Efficacy and safety of TC dose-dense chemotherapy as first-line treatment of epithelial ovarian cancer: a single-institution retrospective cohort study.

BACKGROUND: The optimal first-line therapy of advanced ovarian cancer still remains questionable: standard paclitaxel-carboplatin (TC), dose-dense TC, intraperitoneal chemotherapy or TC plus bevacizumab. In this study, we present the real-life results of dose-dense treatment of the single-institution on Caucasian population. METHODS: A retrospective cohort study was used on consecutive samples of 74 patients treated with the conventional 3-weekly TC protocol (2008-11) and on 70 treated with TC dose-dense protocol (2012-16). The primary endpoint of this study was overall survival (OS). Secondary endpoints were progression free-survival (PFS) and toxicity. We made adjustments for age, pathohistological type, tumor grade, stage and postoperative residual disease by Cox regression. RESULTS: After adjustment for pre-planned clinical and sociodemographic factors, patients treated with dose-dense protocol showed a significantly lower hazard for dying from any cause, than patients treated with conventional protocol (HR = 0.50; 95% CI 0.26-0.98; P = 0.042). Median OS, at 60 months follow-up had not been reached in the dose-dense group, while in the standard treatment group was 48 months (95% CI 33-62). Unadjusted PFS was significantly longer in the dose-dense group (HR = 0.58; 95% CI 0.38-0.88; P = 0.011), but not after the adjustment (P = 0.096). Generally, the level of toxicity was similar in both groups of patients. The need for blood transfusions and usage of filgrastim was significantly higher in the TC dd group. The incidence of neutropenia and thrombocytopenia Grade 3 or 4 were not significantly different in both regimens. CONCLUSIONS: Our retrospective study has shown the superior efficacy and comparable toxicity of dose-dense chemotherapy regimen over the conventional regimen in treatment of ovarian cancer on Caucasian population at a single-institution.

Prognostic significance of MAPK, Topo IIα and E-cadherin immunoexpression in ovarian serous carcinomas.

Ovarian cancer accounts for only 3% of all cancers in women but is the most lethal gynaecologic malignancy. Low-grade and high-grade ovarian serous carcinomas (OSCs) represent two different diseases with different prognosis, approaches to detection and treatment. We assessed correlation between, MAPK, topoIIα, E-cadherin immunoexpression and clinicopathological features with overall survival (OS) in OSCs. The study included 81 patients undergoing surgery between January 1995 and December 2005.Formalin fixed paraffin embedded tumour sections were reviewed and examined immunohistochemically using antibodies against MAPK, topoIIα and E-cadherin. The clinicopathological features included: age at surgery, stage according to the criteria of the International Federation of Gynecology and Obstetrics (FIGO), tumour grade, residual disease and vascular invasion. Only ten patients (12.3%) were diagnosed in early FIGO stage of disease. According to morphological criteria, 13.6% of tumor samples were low-grade OSCs and 86.4% were high-grade OSCs. On uninominal analysis, residual disease (p<0.001), E-cadherin (p<0.001), vascular invasion (p=0.002), high-grade morphology (p=0.025) and FIGO stage III-IV (p=0.010) were related to significantly shorter OS. We found no significant association between, MAPK and topoIIα expression and OS. Multinominal analysis revealed that only residual disease (p<0.001) and negative E-cadherin immunoexpression were useful independent predictors of unfavourable clinical outcome and shorter OS.

Optimisation of breast cancer patients' follow-up - potential way to improve cancer care in transitional countries.

The aim of this analysis was to evaluate adherence of Croatian oncologists to follow-up criteria as suggested by the current national and international guidelines for women with breast cancer receiving adjuvant endocrine therapy. The use of clinical and diagnostic methods was documented in this prospective, non-interventional, multicenter study. A total of 438 post-menopausal patients receiving adjuvant endocrine treatment with non-steroidal aromatase inhibitors were included. Average annual frequency for each clinical and diagnostic method was calculated. Median adjuvant endocrine treatment duration before study recruitment was 10.5 months (interquartile 4.7-26.6). Patients were followed up for an average 23.5 ± 4.9 months. Average number of oncological visits was 5.3. Mammograms were performed at mean annual frequency of 0.7, chest radiographs at 0.5, abdominal ultrasounds at 0.9, breast ultrasounds at 1.2, complete blood counts and chemistry panels at 1.7, carcinoembryonic antigen at 0.8, cancer antigen 15-3 at 1.6, gynaecological examination at 0.3, and densitometry at mean annual frequency of 0.3. In conclusion, among post-menopausal women with breast cancer receiving adjuvant endocrine therapy in this study, more unnecessary and unproven follow-up procedures were done compared to the guidelines' recommendations.

Retrospective analysis of efficacy of trastuzumab in adjuvant treatment of HER 2 positive early breast cancer - single institution experience.

