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Nutritional status is recognized as an independent and modifiable risk factor of outcome in stem cell transplant. Our research aim was to evaluate the impact of body mass index (BMI) and serum albumin on the prevalence of adverse events and survival in autologous transplant in children. A retrospective study was conducted of autologous transplants performed between 2006 and 2017 in the Children’s Hospital Zagreb, Croatia. Nutritional status was assessed at the times of diagnosis, procedure, and discharge using BMI (underweight, normal, obese) and serum albumin (grades 1–4). Adverse events (fever, gastrointestinal toxicity, electrolyte disturbances, dysglycemia) and outcome (3-year, relapse, mortality) were documented. Seventy-seven children (54.5% males, mean age 7.9 years) underwent autologous transplant, mostly for neuroblastoma. In terms of BMI and albumin, which showed significant positive correlation at diagnosis (p = 0.026) and transplant (p = 0.016), most participants were well nourished. Average post-transplant weight loss was 4%. Major toxicities were severe mucositis (72.7%) and hypophosphatemia (31.2%). Relapse and mortality rates were 35.1% and 42.9%, respectively. Hypokalemia (p = 0.041) and hypomagnesemia (p = 0.044) were more prevalent in the underweight group, while obese children experienced significantly less severe mucositis (p = 0.016) and hypophosphatemia (p = 0.038). There was no significant difference regarding outcome among children of different nutritional status, although undernourished children tended to have lower relapse and mortality rates. In conclusion, underweight children are significantly more prone to severe electrolyte disorders and mucositis, and although statistical significance was not reached, are more likely to survive.

Although the incidence of the most frequent malignant gastric tumour, adenocarcinoma, has been decreasing, during the last decades the incidence of proximal localizations of gastric cancer as well as esophagogastric cancer has been increasing. Due to the late detection of initially advanced disease the outcomes of treatment for the patients are unsatisfactory. Diagnosis is set by tumour biopsy during endoscopy. The basis of treatment of locoregional disease is surgery in combination with perioperative chemotherapy. Alternatively, if no preoperative chemotherapy is administered, adjuvant chemoradiotherapy or chemotherapy should be performed. Metastatic disease is treated with palliative chemotherapy and best supportive care. Treatment decisions should be individualized according to patients’ characteristics and made after multidisciplinary team discussion. The following text presents the clinical guidelines in order to standardize the diagnostic procedures, treatment and monitoring of patients with gastric cancers in the Republic of Croatia.

Colorectal cancer (CRC) is one of the most common malignant tumors in Western countries. The treatment outcomes of this disease have improved significantly in recent years due to the improvement of diagnostic methods (pathohistology, radiology, nuclear medicine), screening and treatment improvements: surgical and oncological (chemotherapy, immunotherapy, radiotherapy). Additional progress has been made in the definition of prognostic and predictive factors of CRC. It is very important to emphasize the multidisciplinary approach to patients with CRC and to make a decision on optimal treatment based on evidence.

BACKGROUND The purpose of this study was to detect parameters that could serve as predictors of radioactive iodine (I-131) ablation failure in patients with low-risk and intermediate-risk differentiated thyroid carcinoma (DTC). METHODS Our cohort study included 740 patients with DTC who received postoperative I-131 remnant ablation. Anthropometric, biochemical, and pathohistological parameters were analyzed and correlated with ablation outcome using multivariable logistic regression models. RESULTS Treatment failure rates were higher in patients 2.4 ng/mL predicted treatment failure with 93.8% sensitivity and 52.5% specificity, and in patients with N1b disease, Tg > 14.9 ng/mL with 77.8% sensitivity and 92.9% specificity. I-131 activity was not associated with treatment outcome. CONCLUSION Patients

Purpose: Along with increased cancer incidence, there is also an increased use of targeted cancer therapy. One of the most potent classes of targeted therapy drugs are tyrosine kinase inhibitors (TKIs). Several new TKIs have become available in clinical practice after the correlation of sunitinib and hypothyroidism was documented. The aim of this review is to assess all relevant studies regarding clinically approved TKIs, in respect to hypothyroidism as a side-effect, and to investigate the possible predictive value of hypothyroidism in patients taking these drugs. Methods: Drugs that are approved by the United States Food and Drug Administration (FDA) for clinical use are evaluated in this study. In order to identify studies regarding hypothyroidism as a side-effect of TKIs, a systematic PubMed/Medline literature search was conducted. Results: Currently, the FDA has approved 26 different TKIs for use in clinical practice. The total number of yielded PubMed/Medline results was 232. Conclusions: Sunitnib, sorafenib, imatinib, pazopanib, and axitinib are TKIs with a definitive link to hypothyroidism. According to some current studies, patients who develop hypothyroidism during TKI therapy have prolonged progression-free survival. Despite the fact that hypothyroidism is nowadays a well known side-effect of therapy with many different TKIs, there are still no established guidelines for its treatment. Further studies in this area are needed, especially for lesser investigated drugs. It would be prudent to consider routine monitoring of thyroid function in all patients who receive TKIs, and to recommend endocrinological consultation as necessary.

