Efficacy of neoadjuvant chemotherapy in patients with FIGO stage IB1 to IIA cervical cancer: an international collaborative meta-analysis.

BACKGROUND: The efficacy of neoadjuvant chemotherapy before surgery (NCS) has not been well-established in FIGO stage IB1 to IIA cervical cancer when compared with primary surgical treatment (PST). Thus, we performed a meta-analysis to determine the efficacy of NCS in patients with FIGO stage IB1 to IIA cervical cancer when compared with PST. METHODS: We searched Pubmed, Embase and the Cochrane Library between January 1987 and September 2010. Since there was a relative lack of relevant randomized controlled trials (RCTs), we included 5 RCTs and 4 observational studies involving 1784 patients among 523 potentially relevant studies. RESULTS: NCS was related with lower rates of large tumor size (≥4 cm) (ORs, 0.22 and 0.10; 95% CI, 0.13-0.39 and 0.02-0.37) and lymph node metastasis (ORs, 0.61 and 0.38; 95% CI, 0.37-0.99 and 0.20-0.73) than PST in all studies and RCTs. Furthermore, NCS reduced the need of adjuvant radiotherapy (RT) in all studies (OR, 0.57; 95% CI, 0.33-0.98), and distant metastasis in all studies and RCTs (ORs, 0.61 and 0.61; 95% CI, 0.42-0.89 and 0.38-0.97). However, overall and loco-regional recurrences and progression-free survival were not different between the 2 treatments. On the other hand, NCS was associated with poorer overall survival in observational studies when compared with PST (HR, 1.68; 95% CI, 1.12-2.53). CONCLUSIONS: Although NCS reduced the need of adjuvant RT by decreasing tumor size and lymph node metastasis, and distant metastasis, it failed to improve survival when compared with PST in patients with FIGO stage IB1 to IIA cervical cancer.

Conservative management of young women with endometrial carcinoma or complex atypical hyperplasia: report of three cases and literature review.

BACKGROUND: Although endometrial cancer is primarily a postmenopausal disease, 25% of patients are in premenopausal age with 3-5% being 40 years old or younger. The younger groups of women with endometrial carcinoma are frequently nulligravid with a history of infertility and strong desire to preserve fertility, which may pose a therapeutic dilemma for both patients and physicians. CASE REPORTS: We report on three young women with atypical complex hyperplasia or early-stage endometrial cancer that were treated with conservative hormonal therapy. DISCUSSION/CONCLUSION: Hormonal therapy has been proposed for young women with endometrial cancer (grade 1) who wish to preserve their fertility. However, detailed evaluation including physical examination, history taking, performing D&C, examining the specimen by a skilled pathologist, using imaging techniques, especially contrast enhanced MRI and for some patients explorative laparoscopy with sampling of peritoneal and lymph nodes, and evaluation of adnexa is necessary. Also for patients in Stage I/grade 1, advisory sessions on the benefits and side-effects of high-dose progesterone with evaluation of the endometrium every three months until total regression is recommended.

Uterine involvement in advanced epithelial ovarian cancer.

BACKGROUND: With an increasing trend for sparing fertility in gynecologic malignancies, we tried to assess uterine involvement in all stages of epithelial ovarian cancer (EOC) in an evidence-based study. METHOD AND MATERIAL: From September 1999 to September 2005, 177 patients with epithelial ovarian cancer underwent staging laparatomy in the Gynecologic Oncology Department, Vali Asr University Hospital, Tehran, Iran. Staging data from patient files and pathologic reports were analyzed. RESULT: Of the 177 cases with EOC, 26% of patients were in Stage I, 13.6% Stage II, 53.1% Stage III and 7.3% Stage IV. Uterine Involvement was 17.9% with serosal involvement in 25 cases (78.1%) and myometrial involvement in seven cases (21.9%). Of these cases 84.4% were in Stages III or more and all had omental involvement (Stage IIIa 7.4%, Stage IIIb 14.8%, Stage IIIc 63% and Stage IV 14.8%). Only 15.6% cases of normal appearing omentum had uterine tumoral involvement. CONCLUSION: Only eight cases had myometrial involvement out of 177 cases of EOC (all in Stage III). All the eight patients had omental or gross pelvic tumoral involvement. In this study we found that in the absence of gross pelvic or omental involvement in EOC, there is really none or minimal chance of myometrial involvement. Future multicenter studies with more cases will show whether standard hysterectomy by multiple serosal biopsies could be replaced.

