Browsing by Author "Krivokapić, Zoran (55503352000)"

Aim To assess practical accuracy of revised Bethesda criteria (BGrev), pathological predictive model (MsPath), and histopathological parameters for detection of high-frequency of microsatellite instability (MSI-H) phenotype in patients with colorectal carcinoma (CRC). Method Tumors from 150 patients with CRC were analyzed for MSI using a fluorescence-based pentaplex polymerase chain reaction technique. For all patients, we evaluated age, sex, family history of cancer, localization, tumor differentiation, mucin production, lymphocytic infiltration (TIL), and Union for International Cancer Control stage. Patients were classified according to the BGrev, and the groups were compared. The utility of the BGrev, MsPath, and clinical and histopathological parameters for predicting microsatellite tumor status were assessed by univariate logistic regression analysis and by calculating the sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values. Results Fifteen out of 45 patients who met and 4 of 105 patients who did not meet the BGrev criteria had MSI-H CRC. Sensitivity, specificity, PPV, and NPV for BGrev were 78.9%, 77%, 30%, and 70%, respectively. MSI histology (the third BGrev criterion without age limit) was as sensitive as BGrev, but more specific. MsPath model was more sensitive than BGrev (86%), with similar specificity. Any BGrev criterion fulfillment, mucinous differentiation, and right-sided CRC were singled out as independent factors to identify MSI-H colorectal cancer. Conclusion The BGrev, MsPath model, and MSI histology are useful tools for selecting patients for MSI testing.

Introduction Functional results after low anterior resection for rectal cancer are an issue of increasing attention among colorectal surgeons and others interested in this subject. The consensus on ideal reconstruction type has not been achieved to date, although the number of papers on this subject has been published in recent years. Objective We conducted a prospective, parallel group study comparing latero-terminal with colonic J-pouch anastomosis in terms of defecatory function in patients undergoing stapled low colorectal/ coloanal anastomosis. Methods A total of 80 patients were included in this study with either latero-terminal or colonic J-pouch anastomosis. Defecatory function was evaluated using the modified version of MSKCC questionnaire 6, 12 and 24 months after the operation. Fecal continence was evaluated using the Wexner continence score. Results In both groups, trend towards improvement was registered in all measured variables in all three control intervals. This can apply to bowel frequency, urgency, night soiling, fragmentation and incomplete evacuation. However, the difference was not statistically significant, and when reviewing the trend of results we can note that in the J-pouch group steady state has not been reached even after 24 month control. Conclusion This trial did not reveal any significant differences in defecatory function 6, 12 and 24 months after low anterior resection (LAR) between patients with a latero-terminal anastomosis and those with colonic J-pouch anastomosis. Our results did not confirm superiority of colonic J-pouch over the lateroterminal anastomosis © 2015, Serbia Medical Society. All rights reserved.

