URINARY BLADDER CANCER RECURRENCE AND EXPRESSION OF LYNCH AND HER MARKERS: SEARCHING FOR IMMUNOHISTOCHEMICAL PATTERNS AMONG 113 TUMORS FROM 33 PATIENTS.

The aim was to identify immunohistochemical (IHC) markers able to predict recurrence of urinary bladder tumors. The method of multivariate adaptive regression splines (MARS) was applied to IHC data of 33 patients with urinary bladder cancer that relapsed one to six times (24 male and nine female, age 57-87 years). The MARS analysis was used to predict the total number of recurrences and the Ki-67 value by nine IHC markers (epidermal growth factor receptor (EGFR), HER2, HER3, E-cadherin, Ki-67, MLH1, MSH2, MSH6 and PMS2). Data were divided as initial tumors, first and subsequent recurrences, and tumors that relapsed within nine months of previous surgery or later. The IHC markers were semiquantitatively classified into four groups, as follows: 0 means no positive cells; 1, 10% of positive cells; 2, 11%-30% of positive cells; and 3, 31%-100% of positive cells. In predicting the overall number of recurrences, as a surrogate marker of tumor biology, the R2 value for all tumors was 0.423, for initial tumors 0.686, for first recurrence 0.700, and for subsequent recurrences only 0.233. The key predictors for initial tumors were HER2 and MSH2, while for the first recurrence it was EGFR. For quick recurrences (within nine months), the R2 was 0.474 with EGFR and HER3 as predictors, while for slow recurrences R2 was 0.640 due to EGFR and PMS2. In predicting the Ki-67 value of that tumor, the R2 value for all tumors was 0.300, for initial tumors 0.262, for first recurrence 0.360, and for subsequent recurrences only 0.533. The key predictors for first recurrences were EGFR and MSH6, and for subsequent recurrences HER2, EGFR and all Lynch markers. The R2 was 0.266 for quick recurrences and 0.370 for slow recurrences. The finding of E-cadherin was not found relevant by any of these MARS models. In conclusion, the MARS results associated multiple IHC markers with the number of recurrences and with Ki-67 values. It is important that differences in predictive markers were found between initial tumors and first recurrences, and between quick and slow recurrences, thus suggesting that tumor biology is different among these subgroups regarding the total number of recurrences and Ki-67 values.

WHICH PATIENTS SHOULD RECEIVE RADIOTHERAPY IN POSTOPERATIVE DISEASE RECURRENCE?

After radical prostatectomy (RP), up to 60% of patients with high-risk prostate cancer (PC), such as high Gleason score, extracapsular prostatic extension (ECE), positive margins, seminal vesicle involvement (SVI), will develop biochemical relapse and they will require further local treatment. Radiotherapy (RT) to the prostate bed has been used as adjuvant (ART) or salvage (SRT). In patients with high-risk PC, radiotherapy immediately after RP or adjuvant radiotherapy may eradicate residual localized microscopic disease and improve biochemical, progression-free survival, and overall survival. Only a few observational studies have compared RP patients who have received only RT with patients who have received RT with some form of hormonal therapy. A few of them have reported improved progression-free survival with addition of hormonal therapy to SRT, but benefit in overall survival (OS) is not yet known.

[Clinical recommendations for diagnosing, treatment and monitoring of patients with ovarian cancer -- Croatian Oncology Society and Croatian Society for Gynecology and Obstetrics as Croatian Medical Association units and Croatian Society of Gynecological Oncology]. / Klinicke upute za dijagnostiku, lijecenje i pracenje bolesnica oboljelih od raka jajnika hrvatskoga onkoloskog drustva i hrvatskog drustva za ginekologiju i opstetriciju hrvatskoga lijetnickog zbora te hrvatskoga ginekoloskoonkoloskog drustva.

