Spatiotemporal immunofluorescent evaluation of porcine reproductive and respiratory syndrome virus transmission across the maternal-fetal interface.

Porcine reproductive and respiratory syndrome virus (PRRSV) infection causes severe reproductive failure characterized by high fetal morbidity and mortality leading to substantial economic losses to the swine industry. Evaluation of spatiotemporal transmission of PRRSV at the maternal-fetal interface (MFI) is critical for understanding fetal infection. Localization of PRRSV-2 strain NVSL 97-7895 at different regions of the MFI in 20 pregnant gilts at 2, 5, 8, 12 and 14 days post-inoculation (dpi) were analyzed by immunofluorescence (IF). Samples of MFI were collected from 15 inoculated and 5 control gilts and transplacental PRRSV transmission assessed in randomly selected fetuses from each litter. Localization of NVSL 97-7895 antigen immunoreactivity in the MFI was focused in three major areas: endometrial connective tissues (ENDO), the feto-maternal junction (FMJ) and fetal placenta (PLC). NVSL 97-7895 was detected at the FMJ by 2 dpi. At 2, 5 and 8 dpi, NVSL 97-7895 was localized within the ENDO and FMJ, whereas at 12 and 14 dpi, it was mainly localized in the PLC. Using a novel IF strategy for counting and size sorting NVSL 97-7895 viral antigen in situ, results of this study indicate that non-cell-associated mechanisms are involved in PRRSV transmission across the MFI.

Surgical approaches towards fertility preservation in young patients with early invasive cervical carcinoma.

Cervical cancer still remains one of the major problems in developing countries. The last decade of 20th century has seen a trend towards more conservative surgical approaches in the treatment of early-stage disease in young patients. The trend of delaying childbearing, nowadays, increases preservation of fertility, and reproductive function is a major concern when counseling these young women with regard to the effects of treatment for cervical cancer. Radical trachelectomy, either with abdominal or vaginal surgical approach, showed promise as treatment option in young patients with early cervical cancer. The basic principle of such a surgical approach is an operation aiming at preserving the uterine body and removing the cervix, parametrium, with bilateral pelvic lymphadenectomy, and creating a utero-vaginal anastomosis, either laparoscopically or by laparotomy. Both surgical approaches are evaluated after a search of the relevant literature in Pub Med or Medline.

Clinical staging and histopathological findings after radical hysterectomy in FIGO stage IIB cervical cancer.

PURPOSE: Advanced cervical cancer still represents a major health care challenge in the developing world. According to standard protocols the treatment of choice for stage IIB cervical cancer is cisplatin-based chemoradiotherapy. However, in some European countries, and especially in Japan, patients with stage IIB cervical cancer are generally treated with radical hysterectomy as initial treatment. The aim of this study was to compare clinical stage with pathological findings, and also to correlate any relationship between parametrial infiltration and nodal status. PATIENTS AND METHODS: From 1997 to 2006, 26 patients with FIGO stage IIB cervical cancer were radically operated (Piver class III operation). Preoperative clinical findings were compared with the pathological findings of the surgical material. The correlation between infiltration of the parametria and lymph node status was also examined. Fisher's exact test was used to examine statistical significance. RESULTS: The patients' median age was 48.3 years (range 36-61). The median number of removed lymph nodes was 16 (range 8-40). The histopathological types of cervical tumors were: squamous cell carcinoma 80%, adenosquamous carcinoma 15% and adenocarcinoma 5%. In 50% of the patients the parametria were infiltrated, suggesting that 50% of the patients were clinically overstaged. Positive lymph nodes were found in 69% of patients with positive parametria and 15% in patients with negative parametria (p <0.05). Patients with positive lymph nodes received adjuvant chemoradiotherapy. CONCLUSION: Adequate preoperative staging such as clinical examination under anesthesia or nuclear magnetic resonance could help to exclude parametrial involvement in equivocal cases. Parametrial invasion presents an important risk factor for lymph nodes metastases.

Clinical-sonographic scoring system in noninvasive diagnosis of endometrial cancer.