Liquid biopsy and cell-free DNA (cfDNA) show great promise in cancer diagnostics. In this study, we designed a custom droplet digital PCR (ddPCR) assay for the quantification and quality control of cfDNA isolated from serum. The assay was validated on a group of locally advanced colorectal cancer (CRC) patients and two control groups—patients with hemorrhoids and healthy individuals. The assay shows a high correlation with Qubit measurement (r = 0.976) but offers a higher dynamic range. Mean concentrations of cfDNA were 12.36 ng/µL, 5.17 ng/µL, and 0.29 ng/µL for CRC, hemorrhoid patients, and healthy controls, respectively. The quality of cfDNA was assessed with the measurement of B-cell DNA contamination. On a subset of CRC patients, we compared the mutation status on KRAS (G12A, G12D, G12V, G13D) and BRAF (V600E) genes in the primary tumor and cfDNA isolated from the serum. A total of 70.6% of primary tumor samples were mutated, and the mean fractional abundance of mutations was 9.50%. The matching serum samples were mutated in 38% cases with an average fractional abundance of 0.23%. We conclude that any decisions based solely on the amount of cfDNA present in patient serum must be inter-preted carefully and in the context of co-morbidities. This study explores the potential of ddPCR somatic mutations detection from liquid biopsy as a supplement to tissue biopsy in targeted per-sonalized CRC patient management. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Liquid biopsy and cell-free DNA (cfDNA) show great promise in cancer diagnostics. In this study, we designed a custom droplet digital PCR (ddPCR) assay for the quantification and quality control of cfDNA isolated from serum. The assay was validated on a group of locally advanced colorectal cancer (CRC) patients and two control groups—patients with hemorrhoids and healthy individuals. The assay shows a high correlation with Qubit measurement (r = 0.976) but offers a higher dynamic range. Mean concentrations of cfDNA were 12.36 ng/µL, 5.17 ng/µL, and 0.29 ng/µL for CRC, hemorrhoid patients, and healthy controls, respectively. The quality of cfDNA was assessed with the measurement of B-cell DNA contamination. On a subset of CRC patients, we compared the mutation status on KRAS (G12A, G12D, G12V, G13D) and BRAF (V600E) genes in the primary tumor and cfDNA isolated from the serum. A total of 70.6% of primary tumor samples were mutated, and the mean fractional abundance of mutations was 9.50%. The matching serum samples were mutated in 38% cases with an average fractional abundance of 0.23%. We conclude that any decisions based solely on the amount of cfDNA present in patient serum must be inter-preted carefully and in the context of co-morbidities. This study explores the potential of ddPCR somatic mutations detection from liquid biopsy as a supplement to tissue biopsy in targeted per-sonalized CRC patient management. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Background/Aim. The outcome of rectal cancer is dependant on the stage of the tumour. There are several classification systems used to describe the extent of the disease. The aim of this study was to compare the efficacy of transrectal ultrasonography (TRUS) in preoperative local staging of rectal cancer using endosonographic probes with different views (180° vs 360°), as well as an influence of experience of an endoscopist on the TRUS performance. Methods. TRUS was performed in 127 patients with rectal carcinoma by two endoscopists. Seventy-one patients were examined with a 180° endosonographic probe (group A) and 56 patients with a 360° rotating probe (group B). All findings were compared with a histopathology report. Results. TRUS had a diagnostic overall accuracy of 91.3% for the tumor (T) category (k = 0.866, SE (k) = 0.038, p < 0.0001) and 71.7% for the node (N) category (χ = 0.374, SE (k) = 0.082, p < 0.0001). In the group A, TRUS had a diagnostic overall accuracy of 88.7% for the T category (χ = 0.805, SE (k) = 0.063, p < 0.0001), and 70.4% for the N category (χ = 0.376, SE (k) = 0.101, P < 0.0001). In the group B, TRUS had a diagnostic overall accuracy of 94.6% for the T category (χ = 0.920, SE (k) = 0.044, p < 0.0001), and 73.2% for the N category (χ = 0.379, SE (k) = 0.131, p = 0.004). Experience of the endoscopist had no significant influence on results of preoperative staging of rectal cancer by using TRUS. Conclusion. The accuracy rate of TRUS in the preoperative local staging of rectal cancer is high. Our results imply no significant difference in the overall accuracy rates when using endosonographic probes with different views (180° vs 360°). Also, there was no significant influence of endoscopist experience on results obtained. © 2019 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Introduction/Objective Necrotizing soft tissue infection is a life-threatening condition, characterized by widely spread necrosis of the skin, subcutaneous adipose tissue, fascia, and muscle. This study aimed to determine the risk factors associated with lethality due to necrotizing soft tissue infection of perianal and perineal region, for all patients surgically treated at a tertiary referral hospital. Methods A retrospective review of 38 patients with necrotizing soft tissue infection of the perianal and perineal region, in the period between January 2007 and December 2014, was performed. We reviewed sex and age of the patients, the presence of known risk factors (diabetes mellitus, obesity, alcoholism), localization of necrotizing soft tissue infection, duration of symptoms, length of hospitalization, the number of necessary operations done, the performance of the stoma, and the outcome. We used logistic regression to identify the predictors of lethal outcome in a univariate analysis with estimated odds ratios and 95% confidence intervals. Results There was a significantly higher fatality rate in the group of patients over 60 years of age (p < 0.05), with more than 10 days from the onset of symptoms to the treatment (p < 0.05), with a perianal localization (p < 0.05), and stoma creation (p < 0.05). The overall fatality rate was 18.4%. Conclusion Patients’ age, time passed between the onset of the symptoms and the initiation of the treatment, perianal localization, and stoma creation were related to higher lethality risk. © 2017, Serbia Medical Society. All rights reserved.