The aim of this study was to evaluate the efficacy of different radioactive iodine (I- 131) activities used for re-ablation, to compare various combinations of treatment activities, and to identify predictors of re- ablation failure in low- and intermediate-risk differentiated thyroid carcinoma (DTC) patients. The study included 128 consecutive low- and intermediate-risk patients with DTC with ablation failure after total thyroidectomy. Patient characteristics, T status, tumor size, lymph node involvement, postoperative remnant size on whole-body scintigraphy, serum thyroglobulin (Tg), thyroid-stimulating hormone (TSH), anti-Tg antibody (TgAb), and Tg/TSH ratio were analyzed as potential predictors of the re-ablation success. Re-ablation was successful in 113 out of 128 patients (88.3 %). Mean first I-131 activity was 2868 ± 914 MBq (77.5 ± 24.7 mCi) and mean second I-131 activity 3004 ± 699 MBq (81.2 ± 18.9 mCi). There was no association between the first, second, and cumulative activity with re-ablation treatment outcome. Treatment failure was associated with higher Tg levels prior to re-ablation (Tg2) (OR 1.16, 95 % CI 1.05–1.29, P = 0.003) and N1a status (OR 3.89, 95 % CI 1.13–13.41, P = 0.032). After excluding patients with positive-to-negative TgAb conversion, Tg2 level of 3.7 ng/mL predicted treatment failure with a sensitivity of 75.0 %, specificity of 80.5 %, and a negative predictive value of 97.1 %. Patients with positive-to-negative TgAb conversion had higher failure rates (OR 2.96, 95 % CI 0.94– 9.29). Re-ablation success was high in all subgroups of patients and I-131 activity did not influence treatment outcome. Tg may serve as a good predictor of re-ablation failure. Patients with positive-to-negative TgAb conversion represent a specific group, in whom Tg level should not be used as a predictive marker of treatment outcome.

There is a great interest in molecular markers that would help in the preoperative diagnosis of malignant thyroid nodules in cases of indeterminate fine-needle aspiration cytology. The aim of this study was to determine the diagnostic accuracy of HMGA2 gene expression in discriminating benign from malignant thyroid nodules. In this study, 237 preoperative thyroid fine-needle aspiration samples were analyzed prospectively for the expression of the HMGA2 gene by real-time reverse transcription polymerase chain reaction. The results were evaluated against the postoperative histopathologic diagnosis or definitive cytologic diagnosis in cases of nodular goiter and Hashimoto thyroiditis. Among 237 samples from patients with thyroid nodules that were analyzed, 231 were adequate for real-time reverse transcription polymerase chain reaction analysis. With a cutoff value of 8.71 for relative gene expression, HMGA2 was positive in 19 (16.4%) of 116 nodular goiter, 1 (2.6%) of 39 Hashimoto thyroiditis, 9 (28.1%) of 32 follicular adenoma, 0 (0%) of 5 Hurthle cell adenoma, 32 (88.9%) of 36 papillary carcinoma, and 3 (100%) of 3 follicular carcinoma samples. In discriminating between malignant and benign thyroid nodules, HMGA2 has shown specificity of 84.5%, sensitivity of 91.9%, positive predictive value of 53.1%, and negative predictive value of 98.2%. High sensitivity and negative predictive value of HMGA2 for preoperative detection of malignant thyroid nodules shown in this study indicate that it may have a role as an ancillary marker in cytology in the management of patients with thyroid nodules.

Usage of complementary and alternative medicine (CAM) is steadily increasing over the last decades, gaining medical, economic and sociological importance. Th e aim of the present study was to assess the use of complementary and alternative therapies in cancer patients. A cross-sectional, descriptive survey design was used to collect data through an anonymous questionnaire. A total of 267 patients were included in the study. The prevalence of CAM use among cancer patients in this study was 60.3%. It was found that 61 heterogeneous CAM therapies were used, the most popular among patients being naturopathy/folk medicine. In multivariate logistic regression analysis, independent predictors of CAM use were high income, divorced status, female sex and younger age. In conclusion, considering the fact that a large proportion of patients used at least one CAM approach, we need to continue our efforts to improve the patient-oncologist communication in order to deliver most reliable information to patients and to better understand the possible standard medicine-CAM interactions. According to results of the latest studies, CAM therapies that help manage pain, nausea, fatigue, anxiety, and other symptoms should be integrated into the patient overall care.

