Je li moguće očuvanje plodnosti kod bolesnica s ginekološkim rakom?

The aim of this review article is to present current options for fertility preservation in young women with gynecological tumors (ovarian, endometrial or cervical cancer). An early pretreatment referral to multidisciplinary team which consists of general gynecologists, gynecologic oncologists, embryologists, radiologists, pathologists, and reproductive endocrinologists should be suggested to young women with gynecologic cancer, concerning the risks and benefits of fertility preservation options. Only a small percentage of patients with ovarian cancer and borderline ovarian tumors, are appropriate candidates for fertility preservation (FIGO stage IA and IC epithelial ovarian cancer). Following oophorectomy, ovarian tissue or oocytes are removed from the ovary for the use of cryopreservation; after completion of oncological treatment patient undergoes orthotopic retransplantation of ovarian tissue whereas oocytes may be used for in vitro fertilization. Live birth rates up to 53.8% have been reported after fertility preservation treatment in selected patients. In patients with endometrial cancer fertility preservation treatment means conserving of the uterus. Appropriate candidates for fertility preservation are younger women with well differentiated endometrial cancer, which does not invade the myometrium. Fertility preservation treatment in endometrial cancer is hormonal, based on progestins. After completion of fertility preservation treatment, frequent follow-ups are necessary, with tissue sampling (via curettage or endometrial biopsy) remaining standard approach in follow- up. Live birth rates after progestin therapy are around 60%, or even higher with the help of assisted reproductive procedures. In cervical cancer, fertility preservation treatment can be considered in women with early-stage disease (FIGO IA1, IA2, or IB1). Cone biopsy or conization followed by laparoscopic lymphadenectomy has been described as an appropriate procedure, with conception rates up to 47%.Cilj ovog preglednog rada je prikazati suvremene mogućnosti očuvanja plodnosti kod mladih žena s ginekološkim tumorima (rakom jajnika, trupa maternice ili vrata maternice). S obzirom na rizike i koristi metoda za očuvanje plodnosti, preporuča se bolesnicu prijeterapijski prezentirati na multidisciplinarnom timu koji uključuje ginekologa, ginekološkog onkologa, embriologa, radiologa, patologa i reprodukcijskog endokrinologa. Samo je mali udio bolesnica s epitelnim rakom jajnika ili granično malignim tumorom janika prikladan za očuvanje plodnosti (FIGO IA I IC). Nakon operacijskog uklanjanja jajnika, tkivo jajnika ili jajne stanice se krioprezervaju; nakon završetka onkološkog liječenja obično slijedi ortotopična retransplantacija ovarijskog tkiva bolesnici, dok se jajne stanice mogu koristiti u postupku izvantjelesne oplodnje. Nakon liječenja uz očuvanje plodnosti kod odabranih bolesnica rakom jajnika stopa živorođenih kretala se do 53,8%. Kod bolesnica s rakom endometrija očuvanje plodnosti podrazumijeva očuvanje maternice. Bolesnice pogodne za očuvanje plodnosti su mlađe žene sa dobro diferenciranim tumorom koji ne prodire u miometrij. Za očuvanje plodnosti kod raka endometrija primjenjuje se hormonsko liječenje, utemeljeno na gestagenima, koji stabiliziraju i zaustavljaju nekontroliranu estrogensku stimulaciju endometrija. Po završetku liječenja potrebni su učestali kontrolni pregledi, a uzimanje tkiva sluznice (kiretaža ili biopsija endometrija) predstavljaju standard u praćenju ovih bolesnica. Nakon liječenja gestagenima stopa živorođenih kreće se oko 60% ili čak više kod primjene postupaka potpomognute oplodnje. Očuvanje plodnosti kod karcinoma vrata maternice moguće je kod strogo odabrane skupine bolesnica (FIGO IA1, IA2 ili IB1) motiviranih za trudnoću; kod tih bolesnica konizacija ili biopsija konizata u kombinaciji s laparoskopskom limfadenektomijom predstavlja najprikladniji zahvat sa stopom trudnoća do 47%

