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.

Impact of the number of therapy lines on survival in advanced gastric and esophagogastric adenocarcinoma - a real-world retrospective analysis from Croatia.

The aim of the study was to conduct a retrospective database analysis to understand the current treatment patterns and outcomes to plan potential improvements in therapy delivery and patient selection. The electronic patient medical records of 225 patients with advanced gastric and esophagogastric adenocarcinoma treated at two Croatian high-volume tertiary centers from January 2018 to December 2021 were analyzed. Patients ineligible for chemotherapy (66 of 291, 22.7%) due to poor general condition or co-morbidities were not included in the study. The median overall survival (OS) for the whole cohort was 11.0 months (95% confidence interval (CI) 9.7-12.0). Of the 225 patients who received first-line therapy, 47.6%, 16.9%, and 3.1% received second-, third-, and fourth-line therapy, respectively. Survival correlated significantly with the number of treatment lines received (p<0.001), with a median OS from diagnosis of 7.8 (95% CI 6.6-9.4), 12.0 (95% CI 10.0-14.0), and 20.0 months (95% CI 18.0-23.0) for patients receiving 1, 2, and ≥3 lines of treatment, respectively. This study confirmed the positive impact of the number of chemotherapy lines on OS. This highlights the importance of the ratio of patients receiving multiple lines of therapy as well as the availability of new and effective drugs in real-life clinical practice. The selection of optimal therapy for each patient in the first-line therapy is important because a significant number of patients do not receive second-line therapy.

Correlation between psychological resilience and burnout syndrome in oncologists amid the Covid-19 pandemic.

PURPOSE: Oncologists are predisposed to developing burnout syndrome. Like other health care professionals worldwide, oncologists have endured additional, extreme challenges during the Covid-19 pandemic. Psychological resilience presents a potential protective mechanism against burnout. This cross-sectional study examines whether psychological resilience eased burnout syndrome among Croatian oncologists during the pandemic. METHODS: An anonymized self-reporting questionnaire was electronically distributed by the Croatian Society for Medical Oncology to 130 specialist and resident oncologists working in hospitals. Available for completion from September 6-24, 2021, the survey comprised demographic questions; the Oldenburg Burnout Inventory (OLBI), covering exhaustion and disengagement; and the Brief Resilience Scale (BRS). The response rate was 57.7%. RESULTS: Burnout was moderate or high for 86% of respondents, while 77% had moderate or high psychological resilience. Psychological resilience was significantly negatively correlated with the OLBI exhaustion subscale (r = - .54; p < 0.001) and the overall OLBI score (r = - .46; p < 0.001). Scheffe's post hoc test showed that oncologists with high resilience scored significantly lower on the overall OLBI (M = 2.89; SD = 0.487) compared to oncologists with low resilience (M = 2.52; SD = 0.493). CONCLUSION: The findings thus indicate that oncologists with high psychological resilience are at significantly lower risk of developing burnout syndrome. Accordingly, convenient measures to encourage psychological resilience in oncologists should be identified and implemented.

Differences in Outcomes Between Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer Patients in Upper Middle-Income versus High-Income Countries: A Retrospective Study from 4 Oncology Centers.

BACKGROUND Therapeutic options for human epidermal growth factor 2 (HER2)-positive metastatic breast cancer (mBC) are developing rapidly. This study aimed to determine the differences in the survival outcomes of patients with HER2-positive mBC in relation to access to anti-HER therapy at 3 oncology centers in upper-middle-income countries (UMICs) and 1 oncology center in a high-income country (HIC). MATERIAL AND METHODS We retrospectively identified 42 patients from Croatia (HIC), 71 patients from Serbia (UMIC), and 57 from Bosnia and Herzegovina (UMIC) diagnosed with HER2-positive mBC who were treated between January 2015 and December 2020. The pathohistological features of the tumors were obtained from the pathological findings, which were made according to standard procedures for each center. Patients were treated depending on the availability of therapy, which differed for centers in different countries. We evaluated disease-free survival, progression-free survival, and overall survival (OS) based on the availability of first- and second-line anti-HER2 therapy in UMICs vs HIC. RESULTS OS in first-line therapy was better in patients treated with dual HER2 blockade than in patients treated without dual HER2 blockade, P<0.001. OS in second-line therapy was significantly better in patients treated with trastuzumab emtansine than in patients treated with other reported regimens, P=0.004. CONCLUSIONS Results of our study showed superior survival among patients who were treated with dual first-line HER2 therapy as well as second-line trastuzumab emtansine therapy than in those patients in other centers where these drugs were not available. Raising awareness about this could help improve the situation.

