Radiotherapy for carcinoma of the vagina. Immunocytochemical and cytofluorometric analysis of prognostic factors.

BACKGROUND AND PURPOSE: The aim of this study was to assess the potential prognostic factors in patients with primary invasive vaginal carcinoma (PIVC) treated with radical irradiation. PATIENTS AND METHODS: The analysis was performed on 77 patients with PIVC treated between 1985 and 2005 in the Maria Sklodowska-Curie Memorial Institute of Oncology, Cancer Center in Krakow. A total of 36 patients (46.8 %) survived 5 years with no evidence of disease (NED). The following groups of factors were assessed for potential prognostic value: population-based (age), clinical (Karnofsky Performance Score [KPS], hemoglobin level, primary location of the vaginal lesion, macroscopic type, length of the involved vaginal wall, FIGO stage), microscopic (microscopic type, grade, mitotic index, presence of atypical mitoses, lymphatic vessels invasion, lymphocytes/plasmocytes infiltration, focal necrosis, VAIN-3), immunohistochemical (protein p53 expression, MIB-1 index), cytofluorometric (ploidity, index DI, S-phase fraction, proliferation index SG2M) factors. RESULTS: Significantly better 5-year NED was observed in patients: < 60 years, KPS ≥ 80, FIGO stage I and II, grade G1-2, MIB-1 index < 70, S-phase fraction < 10, and proliferation index < 25. Independent factors for better prognosis in the multivariate Cox analysis were age < 60 years, FIGO stage I or II, and MIB-1 index < 70. CONCLUSION: Independent prognostic factors in the radically irradiated PIVC patients were as follows: age, FIGO stage, MIB-1 index.

Conservative treatment and long-term follow up of endodermal sinus tumor of the vagina.

OBJECTIVE: Six cases of endodermal sinus tumor (EST) of the vagina were reported focusing on the results of conservative treatment and outcome of long-term follow up. METHODS: We reviewed a cohort of six cases with EST of the vagina diagnosed and treated in our hospital. CT scan, detection of serum AFP level, examination under anesthesia and biopsy were performed before and after treatment to evaluate the tumor status. The diagnoses were confirmed by pathological and imaging findings. All patients were treated with bleomycin, etoposide and cisplatin (BEP) combination chemotherapy alone. Complete remission (CR) includes the normal level of serum AFP, no tumor detected by CT scan and the negative result of pathology. Long-term follow up was carried out according to our regulation. RESULTS: The mean onset age was 18.2 months. The average tumor size was 4.5 cm. Serum AFP level was markedly elevated before treatment and decreased dramatically after chemotherapy and drop to the normal level after two to three courses of chemotherapy (average 2.5 courses). The patients received averagely six courses of chemotherapy and all the six patients obtained CR. The mean follow-up time is 75.5 months and there was no evidence of recurrent disease. CONCLUSION: The result of this conservative treatment for EST of the vagina is excellent. BEP chemotherapy without surgery should be considered as a good choice of treatment. Close follow up with serial determinations of serum AFP level together with imaging tests and physical examination in the first two years of follow-up are recommended.

Vaginal yolk sac tumor causing infantile hydrometra: use of multidetector-row computed tomography.

BACKGROUND: A case of vaginal endodermal sinus (yolk sac) tumor resulting in hydrometra in a 9-month-old female infant is reported. CASE: The patient presented with an intermittent bloody discharge on her diapers and a lower abdominal mass on palpation. Multidetector-row computed tomography showed an irregular, dense soft-tissue mass with heterogeneous enhancement within the vagina, obstructing it. On reformatted computed tomography images, there was upstream dilatation of the cervical and uterine cavities, with fluid attenuation contents called hydrometra, resulting from the vaginal obstruction. The histopathological features of the vaginal mass were identical to those of the endodermal sinus tumor (yolk sac tumor). The patient was treated exclusively by means of chemotherapy. CONCLUSION: Examination of the alpha-fetoprotein levels was useful in the diagnosis of the patient and in assessing the patient's response to treatment by chemotherapy.

Blood levels of organochlorine pesticide residues and risk of reproductive tract cancer among women from Jaipur, India.