Targeted therapy has been the standard of care for the treatment of metastatic renal cell carcinoma (mRCC). The current standard of care focuses on tyrosine kinase inhibitors (sunitinib, sorafenib, pazopanib, axitinib), antibodies to circulating VEGF receptor (bevacizumab) and m-TOR inhibitors (temsirolimus, everolimus). New immune-based therapies are emerging as a promising treatment for mRCC. Immune checkpoint blockade has shown clinically signifi cant antitumor response. Monoclonal antibodies against immune checkpoint blockade molecules including PD-1 (programmed cell death 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) have become a major focus in the immune-based therapy since it has been reported that they have impressive antitumor eff ects. The most studied inhibitors in the PD-1 pathway are: nivolumab, pembrolizumab and atezolizumab. Based on the results of the phase III clinical trial (CheckMate025) nivolumab, humanized monoclonal IgG4 antibody against PD-1, is the only agent that is approved by the FDA for the second-line treatment of mRCC. Ipilimumab is the fi rst-in-class immunotherapeutic for blockade of CTLA-4. The immunotherapy combinations have demonstrated promising results in a randomized trials. The use of cancer treatment vaccines is another approach to immunotherapy and will be systematically evaluated in the future. Immunotherapy has demonstrated great clinical potential and it represents crucial component of mRCC treatment. Developing immunotherapy to the point of clinical utility presents a number of issue and challenges, and more rigorous studies are needed., Ciljana terapija danas predstavlja osnovicu sistemskog liječenja metastatskog raka bubrega (mRB), a standard liječenja su tirozin-kinazni inhibitori (sunitinib, sorafenib, pazopanib, aksitinib), protutijela na cirkulirajući VEGF receptor (bevacizumab) i m-TOR inhibitori (temsirolimus, everolimus). Noviji imunoterapijski principi predstavljaju značajne iskorake u liječenju mRB. Jedna forma imunoterapije je inhibicija imunoloških kontrolnih točaka (eng. immune checkpoint). Blokiranjemjednog od dva najistraživanija imunološka receptora; antigen 4 povezan s aktivnošću citotoksičnih T-limfocita (CTLA-4) i receptor programirane stanične smrti (PD-1), potenciramo antitumorski imunološki odgovor. Među najistraživanije anti-PD-1 inhibitore ubrajamo: nivolumab, pembrolizumab i avelumab. Nivolumab je ljudsko monoklonalno antitijelo kojega je Američka agencija za hranu i lijekove odobrila u drugoj liniji liječenje mRB, a na osnovi rezultata kliničke studije faze III (CheckMate025). Ipilimumab je prvi registrirani checkpoint inhibitor koji blokira inhibitorni signal (CTLA-4 receptor) na površini citotoksičnih T limfocita. Veliki pomak u imunoterapiji mRB postigut je primjenom konkomitantnih protokola liječenja. Novija istraživanja primjene imunoterapije u liječenju raka bubrega uključuju i pronalaženje cjepiva koje bi prepoznavalo i uništavalo promijenjene tumorske stanice. Imunoterapija ima jasno mjesto i veliki potencijal u liječenju raka bubrega. Ipak, postoji još niz problema i pitanja te su potrebna brojna daljnja istraživanja kako bi se iskoristio njen puni potencijal.

At the Department of Oncology and Nuclear Medicine UHC “Sestre milosrdnice” patients who had advanced rectal cancer were treated with preoperative radiotherapy and chemotherapy, in cooperation with the IAEA and ESTRO. Fifteen patients who met the criteria and signed informed consent were included. Patients were randomized into two groups: Group 1: standard group, neoadjuvant approach (chemotherapy 5-FU / leucovorin concomitantly with radiotherapy (45-50 Gy in 25 fractions); Group 2: short course group, chemotherapy 5-FU / leucovorin with radiotherapy (25 Gy in 5 fractions). The main objectives were to determine the rate of resectability after completion of neoadjuvant therapy and to determine the percentage of local control and overall survival., U Klinici za onkologiju i nuklearnu medicine KBC “Sestre milosrdnice” u suradnji sa IAEA i ESTRO-m proveli smo ispitivanje o primjeni preoperativne radioterapije i kemoterapije u bolesnika s uznapredovalim karcinomom rektuma. U ispitivanje smo uključili petnaest bolesnika koji su zadovoljili uključne kriterije i potpisali informirani pristanak. Bolesnici su randomizirani u dvije skupine: skupina 1: standardni neoadjuvantni pristup (kemoterapija 5-FU / leucovorin konkomitantno uz radioterapiju (45-50 Gy u 25 frakcija); skupina 2: kemoterapija 5-FU / leukovorin uz radioterapiju (25 Gy u 5x). Glavni cilj bio je utvrditi stopu resektabilnosti nakon provedene neoadjuvantne terapije te odrediti postotak lokalne kontrole i ukupnog preživljenja.