Background/Aim. Colorectal cancer still presents a major health problem, with around 10% of patients in whom the tumor invades surrounding structures or organs. These patients are usually challenging even for an experienced colorectal surgical team. The decision for performing multivisceral resection (MVR) is often made intraoperatively, with no sufficient data on the tumor and patient condition. The percentage of perioperative morbidity and mortality is high and oncological outcome is often unfavorable.The aim of this study was to investigate the poor oncological outcome risk factors after MVR in the patients with colorectal carcinoma. Methods. This was a retrospective analysis of patients operated at the Department for Colorectal Surgery of the First Surgical Clinic, Clinical Centre of Serbia, Belgrade. The en bloc multivisceral resection for the primary adenocarcinoma of the colon and rectum was uniformly performed. Data were collected in prospectively designed database. Follow- up period was minimum 2 years. The patients were analyzed in terms of histopathological, demographical and follow- up data. Survival and time to recurrence were evaluated using the Kaplan-Meier method and the log-rank test. Results. Two hundred and thirteen patients were included in the study Their mean age was 59.9 ±12.0 years. The followup period was 33.8 ±29 months. Histopathology confirmed the true tumor infiltration of surrounding organ/structure in 126 (59.2%) patients. The R0 resection was confirmed in 173 (81.2%) patients. Five-year overall survival was 43.4%. Five-year survival for colon patients was 45.9% and in the rectal cancer group 40.9%. In the N0 group of patients, the overall survival in 5-year period was 66.7%. The N1 and N2 status proved the adverse effect on survival (overall 5-year survival 31.3% and 15.9%, respectively). The five-year local recurrence rate in the R0 group of patients was 17.7% and the percentage of distant metastases was 66.3%. Conclusion. The multivisceral resections are demanding procedures requiring a highly specialized surgical team and a high volume hospital. The oncological outcome of these procedures is still unfavorable. In the cases with the node positive disease, or the R1 resection, the perspective is poor. On the other hand, in the absence of these unfavorable factors, we can expect a good oncological outcome. More meticulous preoperative staging and aggressive preoperative treatment can further improve the results. © 2019 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Reversal of a Hartmann’s resection is often challenging and requires planning, and the assessment of the rectal stump is dependent upon the original indication for the nonrestorative procedure. The reported complication rate after Hartmann’s reconstruction is high, with morbidity rates of 30–40 %, anastomotic leakage rates as high as 15 %, and a reported mortality of up to 10 %. Advanced age and multiple comorbid conditions in a large proportion of patients who recover after Hartmann’s procedure further discourages both surgeons and patients from sometimes opting for reconstruction; 40 % of patients undergoing Hartmann’s resection never have stoma reversal. In this chapter, the technical aspects of Hartmann’s reconstruction are discussed, operative tips are provided, and the selective use of a laparoscopic-assisted approach is considered. © Springer-Verlag London 2013.

This study aimed to examine the expression pattern of tumoral and circulating miR-93-5p in patients with colorectal cancer (CRC) liver metastasis (CRLM) and to explore its predictive and prognostic potential. CRLM tissue, surrounding non-tumor liver tissue, and serum were obtained from 35 patients with CRLM. The expression pattern of tissue and circulating miR-93-5p in patients with CRLM was determined using quantitative polymerase chain reaction, using miR-16-5p for normalization. Sample-based cut-off values for CRLM and serum miR-93-5p expression were calculated using Receiver Operating Characteristic curve analysis to stratify the patients into high and low miR-93-5p expression groups which were that compared with patients' clinicopathological data, therapy response, one-year disease-free survival, and disease recurrence. Relative miR-93-5p expression was higher in CRLM in comparison to the non-metastatic liver tissue (p<0.001). CRLM miR-93-5p expression showed moderate negative correlation with carcinoembryonic antigen levels (r=-0.406; p=0.016). There were no differences in high-/low-miR-93-5p expression and therapy responders vs. non-responders, which was confirmed in vitro using metastatic and normal colonic cells SW620 and HCEC-1CT, respectively. No difference was observed in one-year recurrence-free survival in patients with high vs. low miR-93-5p expression in CRLM or serum. However, high miR-93-5p serum levels were significantly associated with early disease recurrence (p=0.035). In conclusion, miR-93-5p serum levels could be potentially used as a prognostic factor for early disease recurrence in CRLM patients.

Background/Aims: The aim of the study was the evaluation of the clinical validity of immunoscintigraphy with 99mTc labeled antibodies for the detection of metastases and recurrences of colorectal carcinomas. Methodology: We examined 17 patients with colorectal carcinomas. Scintigraphy was performed with anti-CEA MoAb 99mTc-BW 431/26. Results: Recurrences of carcinomas were detected and confirmed by surgery in 6 patients, recurrences with liver metastasis in 5 patients, and only liver metastases in 3 patients. Planar immunoscintigraphy was positive in 5/8 patients with liver metastases and 8/11 patients with recurrences, whereas in 1/8 liver metastases and 3/11 recurrences were detected only by tomography. In two patients with metastases in the abdominal lymph nodes immunoscintigraphic findings both on planar scintigraphy and tomoscintigraphy were false negative. Conclusions: Immunoscintigraphy with 99mTc labeled antibodies can be useful in the diagnosis of recurrences and metastases of colorectal carcinoma, viability assessment after radiotherapy and in the choice of the adequate surgical treatment. © H.G.E. Update Medical Publishing S.A.