PURPOSE: In 90% of all endometrial cancers vaginal bleeding is the leading clinical symptom. Nowadays, scoring systems have become acceptable in medicine as less invasive, adequate, diagnostic methods. The main goal of this study was to examine the clinical-sonographic scoring system as a noninvasive diagnostic method for endometrial cancer. PATIENTS AND METHODS: The study included 122 patients with postmenopausal bleeding (PMB). Transvaginal sonography was performed before curettage. Patients were divided in two groups (A and B). In group A included were patients without endometrial malignancy and in group B were patients with endometrial cancer. A clinical-sonographic scoring system named ONCO 1 was created. Each patient got her own score based on anamnesis, clinical examination, and transvaginal ultrasonography. Evaluations of the clinical-sonographic scoring system were performed by using the test for diagnostic accuracy and receiver operating characteristic (ROC) curve. RESULTS: Patients with endometrial cancer were older (median age in group B 64.49 years vs. 58.81 in group A), the length of corpus uteri was longer (6.41 cm in group B vs. 5.25 cm in group A), and the postmenopausal period was longer (13.67 years median in group B vs. 9.11 in group A). All parameters were statistically significant. The average value of clinical-sonographic scoring system ONCO 1 in group A was 7.13, +/-3.07 SD and in group B it was 9.14, +/-2.32 SD. The difference was statistically significant. CONCLUSION: Postmenopausal bleeding caused by endometrial cancer is usually diagnosed in older patients. It was possible to distinguish high-risk patients with neoplasia from those with benign changes of the endometrium using the clinical-sonographic systems ONCO 1. Nevertheless, histopathological examination is still unavoidable for the final diagnosis of endometrial cancer.

Stage IB2 cervical cancer: brachytherapy followed by radical hysterectomy.

PURPOSE: Stage IB2 squamous cell cervical cancer can be treated by radiation therapy alone or by radical hysterectomy and lymphadenectomy (pelvic-/+para-aortic). Preoperative radiation therapy followed by extrafascial hysterectomy has been recommended as an effective combined treatment method. PATIENTS AND METHODS: During the period January 1994-January 2004, 114 patients with stage IB2 cervical cancer were treated with preoperative brachytherapy followed by radical hysterectomy (Piver class III) with pelvic lymphadenectomy. RESULTS: Histology showed that 56 (49%) patients were without cervical malignant disease. Positive lymph nodes were found in 5 (9%) of them and negative in 51 (91%). In 58 (51%) patients cervical cancer still existed after brachytherapy and among them 26 (45%) were with lymph node metastasis. Patients with residual cervical carcinoma and positive lymph nodes after brachytherapy were older than those with no residual carcinoma and negative lymph nodes. CONCLUSION: Women with stage IB2 squamous cell cervical cancer primarily treated with brachytherapy must be assessed by appropriate diagnostic procedures to evaluate local effects of brachytherapy and the status outside the pelvis. Negative local findings with positive lymph nodes point to further treatment of patients, while positive local findings point to radical surgery which may increase recurrence-free interval.

Effects of folylpolyglutamate synthetase modulation on chemosensitivity of colon cancer cells to 5-fluorouracil and methotrexate.

BACKGROUND: Folylpoly-gamma-glutamate synthetase (FPGS) converts intracellular folates and antifolates (for example, methotrexate (MTX)) to polyglutamates. Polyglutamylated folates and antifolates are retained in cells longer and are better substrates than their monoglutamate counterparts for enzymes involved in one carbon transfer. Polyglutamylation of intracellular 5,10-methylenetetrahydrofolate may also enhance the cytotoxicity of 5-fluorouracil (5-FU) by allowing more efficient formation and stabilisation of the inhibitory ternary complex involving thymidylate synthase and a 5-FU metabolite. AIM: We investigated the effects of FPGS modulation on the chemosensitivity of colon cancer cells to 5-FU and MTX. METHODS: Human HCT116 colon cancer cells were stably transfected with the sense or antisense FPGS cDNA or blank (control). FPGS protein expression and enzyme activity, growth rate, intracellular folate content and composition, and in vitro chemosensitivity to 5-FU and MTX were determined. RESULTS: Compared with cells expressing endogenous FPGS, those overexpressing FPGS had significantly faster growth rates and higher concentrations of total folate and long chain folate polyglutamates while antisense FPGS inhibition produced opposite results. FPGS overexpression significantly enhanced, whereas FPGS inhibition decreased, chemosensitivity to 5-FU. No significant difference in chemosensitivity to MTX was observed. CONCLUSIONS: These data provide functional evidence that FPGS overexpression and inhibition modulate chemosensitivity of colon cancer cells to 5-FU by altering intracellular folate polyglutamylation, providing proof of principle. Thus FPGS status may be an important predictor of chemosensitivity of colon cancer cells to 5-FU based chemotherapy, and FPGS gene transfer may increase the sensitivity of colon cancer cells to 5-FU-based chemotherapy.

