Non-diethylstilbestrol exposed vaginal adenocarcinoma in young patients associated with unilateral renal agenesis: two case reports and literature review.

BACKGROUND: Adenocarcinoma, accounts for up to 14% of all vaginal cancer. In young patients, common histological feature is clear cell adenocarcinoma (CCA) while mesonephric adenocarcinoma (MA) is very rare. The authors report two patients in their early twenties with unilateral renal agenesis and vaginal adenocarcinoma not exposed to diethylstilbestrol (DES). CASES: Two patients with vaginal adenocarcinoma were treated, with external beam radiotherapy of pelvis combined with brachytherapy to a radical dose. In 2000, 25-year-old female, was admitted for radiotherapy after incomplete excision of the tumor localized in left vaginal apex and fornix. Histopathology confirmed CCA and classified as clinical Stage II. CT revealed left renal agenesis.The patient is alive and disease-free 15 years after therapy. Vaginal, urethral stenosis, and hydronephrosis occurred and ureteral stent was inserted. In the second patient, 22-year-old, in 2004, after biopsy of bulky tumor of vagina and histology, revealed MA in Stage III and CT scan also confirmed right renal agenesis. Radiotherapy was followed by chemotherapy. After 11 years, patient is disease-free with vaginal stenosis and incipient renal hydronephrosis. CONCLUSION: Radiotherapy is effective treatment in advance vaginal adenocarcinoma, however, with high morbidity. The authors advise rigorous gynecologic exams in young females with renal agenesis as there may be a risk of malignant changes in vagina.

Outcome of childhood brain tumors in Serbia.

PURPOSE: To present the results of treatment for childhood brain tumors in Serbia. METHODS: The medical records of patients with brain tumors diagnosed and operated at the Institute of Neurosurgery, Clinical Center of Serbia and treated with postoperative radiotherapy and chemotherapy at the Institute of Oncology and Radiology of Serbia, Belgrade, between January 1995 and December 2004, were reviewed. Of the 247 patients who were identified, 212 formed the basis of this study. Overall survival (OS) was determined by the Kaplan-Maier method, using log-rank test for comparisons. RESULTS: With a mean follow up of 46.9-33.6 months (range 7-120), the 5-and 8-year OS rates were 70.0% and 61.5%, respectively. At the time of evaluation 119 (60.1%) patients had no evidence of disease. Among 79 patients who failed therapy, most of them (n=61; 77.2%) had local failure only. According to histologic tumor type most of them (n=27; 34.2%) were in the group of malignant medulloblastoma. Girls had better survival than boys, but without statistical significance (p=0.185). Also, no significant difference in survival in relation to age was seen (p=0.291). Patients with supratentorial tumors had significantly better survival than those with infratentorial localizations (p=0.036). Patients with low grade astrocytomas had significantly better survival than malignant gliomas, ependymomas and primitive neuroectodermal tumors (PNETs) (p=0.0001). CONCLUSION: OS rates were concordant with the results of other modern series. Although the survival rates were encouraging, there is still significant room for improvement in the management of childhood brain tumors.

PTEN protein expression in postmenopausal steroid receptor positive early breast cancer patients treated with adjuvant tamoxifen.

