Predicting Trifluridine/Tipiracil Treatment Outcomes in Refractory Metastatic Colorectal Cancer Patients: A Multicenter Exploratory Analysis.

INTRODUCTION: There are no recommended biomarkers to identify patients with refractory metastatic colorectal cancer (mCRC) who would benefit the most from trifluridine/tipiracil (TTP). The exploratory analysis of the RECOURSE trial revealed that patients with low tumor burden and indolent disease derive greater benefit in terms of both progression-free survival (PFS) and overall survival (OS). Nevertheless, the final answer on the TTP real impact on the well-being of patients with late-stage mCRC will come from real-world data. METHODS: The aim of this retrospective exploratory study was to investigate the effectiveness of TTP in mCRC with regard to the duration of standard treatment and other influencing variables. The study included 260 patients from the three largest Croatian oncology centers who began treatment with TTP in the third or fourth line between 2018 and 2020. RESULTS: The median OS and PFS for the entire cohort were 6.53 and 2.50 months, respectively. Patients with more aggressive disease, defined as those whose time to progression on the first two lines of standard therapy was less than 18 months, had significantly shorter PFS (2.40 vs. 2.57 months, hazard ratio [HR] 1.34, 95% confidence interval [CI]: 1.03-1.84). There was also a tendency toward shorter OS (6.10 vs. 6.30 months, HR 1.32, 95% CI: 0.99-1.78) but without statistical significance. Patients with ECOG PS 0, without liver metastases, and with RAS mutation had both longer OS and PFS. No influence was detected from other variables including age, sex, primary tumor location, and tumor burden. CONCLUSION: With regard to the results of the previously conducted trials, the study concludes that indolent disease, good general condition, and absence of liver metastases are positive predictive factors for TTP treatment.

SIMULTANEOUS METASTASES OF PAPILLARY THYROID CARCINOMA AND NEUROENDOCRINE TUMOR OF THE CECUM TO CERVICAL LYMPH NODES: A CASE REPORT.

We present a case of a patient with simultaneous cervical lymph node metastasis of papillary thyroid cancer (PTC) and cecum neuroendocrine tumor (NET). A 45-year-old male patient with the diagnosis of metastatic NET of the cecum underwent fine needle aspiration (FNA) of a positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG PET) positive nodule in the left thyroid lobe. Due to FNA finding suspect of PTC, the patient underwent total thyroidectomy with central neck dissection. Histopathologic finding revealed PTC of the left thyroid lobe and small solitary lymph node PTC metastasis in the central neck region. Postoperative evaluation with neck ultrasound (US) revealed two enlarged suspected lymph nodes in cervical regions III and IV on the left side of the neck and the patient underwent FNA with measurement of thyroglobulin (Tg) in the aspirates. The FNA finding of the cervical lymph node in the region III revealed PTC metastasis with high Tg value in the aspirate, while FNA finding of the cervical lymph node in the region IV revealed NET metastasis with low Tg value in the aspirate. Postoperative serum Tg value was 17.75 µg/L and the patient underwent 5550 MBq iodine-131 (I-131) therapy. A year after I-131 therapy, follow-up neck US demonstrated complete cure of PTC cervical lymph node metastasis in the region III and stable in size NET cervical lymph node metastasis in the region IV. To our knowledge, this is the first report of simultaneous occurrence of cervical lymph node metastases of PTC and NET of the cecum.

THE CONCENTRATION OF INTERLEUKIN 6 AND TUMOR NECROSIS FACTOR ALPHA IN SALIVA AND BLOOD OF PATIENTS WITH INACTIVE MULTIPLE SCLEROSIS AND COEXISTING HASHIMOTO'S THYROIDITIS.

The concentration of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the blood is higher in patients with active multiple sclerosis (MS) compared to those with inactive disease. The concentration of IL-6 and TNF-α in the blood is higher in patients with Hashimoto's thyroiditis (HT) compared to those with a healthy thyroid. The aim of the study was to assess whether serum IL-6 and TNF-α levels correlated with saliva in patients with inactive MS and whether there was a difference in these groups of patients depending of thyroid status. We also examined the correlation of thyroid stimulating hormone (TSH) levels with thyroid status. The study included 54 patients in the inactive phase of MS. The level of cytokines in the blood was determined by chemiluminescence, and in saliva by ELISA. Blood and saliva IL-6 levels showed positive correlation, while blood and saliva TNF-α levels were not correlated. There was a significantly higher TSH level in patients with inactive MS with positive thyroid antibodies, without therapy, compared with those with negative antibodies.