PSYCHIATRIC DISORDERS AND DRY EYE DISEASE - A TRANSDISCIPLINARY APPROACH

Dry eye disease (DED) is a multifactorial disorder representing one of the most common ocular morbidities and a significant public health problem. It often results in eye discomfort, visual disturbances and potential damage to the corneal surface affecting quality of life (QOL). In recent years, the relationship between DED and psychiatric disorders has been gaining attention. A number of epidemiological studies have reported a possible association between dry eye and psychiatric disorders showing that the subjective symptoms of dry eye can be affected not only by changes of the tear film and ocular surface but also psychological factors such as anxiety, depression, schizophrenia, post-traumatic stress disorder (PTSP) and subjective happiness. Apart from psychiatric disorders, psychiatric medications are also considered as risk factors for DED due to their influence on the tear film status. The incidence of ocular side effects increases rapidly with the use of polypharmacy, a very common form of treatment used in psychiatry. There is often inconsistency between signs and symptoms of DED, where symptoms often are more related to non-ocular conditions including psychiatric disorders than to tear film parameters. Consequently, in many cases DED may be considered as a psychiatric as well as ophthalmological problem. Psychiatrists and ophthalmologists need to be aware of the potential influence of psychiatric disorders and medications on tear film stability. In treatment of psychiatric patients, an integrative and transdisciplinary approach will result in better functioning and higher QOL

Očuvanje plodnosti u mladih žena s ranim rakom dojke

Although breast cancer (BC) occurs more often in older women, it is the most commonly diagnosed malignancy in women of childbearing age. Owing to the overall advancement of modern medicine and the growing global trend of delaying childbirth until later age, we find ever more younger women diagnosed and treated for BC who have not yet completed their family. Therefore, fertility preservation has emerged as a very important quality of life issue for young BC survivors. This paper reviews currently available options for fertility preservation in young women with earlystage BC and highlights the importance of a multidisciplinary approach to fertility preservation as a very important quality of life issue for young BC survivors. Pregnancy after BC treatment is considered not to be associated with an increased risk of BC recurrence; therefore, it should not be discouraged for those women who want to achieve pregnancy after oncologic treatment. Currently, it is recommended to delay pregnancy for at least 2 years after BC diagnosis, when the risk of recurrence is highest. However, BC patients of reproductive age should be informed about the potential negative effects of oncologic therapy on fertility, as well as on the fertility preservation options available, and if interested in fertility preservation, they should be promptly referred to a reproductive specialist. Early referral to a reproductive specialist is an important factor that increases the likelihood of successful fertility preservation. Embryo and mature oocyte cryopreservation are currently the only established fertility preservation methods but they require ovarian stimulation (OS), which delays initiation of chemotherapy for at least 2 weeks. Controlled OS does not seem to increase the risk of BC recurrence. Other fertility preservation methods (ovarian tissue cryopreservation, cryopreservation of immature oocytes and ovarian suppression with gonadotropin-releasing hormone agonists) do not require OS but are still considered to be experimental techniques for fertility preservation.Premda se karcinom dojke češće javlja u starijoj životnoj dobi, to je i najučestaliji malignitet u žena reproduktivne dobi. Zbog sveukupnog napretka moderne medicine i rastućeg globalnog trenda odgađanja rađanja djece za kasniju dob suočavamo se sa sve više mladih žena s dijagnosticiranim i liječenim karcinomom dojke koje još nisu kompletirale obitelj. Stoga je područje očuvanja plodnosti postalo jako bitno u očuvanju kvalitete života mladih žena koje su preboljele karcinom dojke. Ovaj rad iznosi trenutno dostupne metode za očuvanje plodnosti u mladih žena s ranim karcinomom dojke i ističe važnost multidisciplinarnog pristupa u očuvanju plodnosti kao bitnog čimbenika kvalitete života tih žena. Smatra se da trudnoća nakon karcinoma dojke nije povezana s povišenim rizikom od recidiva pa stoga ne treba obeshrabriti žene koje žele ostvariti trudnoću nakon provedenog onkološkog liječenja. Danas se preporuča pričekati s trudnoćom barem 2 godine nakon postavljene dijagnoze za vrijeme kada je rizik od povrata bolesti najveći. No, isto tako bi bolesnice reproduktivne dobi trebalo obavijestiti o mogućem negativnom učinku onkološke terapije na plodnost te o dostupnim metodama očuvanja plodnosti i u slučaju zainteresiranosti za očuvanje plodnosti bolesnice treba žurno uputiti reproduktivnom specijalistu. Rano upućivanje reproduktivnom specijalistu je bitan čimbenik koji povećava izglede za uspješno očuvanje plodnosti. Krioprezervacija embrija i zrelih oocita su trenutno jedine standardne metode očuvanja plodnosti koje zahtijevaju stimulaciju ovarija kojom se odgađa početak kemoterapijskog liječenja barem 2 tjedna. Smatra se da kontrolirana stimulacija ovarija ne povećava rizik od povrata karcinoma dojke. Druge metode očuvanja plodnosti (krioprezervacija tkiva jajnika, krioprezervacija nezrelih oocita, ovarijska supresija GnRH agonistima) ne zahtijevaju primjenu ovarijske stimulacije, ali se i dalje smatraju eksperimentalnim metodama za očuvanje plodnosti

