Psychotraumatization and Treatment of Posttraumatic Stress Disorder in Patients with Newly Diagnosed Breast Cancer.

BACKGROUND: According to DSM-IV cancer is a stress event with influence on development of posttraumatic stress disorder (PTSD) but in many crysis, sometimes it is hard to define concrete stressor. PTSD ussually appears in the first three moths after trauma, but can be delayed for months or years. It is hard to diferentiate psychiatric states and specific treatment methods have different impact on PTSD symptoms. Aim was to evaluate impact of different psychiatric treatment methods on development and treatment of PTSD in patients with newly diagnosed breast cancer. SUBJECTS AND METHODS: Sample consisted of 120 women with breast cancer during radiotherapy on Department for Oncology on University Hospital Osijek. Patients were divided in four groups and each group was treated with different psychiatric treatment method (psychopharmacology and/or psychotherapy, control group with no treatment). We used detailed clinical examination with psychiatric interview (DSM-IV criteria), specially structured non-standardized questionnaire for ethyological factors and LASC for PTSD. Data was analyzed by adequate statistical methods. RESULTS: Although most of participants didn't have complite PTSD, some symptoms were present, and in some women were intensive, so they should be the main group for psychiatric tretment. We found falling values of PTSD symptoms in group treated with combination of psychotherapy and psychopharmacology and raising values in a control group. They are at risk of developing whole clinical picture of PTSD during time. CONCLUSIONS: Our results prove the need for constant evaluation of PTSD development during oncology treatment and positive effects of combined psychiatric treatment on reduction of PTSD symptoms.

High Tumor Stroma Proportion is a Worse Prognostic Factor in Colorectal Cancer

High stroma proportion appears to be a very important prognostic factor in esophageal and breast cancer. Previous researches have shown that it might have a similar effect on colorectal cancer. The aim of this study was to determine whether tumor stroma proportion influenced patient survival. This retrospective study included 236 patients with colorectal cancer having undergone surgery in 2006 and 2007 at Osijek University Hospital Center. Location with the highest stroma proportion at the site of deepest tumor invasion was determined. Patients were divided into the groups with high stroma proportion (>50%) and low stroma proportion (≤50%). Stroma proportion showed a statistically significant correlation with tumor stage. Kaplan-Meier survival curves yielded a statistically significant difference in patient overall survival (Cox ph model p=0.016) and progression-free survival (Cox ph model, p=0.0188) according to stroma proportion. Study results showed a statistically significantly shorter overall survival and progression-free survival in patients with high stroma proportion.

Prognostic role of Nectin-4 expression in luminal B (HER2 negative) breast cancer.

Nectins are Ca2+-independent immunoglobulin (Ig) superfamily proteins that participate in the organization of epithelial and endothelial junctions and regulate several cellular activities including the entry of some viruses. Nectin-4 has recently been shown as a metastasis-associated protein in several cancers. In the following study, we have evaluated the expression of Nectin-4 inthe luminal B HER2 negative subtype breast cancer. The study group consisted of 147 patients presenting with primary unilateral breast carcinoma with no evidence of distant metastases. Nectin-4 protein expression was assessed by immunohistochemistry and the results were correlated with the clinical data using Kaplan-Meier curves, univariate and multivariate stepwise proportional-hazard analysis (Cox model). Nectin-4 overexpression was significantly correlated with the tumour size (p<0.05; Fisher's Exact Test), also Nectin-4 expression was negatively associated with overall survival, disease free survival and distant relapse free survival with the same significance (p<0,001; Kaplan-Meier, Cox model). We did not find statistically significant correlation between Nectin-4 and age, ER, PR, age, lymph node metastasis, tumour differentiation, histologicalsubtype and Ki-67proliferation index. We suggest that Nectin-4 is a relevant prognostic factor and a therapeutic target in luminalB (HER2 negative) breast cancer.

Bone health and adherence to vitamin D and calcium therapy in early breast cancer patients on endocrine therapy with aromatase inhibitors.

