Learning curves of open and endoscopic fetal spina bifida closure: systematic review and meta-analysis.

OBJECTIVE: The Management of Myelomeningocele Study (MOMS) trial demonstrated the safety and efficacy of open fetal surgery for spina bifida aperta (SBA). Recently developed alternative techniques may reduce maternal risks without compromising the fetal neuroprotective effects. The aim of this systematic review was to assess the learning curve (LC) of different fetal SBA closure techniques. METHODS: MEDLINE, Web of Science, EMBASE, Scopus and Cochrane databases and the gray literature were searched to identify relevant articles on fetal surgery for SBA, without language restriction, published between January 1980 and October 2018. Identified studies were reviewed systematically and those reporting all consecutive procedures and with postnatal follow-up ≥ 12 months were selected. Studies were included only if they reported outcome variables necessary to measure the LC, as defined by fetal safety and efficacy. Two authors independently retrieved data, assessed the quality of the studies and categorized observations into blocks of 30 patients. For meta-analysis, data were pooled using a random-effects model when heterogeneous. To measure the LC, we used two complementary methods. In the group-splitting method, competency was defined when the procedure provided results comparable to those in the MOMS trial for 12 outcome variables representing the immediate surgical outcome, short-term neonatal neuroprotection and long-term neuroprotection at ≥ 12 months of age. Then, when raw patient data were available, we performed cumulative sum analysis based on a composite binary outcome defining successful surgery. The composite outcome combined four clinically relevant variables for safety (absence of extreme preterm delivery < 30 weeks, absence of fetal death ≤ 7 days after surgery) and efficacy (reversal of hindbrain herniation and absence of any neonatal treatment of dehiscence or cerebrospinal fluid leakage at the closure site). RESULTS: Of 6024 search results, 17 (0.3%) studies were included, all of which had low, moderate or unclear risk of bias. Fetal SBA closure was performed using standard hysterotomy (11 studies), mini-hysterotomy (one study) or fetoscopy by either exteriorized-uterus single-layer closure (one study), percutaneous single-layer closure (three studies) or percutaneous two-layer closure (one study). Only outcomes for standard hysterotomy could be meta-analyzed. Overall, outcomes improved significantly with experience. Competency was reached after 35 consecutive cases for standard hysterotomy and was predicted to be achieved after ≥ 57 cases for mini-hysterotomy and ≥ 56 for percutaneous two-layer fetoscopy. For percutaneous and exteriorized-uterus single-layer fetoscopy, competency was not reached in the 81 and 28 cases available for analysis, respectively, and LC prediction analysis could not be performed. CONCLUSIONS: The number of cases operated is correlated with the outcome of fetal SBA closure, and the number of operated cases required to reach competency ranges from 35 for standard hysterotomy to ≥ 56-57 for minimally invasive modifications. Our observations provide important information for institutions looking to establish a new fetal center, develop a new fetal surgery technique or train their team, and inform referring clinicians, potential patients and third parties. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Curvas de aprendizaje del cierre de la espina bífida fetal mediante cirugía abierta y endoscópica: revisión sistemática y metaanálisis OBJETIVO: El ensayo del Estudio sobre la Gestión del Mielomeningocele (MOMS, por sus siglas en inglés) demostró la seguridad y eficacia de la cirugía fetal abierta para la espina bífida aperta (EBA). Las técnicas alternativas recientemente desarrolladas pueden reducir los riesgos de la madre sin comprometer los efectos neuroprotectores del feto. El objetivo de esta revisión sistemática fue evaluar la curva de aprendizaje (CA) de diferentes técnicas de cierre de la EBA fetal. MÉTODOS: Se realizaron búsquedas en las bases de datos de MEDLINE, Web of Science, EMBASE, Scopus y Cochrane, así como en la literatura gris, para identificar artículos relevantes sobre cirugía fetal para la EBA, sin restricción de idioma, publicados entre enero de 1980 y octubre de 2018. Se examinaron sistemáticamente los estudios identificados y se seleccionaron los que informaban de todos los procedimientos consecutivos y con seguimiento postnatal ≥12 meses. Los estudios se incluyeron sólo si informaban sobre las variables de resultado necesarias para medir la CA, definidas por la seguridad y la eficacia para el feto. Dos autores recuperaron los datos de forma independiente, evaluaron la calidad de los estudios y clasificaron las observaciones en bloques de 30 pacientes. Para el metaanálisis, los datos se agruparon mediante un modelo de efectos aleatorios cuando fueron heterogéneos. Para medir la CA, se usaron dos métodos complementarios. En el método de división de grupos, la competencia se definió cuando el procedimiento proporcionó resultados comparables a los del ensayo MOMS para 12 variables de resultados que representaban el resultado quirúrgico inmediato, la neuroprotección neonatal a corto plazo y la neuroprotección a largo plazo a ≥12 meses de edad. Luego, cuando se dispuso de los datos brutos de los pacientes, se realizó un análisis de suma acumulada basado en un resultado binario compuesto que definió el éxito de la cirugía. El resultado compuesto combinó cuatro variables clínicamente relevantes en cuanto a la seguridad (ausencia de parto pretérmino extremo <30 semanas; ausencia de muerte fetal a ≤7 días después de la cirugía) y eficacia (reducción de la hernia del rombencéfalo y ausencia de cualquier tratamiento neonatal de dehiscencia o derrame de líquido cefalorraquídeo en el lugar del cierre). RESULTADOS: De los 6024 resultados de la búsqueda, se incluyeron 17 (0,3%) estudios, todos ellos con un riesgo de sesgo bajo, moderado o incierto. El cierre de la EBA fetal se realizó mediante histerotomía estándar (11 estudios), mini histerotomía (un estudio) o fetoscopia, ya fuera mediante el cierre exteriorizado del útero de una sola capa (un estudio), el cierre percutáneo de una sola capa (tres estudios) o el cierre percutáneo de dos capas (un estudio). Sólo se pudieron metaanalizar los resultados de la histerotomía estándar. En general, los resultados mejoraron significativamente con la experiencia. Se alcanzó la competencia después de 35 casos consecutivos para la histerotomía estándar y se predijo que se alcanzaría después de ≥57 casos para la mini histerotomía y ≥56 para la fetoscopia percutánea de dos capas. En el caso de las fetoscopias percutánea y exteriorizada del útero de una sola capa, no se alcanzó la competencia en los 81 y 28 casos disponibles para el análisis, respectivamente, y no se pudo realizar el análisis de predicción de la CA. CONCLUSIONES: El número de casos operados está correlacionado con el resultado del cierre de la EBA fetal, y el número de casos operados necesarios para alcanzar la competencia estuvo entre 35 para la histerotomía estándar y ≥56-57 para las operaciones con mínima agresividad. Las observaciones realizadas proporcionan información importante para las instituciones que buscan establecer un nuevo centro fetal, desarrollar una nueva técnica de cirugía fetal o entrenar a su equipo, e informar a los médicos que remiten a especialistas a los posibles pacientes y a terceros. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Significance of hypoxia in uterine cervical cancer. Multicentre study.

