Stage IVB endometrial cancer confined to the abdomen: is chemotherapy superior to radiotherapy?

PURPOSE: To determine the impact of clinical variables and adjuvant therapy on survival in patients with Stage IVB endometrial cancer (EC) confined to abdomen. METHODS AND METHODS: A total of 65 patients were included. Curative chemotherapy was defined as using only chemotherapy (platin based) or sandwich therapy. Patients receiving only radiotherapy had standard pelvic radiotherapy and extended-field radiotherapy when necessary. RESULTS: The optimal cytoreduction was achieved in 89.3% of patients. With a median follow-up of 18 months, two-year progression free survival (PFS) and overall survival (OS) were calculated as 33.4% and 42.2%, respectively. Optimal cytoreduction provided more longer PFS and OS compared to suboptimal cytoreduction. In univariate analysis, curative chemotherapy instead of radiotherapy improved the two-year PFS and two-year OS. Type of adjuvant therapy, tumor grade, and peritoneal cytology were found as the independent prognostic factors for PFS. Peritoneal cytology, adnexal involvement, and adjuvant therapy were independent prognostic factor for OS. CONCLUSION: Curative chemotherapy significantly improved both two-year PFS and OS in patients with Stage IVB endometrial disease confined to abdomen over only radiotherapy.

The importance of age and menopausal status in endometrial complex hyperplasia with atypia.

The effects of menopausal status and age on the intra-operative and post-operative pathology results of patients operated on with a pre-operative diagnosis of complex hyperplasia with atypia (CHA) were assessed. A hundred and eleven patients diagnosed in our centre between January 1993 and March 2013 were included. Cancer was detected in the paraffin blocks (PBs) of 52 (46.8%) patients. Among these, 50 patients had stage-IA disease. In 31.1% of the pre-menopausal patients and 66% of the post-menopausal patients, PB revealed cancer (p < 0.0001). The results of frozen section (FS) and PB were concordant in 51% and 70% in the pre-menopausal and post-menopausal patients, respectively (p = 0.041). In the patients operated on with a pre-operative diagnosis of CHA, the probability of detecting cancer in PB increases with increasing age and menopause. The reliability of FS is limited in younger and pre-menopausal patients.

Undifferentiated uterine carcinoma: analysis of eighteen cases.

Analysis of the surgicopathological characteristics and clinical follow-up of patients with undifferentiated uterine carcinoma (UUC) was conducted. A total of 18 cases operated between January 1993 and December 2013 were included. Among 1,690 patients with endometrial cancer, 18 patients (1.1%) had UUC. Lymph node involvement was detected in 70.6%; depth of myometrial invasion was ≥ 0.5 in 55.6%; lymphovascular space invasion was detected in 99.3%; cervical stromal invasion was positive in 27.8%; omental and adnexal involvement were detected in 11.8% and 38.9%, respectively. The median follow-up time of the 12 patients evaluated in the survival analysis was 66 months. In the follow-up period, recurrence or progression during adjuvant therapy were observed in four patients (33.3%) and two patients (16.6%) died of the disease. UUC manifests as an aggressive tumour. In conclusion, a high rate of survival could be achieved with complete staging surgery, including an extensive lymphadenectomy with the contribution of adjuvant therapy.

Carboplatin-paclitaxel-induced leukopenia and neuropathy predict progression-free survival in recurrent ovarian cancer.

BACKGROUND: We assess the prognostic value of chemotherapy-induced leukopenia and sensory neuropathy in the CALYPSO trial patients treated with carboplatin-paclitaxel (CP) or carboplatin-liposomal doxorubicin (CPLD). METHODS: We performed a landmark analysis at first month after randomisation to correlate leukopenia (nadir white blood cell <4.0 × 10(9) per litre or severe infection) during cycle 1 of chemotherapy with progression-free survival (PFS). Using time-dependent proportional-hazards models, we also investigated the association between neuropathy and PFS. RESULTS: Of 608 patients with nadir blood and did not receive growth factors, 72% (CP=70%, CPLD=73%) had leukopenia. Leukopenia was prognostic for PFS in those receiving CP (adjusted hazard ratio (aHR) 0.66, P=0.01). Carboplatin-liposomal doxorubicin was more effective than CP in patients without leukopenia (aHR 0.51, P=0.001), but not those experiencing leukopenia (aHR 0.93, P=0.54; interaction P=0.008).Of 949 patients, 32% (CP=62%, CPLD=28%) reported neuropathy during landmark. Neuropathy was prognostic for PFS in the CP group only (aHR 0.77, P=0.02). Carboplatin-liposomal doxorubicin appeared to be more effective than CP among patients without neuropathy (aHR 0.70, P<0.0001), but not those with neuropathy (aHR 0.96, P=0.81; interaction P=0.15). CONCLUSION: First-cycle leukopenia and neuropathy were prognostic for patients treated with CP. Efficacy of CP treatment was similar to CPLD in patients who developed leukopenia. These findings support further research to understand the mechanisms of treatment-related toxicity.