OBJECTIVES: Randomized trials involving aromatase inhibitors (AIs) in the adjuvant treatment of breast cancer patients have reported increased osteoporosis risk. Bone loss can be reduced with appropriate life style, vitamin D and calcium supplements, and with bisphosphonate therapy. The aim of this analysis was to investigate adherence to vitamin D and calcium in postmenopausal breast cancer patients receiving adjuvant non-steroidal AIs, and oncologists' adherence to the bone health guidelines. MATERIAL AND METHODS: This prospective study included 438 newly diagnosed patients and those who have already been receiving non-steroidal AIs for up to 3.5 years. Median endocrine therapy duration before recruitment in the study was 10.5 months (interquartile 4.8-26.6). RESULTS: Densitometry was performed on 142 patients (32.4%) before initiation of endocrine therapy, and on additional 38 (8.6%) patients at second study visit. Densitometry was not performed on 258 (59%) patients. Vitamin D and calcium were prescribed to 329/438 (75.1%) patients at some point during the study. Patients who took more than 80% of the prescribed dose were considered adherent. Self-reported adherence was 88.4%. Osteoporosis was diagnosed in 24 patients (5.5%) of the total study population, bearing in mind that 258/438 (59%) patients did not have densitometry. Bisphosphonates were prescribed to 54/438 (12.3%) patients, whilst only 19 (35.2%) of those had osteoporosis. CONCLUSION: In this analysis, lack of oncologists' adherence to the bone health guidelines was observed. In addition, a significant proportion of the patients did not adhere to the vitamin D and calcium.

[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.

[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.

Efficasy of Different Psychiatric Treatment Methods of Liaison Psychiatrist in Treatment of Women with Breast Cancer.

Being diagnosed with breast cancer is a traumatic event that can lead to development of different mental disorders and influences all aspects of affected woman's life. Anxiety and Depressive Disorders in physically ill people still don't have clear diagnostic criteria which make diagnosis and treatment very difficult since different psychiatric therapeutic approaches have different effects. The aim was to evaluate influence of separate and combined psychotherapeutic approach (psychodynamic and cognitive-behavioral) and psychopharmacotherapy on decrease of anxiety and depression in breast cancer patients. The sample consisted of 120 subjects divided into four groups. The first group of patients was treated with psychopharmacotherapy, the second group received psychotherapy, the third group was treated with the combination of psychopharmacotherapy and psychotherapy, and the fourth group of patients didn't receive any kind of psychiatric treatment. We used psychotherapeutic interview with detailed clinical assessment using DSM-IV criteria for mental disorders, specially structured non-standardized questionnaire for assessment of etiological factors in development of mental disorders, Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D). The subjects filled the questionnaires on entry, one moth and two months after the beginning of research. Psychotherapeutic treatment was conducted once a week. All of the therapeutic approaches of liaison psychiatrist applied in the treatment of women with breast cancer are successful in reduction of anxiety and depression. Liaison psychiatrist's combined approach of psychopharmacological and psychotherapeutic treatment of breast cancer patients with depression obtained better results than separate approach.

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

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.

Phyllodes tumors and fibroadenoma common beginning and different ending.

Phyllodes tumors and fibroadenomas are the most common benign breast tumors. They arise from intralobular fibrous tissue as a unique lesion and after a period of time they differentiate in two direction: to fibroadenoma and to phyllodes tumors. Fibroadenomas grow up to 2-3 cm and then stop growing but phyllodes tumors grow continually and sometimes are to 40 cm big. Both these lesions have two components, epithelial and stromal. Clinically fibroadenomas are well circumscibed, hard, oval, movable lesions. They can be solitary, multiple, unilateral and bilateral. They are hormone dependent changes, because they change their own consistency during menstrual cycle and gravidity. The most commonly used histological classification is in two types: pericanalicular and intracanalicular type. Phyllodes tumors make about 1% of all breast tumors. This tumor has many synonyms. It starts as fibroadenoma in intralobular stromal component. It has continuous growth and biologically it can be benign, borderline and malignant. The first description is from Miller (1838). The main goal is to find the divergence point when the developing is direct to fibroadenoma or phyllodes tumor. The second goal is to investigate the fate of epithelial and stromal component in these two lesions. Retrospective analysis is made of all fibroadenomas and phyllodes tumors in Pathology Department of Medical Center "Bezanijska kosa" in the period from 1998 to 2006. In this period, 2919 women were operated for breast changes. 343 fibroadenoma (24, 4%), were diagnosed, benign phyllodes tumor in 95 women (6.7%) and malignant phyllodes in 4 cases or 0.2%. All slides from these patients were analysed for many different histological parameters and immunohistological investigation for steroid receptors was also used, c-erbB2 (Her2/Neu), PCNA (proliferative cellular nuclear antigen) and Ki-67, androgen receptor and p53. All data were statistically investigated (Odds ratio, confidence interval, Fisher exact test, Wilcoxon sum test and Kendall test). It was concluded that fibroadenomas and phyllodes tumors arise from intralobular fibrous tissue, both changes have very close histology in the beginning and divergent growth starts later. Differences are present in stromal component. Phyllodes tumor has two component stroma. Stromal cells in phyllodes tumors are more PCNA positive than in fibroadenomas, also Ki-67 and androgen receptors are more positive in phyllodes tumors. Histologically phyllodes tumors have perforated capsule with finger like projections. These data determine surgical procedure, wide excision in phyllodes and simple excision in fibroadenomas.

[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.