PURPOSE: The aim of the study was to evaluate hypoxia markers (VEGF, GLUT-1, and HIF-1alpha) in cervical cancer tissue depending on staging (FIGO) and grading. We also analyzed the adverse effects of radiotherapy according to expression levels of hypoxic markers in the studied tissue. MATERIAL AND METHODS: Expression of hypoxia-inducible factor-1alpha (HIF-1alpha), glucose transporter 1 (GLUT-1) and vascular endothelial growth factor (VEGF, also known as proangiogenic factor) were estimated in biopsy or surgical specimens from 106 patients diagnosed with uterine cervical cancer. Immunohistochemical methods with EbVision+ complex using monoclonal antibodies anti-VEGF and anti-HIF-1alpha and polyclonal antibody anti-GLUT-1 were applied. RESULTS AND CONCLUSIONS: Hypoxia features measured by percentage of cells undergoing reaction with antibodies anti-HIF-1alpha, anti-GLUT-1 and anti-VEGF were similar in all clinical stages; however the biggest hypoxia features were shown in low differentiated cancers G2 and G3. The 5-year survival for FIGO Stage III patients was shorter in cases with a high expression of hypoxic markers. We observed adverse effects in 45.3% of patients, which occurred more often in patients with higher expression of the studied factors. The presence of hypoxic cells is established as one of the most important factors affecting resistance against tumor radiotherapy and patient prognosis.

