Dijagnostički i prognostički čimbenici u bolesnika s metastatskim karcinomom nepoznatog primarnog sijela : doktorska disertacija

CILJ ISTRAŽIVANJA: Cilj istraživanja bio je identificirati dijagnostičke i prognostičke čimbenike u bolesnika s karcinomom nepoznatog primarnog sijela (CUP od engl. Cancers of Unknown Primary) koji ne pripadaju u povoljne prognostičke podskupine i razvoj prognostičkog indeksa za predviđanje preživljenja u ovih bolesnika. ISPITANICI i METODE: U ovoj smo disertaciji prospektivnim praćenjem analizirali univarijatnom i multivarijatnom metodom 16 kliničkih i bioloških obilježja kod 145 bolesnika s malignom bolesti nepoznatog primarnog sijela u dvije bolničke ustanove (Klinički bolnički centar Rijeka i Opća bolnica Pula). Bolesnici sa potencijalno izlječivim podskupinama CUP-a nisu analizirani. REZULTATI: jednogodišnje preživljenje iznosilo je 42%, a medijan je bio 330 dana. Preživljenje je bilo povezano sa slijedećim čimbenicima: loš performans status mjeren "Eastern Cooperative Oncology Group Performance Status" kriterijima (ECOG PS) ≥ 2, prisutnost jetrenih metastaza, povišene serumske vrijednosti laktat dehidrogenaze (LDH), leukocitozom, anemijom, starosti 63 godine ili više i produljenju QTc intervala u elektrokardiogramu (EKG). Multivarijatnom analizom četiri čimbenika su iskazali nezavisnu statističku značajnost: povišen LDH (hazard ratio (HR) 2.21; 95% confidence interval (CI) 1.41– 3.47; P = 0.001), produžen QTc u EKG-u (HR 2.10; 95% CI 1.28–3.44; P = 0.003), prisutnost jetrenih metastaza (HR 1.77; 95% CI 1.11–2.81; P = 0.016) i ECOG PS ≥ 2 (HR 1.69; 95% CI 1.05–2.73; P = 0.03). U nastavku smo razvili prognostički indeks koristeći ova četiri čimbenika i formirali tri podskupine: sa dobrom prognozom (bez ili sa jednim čimbenikom), skupina srednjeg rizika (prisutna dva čimbenika) i skupinu loše prognoze (prisutna tri ili sva četiri čimbenika). Medijan preživljenja prema pripadnosti ovim podskupinama iznosio je 420, 152 i 60 dana. Razlika između pojedinih skupina rizika bila je statistički značajna (log rank test P < 0.0001). ZAKLJUČCI: Ovom studijom potvrdili smo prethodno dokazane prognostičke čimbenike u bolesnika s CUP-om. QTc interval u EKG-u je identificiran kao novi nezavisni prognostički čimbenik. Razvili smo i jednostavan prognostički indeks koristeći ova četiri čimbenika čime je bolesnike moguće svrstati u neke od tri prognostičke podskupine sa različitim ishodom bolesti.OBJECTIVES: The aims of this study was to identify independent diagnostic and prognostic factors in patients with cancer of unknown primary site (CUP) who do not belong to prognostically favourable subsets, and to develop a prognostic index for predicting survival in these patients. PATIENTS AND METHODS: In this prospective study, univariate and multivariate analyses of 16 prognostic factors were conducted in a population of 145 patients with CUP in two clinical institutions (General Hospital Pula and Clinical Hospital Rijeka). Subsets of patients with favourable prognostic features and those requiring well-defined treatment were excluded. RESULTS: The 1-year overall survival rate for all patients was 42% and the median overall survival was 330 days. Overall survival was significantly related to the following pre-treatment prognostic factors: poor Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2, presence of liver metastasis, elevated serum lactate dehydrogenase (LDH), high white blood cell count, anaemia, age ≥ 63 years, and prolonged QTc interval in electrocardiogram (ECG). In multivariate analysis, four independent adverse prognostic parameters were retained: elevated LDH (Hazard Ratio (HR) 2.21; 95% Confidence Interval (CI) 1.41–3.47; P = 0.001), prolonged QTc interval (HR 2.10; 95% CI 1.28–3.44; P = 0.003), liver metastasis (HR 1.77; 95% CI 1.11–2.81; P = 0.016) and ECOG PS ≥ 2 (HR 1.69; 95% CI 1.05– 2.73; P = 0.03). We developed a prognostic index for overall survival based on the following subgroups: good prognosis (no or one adverse factor), intermediate prognosis (two adverse factors) and poor prognosis (three or four adverse factors). The median overall survival for the three subgroups was 420, 152 and 60 days, respectively, P < 0.0001. CONCLUSIONS: This study validated previously identified important prognostic factors for survival in patients with CUP. Prolonged QTc was additionally identified as a strong adverse prognostic factor. We developed a simple prognostic index using performance status, LDH, presence of liver metastasis and QTc interval in ECG, which allowed assignment of patients into three subgroups with divergent outcome