Identification of point mutations and large rearrangements in the BRCA1 gene in 667 Turkish unselected ovarian cancer patients.

OBJECTIVE: The aim of this study was to evaluate the prevalence and spectrum of a known founder mutation, 5382insC and large genomic rearrangements (LGRs) in BRCA1 in ovarian cancer patients in Turkey. The additional aim was to determine the genetic testing strategy in Turkish breast/ovarian cancer family. METHODS: Six hundred and sixty-seven ovarian cancer patients from five large geographical regions in Turkey, 61 of which had family history of breast/ovarian cancer, were tested for the mutation 5382insC by mutagenically separated polymerase chain reaction and direct sequencing of the entire coding sequence and the splicing sites. Additionally, multiplex ligation-dependent probe amplification (MLPA) was performed for large mutational scanning of BRCA1 gene in unselected ovarian cancer. RESULTS: In this study, BRCA1 point mutations were observed in 1% of all patients and 9.8% of familial cases: 5382insC, unique novel missense variant-G1748S and unclassified splice site variant IVS20+5A>T. 5382insC was observed in two patients. However, G1748S, previously unreported, was found in four patients and thus led to the conclusion that this mutation may be unique to Turkey. A splice site variant, IVS20+5A>T, was detected in three patients, with two of them including G1748S and IVS20+5A>T, together. Using MLPA, six different distinct LGRs in BRCA1 were observed: the deletion of E1A-1B-2, E11, E17-19, E18 and E18-19 and duplication of E5-9. The prevalence of LGRs in this study was 40.9% among patients with family history. The deletion of E1A-1B-2 was the common mutation, and patients with this deletion were referred to us from four different geographical regions in Turkey. Therefore, it was hypothesized that this deletion covering E1-2 is common in Turkey. CONCLUSION: LGRs in BRCA1 were strongly associated with positive family history among the Turkish population. On the basis of these findings, it can be recommended that a low-cost screening for LGRs in BRCA1 may be the first-line mutation detection method in families with strong breast/ovarian cancer history in Turkey.

Power Doppler properties of endometrial polyps and submucosal fibroids: a preliminary observational study in women with known intracavitary lesions.

OBJECTIVES: To compare power Doppler flow mapping characteristics of endometrial polyps and submucosal fibroids and analyze whether two different power Doppler characteristics, single-vessel pattern and rim-like vessel pattern, can help to differentiate these focal endometrial lesions. METHODS: Patients suspected of having endometrial polyps or submucosal fibroids on sonohysterography were examined prospectively by transvaginal B-mode and power Doppler sonography. Single-vessel pattern and rim-like vessel pattern were considered to be characteristic of endometrial polyps and submucosal fibroids, respectively. Suspected diagnoses of the lesions according to vascular Doppler characteristics were compared with the final diagnosis following histopathological examination. RESULTS: Included in the final analysis were 49 patients with histological confirmation of the type of endometrial lesion: 32 with endometrial polyps and 17 with submucosal fibroids. Power Doppler signals were observed in 47 of these; they were not observed in two patients with endometrial polyps. Of the 32 with endometrial polyps, 26 (81.3%) endometrial polyps showed a single-vessel pattern, three (9.4%) showed a multiple-vessel pattern and one (3.1%) showed a scattered-vessel pattern. Of the 17 with submucosal fibroids, 12 (70.6%) showed a rim-like vessel pattern, three (17.6%) showed a multiple-vessel pattern and two (11.8%) showed a single-vessel pattern. Single-vessel pattern was associated with two false-positive cases, but there were no false-positive cases for rim-like vessel pattern. The sensitivity, specificity and positive and negative predictive values for single-vessel pattern in diagnosing endometrial polyps were 81.2%, 88.2%, 92.9% and 71.4% and for rim-like pattern in diagnosing submucosal fibroids they were 70.6%, 100%, 100% and 86.5%, respectively. CONCLUSIONS: Power Doppler blood flow mapping is a valuable tool in the diagnosis of focal endometrial pathology and is useful in distinguishing submucosal fibroids and endometrial polyps.