Use of prolene mesh in surgical treatment of tissue defects after radical inguinal and pelvic lymph node dissection in vulvar cancer--a brief report.

Surgery is still the procedure of choice in treatment of advanced vulvar cancer. Radical vulvar surgery is often associated with severe vulvar and inguinal skin and fat-tissue deficits resulting from wide "butterfly" shape resection. Primary closure of large vulvar and inguinal defects is hampered by lack of tissue. The study presents the case of using prolene mesh in filling up the tissue defects over femoral vein and artery after radical excision of enlarged inguinal superficial, femoral, and pelvic nodes to prevent vessels in hiatus saphenus. It is the first report describing the use of prolene mesh in such a procedure.

[The analysis of caesarean sections in women residents of Bytom and in other women]. / Analiza ciec cesarskich wykonywanych wsród pacjentek z miasta Bytomia i spoza Bytomia.

Authors analysed indications and number of caesarean sections performed in the I-st Department of Obstetrics and Gynaecology in Bytom in the years 1994-1998. In the analyse we considered place of living of pregnant women, dividing women on residents of Bytom and non-residents of Bytom. The results showed increasing number of caesarean sections. Percentage of caesarean sections in the group of non-residents of Bytom was twice higher as in the group of residents of Bytom. The most common indications were status after prior caesarean section or other uterus operation, fetal distress and fetus malposition.

[The evaluation of complications caused by insertion of Veres needle and trocars placement based on analysis of 4211 laparoscopic operations]. / Ocena powiklan spowodowanych wkluciem igly veresa i troakarów oparta na analizie 4211 operacji laparoskopowych.

The retrospective analysis of 4211 laparoscopic operations was performed. The complications caused by insertion of Veres needle and trocars placement were found in 66 cases (1.6%). There were: retropneumoperitoneum--in 33 cases (8@1000), vascular injuries--22 cases (5@1000), injuries of the gastrointestinal organs--9 cases (2@1000). In 2 cases (0.4@1000) perforation of the wall of urinary bladder occurred. The accurate preparation of patients to laparoscopy, knowledge of management with complications, ability to laying sutures through all of abdominal layers, using of Foley's catheter for haemostasis enabled to cure both the main disease and complications.

[Ovarian endometriomas during pregnancy]. / Guzy endometrioidalne jajników wspólistniejace z ciaza.

OBJECTIVES: Endometriomas are rare in pregnancy. May be difficult to diagnose and may cause significant complications at any stage during gestation. MATERIALS AND METHODS: The author presents 2 cases of ovarian endometriomas diagnosed and treated surgically in 14 and 18 weeks of pregnancy. In the first case laparoscopy was performed, in the second case laparoscopy and then laparotomy due to massive adhesions were performed. RESULTS: In both cases histopathological examinations showed: cystis picea endometriotica ovarii. Both patients delivered at term. CONCLUSIONS: Ovarian endometriomas does not exclude fertility. Surgical management of ovarian endometriomas does not complicate pregnancy course.

Hormonal activity of transposed ovaries in young women treated for cervical cancer.

The purpose of this study was to assess the hormonal function of transposed ovaries in young women treated for cervical cancer. Between 1992 and 1998, in the Silesian Medical Academy in Bytom, 101 women underwent radical hysterectomy with ovarian transposition by the Wertheim-Meigs method. Concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, estradiol and testosterone in blood serum and cytologic indices (maturation index, karyopyknotic index and maturation value) were assessed before surgery and on the ninth day after surgery. Patients were subsequently requested to return in July 1999 to have the hormonal activity of their ovaries assessed from the perspective of a few years after the operation, and the effect of supplementary radiotherapy soon after surgery. There was a statistically significant difference between those who had radiotherapy and those who did not with respect to climacteric complaints and hormonal parameters. A correlation was found between serum estradiol levels and maturation value. Proper ovarian hormonal function was still present in 69.8% of patients, even 60 months after surgery, but a lower bone mineral density was also observed. Ovarian transposition is a procedure that allows ovarian function to be preserved in young women treated for cervical cancer; it also helps to obviate the necessity for long-term hormone-replacement therapy. However attention must be paid to the concomitant possibility that women with cervical cancer may have a lower bone mineral density, and routine follow-up measurement of FSH levels or cytologic indices is advocated.