Dijagnostički i prognostički čimbenici u bolesnika s metastatskim karcinomom nepoznatog primarnog sijela : doktorska disertacija

CILJ ISTRAŽIVANJA: Cilj istraživanja bio je identificirati dijagnostičke i prognostičke čimbenike u bolesnika s karcinomom nepoznatog primarnog sijela (CUP od engl. Cancers of Unknown Primary) koji ne pripadaju u povoljne prognostičke podskupine i razvoj prognostičkog indeksa za predviđanje preživljenja u ovih bolesnika. ISPITANICI i METODE: U ovoj smo disertaciji prospektivnim praćenjem analizirali univarijatnom i multivarijatnom metodom 16 kliničkih i bioloških obilježja kod 145 bolesnika s malignom bolesti nepoznatog primarnog sijela u dvije bolničke ustanove (Klinički bolnički centar Rijeka i Opća bolnica Pula). Bolesnici sa potencijalno izlječivim podskupinama CUP-a nisu analizirani. REZULTATI: jednogodišnje preživljenje iznosilo je 42%, a medijan je bio 330 dana. Preživljenje je bilo povezano sa slijedećim čimbenicima: loš performans status mjeren "Eastern Cooperative Oncology Group Performance Status" kriterijima (ECOG PS) ≥ 2, prisutnost jetrenih metastaza, povišene serumske vrijednosti laktat dehidrogenaze (LDH), leukocitozom, anemijom, starosti 63 godine ili više i produljenju QTc intervala u elektrokardiogramu (EKG). Multivarijatnom analizom četiri čimbenika su iskazali nezavisnu statističku značajnost: povišen LDH (hazard ratio (HR) 2.21; 95% confidence interval (CI) 1.41– 3.47; P = 0.001), produžen QTc u EKG-u (HR 2.10; 95% CI 1.28–3.44; P = 0.003), prisutnost jetrenih metastaza (HR 1.77; 95% CI 1.11–2.81; P = 0.016) i ECOG PS ≥ 2 (HR 1.69; 95% CI 1.05–2.73; P = 0.03). U nastavku smo razvili prognostički indeks koristeći ova četiri čimbenika i formirali tri podskupine: sa dobrom prognozom (bez ili sa jednim čimbenikom), skupina srednjeg rizika (prisutna dva čimbenika) i skupinu loše prognoze (prisutna tri ili sva četiri čimbenika). Medijan preživljenja prema pripadnosti ovim podskupinama iznosio je 420, 152 i 60 dana. Razlika između pojedinih skupina rizika bila je statistički značajna (log rank test P < 0.0001). ZAKLJUČCI: Ovom studijom potvrdili smo prethodno dokazane prognostičke čimbenike u bolesnika s CUP-om. QTc interval u EKG-u je identificiran kao novi nezavisni prognostički čimbenik. Razvili smo i jednostavan prognostički indeks koristeći ova četiri čimbenika čime je bolesnike moguće svrstati u neke od tri prognostičke podskupine sa različitim ishodom bolesti.OBJECTIVES: The aims of this study was to identify independent diagnostic and prognostic factors in patients with cancer of unknown primary site (CUP) who do not belong to prognostically favourable subsets, and to develop a prognostic index for predicting survival in these patients. PATIENTS AND METHODS: In this prospective study, univariate and multivariate analyses of 16 prognostic factors were conducted in a population of 145 patients with CUP in two clinical institutions (General Hospital Pula and Clinical Hospital Rijeka). Subsets of patients with favourable prognostic features and those requiring well-defined treatment were excluded. RESULTS: The 1-year overall survival rate for all patients was 42% and the median overall survival was 330 days. Overall survival was significantly related to the following pre-treatment prognostic factors: poor Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2, presence of liver metastasis, elevated serum lactate dehydrogenase (LDH), high white blood cell count, anaemia, age ≥ 63 years, and prolonged QTc interval in electrocardiogram (ECG). In multivariate analysis, four independent adverse prognostic parameters were retained: elevated LDH (Hazard Ratio (HR) 2.21; 95% Confidence Interval (CI) 1.41–3.47; P = 0.001), prolonged QTc interval (HR 2.10; 95% CI 1.28–3.44; P = 0.003), liver metastasis (HR 1.77; 95% CI 1.11–2.81; P = 0.016) and ECOG PS ≥ 2 (HR 1.69; 95% CI 1.05– 2.73; P = 0.03). We developed a prognostic index for overall survival based on the following subgroups: good prognosis (no or one adverse factor), intermediate prognosis (two adverse factors) and poor prognosis (three or four adverse factors). The median overall survival for the three subgroups was 420, 152 and 60 days, respectively, P < 0.0001. CONCLUSIONS: This study validated previously identified important prognostic factors for survival in patients with CUP. Prolonged QTc was additionally identified as a strong adverse prognostic factor. We developed a simple prognostic index using performance status, LDH, presence of liver metastasis and QTc interval in ECG, which allowed assignment of patients into three subgroups with divergent outcome