Tumor angiogenesis in gynecological oncology.

Angiogenesis, the formation of new blood vessel networks to permit sustained tumor growth, is one of the most rapidly growing fields in basic and applied cancer research. Angiogenesis is a prerequisite for tumor growth and metastasis. Vascular endothelial cell proliferation, migration and capillary formation are stimulated by angiogenic growth factors. It is now accepted, mainly on the basis of knock-out experiments, that the most potent pro-angiogenic factor is the vascular endothelial growth factor (VEGF). VEGF is the prototype of a family of pro-angiogenic peptides, which now comprises several related members. Recent studies in gynecological oncology have shown considerable importance of tumor angiogenesis as independent prognostic factor, or the use of angiogenesis-related factors as possible tumor markers. Immunohistochemical studies have revealed that high microvessel density (MVD) was associated with poor prognosis in carcinomas of the uterine cervix, endometrium, vulva and ovary. Tumor angiogenesis is not a specific process for one type of tumor, and angiogenic growth factors cannot be specific for one type of malignant disease. Immunohistochemical studies also showed importance of angiogenic factors and MVD in other kinds of cancers such as breast cancer, gastrointestinal cancers, soft-tissue sarcomas etc. The importance of tumor angiogenesis in the natural history of cancer, the possible applications of angiogenesis markers as prognostic factors and the emergence of innovative antitumor treatments based on anti-angiogenic strategies may lead to new goals in oncology.

Radical hysterectomy for stage IB1 cervical carcinoma: lymph node metastasis as a prognostic factor.

PURPOSE: Lymph node metastasis is one of the most important factors influencing prognosis and further therapy in patients with cervical carcinoma. The aim of this study was to confirm the impact of nodal metastasis od disease-free interval in women with stage IB1 cancer of the uterine cervix. PATIENTS AND METHODS: From June 1986 to December 1999 269 patients with stage IB1 cervical carcinoma were operated on. Two hundred thirty-six (87.84%) patients had class III and 33 (12.16%) class II radical hysterectomy, according to Piver's classification. RESULTS: The median number of the removed lymph nodes was 21. Positive lymph nodes were found in 71 (25.28%) patients. All patients with positive lymph nodes received postoperative adjuvant external beam radiotherapy. Patients with bulky nodal disease received also chemotherapy.Overall 5-year disease-free interval in 212 patients was 80%. Five-year disease-free interval for patients without lymph node metastasis was 91%, while it was 40% in those with lymph node metastasis (p < 0.0001). CONCLUSION: Surgical staging of cervical cancer, which includes pelvic and para-aortic lymphadenectomy,together with pathological data, can provide potentially useful information for the radiation oncologist and precise analysis of survival and prognostic risk factors.

Bacteriological comparison of parallel and counter flow water chilling of poultry meat.

Parallel flow water chilling and counter flow water chilling of young fattened broiler carcasses "Hybro" line were investigated. The samples were taken at 7 a.m. and 2 p.m. in March and April. The total count of aerobic mesophillic bacteria were determined at three stages of processing (evisceration, chilling using ether counter flow or parallel flow and final wash), and twice during the day (7 a.m. and 2 p.m.). Also, the total count of aerobic mesophilic bacteria was determined in samples of cold water (pre-chilling) and samples of ice water (chilling) at different times (7 a.m. and 2 p.m.). Significantly lower bacterial counts were obtained in carcasses treated with counter flow chilling.

