Showing papers in "International Journal of Gynecological Cancer in 2007"

Risk of developing ovarian cancer among women with ovarian endometrioma: a cohort study in Shizuoka, Japan.

Abstract: Although some studies have indicated that endometriosis may increase the risk of developing ovarian cancer, there are no data from epidemiologic studies in Japan. We prospectively analyzed all cases of ovarian endometrioma enrolled in the prefecture-wide Shizuoka Cohort Study on Endometriosis and Ovarian Cancer Programme, which was initiated in 1985. To evaluate the risk of ovarian cancer by time periods subsequent to ovarian endometrioma diagnosis, a cohort of 6,398 women with a clinically documented ovarian endometrioma in Shizuoka between 1985 and 1995 was identified from the Shizuoka Cancer Registry (SCR), with follow-up through 2002. Ovarian cancer incidence among cohort members was ascertained by linkage to the SCR using a unique person-identification number. Standardized incidence ratios (SIR) and their 95% confidence intervals (CI) were computed by a use of prefecture-wide rates of ovarian cancer, adjusted for age and calendar year. During follow-up of up to 17 years of the ovarian endometrioma cohort, 46 incident ovarian cancers were identified, yielding that the ovarian cancer risk was elevated significantly among patients with ovarian endometrioma (SIR = 8.95, 95% CI = 4.12-15.3). The SIR did not increase with increasing follow-up duration. The risk increased with increasing age at ovarian endometrioma diagnosis, with a SIR equal to 13.2 (95% CI = 6.90-20.9) in women above 50 years of age. Our findings for the first time support the hypothesis that ovarian endometrioma increases the subsequent risk of developing ovarian cancer in Shizuoka, Japan.

Validation and reduction of FACT/GOG‐Ntx subscale for platinum/paclitaxel‐induced neurologic symptoms: a gynecologic oncology group study

Abstract: The FACT/GOG (Gynecologic Oncology Group) Neurotoxicity (Ntx) subscale for assessing platinum/paclitaxel-induced neurologic symptoms was evaluated. The 11-item questionnaire was administered to patients with advanced endometrial cancer treated with doxorubicin/cisplatin (AP) or doxorubicin/cisplatin/paclitaxel (TAP) prior to 1-7 cycles of treatment in GOG 177. The subscale was evaluated in 134 patients in the TAP group for internal reliability, construct validity, criteria validity, sensitivity to treatment differences, and change over time. Cronbach coefficients for internal consistency prior to cycles 1-7 were 0.85, 0.80, 0.84, 0.82, 0.82, 0.85, and 0.84, respectively. The area under the receiver operating characteristic curve was 0.81 for the Ntx score prior to cycle 3. The TAP arm Ntx scores increased significantly from 3.67 at baseline to 8.13 prior to cycle 7; these were higher than the AP arm Ntx scores, which increased from 3.54 at baseline to 4.72 prior to cycle 7. The four sensory items accounted for 80% of treatment differences and 63% of longitudinal changes in the observed subscale score. The 11-item Ntx subscale reliably and validly assesses platinum/paclitaxel-induced peripheral neuropathy. A reduced four-item version is an efficient alternative in measuring this toxicity in clinical trials without compromising its performance.

Hormone therapy in advanced and recurrent endometrial cancer: a systematic review.

Abstract: Endometrial cancer is a hormone-dependent malignancy, and the majority has a precursor phase of endometrial hyperplasia. Histologic subtypes have been recognized with differing natural history. The relationship between hormone response, histology, and molecular profile is not established, but the relevant biology is summarized. This study was a systematic review of the literature to identify which populations should be considered for hormone interventions. Systematic searches were carried out in the English literature for randomized controlled trials and phase II studies of hormone interventions in endometrial cancer. Five randomized trials and 29 phase II studies were identified comprising a total of 2471 patients. In previously untreated patients with grade 1 (G1) or G2 tumors, the response rate for progestogens and the progression-free survival is in the range of 11–56% and 2.5–14 months, respectively. Higher response rates are seen in progesterone receptor–positive cases. Phase II studies comprise the majority of the data and many are of poor quality. There was considerable heterogeneity in patient selection, prior treatment, and type of regimen, and meta-analysis was not possible. G3 or G4 toxicity was less than 5%. We conclude that hormone receptor assessments should be carried out in all patients entered on clinical trials and may aid clinical management in selected cases. Receptor-negative status should not be an absolute contraindication to hormone intervention. Integration of hormone treatment with conventional chemotherapy and growth factor–targeted therapy needs to be explored.

Evaluation of endometrial carcinoma on magnetic resonance imaging

Abstract: Our aims were to assess diagnostic performance of T2-weighted (T2W) and dynamic gadolinium-enhanced T1-weighted (T1W) magnetic resonance imaging (MRI) in the preoperative assessment of myometrial and cervical invasion by endometrial carcinoma and to identify imaging features that predict nodal metastases. Two radiologists retrospectively reviewed MR images of 96 patients with endometrial carcinoma. Tumor size, depth of myometrial and cervical invasion, and nodal enlargement were recorded and then correlated with histology. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) for the identification of any myometrial invasion (superficial or deep) were 0.94, 0.50, 0.93, 0.55 on T2W and 0.92, 0.50, 0.92, 0.50 on dynamic T1W, and for deep myometrial invasion were 0.84, 0.78, 0.65, 0.91 on T2W and 0.72, 0.88, 0.72, 0.88 on dynamic T1W. The sensitivity, specificity, PPV and NPV for any cervical invasion (endocervical or stromal) were 0.65, 0.87, 0.57, 0.90 on T2W and 0.50, 0.90, 0.46, 0.92 on dynamic T1W, and for cervical stromal involvement were 0.69, 0.95, 0.69, 0.95 on T2W and 0.50, 0.96, 0.57, 0.95 on dynamic T1W. Leiomyoma or adenomyosis were seen in 73% of misdiagnosed cases. Sensitivity and specificity for the detection of nodal metastases was 66% and 73%, respectively. Fifty percent of patients with cervical invasion on MRI had nodal metastases. In conclusion, MRI has a high sensitivity for detecting myometrial invasion and a high NPV for deep invasion. MRI has a high specificity and NPV for detecting cervical invasion. Dynamic enhancement did not improve diagnostic performance. MRI may allow accurate categorization of cases into low- or high-risk groups ensuring suitable extent of surgery and adjuvant therapy.