Inflammatory and angiogenic biomarkers in diabetic retinopathy

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus (DM) and a leading cause of blindness in working- age adults in developed countries. Numerous investigations have recognised inflammation and angiogenesis as important factors in the development of this complication of diabetes. Current methods of DR treatment are predominantly used at advanced stages of the disease and could be associated with serious side effects. Therefore, new diagnostic methods are needed in order to identify the initial stages of DR as well as monitoring the effects of applied therapy. Biochemical biomarkers are molecules found in blood or other biological fluid and tissue that indicate the existence of an abnormal condition or disease. They could be a valuable tool in detecting early stages of DR, identifying patients most susceptible to retinopathy progression and monitoring treatment outcomes. Biomarkers related to DR can be measured in the blood, retina, vitreous, aqueous humour and recently in tears. As the retina represents a small part of total body mass, a circulating biomarker for DR needs to be highly specific. Local biomarkers are more reliable as indicators of the retinal pathology; however, obtaining a sample of aqueous humour, vitreous or retina is an invasive procedure with potential serious complications. As a non-invasive novel method, tear analysis offers a promising direction in further research for DR biomarker detection. The aim of this paper is to review systemic and local inflammatory and angiogenic biomarkers relevant to this sight threatening diabetic complication

The influence of body position on cerebrospinal fluid pressure gradient and movement in cats with normal and impaired craniospinal communication

Intracranial hypertension is a severe therapeutic problem, as there is insufficient knowledge about the physiology of cerebrospinal fluid (CSF) pressure. In this paper a new CSF pressure regulation hypothesis is proposed. According to this hypothesis, the CSF pressure depends on the laws of fluid mechanics and on the anatomical characteristics inside the cranial and spinal space, and not, as is today generally believed, on CSF secretion, circulation and absorption. The volume and pressure changes in the newly developed CSF model, which by its anatomical dimensions and basic biophysical features imitates the craniospinal system in cats, are compared to those obtained on cats with and without the blockade of craniospinal communication in different body positions. During verticalization, a long-lasting occurrence of negative CSF pressure inside the cranium in animals with normal cranio-spinal communication was observed. CSF pressure gradients change depending on the body position, but those gradients do not enable unidirectional CSF circulation from the hypothetical site of secretion to the site of absorption in any of them. Thus, our results indicate the existence of new physiological/pathophysiological correlations between intracranial fluids, which opens up the possibility of new therapeutic approaches to intracranial hypertension

