Browsing by Author "Knezevic, Srbislav (55393857000)"

The purpose of this study was to determine the frequency of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and to investigate its role as a potential risk factor in patients with chronic pancreatitis and pancreatic cancer. Deletion polymorphism of the 287-bp fragment of intron 16 of the ACE gene results in higher levels of circulating enzyme and therefore may represent a risk factor for disease development. The study included 55 patients with chronic pancreatitis, 45 patients with pancreatic cancer and 128 healthy subjects. The presence of I and D variants in the ACE gene was analyzed by a polymerase chain reaction (PCR) method. Distribution of ACE ID genotypes was analyzed by means of logistic regression. When chronic pancreatitis and pancreatic cancer groups were compared in the univariate analysis, the following factors were identified as statistically significant predictors of pancreatic disease: age, gender, smoking, fat intake, ACE II genotype and ACE DD genotype. However, in the multivariate analysis, only age, gender and smoking were singled out as predictors for the occurrence of pancreatic disease. Our findings indicate that the ACE I/D polymorphism could play a role in the development of chronic pancreatitis and pancreatic cancer through interaction with other genetic and environmental factors. © 2011 S. Karger AG, Basel.

The key to the successful management of pancreatic cystic neoplasm (PCN), among which intraductal papillary mucinous neoplasm (IPMN) is the one with the highest risk of advanced neo-plasia in resected patients, is a careful combination of clinical, radiological, and histopathological findings. This study aims to perform the comparison of a preoperative evaluation with pathological reports in IPMN and further, to evaluate and compare the diagnostic performance of European evidence-based guidelines on pancreatic cystic neoplasms (EEBGPCN) and Fukuoka Consensus guidelines (FCG). We analyzed 106 consecutive patients diagnosed with different types of PCN, among whom 68 had IPMN diagnosis, at the Clinical Center of Serbia. All the patients diagnosed with IPMNs were stratified concerning the presence of the absolute and relative indications according to EEBGPCN and high-risk stigmata and worrisome features according to FCG. Final histopathology revealed that IPMNs patients were further divided into malignant (50 patients) and benign (18 pa-tients) groups, according to the pathological findings. The preoperative prediction of malignancy according to EEBGPCN criteria was higher than 70% with high sensitivity of at least one absolute or relative indication for resection. The diagnostic performance of FCG was shown as comparable to EEBGPCN. Nevertheless, the value of false-positive rate for surgical resection showed that in some cases, overtreating patients or treating them too early cannot be prevented. A multidisciplinary approach is essential to adequately select patients for the resection considering at the same time both the risks of surgery and malignancy. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Gastrointestinal metastases from invasive lobular breast cancer are uncommon with the stomach and small intestines being the most common metastatic sites. Peritoneal and rectal metastases are very rare and only rarely occur as the frst manifestation of disease. We herein report the case of a 47-year-old woman who presented with abdominal carcinomatosis as a frst sign of invasive lobular breast carcinoma (ILC). Identifying the most important immunohistochemical markers for ILC: gross cystic disease fuid protein 15, estrogen and progesterone receptors enabled a correct diagnosis. After a six year disease-free period, relapse occurred with severe obstruction due to rectal metastasis from lob-ular breast carcinoma. Since there was no widespread metas-tatic disease, surgery with concomitant hormonal therapy was performed. copy; 2011 Korean Breast Cancer Society.

Gastrointestinal metastases from invasive lobular breast cancer are uncommon with the stomach and small intestines being the most common metastatic sites. Peritoneal and rectal metastases are very rare and only rarely occur as the frst manifestation of disease. We herein report the case of a 47-year-old woman who presented with abdominal carcinomatosis as a frst sign of invasive lobular breast carcinoma (ILC). Identifying the most important immunohistochemical markers for ILC: gross cystic disease fuid protein 15, estrogen and progesterone receptors enabled a correct diagnosis. After a six year disease-free period, relapse occurred with severe obstruction due to rectal metastasis from lob-ular breast carcinoma. Since there was no widespread metas-tatic disease, surgery with concomitant hormonal therapy was performed. copy; 2011 Korean Breast Cancer Society.

Purpose: The primary aim of this study was to evaluate the benefit of extended lymphadenectomy in pancreaticoduodenectomy (PD) and to estimate its impact on long-term survival in patients with pancreatic head carcinoma. Secondary endpoints included perioperative mortality, postoperative morbidity and predictors of survival in patients undergoing standard versus extended lymphadenectomy for pancreatic head carcinoma. Methods: From January 2007 to December 2010, 60 patients with potentially resectable pancreatic head carcinoma were operated using pylorus-preserving pancreatoduodenectomy (PPPD) at the Clinic for Digestive Surgery, Clinical Center of Serbia, Belgrade. Intraoperatively patients were randomly stratified into two groups: the first group (Nl=30) underwent PPPD with standard lymphadenectomy whilst the second group (N2=30) was operated with PPPD with extended lymphadenectomy. None of the patients received adjuvant treatments. Results: The number of retrieved lymph nodes, mean operating time and postoperative hospital stay were greater in patients with extended lymphadenectomy. Cox regression analysis showed that stage and lymph node metastasis were independent prognostic factors for survival. Conclusion: Extended lymphadenectomy in PPPD did not improve long-term survival in patients with resectable pancreatic head carcinoma and led to comparable and similar morbidity and mortality rates to those after standard lymphadenectomy.