Pattern and clinical predictors of lymph node metastases in epithelial ovarian cancer

Abstract: Para-aortic lymphadenectomy is part of staging in early epithelial ovarian cancer (EOC) and could be part of therapy in advanced EOC. However, only a minority of patients receive therapy according to guidelines or have attendance to a specialized unit. We analyzed pattern of lymphatic spread of EOC and evaluated if clinical factors and intraoperative findings reliably could predict lymph node involvement, in order to evaluate if patients could be identified in whom lymphadenectomy could be omitted and who should not be referred to a center with capacity of performing extensive gynecological operations. Retrospective analysis was carried out of all patients with EOC who had systematic pelvic and para-aortic lymphadenectomy during primary cytoreductive surgery. One hundred ninety-five patients underwent systematic pelvic and para-aortic lymphadenectomy. Histologic lymph node metastases were found in 53%. The highest frequency was found in the upper left para-aortic region (32% of all patients) and between vena cava inferior and abdominal aorta (36%). Neither intraoperative clinical diagnosis nor frozen section of pelvic nodes could reliably predict para-aortic lymph node metastasis. The pathologic diagnosis of the pelvic nodes, if used as diagnostic tool for para-aortic lymph nodes, showed a sensitivity of only 50% in ovarian cancer confined to the pelvis and 73% in more advanced disease. We could not detect any intraoperative tool that could reliably predict pathologic status of para-aortic lymph nodes. Systematic pelvic and para-aortic lymphadenectomy remains part of staging in EOC. Patients with EOC should be offered the opportunity to receive state-of-the-art treatment including surgery.

Obesity, diabetes, and other factors in relation to survival after endometrial cancer diagnosis.

Abstract: Endogenous and exogenous sources of estrogen and characteristics altering these hormone levels have been related to endometrial cancer risk; however, their relationship to survival following diagnosis is less clear. In a population-based study, we examined whether mortality after endometrial cancer diagnosis was affected by prediagnosis obesity, diabetes, smoking, oral contraceptive use, parity, or postmenopausal hormone (PMH) use. Eligible women, aged 40–79 years, diagnosed from 1991–1994 with incident invasive endometrial cancer and identified through the Wisconsin statewide mandatory cancer registry were invited to participate. Of 745 eligible cases, 166 women were deceased after 9.3 years of follow-up, with 43 attributable to endometrial cancer, based upon vital records linkage. Hazard rate ratios (HRR) and 95% confidence intervals were adjusted for age at diagnosis, menopausal status, stage of disease, and other exposures of interest. Obese women (body mass index [BMI] ≥30 kg/m2) prior to endometrial cancer diagnosis had an increased risk of both all-cause (HRR = 1.6, 95% CI 1.0–2.5) and endometrial cancer (HRR = 2.0, 95% CI 0.8–5.1) mortality, compared with nonoverweight women (BMI

The performance of magnetic resonance imaging in early cervical carcinoma: a long-term experience

Abstract: We report our long-term experience of performance of magnetic resonance imaging (MRI) in localizing cervical tumor, assessing tumor size, staging, and lymph node infiltration in patients with early cervical cancer. MRI of 150 patients with early carcinoma between 1995-2005 was retrospectively reviewed. Tumor location, size, tumor distance from internal os, parametrial invasion, myometrial invasion, lymph node size, and location were documented. All patients underwent surgery, pelvic lymphadenectomy, and histological correlation of MRI findings. For staging, MRI and histopathology had kappa value of 0.89. For parametrial invasion, MRI had specificity, negative predictive value (NPV) of 97% and 100%, respectively. For tumor size, MRI and histology had mean difference of -0.9 mm with 95% limits of agreement between -12.6 to +13 mm. In tumors greater than 10 mm, mean difference was 0.3 mm and limits of agreement were -7.5 to +7.9 mm. For internal os involvement sensitivity, specificity, positive predictive value (PPV) and NPV were 90%, 98%, 86%, 98%. respectively. For myometrial invasion sensitivity, specificity, NPV, and PPV were 100%, 99%, 88%, 100%, respectively. Incidence of nodal metastases was 2.9%. On a per-patient basis, sensitivity, specificity for nodal involvement was 37% and 92% and on node-by-node basis, sensitivity and specificity of MRI was 27% and 99%, respectively. Our study confirms MRI is highly accurate in localizing cervical tumor, excluding parametrial invasion, confirming myometrial and internal os invasion. MRI is therefore useful in selecting patients for surgery and mandatory in patients for fertility-preserving surgery. Using accepted size criteria for nodal involvement, MRI is insensitive and currently will not avoid need for pelvic lymphadenectomy.