[Testosterone and SHBG levels in blood serum in women with anorexia nervosa]. / Stezenia testosteronu i SHBG w surowicy krwi u kobiet z jadlowstretem psychicznym.

The reports concerning serum levels of sex hormone binding globulin (SHBG) and testosterone in women with anorexia nervosa are controversial and few in number. The aim of the study was to assess the levels of FSH, LH, PRL, unbound and bound testosterone, SHBG, estradiol, free T4, TSH in women with anorexia nervosa. The TFI (testosterone free index) used to assess SHBG ability to bind testosterone was also calculated. The studied group consisted of 29 women with anorexia nervosa: 15 women untreated hormonally and 14 women treated with estrogens and progestagens. The control group consisted of 13 women with regular menstrual cycle being in the first phase of menstrual cycle, with proper body weight and mean age comparable to the patients with anorexia nervosa. No statistically significant differences between studied groups concerning the serum concentration of FSH, LH, PRL, free testosterone, LH/FSH ratio, TSH and free T4 were found. The total testosterone concentration was statistically significantly lower in the group without hormonal therapy, contrary to SHBG concentration, which was higher in the group treated hormonally. Although there are reports about elevated SHBG and free testosterone levels in patients with anorexia nervosa, our study has shown no significant differences between women with untreated hormonally anorexia nervosa and healthy control group.

[Photodynamics in gynaecology]. / Zastosowanie metody fotodynamicznej w ginekologii.

Photodynamic procedures were intended for early detection and therapy of neoplastic diseases. Fluorescence diagnosis is based on the detection of the fluorescence of exo- and endogenous photosensitizers selectively accumulated in pathological tissues. Photodynamic therapy is based on the selective destruction of neoplastic tissue resulting from interaction between photosensitizer, light and oxygen. The main fields of the clinical use of photodynamics are pulmonology, gastroneterology, urology and dermatology. The article presents the theoretical principles of fluorescence diagnosis and photodynamic therapy followed by the review of up-to-date literature concerning the use of photodynamics in diseases of the genital tract in women.

[The assessment of expression of kininogen and bradykinin receptors genes in different vulvar pathologies by QPCR (TaqMan)]. / Ocena ekspresji genów kodujacych kininogen oraz receptory kinin w róznych stanach patologii sromu metoda QPCR (TaqMan).

OBJECTIVES: In different vulvar pathologies inflammatory process and pain are often observed. In these processes, kinins, released from kininogen, play an important role. Their effects are mediated by at least two types of bradykinin receptors--B1 and B2. B1 receptor appears in certain pathological states, B2 is widely distributed in normal tissues. The expression of genes coding kininogen, B1 and B2 receptors can be a very sensitive marker of tissue pathology. DESIGN: In the present study, the analysis of expression of genes coding kininogen, B1 and B2 was performed. The relation between the analysed genes expression and the pathology stage was analysed. MATERIALS AND METHODS: The specimens from condylomata accuminata, vulvar cancer and surgical margin were analysed. The number of DNA and mRNA copies of beta-actine, kininogen, B1 and B2 were examined basing on Q-PCR standard curves for beta-actine by use of Perkin Elmer-kit and the sequence detector ABI PRISM 7700-Taq Man application. RESULTS: In condylomata accuminata the high expression of mRNA of kininogen, B1 and B2 was found, while in vulvar cancer tissue, the expression of analysed genes was low. In the tissue from the tumour center, the lowest kinin genes expression was stated. CONCLUSIONS: The absence of kininogen and B2 mRNA expression characterised vulvar cancer tissue. The profile of expression of kininogen and its receptor genes can be a useful marker in the assessment of vulvar cancer surgical margin.

[The quantitative analysis of E6 HPV and P53 genes expression by QPCR (TaqMan) in the assessment of surgical treatment range in vulvar carcinoma induced by HTV infection]. / Ilosciowa analiza ekspresji genów E6 HPV 18 i P53 metoda QPCR (TaqMan) w ocenie marginesu operacyjnego w raku sromu indukowanym infekcja HPV.