Melanom srednje očne ovojnice: kliničke osobitosti i dijagnostičke metode

Uveal melanoma is the most common primary intraocular malignancy in adults and the eye is the second most common site for primary melanoma after the skin. Early recognition is important in protecting visual acuity, saving the eye and preventing metastasis. Signs for early detection of uveal melanoma when it simulates a nevus include thickness >2 mm, presence of subretinal fluid, symptoms, orange pigment, margin of the tumour near the optic disc, acoustic hollowness, surrounding halo, and the absence of drusen. This is essential considering that each millimetre increase in melanoma thickness imparts a 5% increased risk for metastatic disease. Delays or inability to make an accurate and early diagnosis may have grave consequences. Methods of diagnosis have substantially improved, although clinical diagnosis remains the standard method in the eyes with clear media. In eyes with opaque media ultrasound is the most useful ancillary diagnostic technique. Newer imaging modalities such as optical coherence tomography and fundus autofl ouroscence facilitate in detection of subretinal fluid and orange pigment. Additional molecular biomarkers and cytological features which can predict the clinical behaviour of a small melanocytic lesion have been identifi ed. Although the role of a good clinical evaluation cannot be underestimated, it is advisable to assess the various radiological, molecular and cytological features in order to enhance the accuracy of early diagnosis and improvement in the patients’ prognosis.Melanom srednje očne ovojnice najčešća je primarna zloćudna bolest oka u osoba odrasle dobi, a oko je drugo po učestalosti najčešće sijelo primarnog melanoma nakon kože. Kasna ili pogrešno postavljena dijagnoza može imati ozbiljne posljedice. Rano otkrivanje melanoma srednje očne ovojnice ključno je u prevenciji gubitka vidne oštrine, spašavanju oka i sprečavanju razvoja metastaza. Čimbenici koji omogućuju rano otkrivanje malih melanoma srednje očne ovojnice koji se mogu zamijeniti s nevusom su debljina tumora > 2 mm, prisutnost subretinalne tekućine, nazočnost simptoma, narančasti pigment, rub tumora u blizini optičkog diska, određene ultrazvučne karakteristike tumora te odsutnost druza. Rano otkrivanje tumora je vrlo važno obzirom da povećanje debljine melanoma za 1 mm povećava rizik metastatske bolest za 5%. Dijagnostičke metode posljednjih su godina znatno unaprijeđene, no klinička dijagnoza i dalje ostaje standardna metoda kod očiju s prozirnim optičkim medijima. Ultrazvuk predstavlja najkorisniju pomoćnu dijagnostičku metodu, osobito u slučaju zamućenja optičkih medija oka. Novije dijagnostičke metode poput optičke koherentne tomografije i autoflouroscencije fundusa olakšavaju otkrivanje subretinalne tekućine i narančastog pigmenta. Također postoje određeni molekularni biomarkeri i citološke značajke tumorskih stanica koje mogu pomoći u predviđanju kliničkog ponašanja male melanocitne lezije. Iako je uloga dobre kliničke procjene važna i ne smije se podcijeniti, preporuča se i primjena dodatnih dijagnostičkih metoda, te određivanje molekularnih i citoloških značajki tumorskih stanica kako bi se omogućila točna rana dijagnoza i time poboljšala prognoza bolesnika

