Marinko Zuvela

Hepatocellular carcinoma: From clinical practice to evidence-based treatment protocols

Hepatocellular carcinoma (HCC) is one of the major malignant diseases in many healthcare systems. The growing number of new cases diagnosed each year is nearly equal to the number of deaths from this cancer. Worldwide, HCC is a leading cause of cancer-related deaths, as it is the fifth most common cancer and the third most important cause of cancer related death in men. Among various risk factors the two are prevailing: viral hepatitis, namely chronic hepatitis C virus is a well-established risk factor contributing to the rising incidence of HCC. The epidemic of obesity and the metabolic syndrome, not only in the United States but also in Asia, tend to become the leading cause of the long-term rise in the HCC incidence. Today, the diagnosis of HCC is established within the national surveillance programs in developed countries while the diagnosis of symptomatic, advanced stage disease still remains the characteristic of underdeveloped countries. Although many different staging systems have been developed and evaluated the Barcelona-Clinic Liver Cancer staging system has emerged as the most useful to guide HCC treatment. Treatment allocation should be decided by a multidisciplinary board involving hepatologists, pathologists, radiologists, liver surgeons and oncologists guided by personalized -based medicine. This approach is important not only to balance between different oncologic treatments strategies but also due to the complexity of the disease (chronic liver disease and the cancer) and due to the large number of potentially efficient therapies. Careful patient selection and a tailored treatment modality for every patient, either potentially curative (surgical treatment and tumor ablation) or palliative (transarterial therapy, radioembolization and medical treatment, i.e., sorafenib) is mandatory to achieve the best treatment outcome.

Targeted therapy and personalized medicine in hepatocellular carcinoma: drug resistance, mechanisms, and treatment strategies

Hepatocellular carcinoma (HCC) is characterized by a growing number of new cases diagnosed each year that is nearly equal to the number of deaths from this cancer. In a majority of the cases, HCC is associated with the underlying chronic liver disease, and it is diagnosed in advanced stage of disease when curative treatment options are not applicable. Sorafenib is a treatment of choice for patients with performance status 1 or 2 and/or macrovascular invasion or extrahepatic spread, and regorafenib is the only systemic treatment found to provide survival benefit in HCC patients progressing on sorafenib treatment. Other drugs tested in different trials failed to demonstrate any benefit. Disappointing results of numerous trials testing the efficacy of various drugs indicate that HCC has low sensitivity to chemotherapy that is in great part caused by multidrug resistance. Immunotherapy for HCC is a new challenging treatment option and involves immune checkpoint inhibitors/antibody-based therapy and peptide-based vaccines. Another challenging approach is microRNA-based therapy that involves two strategies. The first aims to inhibit oncogenic miRNAs by using miRNA antagonists and the second strategy is miRNA replacement, which involves the reintroduction of a tumor-suppressor miRNA mimetic to restore a loss of function.

Clamp-crushing vs. radiofrequency-assisted liver resection:changes in liver function tests.

BACKGROUND/AIMS Liver resection is the gold standard in managing patients with metastatic or primary liver cancer. The aim of our study was to compare the traditional clamp-crushing technique to the radiofrequency- assisted liver resection technique in terms of postoperative liver function. METHODOLOGY Liver function was evaluated preoperatively and on postoperative days 3 and 7. Liver synthetic function parameters (serum albumin level, prothrombin time and international normalized ratio), markers of hepatic injury and necrosis (serum alanine aminotransferase, aspartate aminotransferase and total bilirubin level) and microsomal activity (quantitative lidocaine test) were compared. RESULTS Forty three patients completed the study (14 had clamp-crushing and 29 had radiofrequency assisted liver resection). The groups did not differ in demographic characteristics, pre-operative liver function, operative time and perioperative transfusion rate. In postoperative period, there were similar changes in monitored parameters in both groups except albumin levels, that were higher in radiofrequency-assisted liver resection group (p=0.047). CONCLUSIONS Both, traditional clamp-crushing technique and radiofrequency assisted liver resection technique, result in similar postoperative changes of most monitored liver function parameters.

Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after curative-intent surgery for hepatocellular carcinoma: experience from a developing country

Purpose The aim of the study was to evaluate a prognostic value of preoperative neutrophil-to-lymphocyte ratio (NLR) on long-term survival of cirrhotic and noncirrhotic hepatocellular cancer (HCC) patients managed by a curative-intent liver surgery in a developing country. Patients and methods During the study period between November 1, 2001, and December 31, 2012, 109 patients underwent potentially curative hepatectomy for HCC. Data were retrospectively reviewed from the prospectively collected database. The median follow-up was 25 months. NLR was estimated by dividing an absolute neutrophil count by an absolute lymphocyte count from the differential blood count. Receiver operating characteristic curve was constructed to assess the ability of NLR to predict long-term outcomes and to determine an optimal cutoff value for all patients group, the subgroup with cirrhosis, and the subgroup without cirrhosis. The optimal cutoff values were 1.28, 1.28, and 2.09, respectively. Results The overall 3- and 5-year survival rates were 49% and 45%, respectively, for low NLR group and 38% and 26%, respectively, for high NLR group. The difference was statistically significant (p=0.015). Overall survival was similar between low and high NLR groups in patients with cirrhosis; no difference was found between the groups (p=0.124). In patients without cirrhosis, low NLR group had longer overall survival compared with high NLR group (p=0.015). Univariate analysis identified four factors as significant predictors of long-term survival: cirrhosis, Child-Pugh score, platelet count, and NLR. On multivariate analysis, only platelet count and NLR were independent prognostic factors of long-term survival. Conclusion Prognostic value of NLR was confirmed in noncirrhotic HCC patients who underwent curative-intent liver surgery. In HCC patients with cirrhosis, the prognostic role of NLR was not confirmed.

Laparotomija kao metoda izbora u postavljanju dijagnoze peripankreaticne tuberkulozne limfadenopatije

Peripancreatic lymph node tuberculosis is a rare disease with a difficult diagnosis. The case of a 61-year-old patient who was admitted because of intermittent dull pain in upper abdomen lasting 3-4 months followed by nausea, loss of appetite and body weight. The applied diagnostic procedures indicate a change in the head of the pancreas. The method of choice for establishing a definitive histopathological diagnosis is the biopsy of the lesion. Biopsy changes can be done using U.S., CT, Endo U.S. and laparoscopy. Surgery is a last resort only to establish a definitive histopathological diagnosis.

Hepatocelularni karcinom udruzen sa ehinokoknom cistom jetre kao dijagnosticki problem

The presence of benign and/or malignant liver lesions is not easy to determine, especially differentiated. Preoperative diagnosis has to include more procedures for correlation of data in order to establish the correct diagnosis and proper treatment. The case of a 72-year-old female patient who was admitted because of the appearance of persistent dull pain under right rib cage. Ultrasound and CT findings verify the presence of two changes in the right liver, various radiographic characteristics. One change was good, other cystic. The presence of easily elevated tumor markers (AFP) in favor of hepatocellular carcinoma. The nature of other types of cystic changes was not clear. Intraoperatively and histologically confirmed to be a simultaneous presence of hepatocellular carcinoma and hydatid cysts in the right lobe of the liver. Surgical treatment is the only solution for the simultaneous treatment of both changes in the liver.

Radiofrequency-assisted liver resections for metastatic colorectal cancer: Technique and feasibility

Radiofrequency (RF)-assisted resection techniques are associated with minimal blood loss providing safe hemostasis of the transected liver 1-3 parenchyma. Different RF-assisted liver resection techniques have been developed. The presented RF technique is the sequentional coagulate-cut liver resection technique (“The Belgrade technique”) and the difference from other techniques is the way the electrode is used. A coagulate-cut liver resection cycle can be described as a process of creating a 30-mm long and 6-8 mm wide cylinder of coagulated and desiccated liver tissue by applying RF energy through the non-insulated tip of the electrode inserted into the liver parenchyma and then dividing the coagulated tissue by surgical scalpel or scissors. From January 2001 to January 2014, 830 RF-assisted liver resections were performed for various indications at the HPB unit of the Clinic for Digestive Surgery, Clinical center of Serbia, Belgrade. Among 830 liver resections, 470 resections were performed in 383 patients with colorectal cancer liver metastasis. Sixty-six patients experienced repeated liver resection ranging from a second to a fifth resection. The majority of patients had bi-lobar spread of the disease before the first liver resection was performed. No difference was found in the postoperative morbidity between the patients after the first, the second and the third liver resection (F=0.168; p=0.846). 90-days mortality was 5.7% after the repeated liver resections and 2.5% in patients with one liver resection (X2=2.278; 4,13 p=0.165). Single HPB unit experience has demonstrated that RF-assisted liver resection technique is feasible, safe and effective procedure in the management of patients with CRC liver metastasis.