[CANCER PATIENTS FOLLOW-UP ­ CROATIAN SOCIETY FOR MEDICAL ONCOLOGY CLINICAL GUIDELINES Part IV: planocellular head and neck cancer, oesophageal cancer, gastric cancer, colorectal cancer].

Treatment of oncological patients must be based upon multidisciplinary approach, and takes place in specialized oncological centers. By the end of a specific oncological treatment further follow-up is being managed mostly by the oncologists, but the role of the general practitioners becomes more important every day and therefore should be precisely defined. Nowadays, most of the existing follow-up guidelines are not being based on prospective studies, yet on the expert's opinion of a precise oncological center or specialists. The aim of the Croatian Society of Medical Oncology (CSMO) with these recommendations is to standardize and rationalize the diagnostic procedures' algorithm in follow­up of oncological patients after primary treatment, in patients with planocellular head and neck cancer, oesophageal cancer, gastric cancer and colorectal cancer.

Indicators of Cellular and Developmental Disorders in Multiple Primary Cancers.

In human organism development is a very complex and highly regulated system that enables the functional balance of each organ in a whole body. Disorders and tumor micro-environment weaken host immune system that is not able to recognize the tumor as a unknown body and fight against its uncontrollable forces. Tumor avoids the immune system in a way that promotes immunosuppression and orientation cytokine production towards Th2 immune responses which are responsible for infection appearances. Some of infectious agents (viruses) can cause oncogene activation and inhibition of tumor suppressor genes. It is also known that oncology treatment can be detrimental to the host immune system. The drugs or radiation can activate different signaling pathways which lead to a vicious circle from which there is no return. Experimental models of tumor biology and molecular events in vivo are patients who have multiple primary cancers (MPC) diagnosed during life. Such patients confirm the complexity of disorders that occur in the cell and explain all the influences and contributions to developmental tumor cascade.

[CANCER PATIENTS FOLLOW-UP ­ CROATIAN SOCIETY OF MEDICAL ONCOLOGY CLINICAL GUIDELINES Part III: neuroendocrine neoplasms, hepatocellular carcinoma, pancreatic cancer, cancer of the bile ducts]. / PRACENJE ONKOLOSKIH BOLESNIKA ­ KLINICKE PREPORUKE HRVATSKOG DRUSTVA ZA INTERNISTICKU ONKOLOGIJU HLZ-a III. dio: neuroendokrine neoplazme, hepatocelularni karcinom, rak gusterace, rak zucnih vodova.

The treatment of oncological patients must be based upon multidisciplinary approach, and takes place in specialized oncological centers. By the end of a specific oncological treatment further follow-up is being managed mostly by the oncologists, but the role of the general practitioners becomes more important every day and therefore should be precisely defined. Nowadays, most of the existing follow-up guidelines are not based on prospective studies, but on the experts opinion of individual oncological centers or specialists. The aim of the Croatian Society of Medical Oncology (CSMO) with these recommendations is to standardize and rationalize the diagnostic procedures algorithm in the follow-up of oncological patients after primary treatment, in patients with neuroendocrine neoplasms, hepatocellular carcinoma, pancreatic cancer and cancer of the bile ducts.

[Clinical recommendations for diagnosis, treatment and monitoring of patients with cancer of unknown primary site]. / Klinicke preporuke za dijagnozu, lijecenje i pracenje bolesnika oboljelih od raka nepoznata primarnog podrijetla.

Cancer of unknown primary (CUP) site comprises very heterogeneous group of various malignant tumors presented in metastatic phase of the disease. Diagnosis is set when primary site remains unidentified after a thorough diagnostic evaluation in patients with histologically proven malignant metastatic disease. Despite poor prognosis in most patients, favorable prognostic clinical entities have been recognized constituting the most important group of patients for oncological treatment. The following text presents the clinical guidelines in order to standardize the diagnosis, treatment and follow-up of patients with cancer of unknown primary site in the Republic of Croatia.

Endoscopic diagnostic of chronic pancreatitis.