Influence of psychical trauma through transgenerational transfer on the development of traumatic reactions in women with diagnosed breast cancer.

Earlier experience of psychological trauma of a close person can through a transgenerational transfer influence traumatic reactions of a person going through a trauma at present, resulting in a repetition of earlier traumatic experiences and a development of a variety of mental disturbances. Purpose of our study was to evaluate the influence of transgenerational transfer on the development of Posttraumatic stress disorder (PTSD) in women with diagnosed breast cancer that had a family member with diagnosed cancer. The sample mainly consisted of 120 women treated in a Department of Oncology, Osijek University Hospital Center with diagnosis of newly discovered breast cancer, during the conduction of radio therapy having values Hamilton depression scale (HAM-D) from > or = 8 to < or = 24 or values Hamilton anxiety scale (HAM-A) from > or = 17 to < or = 30. Psychotherapeutic interview with a detailed clinical overview and with applying diagnostic criteria according to DSM-IV for mental disorders, specially structured non-standardized questionnaire for etiologic factors evaluation of the beginning of examinees' mental disorder, Los Angeles Symptom Checklist of PTSD symptoms (LASC), Hamilton's scale for anxiety evaluation (HAM-A) and Hamilton's scale for depression evaluation (HAM-D) were used. Results show that 61 (51%) of patients have a family member with diagnosed cancer. The average total value on LASC for examinees that had a family member with diagnosed cancer was slightly higher (22.92) in comparison to those who had no such family member (20.88). No statistically significant connection was found between having a family member with diagnosed cancer and the average total value on LASC. Although no connection was established between having a family member with diagnosed cancer and the average value on LASC in women with diagnosed breast cancer, transgenerational transfer of emotions seems to be important in their traumatic reactions, but it is still insufficiently researched and it is a challenge for future researches leaving many complicated issues open.

[Ileus caused by metastasis of cutaneous malignant melanoma: case report]. / Ileus izazvan metastazom koznog malignog melanoma: prikaz bolesnika.

In this case report we describe rare metastatic appearance of cutaneous malignant melanoma ( MM) in small intestine followed by clinical appearance of acute surgical abdomen. A 42-year old women operated in our hospital in April 2009. due to unusual naevus on her right arm. Pathologicaly it was MM grossly 1.5 cm, microscopically Breslow 11 mm, Clark's level IV (T4), number of mitosis 1.4 per mm2, without ulcerations. She was sent to continue treatment at the National Referal Center for Melanoma in KB "S. milosrdnice" Zagreb, Croatia. A month later wider excision (3 cm free margin) and sentinel lymph node biopsy (SLNB) was made there followed by axillary lymphadenectomy due to positive axillary finding. She received six cycles of chemotherapy. She arrived in our hospital in May 2010, under clinical picture of small intestine ileus and acute surgical abdomen. After preparation she was operated the same day. The cause of ileus was metastasis of MM in the small interstine. We made intestinal resection with termino-terminal anastomosis. The patient was released to home care ten days after operation without any complication. This case report demonstrates rarely described case of MM metastasis in the small intestine found causing ileus.

[Clinical recommendations for diagnosing, treatment and monitoring patients with non-small cell lung cancer]. / Klinicke upute za dijagnozu, lijecenje i pracenje bolesnika oboljelih od karcinoma pluca nemalih stanica.

In Croatia, lung cancer is the most common malignant disease among male population and the third common among female population where 85% of patients have non-small cell lung cancer. Due to significance of this disease it is necessary to define and implement standardized approach for diagnostic and treatment algorithm as well to patients monitoring. Several multidisciplinary sessions were organized in achieving this goal. The sessions' results are given in the form of the Clinical guidelines.

[Croatian guideliness for prevention of chemotherapy induced nausea and vomiting]. / Hrvatske smjernice za prevenciju mucnine i povracanja uzrokovanih kemoterapijom.

Approximately 70-80% of all cancer patients receiving chemotherapy experience nausea and/or vomiting. Nausea and vomiting are important side effects of cancer treatment, which can significantly affect a patient's quality of life, leading to poor compliance with further chemotherapy treatment. The main principle of emesis control is prevention. Currently available antiemetic agents corticosteroids, 5-hydroxytriptamine receptor antagonists, and neurokinin-1 antagonists, are used alone or in combination. Antiemetic regimen should be chosen based on the emetogenic potential of the chemotherapy regimen, previous experience with antiemetics, and patient-specific risk factors. Newer agents, including second generation 5-HT3 receptor antagonist palonosetron and the NK-1 antagonist aprepitant, offer additional clinical benefit in highly and moderately emetogenic therapy, especially in delayed nausea and vomiting. The aim of this Guidelines is to achieve same standards of care in the treatment of nausea and vomiting across Croatia that are applicable in our environment--only available drugs are included in the Guidelines.

