Browsing by Author "Bogdanovic, Aleksandar (56893375100)"

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 cancerrelated 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. © 2015 Baishideng Publishing Group Inc.

Introduction: Limited data can be found about surgical outcome of patients with hepatocellular carcinoma (HCC) arising in non-diseased liver. The study aim was to compare short- and long-term outcomes among HCC patients with normal and diseased liver parenchyma, undergoing potentially curative liver resection in a developing country. Materials and methods: From November 2001 until January 2017, 228 patients with HCC underwent curative-intent hepatectomy at the University Clinic for Digestive Surgery. From that number, 190 patients were eligible for analysis. Diseased liver (DL) was present in 112 patients while 78 patients had HCC in non-diseased liver (NDL). Results: Median age, sex, ASA score, the presence of extrahepatic disease and lobar distribution of tumors were similar in both groups. The number of tumors was higher in DL group, while tumor diameter was higher in NDL group. Anatomic liver resection and major liver resections were performed more commonly in NDL than in DL group (66.7 vs 47.4%, p = 0.008; 33.3 vs. 15.2%, p = 0.003). Postoperative morbidity was significantly higher in DL group (p = 0.004). Overall survival was statistically longer in NDL group (p = 0.024). By univariate analysis potential prognostic factors for long-term survival were identified: presence of chronic HCV infection, presence of cirrhosis, Child-Pugh score B and operative time longer than 240 min. The last two were confirmed by multivariate analysis as independent negative prognostic factors for overall survival. Conclusion: Liver resection in patients with HCC arising in non-diseased livers, despite of need for extended hepatectomies, provides favorable long-term prognosis. © 2020 Elsevier Ltd

Background: The aim of this study was to compare postoperative outcomes following liver resection between patients with prolonged cumulative ischemia time (CIT) which exceeded 60 min and patients with CIT less than 60 min. Methods: Between March 2020 and October 2022, 164 consecutive patients underwent liver resection at the Unit for hepato-bilio-pancreatic surgery, University Clinic for Digestive Surgery in Belgrade, Serbia. Intermittent Pringle maneuver was routinely applied. Depending on CIT during transection, patients were divided into two groups: group 1 (CIT <60 min) included 101 patients, and group 2 (CIT ≥60 min) included 63 patients. Results: Median operative time (210 vs. 400 min) and CIT (30 vs. 76 min) were longer in the Group 2 (p < 0.001). Intraoperative blood loss was higher in the Group 2 (150 vs 500 ml), p < 0.001. The perioperative transfusion rate was similar between the groups (p = 0.107). There was no difference in postoperative overall morbidity (50.5% vs. 58.7%, p = 0.337) and major morbidity (18.8 vs. 19%, p = 0.401). In-hospital mortality, 30-day mortality, and 90-day mortality were similar between the groups (p = 0.408; p = 0.408; p = 0.252, respectively). Non-anatomical liver resection was the only predictive factor of 90-day mortality identified by multivariate analysis (p = 0.047; Relative Risk = 0.179; 95% Confidence Interval 0.033–0.981). Conclusion: Intermittent Pringle maneuver with CIT exceeding 60 min is a safe method for bleeding control during liver resection with no impact on postoperative morbidity and mortality. Keywords: intermittent Pringle maneuver, liver ischemia, liver resection. © 2024 Asian Surgical Association and Taiwan Society of Coloproctology

BACKGROUND: Transarterial chemoembolisation (TACE) is the primary treatment for intermediate-stage hepatocellular carcinoma (HCC), according to the updated Barcelona Clinic Liver Cancer (BCLC) staging system. Although growing evidence favours liver resection (LR) over TACE for intermediate-stage HCC, the best treatment option remains controversial. This meta-analysis aimed to compare the overall survival (OS) after LR versus TACE for intermediate-stage HCC. METHODS: A comprehensive literature review of PubMed, Embase, Cochrane Library, and Web of Science was performed. Studies that compared the efficacy of LR and TACE in patients with intermediate (BCLC stage B) HCC were selected. According to the recent updated BCLC classification, intermediate stage of HCC was defined as follows: (a) four or more HCC nodules of any size, or (b) two or three nodules, but if at least one tumour is larger than 3 cm. The main outcome was OS, expressed as the hazard ratio. RESULTS: Nine eligible studies of 3355 patients were included in the review. The OS of patients who underwent LR was significantly longer than that of patients who underwent TACE (hazard ratio=0.52; 95% CI: 0.39-0.69; I2=79%). Prolonged survival following LR was confirmed after sensitivity analysis of five studies using propensity score matching (HR=0.45; 95% CI: 0.34-0.59; I2=55%). CONCLUSION: Patients with intermediate-stage HCC who underwent LR had a longer OS that those who underwent TACE. The role of LR in patients with BCLC stage B should be clarified in future randomised controlled trials. Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.