Symptoms of ovarian cancer in young patients 2 years before diagnosis, a case-control study.

Ovarian cancer is usually diagnosed after it has spread and is difficult to cure. Most of attempts to identify early symptoms have lacked control group or have been based on interviews. We examined early symptoms of ovarian cancer in young women and compared with a matched control group. Symptoms recorded in medical files of 100 women aged 15-35 years with ovarian cancer who were referred to Vali-Asr hospital between 1995 and 2005. Symptoms of cases were compared with 100 matched controls during 2 years before diagnosis. More cases (95%) than controls (28%) complained of at least one symptom up to 2 years before diagnosis, most of these symptoms were abdominal. Others included urinary symptoms, infertility and abnormal vaginal bleeding. The most common symptoms among cases were: unusual abdominal or lower back pain 52%, unusual bloating, fullness and pressure in the abdomen 37%, gastro-intestinal problems 36%. In total, 11%, 3% and 12% of controls reported these symptoms respectively, resulting in odds ratios of 8.7, 18.9 and 4.1 respectively for these symptoms. Unusual abdominal or lower back pain, fullness and pressure, gastrointestinal, urinary problems and infertility should make women and physicians more aware of changes associated with ovarian cancer.

Preservation of pregnancy in a patient with advanced ovarian cancer at 20 weeks of gestation: case report and literature review.

To report a case of FIGO stage III papillary serous carcinoma of ovary, diagnosed during pregnancy at 20 weeks of gestation and treated with unilateral salpingo-oophorectomy and surgical staging, then initial combination chemotherapy while preserving the pregnancy. The patient underwent cesarean section at 35 weeks after four courses of taxol plus carboplatin. She delivered a healthy baby. After that total hysterectomy, omentectomy, pelvic and para-aortic lymphadenectomies were carried out. The surgical resection was complete and no macroscopic residual diseases were seen. During histologic examination, traces of resistant disease were found. The patient underwent three postoperative courses of chemotherapy (carboplatin plus paclitaxel regimen). After 6 months follow-up, the patient remained in complete remission and the child's development was normal. Combination chemotherapy during pregnancy with preservation of the fetus could be considered, and should be discussed with caution in case of epithelial ovarian cancer diagnosed during the second trimester of the pregnancy.

Neoadjuvant chemotherapy and radical surgery compared to radical surgery alone in bulky stage IB-IIA cervical cancer.

AIM: The aim of this study was evaluation of the efficacy of neoadjuvant chemotherapy (NACT) and radical hysterectomy on long-term survival in stage IB-IIA locally advanced cervical cancer as compared with radical surgery alone. METHODS: We reviewed all patients with cervical cancer stage IB-IIA who were treated with two treatment modalities, i.e. NACT followed by radical hysterectomy and lymphadenectomy, and radical hysterectomy alone between March 1996 and March 2004. There were 22 patients in the NACT group (group 1) and 160 patients in the immediate radical surgery group (group 2). All patients in group 1 were followed for more than 108months, and long-term survival and factors affecting recurrence were evaluated. RESULTS: Nineteen patients in the NACT arm underwent radical surgery. Pelvic lymph node metastasis was found in 8 patients in this group and in 36 in the radical surgery group. Eighteen patients in the NACT group and 96 patients in the radical surgery group were scheduled for adjuvant postoperative chemoradiation. During the 9-year follow-up, recurrence rate was 47.1% and 30.2% in NACT and control groups, respectively. In the NACT group lymph node metastasis was a significant independent risk factor for recurrence. Overall survival in the NACT arm was not statistically significantly lower than the control arm (p=0.06). CONCLUSION: NACT did not improve long-term overall survival of bulky early-stage cervical cancer patients compared to primary radical surgery.