Ovarian cancer together with fallopian tube represents the fifth most common female cancer in the Republic of Croatia. Epithelial ovarian cancer, serous subtype, encompasses most of malignant ovarian neoplasms. Less common are various non-epithelial ovarian malignancies. A special group consists of epithelial carcinomas of low malignant potential with clinically indolent flow, good prognosis and no invasion, and primary cancer of the peritoneum and fallopian tube cancer. Clinically, these malignant tumors are generally asymptomatic in early stages, and usually diagnosed in advanced stages. The diagnosis is confirmed by pathological examination, and occasionally, cytological findings after completing diagnostic procedures. Multidisciplinary team makes treatment decisions, taking into account age, general condition and comorbidities of the patient and characteristics of the tumor itself, including disease stage, histological type and grade of the tumor. The principles of treatment of primary peritoneal and fallopian tube cancer are based on the principles of treatment of epithelial ovarian cancer involving surgery, chemotherapy, immune and hormone therapy, and symptomatic-supportive care throughout the treatment. Less common histological types have a different treatment approach being more frequently diagnosed in the early stages of the disease, have more indolent flow, so in these patients conservative surgeries with the goal of preserving fertility are more often employed. The following text presents the clinical guidelines in order to standardize the procedures and criteria for the diagnosis, management, treatment and monitoring of patients with ovarian carcinoma, fallopian tube and primary peritoneal cancer in the Republic of Croatia.

[Clinical recommendations for diagnosing, treatment and monitoring of patients with uterine cervical cancer -- Croatian Oncology Society and Croatian Society for Gynecology and Obstetrics as Croatian Medical Association units and Croatian Society of Gynecological Oncology]. / Klinicke upute za dijagnostiku, lijecenje i pracenje bolesnica oboljelih od raka vrata maternice hrvatskoga onkoloskog drustva i hrvatskog drustva za ginekologiju i opstetriciju hrvatskoga lije nickog zbora te hrvatskoga ginekoloskoonkoloskog drustva.

Cervical cancer, in comparison with other gynecological malignancies, mainly affects younger women. It can be prevented trough educational programs, screening and early detection. It also can be efficiently treated when it appears. Treatment modalities include surgery, chemotherapy and radiotherapy, according to the stage of the disease and patient condition. Treatment decisions should be made after multidisciplinary team discussion. Due to the significance of this disease it is important to define and implement standardized approach for diagnostic, treatment and monitoring algorithm as well. The following text presents the clinical guidelines in order to standardize the procedures and criteria for the diagnosis, management, treatment and monitoring of patients with uterine cervical cancer in the Republic of Croatia.

Influence of silicone oil tamponade after vitrectomy on intraocular pressure.

The aim of this prospective study was to determine the possible influence of the silicone oil tamponade after vitrectomy on the early intraocular pressure (IOP) elevation, which is a major risk factor for developing secondary glaucoma in patients with vitreal and retinal proliferative changes. The research included 110 patients which were allocated in three groups according to the medical history data. The surgical procedures were performed at the Eye Clinic, University of Zagreb School of Medicine. The control group comprised 40 patients who underwent vitrectomy with air or saline solution tamponade. The second group consisted of 40 patients with retinal detachment and proliferative retinopathy who had vitrectomy with silicone oil tamponade and the third group were 30 patients with diabetic retinopathy who underwent vitrectomy and tamponade with silicone oil. The intraocular pressure was measured and gonioscopy was performed in all patients one month before and after vitrectomy. The results showed that there is no statistically significant difference among IOP values before and after vitrectomy in the control group (p = 0.104) as well as in the preoperative IOP values among all three groups of patients. The data analysis determined that in both groups of patients with silicone oil tamponade after vitrectomy, there is a statistically significant difference in IOP values one month after the surgical procedure (p = 0.000). The mean IOP values in those patients a month after vitrectomy were significantly higher compared to the control group (p < 0.05). Comparison of the IOP one month after vitrectomy between the patients with retinal detachment and those with diabetic retinopathy showed no statistically significant difference (p = 0.331) but the qualitative analysis showed that the IOP one month after vitrectomy was 2 mmHg higher in the diabetic retinopathy group. The results suggest that there is no difference in angle width before and after vitrectomy among different groups of patients. Emulsified silicone oil was confirmed in 18% of patients in the retinal detachment group. In 17% of patients in the diabetic retinopathy group the emulsified oil was found in the angle, whereas a 10% of patients had neovascularization of the angle one month after vitrectomy. The IOP elevation in the early postoperative course may be caused by intravitreal instillation of the silicone oil after vitrectomy. Emulsification of the silicone oil may lead to the early IOP rise; especially in the diabetic patients with angle neovascularization which itself can additionally accelerate the development of the secondary glaucoma.