Surveillance procedures for patients treated for epithelial ovarian cancer: a review of the literature

Abstract: Epithelial ovarian cancer is the leading cause of death from gynecological cancer in the Western countries. Approximately 20%-30% of patients with early-stage disease and 50%-75% of those with advanced disease who obtain a complete response following first-line chemotherapy will ultimately develop recurrent disease, which more frequently involves the pelvis and abdomen. Few formal guidelines exist regarding the surveillance of these patients, and there is no agreement in the literature about the type and timing of examinations to perform. Moreover, the objective of follow-up is unclear as recurrent epithelial ovarian cancer continues to be a therapeutic dilemma and quite all the relapsed patients will eventually die of their disease. The follow-up of asymptomatic patients generally include complete clinical history, serum cancer antigen (CA)125 assay, physical examination, and often ultrasound examination, whereas additional radiologic imaging techniques are usually performed when symptoms or signs appear. (18)Fluoro-2-deoxy-glucose ((18)FDG)-positron emission tomography (PET) has a sensitivity of 90% and a specificity of 85% approximately for the detection of recurrent disease, and this examination appears to be particularly useful for the diagnosis of recurrence when CA125 levels are rising and conventional imaging is inconclusive or negative. Recently, technologic advances have led to novel combined (18)FDG-PET/computed tomography (CT) devices, which perform contemporaneous acquisition of both (18)FDG-PET and CT images. The role of (18)FDG-PET/CT for the detection of recurrent ovarian cancer is very promising, and this technique may be especially useful for the selection of patients with late recurrent disease who may benefit from secondary cytoreductive surgery.

A phase II study of outpatient first-line paclitaxel, carboplatin, and bevacizumab for advanced-stage epithelial ovarian, peritoneal, and fallopian tube cancer.

Abstract: The purpose of this study was to assess the response rate and toxicity of paclitaxel, carboplatin, and bevacizumab (PCB) primary induction therapy for the treatment of advanced-stage ovarian carcinoma. Twenty patients were treated with paclitaxel (175 mg/m2), carboplatin (AUC of 5 IV), and bevacizumab (15 mg/kg) of body weight; q21 days for six cycles. Bevacizumab was administered at cycles two through six. Patients received 116 cycles of PCB chemotherapy (median = 6, range 2–6) and were evaluable for toxicity assessment. Grade 3 and 4 neutropenia developed in 23.3% and 25% of cycles, with no incidence of grades 3/4 thrombocytopenia or anemia. Prior to cycle six, one patient was removed from the study due to grade 3 neuropathy and another patient was excluded due to clinical deterioration. There was no incidence of gastrointestinal perforations, and only two patients demonstrated grade 3 hypertension (HTN). No grade 4 HTN was observed. Eighteen patients were evaluated for response following induction therapy. Six demonstrated a complete response (30%) and ten exhibited a partial response (50%), resulting in a total response rate of 80%. One patient exhibited stable disease (5%), and one demonstrated disease progression (5%). The lack of bowel perforations and wound complications should mitigate some concerns regarding these side effects. This study suggests that first-line treatment with PCB can be safely administered to previously untreated advanced-stage ovarian carcinoma patients. The favorable toxicity results and reasonable response rate warrant additional study in a larger patient population.

Gene expression profiles in squamous cell cervical carcinoma using array‐based comparative genomic hybridization analysis

Abstract: Our aim was to identify novel genomic regions of interest and provide highly dynamic range information on correlation between squamous cell cervical carcinoma and its related gene expression patterns by a genome-wide array-based comparative genomic hybridization (array-CGH). We analyzed 15 cases of cervical cancer from KangNam St Mary's Hospital of the Catholic University of Korea. Microdissection assay was performed to obtain DNA samples from paraffin-embedded cervical tissues of cancer as well as of the adjacent normal tissues. The bacterial artificial chromosome (BAC) array used in this study consisted of 1440 human BACs and the space among the clones was 2.08 Mb. All the 15 cases of cervical cancer showed the differential changes of the cervical cancer-associated genetic alterations. The analysis limit of average gains and losses was 53%. A significant positive correlation was found in 8q24.3, 1p36.32, 3q27.1, 7p21.1, 11q13.1, and 3p14.2 changes through the cervical carcinogenesis. The regions of high level of gain were 1p36.33-1p36.32, 8q24.3, 16p13.3, 1p36.33, 3q27.1, and 7p21.1. And the regions of homozygous loss were 2q12.1, 22q11.21, 3p14.2, 6q24.3, 7p15.2, and 11q25. In the high level of gain regions, GSDMDC1, RECQL4, TP73, ABCF3, ALG3, HDAC9, ESRRA, and RPS6KA4 were significantly correlated with cervical cancer. The genes encoded by frequently lost clones were PTPRG, GRM7, ZDHHC3, EXOSC7, LRP1B, and NR3C2. Therefore, array-CGH analyses showed that specific genomic alterations were maintained in cervical cancer that were critical to the malignant phenotype and may give a chance to find out possible target genes present in the gained or lost clones.

Less radical fertility-sparing surgery than radical trachelectomy in early cervical cancer.

