. Estimated disease-free survival for five years was 82%. Stage and presence of residual tumor were calculated to be the only associated risk factors for recurrence and prognosis (p < 0.05). CONCLUSION: Recurrences in GCT might be associated with stage and presence of residual tumor during primary surgery. Although rarely present during diagnosis, lymph node metastasis might be more common in recurrent disease.

Invasive squamous carcinoma of the vulva in women aged less than 40 years: report of two cases and a third case diagnosed during pregnancy.

PURPOSE OF INVESTIGATION: Invasive squamous cell cancer of the vulva (ISCC) is a rare disease in young patients and in pregnant women. The purpose of this paper was to investigate this type of cancer in women less than 40 years old and to present three cases, one which was diagnosed in the third trimester of pregnancy. METHODS: Three cases of invasive squamous cell cancer in women under age 40 among the retrospectively analyzed 52 vulvar cancer cases diagnosed between 1995-2002 were investigated. RESULTS: Women aged 25, 39 and 31, respectively, had Stage 1, 2 and 3 ISCC of the vulva. The first two cases had been spared by surgery and radiotherapy. The third patient was diagnosed during the last trimester of pregnancy. Although she was treated by radical surgery and postoperative radiotherapy, she had a recurrence in the inguinal region at 36 months, and died of disease 12 months later. CONCLUSION: Vulvar ISCC in young women may occur in association with or without predisposing factors. Although HPV-related type is predominant in the literature, keratinizing type of carcinoma may also be seen in this group of patients. Biopsy from suspected lesions is of paramount importance.

Malignant germ cell tumors of the ovary: a review of 41 cases and risk factors for recurrence.

OBJECTIVE: To review the outcome of treatment in patients with malignant ovarian germ cell tumors and to define the risk factors for recurrence. MATERIAL AND METHODS: Forty-one patients with malignant ovarian germ cell tumors were reviewed retrospectively. Survival time and survival rate were obtained. Risk factors such as stage, histological type, and type of operation were evaluated for reccurrence. RESULTS: Twenty-three (56%) had dysgerminomas, eight (19.5%) had mixed germ cell tumors, three (7.3%) had yolk sac tumors, three (7.3%) had immature teratomas, two (4.8%) had squamous cell carcinoma arising from a mature teratoma, one (2.4%) had embryonal carcinoma and one choriocarcinoma. Most of the cases (73%) were in Stage I. Twenty-nine patients (70.7%) underwent conservative surgery and 12 patients (29.3%) had at least bilateral salpingo-oophorectomy. Thirty patients were operated on optimally with surgical staging and 11 suboptimally. Seven patients (17%) had recurrence after remission. The overall survival time was 187 +/- 8.43 months for all cases, 195 +/- 8.49 for dysgerminoma and 161 +/- 10.96 for non-dysgerminoma cases with a median follow-up time of 98.52 (8-204) months. Non-dysgerminoma histologic type, being operated on suboptimally and radically, and advanced tumor stage have been found to be risk factors for recurrence. CONCLUSION: Regardless of histologic types and stages the prognosis of germ cell tumors are satisfactory with current therapeutic strategies.

Life-saving hysterectomy in choriocarcinoma: presentation of two cases.

BACKGROUND: Choriocarcinoma is a malignant tumor of the placenta. Life-saving hysterectomy was performed in two cases with choriocarcinoma who had profuse vaginal bleeding. CASE 1: A 25-year-old, gravida 3, para 1, woman was referred to our emergency clinic with the diagnosis of choriocarcinoma and massive vaginal bleeding. She had been transfused seven units of blood at the hospital where she was first admitted. Pelvic examination demonstrated heavy vaginal bleeding and a uterus equivalent to the size of 14 weeks of gestation. Her beta-hCG level was 560,000 mIU/ml. Despite four units of blood transfusion, she had a pulse rate of 130/min, arterial pressure of 90/60 mm/Hg and HCT of 19%. An emergency hysterectomy with vertical incision was performed. CASE 2: A 54-year-old, gravida 3, para 3, woman was referred to our clinic with heavy bleeding with the diagnosis of choriocarcinoma. She was scanned to look for possible metastases and pulmonary metastasis was detected. Chemotherapy was planned but as sudden vaginal bleeding began she was referred to the Gynecology Department. At pelvic examination a soft uterus the size of 20 weeks of gestation was palpated. The beta-hCG level was 554,700 mIU/ml. Due to hemodynamic instability and continuous vaginal bleeding an emergency hysterectomy was performed. CONCLUSION: Although chemotherapy is the cornerstone of treatment for choriocarcinoma, optimal treatment results may depend on the addition of surgery in selected circumstances. Hysterectomy is indicated in cases with life-threatening hemorrhage.

Value of glutathion-S transferase pi as a prognostic factor in epithelial ovarian carcinoma.