Chalazion management--surgical treatment versus triamcinolon application.

The aim of the study was to compare the length of treatment and efficiency of applied therapy in two groups of patients with chalazion who underwent surgical procedure or got triamcinolone application in chalazion. Our study included 30 patients with chalazions that persisted for about one month. All of them were resistant to applied topical antimicrobial therapy. These patients were devided in two groups. 15 patients underwent surgical procedure that included incision, excochleation and excision of the capsule of chalazion, while other 15 patients underwent triamcinolone aplication directly in chalazion (dosage of 2-4 mg). Patients were followed up a day after therapy, two weeks after therapy and one month after applied therapy. We found that chalazion treatment with triamcinolone application directly in the lesion was to be more comfortable for patients, took less time to treat and needed no additional topical antimicrobial therapy.

Computer-aided evaluation of radiologist's reproducibility and subjectivity in mammographic density assessment.

Mammographic density is an independent risk of breast cancer. This study has evaluated the radiologists' reproducibility and subjectivity in breast density estimation and in order to decrease the radiologists' subjective errors the computer software was developed. The very good reproducibility existed in the strong correlation with the first and the second mammogram assessment after three month period for each radiologist (correlation coefficient 0.73-1, p < 0.001). The strong correlation was present in the case of all 5 radiologists when compared among themselves and compared with software aided MDEST-Mammographic Density Estimation (correlation coefficient 0.651-0.777, p < 0.001). Detected differences in glandular tissue percentage determination occurred in the case of two experienced radiologists, out of 5 (one radiologist with more than 5 year experience and one with more than 10 year experience, p < 0.01), but in the case of breast type determination (American College of Radiology-ACR I-IV), the detected difference occurred in one radiologist with the least experience (less than 5 years, p < 0.001). It can be concluded that the estimation of glandular tissue percentage in breast density is rather subjective method, especially if it is expressed with absolute percentage, but the determination of type of breast (ARCI-IV) depends on the radiologist's experience. This study showed that software aided determination of glandular tissue percentage and breast type can be of a great benefit in the case of less experienced radiologists.

[Clinical guidelines for diagnosing, treatment and monitoring patients with bladder cancer--Croatian Oncology Society and Croatian Urology Society, Croatian Medical Association]. / Klinicke upute za dijagnostiku, lijecenje i pracenje bolesnika oboljelih od raka mokracnog mjehura Hrvatskoga Onkolokog Drustva i Hrvatskoga Uroloskog Drustva Hrvatskoga Lijecnickog Zbora.

Urothelial cancer is the most common bladder cancer. Hematuria is the most common presenting symptom in patients with bladder cancer. The most common diagnostics of bladder cancer is performed by transurethral resection of bladder after which pathohistological diagnosis is set. It is necessary to determine whether the cancer penetrated in muscle layer (muscle-invasive cancer) or not (muscle-noninvasive cancer). Decision on therapeutic modality depends on the clinical stage of disease and on prognostic and risk factors. For muscle non-invasive bladder cancer transurethral resection is preferred with or without intravesical instillation of Bacillus Calmette-Guérin (BCG). For invasive cancer the method of choice is radical cystectomy. Radiotherapy is used in radical and palliative purposes. Metastatic disease is most frequently treated by chemotherapy metotrexate/vinblastine/doxorubicine/cisplatin (MVAC) or gemcitabine/cisplatin (GC). The purpose of this article is to present clinical recommendations to set standards of procedures and criteria in diagnostics, treatment and follow up of patients with bladder cancer in the Republic of Croatia.