Early Assessment of Neoadjuvant Chemotherapy Response Using Multiparametric Magnetic Resonance Imaging in Luminal B-like Subtype of Breast Cancer Patients: A Single-Center Prospective Study.

This study aimed to evaluate the performance of multiparametric breast magnetic resonance imaging (mpMRI) for predicting response to neoadjuvant chemotherapy (NAC) in patients with luminal B subtype breast cancer. The prospective study included thirty-five patients treated with NAC for both early and locally advanced breast cancer of the luminal B subtype at the University Hospital Centre Zagreb between January 2015 and December 2018. All patients underwent breast mpMRI before and after two cycles of NAC. Evaluation of mpMRI examinations included analysis of both morphological (shape, margins, and pattern of enhancement) and kinetic characteristics (initial signal increase and post-initial behavior of the time-signal intensity curve), which were additionally interpreted with a Göttingen score (GS). Histopathological analysis of surgical specimens included grading the tumor response based on the residual cancer burden (RCB) grading system and revealed 29 NAC responders (RCB-0 (pCR), I, II) and 6 NAC non-responders (RCB-III). Changes in GS were compared with RCB classes. A lack of GS decrease after the second cycle of NAC is associated with RCB class and non-responders to NAC.

Role of breast imaging in predicting outcome of lesions of uncertain malignant potential (B3) diagnosed at core needle biopsy.

AIMS: To elucidate whether breast imaging can predict final histologic diagnosis of lesions of uncertain malignant potential diagnosed at ultrasound core needle biopsy (CNB). METHODS: The imaging characteristics (mammography, ultrasound, and magnetic resonance imaging [MRI]) of lesions of uncertain malignant potential in the breast that were obtained by ultrasound CNB were retrospectively analyzed in 87 women. Radiologic characteristics of lesions were compared to definitive histopathologic findings. RESULTS: Out of 87 breast lesions of uncertain malignant potential, 27 (31%) were diagnosed as papillary lesions, 24 (28%) atypical ductal hyperplasia, 19 (22%) lobular intraepithelial neoplasia, 9 (10%) phyllodes tumors, 3 (3%) radial sclerosing lesions, and 5 (6%) unspecified lesions of uncertain malignant potential. The underestimation rate of malignancy at CNB based on the total number of lesions on final follow-up was 22%. Using multivariate logistic regression, Breast Imaging-Reporting and Data System (BI-RADS) score (odds ratio [OR] = 12.29, p = 0.027) and Göttingen MRI scoring system (OR = 8.1, p = 0.008) were found to be independent predictors of malignancy. Receiver operating characteristic analysis showed that Göttingen MRI score >3 provides a plausibly good cutoff value with sensitivity of 100 (95% confidence interval [CI] 74%-100%) and specificity of 76% (95% CI 61%-88%). CONCLUSIONS: Lesions of uncertain malignant potential classified as BI-RADS 5 and Göttingen score 4 or higher are at significantly higher risk of harboring malignancy and therefore should be recommended for surgical excision.

[Diffuse infantile hepatic hemangioendothelioma: a case report]. / Difuzni infantilni hepatalni hemangioendoteliom: prikaz bolesnika.

Infantile hepatic hemangioendothelioma (IHHE) is the most common benign hepatic tumor in children (12% of hepatic tumors), that usually responds well to therapy and has low mortality rates. In extremely rare cases of diffuse tumors resistant to therapy, size and blood flow can lead to cardiorespiratory failure and death. A 3-month-old male infant presented with respiratory infections and an abdominal mass, with frequent broncho-obstructive attacks. The CT, MRI and DSA exams showed typical morphology of hemangiendothelioma that was proven on histopathological biopsy. The tumor was resistant to standard medical therapy, and its volume led to cardiopulmonary arrest and death at 13 months of age. In rare cases of diffuse therapy-resistant IHHE a liver transplantation should be considered as an earlier treatment.

Reduced E-cadherin expression is a predictor of lower overall survival and metastatic disease in invasive ductal breast cancer.

BACKGROUND: E-cadherin, a transmembrane adhesion molecule, is implicated in the development of many solid tumors as well as in the acquisition of metastatic potential of epithelial tumors. Its clinical use has yet to be established. PATIENTS AND METHODS: The prognostic value of E-cadherin expression in 134 invasive ductal breast carcinoma patients over a 10-year follow-up period was investigated. Additionally, the correlation between E-cadherin expression and other traditional prognostic factors was investigated. RESULTS: A statistically significant influence on overall survival was found for estrogen receptor, tumor size, histological and nuclear grade, HER2, lymph node involvement, vascular invasion, proliferative index, and E-cadherin. E-cadherin expression had a significant impact on overall survival and development of metastases in the group of patients not receiving chemotherapy, while it had no such effect in the group of patients who received chemotherapy. CONCLUSION: We conclude that determination of E-cadherin expression can be used as an adjunct in selecting patients who may benefit from adjuvant chemotherapy in the presence of otherwise favorable prognostic factors.