Successful treatment of two patients with gestational trophoblastic neoplasm presenting with emergent neurologic symptoms.

The objective of this study is to present the successful treatment of two young patients with gestational trophoblastic neoplasms (GTN) presenting with emergent neurologic symptoms without any gynecological problems. Case 1, a 22-year-old patient, was admitted to an infectious disease ward, with admitting diagnosis of encephalitis due to neurologic symptoms. Case 2, a 33-year-old patient, underwent craniotomy due to hemorrhagic brain tumor in the neurosurgery department. The diagnosis of GTN should be considered in any woman of reproductive age who has neurologic symptoms. It seems that multiagent chemotherapy in conjunction with whole-brain irradiation results in acceptable survival rate in brain metastatic GTN patients. Craniotomy is often necessary in fulminant cases.

Successful pregnancy after localized resection of perforated uterus in choriocarcinoma and a literature review.

Choriocarcinoma is an aggressive neoplasm arising in the body of the uterus. Rapid growth and myometrial invasion may be followed by uterine perforation. In this study, we present the cases of two young patients (18 and 19 years of age) with acute abdominal pain and shock, while they were under chemotherapy due to persistent trophoblastic disease. During emergent exploratory laparotomy, localized resection of uterus was performed. They had their first successful term pregnancy 5 and 4 years after surgery, respectively. Uterine perforation following choriocarcinoma is a rare event. Hysterectomy is recommended in emergency conditions, but localized resection of uterus should be considered in women who are desirous of future fertility.

Comparative study of chemoradiation and neoadjuvant chemotherapy effects before radical hysterectomy in stage IB-IIB bulky cervical cancer and with tumor diameter greater than 4 cm.

Tumor size seems to be a determinant in the prognosis of early cervical cancer. Patients with tumor greater than 4 cm (bulky) in diameter have worse outcome. The purpose of this study was to compare the efficacy of preoperative combined chemoradiation and neoadjuvant chemotherapy (NAIC) programs followed by radical hysterectomy in stage IB-IIB bulky cervical cancer. From September 1999 to April 2002, 60 patients with stage IB-IIB bulky cervical cancer were treated with preoperative external-beam radiotherapy to 45 Gy plus weekly cisplatin 50 mg/m2 or preoperative NAIC by cisplatin 50 mg/m2 and vincristin 1 mg/m2 every 7-10 days, for three courses. Surgery was performed 4-6 weeks after the completion of the preoperative treatment. There were no significant difference between age, stage, tumor size, and histopathologic type in two groups (P > 0.05). Toxicity associated with two treatment methods was usually mild. In chemoradiation group, two patients developed vesicovaginal fistula, and four patients developed long-term hydronephrosis that needed urethral stenting. Before surgery, complete and partial clinical response had no significant difference between two groups (P > 0.05). After surgery, lymph node and parametrial involvement had no significant difference between two groups (P > 0.05). In NAIC group, more patients had significantly residual tumor (P = 0.012), but residual tumor size had no significant difference between two groups (P > 0.05). Pathologic complete response was significantly higher in chemoradiation group (P = 0.004). According to the result of this study, it seems that NAIC and chemoradiation had similar effects in survival prognostic factors.

Evaluation and management of brain metastatic patients with high-risk gestational trophoblastic tumors.

A retrospective study to evaluate the characteristics of brain metastatic patients with gestational trophoblastic tumors (GTT) and to analyze the results of treatment has been performed. During 1996-2001, 40 patients with metastatic GTT were diagnosed at Vali-e-Asr Hospital, Tehran, Iran. Of them, nine with brain metastases, which were documented with the help of computed tomography scan, were evaluated retrospectively. Eight patients received EMA-EP regimen (etoposide, methotrexate, actinomycin, etoposide, and cisplatinum) and one received EMA-CO (etoposide, methotrexate, actinomycin, cyclophosphamide, and vincristin). All cases received whole brain irradiation therapy concurrently. The median age of the patients at diagnosis was 30 years (range: 17-53). Six of them were of early group (five with symptoms of central nervous system and one was detected during workup) and three were of late group (relapsed group). Five (56%) patients responded to treatment and four (44%) were deceased (three of them belonged to late group). It seems that multi-agent chemotherapy (EMA-EP) concurrently with whole brain irradiation results in acceptable survival rates in GTT patients with brain metastases.