Residues of organochlorine pesticides are integral part of our environment. Because of their strong lipophilic and non-biodegradable nature, organisms at higher trophic levels in the food chain tend to accumulate them. The aim of the present study was to assess the influence of organochlorine pesticides upon the occurrence of reproductive tract cancers in women from Jaipur, India. Blood samples were collected from 150 females. In that group, 100 females suffered from reproductive tract cancers like cervical, uterine, vaginal and ovarian cancers, while the rest did not suffer from cancers or any other major disease and were treated as control group. The collected blood samples were subjected to pesticide extraction and analyzed with the help of gas chromatography. The pesticides detected were benzene hexa chlororide and its isomers, dieldrin, heptachlor, dichloro diphenyl trichloro ethane and its metabolites. The data obtained indicate that the organochlorine pesticide residue levels were significantly higher in all the cancer patients as compared with the control group.

Immunohistochemical determination of estrogen receptor-alpha in vaginal and tumor tissues of healthy and TVT-affected bitches and their relation to serum concentrations of estradiol-17beta and progesterone.

One of the most frequent canine neoplasms is the transmissible venereal tumor (TVT), which affects the male and the female genital tract. The objective of this study was to determine (immunohistochemically) estrogen receptor (ER-alpha) expression in vaginal tissue of healthy bitches and in the vaginal and neoplastic tissues of TVT-affected bitches. Fifty-eight bitches were divided into two groups: tumor group (TVT) and control group (healthy). Canine estrous cycle stages were determined by means of exfoliative vaginal cytology, hormone assays, and macroscopic appearance of ovaries. Samples from vaginal and neoplastic tissues were obtained under general anesthesia, fixed in 10% buffered formaldehyde, embedded in paraffin, and sectioned. Anestrus, proestrus and estrus control females had higher ER-alpha expression than diestrus bitches. Within the tumor group, diestrus bitches had significantly higher ER-alpha expression. Although some samples had expression in the endothelium of blood vessels, no ER-alpha expression was observed in neoplastic tissues. In conclusion, vaginal tissue of tumor and control bitches, under different distinct steroid influences, had different ER-alpha expression, whereas ER-alpha expression was not present in neoplastic tissues.

Yolk sac tumor of vagina.

Yolk sac tumors are common in children. By virtue of being chemosensitive, they are amenable to cure by chemotherapy alone and radical surgery is often not required. Yolk sac tumors occurring in the vagina are rare and thus may not be recognized early or may be inadvertently subjected to radical surgery. The authors report a case that presented to them after radical surgery with elevated Alpha-fetoprotein level is reported. The management of this case and review of the relevant literature are discussed here.

[Diagnostic image (224). A pregnant woman with vaginal blood loss]. / Diagnose in beeld (224). Een zwangere met vaginaal bloedverlies.

In a pregnant woman presenting with vaginal bleeding and a vaginal tumour, vaginal metastasis ofa trophoblast tumour from a mola pregnancy was diagnosed.

A study on the microheterogeneity of alpha-fetoproteins produced by yolk sac and germ cell tumors.

BACKGROUND: It is generally believed that the lower the grade of differentiation of glycoprotein-producing cells, the more often modification by bisecting N-acetylglucosamine (GlcNAc) or fucose (Fuc) at the sugar chain of the glycoprotein or increase in branching of side chains occurs. We examined the characteristics of the alpha-fetoprotein (AFP) sugar chain stored in amniotic and exocoelomic fluid during 5-9 weeks of gestation and analyzed serum-derived AFP of patients with germ cell tumors. METHODS: Total AFP concentrations in embryonic fluid at 5-9 weeks of gestation (n = 11) and serum of patients with germ cell tumors (n = 7) were measured using a radioimmunoassay (RIA) method. The percentages of AFPs reactive with Lens culinaris agglutinin (LCA), concanavalin A (Con A), erythroagglutinating phytohemagglutinin-E4 (E-PHA) and Ricinus communis agglutinin-120 (RCA 120) were obtained by lectin-affinity electrophoresis coupled with antibody-affinity blotting. RESULTS: It was revealed that at 5-9 weeks of gestation, AFP variants that had been modified by the Fuc residue, which bound to the GlcNAc residue at the reducing end of the sugar chain, and bisecting GlcNAc residues gradually decreased as pregnancy advanced; however, the presence of N-acetylneuraminic acid (Neu5Ac) at the nonreducing ends changed little. CONCLUSIONS: It appears very likely that the changes in the relative amounts of AFP variants in the embryonic fluid during early pregnancy were due to differentiation of the yolk sac. The grade of differentiation of yolk sac tumors was very similar to that of the normal yolk sac at around 6 weeks of gestation.

A case of pT4 vaginal adenocarcinoma in which surgery prolonged disease-free interval.