OBJECTIVES: Human Papilloma Virus (HPV) infections especially 16 and 18 are risk factors for squamous cell vulvar cancer. E6 protein of HPV joins the tumor suppressor protein P53 and promotes its degradation. This is one of the possible mechanisms of viral oncogenes action. DESIGN: In this study the quantitative analysis of mRNA copies E6 HPV 18 and mRNA P53 expression in vulvar cancer tissue was performed. The expression of analysed genes was applied in the assessment of surgical treatment range. MATERIALS AND METHODS: The specimens from a 26 year old woman with vulvar squamous cell cancer stage II FIGO treated surgically modo Way were analysed. The number of DNA and mRNA copies E6 HPV and P53 were examined basing on Q-PCR standard curves for beta-actine by use of Perkin Elmer-kit and the sequence detector ABI PRISM 7700-Taq Man application. RESULTS: The overexpression of mRNA E6 HPV and P53 in analysed specimens was found. The highest number of mRNA copies in cancer tissue was ascertained. In lichen sclerosus and lymphonoduli tissue lower number of analysed copies was found. CONCLUSION: The quantitative analysis of E6 HPV and P53 genes expression can be useful in the assessment of surgical treatment range in vulvar cancer and can also be used as a prognostic marker.

Quantitative RT-PCR assay for mRNA of VEGF and histone H4 in the determination of proliferative and angiogenic activity in vulvar pathology.

Proliferative and angiogenic activity of tissue specimens taken from women with various vulvar pathologies were evaluated by determining the number of mRNA VEGF molecules and H4 histone mRNA molecules, by means of the QRT-PCR (TaqMan) technique. Following a cluster analysis the results, where normalised. Euclidean distances were used, all the cases were classified into three groups of pathologies. Group I included low degree vulvar pathologies, group II included high degree vulvar pathologies and group III included vulvar pathologies with high proliferative and angiogenic activity. Significant differences were found in the proliferative and angiogenic activity between groups I and III, and between groups II and III, while no statistically significant differences were found between groups I and II.

Expression of telomerase genes as potential marker of neoplastic changes.

We conducted a quantitative analysis of TERT, TP1 and hTR mRNA expression in various types of endometrial hyperplasia in perimenopausal women, taking advantage of the real-time PCR assay. All women underwent hysterectomy for gynecological reasons. Endometrial dating was determined from the patomorphology of the endometrium and classified into endometrial hyperplasia: simplex, complex and atypica. Our data suggest that only hTR was observed in each normal and hyperplastic endometrium specimens, suggesting that this factor constitutively expressed in endometrium. The results obtained indicate that the expression activity of the TERT subunit changes but not significantly, depending on the stage of development of the hyperplasia.

[Concentration of oxidized cholesterol forms in normal and gestational diabetic pregnancy]. / Stezenie utlenowanych pochodnych cholesterolu u kobiet ciezarnych z cukrzyca ciazowa.

OBJECTIVES: The aim of our study was to examine, if gestational diabetes mellitus had influence on cholesterol oxidation processes. MATERIAL AND METHODS: Examined patients were divided into two groups: 35 patients with gestational diabetes mellitus and 24 health pregnant women. Oxycholesterols were estimated by thin layer chromatography. RESULTS: Among substances examined in our study we stated considerable levels of 5 alpha,6 alpha-epoxycholesterol and 5 beta,6 beta-epoxycholesterol: average 3.28 micrograms/ml for pregnant women with gestational diabetes mellitus and 4.03 micrograms/ml for control group. Besides we obtained statistically important increase of 7-hydroxycholesterols concentration and epoxycholesterols sum level at third trimester of pregnancy in comparison with values for the second trimester. CONCLUSIONS: Obtained results suggest that in pregnancy cholesterol oxidation processes are intensified, especially at the third trimester. The authors thing, that oxycholesterols can be valuable supplement examined biochemical markers at different states of pregnant pathology.

[Influence of tobacco smoking on the sum epoxycholesterols levels in serum of pregnant women with diabetes]. / Wplyw palenia tytoniu na poziom sumy epoksycholesteroli w surowicy kobiet ciezarnych z cukrzyca.

