Ulcerozni kolitis (UC) je kronična bolest multifaktorske etiologije čiji detaljan mehanizam imunološkog procesa još nije sasvim razjašnjen, ali ključnu ulogu svakako imaju granulociti i ...monociti/makrofazi koji reguliraju i pojačavaju upalni proces lučenjem proupalnih citokina. Leukocitofereza (LCAP) je terapijski postupak kojim se prolaskom krvi kroz sustav za aferezu odstranjuju limfociti i plazma prije nego što se krv ponovno vrati u krvotok. U ovom radu je prikazan o steroidima ovisan bolesnik s teškim relapsom UC-a koji je, prvi put u Hrvatskoj, liječen protokolom LCAP. Nakon 12 terapijskih protokola LCAP kod bolesnika je došlo do značajnog kliničkog poboljšanja bez razvo-ja nuspojava. Bolesnik je ostao u kliničkoj remisiji tijekom dvije godine ambulantnog praćenja, a unutar 10 godina praćenja nakon LCAP bolesnik je imao tek povremene simptome aktivnosti bolesti. Klinički tijek bio je kompliciran razvojem metastatskog karcinoma debelog crijeva, što prvenstveno upućuje na važnost redovitog praćenja bolesti, a ne na povećan rizik maligne bolesti nakon LCAP. Bolesnici s UC-om su zahtjevna skupina pacijenata koja zahti-jeva potragu za novim terapijskim strategijama osim onih konvencionalnih farmakoloških. Iako LCAP nije čest modalitet liječenja u svakodnevnoj kliničkoj praksi, novije studije upućuju na to da je postupak učinkovit i siguran u liječenju bolesnika s aktivnim UC-om.
The objective of the Zagreb 2016 classification as the third modification of the unique classification of cervical cytology findings based on the previous Zagreb 2002 and the latest Bethesda 2014 ...classifications is standardization of cervical cytology findings for the whole Croatia, according to the latest concepts on the biologic behavior of cervical cancer and its precursors. Besides cytomorphological lesions, Zagreb 2016 includes recommendations for diagnostic therapeutic procedures in line with the international recommendations and the experience of Croatian cytologists and gynecologists. It was presented and accepted by Croatian clinical cytologists at the Croatian Society of Clinical Cytology Convention held on December 12, 2016 in Zagreb. The main modifications relative to the Zagreb 2002 classification refer to the following: classification of ‘koilocytosis’, i.e. cytomorphological lesions associated with human papillomavirus, into the category of low-grade squamous intraepithelial lesions (LSIL); classification of ‘atypical glandular cells – probably reactive lesions’ into the category of non-neoplastic lesions; and the introduction of ‘atypical glandular cells – not othervise specified’ (AGC-NOS) into the category of abnormal glandular cells. In addition, the finding of endometrial cells in women aged ≥45 and absence of the transformation zone elements is highlighted.
Treća modifi kacija jedinstvene klasifikacije citoloških nalaza vrata maternice „Zagreb 2016“ temeljena je na ranijoj „Zagreb 2002“ i najnovijoj „Bethesda 2014“ klasifikaciji, a u cilju ...standardizacije citoloških nalaza vrata maternice za cijelu Hrvatsku, prema najnovijim spoznajama o biološkom ponašanju raka vrata maternice i njegovih predstadija. „Zagreb 2016“ uključuje uz citomorfološke promjene i preporuke za dijagnostičko-terapijske postupke prema svjetskim preporukama kao i iskustvu citologa i ginekologa u Hrvatskoj, a predstavljena je i prihvaćena od kliničkih citologa Hrvatske 12. prosinca 2016. g. u Zagrebu na Stručnom sastanku Hrvatskog društva za kliničku citologiju. Glavne izmjene u odnosu na „Zagreb 2002“ odnose se na klasificiranje „koilocitoze“ odnosno citomorfoloških promjena povezanih s humanim papiloma viruom (HPV) u kategoriju skvamozne intraepitelne lezje niskog stupnja (LSIL), klasificiranje „atipičnih glandularnih stanica – vjerojatno reaktivne promjene“ u kategoriju ne-neoplastičnih promjena te uvođenje nalaza “atipične glandularne stanice – nespecificirane“ (AGC–NOS) u kategoriju abnormalnih glandularnih stanica. Osim toga, u klasifikaciji „Zagreb 2016“ poseban naglasak se daje i na nalaz endometralnih stanica kod žena nakon ≥45g., kao i na odsutnost elemenata transformacijske zone.