Chronic pancreatitis is defined as a continuous inflammatory pancreatic disease, one characterized by irreversible morphological changes, often associates with pain and sometimes with the loss of endocrine and exocrine function. As a histological confirmation of chronic pancreatitis is often unavailable, the diagnosis is traditionally based on imaging methods such as computerized tomography (CT) or endoscopic retrograde cholangiopancreatography (ERCP), and recently magnetic resonance cholangiopancreatography (MRCP) as a noninvasive alternative to ERCP. Developments in the classification system of CP include the Marseille classification of 1963 which offered histopathologic criteria for CP, the Cambridge classification of 1984 which introduced imaging features of computed tomography (CT), transabdominal ultrasound (TUS) and endoscopic retrograde cholangiopancreatography (ERCP) for classification of CP as well as Rosemont classification system of 2007 which presented the endoscopic ultrasonography diagnosis of CP. Endoscopic ultra-sonography (EUS) was first introduced as a diagnostic method for evaluation of pancreatic disease in 1986. It has experienced significant improvements since then and allowed for an alternative approach in diagnosing patients with pancreatic diseases. In patients with suspected pancreatic masses EUS-guided fine needle aspiration (EUS-FNA) is the best method for obtaining tissue diagnosis and differentiating CP from pancreatic carcinoma. The recent studies indicate that EUS is the method of choice when compared with other imaging methods such as ERCP because it frequently provides more accurate diagnostics. The aim of this review is to discuss the findings in endoscopic diagnostics up to the present moment and to indicate advantages, limitations and possible complications along with the current recommendations in CP diagnostics.

Nutrition in cancer patients.

Cachexia is defined as an unintended loss of stable weight exceeding 10%. Patients with advanced cachexia express anorexia, early satiety, severe weight loss, weakness, anemia, and edema. Anorexia represents the result of a failure of the usual appetite signals whereas cachexia is the debilitating state of involuntary weight loss. This syndrome, referred to as the cancer anorexia-cachexia syndrome, (CACS) and usually consists of a combination of anorexia, tissue wasting, malnutrition, weight loss and loss of compensatory increase in feeding. CACS represents the result of a complex interaction between cancer growth and host response and is associated with a poor response to chemotherapy and with an increase in drug-related toxicity. In advanced cachexia (mostly in metastatic cancer and terminally disease) any interventions with nutritional suplements are ineffective. Therefore, nutritional support in the reversion of tumor cachexia and in the importance of maintaining patient weight, muscle mass, quality of life, has the exceptional importance, becouse good nutritional status of patients leads to the possibility of more aggressive and longer treatment and thus to longer survival.

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

Colorectal cancer is the third most common malignant tumour in males and the fourth most common malignancy in women in the Republic of Croatia. It is usually manifested as stool forming disorders, feeling that bowel does not empty completely, finding blood in the stool, weight loss and fatigue. In-time diagnosis, confirmed by pathohistological findings, is cornerstone of successful treatment. The decision about treatment is made based on clinical assessment of disease stage and other risk factors, after completion of the diagnostic process. Depending on that, treatment options include surgery, the application of systemic therapy (chemotherapy, immunotherapy) and radiotherapy. The following text presents the clinical guidelines in order to standardize procedures and criteria for the diagnosis, management, treatment and monitoring of patients with colorectal cancer in the Republic of Croatia.

[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.

Effects of nutritional support in patients with colorectal cancer during chemotherapy.