OBJECTIVES: The aim of our study was to estimate concentration of epoxycholesterols sum (5 alpha,6 alpha and 5 beta,6 beta) in groups of pregnant women with diabetes mellitus and/or PIH, who had been exposed to tobacco smoke. MATERIAL AND METHODS: Examined patients were divided into the following groups: 35 patients with gestational diabetes, 25 patients with diabetes mellitus, 17 patients with gestational diabetes coexisting with PIH. The control group consist with 24 health pregnant women. Epoxycholesterols were estimated by thin layer chromatography. RESULTS: We stated exact relationship between sum of epoxycholesterols and degree of exposition to tobacco smoke in group of patients with diabetes mellitus and gestational diabetes mellitus. In group of pregnant women with gestational diabetes mellitus coexisting with PIH we didn't find statistically important differences in concentrations of examined value, although it was on permanently high level. CONCLUSIONS: The authors concluded, that free oxygen radicals enclosed in tobacco smoke catalyzed processes of cholesterol oxygenation in pregnant women bodies. Besides we stated, that increased levels of epoxycholesterols cold be one of the factors responsible for PIH. Our results indicate to need of further studies possible part of oxycholesterols in prenatal pathology.

[Expression of VEGF, KDR, p53, E6 HPV16 and HPV18 in vulvar and cervix cancer]. / Ekspresja genów angiogenezy--VEGF i jego receptora KDR, genu supresorowego P53 oraz E6 HPV16 i HPV18 w raku sromu i szyjki macicy.

The aim of the study was a comparison of expression of angiogenesis genes: vascular endothelial growth factor (VEGF), KDR, suppressor gene p53, E6-HPV16 and HPV18, in tissue samples of normal, dystrophic, lymph nodes and malignant cancers of vulva and uterine cervix. The results demonstrate that molecular diagnostics of cancers using gene expression profiling indicates the definitive difference in expression profiles of aforementioned genes in tissues of the same malignancy.

[Profiles of expression of genes coding kininogen and kinin receptors as a marker of tissue pathology in cervical cancer coexisting with HPV infection]. / Ekspresja genów receptorów dla kinin i kininogenu w raku szyjki macicy wspólistniejacym z infekcja HPV.

Kinins are peptides involved in inflammatory processes, vascular permeability, proliferation and mitogenesis of tumor cells. The majority of kinins actions are mediated through an interaction with cell surface bradykinin receptors BR1 and BR2. Kinins precursor is kininogen (kng). The changes in proteins are initiated by changes in the expression of genes coding these proteins, thus can be a valuable diagnostic markers of malignant processes including cervical carcinoma. The paper presents an analysis of kininogen-kinins receptor genes expression in women treated surgically because of a carcinoma of uterine cervix. Among the studied women in 5 cases previously brachyHDR therapy was applied. In all studied cases HPV 18 infection and in 2 cases a co-infection HPV 16/18 by use of Consensus Primers MY09, MY 11 and type specific primers for HPV 16, 18 was ascertained. In RNA extracts the number of the mRNA copies for kiningen, BR1 and BR2 was assessed using QRT-PCR Taq Man. The higher expression of BR1 than BR2 was marked in the tissue with cancer cells. In the patients after brachytherapy higher expression of BR2 than BR1 mRNA was found. The higher BR1 expression was also shown in iliac lymph nodes in patients with active neoplastic process, opposite to the patients after brachytherapy in whom higher BR2 expression was ascertained. The lack of expression of kng mRNA was found only in 3 specimens. The high expression of kinin receptors especially BR1 in infiltrating carcinoma margin can be a marker of pathology intensity: proliferative potential of neoplasms cells or chronic inflammatory state in the presence of invasive carcinoma.

[The results of prenatal treatment of fetal hemolytic disease in clinic material]. / Wyniki opieki perinatalnej nad ciezarna z konfliktem serologicznym w materiale klinicznym.

Authors analysed results of prenatal treatment of 68 cases of fetal haemolytic disease in the Department of Obstetrics and Gynaecology in Bytom in the years 1994-1999. We evaluated a clinic value of umbilical vessels punctures and intrauterine intra-vessel transfusions as a basic methods of treatment of this disease. In the analysis we took into consideration frequency of complications, character of complications and condition of neonates. The most important in the treatment of fetal haemolytic disease are early diagnostics and treatment procedures performed in the appropriate prepared Centres.