The first organized national cytology screening program for detecting cervical lesions in Croatia was initiated at the end of 2012. This screening program is currently under review. The working ...proposal is to screen women aged 20–29 by cytology alone, those aged 30–34 by cytology and hrHPV cotesting, and woman 35–64 years old by high risk Human papillomavirus (hrHPV testing) without cytology cotesting. The objective is to contribute to the selection of cervical screening options among various possibilities in our population. Methods: We conducted a retrospective analysis of preceding cervicovaginal cytology and hrHPV test results in biopsy proven HSIL between January 1, 2016 and December 31, 2016. This included 143 HSIL cases from patients aged 18–85. Results: In detecting HSIL Pap test has been abnormal in 99% (142/143), and hrHPV test in 80% (115/143). The cytology, analyzed within one year prior to the HSIL biopsy, has reported ASC-H/HSIL in 87% (125/143) cases, whereas 12% (17/143) and 0.7% (1/143) have reported ASC-US/LSIL and negative respectively. The hrHPV negative test has been found in 13% (5/39) of the 20–29 age group, 21% (7/33) of the 30–34 age group, and 22% (15/68) of the 35–65 age group. Conclusions: Our data suggest that approximately 22% of analyzed woman in the 35–64 age group may be misdiagnosed for HSIL, when using HPV testing as the only cervical screening method. The widespread replacement of cytology by hrHPV testing should be subject to further investigation and given careful consideration.
Adenoid cystic carcinoma is a rare malignancy, usually found in the salivary glands, although this unusual tumor can be found at other sites of the body. In particular, regarding adenoid cystic ...carcinoma of the cervix (ACCC) most frequently reports are given for postmenopausal women. In this respect, our work is one among very few in the literature that considers a cytologic picture of this uncommon cervix carcinoma. The case of 74 year old patient with postmenopausal bleeding is described. Both Pap smear and air dried smear of the uterine cervix were analyzed. The cytologic findings revealed very few small clusters of abnormal glandular cells, as well as some amorphous eosinophilic globule-like material, with granulomatous and necrotic background. The latter includes a lot of histiocytes, multinucleated giant cells, large aggregates of epitheloid cells and lymphocytes. Histology revealed the diagnosis of ACCC. We emphasize the importance of careful screening of Pap smear that might be crucial in the case of suspicious clinical findings in postmenopausal women, when the possibility of ACCC has to be considered.
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare disorder commonly diagnosed in later disease stages when it prominently manifests as malnutrition. We report on a female ...patient diagnosed with MNGIE at the age of 36. She was severely malnourished due to loss of resorptive surface after several surgical procedures, gastrointestinal dysmotility, and small intestinal bacterial overgrowth. Therefore, early and aggressive total parenteral nutrition was introduced. Although no reports have shown that nutritional support can modify the clinical outcome, this case suggests that adequate nutritional support, particularly parenteral nutrition, supervised by an experienced nutritional team, may prolong the lifespan of patients with MNGIE.
Croatia still has opportunistic screening and the organized national screening has been planned. The European Cervical Cancer Prevention Week was held twice in Croatia, in January 2008 and 2009. ...Within the first one in 2008, information campaign »For All Women« via mass media was held, and women were invited to the organized free gynecological examination and Papanicolaou test (Pap test) in the University Department of Gynecology and Obstetrics, Zagreb University Hospital Center. Following invitation 481 women attended the testing; the median age was 55 years. There were more women aged ³50 (n=353), with the highest participation in the age group 55–59 years (n=94). Some women came because of subjective symptoms (n=10), but the majority of them came only for testing (n=471). According to history of previous cytological testing, 400 women have had ³1 negative findings, 71 women have had ³1 positive findings, 9 women attended Pap test for the first time, and 1 woman does not know about previous testing. Cervical cytology was abnormal in 35 women (7.28%), the median age was 42 years with the highest proportion in the age group 30–34 years (n=7); among all of them 21 women (60%) had no abnormal Pap test previously. The findings were: Atypical squamous cells of undetermined significance – ASC-US (n=9), ASC cannot exclude high-grade squamous intraepithelial lesion – ASC-H (n=1), cervical intraepithelial neoplasia – CIN 1 (n=13), CIN 2 (n=1), CIN 3 (n=6), carcinoma planocellulare (n=2), atypical glandular cells – AGC-favor reactive endocervical cells (n=3). Among women aged £49 there were 20.47% abnormal findings and among those aged ³50, 2.55%. According to ³1 positive Pap tests previously, among women aged £49 there were 30.71% while among those aged ³50 there were 9.07%. Within the European Cervical Cancer Prevention Week in 2009, employed women from one national company were invited by internal information to the same procedure. A smaller group of younger asymptomatic women came for testing (n=53), median age 39 years. According to history of previous cytological testing, 50 women have had ³1 negative findings, 3 women have had ³1 positive findings. In this study, Pap test was positive in 3.77% (n=2). National screening programme should be focused on the participation of all personally invited women, especially younger age groups and under-screened women. Well designed information campaign should be implemented in national screening programme.