Is normal beta-hCG regression curve helpful in the diagnosis of persistent trophoblastic disease?

OBJECTIVE: The aim of this study was to evaluate the probable usefulness of normal beta-human chorionic gonadotropin (beta-hCG) regression curve in the diagnosis of persistent trophoblastic disease (PTD). METHODS: A log-value regression curve was developed from the means and 95% confidence limits of serial weekly serum beta-hCG titers of 43 patients with uneventful complete hydatidiform moles and 14 patients, who were previously confirmed as PTD. RESULTS: All 14 PTD patients (100%) had abnormal values, beyond normal range, within 4 weeks. beta-hCG was in its upper values, compared to normal regression curve at 2.29 +/- 0.19 weeks. This was earlier than plateau or rise detection at 4.21 +/- 0.33 weeks (P < 0.001). Within 3 weeks of evacuation, 13 of 14 (92.86%) PTD patients' beta-hCG values exceeded the normal range, whereas only six of 14 (42%) showed a rise or plateau. CONCLUSION: Our finding indicates that the normal beta-hCG regression curve may be useful for quicker detection of PTD than the plateau or rise of level.

Visual inspection with acetic acid as a feasible screening test for cervical neoplasia in Iran.

The aim of this study was to estimate the sensitivity and specificity of visual inspection of the uterine cervix with acetic acid (VIA) as a screening test for cervical carcinoma and its precursors. One thousand and two hundred eligible women were screened by VIA and Papanicolaou smear. Those positive on one or both of these screening tests (n = 308) or those who had clinically suspicious lesions, even if the tests were negative [25% of remainders (n = 290)], were referred for colposcopy. Three hundred and fifty five of 598 women at colposcopy underwent biopsies or endocervical curettage. Those with cervical intraepithelial neoplasia I (CIN I) or worse lesions, diagnosed by histology, were considered true positive. VIA was positive in 191 women (16.1%). In 175 true-positive cases, VIA detected 130 cases, yielding a sensitivity of 74.3% and a specificity of 94%. By considering atypical squamous cell of undetermined significance or worse lesions on Papanicolaou smear as referring threshold for colposcopy, the sensitivity and specificity of cytology were 72 and 90.2%, respectively. In conclusion, the sensitivity and specificity of VIA is high and comparable with that of cytology. Hence, VIA can be undertaken as a feasible method of screening in cervical cancer in countries where access to cytopathology is limited.

EMA-EP regimen, as firstline multiple agent chemotherapy in high-risk GTT patients (stage II-IV).

Multiple agent chemotherapy in high-risk metastatic gestational trophoblastic tumor patients is a problem for any medical team. In this study, EMA-EP chemotherapy (etoposide, methotrexate, actinomycin, and cisplatinum) was evaluated as firstline chemotherapy to manage high-risk GTT metastatic patients. Seventeen high-risk metastatic patients, including 14 without and 3 with brain metastasis, who were candidates to firstline multiple agent chemotherapy between April 2000 and March 2003 in Vali-e-Asr hospital took part in a prospective study under EMA-EP regimen. EMA-EP was prescribed in two periods: EMA in two consecutive days in week 1 and EP in 1 day in the following week with a week interval between these two (each cycle was repeated every 2 weeks). In brain metastasis group, patients got high-dose medication (methotrexate) together with brain radiotherapy. Remission, toxicity, full dose tolerance, and recurrences of patients were evaluated. Median age of patients was 30 (15-49), and they received 100 courses of chemotherapy including 75 low-dose courses and 25 high-dose courses. 71% of courses were done in full dosage (83% in low dose and 36% in high dose). The most common cause for dosage reduction was leukopenia. Two patients did not complete the regimen, one due to hypersensitivity and the other due to fever and leukopenia leading to death. All others, who received complete courses, achieved remission. In the group without brain metastasis, one case of recurrence was observed. Grade 3 anemia, grade 3 and 4 leukopenia, and grade 3 and 4 thrombocytopenia were observed in 3, 12, and 3% of patients, respectively. In current study, EMA-EP regimen in patients with high-risk metastatic GTN patients (with or without brain metastasis) lead to remission in all patients who completed the treatment courses.

