Renal function in patients with chronic hepatitis B during antiviral therapy.

Aim To analyse the impact of the length of antiviral therapy with tenofovir disoproxil fumarate (TDF) on the renal function in patients with chronic hepatitis B (CHB). Methods A cross-sectional study included 75 patients with CHB treated with tenofovir, who had a normal renal function at the beginning of the treatment. Renal function was determined based on glomerular filtration rate (eGFR) value using the Modification of Diet in Renal Disease formula (MDRD). Measurement of serum creatinine concentration and urinary protein excretion were performed using standard laboratory analyses. Viral load quantification (HBV-DNA) was determined by polymerase chain reaction (PCR). The degree of liver fibrosis was determined using fibrosis4 (FIB-4) and aspartate transaminase to platelet ratio index (APRI) fibrosis score. Results Out of 75 CHB patients, 37 were on antiviral treatment for up to 2 years (group 1) and 38 patients on antiviral treatment longer than two years (group 2). Mean age of patients was not significantly different between the groups (p=0.076), nor was the gender distribution. There was no statistically significant difference between the mean values of the eGFR in the two groups (91.89±9.24 vs. 88.42±7.84 mL/min/1.73m2; p=0.42), as well as between the mean values of serum creatinine (p=0.360) and 24-hour urine protein excretion (p=0.380). There was no statistically significant correlation between renal parameters and viral load, APRI and FIB-4 fibrosis score. Conclusion Results of our study did not show significant changes in the measured parameters of renal function in group 1 and group 2 of patients, regardless of the length of antiviral treatment, indicating a good renal safety profile of TDF.

Rare giant female adnexal tumor of probable Wolffian origin: a case report.

Female adnexal tumors of probable Wolffian origin (FATWOs) are extremely rare tumors, with only around 100 cases published worldwide. FATWOs are most frequently found in the broad ligament, but these can also appear in the mesosalpinx, Fallopian tube, ovary, paravaginal region or peritoneum. We present a case of a 68-year-old female with a history of painless abdominal distension and frequent urination, with palpable big abdominal mass. Initial diagnosis was made using ultrasound and computed tomography scan that showed 22 × 21-cm tumor with solid and cystic components. Blood test showed elevated serum levels of CA 125, HE4 and Roma index. Intraoperatively, a large abdominopelvic encapsulated mass, fixated to surrounding tissue, was found. Our patient underwent hysterectomy 12 years ago. Total tumor resection, including bilateral adnexectomy, was performed. At 6 months of following, there was no evidence of disease. Here, we report extremely rare abdominal tumors and one of the biggest FATWOs reported so far.

Challenges of Surgical Treatment of Atypical Giant Choledochal Cyst with the Absence of Gallbladder in Adult Patient.

Choledochal cysts (CCs) are rare congenital anomalies in the form of cystic dilatation of any part of the biliary tree, and they rarely reach the size over 10 cm. We present a case of a 51-year-old female with a one-year history of abdominal pain and palpable mass in the epigastrium and right upper abdomen. Diagnosis of giant CC was made using magnetic resonance cholangiopancreatography. Intraoperatively, a large CC without gallbladder (no previous cholecystectomy was performed) was found under the liver pushing the surrounding structures, extending into the intrapancreatic portion of bile ducts and leading to the destruction of the backside of the pancreas head. Complete excision of CC and biliopancreatic reconstruction was achieved by Roux-en-Y pancreaticojejunostomy and hepaticojejunostomy. This case report describes an extremely rare association between an atypical giant choledochal cyst and gallbladder agenesis.

Is preoperative hypoproteinemia associated with colorectal cancer stage and postoperative complications?

Aim To investigate the relationship between preoperative level of serum albumin in patients with colorectal cancer (CRC), stage of CRC and postoperative complications. Methods This cross-sectional retrospective study was conducted at the Clinic for General and Abdominal Surgery of the University Clinical Centre Sarajevo (UCCS). A total of 107 patients surgically treated for CRC in the period between 2013 and 2018 were enrolled in this study and divided into two groups: with hypoalbuminemia (group A) and without hypoalbuminemia (group B). Results The average level of albumin in group A was 29 (25-32) g/L versus 39 (37-41) g/L in group B (p<0.05). The average length of hospital stay in group A was 18 (13-25) days, and in group B 14.5 (12-21) days. Patients with hypoalbuminemia (group A) had wound dehiscence more often and more re-interventions compared to group B (p<0.05). Binary logistic regression found that serum protein, albumin and globulin levels were not statistically significant in the prediction of CRC stadium or postoperative complications (p>0.05). Conclusion Study results show that preoperatively measured levels of serum albumin are not associated with the stage of colorectal cancer and cannot serve as predictors for postoperative complications.