PURPOSE: Since one of possible causes of resistance to antiestrogen therapy in steroid receptor positive (SR+) breast cancer (BC) patients is an alteration of PTEN (phosphatase and tensin homolog deleted on chromosome 10) signaling pathways, the aim of this study was to determine the PTEN protein expression in postmenopausal patients with steroid SR+ BC treated with adjuvant tamoxifen, to investigate the association of PTEN protein expression with tumor histology, size and grade, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) statuses and disease outcome. METHODS: This was a retrospective analysis of 78 postmenopausal stage I/II SR(+)BC patients treated with adjuvant tamoxifen. PTEN protein expression and ER, PR and HER2 status were determined using immunohistochemistry. RESULTS: The distribution of PTEN protein expression according to tumor histology was as follows: PTEN+ status in 27/43 (62.8%) patients with ductal and in 26/35 (74.3%) patients with lobular carcinomas; and PTEN(-) status in 16/43 (37.2%) patients with ductal and in 9/35 (25.7%) patients with lobular carcinomas. Disease relapse was observed in 38/78 patients: 14/53 (26.4%) of PTEN(+) BC subgroup and 24/25 (96%) of PTEN(-) subgroup (x(2), p=0.018). There were no significant associations between PTEN protein expression and tumor histology, size and grade, and ER, PR and HER2 expression. Patients with PTEN(-) had significantly shorter disease-free interval (DFI) and overall survival (OS) (for both, log rank test, p <0.01) compared to PTEN(+) BC patients. CONCLUSION: Our results suggest that PTEN protein expression might be of prognostic significance in postmenopausal SR(+) BC patients treated with adjuvant tamoxifen.

Percutaneous nephrostomy in the management of advanced and terminal-stage gynecologic malignancies: outcome and complications.

PURPOSE: The goal of the study was to evaluate the outcome and complications after percutaneous nephrostomy (PCN) insertion in advanced and terminal-stage gynecological malignancies with ureteral obstruction (UO). MATERIALS AND METHODS: We analyzed data of 117 patients with UO due to gynecological malignancies, who had undergone PCN between 1996 and 2006. Cervical cancer was evidenced in 108 patients, uterine carcinoma in six and ovarian cancer in three patients. Eighty-nine had UO at the initial manifestation of the disease, 22 had persistent or recurrent cancer, and six were disease-free after initial therapy. Oliguria was observed in 22.2% and creatine elevation in 79.5%. Mean follow-up was 11.43 months (range 0-112). RESULTS: The median age was 51 years (range 28-85). Bilateral nephrostomy was performed in 36.7% and unilateral in 63.3%. Renal function normalization occurred in 24.8%. Overall two-year survival (OS) was 16.8%. Higher OS occurred in patients without initial azotemia versus those with azotemia (26.8% vs 13.9%). Median survival time for all the patients was seven months, eight in primary cases versus six in recurrent ones, and eight months in patients after initial therapy. Complications appeared in 53.85%. Most frequent were the loss of the nephrostomy catheter in 37.61% and urinary tract infections in 19.6%. CONCLUSION: Improvement of renal function after PCN can be of clinical benefit in patients who might be cured or for prolonged palliative care. Azotemia seems to be poor prognostic sign.

Therapeutic cancer vaccines in cervical cancer: phase I study of Lovaxin-C.

Producing effective therapeutic vaccines has proved much more difficult and challenging than developing cancer preventive vaccines. Despite huge research in the area of cancer immunology, FDA/EMEA have not approved any type of cancer treatment vaccine so far. More than 99% of cervical cancers have detectable amounts of human papillomavirus (HPV) DNA. Integration of high-risk HPV into the host cell genome is followed by continual expression of HPV E6 and E7 oncoproteins, making them excellent targets for developing vaccines which could be used in high grade precancerous (CIN) lesions or invasive cancer or in the prevention of cancer recurrence. Therapeutic cervical cancer vaccines have been extensively studied. Strategies used were vaccination with HPV peptides or proteins, alone or in pulsed dendritic cells, DNA vaccines, virus-like particles or viral and bacterial vectors. Lovaxin-C is a recombinant live-attenuated Listeria monocytogenes (Lm) that secretes the antigen HPV-16 E7 fused to a non-hemolytic listeriolysin O protein. In a phase I study Lovaxin-C was administered to advanced cervical cancer patients refractory to existing therapies. The dose-limiting toxicity was hypotension and flue-like syndrome. There were no serious adverse events. Specific T-cell response was detected as well as clinical response to Lovaxin-C. Several other therapeutic HPV vaccines are in clinical development and in most of the studies specific immunological and clinical responses were seen. Efficacious therapeutic vaccine for the treatment of cervical cancer should be expected in the near future.