Purpose: The primary aim of this study was to evaluate the benefit of extended lymphadenectomy in pancreaticoduodenectomy (PD) and to estimate its impact on long-term survival in patients with pancreatic head carcinoma. Secondary endpoints included perioperative mortality, postoperative morbidity and predictors of survival in patients undergoing standard versus extended lymphadenectomy for pancreatic head carcinoma. Methods: From January 2007 to December 2010, 60 patients with potentially resectable pancreatic head carcinoma were operated using pylorus-preserving pancreatoduodenectomy (PPPD) at the Clinic for Digestive Surgery, Clinical Center of Serbia, Belgrade. Intraoperatively patients were randomly stratified into two groups: the first group (Nl=30) underwent PPPD with standard lymphadenectomy whilst the second group (N2=30) was operated with PPPD with extended lymphadenectomy. None of the patients received adjuvant treatments. Results: The number of retrieved lymph nodes, mean operating time and postoperative hospital stay were greater in patients with extended lymphadenectomy. Cox regression analysis showed that stage and lymph node metastasis were independent prognostic factors for survival. Conclusion: Extended lymphadenectomy in PPPD did not improve long-term survival in patients with resectable pancreatic head carcinoma and led to comparable and similar morbidity and mortality rates to those after standard lymphadenectomy.

Background: The tumor suppressor gene SMAD4 (DPC4) encodes for the common intracellular mediator of the TGF-β superfamily pathway, which regulates numerous cellular processes, such as cell proliferation, cell differentiation, apoptosis, cell fate and migration. This study was aimed to investigate the presence of genetic variants in SMAD4 gene promoter in malignant pancreatic and colorectal tissue and to analyze their functional consequences. Methods: The study was performed on genomic DNA isolated from malignant tissue samples obtained on surgery from 50 patients with pancreatic carcinoma and 50 patients with colorectal cancer. Screening for mutations within an 800. bp-long fragment of the SMAD4 gene promoter was performed by DNA sequencing and two mononucleotide repeats, at positions -462 and -4, were found to be polymorphic in malignant tissue. The exact number of thymidines in the tracts -462T(15) and -4T(12) was determined by PCR with fluorescently labeled primers followed by capillary electrophoresis. Functional analysis of -462T(15)/-4T(12) haplotypes was performed by luciferase reporter assays. Results: Haplotype -462T(14)/-4T(10) was found in 85% of pancreatic cancer tissues, but it was not present in any of colorectal cancer tissues. Statistically significant reduction (p< 0.001) in activity was observed in the haplotype -462T(14)/-4T(10) in comparison with the haplotypes -462T(15)/-4T(12) and -462T(14)/-4T(11). Conclusion: Results of this study indicate that novel genetic variant -4T(10) in the SMAD4 gene promoter affects its activity and that element -4T(12) may play a role in transcriptional regulation of SMAD4 gene expression. Obtained results, though preliminary, also indicate that SMAD4 gene promoter haplotype -462T(14)/-4T(10) may represent a genetic marker of potential relevance for pancreatic and colorectal cancer. The findings of this study should be confirmed by further investigation in these two and other tumors, on larger number of patients and with different tumor stages. Translational research aimed at investigating potential application of mononucleotide repeats -462T(15) and -4T(12) in SMAD4 gene promoter as molecular markers in cancer may also prove useful. © 2010 Elsevier Ltd.

Background: The tumor suppressor gene SMAD4 (DPC4) encodes for the common intracellular mediator of the TGF-β superfamily pathway, which regulates numerous cellular processes, such as cell proliferation, cell differentiation, apoptosis, cell fate and migration. This study was aimed to investigate the presence of genetic variants in SMAD4 gene promoter in malignant pancreatic and colorectal tissue and to analyze their functional consequences. Methods: The study was performed on genomic DNA isolated from malignant tissue samples obtained on surgery from 50 patients with pancreatic carcinoma and 50 patients with colorectal cancer. Screening for mutations within an 800. bp-long fragment of the SMAD4 gene promoter was performed by DNA sequencing and two mononucleotide repeats, at positions -462 and -4, were found to be polymorphic in malignant tissue. The exact number of thymidines in the tracts -462T(15) and -4T(12) was determined by PCR with fluorescently labeled primers followed by capillary electrophoresis. Functional analysis of -462T(15)/-4T(12) haplotypes was performed by luciferase reporter assays. Results: Haplotype -462T(14)/-4T(10) was found in 85% of pancreatic cancer tissues, but it was not present in any of colorectal cancer tissues. Statistically significant reduction (p< 0.001) in activity was observed in the haplotype -462T(14)/-4T(10) in comparison with the haplotypes -462T(15)/-4T(12) and -462T(14)/-4T(11). Conclusion: Results of this study indicate that novel genetic variant -4T(10) in the SMAD4 gene promoter affects its activity and that element -4T(12) may play a role in transcriptional regulation of SMAD4 gene expression. Obtained results, though preliminary, also indicate that SMAD4 gene promoter haplotype -462T(14)/-4T(10) may represent a genetic marker of potential relevance for pancreatic and colorectal cancer. The findings of this study should be confirmed by further investigation in these two and other tumors, on larger number of patients and with different tumor stages. Translational research aimed at investigating potential application of mononucleotide repeats -462T(15) and -4T(12) in SMAD4 gene promoter as molecular markers in cancer may also prove useful. © 2010 Elsevier Ltd.