Association of prior local therapy and outcomes with programmed-death ligand-1 inhibitors in advanced urothelial cancer.

OBJECTIVES: To compare clinical outcomes with programmed-death ligand-1 immune checkpoint inhibitors (ICIs) in patients with advanced urothelial carcinoma (aUC) who have vs have not undergone radical surgery (RS) or radiation therapy (RT) prior to developing metastatic disease. PATIENTS AND METHODS: We performed a retrospective cohort study collecting clinicopathological, treatment and outcomes data for patients with aUC receiving ICIs across 25 institutions. We compared outcomes (observed response rate [ORR], progression-free survival [PFS], overall survival [OS]) between patients with vs without prior RS, and by type of prior locoregional treatment (RS vs RT vs no locoregional treatment). Patients with de novo advanced disease were excluded. Analysis was stratified by treatment line (first-line and second-line or greater [second-plus line]). Logistic regression was used to compare ORR, while Kaplan-Meier analysis and Cox regression were used for PFS and OS. Multivariable models were adjusted for known prognostic factors. RESULTS: We included 562 patients (first-line: 342 and second-plus line: 220). There was no difference in outcomes based on prior locoregional treatment among those treated with first-line ICIs. In the second-plus-line setting, prior RS was associated with higher ORR (adjusted odds ratio 2.61, 95% confidence interval [CI]1.19-5.74]), longer OS (adjusted hazard ratio [aHR] 0.61, 95% CI 0.42-0.88) and PFS (aHR 0.63, 95% CI 0.45-0.89) vs no prior RS. This association remained significant when type of prior locoregional treatment (RS and RT) was modelled separately. CONCLUSION: Prior RS before developing advanced disease was associated with better outcomes in patients with aUC treated with ICIs in the second-plus-line but not in the first-line setting. While further validation is needed, our findings could have implications for prognostic estimates in clinical discussions and benchmarking for clinical trials. Limitations include the study's retrospective nature, lack of randomization, and possible selection and confounding biases.

GENOMICS OF PROSTATE CANCER: CLINICAL UTILITY AND CHALLENGES.

The studying of prostate cancer genomics is important for understanding prostate cancer biology, it can provide clinically relevant stratification into subtypes, the development of new prognostic and predictive markers in the context of precision medicine, and the development of new targeted therapies. Recent studies have provided detailed insight into genomics, epigenomics and proteomics of prostate cancer, both primary and metastatic castration-resistant (mCRPC). Many mutations have been discovered, both those that occur early in the carcinogenesis and progression as well as those responsible for the resistance to therapy occurring later under the influence of treatment. A large number of characteristic mutated signaling pathways has been identified, e.g. the mutations in DNA repair pathway were found in 23% of mCRPC, which suggests potential response to PARP inhibitors. Multifocality and intralesional genomic heterogeneity of prostate cancer make the clinical application of genomics complicated. Although a great progress was made in understanding prostate cancer genomic, and clinical studies related to its routine application are ongoing, prostate cancer genomics still needs to find its standard wide routine application in patients with prostate cancer.

RECENT ADVANCES IN RADIOTHERAPY MODALITIES FOR PROSTATE CANCER.

Radiotherapy is the attractive treatment option for prostate cancer and has a clear role in all stages of the disease. Over the last decade, advances in technology, imaging capabilities, and improved radiobiological understanding have deeply transformed radiotherapy for prostate cancer, allowing dose escalation and wide adoption of hypofractionation. Furthermore, the integration of magnetic resonance imaging (MRI) and improved physical precision of dose delivery have given an impetus to additionally target intraprostatic tumor lesions, previously agnostic to conventional radiotherapy target definition concept. The emerging data from randomized clinical trials and observation research show that ultra-hypofractionation is a safe approach while further follow-up is needed to assess its efficacy compared to standard fractionation. There is an ongoing uncertainty surrounding true alpha/beta ratio for prostate cancer since hypofractionation has so far failed to yield theoretically envisioned superior biochemical control outcomes. Finally, recently published randomized trial settled ongoing controversy regarding the role of elective pelvic lymph node radiotherapy in patients with high-risk prostate cancer, showing clear benefit when pelvic nodes were treated to 50 Gy. The role of partial gland dose escalation/tumor boosting is evolving, and more data is needed to adopt this approach in routine clinical care. Going forward, molecular imaging will be crucial to assess biology of the disease, predict a response potentially, and optimally personalize radiotherapy treatment decisions. In this narrative review, we critically analyzed the published literature and provided practical summary of recent prostate radiotherapy advances for busy clinicians.