Multiple, disseminated cutaneous metastases of vulvar squamous cell carcinoma.

Cutaneous metastases of vulvar carcinoma are extremely rare and have been reported in six patients so far. Our patient, who is the seventh one, is a 38-year-old woman with a history of diabetes mellitus. After detecting stage III squamous cell carcinoma of the vulva, she underwent radical vulvectomy and bilateral inguinal lymphadenectomy. She received 6000 cGy external beam radiation for positive margins. Six months later, she came back with multiple advanced skin lesions. Biopsy was performed and lesions were confirmed as cutaneous metastases. For her palliation, some chemotherapy drugs were prescribed. She is on her sixth chemotherapy cycle, but these skin lesions are somewhat a preterminal event and there is no well-established treatment for this phase of disease.

Borderline ovarian tumours: clinical analysis of 38 cases.

Thirty-eight patients with ovarian tumours of low malignant potential (borderline) were diagnosed and treated in Tehran University Gynecology Oncology Department from 1991 to 2002, and have been reviewed. In this study age, clinical behavior, symptoms, surgical stage, type of tumour, surgery, adjuvant treatment, survival and recurrences were evaluated. A retrospective chart review was performed on these 38 patients who were treated for histopathologically confirmed tumours of low malignant potential between 1991-2002. The mean age was 34.4 years, range (14-83) (SD: 18.33). Post surgical FIGO staging was: Stage I=93.75%, stage III 6.25%. Histologic subtypes were: Serous 76.31% (29 patients), Mucinous 21.05% (8 patients), Mixed types 2.63% (1 patient). Mean pre-operative CA125 value was 114.90 (SD: +/- 90.30). Thirty-three percent of patients had only a simple cyst in ultrasonography. Conservative surgery was performed in 76.32% (29 patients). More radical surgery (TAH + BSO) was performed in 9 patients (23.68%). There were 6 recurrences. Three patients with recurrence and invasive implants received chemotherapy and secondary surgery was performed. Survival rate was 100% at 3 years for all stages and 89% at 5 years. One patient died of recurrent disease at 48 months after initial diagnosis. Our data suggest that LMP tumours are most frequently diagnosed in stage I. Most common histological type was serous, and 5 of the recurrences of (6 patients) were initially diagnosed at stage I, and had been treated with conservative surgery with no adjuvant therapy.

First-line chemotherapy with 5-FU and platinum for advanced and recurrent cancer of the cervix: a phase II study.

This study was designed to assess the role of first-line chemotherapy with 5-fluorouracil (5-FU) and platinum in the treatment of advanced or recurrent cervical cancer. Ten patients with advanced or recurrent cancer of the cervix with no prior chemotherapy were entered in a phase II trial from October 2000 to November 2001. Eight patients were treated with Cis-platinum (50 mg/m2 over 60 minutes on the first day) followed by 5-FU (1 g/m2 over 24 hours for 4 days) and two patients with impaired renal function were treated with carboplatin (300 mg/m2 over 15 minutes on the first day) followed by 5-FU (1 g/m2 over 24 hours for 4 days) every 3 weeks until progression of disease or prohibitive toxicity had been observed. Median age was 52 years (range 28-70 years). Ten patients received a total of 42 cycles of chemotherapy. The mean number of chemotherapy cycles was 4.2 (median 4, range 3-7). Three patients had a partial response (30%, 95% CI, 1.7-58.5%). Mean duration of response was 198 days (range 122-273 days). Four patients required red blood cell transfusions; three of them had Grade II and one of the Grade III nausea and vomiting. Two had fever and neutropenia (one developed acute renal insufficiency), and there were no treatment related mortalities. First-line chemotherapy with platinum and 5-FU for advanced and recurrent cervical cancer is promising and deserves consideration for a larger phase III trial.