Abstract: The purpose of this pilot study was to determine feasibility and safety of a novel and less radical fertility-preserving surgery; laparoscopic lymphadenectomy with sentinel lymph node identification (SLNI) followed by large cone or simple trachelectomy Obstetrical and oncologic outcomes were evaluated Twenty-six patients (6-IA2, 20-IB1) selected on basis of favorable cervical tumor characteristics and the desire to maintain fertility underwent laparoscopic SLNI, frozen section (FS), and a complete pelvic lymphadenectomy as first step of treatment All of nodes were submitted for microscopic evaluation (sentinel nodes for ultramicrostaging) After a 7-day interval, large cone or simple vaginal trachelectomy was performed in patients with negative nodes The average of sentinel nodes per side was 150 and the average of total nodes was 280 Four FS were positive (154%) In these cases, Wertheim radical hysterectomy type III was immediately performed We had no false-negative SLN neither on FS nor on final pathology assessment Median follow-up was 49 months (18-84) One central recurrence (isthmic part of uterus) was observed 14 months after surgery This patient was treated with radical chemoradiotherapy, and there was no evidence of the disease 36 months after treatment Fifteen women planned pregnancy, 11 women became pregnant (15 pregnancies), and 7 women delivered eight children (one in 24 weeks, one in 34 weeks, one in 36 weeks, and five between 37 and 39 weeks) We conclude that lymphatic mapping and SLNI improves safety in this fertility sparing surgery Large cone or simple trachelectomy combined with laparoscopic pelvic lymphadenectomy can be a feasible method with a high successful pregnancy rate

Aldo‐keto reductase family 1, member B10 in uterine carcinomas: a potential risk factor of recurrence after surgical therapy in cervical cancer

Abstract: Aldo-keto reductase family 1, member B10 (AKR1B10), an enzyme that converts retinals into retinols is known to detect in non-small cell lung carcinoma (squamous cell- and adeno-carcinomas), but is barely expressed in normal tissues. Since these types of carcinoma occur frequently in the uterus (like in the lung), AKR1B10 may also be overexpressed in two major types of uterine cancer, cervical cancer (CC), and endometrial cancer (EMC). The objective of this study is to investigate AKR1B10 expression in uterine cancer and to analyze its clinical significance. In samples from uterine cancer patients, AKR1B10 was detected in 6 out of 30 (20.0%) CC cases and 6 out of 38 (15.8%) EMC cases. Statistical analysis indicated that AKR1B10 expression was associated with tumor recurrence after surgery and keratinization of squamous cell carcinoma only in CC. Although retinol (a metabolic product by AKR1B10) was observed in the normal epithelium, the molecule was not observed in cancer cells of AKR1B10-positive CC samples suggesting that the recurrence in CC may not depend on the convert of retinals into retinols via AKR1B10, a potential indicator in the management of patients with CC.

Long-term outcome and prognostic factors in patients with cervical carcinoma: a retrospective study.

Abstract: This study evaluates treatment outcomes and possible prognostic factors of inoperable cervical cancer patients treated with external beam radiotherapy (EBRT) and high–dose rate brachytherapy (HDR BRT). Between 1993 and 2000, 183 patients with cervical cancer were treated at our institute. Radiotherapy was the sole treatment modality until January 1997; after the announcement of National Cancer Institute in 1999, 40 mg/m2 of cisplatin (49%) was routinely applied every week. Median age was 54 years (32–92 years). Most patients (88%) had advanced-stage disease (IIB–IIIB). With a median follow-up time of 45 months (6–121 months), the 5-year overall survival (OS), local recurrence–free survival, disease-free survival (DFS), and distant metastasis–free survival (DMFS) rates were 55%, 71%, 51%, and 77%, respectively. Univariate analysis revealed that age, tumor size, lymph node status, and concomitant cisplatin were prognostic factors for OS. The DFS rates were lower in young age group. Patients with tumor greater than 4 cm and age greater than 40 were at greater risk for local recurrence. Distant metastases were more frequent in patients with adenocarcinoma. Concurrent cisplatin use increases DMFS rates (91% vs 78%; P= 0.05). In multivariate analysis, extensive stage, parametrial infiltration, young age, adenocarcinoma histopathology, and lymph node metastasis were negative prognostic factors for OS while concomitant cisplatin increases OS. Likewise, patients with extensive stage, adenocarcinoma, and without concurrent cisplatin administration had more risk for distant metastasis. There was no treatment-related mortality. Grade 3–4 morbidity rates were seen only in eight patients (4%). The combination of EBRT and HDR BRT together with concomitant chemotherapy in the treatment of locally advanced carcinoma of cervix is safe and well tolerated with acceptable morbidity.

Ovarian tumors of borderline malignancy: a review of 247 patients from 1991 to 2004

Abstract: Borderline ovarian tumors account for 15% of epithelial ovarian cancers and are different from invasive malignant carcinoma. Majority are early stage, occurring in women in the reproductive age group, where fertility is important. We reviewed retrospectively 247 such cases treated at the Gynaecological-Oncology Unit, KK Women9s and Children9s Hospital, between January 1991 and December 2004. The mean age was 38 years (16–89 years). Majority of the cases (92%) were FIGO stage I (Ia, 75%; Ib, 1%; and Ic, 16%). Seven (3.5%) patients were diagnosed as having stage II disease, six (2.5%) as stage IIIa, two (1%) as stage IIIb, and four (2%) as stage IIIc. Histological origin was as follows: mucinous (68%), serous (26%), endometrioid (2.6%), and clear cell (1.2%). Primary surgical procedures undertaken were as follows: hysterectomy with bilateral salpingo-oophorectomy (52%), unilateral salpingo-oophorectomy (33%), or ovarian cystectomy (15%). Adjuvant chemotherapy was administered in 13 patients (5.2% of cases), of which 4 patients were given chemotherapy only because of synchronous malignancies. There were six recurrences (2.4% of cases). Overall mean time to recurrence was 59 months. Recurrence rate for patients who underwent a primary pelvic clearance was 1.6% compared to fertility-sparing conservative surgery (3.3%; although P= 0.683). No significant difference was noted in recurrence and mortality between staged versus unstaged procedures. The overall survival rate was 98.0%. There were a total of five deaths (2.8%): three (1.5%) from invasive ovarian/peritoneal carcinoma and two from synchronous uterine malignancies. It appears that surgical resection is the mainstay of treatment, with conservative surgery where fertility is desired or pelvic clearance if the family is complete. Surgical staging is important to identify invasive extraovarian implants that portend an adverse prognosis. The role of adjuvant chemotherapy is not established.