ROLE OF ANDROGEN RECEPTOR-TARGETED AGENTS IN LOCALIZED PROSTATE CANCER.

Anti-androgen therapy continues to be a basic pilar of treatment for both localized and metastatic prostate cancer. The advent of new generation of androgen receptor targeted agents (ARTA) transformed the care of patients with advanced disease. After such a success, the steps were taken to incorporate a new generation of ARTAs into the treatment landscape of localized prostate cancer. High-risk prostate cancer represents the most aggressive form of localized disease with significant metastatic potential and poor outcome. Here, the impact of novel therapies will likely be profound and transforming. This clinical space has already been a showcase for multidisciplinary treatment where the combination of local therapies with systemic treatment gradually improved patient outcomes and the chances of cure. The most recent step in redefining the treatment of localized disease is the adoption of novel ARTAs moving forward the multidisciplinary platform. In this narrative review, we discuss current clinical evidence supporting the use of novel ARTAs in patients with localized high-risk prostate cancer and cover recent developments in biomarker-driven strategies for treatment individualization in this clinical context.

99mTc-MIBI SPECT/CT SCINTIGRAPHY AND ULTRASOUND OF THE ANTERIOR NECK REGION IN DIAGNOSING PARATHYROID GLAND PATHOLOGY IN PATIENTS WITH THYROID NODULES.

Parathyroid scintigraphy with 99mTc-MIBI is an imaging technique used in nuclear medicine and performed in patients with suspected hyperparathyroidism (HPT). The objective of this study was to evaluate the role of this technique in patients who, along with suspected HPT, also have thyroid nodules. Retrospective analysis included a period of 8 years (2006-2013). The study included 91 patients with clinical or laboratory suspected HPT. Pathologic changes in parathyroid glands were demonstrated in 47 (70%) of 67 patients with positive scintigraphy. Pathologic changes in parathyroid glands were not evident in the remaining 20 (30%) patients. Out of nine patients with negative scintigraphy results but with suspected enlargement of the parathyroid gland examined by ultrasound, eight (89%) patients did not show pathologic changes in the parathyroid gland, whereas one (11%) patient had evident changes. Eight (54%) of 15 patients with suspected scintigraphy had positive ultrasound findings, as well as fine needle aspiration cytology (FNAC) findings with parathyroid hormone (PTH) determination in the aspirate. Seven (46%) patients had negative FNAC findings and PTH in the aspirate. The study showed scintigraphy to have high sensitivity (98%) in detecting patients with pathologic changes in the parathyroid glands. In patients with suspected HPT, scintigraphy needs to be combined with FNAC and PTH determination in the aspirate due to its low specificity of 28%.

MRI-GUIDED RADIOTHERAPY FOR PROSTATE CANCER: A NEW PARADIGM.

Radiotherapy is one of the key treatment modalities for primary prostate cancer. During the last decade, significant advances were made in radiotherapy technology leading to increasing both physical and biological precision. Being a loco-regional treatment approach, radiotherapy requires accurate target dose deposition while sparing surrounding healthy tissue. Conventional radiotherapy is based on computerized tomography (CT) images both for radiotherapy planning and image-guidance, however, shortcomings of CT as soft tissue imaging tool are well known. Nowadays, our ability to further escalate radiotherapy dose using hypofractionation is limited by uncertainties in CT-based image guidance and verification. Magnetic resonance imaging (MRI) is a well established imaging method for pelvic organs. In prostate cancer specifically, MRI accurately depicts prostate zonal anatomy, rectum, bladder, and pelvic floor structures with previously unseen precision owing to its sharp soft tissue contrast. The advantages of including MRI in the clinical workflow of prostate cancer radiotherapy are multifold. MRI allows for true adaptive radiotherapy to unfold based on daily MRI images taken before, during and after each radiotherapy fraction. It enables accurate dose escalation to the prostate and intraprostatic tumor lesions. Technically, MRI high-strength magnetic field and linear accelerator high energy electromagnetic beams are hardly compatible, and important efforts were made to overcome these technical challenges and integrate MRI and linear accelerator into one single treatment device, called MRI-linac. Different systems are produced by two leading vendors in the field and currently, there are around 100 MRI-linacs worldwide in clinical operations. In this narrative review paper, we discuss historical perspective of image guidance in radiotherapy, basic elements of MRI, current clinical developments in MRI-guided prostate cancer radiotherapy, and challenges associated with the use of MRI-linac in clinical practice.