Melanoma is considered to be the most immunogenic malignant tumour. This fact is recognized for many years, and certain forms of immunotherapy have been used in melanoma therapy for a considerable time. Treatment options for patients with metastatic melanoma have changed dramatically in the past 5 years, with the FDA approval of eight new therapeutic agents (immunotherapies and targeted therapies). During this period, melanoma immunotherapy has transitioned from cytokine-based treatment to antibody-mediated blockade of the cytotoxic Tlymphocyteassociated antigen4 (CTLA4) and, recently, the programmed cell-death protein 1 (PD1) immune checkpoints. These changes in the treatment options have dramatically improved patient outcomes, with the median overall survival of patients with metastatic melanoma increasing from approximately 9 months before 2011 to at least 2 years, and probably longer. Various types of immunotherapy, like pembrolizumab, nivolumab, ipilimumab, combined therapy with nivolumab and ipilimumab, and T-VEC, have been established in recent years as the standard-of-care treatment for metastatic melanoma patients., Melanomi se smatraju najimunogenijim zloćudnim tumorima. Ova je činjenica prepoznata već niz godina, te se neki oblici imunoterapije već dugo primjenjuju u liječenju melanoma. Terapijske opcije za liječenje bolesnika s metastatskim melanomom dramatično su se promijenile u zadnjih pet godina, te je Američka agencija za lijekove (FDA) odobrila osam novih lijekova (imunoterapije i ciljane terapije). Tijekom ovog razdoblja, imunoterapija melanoma promijenila se iz terapije bazirane na citokinima u protutijelima posredovanu blokadu citotoksičnog T-limfocitnog antigena 4 (CTLA-4), a u zadnje vrijeme u protutijelima posredovanu inhibiciju imunoloških kontrolnih točaka, prvenstveno proteina programirane stanične smrti 1 (PD-1). Ove su promjene terapijskih opcija dramatično poboljšale ishod liječenja bolesnika, te se medijan ukupnog preživljenja kod bolesnika s metastatskim melanomom povisio s približno 9 mjeseci prije 2011. godine, na najmanje 2 godine, a vjerojatno i dulje. Različiti oblici imunoterapije, poput pembrolizumaba, nivolumaba, ipilimumaba, kombinirane terapije nivolumabom i ipilimumabom, te T-VEC, postali su zadnjih godina standardni oblici liječenja bolesnika s metastatskim melanomom.

Purpose : colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, and detection of new prognostic markers is mandatory for patients to receive optimal oncological treatment. The aim of the study was to assess clinical and prognostic value of red cell distribution width (RDW) in patients with CRC. Methods : RDW values in 90 patients with CRC undergoing surgery for primary disease were analyzed in pre- and postoperative setting, and correlated with clinical and hematological parameters. Results : Both pre- and postoperative RDW measurements were found to be associated with features of iron deficiency anemia, inflammatory response to tumor, advanced age and depth of tumor invasion. Optimal cutoff points were calculated to be 14% for preoperative and 13.6% for postoperative RDW measurements. Elevations in both pre- and postoperative RDW values had significant effects on survival in univariate and multivariate analyses. Effects were found to be independent of tumor related features, stage of the disease, development of anemia and aberrant inflammatory response to tumor. Conclusions : RDW is an integrative parameter reflecting tumor specific features and shows significant association with overall survival in patients with CRC. This is especially important in patients with stage 2 disease where elevation in preoperative RDW values can contribute to recognition of higher risk patients.

Pancreatic cancer is a malignant neoplasm of the pancreas. It does not cause any symptoms in the early stage, and later symptoms are nonspecific, thus the disease is usually diagnosed when already advanced. In 2008, pancreatic cancer ranked eighth on the list of the 10 most common cancers among men in Croatia and tenth on the list of the most common cancers among Croatian women. Pancreatic cancer has a poor prognosis, with a survival time of only 6-8 months for metastatic disease. Gemcitabine is the standard chemotherapeutic option. Other chemotherapeutic agents include 5-fluorouracil and leucovorin. In this paper, we present a case of a patient diagnosed with locally advanced and metastatic pancreatic cancer, who is still alive and currently receives his fourth line of chemotherapy 5 years after the diagnosis. Following disease progression on gemcitabine chemotherapy, he was treated with chemoradiotherapy which, however, had no effect. We then applied cisplatin monochemotherapy which offered excellent disease control, was well tolerated by the patient and, although somewhat obsolete in this form, showed to be a valuable chemotherapeutic option.