Frequency of Body Weight Loss is an Independent Prognostic Factor of First-Line Treatment Outcomes in Metastatic Colorectal Cancer.

One of the main features of wasting in cancer is an involuntary weight loss which is most pronounced in gastrointestinal tract tumors and leads to worse clinical outcomes. The aim of this study is to analyze the frequency of body weight loss (FBWL) as an additional prognostic factor in the treatment of patients with metastatic colorectal cancer (mCRC).In this observational, single-center study, data were retrieved for 236 patients treated for mCRC. FBWL was defined as a percent of change in weight divided by weeks of therapy. Patients were stratified into two groups according to the median of FBWL which equaled to the loss of 0.05%/week. Patients who lost >0.05%/week (N = 116) had shorter progression-free survival (PFS) in the first-line treatment, then the ones who lost <0.05%/week (N = 120); 28.3 vs 46.3 weeks, respectively. Cox regression model showed that FBWL and sidedness were significant predictors of PFS, while age, sex and ECOG were not. Significantly more patients with stable weight were also eligible for second-line treatment. In conclusion, stabilization of body weight is important and independent predictor of longer PFS in first-line therapy of patients with mCRC.

DPYD polymorphisms c.496A>G, c.2194G>A and c.85T>C and risk of severe adverse drug reactions in patients treated with fluoropyrimidine-based protocols.

AIMS: Cancer patients with reduced dihydropyrimidine dehydrogenase (DPD) activity are at increased risk of severe fluoropyrimidine (FP)-related adverse events (AE). Guidelines recommend FP dosing adjusted to genotype-predicted DPD activity based on four DPYD variants (rs3918290, rs55886062, rs67376798 and rs56038477). We evaluated the relationship between three further DPYD polymorphisms: c.496A>G (rs2297595), *6 c.2194G>A (rs1801160) and *9A c.85T>C (rs1801265) and the risk of severe AEs. METHODS: Consecutive FP-treated adult patients were genotyped for "standard" and tested DPYD variants, and for UGT1A1*28 if irinotecan was included, and were monitored for the occurrence of grade ≥3 (National Cancer Institute Common Terminology Criteria) vs. grade 0-2 AEs. For each of the tested polymorphisms, variant allele carriers were matched to respective wild type controls (optimal full matching combined with exact matching, in respect to: age, sex, type of cancer, type of FP, DPYD activity score, use of irinotecan/UGT1A1, adjuvant therapy, radiotherapy, biological therapy and genotype on the remaining two tested polymorphisms). RESULTS: Of the 503 included patients (82.3% colorectal cancer), 283 (56.3%) developed grade ≥3 AEs, mostly diarrhoea and neutropenia. Odds of grade ≥3 AEs were higher in c.496A>G variant carriers (n = 127) than in controls (n = 376) [OR = 5.20 (95% CI 1.88-14.3), Bayesian OR = 5.24 (95% CrI 3.06-9.12)]. Odds tended to be higher in c.2194G>A variant carriers (n = 58) than in controls (n = 432) [OR = 1.88 (0.95-3.73), Bayesian OR = 1.90 (1.03-3.56)]. c.85T>C did not appear associated with grade ≥3 AEs (206 variant carriers vs. 284 controls). CONCLUSION: DPYD c.496A>G and possibly c.2194G>A variants might need to be considered for inclusion in the DPYD genotyping panel.

The First Wave of the COVID-19 Pandemic and Its Impact on the Level of Distress in Patients with Breast Cancer, a Multicentric Study.