Invasive inflammatory pseudotumor of the pelvis: a case report with review of the literature.

Inflammatory pseudotumor (IPT) is a rare benign lesion of unknown etiology, which mimics malignant neoplasm and may arise from various organs. A 53-year-old woman was submitted to diagnostic evaluation because of bilateral, hydroureteronephrosis and oedema of the left leg after a 3-month history of fever of unknown origin. On bimanual vaginal and rectal examination, a mass was involving the uterus, parametria and mostly left adnexa, while the cervix appeared normal. Computed tomographic (CT) scan revealed a 13x10.5 cm mass in the pelvis, mostly at the place of the left adnexa, uterus and both parametria, also involving the surrounding tissues and producing bilateral hydroureteronephrosis. At laparotomy, a grey solid mass was seen, mainly involving the reproductive system. As no radical operation could be performed, the mass was only biopsied and histology showed an inflammatory pseudotumor. Antibiotic therapy was given for one month. Follow-up CT 4 and 8 months after laparotomy showed local regression of IPT. The last follow-up CT, 20 months after laparotomy, revealed no evidence of tumor.

[Pediatric brain tumors--diagnostic and treatment].

During the period 1995-2004 we treated 212 patients (pts) with brain tumors. There were 133 boys and 79 girls, aged from 2,5 yrs up to 18 yrs (Me = 9, 7 yrs). The majority of pts were in age group (4-16) yrs-179 pts. Supratentorial tumors were diagnosed in 118 pts vs. infratentorial 94 pts. Therapy involved surgery, postoperative radiotherapy with or without chemotherapy. Survival rates were calculated using Caplan-Meier method and differences between curves with log-rank test. During the follow-up period from 1 to 9 year (Me = 3 yrs) 5-year disease free survival rate was 55.7%. 79 pts failed to therapy. There was no statistically significant difference in survival according to sex (p = 0.123) and age (p = 0.367). Pts with supratentorial tumors had statistically significant better survival (p = 0.036). Pts with histologic type low grade astrocitomas had statistically significant better survival than malignant gliomas, ependymomas and PNET (p = 0.0001). Surgery, postoperative radiotherapy and chemotherapy in selected cases are efficient therapeutic approach for pediatric brain tumors.

[Postoperative radiotherapy of cervival carcinoma: treatment results and analysis of prognostic factors].

The purpose of the study was to evaluate the efficacy of postoperative radiotherapy (RT) and to investigate prognostic factors for early-stage cervical cancer patients. We reviewed the medical records of 162 cervical cancer patients treated by RT during 2003 year. RT included 30-45 Gy of external photons to pelvis in 12-25 fractions. Brachytherapy with 192Ir was delivered in 3-5 fractions to a dose of 27-32 Gy. The mean age was 49 years (range 27-71). Majority of patients 130 had Stage Ib. Radical hysterectomy with lymphadenectomy was performed in 122 pts. and simple hysterectomy in 40 pts. The 5-year actuarial overall survival (OS) for all patients was 92.6% and disease-free survival (DFS) was 90.9%.There was statistically significant differences in OS and DFS in pat. with positive vs. negative pelvic lymph nodes; tumor 4 cm vs. tumor < or = 4 cm; positive vs. negative surgical margin/residual tumor (p < 0.05). Late GIT complications were determined in 35.8% and UT in 12.3%. In conclusion, postoperative radiotherapy has achieved high-satisfactory survival with acceptable complications. The survival benefit was less evident among patients with positive lymph nodes, tumor > 4 cm and positive surgical margin/residual tumor.

[Implementation of 3D- CT based brachytherapy in the postoperative radiotherapy of cervical cancer: treatment technique and dose-volume parameters].