Addition of trastuzumab to chemotherapy is the cornerstone of adjuvant treatment of early HER2 positive breast cancer. Clinical trials and metaanalyses of adjuvant trastuzumab have shown significant reduction in risk of recurrence and death. Nevertheless, the real magnitude of the effect of any drug must be reevaluated in daily clinical conditions, due to the fact that daily clinical practice often differs from conditions in clinical trials. In order to measure the benefit of adding adjuvant trastuzumab in HER 2 positive early breast cancer treatment, we have performed retrospective analysis in a single institution on consecutive patients divided in 2 cohorts: one, treated in "pre - trastuzumab" and the other in "trastuzumab era". Between 2003 and 2012, 258 consecutive HER 2 positive patients with early breast cancer have been treated with adjuvant chemotherapy, 103 patients did not received trastuzumab (patients treated from 2003 till 2007), and 155 (patients treated from 2008 till 2012) received trastuzumab. Patients who received trastuzumab experienced significantly longer median disease-free survival (107 vs. 92 months, LR: 11.6, p <0.001); breast cancer-specific survival (130 vs. 117 months, LR: 10.7, p < 0.001) and median overall survival (123 vs. 108 months LR = 11.6, p < 0.001). The benefits of adding trastuzumab were independent of chemotherapy regimen and hormonal therapy. This retrospective analysis has shown a clear, statistically significant benefit of adjuvant trastuzumab in treatment of early, HER2 positive breast cancer in daily clinical practice, and confirmed the results of the registration clinical trials.

"Compensated hyperosmolarity" of cerebrospinal fluid and the development of hydrocephalus.

Acute osmolar loading of cerebrospinal fluid within one lateral ventricle of dogs was examined as a cause of water extraction from the bloodstream and an increase in intracranial pressure. We have shown that a certain amount of (3)H2O from the bloodstream enters osmotically loaded cerebrospinal fluid significantly faster, hence causing a significant increase in intracranial pressure. The noted phenomenon in which intracranial pressure still significantly increases, but in which the hyperosmolarity of the cerebrospinal fluid is no longer present, was named "compensated hyperosmolarity". In the case of the sub-chronic application of hyperosmolar solutions into cat ventricles, we observed an increase in cerebrospinal fluid volume and a more pronounced development of hydrocephalus in the area of application, but without significant increase in intracranial pressure and without blockage of cerebrospinal fluid pathways. These results support the newly proposed hypothesis of cerebrospinal fluid hydrodynamics and the ability to develop new strategies for the treatment of cerebrospinal fluid-related diseases.

Chlamydia pneumoniae and Mycoplasma pneumoniae pneumonia: comparison of clinical, epidemiological characteristics and laboratory profiles.

The purpose of our retrospective 3-year study was to analyse and compare clinical and epidemiological characteristics in hospitalized patients older than 6 years with community-acquired pneumonia (CAP) caused by Chlamydia pneumoniae (87 patients) and Mycoplasma pneumoniae (147 patients). C. pneumoniae and M. pneumoniae infection was confirmed by serology. C. pneumoniae patients were older (42.12 vs. 24.64 years), and were less likely to have a cough, rhinitis, and hoarseness (P<0.001). C. pneumoniae patients had higher levels of C-reactive protein (CRP), and aspartate aminotransferase (AST) than M. pneumoniae patients (P<0.001). Pleural effusion was recorded more frequently in patients with M. pneumoniae (8.84 vs. 3.37%). There were no characteristic epidemiological and clinical findings that would distinguish CAP caused by M. pneumoniae from C. pneumoniae. However, some factors are indicative for C. pneumoniae such as older age, lack of cough, rhinitis, hoarseness, and higher value of CRP, and AST.

Experimental hydrocephalus and hydromyelia: a new insight in mechanism of their development.

One group of cats had an acrylic screw implanted into the adqueduct of Sylvius, while the other group of animals received a solution of kaolin into the cisterna magna. Three weeks later the dye phenolsulphonphthalein was instilled into the lateral ventricle to ascertain communication between CSF compartments, and thereafter the brain was perfused with formalin. As shown by planimetry of brain ventricles both groups of experimental animals developed hydrocephalus, i.e., coronal surface of brain ventricles was about 10 times larger in kaolin and about 3 times in aqueductal screw experiments than in the controls, respectively. In aqueductal screw experiments communication of CSF between lateral ventricle and subarachnoid spaces was not blocked but only restricted, i.e., an aqueductal stenosis was produced. In kaolin experiments communication of CSF between lateral ventricles and spinal subarachnoid space was blocked by thick meningeal adhesions in the upper cervical region, while the central spinal canal was dilated (hydromyelia) with enhanced CSF communication between it and the lumbar subarachnoid space. We assume that during systolic expansion of brain the CSF is displaced from the cranial cavity toward the spinal subarachnoid space which accommodates an additional volume of CSF primarily due to compliance of the spinal dural sac, while during diastole CSF recoils in the opposite direction. Thus, in case of aqueductal stenosis the undisplaced volume of CSF from the ventricles can be accommodated due to diminution of cerebral blood volume and brain parenchyma so that hydrocephalus develops over time. Since the cervical subarachnoid space is blocked in kaolin experiments the systolic brain expansion forces CSF from basal cisterns via the fourth ventricle into the aqueduct and central canal with consequent development of hydrocephalus and hydromyelia.