BACKGROUND: Information on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), later termed coronavirus disease (COVID-19), first emerged by the end of 2019. As the pandemic spread, cancer patients were immediately recognized as a high-risk population with regard to COVID-19 infection. Moreover, epidemiological measures, like social distancing and lockdowns, additionally burdened patients with cancer. Even outside pandemic breast cancer patients are prone to psychological distress with prevalence ranging approximately 20-40%. This multicentric study aimed to examine the impact of COVID-19 pandemic on the level of distress among breast cancer patients in Croatia while the first wave of COVID-19 pandemic. SUBJECTS AND METHODS: Fife hundred forty-five breast cancer patients were offered to participate in the study. A total of two hundred and one patient, with disease stages ranging I-IV, completed the questionnaire. The questionnaire consisted of disease and socio-demographic characteristics followed by the Distress Thermometer and a problem list. The cut off value of 4 was used to define the high level of distress within Distress Thermometer. RESULTS: High distress level was reported in 54.2% of patients. The most significant problems reported by the participants of our study affected emotions, causing worry, sadness, depression, fear, and nervousness. Additionally, specific practical problems emerged (e.g., child care, housing, and work/school), most probably partly due to the lockdowns and social distancing. Interestingly enough, none of the socio-demographic or disease characteristics were linked to the level of distress. CONCLUSIONS: During first wave of COVID-19 pandemic more than half of breast cancer patients, undergoing active oncologic treatment, experienced a high level of distress. Therefore, distress driven by the COVID-19 pandemic should be promptly addressed and additional psychological and social support, targeting specific practical and emotional problems, should be provided for those patients. All the more so as global COVID-19 pandemic far exceeded the duration of the first wave.

Leukocytoclastic vasculitis associated with sorafenib treatment for hepatocellular carcinoma.

Small-vessel vasculitis is an uncommon diagnosis associated with many causes, including certain medication. Characteristic findings are immune complex deposition, vessel wall damage, and erythrocyte extravasation. We present a case of a 77-year-old man with advanced hepatocellular carcinoma who was treated with sorafenib. Twenty days post introduction to sorafenib, the patient experienced high fever and painful purpura on the lower limbs. The results of the skin biopsy confirmed the diagnosis. More extensive diagnostics was undertaken, which excluded other possible causes of vasculitis and infectious disease. Following a full recovery, after the steroid treatment was completed, sorafenib has been continued until the progression of the carcinoma. This is the second described case of hepatocellular carcinoma associated with sorafenib treatment and leukocytoclastic vasculitis. Sorafenib is a potential cause of vasculitis, and clinicians should bear in mind to differentiate it from hand-foot skin reaction, which is a common side effect of multikinase inhibitors. The result of our assessment is important considering that vasculitis requires more specific diagnostic procedures, treatment, and often drug discontinuation.

[CLINICAL GUIDELINES FOR DIAGNOSIS, TREATMENT AND MONITORING OF PATIENTS WITH INVASIVE BREAST CANCER--CROATIAN ONCOLOGY SOCIETY]. / KLINICKE UPUTE HRVATSKOGA ONKOLOSKOG DRUSTVA ZA DIJAGNOZU, LIJECENJE I PRACENJE BOLESNICA/KA OBOLJELIH OD INVAZIVNOG RAKA DOJKE.

Breast cancer is the most common cancer in women. It can be diagnosed in early stage through screening, early detection and educational programs, and when diagnosed early it can be efficiently treated. Treatment modalities include surgery, chemotherapy, radiotherapy, hormonal therapy and targeted biologic therapy, 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 diagnosis, management, treatment and monitoring of patients with breast cancer in the Republic of Croatia.

Consensus statement on screening, diagnosis, classification and treatment of endemic (Balkan) nephropathy.

Currently used diagnostic criteria in different endemic (Balkan) nephropathy (EN) centers involve different combinations of parameters, various cut-off values and many of them are not in agreement with proposed international guidelines. Leaders of EN centers began to address these problems at scientific meetings, and this paper is the outgrowth of those discussions. The main aim is to provide recommendations for clinical work on current knowledge and expertise. This document is developed for use by general physicians, nephrologists, urologist, public health experts and epidemiologist, and it is hoped that it will be adopted by responsible institutions in countries harboring EN. National medical providers should cover costs of screening and diagnostic procedures and treatment of EN patients with or without upper urothelial cancers.