The association between glutathione S-transferase pi (GSTpi) and other clinicopathological parameters, response to chemotherapy and clinical outcome were investigated in chemotherapy naive epithelial ovarian cancer patients. Paraffin-embedded material from 55 patients were used for immunohistochemical analysis. All patients had received six cycles of cisplatinum-based chemotherapy and 41 of them were revalued by laparotomy. Pre- and post-chemotherapy GSTpi staining were detected in the cancer tissues of 18/55 (32.7%) and 5/14 (35.7%) patients, respectively. GSTpi expression was not associated with other clinicopathologic parameters. Of 17 patients with postoperative measurable residual disease clinical response was observed in 4/7 of GSTpi positive and in 9/10 GSTpi negative patients (p = 0.25). Pathologic complete response (pCR) was achieved in 5/8 of GSTpi positive and 11/22 of GSTpi negative cases (p = 0.69). There was no significant difference in overall survival and progression-free survival (PFS) according to initial GSTpi status. However the PFS of the five patients (median 22 +/- 5.9 months) who had postchemotherapy positive GSTpi was significantly shorter than the nine patients (10.0 +/- 2.19 months) who had negative GSTpi (p = 0.006). This difference was not observed in overall survival. These results suggest that initial immunohistochemical staining of GSTpi does not aid in the prediction of pCR and clinical outcome in patients with epithelial ovarian cancer. Nonetheless investigation of GSTpi expression after chemotherapy needs further evaluation.

Brain metastasis of ovarian cancer after negative second-look laparotomy.

We present a case of ovarian carcinoma that had brain metastasis seven months after having a negative second-look laparotomy and 13 months after the onset of diagnosis. Despite intense multidisciplinary treatment with surgery, chemotherapy and radiotherapy, the patient died seven months after second-look laparotomy.

The efficacy of combination chemotherapy including intraperitoneal cisplatinum and mitoxantrone with intravenous ifosfamide in patients with FIGO stage I C ovarian carcinoma.

OBJECTIVE: Patients with stage I ovarian cancer show a high incidence of recurrent disease ranging from 30% to 50%, which may be associated with a shortened survival. Therefore, a subset of early-stage patients with poor prognostic factors who are most likely to present with recurrent disease in the next few years may benefit from adjuvant treatment. PATIENTS AND METHOD: In this pilot study, we evaluated the efficacy of combination chemotherapy including intraperitoneal mitoxantrone (12 mg/ml) and cisplatinum (75 mg/ml) on day 1, in addition to intravenous ifosfamide (4000 mg/m2) given on day 15 with mesna protection. Thirteen patients with a median age of 44 years were included in the study. RESULTS: Following a median of 5 cycles of chemotherapy, 12 patients had a complete response (92.3%), while one patient had progressive disease. At the latest follow-up, ten patients were alive with no evidence of disease, two patients had died and one patient was lost to follow-up. Overall and progression-free survival rates at eight years were 82.5+/-11.3% and 83.9+/-10.5%, respectively. Excluding grade 3 and 4 abdominal pain in three (23.1%) patients, there were no serious complications associated with this combination. Dose delay not longer than one week was observed in 3 cycles (5.6%). Port-related complications observed in three patients were colonic perforation, hematoma and leakage. CONCLUSION: This combination has moderate efficacy and tolerable toxicity. However, further studies are required to make definite conclusions regarding the efficacy of this combination in the adjuvant setting in patients with high-risk early stage ovarian carcinoma.

Nongenital metastatic cancers of the ovary: a clinical analysis.

OBJECTIVES: The aim of this study was to outline the parameters affecting the extent and type of surgery for metastatic tumors of the ovary. MATERIAL-METHOD: The data of 34 operated patients diagnosed with metastatic tumors of the ovary at the Istanbul University, Medical Faculty Gynecologic Oncology Department between 1991 and 1999 were evaluated retrospectively. The patients were divided into two study groups according to the origin of the tumor: 1. Metastatic tumors of the ovary originating from the organs apart from the gastrointestinal system (MT-NonGIS). 2. Metastatic tumors of the ovary originating from the gastrointestinal system (MT-GIS). Survival rates were calculated in months from the time of ovarian surgical intervention to the date of last known data of patient status. Mean survival rates for the noncensored data were calculated by the Kaplan-Meier method and resulting curves were compared by the log-rank procedure. Statistical significance was determined at the level of 0.05. RESULTS: The survival rate for all cases was 24.21 months: the same rate was calculated to be 45.36 months for the MT-nonGIS group while it was 15.8 months for the MT-GIS group. When both groups were compared in terms of survival rates, the difference was significant (p: 0.0025, log rank: 9.14). Overall cumulative survival rates for 9, 14, 24 and 50 months were 61.59%, 50.05%. 41.7% and 11.58%, respectively. It was also found that surgery performed on patients in the MT-GIS group did not alter the survival rate but if peritoneal metastasis was observed during surgery, life expectancy for these cases was significantly less. CONCLUSION: Although the number of patients included in our study was small, it is important because it gives us a clue about the type of surgery that should be performed in GIS-originating metastatic tumors of the ovary. Our study shows that aggressive surgery should be avoided in patients with peritoneal metastasis/spread.

Celsite port and catheter as an intraperitoneal access device in the treatment of ovarian cancer.