A case-controlled study of total laparoscopic radical hysterectomy with pelvic lymphadenectomy versus radical abdominal hysterectomy in a fellowship training program.

Abstract: To determine whether total laparoscopic radical hysterectomy (TLRH) is a feasible alternative to an abdominal radical hysterectomy (ARH) in a gynecologic oncology fellowship training program. We prospectively collected cases of all of the patients with cervical cancer treated with TLRH and pelvic lymphadenectomy by our division from 2000 to 2006. All of the patients from the TLRH group were matched 1:1 with the patients who had ARH during the same period based on stage, age, histological subtype, and nodal status. Thirty patients were treated with TLRH with a mean age of 48.3 years (range, 29-78 years). The mean pelvic lymph node count was 31 (range, 10-61) in the TLRH group versus 21.8 (range, 8-42) (P < 0.01) in the ARH group. Mean estimated blood loss was 200 cc (range, 100-600 cc) in the TLRH with no transfusions compared to 520 cc in the ARH group (P < 0.01), in which five patients required transfusions. Mean operating time was 318.5 min (range, 200-464 min) compared to 242.5 min in the ARH group (P < 0.01), and mean hospital stay was 3.8 days (range, 2-11 days) compared to 5.6 days in the ARH group (P < 0.01). All TLRH cases were completed laparoscopically. All patients in the TLRH group are disease free at the time of this report. In conclusion, it is feasible to incorporate TLRH training into the surgical curriculum of gynecologic oncology fellows without increasing perioperative morbidity. Standardization of TLRH technique and consistent guidance by experienced faculty is imperative.

A meta-analysis of the efficacy of intraperitoneal cisplatin for the front-line treatment of ovarian cancer.

Abstract: Hess LM, Benham-Hutchins M, Herzog TJ, Hsu C-H, Malone DC, Skrepnek GH, Slack MK, Alberts DS. A meta-analysis of the efficacy of intraperitoneal cisplatin for the front-line treatment of ovarian cancer. Int J Gynecol Cancer 2007;17:561-570. Ovarian cancer is the fourth leading cause of cancer death among women in the United States. First-line chemotherapy offered to patients with ovarian cancer generally consists of an intravenous (IV) platinum plus taxane regimen and has remained virtually unchanged for the past 10 years. A number of recently completed phase III randomized trials in the United States have reported improved progression-free sur- vival (PFS) and/or overall survival (OS) with the intraperitoneal (IP) administration of cisplatin. The pur- pose of this study was to pool the published data to perform a meta-analysis of randomized trials of IP cisplatin in the initial chemotherapy treatment of ovarian cancer patients. This study was initiated to obtain a more valid estimate of the therapeutic impact of IP treatment for these patients. A search strategy was initiated that searched published findings of randomized trials of IP cisplatin therapy from multiple sources from January 1990 through January 2006. Six randomized trials of 1716 ovarian cancer patients were identified and included in this analysis. The pooled hazard ratio (HR) for PFS of IP cisplatin as com- pared to IV treatment regimens is 0.792 (95% CI: 0.688-0.912, P ¼ 0.001), and the pooled HR for OS is 0.799 (95% CI: 0.702-0.910, P ¼ 0.0007). These findings strongly support the incorporation of an IP cisplatin regi- men to improve survival in the front-line treatment of stage III, optimally debulked ovarian cancer.

Principles and practice of intraperitoneal chemotherapy for ovarian cancer

Abstract: Intraperitoneal (IP) chemotherapy has been studied for years to improve the survival of patients with ovarian cancer. Recently, the result of Gynecologic Oncology Group 172 trial comparing IP versus intravenous administration of cisplatin-based chemotherapy was published, demonstrating the improvement of survival benefit in favor of the IP arm. This trial is the third trial that showed a survival benefit on IP chemotherapy. The National Cancer Institute (NCI) and Gynecologic Oncology Group have done a meta-analysis on the results of these three US trials and other phase III trials of IP versus intravenous chemotherapy, and significant improvement of survival was shown with IP therapy. Based on this meta-analysis, NCI has released a clinical announcement encouraging the gynecological oncology community to consider IP chemotherapy as the standard treatment for optimally debulked advanced ovarian cancer patients. However, there still are controversial issues regarding the use of IP chemotherapy. It is important to understand how IP chemotherapy works to solve those issues in the future. In this review article, we discuss the principles and clinical aspects of IP chemotherapy and also discuss the current problems and future perspectives in IP chemotherapy.

Validity of positron emission tomography using fluoro-2-deoxyglucose for the preoperative evaluation of endometrial cancer.

Abstract: To clarify the validity of positron emission tomography using fluoro-2-deoxyglucose (FDG-PET) for the preoperative evaluation of endometrial cancer, we analyzed the preoperative FDG-PET images of both primary and metastatic lesions of 30 patients with endometrial cancer, and compared them with computed tomography (CT) and/or magnetic resonance imaging (MRI) images and the results of postoperative pathologic findings As to the primary lesions, FDG-PET could easily identify the cancer, and the sensitivity was 967%, which tended to be higher than that of 833% by CT/MRI As to the evaluation of retroperitoneal lymph node metastasis, FDG-PET could detect none of five cases of lymph node metastatic lesions of up to 06 cm in diameter but had higher specificity (100%) compared with CT/MRI (857%) The sensitivity of FDG-PET for detection of extrauterine lesions excluding retroperitoneal lymph nodes was 833% and was superior to that of CT/MRI (667%), although there was no difference in the specificity between the modalities (100%) The diagnostic ability of FDG-PET was limited if used alone, but FDG-PET gave additional information especially with regard to the extrauterine lesions whose significance could not be determined on CT/MRI However, we also found that FDG-PET could not identify any lymph node metastasis less than 1 cm in diameter; therefore, a negative finding of lymph node metastasis on FDG-PET should not be interpreted as a reason for omitting retroperitoneal lymph node dissection for the precise surgical staging of endometrial cancer