Melanom srednje očne ovojnice: kliničke osobitosti i dijagnostičke metode

Uveal melanoma is the most common primary intraocular malignancy in adults and the eye is the second most common site for primary melanoma after the skin. Early recognition is important in protecting visual acuity, saving the eye and preventing metastasis. Signs for early detection of uveal melanoma when it simulates a nevus include thickness >2 mm, presence of subretinal fluid, symptoms, orange pigment, margin of the tumour near the optic disc, acoustic hollowness, surrounding halo, and the absence of drusen. This is essential considering that each millimetre increase in melanoma thickness imparts a 5% increased risk for metastatic disease. Delays or inability to make an accurate and early diagnosis may have grave consequences. Methods of diagnosis have substantially improved, although clinical diagnosis remains the standard method in the eyes with clear media. In eyes with opaque media ultrasound is the most useful ancillary diagnostic technique. Newer imaging modalities such as optical coherence tomography and fundus autofl ouroscence facilitate in detection of subretinal fluid and orange pigment. Additional molecular biomarkers and cytological features which can predict the clinical behaviour of a small melanocytic lesion have been identifi ed. Although the role of a good clinical evaluation cannot be underestimated, it is advisable to assess the various radiological, molecular and cytological features in order to enhance the accuracy of early diagnosis and improvement in the patients’ prognosis.Melanom srednje očne ovojnice najčešća je primarna zloćudna bolest oka u osoba odrasle dobi, a oko je drugo po učestalosti najčešće sijelo primarnog melanoma nakon kože. Kasna ili pogrešno postavljena dijagnoza može imati ozbiljne posljedice. Rano otkrivanje melanoma srednje očne ovojnice ključno je u prevenciji gubitka vidne oštrine, spašavanju oka i sprečavanju razvoja metastaza. Čimbenici koji omogućuju rano otkrivanje malih melanoma srednje očne ovojnice koji se mogu zamijeniti s nevusom su debljina tumora > 2 mm, prisutnost subretinalne tekućine, nazočnost simptoma, narančasti pigment, rub tumora u blizini optičkog diska, određene ultrazvučne karakteristike tumora te odsutnost druza. Rano otkrivanje tumora je vrlo važno obzirom da povećanje debljine melanoma za 1 mm povećava rizik metastatske bolest za 5%. Dijagnostičke metode posljednjih su godina znatno unaprijeđene, no klinička dijagnoza i dalje ostaje standardna metoda kod očiju s prozirnim optičkim medijima. Ultrazvuk predstavlja najkorisniju pomoćnu dijagnostičku metodu, osobito u slučaju zamućenja optičkih medija oka. Novije dijagnostičke metode poput optičke koherentne tomografije i autoflouroscencije fundusa olakšavaju otkrivanje subretinalne tekućine i narančastog pigmenta. Također postoje određeni molekularni biomarkeri i citološke značajke tumorskih stanica koje mogu pomoći u predviđanju kliničkog ponašanja male melanocitne lezije. Iako je uloga dobre kliničke procjene važna i ne smije se podcijeniti, preporuča se i primjena dodatnih dijagnostičkih metoda, te određivanje molekularnih i citoloških značajki tumorskih stanica kako bi se omogućila točna rana dijagnoza i time poboljšala prognoza bolesnika

Liquid-based cytology - new possibilities in the diagnosis of cervical lesions [Tekuća citologija - nove mogućnosti u dijagnostici lezija vrata maternice]

Liquid-based cytology (LBC) enables the use of supplementary methods in the diagnosis and prognosis of cervical lesions. The aim of this study was to analyze the correlation between p16INK4a immunoexpression in ThinPrep cervical cytologic samples and human papillomavirus (HPV) detection by polymerase chain reaction (PCR) from the same sample. LBC-ThinPrep (Cytyc, USA) cervical cytology samples, prepared and stained by Papanicolaou method, were analyzed using modified Bethesda cytologic classification named »Zagreb 2002«. A second ThinPrep slide, prepared from the same sample, was immunostained for p16INK4a using CINtec p16INK4a Cytology Kit (DakoCytomation, Denmark). Increased expression of the high-risk (HR) HPV E6 and E7 oncogenes results in a highly specific increase in p16 protein expression and overexpression of p16INK4a acts as a potential biomarker for cervical cancer progression from premalignant lesions. Brown nuclear and/or cytoplasmic staining of abnormal cells was considered a positive result. Residual material was used for 13 HR HPV-DNA detection by the PCR based AMPLICOR HPV test (Roche Molecular Systems). A total of 120 ThinPrep Pap tests with the following cytologic diagnoses: 17 within normal limits, 17 atypical squamous cell (ASC) (7 ASC of undetermined significance /ASCUS/ and 10 ASC of high-grade squamous intraepithelial lesions cannot be excluded /ASC-H/), 26 low-grade squamous intraepithelial lesions (LSIL) corresponding cervical intraepithelial neoplasia (CIN) I, 57 high-grade SIL (HSIL) i.e. 24 CIN II and 33 CIN III and 3 squamous cell carcinoma (SCC) were included in the study. All CIN III (n=33) and SCC (n=3) specimens expressed p16INK4a immunoreactivity, whereas the HR HPV test was positive in 97% (32/33) of CIN III and 100% (3/3) of SCC specimens. The p16INK4a biomarker was positive in 87.5% (21/24) of CIN II and 69% (18/26) of CIN I, while the HR HPV was positive in 75% (18/24) of CIN II and 50% (13/26) of CIN I. In ASCUS cytology, p16INK4a and HR HPV showed the same rate of positivity (28.5%; 2/7). Expression of p16INK4a was detected in all cytologic (10/10) ASC-H lesions, in contrast to HR HPV detected in only 20% (2/10) of ASC-H cases. These data suggest the p16INK4a evaluation in ThinPrep cervical samples to be significantly associated with HR HPV testing by PCR in the same sample for the diagnosis of HSIL lesions and cervical carcinomas. A prospective study with longer follow up may clarify the predictive values in the management of LSIL and ASC diagnosis