Appropriateness of colonoscopy at a tertiary care centre - are we overdoing gastrointestinal endoscopy?

Aim To evaluate the pattern of indications and a spectrum of colonic pathology, and to determine appropriateness of indications for colonoscopy in order to improve patient selection for colonoscopy. Methods This retrospective study includes 294 patients who were referred to the Gastroenterology Department from a primary care physician in order to approach endoscopic examination. Study data included patients' anamnestic data (comorbidities, positive family history, performed radiological examinations) an indication for the procedure, and colonoscopy findings. Results Haematochezia was confirmed in 186 (63.26%), positive radiologic finding in183 (62.24%) and anaemia in 157 (53.40%) patients. Adenoma and colorectal carcinoma were detected in 40 (13.6%) and 53 (18%) patients, respectively. A significant association between haematochezia and colorectal neoplasm was confirmed (p=0.019), haematochezia and inflammatory bowel disease (p=0.027), and between radiological finding and colorectal neoplasm (p=0.018). There was no significant association between anaemia and any of the colonoscopic findings. According to EPAGE II criteria indications were appropriate in 187 (63.6%), uncertain in 67 (22.8%) and inappropriate in 40 (13.6%) patients. Conclusion This study confirmed a slightly larger number of uncertain and inappropriate indications for colonoscopy compared to other studies that examined indications for colonoscopy, which can be attributed to a high number of patients with functional bowel disorders.

The Importance of Determining Preoperative Serum Concentration of Carbohydrate Antigen 19-9 and Carcinoembryonic Antigen in Assessing the Progression of Colorectal Cancer.

INTRODUCTION: Many evidence indicates that Carcinoembryonic antigen (CEA) and Carbohydrate antigen 19-9 (CA 19-9) have strong reactivity with tumor cells and may serve as a useful marker in identifying patients with colorectal cancer (CRC). OBJECTIVES: The goal of this study was to evaluate the relationship between preoperative concentration of serum levels of CEA and CA 19-9 and progression of colorectal cancer. METHODS: The retrospective study included 80 patients operated for colorectal cancer at the Clinic for General and Abdominal Surgery, Clinical Center of University of Sarajevo, from 2013 to 2018. The following clinical and laboratory parameters were observed: age, sex, preoperatively measured concentrations of CEA and CA 19-9 antigens, CRC localization, postoperative histopathological findings and CRC stage (TNM classification). All of the data above were processed by relevant statistical methods, with an accepted level of statistical significance of p <0.05. RESULTS: The highest serum levels of CEA and CA 19-9 were observed in stage IV of CRC. Average CEA and CA 19-9 values did not differ significantly between tumor stages (p>0.05). Preoperatively measured serum concentrations of CEA and CA 19-9 in patients with CRC were significantly correlated (rho = 0.328, p = 0.001). An increase in the depth of tumor invasion of the intestinal wall tumor (pT) is followed by an increase in the serum value of the CEA marker, but this ratio was not statistically significant (rho=0.194, p=0.080), while the relationship between depth of intestinal wall invasion and serum level of CA 19-9 was significantly positive correlation (rho = 0.252, p = 0.024). However, the linear regression analysis model showed that serum levels of CEA and CA 19-9 could not be predictors of CRC stage and depth of tumor invasion of the intestinal wall (p> 0.05). CONCLUSION: Preoperatively measured serum values of CEA and CA 19-9 cannot indicate the specific stage and histopathological size of the CRC.

Effects of adding taxane to anthracycline-based neoadjuvant chemotherapy in locally advanced breast cancer.