Cytological criteria for the identification of glandular intraepithelial lesions (GIL) have not yet been fully described, especially for the precursors of adenocarcinoma in situ (AIS), thus these ...lesions may frequently remain unrecognized. As most patients diagnosed with AIS or mild to moderate GIL (grades I, II) are free from clinical symptoms, cytology has a very responsible role in the detection of these lesions. The aim of the study was to achieve the most appropriate cytologic diagnosis of intraepithelial lesions of endocervical columnar epithelium, analyzing the cytology findings in patients with histologically verified AIS and GIL (I, II). The value of cytology in the detection and differential diagnosis was assessed in 123 patients with definitive histologic diagnosis of glandular lesions (AIS, n=13; GIL I, n=11; and GIL II, n=7), and glandular lesions associated with squamous component (AIS associated with cervical intraepithelial neoplasia (CIN) or invasive squamous cell carcinoma (SCC), n=58; GIL I or GIL II associated with CIN, n=28; and GIL associated with microinvasive squamous carcinoma (MIC), n=6). In 95.1% of patients, lesions were detected by cytologic analysis that indicated additional diagnostic procedure. In terms of differential diagnosis, cytology showed higher accuracy in predicting lesion severity vs. type of epithelial alteration (75.6% vs. 55.3%) and abnormalities of columnar epithelium (95.7%; vs. 74.2%). The accuracy of cytology was higher in pure (AIS, 61.5% and GIL I, II, 22.2%) than in mixed lesions (25.9% and 20.6%). Continuous improvement in cervical specimens and cytodiagnostic skills, better understanding of intraepithelial adenocarcinoma and precursors, and their inclusion in the classification of cytologic and histologic findings are expected to upgrade the detection of these lesions, and to reduce the invasive cervical adenocarcinoma morbidity and mortality.
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.
Unlike cervical cytology, morphological cytology criteria in the differential diagnosis of endometrium have not yet been clearly defined, and methods to allow for more precise evaluation of ...endometrium status have been searched for. The aim of the present study was to assess the value of morphometric nucleus analysis of cytologic aspirate endometrial samples in proliferative, hyperplastic and malignant endometrium by use of digital image analysis. Morphometric analysis was performed on archival cytologic aspirate endometrial samples (at least 10 per group) stained according to Papanicolaou (n=77) and May-Grünwald-Giemsa (MGG; n=80) with the following histopathologic diagnoses: proliferative endometrium, hyperplasia simplex, hyperplasia complex, hyperplasia complex atypica, and adenocarcinoma endometriodes endometrii (grade I, II and III). Interactive image analysis (nuclear area, convex area, perimeter, maximum and minimum radius, length and breadth, as well as nucleus form factor and elongation factor) was performed by use of the Sform software (Vamstec, Zagreb) on at least 50 (Papanicolaou stain) and 100 (MGG stain) well preserved endometrial epithelial cell nuclei without overlapping, at magnification of ´1000. Statistical data analysis was done by use of the Statistica Ver. 6 statistical package. Multivariate analysis (ANOVA) distinguished malignant, hyperplastic and proliferative endometrium according to all morphometric variables with both staining methods (p<0.05). However, on interactive testing of the groups (Kruskal-Wallis test), hyperplasias without atypia yielded no significant differences (p>0.05) from atypical hyperplasia, adenocarcinoma and proliferative endometrium only according to the nucleus form factor and elongation factor (Papanicolaou stain), whereas malignant and atypical hyperplastic endometrium (MGG stain) differed statistically significantly (p<0.05) from proliferative and hyperplastic endometrium without atypia according to all study parameters except for the nucleus form factor (p>0.05). According to the cytologic staining method, morphometric parameters were considerably higher in MGG stained endometrial samples, reaching the level of statistical significance (p<0.05) except for the nucleus form factor and elongation factor (p>0.05) in the groups of hyperplasia simplex and complex, well differentiated adenocarcinoma (form factor) and atypical hyperplasia (elongation factor). A combination of cytomorphology and the morphometric variables assessed in this study can yield useful information on the cytologic state of endometrium, with special reference to the possible differentiation of the group of hyperplasia without atypia from the group of adenocarcinoma and atypical hyperplasia.
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