Simple hysterectomy in the presence of invasive cervical cancer in Iran.

The objective of this study was to determine the reasons leading to an inappropriate simple hysterectomy in the presence of invasive cervical cancer. During 1997-2001, 62 cases of invasive cervical carcinoma that had been treated by simple hysterectomy were referred to the gynecology oncology service in Vali-e-Asr hospital, Tehran, Iran. Five had microinvasive carcinoma. The remaining 57 women had either adenocarcinomas or squamous cell carcinoma (SCC). Medical records were reviewed retrospectively to determine the reasons for inappropriate hysterectomy. Reasons for inappropriate hysterectomy were as follow: lack of preoperative Pap smear (P/S) (29%), deliberate hysterectomy for biopsy-proven cancer (25.8%), negative P/S (6.5%), inadequate evaluation of abnormal P/S (6.5%), failure to perform an indicated conization (3.2%), and emergent operation because of uterine perforation (1.6%). Reasons for inappropriate hysterectomy in the remainder of patients (27.4%) were not found because of lack of sufficient information. Although 45.2% of these patients had complained for vaginal bleeding, only four of them had preoperative endocervical and endometrial sampling. Despite the increasing emphasis on performing cervical cancer screening before hysterectomy, only 18 (29%) referral patients had preoperative P/S. We conclude that by close adherence to the cervical cancer screening guidelines and appropriate evaluation of the presenting symptoms, we may avoid inappropriate management of cervical carcinomas with simple hysterectomy. Many cases of simple hysterectomy in the presence of biopsy-proven squamous cell carcinoma of the cervix necessitates some reconsideration of gynecology oncology postgraduate courses for general gynecologists.

Uterine papillary serous carcinoma after pelvic radiation therapy for cancer of the cervix.

The carcinogenic effect of ionising radiation in humans has well documented in both atomic bomb survivors and patients exposed to therapeutic radiation. Patients irradiated for cancer of cervix have frequently been studied for the later development of secondary malignancies because treatment is relatively successful and many patients survive long enough to be at risk for late complications of radiotherapy. Most investigations have revealed an increased incidence of uterine sarcoma following pelvic radiation therapy for a variety of gynecologic disorders (Norris and Taylor, 1965; Fehr and Prem, 1974). Wagoner, in a review of over 1800 women treated with ionising radiation for invasive cervical cancer, reported a fourfold increase in risk for the later development of uterine sarcoma (Wagoner, 1984). In this paper we report the case of uterine papillary serous carcinoma 16 years after pelvic X-ray therapy for cervical cancer.

To peritonealise or not to peritonealise? A randomised trial at abdominal hysterectomy in Iran.

We conducted a trial to determine whether non-closure of the visceral and parietal peritoneum alters the intraoperative or post-operative course at abdominal hysterectomy. This was a parallel-group double-blind randomised controlled trial was performed on 66 women who underwent abdominal hysterectomy with or without salpingo-oophorectomy. Twenty-seven were allocated to the control 'closed' group and 39 women to the study 'open' group. The main outcome measures were operative time, estimated blood loss, postoperative pain assessed by visual analogue scale and amount of postoperative analgesia. The study was conducted in the Department of Gynecological Oncology in a university teaching hospital. The operative time was shorter (P < 0.05) and the time to ambulation without assistance was significantly shorter in study group. There were no difference in postoperative pain, blood loss, amount of postoperative analgesia and antibiotics in the two groups. Peritoneal closure at abdominal hysterectomy provides no immediate postoperative benefits while unnecessarily lengthening surgical time and anaesthesia exposure. We suggest that the traditional practice of visceral and parietal closure be abolished at abdominal hysterectomy.