Prognostic importance of PAI-1 in node negative breast cancer patients--results after 10 years of follow up.

The serine protease urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play key roles in the proteolytic cascade involved in physiological and pathological degradation of the extracellular matrix. The aim of this study was to determine the prognostic importance of PAI-1 expression in tumor cells in node-negative breast cancer patients that did not receive adjuvant chemotherapy. We used immunohistochemistry (IHC) as a detection method. The study retrospectively included 133 ductal invasive breast cancer patients from the Clinical Hospital Center Zagreb, Croatia, surgically treated in a two-year interval (1998-1999) with 10 years of follow up. The Cox proportional hazard regression test with stepwise variable selection was used to calculate the relative effect of investigated data on patients' prognosis. Univariate analysis showed that all investigated factors, such as lymph node involvement (p=0.025), tumor grade (p<0.001), estrogen receptor status (p=0.011), vascular invasion (p=0.001), HER2 overexpression (p<0.001), and proliferative index (p<0.001), had a statistically significant influence on patients' OS. Multivariate statistical analysis showed that only HER-2 (p<0.001) can be considered an independent, statistically significant poor prognostic factor. In patients with negative lymph nodes that did not receive adjuvant chemotherapy, we found a significant correlation in overall survival (p=0.009), which is favorable for PAI-1 negative tumors. In conclusion, it seems that PAI-1 in primary breast cancer tissue correlates with disease aggressiveness and has a strong prognostic impact on primary breast cancer, and is a strong prognostic factor for node-negative patients that did not receive chemotherapy.

Informed consent for gastrointestinal endoscopy: a view of endoscopists in Croatia.

BACKGROUND/AIM: There are many differences and deficiencies in the process of informed consent. The aim of this study was to get the view of gastrointestinal endoscopists in Croatia on obtaining patients' consent before endoscopic procedures. METHODS: During the 2004 annual meeting of the Croatian Society of Gastroenterology, endoscopists were asked to answer a questionnaire according to common clinical practice in affiliated institutions. It included questions on endoscopists' experience and education in medical ethics, as well as on the nature and quality of information given to patients and their opinion on proposed measures for improvement of the informed consent process. RESULTS: The questionnaire was distributed to 96 endoscopists attending the meeting and the response rate was 54% (52/96). In only 50% of institutions was the obtained consent written and potential complications of endoscopic procedures are occasionally given to the patient. In the minority of cases the patient is provided with information about alternative diagnostic tests and/or treatment options, and the information about mortality rate was almost never discussed. CONCLUSIONS: In Croatia, the process of informed consent for endoscopy needs improvement and should be regarded against the background of education in medical ethics, regional burden in endoscopic practice and appropriateness of by-laws and local guidelines.

Adenocarcinoma of the uterine cervix: prognostic significance of clinicopathologic parameters, flow cytometry analysis and HPV infection.

BACKGROUND: This study was designed to determine the possible impact of status of human papillomavirus (HPV) infection (no infection, single, multiple infections) on the survival of patients with cervical adenocarcinoma, to correlate the HPV status with other clinicopathologic parameters, and to examine clinical, histological and flow cytometric parameters as predictors of survival in cervical adenocarcinoma. METHODS: The clinical data of 51 patients with adenocarcinoma of the cervix who were treated at the Department of Gynecology and Obstetrics, Zagreb University School of Medicine, from 1978 to 2004 were analysed: age at presentation, menstrual status, clinical stage, relapse, survival. Exact histologic subtype, architectural grade and nuclear grade were determined. DNA flow cytometry was performed to determine DNA ploidy and proliferative index. Polymerase chain reaction (SPF primers), followed by reverse hybridisation for genotyping, was used to determine the HPV status. RESULTS: The status of HPV infection had no impact on patient survival, and could not be correlated with any of the analysed clinicopathologic parameters. Univariate analysis showed significant association between patient survival and clinical stage (p=0.002) and architectural grade (p=0.033). Multivariate analysis confirmed both parameters as significantly associated with survival. Menstrual status, nuclear grade, DNA ploidy and proliferative activity had no impact on patient survival. CONCLUSION: Clinical stage and architectural grade are significant predictors for survival of patients with cervical adenocarcinoma. Status of HPV infection, flow cytometric parameters, nuclear grade and menstrual status do not predict patient survival.