THE PREVALENCE OF SUBCLINICAL HYPOTHYROIDISM IN THE POPULATION OF ELDERLY NURSING HOME RESIDENTS IN ZAGREB.

The aim of the study was to investigate the prevalence of thyroid dysfunction, positive thyroid peroxidase antibodies (TPOAb) and hypercholesterolemia in elderly and younger subjects, and the association of subclinical hypothyroidism with hypercholesterolemia. The study included 204 elderly (136 females and 68 males, age median 71, range 60-92 years), and 83 younger control subjects (63 females and 20 males, age median 45, range 19-55 years). Subjects with prior thyroid dysfunction were excluded. Serum thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), TPOAb, total cholesterol, height and weight were measured. Mann-Whitney, χ2-test and Student's t-test were used on statistical analysis. The prevalence of subclinical hypothyroidism (TSH >5 mU/L) in elderly was 7.4% vs. 3.6% in younger subjects, with the highest prevalence of 8.8% in elderly women vs. 4.8% in younger women, and 4.4% in elderly men. The prevalence of hypothyroidism and subclinical hyperthyroidism in elderly subjects was 0.5% and 1.5%, respectively. In women with subclinical hypothyroidism, the prevalence of TPOAb was 77% in elderly women and 67% in younger women (overall 19.9% in elderly and 14.3% in younger women). The mean FT3 level was lower in elderly women as compared with elderly men (p<0.01) and younger women (p<0.05). The mean cholesterol level was higher in elderly subjects in comparison with younger ones (p<0.01), and in elderly women vs. elderly men (p<0.01), but without difference between subclinical hypothyroidism and euthyroid subjects (6.0 mmol/L). In conclusion, subclinical hypothyroidism is the most prevalent thyroid dysfunction in elderly, with the highest prevalence in elderly women, and autoimmune thyroiditis is the most common etiology. Hypercholesterolemia was more related to older age, especially elderly females, but not influenced by subclinical hypothyroidism.

DOSIMETRIC VERIFICATION OF INTENSITY MODULATED RADIOTHERAPY (IMRT) TREATMENT PLANS FOR PROSTATE CANCER PATIENTS.

Intensity modulated radiotherapy (IMRT) has become widely used as a standard radiation therapy technique for the treatment of localized prostate cancer. The transition from conformal radiotherapy (3D CRT) to a more complex IMRT technique triggered the need for more thorough verification of the accuracy in the dose delivery. In this work we present the clinical workflow and the results of patient specific quality assurance (PSQA) procedures for 40 prostate cancer patients who have been treated with step and shot IMRT ever since its implementation in our routine clinical practice. PSQA procedures include dosimetric verification of each treatment plan with dedicated rotational phantom and high-resolution matrix detector system Octavius 4D (PTW Freiburg) that allows three-dimensional comparison of the calculated and delivered radiation dose distribution. Our results proved the compliance with the universal tolerance limits recommended for those procedures (1), assuring the safety of the treatment and providing the possibility for the adoption of more stringent constraints in the future.

Immune checkpoint inhibitors in advanced upper and lower tract urothelial carcinoma: a comparison of outcomes.

OBJECTIVES: To compare clinical outcomes between patients with locally advanced (unresectable) or metastatic urothelial carcinoma (aUC) in the upper and lower urinary tract receiving immune checkpoint inhibitors (ICIs). PATIENTS AND METHODS: We performed a retrospective cohort study collecting clinicopathological, treatment, and outcome data for patients with aUC receiving ICIs from 2013 to 2020 across 24 institutions. We compared the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) between patients with upper and lower tract UC (UTUC, LTUC). Uni- and multivariable logistic and Cox regression were used to assess the effect of UTUC on ORR, OS, and PFS. Subgroup analyses were performed stratified based on histology (pure, mixed) and line of treatment (first line, subsequent line). RESULTS: Out of a total of 746 eligible patients, 707, 717, and 738 were included in the ORR, OS, and PFS analyses, respectively. Our results did not contradict the hypothesis that patients with UTUC and LTUC had similar ORRs (24% vs 28%; adjusted odds ratio [aOR] 0.73, 95% confidence interval [CI] 0.43-1.24), OS (median 9.8 vs 9.6 months; adjusted hazard ratio [aHR] 0.93, 95% CI 0.73-1.19), and PFS (median 4.3 vs 4.1 months; aHR 1.01, 95% CI 0.81-1.27). Patients with mixed-histology UTUC had a significantly lower ORR and shorter PFS vs mixed-histology LTUC (aOR 0.20, 95% CI 0.05-0.91 and aHR 1.66, 95% CI 1.06-2.59), respectively). CONCLUSION: Overall, patients with UTUC and LTUC receiving ICIs have comparable treatment response and outcomes. Subgroup analyses based on histology showed that those with mixed-histology UTUC had a lower ORR and shorter PFS compared to mixed-histology LTUC. Further studies and evaluation of molecular biomarkers can help refine patient selection for immunotherapy.