Reproducibility of grading systems for endometrial endometrioid carcinoma and their relation with pathologic prognostic parameters.

The FIGO grading for endometrial endometrioid carcinomas is widely accepted. In 2000, a novel binary architectural grading system was suggested that divided endometrioid carcinomas into low- and high-grade tumors. We aimed to evaluate the interobserver reproducibility of the FIGO, the architectural binary, and nuclear grading systems and the correlation between these grading systems and pathologic prognostic factors for endometrial endometrioid carcinoma. Eighty-eight endometrial endometrioid carcinomas from hysterectomy specimens were reevaluated by two pathologists independently. Kappa values for the FIGO, the binary, and the nuclear grading systems were 0.65, 0.67, and 0.09, respectively. The reproducibility of the FIGO and the binary grading systems was similar and substantial. FIGO grade 1 (60.2%) patients were comparable to binary low-grade (63.6%) patients. Most of the FIGO grade 3 (83%) patients were binary high grade. FIGO grade 2 patients were distributed between binary low and high grades. The FIGO grade 1 and 2 cases judged to be of binary high grade had deep myometrial invasion, and more cases had vascular invasion in comparison with FIGO grade 1 and 2 cases judged to be of binary low grade. In uni- and multivariate analyses, both grading systems, depth of myometrial invasion, vascular invasion, cervical involvement, and stage had no effect on overall survival. But binary high grade and vascular involvement are adverse prognostic factors on recurrence-free survival. Binary high-grade patients can be assigned as high-risk patients.

Does synchronous endometrioid endometrial cancer have any prognostic effect on Stage I endometrioid ovarian cancer?

OBJECTIVE: To determine the effect of synchronous endometrial endometrioid cancer (SEEC) on the prognosis of patients with Stage 1 endometrioid ovarian cancer (EOC). STUDY DESIGN: Clinicopathological data of cases with Stage 1 EOC from January 2000 to November 2013 were retrieved from the computerized database of Etlik Zubeyde Hanim Women's Health and Research Hospital. Of the 31 patients included in the study, 15 patients had primary synchronous endometrial and ovarian cancer (SEOC) (Group 1) and 16 patients had EOC alone (Group 2). RESULTS: Ovarian cancer substage and grade were compared between the two groups, and no significant differences were found. Most of the patients with SEEC had Grade 1 tumours (n=13, 86.7%). In Group 1, nine (60.0%) patients had endometrial tumours with superficial myometrial invasion, and six (40.0%) patients had deep myometrial invasion. Median follow-up was 94 months. Ten-year disease-free survival rates were 92.9% for Group 1 and 84.6% for Group 2 (p=0.565). CONCLUSION: Patients with Stage 1 EOC have excellent long-term survival. The presence of SEEC does not influence the prognosis of patients with Stage 1 EOC, even in the presence of deep myometrial invasion.

Radical versus conservative surgery for vulvar carcinoma.

OBJECTIVE: The comparison of the radical and conservative surgical approaches for vulvar carcinoma in relation to the rate of recurrence and complications. METHODS: The records of invasive vulvar carcinoma cases were retrospectively reviewed in Istanbul University, Cerrahpasa School of Medicine, Gynecologic Oncology Division and Social Insurance Institution, Ankara Maternity Hospital, Gynecologic Oncology Department. Surgically treated cases with squamous histology were divided into radical vulvectomy and conservative procedures groups and were compared with respect to recurrence, complications, and disease-free survival. RESULTS: One hundred thirteen cases of invasive vulvar carcinoma cases were of squamous histopathology and 92 of these were surgically treated. The rate of local recurrence was lower in the radical vulvectomy group (25%) compared to conservative procedures groups (42.5%; p>0.05). The complication rates were comparable between the radical vulvectomy and conservative procedures groups (32.7% versus 35%, respectively; p>0.05). At the end of five years of the follow-up, the disease-free survival rates were 51.5% in radical vulvectomy group versus 35.7% in conservative procedures group (p>0.05). CONCLUSION: The rate of recurrence, complication, and disease-free survival are similar for the radical vulvectomy and the conservative procedures. Deciding the surgical strategy for vulvar carcinoma should depend on the experience of the surgeon for the short-term adequate results.