Aim To compare the effect of neoadjuvant chemotherapy based on taxane and/or anthracycline to the extent of an objective response in female patients with unresectable breast cancer with evaluation of the toxic profile of applied chemotherapy. Methods One hundred patients with histologically verified breast cancer, treated with neoadjuvant chemotherapy were divided into two groups: a study group A (50 patients), who had received 4 to 6 cycles of taxane-based chemotherapy, and control group B (50 patients), who had received 4 to 6 cycles of anthracyclines-based chemotherapy. Pathohistological response was evaluated after tumour excision and axillary resection at the end of chemotherapy and it was defined as pathologic complete (pCR), partial (pPR), or no response (pNR). Toxic effects were evaluated and quantified by the Common Terminology Criteria for Adverse Events v4.0. Results After neoadjuvant chemotherapy, 8% of patients in the group A achieved pCR, 54% achieved pPR, while 38% of patients had no tumour response to applied chemotherapy. In the group B pCR was achieved in 6%, pPR in 42% of patients, while 51% of patients were pNR to the administered chemotherapy. Significant reduction of tumour mass was achieved in the group of patients treated with taxanes: 20.00 (7.75-30.25) vs. 13.50 (6.00-25.00) mm (p=0.024). Toxicity of chemotherapy in group A and group B was within the limits of grade 2. Conclusion The addition of taxane to anthracycline-based neoadjuvant chemotherapy in patients with breast cancer resulted in a significant reduction in tumour mass compared to the group of patients treated with anthracyclines, but without increasing the overall side effects.

The Association of Simultaneous Increase in Interleukin-6, C Reactive Protein, and Matrix Metalloproteinase-9 Serum Levels with Increasing Stages of Colorectal Cancer.

BACKGROUND: Tumor development and growth are driven in many cases by inflammatory cells, which can produce cytokines and other factors that can stimulate the development of the malignant process. The aim of this study was to evaluate interleukin-6 (IL-6), C-reactive protein (CRP), matrix metalloproteinase-9 (MMP-9), serum levels in patients with colorectal cancer (CRC), and their association with the stage of CRC. METHODS: IL-6, MMP-9, and CRP serum levels were measured in 75 patients with CRC just before surgical treatment, as well as in 20 healthy individuals as controls. Surgically obtained tissue material was subjected to pathological analysis. RESULTS: Significant increase in CRP and IL-6 serum concentration is associated with increasing stage of CRC (p <0.05), where MMP-9 serum level was significantly higher in stages III and IV compared to the stage II CRC. Significant correlation was found between IL-6 and MMP-9 serum levels (rho=0.478; p <0.001) as well as between IL-6 and CRP serum levels (rho=0.720; p <0.001) and between MMP-9 and CRP serum levels (rho=0.379; p <0.001). Serum levels of MMP-9 and CRP have been shown to be independent predictors of the CRC stage. CONCLUSION: Combined quantification of IL-6, MMP-9, and CRP serum levels seems to be a reliable index of inflammation-related processes during colorectal carcinogenesis.

THE RELATIONSHIP BETWEEN SERUM LEVEL OF MALONDIALDEHYDE AND PROGRESSION OF COLORECTAL CANCER.

- The purpose of the study was to assess the level of serum malondialdehyde (MDA) concentration and its association with the stage and histopathologic sizes of colorectal cancer (CRC). One hundred and two patients having undergone surgical treatment of CRC between January 2014 and December 2015 were included in this cross-sectional study. The patients were divided into four groups (stage I-IV) according to the TNM classification. Control group included 30 subjects with no signs of malignancy and inflammatory diseases. In each patient, preoperative blood samples were obtained for determination of MDA concentration by ELISA immunoassay. Serum levels of MDA were progressively increased in patients with CRC, reaching the highest value in the fourth stage of CRC. Serum concentrations of MDA were significantly higher in pT4 group as compared with pT3 and pT2 groups of CRC patients (p<0.01). Significantly higher levels of MDA were found in the N1 and N2 groups of CRC patients as compared with N0 group, as well as in patients with metastatic disease as compared with those without metastasis (p<0.001). In conclusion, the progression of CRC is associated with a significant increase in serum MDA levels.

The association between the serum levels of matrix metalloproteinase 9 and colorectal cancer.