Intracavitary brachytherapy has an important roll in developing complications in postoperative radiotherapy of cervical cancer. 3D- CT based brachytherapy gives precisely estimating doses to organ at risk. In this study, we show our preliminary results in implementation of 3D-imaging based postoperative brachytherapy of cervical cancer: treatment technique and dose-volume parameters. During 2009 year, in 6 patients with early stage I-II of cervical cancer, brachytherapy treatment planning was based on the radiographs and CT imaging brachytherapy technique. Mean values of ICRU reference points of rectum was R max 4,2 Gy and bladder B max 4,5 Gy, while estimated volume-dose parameters D0.1 cm3 D1.0 cm D2.0 cm3 were presented with higher dose.Volume of organ at risk reflected the need for better bladder preparation. Our initial experience in performing CT-based brachytherapy, enabled us to introduce the characteristics of the parameters, assessment of their significance from the aspect of mutual relations applicators and organs at risk. Further analysis are needed, for monitoring the effects of 3D planning on complications.

[Postoperative radiotherapy of the cervical carcinoma in elderly patients (over 60 years)].

The purpose of the study was to analyze survival and late radiation effects according to performed surgery and radiation therapy in elderly patients. Between 1996-1997. year 44 patients with cervical carcinoma older then 60 years were treated with postoperative radiotherapy. Radiotherapy included external beam irradiation with TD 36-45 Gy in 18-22 fractions and endocavitar brachy-therapy with TD 28-35Gy in 4-5 fractions. We analyzed two groups of patients group I 29/44 (65.9%) had radical operation by Werthaim-Meigs vs group II 15/44 (34.1%) patients had standard operation. Median follow-up was 48 months. Survival for all patients was 70.43%. Late postirradiation effects in the gastrointestinal tract were 40.9% and in urinary tract 25%--in both groups. A larger percent of late postirradiation sequeles were on GIT in group I vs group II (44.8% vs 33.3%) and on UR tract also (31.03% vs 13.3%). The doses of external beam irradation were equalize in both groups, while brachytherapy regime 4xTD7,5Gy was more represent in group I. Late side effects and complications after postoperative radiotherapy are acceptable, but it is necessary to carry out randomized trials with different dose regime in brachytherapy.

Development of paraaortic lymph nodes metastases in carcinoma of the cervix: analysis of treatment outcome.

PURPOSE: To evaluate treatment outcomes in patients with cervical cancer and paraaortic lymph nodes metastases using radiotherapy (RT), chemotherapy (CT), or chemo/radiotherapy (CT/RT). PATIENTS AND METHODS: From 184 stage IIB-IVA patients with cervical cancer who were randomly treated with RT or CT/RT, 15 relapsed after the initial therapy only in the paraaortic lymph nodes. The median age of these 15 patients was 53 years (range 30-69). Fourteen patients had squamous cell carcinoma and one adenocarcinoma. The initial stage was IIB (n=3), and IIIB (n=12). The treatment consisted of RT to the paraaortic region (3 patients), CT (4 patients 4-6 cycles) and CT/RT sequentially (8 patients 1-2 cycles of CT before RT and 4 cycles after RT). RT was delivered as external beam radiotherapy (EBRT), total dose 45 Gy, 24 fractions, antero-posterior (AP)/postero-anterior (PA) field technique. RESULTS: With median follow up of 7 months (range 4-24), the 2-year overall survival (OS) was 17%. There was no difference in OS between therapy groups. CT/RT had not significant impact on OS. There were 7 (46.6%) objective responses (complete response-CR-5/15 and partial response-PR-2/15 patients; the best response was seen in the CT/RT group (5/8 patients). Treatments were well tolerated, while 40% of the 15 patients experienced late complications. There was no significant correlation between the initial patient therapy (RT vs. concurrent CT/RT) and the development of metastases in the paraaortic region (median time to relapse 5 vs. 6 months, respectively). CONCLUSION: Development of metastatic disease of cervical carcinoma to the paraaortic lymph nodes is associated with poor prognosis and the treatment has palliative aim. The use of different therapy approaches didn't improve the therapeutic ratio. The sequential use of CT/RT might improve results but further studies are needed.