Protein connexin 43 (Cx43), a part of intercellular gap junctions, is frequently down-regulated in tumors. The aim of the study was to compare Cx43 expression in primary colorectal tumors of patients with stage III and IV disease.Immunohistochemical expression of Cx43 was analyzed in 50 colorectal adenocarcinomas from surgically-treated patients of stage pT3N1-2 without metastases (M0) and 50 specimens of the same pTN stage from patients with synchronous liver metastases (M1). Association of Cx43 expression with clinicopathological factors and tumor site was also analyzed.There was no significant difference in Cx43 expression between M0 and M1 tumor specimens (p=0.817), as well as in Cx43 expression between colonic and rectal tumors (p=0.116), respectively. Stromal expression of Cx43 was higher in M1 than in M0 tumors (p=0.004).Stromal Cx43 expression is possible indicator of metastatic potential of colorectal adenocarcinoma.

The tyrosine kinase inhibitor (TKI) sunitinib malate is nowadays a standard first-line treatment option for patients with metastatic clear-cell renal cell carcinoma (mRCC). The aim of this study was to evaluate the incidence and clinical course of thyrotoxicosis in our cohort of patients treated with sunitinib.Medical records of all patients treated with first-line sunitinib for mRCC at our Institution between November 2008 and March 2014 were retrospectively reviewed. Thyroid function was assessed after every 2 cycles of therapy, during the 2 weeks off period.Out of the 62 included patients, hypothyroidism has developed during therapy in 12 patients (19%) and it was preceded by thyrotoxicosis in 2 (3.2%).Sunitinib-induced thyrotoxicosis (SIT), a not so rare entity, was followed by hypothyroidism. The patterns of occurrence and possible significance of SIT, as predictive marker of better treatment response to sunitinib, need to be validated in further studies.

Colorectal cancer (CRC) is the most common malignancy of the gastrointestinal tract worldwide, and also one of the leading causes of cancer-related mortality, accounting for more than 600000 deaths every year. Depending on the stage of the disease some patients who were surgically treated for CRC with curative intent require adjuvant chemotherapy (fluorouracile-based), which reduces the risk of recurrence and death in patients with stage III CRC, but its role in stage II is still controversial. Pathogenesis of CRC is a result of two different genetic pathways: chromosomal instability (CIN), and inactivation of mismatch repair (MMR) genes. Stage II patients with deficient MMR tumor status do not benefit from adjuvant therapy and should receive surgery alone. For patients with metastatic CRC optimal sequence of chemotherapy regimens and targeted therapy is still debated. Epidermal growth factor receptor (EGFR) has been validated as a therapeutic target in several human tumors including CRC. Recently it has been reported that activating mutations in exons 2, 3, and 4 of both KRAS and NRAS all predict a lack of response to EGFR trageted agents. Recent studies suggest BRAF is another prognostic and potential predictive biomarker of CRC. It is necessary to indentify new prognostic and predictive markers, to acquire maximal benefit from every therapy line and to improve prognosis of these patients., Rak debelog crijeva (CRC) najučestalija je maligna neoplazma gastrointestinalnog trakta, te je sa preko 600.000 smrti godišnje jedan od vodećih uzroka smrtnosti od zloćudnih bolesti. Ovisno o stadiju bolesti, neki od bolesnika koji su kirurški liječeni radi raka debelog crijeva s ciljem izlječenja zahtijevaju primjenu adjuvantne kemoterapije (bazirane na fluorouracilu) koja smanjuje rizik povrata bolesti i smrti u III. stadiju bolesti, no njena uloga u stadiju II još je uvijek nedovoljno jasna. Patogeneza u CRC rezultat je dvaju različitih molekulsko-genskih mehanizama: kromosomske nestabilnosti (CIN) te inaktivacije gena koji sudjeluju u popravku pogrešno spojenih fragmenata DNA (MMR). Na temelju provedenih istraživanja, u bolesnika stadija II u kojih je prisutan deficijentan MMR status ne postoji dobit od primjene adjuvantne terapije te je u toj skupini bolesnika kirurško liječenje dostatno. U bolesnika s metatastatskim CRC još uvijek nema konsenzusa o optimalnom redoslijedu kemoterapijskih protokola i ciljane biološke terapije. Receptor za epidermalni čimbenik rasta (EGFR) potvrđen je kao terapijski cilj u više humanih tumora, uključujući CRC. Odnedavno, istraživanja su pokazala da aktivirajuće mutacije na eksonima 2, 3 i 4 KRAS i NRAS gena dovode do izostanka odgovora na ciljanu terapiju usmjerenu na EGFR. BRAF je još jedan od istraživanih biljega u raku debelog crijeva, te je pokazano da je povezan sa lošijom prognozom. Potrebna su daljnja istraživanja i identifikacija novih prognostičkih i prediktivnih biljega kako bi se postigla maksimalna učinkovitost svake terapijske linije te poboljšala prognoza ovih bolesnika.