Gastroenteropancreatic neuroendocrine tumour arising in Meckel's diverticulum coexisting with colon adenocarcinoma.

Although colon cancer is the third most common cause of cancer-related death worldwide, the prevalence of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) remains rare. To date, very few cases of GEP-NETs within Meckel's diverticulum and synchronous colorectal cancer have been reported. Although the coexistence of these two tumour types is uncommon, it is important to be aware of their disease patterns. We present a rare case of a patient with an intestinal GEP-NET arising in Meckel's diverticulum coexisting with metastatic colon adenocarcinoma, and we discuss the clinical manifestations and the diagnostic procedures and treatment modalities used. This case report underlines the importance of being aware of this particular coexistence, as well as the unlikely metastatic spread of GEP-NETs and the importance of a multidisciplinary approach to cancer treatment. Finally, individualizing the treatment according to the stages of the primaries will result in durable cancer control, particularly in synchronous double malignancy.

Successful resection of hepatocellular cancer not amenable to Milan criteria and durable complete remission induced by systemic polichemotherapy after development of metastases - should we think about revising the current treatment guidelines in selected patients?

OBJECTIVES: To refresh clinical diagnostic and therapeutic dilemmas in patients presenting with hepatocellular cancer (HCC) and to report a rare success of systemic polichemotherapy in metastatic HCC. METHODS: Case report of a patient with successfully resected HCC although initially deemed inoperable according to current guidelines, and who was successfully treated by systemic polichemotherapy after development of metastatic disease, resulting in a sustained complete remission. RESULTS: We describe a 71-year-old female with HCC initially treated by atypical liver resection, although not amenable to initial surgery according to current treatment guidelines, which resulted in 6 months disease-free interval. After development of pulmonary metastases, the patient was treated by systemic polichemotherapy, due to local unavailability of novel biologic agents. After 3 months of chemotherapy biochemical remission was confirmed, and after 10 months of active treatment complete radiological remission was verified according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, now exceeding 9 months in duration. CONCLUSION: There is an increasing body of evidence that criteria for surgical interventions in HCC should be revised and expanded, and our case is an example of such an approach. Although novel biologic therapies are not widely available in all regions of the world due to their cost, currently there are no hard recommendations for use of chemotherapy in such areas. Since this is a large problem in clinical practice, we conclude that chemotherapy should be offered to selected patients of good performance status if novel agents are unavailable.

Symptomatic cardiac metastases of breast cancer 27 years after mastectomy: a case report with literature review--pathophysiology of molecular mechanisms and metastatic pathways, clinical aspects, diagnostic procedures and treatment modalities.

Metastases to the heart and pericardium are rare but more common than primary cardiac tumours and are generally associated with a rather poor prognosis. Most cases are clinically silent and are undiagnosed in vivo until the autopsy. We present a female patient with a 27-year-old history of an operated primary breast cancer who was presented with dyspnoea, paroxysmal nocturnal dyspnoea and orthopnoea. The clinical signs and symptoms aroused suspicion of congestive heart failure. However, the cardiac metastases were detected during a routine cardiologic evaluation and confirmed with computed tomography imaging. Additionally, this paper outlines the pathophysiology of molecular and clinical mechanisms involved in the metastatic spreading, clinical presentation, diagnostic procedures and treatment of heart metastases. The present case demonstrates that a complete surgical resection and systemic chemotherapy may result in a favourable outcome for many years. However, a lifelong medical follow-up, with the purpose of a detection of metastases, is highly recommended. We strongly call the attention of clinicians to the fact that during the follow-up of all cancer patients, such heart failure may be a harbinger of the secondary heart involvement.

Leptomeningeal and intramedullary metastases of glioblastoma multiforme in a patient reoperated during adjuvant radiochemotherapy.