Expression of claudin-3 and claudin-4 in normal, hyperplastic, and malignant endometrial tissue

Abstract: To clarify the roles of claudins in endometrial tumorigenesis, we determined levels of protein and messengerRNA (mRNA) expression of claudin-3 and claudin-4 in human endometrial tissue (proliferative phase [PE, n= 25]; secretory phase [SE, n= 25]; simple hyperplasia [SH, n= 20]; complex hyperplasia [CH, n= 12]; atypical hyperplasia [AH, n= 15]; endometrioid adenocarcinoma [EEC, n= 30]) using immunohistochemistry, western blotting, and real-time polymerase chain reaction, respectively. Morphologic changes of tight junctions (TJs) were also observed in normal, hyperplastic, and malignant endometrial tissue. Absence or weak staining for claudin-3 and claudin-4 was observed in PE, SE, SH, and CH, while medium to intense staining was detected in AH and EEC. Staining of claudin-3 and claudin-4 was predominantly localized to the glandular epithelial cell membrane. Expression of claudin-3 and claudin-4 was significantly increased in the groups of AH and EEC in comparison with the groups of CH, SH, and normal cyclic endometrium at both protein and mRNA levels. The highest expression was observed in EEC. Although no relevance was found with regard to FIGO stage and histologic grade, overexpression of claudin-3 and claudin-4, especially claudin-4, significantly correlated with myometrial invasion. Transmission electron microscopy analysis indicated morphologic disruptions of TJs may lag behind the increase of claudins expression. These results demonstrate that claudin-3 and claudin-4 are strongly expressed in AH and EEC, but less frequently in normal endometrium. The upregulation of claudins expression during endometrial carcinogenesis suggests their potential utility as diagnostic and prognostic biomarkers.

Advanced stage of cervical carcinoma undiagnosed during antenatal period in term pregnancy and concomitant metastasis on episiotomy scar during delivery: a case report and review of the literature.

Abstract: The objective of this study is to review the implantation of malignant cells of cervical cancer in an episiotomy site. This is the second case of cervical cancer with concomitant episiotomy metastasis in the literature. The treatment consisted of radiochemotherapy. There was no confirmed recurrent disease after 1 year of follow-up in our reported case. In conclusion, pregnancy appears to be a chance for cervical cancer screening as a part of prenatal care. If cervical cancer is diagnosed in a woman after vaginal delivery, she must be examined carefully including the episiotomy site.

Transketolase-like 1 expression correlates with subtypes of ovarian cancer and the presence of distant metastases.

Abstract: Tumorbiology of ovarian cancer remains unclear. However, it is known that ovarian tumors, especially carcinomas, show elevated expression of glucose membrane transporters for facilitated glucose uptake. It can be assumed that increased glucose uptake leads to higher glucose metabolism. The energy resources of fully malignant transformed carcinomas are mainly supplied by aerobic glycolysis, for which several pathways are known. A key role in aerobic glycolysis is described for the transketolase enzymes. Recently, a novel transketolase-like enzyme called transketolase-like 1 (TKTL1) has been described that links aerobic glycolysis to the synthesis of fatty acids via production of acetyl-CoA. In order to investigate the role of TKTL1 for the progression of ovarian carcinomas, we examined paraffin sections of normal ovarian tissues, ovarian borderline tumors, and mucinous or serous papillary ovarian adenocarcinomas with respect to their expression of TKTL1. We identified a significantly elevated expression of TKTL1 in serous papillary ovarian adenocarcinomas, which correlates with poor prognostic parameters in the examined study group. Therefore, it can be assumed that TKTL1 plays a crucial role in ovarian cancer metabolism and that its expression predicts poor prognosis. Further investigations should be performed in order to evaluate whether this new enzyme is important for ovarian cancer tumorbiology and to analyze the potential role of TKTL1 as new target for specific antitumoral therapy.

Phase II trial of imatinib mesylate in recurrent, biomarker positive, ovarian cancer (Southwest Oncology Group Protocol S0211)

Abstract: Platinum-resistant ovarian cancer continues to be a difficult therapeutic problem. Clearly, molecularly targeted agents should be evaluated in this patient population. Patients were eligible for this phase II study with stage III or IV ovarian cancer, whose tumor expressed Kit (CD117) or platelet-derived growth factor receptor (PDGFR) and with relapse of measurable disease within 6 months of completing frontline, platinum- and taxane-based chemotherapy. Patients were treated daily with 400 mg of imatinib mesylate orally. It was assumed that the agent would be of no further interest if the population response rate was less than 10%. A two-stage design was used for patient accrual. A total of 34 patients were registered to the study. Of these, 15 were found to be ineligible or not evaluable (8 because their tumor samples were negative for both DC117 and PDGFR). Of 19 evaluable patients, 2 (11%) tested positively for c-Kit and 17 (89%) tested positively for PDGFR. There were no objective responders. Thirteen patients (68%) had increasing disease or symptomatic deterioration, and six (32%) went off protocol during the first month due to adverse events. Median progression-free survival was 2 months (95% CI 1–3 months) and median overall survival was 10 months (95% CI 6–18 months). Eleven percent of patients experienced grade 4 hematologic/metabolic toxicity and 37% experienced grade 3 nonhematologic toxicity. We conclude that imatinib mesylate as a single agent does not appear to have useful clinical activity in c-Kit and/or PDGFR positive, recurrent ovarian cancer in heavily pretreated patients with ovarian cancer

Ovarian metastases in early-stage cervical cancer (IA2-IIA): a multicenter retrospective study of 1965 patients (a Cooperative Task Force study).