Purpose: Management of giant inguinoscrotal hernia (GIH) is still a challenging procedure associated with a higher risk of intraabdominal hypertension and abdominal compartment syndrome as a life-threatening condition. The aim of the study was to present our management strategy for GIH. Methods: This is a retrospective review of a case series including 24 consecutive patients with 25 GIH who underwent reconstructive surgery from January 2006 to June 2023, at the University Clinic for Digestive Surgery and Hernia Center Zuvela. A combined surgical strategy was applied: the modified Rives repair for groin hernias alone, Rives combined with organ resection to reduce hernia contents, and Rives combined with procedures for abdominal cavity enlargement. A surgical approach was defined based on the patient’s general health, the volume of the hernia sac, and perioperative parameters. Results: All patients were male aged between 43 and 82 years. Rives was the only procedure in 12 patients. In addition to Rives, omentectomy was performed in four patients and intestinal resection in one. Abdominal cavity enlargement was performed following Rives hernioplasty in 9 patients. The median operative time was 215 min (range, 70–720). Surgical complications occurred in seven patients. In-hospital mortality was 12.5%. There was no groin hernia recurrence. Conclusion: Our strategy is a single-stage treatment including modified Rives repair with or without additional procedures for abdominal cavity enlargement or hernia volume reduction, tailored to the individual patient characteristics. The procedure is associated with a higher risk of major morbidity requiring a well-trained intensive care unit team. © The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature 2024.

Hepatocellular carcinoma (HCC) is one of the major malignant diseases worldwide, charac-terized by growing incidence and high mortality rates despite apparent improvements in surveillance programs, diagnostic and treatment procedures, molecular therapies, and numerous research initia-tives. Most HCCs occur in patients with liver cirrhosis, and the competing mortality risks from the tumor and the cirrhosis should be considered. Presently, previously identified risk factors, such as hepatitis virus infection, hepatic inflammation and fibrosis, and metabolic syndrome, may be used as chemoprevention targets. The application of precision medicine for HCC management challenges the one-size-fits-all concept; moreover, patients should no longer be treated entirely according to the histology of their tumor but based on molecular targets specific to their tumor biology. Next-generation sequencing emphasizes HCC molecular heterogeneity and aids our comprehension of possible vulnerabilities that can be exploited. Moreover, genetic sequencing as part of a precision medicine concept may work as a promising tool for postoperative cancer monitoring. The use of genetic and epigenetic markers to identify therapeutic vulnerability could change the diagnosis and treatment of HCC, which so far was based on Barcelona clinic liver cancer (BCLC) staging. In daily clinical practice, the shift from a stage-oriented to a therapeutic-oriented approach is needed to direct the choice of HCC treatment toward the potentially most effective option on an individual basis. The important factor in precision medicine is the promotion of patient management based on the individual approach, knowing that the final decision must be approved by a multidisciplinary expert team. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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. © 2018 Galun et al.

Purpose: There are limited data on expression of epithelial–mesenchymal transition (EMT) markers in patients with colorectal liver metastases (CRLM). The study aim was to evaluate the expression and prognostic significance of E-cadherin (CDH1), fibronectin (FN1) and vimentin (VIM) in patients with CRLM after curative-intent liver resection. Patients and Methods: Thirty patients with CRLM managed by curative-intent liver resection were included in this prospective pilot study. Blood samples, colorectal liver metastases and surrounding non-tumor liver tissue were collected. Expression of CDH1, FN1 and VIM was analyzed by quantitative real-time polymerase chain reaction. Expression in CRLM and non-tumor liver tissue was compared, while expression in serum was correlated with CRLM expression. One-year recurrence-free survival was compared between patients with low and high CDH1, FN1 and VIM expression. Results: The expression of CDH1 was similar in CRLM and non-tumor liver tissues, while FN1 and VIM expression was significantly lower in metastatic tissue (P=0.003 and pP<0.001, respectively). Serum expression of CDH1 and VIM was detected in 66.7% and 93.3% of patients, respectively, while FN1 was not detected in any of the patients. The correlation of CDH1 and VIM expression between CRLM and serum was not statistically significant. Decreased CDH1 expression in CRLM and decreased VIM expression in serum were associated with early recurrence after surgical treatment of CRLM. Conclusion: Lower expression of CDH1 in CRLM and lower serum expression of VIM were found to be associated with early recurrence after liver resection for CRLM. © 2021 Bogdanovic et al.