Despite huge advances in medicine, glioblastoma multiforme (GBM) remains a highly lethal, fast-growing tumour that cannot be cured by currently available therapies. However, extracranial and extraneural dissemination of GBM is extremely rare, but is being recognised in different imaging studies. To date, the cause of the GBM metastatic spread still remains under discussion. It probably develops at the time of intracranial progression following a surgical procedure. According to other hypothesis, the metastases are a consequence of spontaneous tumour transdural extension or haematogenous dissemination. We present a case of a 59-year-old woman with symptomatic leptomeningeal and intramedullary metastases of GBM who has been previously surgically treated with primary subtotal resection and underwent a repeated surgery during adjuvant radiotherapy and chemotherapy with temozolomide. Today, the main goal of surgery and chemoradiotherapy is to prevent neurologic deterioration and improve health-related quality of life. With this paper, we want to present this rare entity and emphasise the importance of a multidisciplinary approach, a key function in the management of brain tumour patients. The prognosis is still very poor although prolongation of survival can be obtained. Finally, although rare, our case strongly suggests that clinicians should be familiar with the possibility of the extracranial spread of GBM because as treatment improvements provide better control of the primary tumour and improving survival, metastatic disease will be increasingly encountered.

Paraneoplastic stiff person syndrome associated with colon cancer misdiagnosed as idiopathic Parkinson's disease worsened after capecitabine therapy.

OBJECTIVES: To refresh clinical diagnostic dilemmas in patients presenting with symptoms resembling to those of parkinsonism, to report rare association of colon cancer and paraneoplastic stiff person syndrome (SPS), and to draw attention on the possible correlation of capecitabine therapy with worsening of paraneoplastic SPS. METHODS: Case report of the patient with paraneoplastic SPS due to colon cancer that was misdiagnosed as idiopathic Parkinson's disease (iPD), whose symptoms worsened after beginning adjuvant capecitabine chemotherapy. RESULTS: We describe a 55-year-old woman with subacute onset of symmetrical stiffness and rigidity of the truncal and proximal lower limb muscles that caused lower body bradykinesia, gait difficulties, and postural instability. Diagnose of iPD was made and levodopa treatment was initiated but failed to provide beneficial effect. Six months later, colon cancer was discovered and the patient underwent surgical procedure and chemotherapy with capecitabine thereafter. Aggravation of stiffness, rigidity, and low back pain was observed after the first chemotherapy cycle and capecitabine was discontinued. Furthermore, levodopa was slowly discontinued and low dose of diazepam was administered which resulted in partial resolution of the patient's symptoms. CONCLUSION: Paraneoplastic SPS is rare disorder with clinical features resembling those of parkinsonian syndrome and making the correct diagnosis remains a challenge. The diagnosis of parkinsonian syndrome should be re-examined if subsequent examinations discover an associated malignant process. Although it remains unclear whether the patients with history of SPS are at the greater risk for symptoms deterioration after administration of capecitabine, clinicians should be aware of capecitabine side effects because recognition and appropriate management can prevent serious adverse outcomes.

Long-term follow-up of complete remission in a patient with advanced hepatocellular carcinoma treated with sorafenib: a case report.

Introduction: Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancer and can be caused by well-known risk factors, including infection with hepatitis B and C viruses, alcohol intake, and metabolic syndrome. The overall prognosis remains poor with a median survival of 1 year for symptomatic advanced-stage cases treated with systemic therapies. Case description: In July 2020, a 73-year-old male patient presented at our institution with mild abdominal pain and an attack of intense cold. After a radiological workup, the diagnosis of HCC located in the caudate lobe was established. The patient underwent atypical caudate lobe resection, and pathology confirmed the diagnosis of grade 3 HCC. Postoperative MRI showed a new metastasis in the 6th liver segment 1.3 cm in diameter, and a PVT progression which now affected the whole right lobe. The patient was started on sorafenib and demonstrated a complete response which still lasts for more than two years. Conclusion: We present a rare case of a patient who demonstrated a complete response to sorafenib treatment in advanced HCC with unfavorable prognostic factors.