Abstract: This is a retrospective study of patients treated for early-stage cervical cancer to identify pathologic risk factors associated with ovarian metastases and, therefore, to establish when ovarian preservation can be performed without increasing the risk of relapse in order to improve the quality of life in premenopausal patients. Between 1982 and 2004, 1965 patients with FIGO stage IA2-IB-IIA cervical squamous cell carcinoma and nonsquamous histology types were surgically treated; 1695 (86%) patients underwent primary radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic node dissection, the remaining 270 patients (14%) had their ovaries preserved. The clinical records were reviewed for all patients and clinical features at presentation, the histopathology and follow-up data were recorded. Overall, ovarian metastases were diagnosed in 16 of 1695 patients, for an incidence rate of 0.9%. Univariate analysis shows age ( 45 years: P = 0.0079), FIGO stage (IB1-IIA 4 cm: P = 0.0133), histology (squamous vs nonsquamous, P = 0.0014), noninvolved peripheral stromal thickness ( 3 mm: P = 0.0001), lymphvascular space involvement (present vs absent, P = 0.0007), lymph node status (positive vs negative, P = 0.00009) to be statistically associated with the presence of ovarian metastases. Multivariate analysis shows only age (P = 0.0119), FIGO stage (P = 0.011), histology (P = 0.001), and unaffected peripheral stromal thickness (<3 mm: P = 0.037) to be independent risk factors for ovarian metastases. Based on the present data and on the data available in the literature, ovarian preservation could be safely performed in young patients with early-stage squamous cell carcinoma (histology as the most significant risk factor), with macroscopically normal ovaries, and with preserved peripheral unaffected cervical stroma.

Current management of ovarian carcinosarcoma.

Abstract: Ovarian carcinosarcomas (OCS), also known as malignant mixed mullerian tumors, are uncommon malignancies that carry a poor prognosis. The presentation of OCS is usually indistinguishable from that of epithelial ovarian cancer. Due to its low frequency, prospective trials have been difficult to perform, but there is evidence that OCS are sensitive to platinum-based chemotherapy. Recent studies have shown encouraging results with platinum-ifosfamide and platinum-taxane schedules, which are usually considered the treatment of choice. However, poor performance status at presentation is also a common problem, so that many patients may be unsuitable for combination chemotherapy but may still benefit from single-agent platinum or ifosfamide or, occasionally, from nonplatinum schedules such as ifosfamide plus paclitaxel. Aggressive cytoreductive surgery appears to have a positive impact on outcome and should probably be offered to most patients. However, this procedure has been associated with higher rates of complication in OCS and should only be attempted by experienced (gynecological) surgeons in centers with expertise in the management of gynecological malignancies.

The prognostic importance of cyclooxygenase 2 and HER2 expression in epithelial ovarian cancer

Abstract: Both cyclooxygenase 2 (COX2) and human epidermal growth factor receptor 2 (HER2, also called c-erbB-2) overexpression have been related to a worse prognosis in epithelial ovarian cancer (EOC), but the data are conflicting and the percentage of tumors with overexpression varies widely in different studies. The aim of this study was to investigate the potential prognostic value of COX2 and HER2 expression in EOC. A further purpose was to investigate a possible coexpression of the two markers, and finally, to elucidate the agreement between fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) for evaluation of the HER2 status in EOC. Immunostaining was performed for COX2/HER2 together with FISH analysis for HER2 gene amplification in 160 patients with EOC, FIGO stages IIB–IV. Follow-up was more than 10 years. COX2 overexpression was found in 20.0% of the tumors. With HER2 staining, 64.4% were scored as 0, 24.4% as 1+, 6.9% as 2+, and 4.4% as 3+. Median survival time for COX2-negative tumors was 21.6 versus 36 months for COX2-positive tumors. The longer survival for COX2 positive was significant by both univariate analysis (P= 0.015) and multivariate analysis (P= 0.025). Positive immunostaining for HER2 was associated with poor overall survival (P= 0.03). Agreement between IHC and FISH was seen in all cases (P

Comparison of trace element concentrations in cancerous and noncancerous human endometrial and ovary tissues.

Abstract: Question of whether trace metal concentrations in tissues are increased or decreased in cancerous patients in comparison with noncancerous patients has not been answered yet, due to the fact that the data known in this field are rare and have contradictory results. Although Zn and Cu concentrations in serum and tissues of cancerous patients have extensively been studied, the precise role of these metals in carcinogenesis is not clearly understood. There are few studies on the concentrations of essential and toxic trace/minor metals in human tissue samples in comparison with serum and plasma samples. Trace metal concentrations including Cd, Cu, Zn, Fe, Mg, Ca, and Ni in both cancerous and noncancerous endometrial, ovary, and cervix uteri tissues were determined by atomic absorption spectrometry. The tissue samples were digested by using microwave energy. Slotted tube atom trap was used to improve the sensitivity of copper and cadmium in flame atomic absorption spectrometry determination. The concentrations of iron in cancerous endometrial tissues were found to be significantly higher than those in noncancerous samples (P < 0.01). On the contrary Fe, Zn concentration in cancerous endometrial tissue was found to be lower significantly than those in noncancerous samples (P= 0.005), whereas the other studied metals were not observed different. Furthermore, Cu and Ca concentrations in cancerous ovary samples were observed to be higher than those in noncancerous ovary tissues (P < 0.01 for Cu and P= 0.1 for Ca), whereas Mg, Fe, and Zn levels in cancerous ovary samples were not found to be different than those in noncancerous tissues.