Tyrosine kinase inhibitors are standard treatment in patients with metastatic renal cell carcinoma (mRCC). Several studies have indicated that side-effects including hypothyroidism may serve as potential predictive biomarkers of treatment efficacy.All patients with clear cell mRCC treated with sunitinib in the first-line setting in our Center between November 2008 and October 2013 were included. Thyroid function was assessed after every 2 cycles. Prognostic factors were tested using Cox proportional hazards model for univariate analysis.During treatment, 29.3% developed hypothyroidism, with a median of peak TSH values of 34.4 mIU/L. Patients who had both TSH4 mIU/L and were receiving substitution therapy with levothyroxine had prolonged PFS compared to all other patients (25.3 months vs. 9.0 months; p=0.042).The rate of hypothyroidism as a side-effect of sunitinib in patients with mRCC is significant. Patients with symptomatic hypothyroidism experienced significantly longer PFS, but without difference in OS.

To evaluate the significance of plasma free serotonin (5-hydroxytryptamine) and Ca15.3 for the early detection of breast cancer recurrence.Free serotonin and Ca15.3 levels were measured by I-125-Serotonin RIA (DDV Diagnostica, Marburg, Germany) in plasma and an ELISA kit (Roche Diagnostic GmbH, Mannheim, Germany) in serum, respectively in women (N=29) who responded to primary treatment for breast cancer and who were followed-up for recurrence. For analysis, patients were sub-divided according to TNM staging into groups with localized (T1-2N0-M0) and advanced (T1-2N1-2M0-1) disease. The control group were healthy blood donors.Patients with advanced disease had a significantly higher plasma serotonin level than those with localized disease or controls, whereas Ca15.3 levels remained in normal range in all groups. At the time of serotonin measurement, radiological findings were negative for all patients in the localized-disease group, but positive in nine patients in the advanced-disease group.Plasma free serotonin may be used for the early detection of recurrent/metastatic breast cancer disease, but validation on a larger number of patients is needed.

Background: Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited syndrome characterized by the development of numerous polyps in the colon and rectum. If left untreated, the affected patients inevitably develop colon cancer by the age of 40 years. A resection of the colon (colectomy) or of the colon and rectum (proctocolectomy) is needed to minimize the risk of cancer. Case Presentation: We report a case of FAP through three generations of a single family, in which the grandmother and granddaughter underwent total colectomy with ileoanal anastomosis and did not develop colon cancer, while the son underwent subtotal colectomy with ileorectal anastomosis and developed recurrent rectal cancer. Data regarding timely surgery, surveillance, and chemoprevention are discussed. Conclusion: The FAP phenotype determines the type of treatment. In severe polyposis, proctocolectomy with ileoanal anastomosis seems to be the optimal method for minimizing the risk of cancer development. This case report advocates complete rectal removal, especially in cases of poor patient compliance with colonoscopic surveillance.

Tumori testisa najčešći su solidni tumori u muškaraca u dobi od 15. do 34. godine. Njihova je incidencija u svijetu podvostručena u posljednjih 40 godina. Tumori zametnih stanica obuhvaćaju 95% svih tumora testisa, a podijeljeni su u dva osnovna histološka tipa: seminomi i neseminomi. Osobito značenje daje im visok postotak izlječivosti i u diseminiranoj fazi bolesti. Ovom uspjehu najviše je pridonijela kemoterapija, ali i dalje je kirurgija neizostavni dio uspješnog liječenja. Kod znatnog dijela ovih bolesnika danas se nastoji odrediti terapijski minimum kojim se izbjegava niz nuspojava, a koji dovodi do jednakog uspjeha kao i donedavno agresivniji terapijski pristup. U tekstu koji slijedi iznesene su kliničke upute radi standardizacije dijagnostike, terapije i kontrole bolesnika s tumorima zametnih stanica testisa u Republici Hrvatskoj., Testicular tumors are the most common solid tumors in men between 15 and 34 years of age. The worldwide incidence of these tumors has doubled in the past 40 years. Germ cell tumors comprise 95% of malignant tumors arising in the testes and they are classified either as seminoma or nonseminoma. Testicular cancers have a high cure rates even in disseminated stage of the disease. The chemotherapy mostly contributed to these results but surgery is an inevitable part of successful treatment. In a significant number of these patients treatment algorithms with minimum side effects are designed with the intention to maintain same cure rates as previously used, more aggressive therapy. The following text presents the clinical guidelines in order to standardize the procedures and criteria for diagnosis, management, treatment and follow-up of patients with testicular cancer in Republic of Croatia.