INTRODUCTION: There is no established treatment for vaginal cancer at present. Cases of squamous cell carcinoma reported in the literature have been treated primarily by radiotherapy. We report a case of pT4 vaginal adenocarcinoma, in which radical surgery seemed to prolong the disease-free period.

A population-based study of squamous cell vaginal cancer: HPV and cofactors.

BACKGROUND: Little is known about the etiology of in situ or invasive squamous cell cancer of the vagina. It is thought that some vaginal cancers may have the same etiology as cervical cancer. It is also not known whether in situ and invasive vaginal cancer share the same etiologic factors. We conducted a study to evaluate risk factors for in situ and invasive vaginal cancer and their potential relationship to prior exposure to human papillomaviruses (HPV). METHODS: A population-based case-control study included 156 women with squamous cell in situ or invasive vaginal cancer diagnosed between January 1981 and June 1998 and 2041 control women identified through random-digit dialing in western Washington state. Cases and controls were interviewed in person and provided blood samples; archival tumor tissue was retrieved for cases. Blood samples were tested for antibodies to HPV, and tumor tissue was tested for HPV DNA. RESULTS: Women with vaginal cancer were more likely to have five or more lifetime sexual partners (OR = 3.1, 95% CI 1.9 to 4.9), to have an early age at first intercourse (<17 years OR = 2.0, 95% CI 1.2 to 3.5), and to be current smokers at diagnosis (OR = 2.1, 95% CI 1.4 to 3.1) than control women. Approximately 30% of all cases had been treated for a prior anogenital tumor, most often of the cervix. Prior hysterectomy was a risk factor only among women who had no history of prior anogenital cancer (OR = 3.9 95% CI 2.5 to 6.1). Antibodies to HPV16 L1 were strongly related to risk of vaginal cancer (OR = 4.3, 95% CI 3.0 to 6.2). We detected HPV DNA in tumor blocks from over 80% of the patients with in situ and 60% of the patients with invasive cancers. CONCLUSIONS: In situ and invasive vaginal neoplasia have many of the same risk factors as cervical cancer, including a strong relationship to HPV infection. Women who have been treated for a prior anogenital cancer, particularly of the cervix, have a high relative risk, although low absolute risk, of being diagnosed with vaginal cancer.

Increased serum levels of 5-S-cysteinyldopa and intercellular adhesion molecule-1 in a patient with a uterine amelanotic metastasis from a primary vaginal malignant melanoma.

A 75-year-old Japanese woman, who had an enlarged uterus and two nodules on the anterior vaginal wall, underwent wide excision of the anterior vaginal wall, bilateral inguinal lymphadenectomy, modified radical hysterectomy, and pelvic lymph node dissection. Her serum level of 5-S-cysteinyldopa (5-S-CD) was elevated, but her serum intercellular adhesion molecule-1 (ICAM-1) level was within normal limits. Histologic examination of the vaginal wall revealed atypical melanocytes at the dermoepidermal junction and numerous melanin-containing granules in the cytoplasm of the tumor cells. The tumor in the uterus consisted of sheets of anaplastic cells with evidence of diminished melanization. Five months after her initial presentation, she developed a recurrence and expired. The serum level of ICAM-1 was beyond the normal limit at the time of recurrence. Both the serum 5-S-CD and the ICAM-1 levels became elevated after recurrence and appeared to be correlated with disease progression.

Effect of recombinant human interleukin-3 (rhIL-3) on persisting chemotherapy-induced thrombocytopenia.

A 57 year old woman with heavily pretreated advanced vaginal cancer (FIGO III) developed severe thrombocytopenia (7000/microliter) with bleedings after chemotherapy. This patient was treated with recombinant human interleukin-3 (rhIL-3) after 26 platelet transfusions (25 pooled transfusions and one HLA-matched platelet transfusion) had not been effective. Increase of thrombocyte counts began 2 days after rhIL-3 therapy. Side-effects due to rhIL-3 administration (flu-like symptoms) were mild and could be treated effectively with paracetamol and clemastin. These data support first evidence for efficacy of rhIL-3 in chemotherapy-induced thrombocytopenia and may open new perspectives for its clinical application.

Establishment and characterization of human vaginal malignant melanoma xenotransplants.