BACKGROUND AND OBJECTIVES: In ovarian cancer, development of safe and effective methods for providing long-term access to the peritoneal cavity has become increasingly important. METHODS: A modified Port-A-Cath (Celsite-port and catheters, B. Braun, Chasseneuil, France) was used in 56 patients with presumed epithelial ovarian cancer at the conclusion of primary or second-look laparotomy. In 37 patients, ports were located on the right costal margin in the midclavicular region and in 19 in the xiphoid region. RESULTS: In 56 catheters, 8 (13.8%) complications of severe or moderate degree during the treatment were registered. In-flow obstruction of device occurred in 6 patients, and there was 1 viscous perforation and 1 catheter related infectious peritonitis. Grade III-IV pain and in-flow obstruction were developed in the patients with ports implanted on the right costal margin but not with ports implanted in the xiphoid region. CONCLUSION: The complication rate of intraperitoneal access devices is comparatively low.

BRCA1 and BRCA2 mutations in Turkish breast/ovarian families and young breast cancer patients.

To date, BRCA1 and BRCA2 mutations in breast and/or ovarian patients have not been characterized in the Turkish population. We investigated the presence of BRCA mutations in 53 individuals with a personal and family history of breast and/or ovarian cancer, and 52 individuals with a personal history of breast cancer diagnosed below age 50 without additional family history. We have identified 11 mutations (nine BRCA1 and two BRCA2) using combined techniques involving protein truncation test, direct sequencing and heteroduplex analysis. We found eight out of 53 patients (15.1%) with a family history to carry BRCA gene mutations (seven BRCA1 and one BRCA2). Of these, four were found in 43 families presenting only breast cancer histories, and four were found in families presenting ovarian cancer with or without breast cancer. We also demonstrated two BRCA1 and one BRCA2 mutations in three out of 52 (5.8%) early-onset breast cancer cases without additional family history. Three of nine BRCA1 and both BRCA2 mutations detected in this study were not reported previously. These mutations may be specific to the Turkish population. The BRCA1 5382insC mutation, specific to Ashkenazi and Russian populations, was found twice in our study group, representing a possible founder mutation in the Turkish population.

Intraperitoneal cisplatin-mitoxantrone and intravenous ifosfamide combination as first-line treatment of ovarian cancer.

Twenty-one chemotherapy naive ovarian cancer patients with stage III and minimal residual tumor were treated with cisplatin 75 mg/m2 and mitoxantrone 15 mg/m2 (1st day) by intraperitoneal (i.p.) route and ifosfamide 4 g/m2 (15th day) by i.v. route every 4 weeks for a total of 6 cycles. Pathologic complete response (pCR) was achieved in 9/20 (45%, 95% Confidence Interval - CI - 23-68) of the patients. The median progression free interval (PFI) of the patients with pCR was 45 (range: 18-70) months. For patients with residual tumor <1 cm (n: 11); pCR was 82% and could be achieved only in this subgroup of patients. The cumulative (PFI) and overall survival rate of all patients at 3 years were 40% and 52%, respectively. The median PFI was found to be significantly different between the patients with residual tumor <1 cm (48 months, 95% CI 42-54) and 1-2 cm (9 months, 95% CI 1-16) p<0.001. Main toxicities were emesis and abdominal pain which occurred in 53% and 65% of the courses, respectively. This combination seems to be an effective and feasible approach to previously untreated ovarian cancer patients with minimal tumor burden.

Intraperitoneal cisplatin--mitoxantrone in ovarian cancer patients with minimal residual disease.

A phase II trial was conducted to further explore the potential of salvage intraperitoneal (IP) cisplatin-based therapy in patients with residual ovarian cancer. Twenty-five patients were treated with a regimen of cisplatin (75 mg/m2) and mitoxantrone (15 mg/m2) delivered IP every three weeks for a maximum of six cycles. Ten patients achieved a pathologically complete response (pCR) and six were clinically stable without evidence of disease. After a median follow-up of 18 months, the median progression-free survival (PFS) was 16 months (95% confidence interval-CI-3-29%). The actuarial PFS at 24 months was 36% (95% CI 13-59). Overall eight out of 25 patients (32%) had an IP relapse and thus were considered as local treatment failures. The major toxic side effects were nausea, vomiting, abdominal pain and renal toxicity. Future trials exploring IP delivery of these drugs should attempt to optimize drug dose and schedule and subset analysis of clinical studies should help in identifying patients who are particularly sensitive to this therapeutic approach.

High-dose intravenous immunoglobulin therapy for rhesus haemolytic disease.

Rhesus haemolytic disease is a continuing problem in the newborn especially in countries where the use of anti-D immunoglobulin is not prevalent. The fetuses may need intrauterine transfusions to prevent hydrops faetalis and they also may need exchange transfusions to treat the hyperbilirubinaemia that develops after birth. These interventions expose the baby to several blood donors, hence the risk of infection and exchange transfusions. This study was performed to test whether the use of high-dose intravenous immunoglobulin soon after the birth of these infants reduced the need for exchange transfusions. After randomization, intravenous immunoglobulin was given at a dose of 500 mg/kg to 22 infants in the treatment group. Nothing was given to the 19 controls. The number of exchange transfusions needed decreased significantly in the treatment group. No side-effects of intravenous immunoglobulins were seen.