Nutritional support, addressing the specific needs of this patient group, is required to help improve prognosis, and reduce the consequences of cancer-associated nutritional decline. Early intervention with nutritional supplementation has been shown to halt malnutrition, and may improve outcome in some patients. In our study we tried to assess the influence of nutritional support (counseling, oral liquids, megestrol acetate) on nutritional status and symptoms prevalence in patients with colorectal cancer during chemotherapy. Group I consisted of 215 (55%) patients with medium age 68 +/- 2.6 years who were monitored prospectively and were given nutritional support. Group II included 173 (45%) patients (medium age 67 +/- 2.9 years) without the proper nutritional counseling, in whom the data were collected retrospectively during a 6 years period of time. After evaluation Nottingham Screening Tool Score, Appetite Loss Scale and Karnofsky Performance Status) all patients in the group I received nutritional counseling, 153 of them (72%) were taking form of enteral food supplement and 103 (48%) patients were using megestrol acetate. Evaluating the initial risk measurements according to BMI, decrease in weight gain and NST, we did not find any significant difference between the two groups. After chemotherapy completion, patients in group I had a 15.3% drop of those who's BMI was < 20.65% patients increased their body weight, with an average weight gain of 1.5 kg (0.6-2.8 kg). Contrary, in group II we found increase in weight loss > or = 2 kg/month in 39% of patients. The appetite improvement was detected on Appetite Loss Scale from 3.1 (pre-chemotherapy) to 4.7 (post-chemotherapy) in group I, especially in those receiving megestrol acetate. In both groups Karnofsky Performance Status didn't change significantly reflecting the impact of the disease itself and chemotherapy procedures to the patient's condition. Nutritional counseling, supplemental feeding and pharmacological support do temporarily stop weight loss and improve appetite, social life and quality of life in those groups of patients. However, this improvement have no implications on patients KPS and course of their disease.

[Croatian guidelines for use of eicosapentaenoic acid and megestrol acetate in cancer cachexia syndrome]. / Hrvatske smjernice za primjenu eikozapentaenske kiseline I megestrol-acetata u sindromu tumorske kaheksije.

Among many oncological patients we can notice a substantial loss of body weight, fat and proteins with significant proinflammatory activity at the time of diagnosis. This wasting condition is well known as cancer cachexia syndrome. Anorexia is important part of this syndrome. Because cancer cachexia reduces tumor response to treatment and it is an indicator of poor prognosis, we need to start correcting these nutritional deficits at once. In the presence of cancer cachexia it is extremely difficult to achieve protein anabolism and stop the body wasting by standard nutritional formulas only. During the last few years, the use of eicosapentaenoic acid (EPA) and megestrol acetate (MA) as anticahectic agents has been tested. These guidelines are intended to give evidence-based recommendations for the use of eicosapentaenoic acid and megestrol acetate in cancer cachexia syndrome. These guidelines have been developed by interdisciplinary expert group of Croatian clinicians. Based on relevant literature, we have concluded that the use of metabolic modulators such as eicosapentaenoic acid and megestrol acetate for 8 weeks may help to improve nutritional status in cachectic patients.

Androgenic/Anabolic steroid-induced toxic hepatitis.

Athletes and bodybuilders often misuse androgenic/anabolic steroids. When used in therapeutic doses, these drugs produce clinical jaundice in just a small number of recipients. We present a 26-year-old male bodybuilder who self-administered high doses of androgenic/anabolic steroids that induced liver damage. One month before admission to the hospital, he used testosterone enanthate (500 mg intramuscularly, twice weekly), stanozolol (40 mg/d), and methylandrostenediol (30 mg/d by mouth, for 5 weeks). On admission, his bilirubin level was 470 micromol/L (direct, 360 micromol/L), his aspartate aminotransferase (AST) level was 5,870 IU/L, his alanine aminotransferase (ALT) level was 10,580 IU/L, his alkaline phosphatase (ALP) level was 152 IU/L, his gamma-glutamyl-transpeptidase level was 140 IU/L, his albumin level was 27.6 g/L, and his prothrombin time was 29%. During the patient's prolonged hospitalization, multiple tests and liver biopsy were performed, showing only toxic hepatic lesions. The patient was provided with supportive medical treatment. Clinical signs and laboratory findings improved substantially 12 weeks after the patient discontinued androgenic/anabolic steroids. The reasons for presenting this case were the much higher values of AST and ALT levels than reported in other studies, although the values of bilirubin and ALP were similar to those found in the literature. To our knowledge, it is the first case of toxic hepatitis induced by androgenic/anabolic steroids with predominantly hepatocellular necrosis instead of intrahepatic cholestasis.