OVARIAL AND EXTRAOVARIAL CARCINOMA (diagnosis and treatment)

Ovarian cancer is one of the most malignant tumors in women, and its mortality rate is higher than in all other gynecological malignancies, both in our country and throughout the world. Ovarian cancer is one of the five most recurrent cancers in women in developed countries. The highest rate in Europe is found in the northern European countries and the lowest in the countries of East and South Europe. According to data from the year 1995, Lithuania had the highest ovarian cancer rate in Europe (23/100.000 women), and Macedonia the lowest (7,8/100.000 women). The mean rate for entire Europe was 13,4/100.000. The ovarian cancer rates vary significantly from country to country, and they reflect trends in fertility and the use of oral contraceptives

Effects of Dietary Counseling on Patients with Colorectal Cancer

Cancers of the colon and rectum together are second most common tumor type worldwide. The prognosis for the survival after disease progression is usually poor (1). Cancer anorexiacachexia syndrome is highly prevalent among patients with colorectal cancer, and has a large impact on morbidity and mortality, and on patient quality of life. Early intervention with nutritional supplementation has been shown to halt malnutrition, and may improve outcome in some patients (2). The etiology of cancer-associated malnutrition appears to be related to the pathological loss of inhibitory control of catabolic pathways, whose increased activities are not counterbalanced by the increased central and peripheral anabolic drive (3). The goals of nutritional support in patients with colorectal cancer are to improve nutritional status to allow initiation and completion of active anticancer therapies (chemotherapy and or radiotherapy) and improve quality of life (3, 4). Cancer growth and dissemination but also cancer treatments, including surgery, chemotherapy, and radiation therapy, interfere with taste, ingestion, swallowing, and digest food which leads to hypophagia. Also, chemotherapy agents may cause nausea and diarrhea (3, 4). Although many new agents are on the market to combat these symptoms, prevalence of colorectal cancer is still high (1). We studied the influence of nutritional support (counseling, nutritional supplements, megestrol acetate) on physical status and symptoms in patients with colorectal cancer during chemotherapy. The study was designed to investigate whether dietary counseling or oral nutrition commercial supplements during chemotherapy and/or BSC affected nutritional status and influence survival status prevalence in patients with colorectal cancer. Results: Three hundred and eighty-eight colorectal cancer patients were included in the study. Nottingham Screening Tool Questionnaire, Appetite Loss Scale and Karnofsky Performance Status were taken to evaluate the nutritive status of patients. Group I consisted of 215 patients who were monitored prospectively and were given nutritional support and in this group weight gain of 1,5 kg (0,6-2,8 kg) and appetite improvement was observed in patients with colorectal cancer. In both groups Karnofsky Performance Status didn’t change significantly reflecting the impact of the disease itself. Nutritional counseling, supplemental feeding and pharmacological support do temporarily stop weight loss and improve appetite, QoL and social life, but this improvement has no implications on patients KPS and course of their disease. Conclusion: These results encourage further studies with more specific nutritional supplementation in patients with colorectal cancer and probably in gastrointestinal oncology

Prikaz novootkrivenih karcinoma dojke, liječenih u Općoj bolnici Pula u razdoblju od 2008-2010 godine (s posebnim osvrtom na male karcinome)

Prognosis in breast carcinoma mostly depends of clinical staging at time of diagnosis. National screening mammography program is orientated to find breast cancer in earlyest stage, when prognosis and therapy is favourable. This program that way can directly have influence in reducing number of people who die because of cancer. We showed our results with new-founded breast carcinoma, treated in General Hospital Pula, with special review on small carcinoma, that measured less than 1 cm

OLIGODENDROGLIOMA MIMICKING POST-TRAUMATIC SYNDROME

A 44 year old man suffered an explosive neck injury and blunt head trauma in the war. Head CT scan showed a hypodensity of the left parieto-temporo-occipital area, which did enhance following contrast administration. During following 6 years, the patient was treated for post-traumatic stress disorder until admission to the hospital in an epileptic status. In the repeated neurological investigation, oligodendroglioma was diagnosed. Reevaluation of the first CT scan showed oligodendroglioma. The chance for early diagnosis was missed because the symptoms and imaging findings were ascribed to post-traumatic changes