Nicotinamide N-Methyltransferase in Acquisition of Stem Cell Properties and Therapy Resistance in Cancer.

The activity of nicotinamide N-methyltransferase (NNMT) is tightly linked to the maintenance of the nicotinamide adenine dinucleotide (NAD+) level. This enzyme catalyzes methylation of nicotinamide (NAM) into methyl nicotinamide (MNAM), which is either excreted or further metabolized to N1-methyl-2-pyridone-5-carboxamide (2-PY) and H2O2. Enzymatic activity of NNMT is important for the prevention of NAM-mediated inhibition of NAD+-consuming enzymes poly-adenosine -diphosphate (ADP), ribose polymerases (PARPs), and sirtuins (SIRTs). Inappropriately high expression and activity of NNMT, commonly present in various types of cancer, has the potential to disrupt NAD+ homeostasis and cellular methylation potential. Largely overlooked, in the context of cancer, is the inhibitory effect of 2-PY on PARP-1 activity, which abrogates NNMT's positive effect on cellular NAD+ flux by stalling liberation of NAM and reducing NAD+ synthesis in the salvage pathway. This review describes, and discusses, the mechanisms by which NNMT promotes NAD+ depletion and epigenetic reprogramming, leading to the development of metabolic plasticity, evasion of a major tumor suppressive process of cellular senescence, and acquisition of stem cell properties. All these phenomena are related to therapy resistance and worse clinical outcomes.

PRIMARY HYPERPARATHYROIDISM AND SERUM CALCIUM IN BREAST CANCER PATIENTS EVALUATED FOR LOW BONE MASS - A SINGLE CENTER EXPERIENCE.

The bone health guidelines for breast cancer (BC) patients recommend bone mineral density (BMD) testing. Patients with low BMD and elevated serum calcium levels (SCLs) are further evaluated for primary hyperparathyroidism (PHPT). We aimed to determine the prevalence of PHPT in treated BC patients with low BMD and analyze the association of SCLs with histopathologic tumor features and cancer treatment. This retrospective study included postmenopausal BC patients examined at Osteoporosis Clinic between 2013 and 2020. Clinical and BMD data were collected from patient medical records. Patients with biochemical suspicion of PHPT underwent standard parathyroid imaging procedures. Nine out of 137 (6.6%) patients were diagnosed with PHPT; 8/9 patients underwent parathyroidectomy and one patient was advised to follow-up. Among the rest of 128 non-PHPT patients, higher SCLs showed a trend of positive association with higher tumor grade and axillary lymph node involvement, and received immunotherapy, although without statistical significance. We found a higher prevalence of PHPT in treated BC patients compared to the general population. Higher SCLs show a trend of positive correlation with some more aggressive histopathologic tumor features and with immunotherapy. The results of this study suggest that assessment of SCLs should be routinely performed to rule out PHPT in treated BC patients with low BMD.

Medullary Thyroid Cancer - Feature Review and Update on Systemic Treatment.