The prognostic value of PTEN, p53, and beta‐catenin in endometrial carcinoma: a prospective immunocytochemical study

Abstract: Mutations of the PTEN, p53, and beta-catenin genes are the most frequent molecular defects in endometrial carcinomas The aim of this study was to investigate their prognostic significance in this form of cancer Imprint smears were obtained from 80 fresh endometrial tumor specimens and studied immunocytochemically for the expression of PTEN, p53, and beta-catenin proteins The staining pattern was correlated with several well-established prognostic parameters, including 5-year survival Positive staining of p53 was significantly correlated with increased stage (P < 00001), lymph node metastases (P = 0001), and a nonendometrioid histology (P = 0001) On the contrary, positive beta-catenin expression was significantly associated with decreased stage (P = 0002), decreased grade (P = 0007), and a negative lymph node status (P = 0023) PTEN positivity was correlated with decreased stage (P = 0002) and negative lymph nodes (P = 0008) All the three markers affected survival significantly in univariate analysis but only beta-catenin had an independent prognostic impact An independent prognostic significance was also shown for PTEN in the stage I subgroup of patients The results of our study indicate that loss of beta-catenin expression is a strong and independent predictor of an unfavorable outcome in patients with endometrial carcinoma Loss of PTEN may also be associated with a worse prognosis in patients with early-stage disease

A comparative profile of the prevalence and age distribution of human papillomavirus type 16/18 infections among three states of India with focus on northeast India

Abstract: Human papillomavirus (HPV) DNA in cervical scrape samples of married women from Manipur (n= 692) and Sikkim (n= 415) in northeast India was determined and compared with that of women from West Bengal (n= 1112) in eastern India by polymerase chain reaction. HPV prevalence was lower in Manipur (7.4%) than in Sikkim (12.5%), which was closely followed by West Bengal (12.9%). HPV18 was predominant in Manipur (2.03%) and strikingly lower (0.2%) in Sikkim and West Bengal (0.9%), while the reverse was true for HPV16. The proportion of HPV16/18 infections in Manipur (3.3%, 22/672) and Sikkim (3.89%, 14/359) were comparable and significantly lower compared to that in West Bengal (7.8%, 79/1007) among women having normal cervical cytology. Such prevalence was similar among all age groups in Manipur: increased with age for women in Sikkim and dropped with age for those in West Bengal similar to that reported previously. At age ≤30 years, HPV16/18 prevalence in Manipur (3.3%) and Sikkim (2.5%) was comparable but was significantly lower (P 30 years and equally among those in West Bengal aged ≤30 or >30 years. Thus, women from northeast India, particularly from Manipur, appear less susceptible to HPV16/18 infection and related cervical lesions compared to those from West Bengal, where such proneness was prominently evident at age ≤30 years.

Cytokine profile in Indian women with cervical intraepithelial neoplasia and cancer cervix.

Abstract: Cervical cancer develops from the preneoplastic cervical intraepithelial neoplasia (CIN). Host factors are critical in regulating tumor growth and cytokines, which modulate immunologic control may be of particular importance. The objective of this study was to assess the production of cytokines by peripheral blood mononuclear cells (PBMCs) in Indian women with cancer cervix and CIN. Sixty patients with cancer cervix (including all FIGO stage I–IV), 35 patients with CIN, and 30 healthy controls were enrolled in this study. The human papillomavirus (HPV) 16 and 18 status was determined in all the study groups. The PBMC culture supernatant was collected for cytokine estimations by enzyme-linked immunosorbent assay (interleukin-2 [IL-2], interferon-gamma [IFN-γ], interleukin-4 [IL-4], and interleukin-10 [IL-10]). IL-2 levels showed a significant decline in high-grade CIN and cancer patients, whereas IFN-γ levels were decreased only in patients with advanced cancer cervix. An increase in the levels of IL-4 and IL-10 was found in all cancer cervix and CIN grade III patients, as compared to those with early CIN grades and healthy controls. The cytokine ratios decreased significantly (P

Sentinel lymph node in endometrial cancer.

Abstract: The aim of this study was to evaluate the possibility of identifying the sentinel lymph node and involvement of neoplastic cells in patients with endometrial carcinoma limited to the uterus, and also its correlation with the conditions of other pelvic and para-aortic lymph nodes. Forty patients with endometrial carcinoma, clinical staging I and II, were submitted to complete surgical staging through laparotomy, as recommended by FIGO in 1988. The sentinel node was investigated using patent blue dye in the myometrial subserosa. The sentinel node was excised and submitted to frozen section examination of specimen, stained with hematoxylin and eosin (H&E). Afterward, selective bilateral para-aortic and pelvic lymphadenectomy, total hysterectomy with bilateral salpingo-oophorectomy were performed. The lymph nodes excised were examined by means of paraffin-embedded slices stained with H&E and of imunohistochemistry with antikeratin antibody AE1/AE3. The sentinel lymph node was identified in 77.5% of patients (31/40), and 16.1% (5/31) presented neoplastic involvement in the node. In 25 cases of negative sentinel node, 96% (24/25) had no neoplastic involvement, and 4% (1/25) had other lymph node affected (false negative). In nine cases with no sentinel node identified, 55.5% (5/9) had lymph node involvement. The results of this study allow us to conclude that it is possible to identify the sentinel node using the methods described, and the pathologic examination significantly represents the same conditions of other pelvic and para-aortic lymph nodes.