Aim To determine the serum levels of matrix metalloproteinase 9 (MMP-9) concentration and their association with the stage and histopathologic sizes of colorectal cancer (CRC). Methods One hundred and two patients with clinically diagnosed and histologically confirmed colorectal cancer ready for surgical treatment were included in the study. In each patient, preoperative peripheral venous blood samples were taken for determination of the concentration of MMP-9 using ELISA immunoassay test. Resected tumour specimens were studied pathologically according to the criteria of the TNM classification. All patients were divided into groups according to the TNM classification. The control group presented 30 subjects of the appropriate age and gender with no family history of cancer, clinical signs of malignancy or inflammatory bowel disease. Results The serum levels of MMP-9 were progressively increased in patients with CRC reaching the highest value in the fourth stage of CRC. It was also confirmed that the serum concentrations of MMP-9 were significantly higher in patients with pericolonic lymph nodes involvement compared to the patients with no involvement of lymph nodes, 456.4 (445.9-464.7) ng/mL vs. 438.4 (418.4-447.8) ng/mL (p<0.001). Significantly higher serum levels of MMP-9 were found in the patients with metastatic CRC, 458.5 (452.0-468.1) ng/mL compared with the CRC patients without metastasis, 445.8 (436.9-456.5) ng/mL (p<0.001). Conclusion It was confirmed that serum concentration of MMP-9 presented the significant independent risk factors for the progression of CRC.

Evaluation of Risk Factors of Surgical Wound Dehiscence in Adults After Laparotomy.

OBJECTIVES: The percentage of patients with difficult and prolonged healing of the wound is still high, while the immediate complications such as wound dehiscence occurs in up to 3 % of all treated patients in abdominal surgery. The aim of study was to analyze the risk factors and comorbidities in the group patients undergoing laparotomy and associated with early postoperative wound dehiscence. METHODS: The retrospective study included all patients treated surgically at Clinic of General and Abdominal surgery, Clinical Center of the University of Sarajevo in the period from January 1, 2013 until January 1, 2016, with clinically verified surgical wound dehiscence. RESULTS: The results showed statistically proportion of male patients (70%) compared to female (30%). The largest number of respondents were in age group 71-80. Surgical wound infection was evident in 61% of patients, malignant staining in 52%, hypoproteinemia was found in 50% of patients, anemia in 43%, peritonitis in 36% and diabetes in 14% of respondents. Of the total respondents with surgical wound dehiscence, 30 (68%) had comorbidities present. By analyzing the prevalence of comorbidity and risk factors recorded in relation to comorbidity, it was noted that hypertension is most often associated with hypoproteinemia (X2=4.399; p=0.036), wound infection (X2=4.112; p=0.043) and malignant diseases (X2=4.016; p=0.045). The frequency of the anemia, peritonitis and diabetes in the sample was not different in relation to the comorbidity conditions (p >0.05). CONCLUSIONS: The risk factors occurrence of surgical wound dehiscence in our study were identified as hypoproteinemia, malignant disease, anemia and peritonitis. The highest incidence of dehiscence was in patients operated on in medical emergencies, and in patients with malignant disease.

Relationship Between Chronic Inflammation and the Stage and Histopathological Size of Colorectal Carcinoma.

OBJECTIVES: The association of inflammatory reactions with almost all types of cancer supports the concept that inflammation is a critical component of tumor progression. The present study aimed to evaluate the relationship of serum markers of chronic inflammation with the stage of and histopathological size of colorectal carcinoma (CRC). METHODS: This cross-sectional study included 90 patients of both sexes, mean age 66.2 (range 47-78) years, with clinically and histologically confirmed CRC, who were admitted to the Clinic for abdominal surgery UCCS for surgical treatment of CRC. The patients according to the stage of disease were divided into three groups (stage II-IV). The control group consisted of 30 subjects with no signs of malignancy and acute inflammatory diseases. Staging of CRC was done according to the TNM classification. In each patient, the preoperative blood samples were taken for determination of the parameters of inflammation: the erythrocyte sedimentation rate, white blood cells, C-reactive protein (CRP), fibrinogen and alpha 2 globulins. RESULTS: It was confirmed that increasing markers of inflammation followed increasing stages of colorectal cancer, depth of tumor invasion and the occurrence of metastatic disease. CRP is a biomarker that consistently and significantly increases from the second to the fourth stage of colorectal cancer (7.2 (2.3-14.6) mg/L vs. 21.85 (12.3-41) mg/L vs. 38.6 (21.5-79) mg/L; p<0.01) and significantly correlates positively with the stage of CRC (r= 0.783, p<0.001), and the tumor size (r=0.249, p<0.05). CONCLUSION: The study results point to an increase in the degree of chronic inflammation throughout the progression of colorectal cancer. The most consistent marker of chronic inflammation that accompanies the progression of colorectal carcinoma is CRP.