Treatment results and prognostic factors in inoperable carcinoma of the cervix treated with external plus high dose brachytherapy.

Patients with inoperable carcinoma of the cervix treated with external plus high dose rate brachytherapy (HDRB), between 1988 and 1995 were evaluated retrospectively. According to stage, 5 year survival rates were 67.3% in stage IIb and 52.6% in stage III (P = 0001) and disease free survival (DFS) rates were 54.0% in stage IIb and 43.9% in stage III (P = 0.01). The following parameters were studied: age; stage; external beam dose; brachytherapy dose; total dose to point A; tumor mass; tumor response rate; bilateral or unilateral invasion of parametria in stage IIb; and bilateral or unilateral invasion of pelvic wall in stage IIIb; and the existence of hydronephrosis. The only significant parameter of 5 year survival and local control was tumor mass (P = 0.003).

Adding concurrent low dose continuous infusion of cisplatin to radiotherapy in locally advanced cervical carcinoma: a prospective randomized pilot study.

The tolerability and efficacy of the continuous infusion of cisplatin during radiotherapy was studied by tumour response, survival and pelvic control, in carcinoma of the cervix. 44 patients with stage IIB-IIIB cervical carcinoma were prospectively randomized into two groups: radiation alone (control group) versus radiation plus cisplatin (study group). While there was no significant difference in diarrhoea and urinary complication scores, emesis and appetite changes were significantly greater in the study group. Tumour responses were no different at the end of the treatment and 3 months after completion of treatment. After 40 months median follow-up, 40/44 patients were assessed (one had a second primary tumour and three were lost to follow-up). Persistent disease was found in 3 patients: one in the study arm and two in the control arm. Recurrence was seen in 10 patients in the first 2 years. 5-year pelvic control rates were; 69.4% and 63.9% (p=0.7), survival rates were 52.0% and 48.9% (p=0.7) and disease-free survival rates were 67.5% and 58.7% (p=0.3) for the control and the study groups, respectively. Although the continuous infusion of cisplatin during radiotherapy was well tolerated, this additional treatment did not appear to show an improvement in pelvic control, survival, or disease-free survival.

Borderline tumor of the lymph node associated with bilateral serous borderline tumor of the ovary: case report.

The pathological diagnosis of a patient who was operated on for ovarian cancer was serous borderline tumor of the ovary. At the same time, pathological examination of one of the paraaortic lymph nodes revealed borderline tumor of the lymph node. We also searched the literature associated with this case.

Prognostic factors in stage IB-IIA cervical carcinomas treated with postoperative radiotherapy.

PURPOSE: This study investigated the prognostic significance of age, stage, tumor size, pelvic lymph node metastasis (PLM), surgical margin invasion, overall radiotherapy time (ORT), and interval between radiotherapy and surgery (IRS) in stage IB-IIA cervical carcinoma. METHOD AND MATERIALS: 100 patients treated with radical hysterectomy and postoperative radiotherapy were evaluated retrospectively. RESULTS: The 5-yr overall survival (OS), disease-free survival (DFS), and pelvic control rate (PC) were 83.6%, 82.8%, and 91.8%, respectively. PLM (p=0.008), IRS (p=0.01), ORT (p=0.007), and tumor size (p=0.028) were found to be significant on PC. PLM (p=0.04), ORT (p=0.04), and IRS (p=0.001) were significant on OS. PLM was significant (p=0.04) and IRS was marginally significant (p=0.06) on DFS. After multivariate analysis, PLM was significant on OS, DFS and PC. Recurrences were seen in 14 patients. CONCLUSION: According to this study PLM, IRS, and ORT are the most important prognostic factors. Recurrences outside the radiation volume leads to treatment failure.