Influence of liaison psychiatric approach on quality of life in patients with newly diagnosed breast cancer.

Having breast cancer represents traumatic stress event that can influence development of psychiatric disorders during psychological adjustment. The aim of research was to investigate influence of liaison psychiatric approach on quality of life in patients with breast cancer. Sample consisted of 120 women with breast cancer treated on Department for Oncology in University Hospital Osijek. Patients were in liaison psychiatric treatment for two months. They were estimated on the first day, after one and two months of treatment. We used psychiatric interview and DSM-IV criteria, specially structured non-standardized questionnaire for estimation of potential ethyological factors for psychiatric disorders and WHOQOL-BREF for estimation of quality of life. We found that liaison psychiatric approach improved quality of life in patients with newly diagnosed breast cancer.

[Morphological characteristics of the phyllodes tumours of the breast]. / Morfoloske karakteristike filodnih tumora dojke.

Tumor phyllodes arise from stroma component of the terminal ductulo-lobular unit (TDLU). Stromal and epithelial proliferation are present in the same time. The stromal component grow th more intensive and dominante over the epithelial component. Clinically, macroscopically and microscopically tumor phyllode look like fibroadenoma which is more common lesion than tumor phyllodes. The differentiation between these two lession is important because the fibroadenoma almost never reccur bur the reccurence is ofthen in tumor phyllodes especially in incomplete excision. The fibroadenoma growth is never over 3 cm, but the growth of tumor phyllodes is sometimes over the 20 cm. The clinica differentiation in smaller lesions is very hard, macroscopical differentiation is a litle better, but the final diagnosis is microscopical. Biological behavior is not in the correlation with histological picture. Histologically, we can differentiate benign, borderline and malignant tumor phyllodes.

Unilateral multicentric breast cancer.

Clinical characteristics of unilateral multicentric breast cancer (UMBC) were explored depending on aggressiveness, survival rate, disease-free period and local recurrence. The study included 296 women with breast cancer, surgically treated between 1990 and 2001. UMBC was histologically proved in 29 (9.8%) patients. Multicentricity was defined by following criteria: a) tumor with minimum one satellite node in the same or other quadrant of the breast; b) minimum one cut through the breast without tumor cells; c) histopathologically, discontinued tumors with intra-ductal invasion. The average age of patients was 63.4 (range 36-85). There were 9 (31.0%) women with one satellite node, 7 (24.1%) women with two satellite nodes, and 13 (44.8%) women with three or more satellite nodes. At the operation, axilla was positive in 20 (68.9%) women. Steroid receptors were highly positive in 12 (41.4%) patients. Primary and secondary tumors were of the same histological type in 26 (89.6%) patients. Local recurrence was found in only 3 (10.3%) patients. A five-year period without disease was achieved in 24 (82.7%) women. Kaplan-Meier analysis showed a significantly higher survival rate at lower tumor stages (I or II) unlike in advanced stages with predominantly N2 grade. The results of this study showed a slightly lower five-year disease-free period than in the case of patients with monocentric breast cancer (MOBC). The survival rate was significantly lower at all advanced stages, especially determined by N2 axilla. Therefore, the conclusion is that multicentricity doesn't increase the risk of poor prognosis, especially at lower tumor stages.

Effects of war aggression in Croatia on histopathological manifestations of breast cancer in defined population of one county.

The aim of the present study was to determine the differences in epidemiological and clinical manifestations of breast cancer during the war in Croatia and in peacetime. 660 consecutive patients were recorded (656 female and 4 male patients) from Pozesko-Slavonska County. The changes in histopathological features were recorded in war period (1991-1995, 156 patients) and through two control periods, before the war (1981-1990, 282 patients) and after the war (1995-2000, first five months, 223 patients). The relative predictive value was calculated using chi 2-test. The survival was calculated according to Kaplan-Meier analysis of survival. The histopathological analysis showed an equal distribution of noninvasive cancer (in situ cancer) across periods. In the war period, the level of the most common invasive cancer, ductal breast cancer, was lower (57.7%), compared to control periods (71.2%:63.7%:68.2%). Opposite to that, invasive lobular cancer was more common in the war period (3.2%), compared to control periods (0.7%-1.3%). Furthermore, mixed cancer was also increased in the war period (7.1%) compared to control periods (0.7%-2.2%), as was medullar cancer (10.9% vs. 5.5%-5.9%). The study showed statistically significant differences in the survival of patients with different histopathological diagnoses (Log Rank = 47.49, df = 7, p < 0.0001), while the histological grade of tumor, as a predictive factor was not proved to be statistically significant (p > 0.05). This study confirmed the influence of war of war on histopathological incidence of some forms of breast cancer.