Influence of Malondialdehyde and Matrix Metalloproteinase-9 on Progression of Carotid Atherosclerosis in Chronic Renal Disease with Cardiometabolic Syndrome.

Objective was to assess whether the concentration of malondialdehyde (MDA) as a marker of lipid peroxidation and serum concentration of matrix metalloproteinase-9 (MMP-9) are involved in the process of atherosclerosis in chronic kidney disease (CKD) patients nondialysis-dependent and those on peritoneal dialysis (PD), both with signs of cardiometabolic syndrome (CMS). Thirty CKD and 22 PD patients were included in a study. All observed patients were divided into three subgroups depending on the degree of atherosclerotic changes in the carotid arteries (CA). Severity of atherosclerotic changes in the CA was evaluated by ultrasonography. We confirmed significantly lower level of serum MDA throughout all the stages of atherosclerosis in PD patients compared with observed CKD patients (P < 0.05) and increased serum concentration of MDA and MMP-9 with the progression of severity atherosclerotic changes in both groups of patients. The multiple regression analysis revealed that MDA and MMP-9 are significant predictors of changes in IMT-CA CKD patients (P < 0.05) and plaque score on CA in these patients (P < 0.05). The results suggest that MDA and MMP-9 could be mediators of CKD-related vascular remodeling in CMS.

Evaluation of standardized and applied variables in predicting treatment outcomes of polytrauma patients.

INTRODUCTION: Polytrauma is defined as an injury where they are affected by at least two different organ systems or body, with at least one life-threatening injuries. Given the multilevel model care of polytrauma patients within KCUS are inevitable weaknesses in the management of this category of patients. OBJECTIVE: To determine the dynamics of existing procedures in treatment of polytrauma patients on admission to KCUS, and based on statistical analysis of variables applied to determine and define the factors that influence the final outcome of treatment, and determine their mutual relationship, which may result in eliminating the flaws in the approach to the problem. MATERIAL AND METHODS: The study was based on 263 polytrauma patients. Parametric and non-parametric statistical methods were used. Basic statistics were calculated, based on the calculated parameters for the final achievement of research objectives, multicoleration analysis, image analysis, discriminant analysis and multifactorial analysis were used. From the universe of variables for this study we selected sample of n = 25 variables, of which the first two modular, others belong to the common measurement space (n = 23) and in this paper defined as a system variable methods, procedures and assessments of polytrauma patients. RESULTS AND DISCUSSION: After the multicoleration analysis, since the image analysis gave a reliable measurement results, we started the analysis of eigenvalues, that is defining the factors upon which they obtain information about the system solve the problem of the existing model and its correlation with treatment outcome. CONCLUSION: The study singled out the essential factors that determine the current organizational model of care, which may affect the treatment and better outcome of polytrauma patients. This analysis has shown the maximum correlative relationships between these practices and contributed to development guidelines that are defined by isolated factors.

Acute renal failure and ureteral leak after open surgery aortoiliac aneurysm repair.

We present a case of 52 year old male with an acute renal failure that took place 4 days after open transabdominal surgery repair of infrarenal abdominal aneurysm along with aneurysm of left common iliac artery and dilatation of left external iliac artery. Patient was subjected to 13 hemodialysis treatments that resulted in satisfactory recovery of renal function. One month after aneurysm repair he developed the right ureteral leak, consequently urinoma and acute renal failure once again. We suppose that ureteral leak was related to segmental ischemic necrosis of right ureter but not to traction or other iatrogenic ureteral injury. Percutaneous nephrostomy and insertion of ureteral stent was resulted in complete recovery of renal function.