Primary fallopian tube carcinoma: a retrospective multicenter study.

PURPOSE: This retrospective multicenter study aimed to assess the survival and prognostic factors of primary fallopian tube carcinoma. METHODS: The medical records of 29 patients with fallopian tube carcinoma from two centers were reviewed for age, stage, surgical intervention, relapse and survival. RESULTS: The mean age of the patients was 56 years (range, 37-76). Six patients were in Stage I (20.7%), eight cases in Stage II (27.6%), nine cases in Stage III (31%) and two cases in Stage IV (6.9%). Data on stage was not available in four cases (13.8). Fifteen patients underwent lymph node evaluation. The median follow-up was 29 months (range, 3-122). The median survival was 95 months with a 5-year survival rate of 69.7%. The median progression-free survival was 76 months with a 5-year survival rate of 51.8%. CONCLUSION: Age, stage and lymphadenectomy were found to be significant prognostic factors on overall survival.

Radiotherapy in the adjuvant setting of cervical carcinoma: treatment, results, and prognostic factors.

To evaluate the efficacy of postoperative radiotherapy and to investigate prognostic factors for early-stage cervical cancer patients. From December 1993 to December 2001, 141 patients with stage I-II cervical cancer without para-aortic lymph node (LN) metastases and treated by surgery and postoperative radiotherapy (RT) were included in this study. Indications for postoperative external RT were based on pathologic findings, including LN metastasis, positive surgical margins, parametrial involvement, pT2 tumor, and presence of any two minor risk factors like lymphvascular space involvement, deep stromal invasion, and tumor diameter between 2-4 cm. Sixty-six (47%) patients received RT alone, whereas 59 (42%) were treated with RT and concomitant chemotherapy (CT), and 16 received neoadjuvant CT. Patients with positive vaginal margins also received 27.5 Gy high-dose rate vaginal cuff brachytherapy in five fractions. Median follow-up time was 55 months. The actuarial 5-year overall (OS), disease-free (DFS), locoregional recurrence-free (LRFS), and distant metastases-free (DMFS) survival rates are 70%, 68%, 77%, and 88%, respectively. Univariate and multivariate analyses revealed that level and number of metastatic LNs and concomitant CT were unique significant prognostic factors for OS, DFS, and LRFS. Endometrial involvement, on the other hand, was proven to be significant for DFS and DMFS. Patients with less than three LN metastases or having only obturator LN involvement showed similar prognosis with their counterparts having no LN metastases. On the other hand, patients with either common iliac LN or more than three LN metastases had significantly worse outcome. Our results indicate that level and number of metastatic LNs are the most important prognostic factors determining the survival rates, and patients with upper lymphatic involvement or more than three metastatic LNs seem to need more effective treatment approaches.

Recovery of ovarian function after detorsion: Doppler findings.

Adnexal torsion is one of the most common surgical gynecologic emergencies and needs prompt diagnosis. It usually occurs during reproductive age, which makes the early diagnosis all the more important in attempting to preserve ovarian function. If adnexal torsion is suspected from the clinical findings, Doppler ultrasound can be the best tool in diagnosis. It can also be helpful in assessing recovery of the ovary after surgical treatment. We present a case of adnexal torsion successfully diagnosed with power Doppler ultrasound and managed by detorsion. The postoperative gray-scale and power Doppler examination confirmed the recovery of ovarian follicles and stoma.

Recurrent partial hydatidiform mole: a report of a patient with three consecutive molar pregnancies.

Hydatidiform mole (HM) is the most common form of gestational trophoblastic neoplasia and is characterized by atypical hyperplastic trophoblasts and hydropic villi. Recurrence of HM is extremely rare. Here, we report the case of a patient with three consecutive partial HMs without normal pregnancy. A 28-year-old woman with gravida 3, para 0, was referred to our hospital with a diagnosis of an invasive mole in December 2003. She had three consecutive molar pregnancies in 2000, 2001, and 2003. All three molar pregnancies were evacuated by suction curettage and the patient was followed by serial beta-human chorionic gonadotropin levels. All three moles were histologically confirmed as partial moles. In the first two molar events no additional treatment after evacuation was required, but in the last event, the beta-human chorionic gonadotropin levels increased and an invasive mole was suspected. Diagnostic workup ruled out an invasive mole and choriocarcinoma. Karyotypic analysis of the patient and her husband was normal. The patient required chemotherapy for treatment of persistent disease. Recurrent partial HM is a very rare clinical disorder. Repetitive molar pregnancy is not an indication for chemotherapy, but persistent disease does require chemotherapy.