Rak kolorektuma treći je najčešći maligni tumor muškaraca i četvrti najčešći maligni tumor žena u Republici Hrvatskoj. Klinički se najčešće očituje poremećajem formiranja stolice, osjećajem nedovoljnog pražnjenja crijeva, prisutnošću krvi u stolici te gubitkom tjelesne težine i umorom. Pravodobna dijagnoza, potvrđena patohistološkim nalazom, temelj je uspješnog liječenja. Odluka o liječenju donosi se temeljem kliničke procjene stadija bolesti te drugih čimbenika rizika, a nakon provedene dijagnostičke obrade. Ovisno o tome, mogućnosti liječenja uključuju kirurški zahvat i primjenu sistemske terapije (kemoterapija, imunoterapija) te radioterapiju. U tekstu koji slijedi predstavljene su kliničke upute s ciljem standardizacije postupaka i kriterija postavljanja dijagnoze, upravljanja i liječenja te praćenja bolesnika s kolorektalnim rakom u Republici Hrvatskoj, Colorectal cancer is the third most common malignant tumour in males and the fourth most common malignancy in women in the Republic of Croatia. It is usually manifested as stool forming disorders, feeling that bowel does not empty completely, finding blood in the stool, weight loss and fatigue. In-time diagnosis, confirmed by pathohistological findings, is cornerstone of successful treatment. The decision about treatment is made based on clinical assessment of disease stage and other risk factors, after completion of the diagnostic process. Depending on that, treatment options include surgery, the application of systemic therapy (chemotherapy, immunotherapy) and radiotherapy. The following text presents the clinical guidelines in order to standardize procedures and criteria for the diagnosis, management, treatment and monitoring of patients with colorectal cancer in the Republic of Croatia.

Splenic irradiation has long been known as a palliative treatment modality in patients with various malignant hematologic diseases aiming to ameliorate clinical symptoms of splenomegaly as well as clinical sequels of hypersplenism. It provides considerable effect with low toxicity although exact radiotherapy dose and fractionation schedule are not known. During the 1996-2010 period, eleven patients were treated at our institution with splenic irradiation. They received 16 courses of fractionated radiotherapy. There were six patients with non-Hodgkin’s lymphoma, four with chronic lymphocytic leukemia, and one patient with myelofibrosis. The median of the dose received was 7 Gy, while the median of dose received per fraction was 1 Gy. Both parallel opposed anterior-posterior fields and tangential fields were used. Due to the clinical target volume shrinkage, the treatment field was reduced in 44% of courses. Of the courses initiated for symptom control, 71% resulted in effective palliation, whereas of the courses started to treat hematologic sequels of hypersplenism 50% produced desirable effects. The most common side effects included thrombocytopenia and anemia. Splenic irradiation provides effective and low-toxic palliation of symptoms but it is much less successful in treating hematologic disorders caused by hypersplenism., Ozračivanje slezene je najstariji poznati način palijativnog liječenja bolesnika s različitim zloćudnim hematološkim bolestima. Ima za cilj umanjiti kliničke simptome splenomegalije, kao i posljedice hipersplenizma. Ozračivanje slezene ima značajan učinak uz nisku toksičnost, ali točna radioterapijska doza kao i način frakcioniranja nisu poznati. Između 1996. i 2010. godine 11 bolesnika je liječeno u našoj ustanovi ovim postupkom. Ti bolesnici su primili ukupno 16 aplikacija frakcioniranog zračenja. Šest bolesnika je imalo ne-Hodgkinov limfom, četiri kroničnu limfatičnu leukemiju, a jedan bolesnik je imao mijelofibrozu. Medijan aplicirane tumorske doze bio je 7 Gy, a medijan aplicirane doze po frakciji 1 Gy. Korištena su nasuprotna paralelna te tangencijska radioterapijska polja. Zbog smanjenja kliničkog ciljnog volumena terapijsko polje je tijekom postupka radioterapije smanjeno u 44% radioterapijskih aplikacija. Od radioterapijskih postupaka započetih s ciljem kontrole simptoma 71% ih je rezultiralo uspješnom palijacijom, dok je od postupaka koji su započeti radi popravka hematoloških posljedica hipersplenizma njih 50% izazvalo željeni učinak. Najčešće nuspojave bile su trombocitopenija i anemija. Ozračivanje slezene omogućuje učinkovitu i nisko toksičnu palijaciju simptoma, ali je manje uspješno u liječenju hematoloških poremećaja uzrokovanih hipersplenizmom.