Treatment of IgA nephropathy of adults presented by nephrotic syndrome.

The aim of this retrospective study was to evaluate the results of the immunosuppressive regiment in managing of IgA nephropathy associated with primary nephrotic syndrome at the Nephrology Clinic, University of Sarajevo Clinics Centre in period of 1997-2007. We studied 19 patients (4 women and 15 men) with idiopathic nephrotic syndrome, where pathomorphologic changes of IgA nephropathy were proved by kidney biopsy. The levels of diuresis, proteinuria, albuminemia, lipidemia and kidney function, as measure of efficiency of used therapy, were monitored. The IgA nephropathy present with the nephrotic syndrome was shown in 15.8% (19) patients underwent renal biopsy due to primary nephrotic syndrome in the period of observation. The average age of patients with IgA nephropathy was 34.9+/-14.1 years. Eight patients from this group were treated with corticosteroid therapy (1-1.5 mg/kg of body weight for 4 weeks, followed by 0.5 mg/ kg of body weight until therapeutic response was achieved, and finally gradual exclusion of therapy after eight weeks in responsive patients), 6 patients with corticosteroids and bolus cyclophosphamide (10-15 mg/kg BW), and in 5/19 patients cyclosporine therapy was used (3 mg/kg BW). Complete remission of nephrotic syndrome was achieved in 42.1% of the patients. In conclusion, in adults patients with primary nephrotic syndrome associated with IgA nephropathy, used immunosuppressive therapy resulted in a high percentage of achieved remissions.

Treatment aspects of primary nephrotic syndrome in adults.

Strict therapy protocol, which would be used universally for certain morphological forms of primary nephrotic syndrome, does not exist. The aim of the study was to show the effects of used therapy protocol in treatment of primary nephrotic syndrome at the Institute of Nephrology, Clinical Center University of Sarajevo in period of 2000-2005. The retrospective analysis covered 48 patients (17 women and 31 men) with idiopathic nephrotic syndrome, where pathomorphological changes were proved by kidney biopsy. Minimal change disease was confirmed with 6 (12.5%) patients. All patients were initially treated with corticosteroids with dose of 1 mg/kg of body weight. Five patients were in the group of primary responders (83.3%) with long term total remission, and 1 patient (16.6%) was a primary responder with 3 relapses in 8 months with a therapy of corticosteroids and bolus of cyclophosphamide. Diffuse mesangial proliferative glomerulonephritis was shown in 13 patients (27.1%). Seven patients from this group were treated with corticosteroid therapy (1 mg/kg of body weight for 4 weeks, followed by 0.5 mg/ kg of body weight until therapeutical response was achieved, and finally gradual exclusion of therapy after eight weeks in responsive patients). Six patients were treated with corticosteroids and one-month of bolus cyclophosphamide during half of year (10-5 mg/kg of body weight). Total remission was achieved in 37,9% of the patients. The IgA nephropathy presented with the nephrotic syndrome was shown in 10.4% (5) of the patients. Three patients from this group were treated with corticosteroid therapy (1 mg/kg of body weight for 4 weeks, followed by 0,5 mg/ kg of body weight until therapeutical response was achieved, and finally gradual exclusion of therapy after eight weeks in responsive patients) and.2 patients with corticosteroids and cyclophosphamide (1.5 mg/kg of body weight) during 6 months. Complete remission of nephrotic syndrome from this pathomorphological category was achieved in 2 patients. Membranoproliferative glomerulonephritis was shown in 6 patients (12.5%). All were treated with corticosteroids plus bolus of cyclophosphamide. Partial remission was achieved in one patient. Membranous glomerulonephritis was confirmed in 18 patients (37.5 %). Combined therapy of corticosteroids and bolus of cyclophosphamide was used in 7/18 patients, in 2/18 patients therapy of corticosteroids and per os cyclophosphamide (2 mg/kg of body weight) and in 9/18 patients cyclosporine therapy (3 mg/kg of body weight). Complete remission was achieved in 38.8% of the patients. A high percentage of achieved remissions of primary nephrotic syndrome in adults shows the efficiency of immunomodulating therapy used. Membranoproliferative glomerulonephritis still remains a therapy problem.