Mining for the data about glycosylation in the bovines-the analysis of the recently published studies

potential for improvement regarding reproduction, herd health management, and the quality and safety of milk and meat products. The PubMed database was searched for “glycosylation” and “B. taurus” using the following filters: full text available, the publication date of five years, and the preprints excluded. The search retrieved 244 results, and after the content analysis by the authors, 88 remained relevant. All publications were Research Articles except one Review. The assessment of the glycan profile composition was among the aims in 34, the functional aspects in 33, and the protein glycoforms in 12 studies. Ten studies brought data about the total glycome profile of the milk, tissue, or meat sample, while the other contained glycosylation-related features of the individual protein(s). Most often, the studies used milk (25), individual proteins (23), or tissue (20 studies) as the samples. Usually, the milk was material to analyze the glycosylation of casein, immunoglobulin G, or the total glycans. The studies involving the individual proteins most frequently analyzed fetuin, and the glycosylation of submaxillary gland mucin was the target in the studies using tissue samples. These pioneer data mining results allow for the conclusion on the availability of reliable data about glycosylation in the bovines, eligible as the starting point for further scientific efforts on their continuous appending, systematization, and multidisciplinary analyses.Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 202

MoCA test and general anesthesia for a two different surgical techniques

Introduction Postoperative cognitive dysfunction (POCD) is defined as a new cognitive impairment shown after operation. Many factors may contribute to POCD and has potentially two different patterns: acute cognitive dysfunction, known as postoperative delirium and a later onset and more per- sistent POCD. The reported incidence vary depending on the group of patients studied, the test used, the time of testing and the choice of control group. POCD can only be diagnosed and measured using tests both pre- and postoperative. In our research we use Montreal Cognitive Assessment (MoCA) test. It is a widely used screening assessment for detecting cognitive impairment. Materials and Methods The prospective study included 30 patients who were treated at the University Hospital Centre Zagreb. They were anaesthetized for radical prostatectomy using the TIVA technique and divided into two groups: 19 patients who underwent classical surgery and 11 patients who underwent laparoscopic surgery. The MoCA test was analysed pre-operatively and 48 hours after surgery. Parametric tests were not used due to deviations of individual distributions from normal, as determined by Shapiro-Wilk tests (p <, 05) and due to the small number of participants. Precise p-values were calculated, except for the Spearman correlation coefficient, which does not use them. Two-way tests and an alpha value of 5% were used. Results Patients who underwent laparoscopic prostatectomy did not have statistically significantly different MoCA test results before surgery than those who underwent classical prostatec- tomy (U = 59.9, z = 1.96, p = .052). After the operation, patients undergoing laparoscopic prostatec- tomy achieved statistically significantly higher results (U = 46.0, z = 2.54, p = .011), with a moderate effect (r = .463). The results of the MoCA test were statistically significantly higher after surgery than before surgery (W = 346.5, z = -3.81, p <.001; not in the table), with a strong effect size (r = .696). The amount of improvement in MoCA test results was not statistically significantly different for lapa- roscopic and classical prostatectomy (U = 78.0, z = 1.16, p = .268). Conclusion Postoperative values of the MoCA test are higher than the preoperative in both groups- laparoscopic and classical prosta- tectomy. The results of the research can be explained by the fact that anxiety and concern about the upcoming operation affect the results of the examination pre-operatively. Other observed parameters did not affect the MoCA test results