Secondary angiosarcoma is an aggressive tumor that can develop in breast cancer patients treated with conserving therapy and radiotherapy. The symptoms can be misleading, whereas mammography and fine-needle aspiration (FNA) are typically negative in early stage of the disease. A high grade of clinical suspicion is very important for early diagnosis. A case of angiosarcoma involving breast parenchyma in a patient treated with quadrantectomy and radiotherapy for T1cN1Mx breast carcinoma is presented., Sekundarni angiosarkom je agresivni tumor koji se može razviti kod bolesnica s rakom dojke liječenih terapijom očuvanja i radioterapijom. Simptomi mogu dovesti u zabunu, dok su mamografija i citološka punkcija redovito negativne u ranom stadiju bolesti. Za ranu dijagnozu vrlo je važna visoka klinička sumnja na ovu bolest. Prikazuje se slučaj angiosarkoma koji je zahvatio parenhim dojke u bolesnice liječene kvadrantektomijom i radioterapijom zbog raka dojke T1cN1Mx.

BACKGROUND AND AIM: Soluble c-erbB-2 oncoprotein has been proven as a useful marker in the management of breast cancer patients, but its value in diagnostics and follow-up of colorectal cancer patients remains controversial. The aim of this study was to evaluate the usefulness of serum c-erbB-2 monitoring in diagnostics and prediction of disease outcome in rectal cancer patients. - - - - - MATERIALS AND METHODS: Serum samples from 88 patients with rectal adenocarcinoma before surgery and from 41 healthy controls were tested for the presence of c-erbB-2 oncoprotein by ELISA, and the patients were followed up for at least 5 years after the surgery. - - - - - RESULTS: Preoperative serum c-erbB-2 levels were significantly higher in stage IV patients than in healthy controls (P

e15603 Background: Five-years survival of patients with metastatic renal cell carcinoma (mRCC) is only 10%. A complete response (CR) to therapy is rare but has been achieved in minority of patients using high-dose interleukin-2. Sunitinib is an oral multitargeted receptor tyrosin kinase inhibitor and is currently considered the standard of care for first-line therapy of mRCC. CRs and long-term responders (LTR) to sunitinib have been documented in the literature. However, a detailed description and analysis of these patients is lacking. We report LTR, defined as patients achieving ongoing CR or remaining progression-free for ≥ 18 months on sunitinib. Methods: From 10/2008 till 12/2012, 48 patients were treated with sunitinib (50 mg/day, 4 weeks on/2 weeks off) as the first line therapy of clear cell mRCC. Tumor assessments were performed at baseline and every two cycles thereafter until the end of treatment, using RECIST criteria. Results: Nine patients were identified as LTR (18.8%). Retrospective data of these patients are reported in the Table. Conclusions: Sunitinib achieves LTR in a subset of patients with mRCC. Lung metastases and favourable MSKCC risk group may predict LTR. Maintaining full-dose sunitinib and management of therapy- related toxicity are crucial for treatment efficacy. [Table: see text]

The number of leukocytes, proportion and absolute number of granulocytes, lymphocytes, CD4+ cells, CD8+ cells, CD16+ cells, B-lymphocytes, monocytes, natural killer cell (NK) activity, and granulocyte and monocyte phagocytic functions--ingestion and intracellular killing--were determined in a group of 27 patients with ductal invasive breast carcinoma, stage I-III, before and 7 months following postsurgical telecobalt radiotherapy, divided into two subgroups, one of them receiving tamoxifen (TMX group) and the other one not receiving any further therapy (control group). In control group, proportion of all lymphocytes and CD8+ cells as well as absolute number of all lymphocytes, CD4+, CD8+, CD16+ and B lymphocytes were decreased following TCT in comparison to their pre-TCT values, while in TMX group only absolute number of all lymphocytes remained decreased following TCT. Moreover, post-TCT proportions of all and CD8+ lymphocytes as well as absolute numbers of all and CD4+ and CD8+ lymphocytes in TMX patients were significantly increased in comparison to the same parameters in control post-TCT patients, although there was no difference between the two subgroups before TCT. At the other hand, granulocyte ingestion was decreased in post-TCT TMX patients compared to post-TCT values in control patients and NK cell activity showed a similar, although statistically not significant, tendency. It seems that TMX helps recovery of lymphocyte populations decreased by radiotherapy, probably by stimulation of cells carrying estrogen receptors, but its effects on phagocytic functions and probably NK cell activity seemed to be rather inhibitory than stimulatory.

Prognostic significance of phagocytic functions in breast cancer patients