Human vaginal malignant melanoma represents rare gynecological malignancies of poor prognosis. We have established a melanoma tumor line in nude mice, designated Mela-1, and have examined the histological and biological characteristics of this tumor. The Mela-1 tumor has preserved the histological, histochemical and biological characteristics of malignant melanoma even after 20 passages. Tumor cells are of epitheloid shape varying in size. An ultrastructural study revealed that the tumor cells were characterized by the presence of cells with deeply indented nuclei, and both types of melanosomes, eumelanosomes and pheomelanosomes, in various stages of maturation with vesiculo-globular bodies in the cytoplasm. Melanin analysis of the tumor indicated the Mela-1 tumor to be pheomelanic. Immunohistochemical examinations revealed that the Mela-1 cells were stained positively by melanoma-associated antibody (NKI/C3) and by antibodies for S-100 protein and vimentin, and negatively for keratin and CEA. The levels of AFP, CA125 and CEA in sera of tumor-bearing mice were within normal range. The 5-S-cysteinyldopa level in sera of tumor-bearing mice correlated well with the size of the tumor. Chromosomal analysis showed the human karyotype with great heterogeneity and a modal number of 102 chromosomes. Thus the Mela-1 tumor will be useful in establishing the biological characteristics in the search for an effective treatment of human malignant melanoma of the vagina.

[Plasma fibrinogen in female patients with genital cancer and its early stage]. / Untersuchungen über das Plasmafibrinogen bei Patientinnen mit Karzinom des Genitalsystems und seine Vorstufen.

Changes of plasma fibrinogen derivates in 54 female patients suffering from carcinomas of the genital system (36 with cervix carcinoma, 9 with ovarian carcinomas, 7 with carcinomas of the corpus uteri, 1 woman with a vulva and 1 patient with vaginal carcinoma) and 6 females with cervical intraepithelial neoplasia were investigated. It was shown, that the fibrinogen content and the concentration of soluble fibrin monomer complexes in blood plasma depend on the extension of the clinically diagnosed tumor. Furthermore, differently degraded fibrinogens were demonstrated to exist in the blood circulation. The extent of fibrinogenolysis did not correlate with the clinically diagnosed tumor stage.

Carcinoembryonic antigen in gynecologic patients. II. Immunohistological expression.

Certain tumors of the female genital tract have a very probability of expressing CEA activity. These include endocervical carcinomas and ovarian Brenner tumors. This information may be helpful in allowing one to distinguish among several diagnostic possibilities on a given biopsy. CEA detection apparently fails to distinguish between endometrial hyperplasias versus endometrial carcinomas. Gonadal stromal tumors of the ovary are generally negative, whereas the common epithelial tumors (depending on the histological type) have a reasonable probability of having detectable antigen. Since plasma CEA levels have had a demonstrated usefulness in following patients who were known to have elevated CEA levels prior to the removal of their primary tumor in the endometrium, ovary, and cervix, it is valuable to have an estimate of probability that a tumor will express CEA in evaluating the results of plasma radioimmunoassays for this antigen.

[Serum concentration of the pregnancy-associated alpha2 glycoprotein (alpha2-PAG, protein of the "pregnancy zone", PZ) in malignant gynecologic diseases]. / Die Serumkonzentration des schwangerschaftsassoziierten alpha2-glykoproteins (alpha2-PAG, Protein der "pregnancy zone", PZ) bei malignen gynäkologischen Erkrankungen.

The concentration of pregnancy-associated alpha2-glycoprotein (alpha2-PAG, PZ) was investigated by means of electroimmunodiffusion and single radial immunodiffusion in sera of 30 patients suffering from malignant genital diseases. Results of electroimmunodiffusion indicate that surgical and/or radiological treatment is followed by a significant decrease of PZ serum level. But few months later values have been measured as detected before therapy. There were no significant differences of PZ levels in dependence on localization, histological findings and stage of gynaecological cancer. These findings indicate that periodic determinations of serum PZ do not supply the diagnosis for controlling the course of gynaecological cancer.

[Pregnancy associated alpha2-glycoprotein (alpha2-PAG) in the serum of patients with gynecologic carcinomas]. / Das schwangerschaftsassoziierte alpha2-Glykoprotein (alpha2-PAG) im Serum von Patientinnen mit gynäkologischen Karzinomen.

alpha2-PAG is a high-molecular, carbohydrate-containing glycoprotein. It occurs in traces in normal human serum. The variations in serum levels of this protein were studied during treatment of 32 gynecological cancer patients in the course of 2 years. The periodic alpha2-PAG determinations were done with an electro-immuno-assay. A correspondence between alpha2-PAG serum levels and the clinical course could be found in 60%. In 5 of 13 patients who did not respond to therapy alpha2-PAG levels rose, additional 4 had unchanged high levels, whereas 13 of 17 patients had significantly decreased levels on successful treatment. The relevance of periodic alpha2-PAG determinations is discussed.