Employment outcomes among junior researchers in medicine in Croatia.

AIM: To investigate fellowship outcomes among junior researchers in medicine, supported by the Ministry of Science, Education, and Sports of the Republic of Croatia. METHODS: We used the data on junior researchers whose fellowships terminated between 1999 and 2005. Employment outcomes and scientific productivity, measured by the number of published articles indexed in the Web of Science database, were analyzed for every junior researcher. The data were analyzed using chi2 test, Mann-Whitney test, Kruskal-Wallis test, Breslow test, and logistic regression. RESULTS: Only 12% of junior researchers obtained a degree of Doctor of Philosophy (PhD) during fellowship. At the same time, 55% of junior researchers with a Medical Doctor degree terminated the fellowship and got employed in the health system during the same month. Terminating and re-employing in same month was most common among junior researchers who got employed by clinics and hospitals (odds ratio, 7.78; 95% confidence interval, 2.22-27.24). Also, it was less common among female than male junior researchers (odds ratio, 0.50; 95% confidence interval, 0.28-0.90). CONCLUSION: This study suggests that junior researchers in medicine commonly used their fellowship as a short-term employment option. The direct consequence of this is the low percentage of obtained PhD degrees during the fellowship period. Additionally, this article provides an insight into the current status and future of the fellowship programs in medicine, with special emphasis placed on the potential changes that might occur as a consequence of physician shortage in Croatia.

Outcome and prognostic factors in ocular adnexal lymphoma.

AIM: To classify ocular lymphomas in patients treated at the Zagreb University Hospital Center according to the new classification of the World Health Organization (WHO) and to determine factors with prognostic significance. METHODS: From 1986 to 2003, histological diagnosis of ocular lymphoma was made in 24 patients. The median age of patients was 62 years, with 2:1 female predominance. The patients underwent staging procedures and clinical evaluations prior to the date of the initial therapy. Histopathologic slides were reviewed and tumors were classified according to the new WHO classification. Additional immunohistochemical studies were performed on 35 available specimens. The antibodies used were CD3, CD5, CD10, CD20, CD43, and bcl-6; and in a few cases cyclin D1, bcl-2, CD23, CD79a, and CD138. The main outcome measures were development of distant recurrence after new presentation with solely ocular adnexal disease, and death attributable to widespread lymphoma. RESULTS: Ocular adnexal lymphomas were found in orbit in 20 patients, in eyelid in two, and conjunctiva in two patients. Twenty patients had lymphoma stage IE, one had IIE, and three had stage IV. Three patients had prior or concurrent systemic disease and 21 patients had primary lymphoma. The main subtypes of non-Hodgkin lymphoma according to the WHO classification were extranodal marginal zone B-cell lymphoma (n=20), diffuse large cell B-cell lymphoma (n=2), mantle cell lymphoma (n=1), and plasmacytoma (n=1). Six lymphomas were CD43 positive and five of them were extranodal marginal zone B-cell lymphomas. Radiotherapy was given to 11 patients, chemotherapy in 8 patients, whereas radiotherapy and chemotherapy were implemented in three patients. Two patients underwent only surgical excision of the tumor. Local relapse was found in three and distant recurrence in four patients. Distant recurrence was found in four patients with stage IE (two of them also had a local relapse). In the group of patients with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (B-EMZL), the estimated 5-year overall survival was 92.9+/-6.6% (mean+/-standard deviation) and the 5-year failure-free survival was 80.1+/-10.3%. Age, sex, side of involvement, anatomic localization of the lesion, clinical stage of disease, and mode of therapy did not have any prognostic significance during the follow-up period (median, 53; range, 9-131 months). Immunohistochemical marker CD43 was the only parameter of prognostic significance (p=0.035). Patients with B-EMZL had almost 14 times higher chance for an unfavorable outcome if the tumor cells expressed CD43 on their surface, than the CD43-negative cases. CONCLUSION: Most ocular adnexal lymphomas usually have a B-cell immunophenotype, the morphologic and immunohistochemical features of extranodal marginal zone B-cell lymphoma, and a favorable prognosis. Our data suggest that CD43 could be useful to separate the group of patients with extranodal marginal zone B-cell lymphomas with unfavorable prognosis from those that have a good prognosis. CD43 positive ocular lymphomas are associated with a higher rate of subsequent distant recurrence and the rate of lymphoma-related death.