Medullary thyroid carcinoma (MTC) is a rare malignancy that originates from parafollicular (C cells) of the thyroid and accounts for 2-4% of all thyroid malignancies. MTC may be sporadic or inherited, the latter as part of the MEN 2 syndromes. Germline mutations in the RET proto-oncogene (REarranged during Transfection) are driver mutations in hereditary MTC, whereas somatic RET mutations and, less frequently, RAS mutations, have been described in tumor tissues of sporadic MTC. Genetic screening for germline mutations in RET proto-oncogene identifies gene carriers of germline mutations. That enables primary prevention (the avoidance of disease onset by total prophylactic thyroidectomy), or at least secondary prevention (early detection) of the disease. Radical surgery with complete tumor resection is still pivotal in attaining cure for MTC. Despite recent advances, the treatment of advanced, metastatic, and progressive MTC remains challenging. Metastatic MTC can have an indolent clinical course; therefore, it is necessary to assess which patient to cure and when to initiate the treatment. Multidisciplinary boards of various specialists involved in the diagnostics and therapy of the patients with MTC in highly specialized centers with a high volume of patients provide optimal patient management. Multikinase inhibitors (MKI) vandetanib and cabozantinib were approved for the treatment of progressive or symptomatic metastatic/unresectable MTC. Although these treatments have been shown to improve progression-free survival (PFS) with higher overall response rates (ORR) compared with placebo, no MKI has been shown to increase the overall survival (OS) yet, except in the subgroup of patients with RETM918T-mutations on cabozantinib therapy. As these drugs are nonselective, significant off-target toxicities may occur. Recently, next-generation small-molecule tyrosine kinase inhibitors (TKIs) have been developed. These highly selective RET-inhibitors are specifically designed for highly potent and selective targeting of oncogenic RET alterations, making them promising drugs for the treatment of advanced MTC. The selective RET-inhibitor selpercatinib has been very recently registered for the treatment of RET-mutated thyroid cancer.

CHALLENGES IN MANIPULATING IMMUNE SYSTEM TO TREAT PROSTATE CANCER.

First cancer vaccine that was approved for routine therapy was sipuleucel-T for treatment of patients with metastatic castration resistant prostate cancer. However, other immunotherapy drugs evaluated in prostate cancer, particularly immune checkpoint inhibitors, have failed to show therapeutic effect. There are several potential explanations for lack of response of prostate cancer to these drugs. These explanations, which are related to specific genetic (e.g. low mutational burden) and immunological (e.g. immunosuppressive tumor immune microenvironment) background of prostate cancer are discussed in this review. Also, new therapeutic strategies to overcome prostate cancer immunotherapy resistance and to select subgroups of patients that could benefit from immunotherapy are outlined.

The effects of lumboperitoneal and ventriculoperitoneal shunts on the cranial and spinal cerebrospinal fluid volume in a patient with idiopathic intracranial hypertension.

Lumboperitoneal (LP) and ventriculoperitoneal (VP) shunts are a frequent treatment modality for idiopathic intracranial hypertension (IIH). Although these shunts have been used for a long time, it is still not clear how they change the total craniospinal CSF volume and what portions of cranial and spinal CSF are affected. This report for the first time presents the results of a volumetric analysis of the total cranial and spinal CSF space in a patient with IIH. We performed an automated segmentation of the cranial and a manual segmentation of the spinal CSF space first with an LP shunt installed and again after the LP shunt was replaced by a VP shunt. When the LP shunt was in place, the total CSF volume was smaller than when the VP shunt was in place (222.4 cm(3) vs 279.2 cm(3)). The difference was almost completely the result of the spinal CSF volume reduction (49.3 cm(3) and 104.9 cm(3) for LP and VP, respectively), while the cranial CSF volume was not considerably altered (173.2 cm(3) and 174.2 cm(3) for LP and VP, respectively). This report indicates that LP and VP shunts in IIH do not considerably change the cranial CSF volume, while the reduction of CSF volume after LP shunt placement affects almost exclusively the spinal part of the CSF system. Our results suggest that an analysis of both the cranial and the spinal part of the CSF space is necessary for therapeutic procedures planning and for an early recognition of numerous side effects that often arise after shunts placement in IIH patients.

[CLINICAL RECOMMENDATIONS FOR DIAGNOSIS, TREATMENT AND MONITORING OF PATIENTS WITH ESOPHAGEAL AND ESOPHAGOGASTRIC JUNCTION CANCERS].

Esophageal and esophagogastric junction cancers comprise histologically and biologically different malignant tumors in which the progress in the understanding of the disease has not been followed by the improvement in the survival. Diagnosis is set by tumor biopsy during endoscopy. Multimodal approaches containing surgery, radiotherapy and chemotherapy are frequently applied in the treatment of locoregionally advanced disease. However, the optimal sequence of the treatment options is still the issue of numerous clinical trials and meta-analyzes. 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 esophageal and esophagogastric junction cancers in the Republic of Croatia.

Use of Alternative and Complementary Medicine in Patients with Malignant Diseases in High-Volume Cancer Center and Future Aspects

Usage of complementary and alternative medicine (CAM) is steadily increasing over the last decades, gaining medical, economic and sociological importance. The 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.