Inhibitory SMAD7 and common mediator SMAD4 play crucial roles in SMAD-dependent TGF-β signaling that is often disrupted in colorectal cancer (CRC). This study aimed to profile the expression of SMAD7 and SMAD4 in primary and metastatic CRC and to evaluate their significance in disease progression and therapy response. The expression of SMAD7 and SMAD4 genes was analyzed by quantitative real-time PCR in tissues from 35 primary and metastatic CRC patients and in vitro in 7 human cell lines originating from colon tissue. Expression levels of SMAD7 and SMAD4, as well as their ratio, were determined and their association with tumor characteristics and response to therapy were evaluated. SMAD4 level was significantly lower in tumors compared to non-tumor tissues in both primary (p = 0.001) and metastatic (p = 0.001) CRC patients, while tumor expression of SMAD7 was significantly lower from non-tumor tissue only in metastatic patients (p = 0.017). SMAD7/SMAD4 ratio was elevated in CRC primary tumor tissues and cell lines compared to corresponding non-tumor tissues and cell line, respectively (p = 0.003). SMAD7 expression was significantly elevated in primary tumor tissues obtained from responders to neoadjuvant chemoradiotherapy (nCRT) compared to non-responders (p = 0.014). Alterations of expression and ratio of SMAD7 and SMAD4 in CRC cell lines, primary rectal cancer, and liver metastasis emphasize the importance of these genes in different stages of disease progression. Differential expression of SMAD7 in responders versus non-responders to nCRT should be further investigated for its potential predictive value. © 2021 Elsevier Inc.

Inhibitory SMAD7 and common mediator SMAD4 play crucial roles in SMAD-dependent TGF-β signaling that is often disrupted in colorectal cancer (CRC). This study aimed to profile the expression of SMAD7 and SMAD4 in primary and metastatic CRC and to evaluate their significance in disease progression and therapy response. The expression of SMAD7 and SMAD4 genes was analyzed by quantitative real-time PCR in tissues from 35 primary and metastatic CRC patients and in vitro in 7 human cell lines originating from colon tissue. Expression levels of SMAD7 and SMAD4, as well as their ratio, were determined and their association with tumor characteristics and response to therapy were evaluated. SMAD4 level was significantly lower in tumors compared to non-tumor tissues in both primary (p = 0.001) and metastatic (p = 0.001) CRC patients, while tumor expression of SMAD7 was significantly lower from non-tumor tissue only in metastatic patients (p = 0.017). SMAD7/SMAD4 ratio was elevated in CRC primary tumor tissues and cell lines compared to corresponding non-tumor tissues and cell line, respectively (p = 0.003). SMAD7 expression was significantly elevated in primary tumor tissues obtained from responders to neoadjuvant chemoradiotherapy (nCRT) compared to non-responders (p = 0.014). Alterations of expression and ratio of SMAD7 and SMAD4 in CRC cell lines, primary rectal cancer, and liver metastasis emphasize the importance of these genes in different stages of disease progression. Differential expression of SMAD7 in responders versus non-responders to nCRT should be further investigated for its potential predictive value. © 2021 Elsevier Inc.

[No abstract available]

Background: The aims of this study were to present the concept of original technique in the management of major incisional subcostal hernias and to evaluate short- and long-term outcome. Method: Between January 2010 and January 2020, 280 patients underwent hernia repair surgery for incisional lateral abdominal hernia at Clinic for Digestive Surgery, Clinical Center of Serbia. Among them, 37 patients underwent the modified sublay technique for major incisional subcostal hernia with minimal hernia defect surface of 100 cm2 or greater or minimal hernia defect width or height of 10 cm or greater. The operative techniques are as follows: retromuscular dissection of rectus muscle from posterior sheath on the both sides of hernia defect, external oblique muscle dissection from internal oblique muscle in a circle around hernia defect at the side of the hernia defect, complete reconstruction of the posterior myofascial layer, large heavyweight polypropylene mesh placement in a sublay position, and complete or partial reconstruction of anterior myofascial layer. Results: A median (range) hernia defect surface was 150 (100-500) cm2. A median operative time was 130 (90-330) minutes. The morbidity rate was 18.9%. A median (range) postoperative hospital stay was 7 (2-24) days. After the median follow-up of 50 (1-108) months, 2 patients (5.4%) developed recurrent hernia. Conclusions: The modified sublay technique using large heavyweight polypropylene mesh provides good results in the management of major subcostal abdominal wall defects. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.