Pregnancy following treatment of an adolescent with Yolk sac tumour.

The Authors present the case of a patient suffering from a highly malignant tumour, Yolk sac tumour, who received a combined treatment of operation and chemotherapy. The treatment was applied selectively, i.e. surgery was as radical and as conservative as deemed necessary. The patient was cured and after getting married, she gave birth to a baby girl with pes varus. Because of lack of experience with Yolk sac tumours, which up to the cytologic era had had bad prognoses, and of insufficient knowledge with the consequences of chemotherapy on the generative and reproductive functions of the patients cured, we consider our case to be worthy of attention.

[Thrombophlebitis in the minor pelvis in problems with differential diagnosis in gynecologic oncology]. / Tromboflebitis u maloj karlici kao diferencijalno-dijagnosticki problem u ginekoloskoj onkologiji.

The oncologic-gynecology practice shows that vein thrombophlebitis of the pelvis minor causes retroperitonal spreading of malignant tumor of the cervix or growth of the ovarian neoplasm. In cases of unexplained etiology, the existance of malignant tumors as an etiologic factor, should be excluded by the examination performed by an experienced gyneocologist-oncologist, by ultrasonography, computerized tomography and in case of doubt by explorative laparotomy.

[Anterior pelvic exenteration with ileocystoplasty in advanced cancer of the uterine cervix]. / Prednja pelvicna egzocentracija sa ileocistoplastikom kod odmaklog raka grlica materice.

A female patient with the IV grade cervical carcinoma without distant metastases is presented. The patient underwent a radical surgical intervention. An anterior pelvic exenteration with ileocystoplasties was successfully performed. The patient is alive 14 months after the initial treatment. No greater complications were observed during the operation and after it, but in spite of a satisfactory general status, the patient has had nocturnal incontinence all the time. It is believed that this complication is the sequel of the newly formed urinary bladder, as the convolution of the ileum is only 30 cm long which has proved insufficient.

Childhood leukaemia: relapse in the anterior segment of the eye.

A proved first relapse occurred in the anterior segment of eight children with acute leukaemia, two of whom had concurrent central nervous system or bone marrow relapse. A further child developed uveitis after remission was induced, but in this patient no causal relationship with leukaemia was established. Uveitis in children who have had acute leukaemia should be regarded as evidence of relapse, and anterior chamber aspiration and iris biopsy are essential procedures in their evaluation. The outlook for children with anterior segment relapse remains poor despite intensive local and systemic treatment.

The infant corneal endothelium.

Specular microscopy of the in vivo corneal endothelium of 48 clinically normal eyes of 31 infants less than 1 year old revealed a regular mosaic of small cells. The cell population density of individuals varied greatly, as it does in age-related adults. Reexamination of five eyes indicated a reduction of the cell population density during the first year. This change could be accounted for by corneal growth in the absence of endothelial mitoses and not necessarily by true cell loss. There were morphologic indications of mitoses, but their interpretation is open to doubt.

Localising patterns of optic nerve hypoplasia--retina to occipital lobe.

Six cases are presented which provide clinical evidence that optic nerve hypoplasia can occur as a result of a lesion at any site in the developing visual system. The mechanisms of hypoplasia are discussed in the light of recent understanding of optic nerve development.

Age-related changes of the corneal endothelium and stroma as seen in vivo by specular microscopy.

Two age-related changes of the human cornea are revealed in vivo by specular microscopy, (1) loss (and enlargement) of endothelial cells and (2) wrinkling of the posterior corneal layers when the cornea is applanated. A comparison of the rate of loss of cells and the effect upon the morphology of the endothelium as determined in several studies, indicates that cell loss and enlargement are rapid in the first year of life, slower up to the age of about 25 years, and fairly stable thereafter. In some individuals the remaining cells appear to enlarge regularly and in others irregularly. Posterior wrinkles on applanation of the cornea occur in the adult cornea only, and suggest an increasing rigidity of the stroma with increasing age.