DPYD genotyping and predicting fluoropyrimidine toxicity: where do we stand?

Fluoropyrimidines (FPs) are antineoplastic drugs widely used in the treatment of various solid tumors. Nearly 30% of patients treated with FP chemotherapy experience severe FP-related toxicity, and in some cases, toxicity can be fatal. Patients with reduced activity of DPD, the main enzyme responsible for the breakdown of FP, are at an increased risk of experiencing severe FP-related toxicity. While European regulatory agencies and clinical societies recommend pre-treatment DPD deficiency screening for patients starting treatment with FPs, this is not the case with American ones. Pharmacogenomic guidelines issued by several pharmacogenetic organizations worldwide recommend testing four DPD gene (DPYD) risk variants, but these can predict only a proportion of toxicity cases. New evidence on additional common DPYD polymorphisms, as well as identification and functional characterization of rare DPYD variants, could partially address the missing heritability of DPD deficiency and FP-related toxicity.

Analysis of the Gut Microbiome and Dietary Habits in Metastatic Melanoma Patients with a Complete and Sustained Response to Immunotherapy.

Immunotherapy has improved the prognosis of metastatic melanoma patients, although most patients do not achieve a complete response. While specific gut microbiome and dietary habits might influence treatment success, there is a lack of concordance between the studies, potentially due to dichotomizing patients only into responders and non-responders. The aim of this study was to elucidate whether metastatic melanoma patients with complete and sustained response to immunotherapy exhibit differences in gut microbiome composition among themselves, and whether those differences were associated with specific dietary habits. Shotgun metagenomic sequencing revealed that patients who exhibited a complete response after more than 9 months of treatment (late responders) exhibited a significantly higher beta-diversity (p = 0.02), with a higher abundance of Coprococcus comes (LDA 3.548, p = 0.010), Bifidobacterium pseudocatenulatum (LDA 3.392, p = 0.024), and lower abundance of Prevotellaceae (p = 0.04) compared to early responders. Furthermore, late responders exhibited a different diet profile, with a significantly lower intake of proteins and sweets and a higher intake of flavones (p < 0.05). The research showed that metastatic melanoma patients with a complete and sustained response to immunotherapy were a heterogeneous group. Patients with a late complete response exhibited microbiome and dietary habits which were previously associated with an improved response to immunotherapy.

Psychological status and recurrent aphthous ulceration.

Recurrent aphthous ulceration (RAU) are a disease of an unknown etiology and mediated through T-cell lymphocytes. Evidence suggests that RAU is connected with chronic bowel disease, haematinic deficiencies, AIDS, food hypersensitivity and severe stress. The aim of this study was to determine whether differences in anxiety and depression could be seen in patients with RAU during acute phase and remision period and in comparison to the healthy controls. There were 30 patients with RAU (age range 36.27 +/- 15.308) and 30 controls aged 29.83 +/- 9.082. Every participant with RAU fullfilled STAI and Beck Depression Inventory II test during acute phase and during remission period as well as controls. Statistical analysis was performed by use of descriptive statistics and t-test. There are no differences in the level of depression and stress between the two phases of the RAU (acute versus remission period) as well as in comparison to the controls. Patients with acute RAU are more anxious than patients with RAU during remission period. We might conclude that psychological disturbances do not preceed the development of RAU and that the patients with acute RAU are more anxious when compared to the condition when they do not have RAU due to the discomfort they experience.

[Clinical recommendations for diagnosis, treatment and monitoring of patients with invasive breast cancer]. / Klinicke upute za dijagnozu, lijecenje i pracenje bolesnika oboljelih od invazivnog raka dojke.

Breast cancer is the most common malignancy in women. Preventive measures, early diagnosis and development of all treatment modalities (surgery, radiotherapy, chemotherapy, hormonal and targeted biologic therapy) led to improvement in survival and quality of life of the patient. In order to standardize and optimize the approach, following good clinical practice standards, we bring consensus guidelines for diagnosis, treatment and monitoring of breast cancer patients as a result of consensus of a multidisciplinary team of experts for breast cancer.