Results with EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) chemotherapy in gestational trophoblastic neoplasia.

The aim of this study was to evaluate the efficacy and toxicity of EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) regimen for the treatment of high-risk gestational trophoblastic neoplasia (GTN). Thirty-three patients with high-risk GTN, scored according to World Health Organization, received 159 EMA/CO treatment cycles between 1994 and 2004. Twenty-three patients were treated primarily with EMA/CO, and 10 patients were treated secondarily after failure of single agent or MAC (methotrexate, actinomycin D, cyclophosphamide, or clorambucile) III chemotherapy. Adjuvant surgery and radiotherapy were used in selected patients. Survival, response, and toxicity were analyzed retrospectively. The overall survival rate was 90.9% (30/33). Survival rates were 91.3% (21/23) for primary treatment and 90% (9/10) for secondary treatment. Six (18.2%) of 33 patients had drug resistance. Four of them underwent surgery for adjuvant therapy. Three of these patients with drug resistance died. Survival and complete response to EMA/CO were influenced by liver metastasis, antecedent pregnancy, and histopathologic diagnosis of choriocarcinoma. Survival rate was also affected by blood group. The treatment was well tolerated. The most severe toxicity was grade 3-4 leukopenia that occurred in 24.3% (8/33) of patients and 6.9% (11/159) of treatment cycles. Febrile neutropenia occurred in one patient (3%). EMA/CO regimen is highly effective for treatment of high-risk GTN. Its toxicity is well tolerated.

Which surgical procedure for patients with atypical endometrial hyperplasia?

OBJECTIVE: To determine the occult coexistence of endometrial carcinoma in patients with atypical endometrial hyperplasia and to compare histological prognostic factors according to lymph node status in occult endometrial carcinoma. MATERIALS AND METHODS: Two hundred and four patients from two referral centers (during the period 1990-2003) who were operated on within 1 month of endometrial biopsy for symptomatic endometrial hyperplasia without receiving any medical treatment were included retrospectively. Patients having preoperative endometrial biopsy results of concomitant endometrial hyperplasia and carcinoma were excluded from the study. Fifty-six patients having atypia in preoperative biopsy (group I) were compared with 148 patients without atypia (group II). Chi-square and Mann-Whitney U-tests were used for statistical analyses. RESULTS: No significant difference was observed between the two groups according to age or menopausal status. Patients in group II had significantly higher parity than patients in group I. In group I, 62.5% of the patients had endometrial carcinoma, 21.4% had endometrial hyperplasia, and 16.1% had normal endometrium in hysterectomy specimens. In group II, the percentages were 5.4, 38.5, and 56.1%, respectively. Complete surgical staging was performed in 20 patients. Four patients had metastatic lymph nodes. All of them had grade 2 tumors with lymphovascular space involvement. Three of them had nonendometrioid tumors. CONCLUSION: Careful intraoperative and preoperative evaluation of the endometrium must be the sine qua non for patients with atypical endometrial hyperplasia. It is reasonable to do frozen section at the time of hysterectomy for atypical endometrial hyperplasia, and if grade 2/3 of nonendometrioid cancer with lymphovascular space involvement is found, complete surgical staging should be performed.

High-grade neuroendocrine carcinoma of the cervix. A case report.

Neuroendocrine tumor of the uterine cervix is a rare and aggressive malignancy. Despite controversial, multimodal treatment methods, prognosis and treatment outcomes are worst in advanced stages. We report an early-stage case treated with the multimodal approach. The nomenclature proposed for this tumor type in 1997 by the College of American Pathologists still has some points of discussion. As in our case some of the tumors cannot be defined exactly into small or large cell types, and this causes confusion at least for nomenclature purposes. A 'mixed' type for this tumor may be appropriate.