Exploring Perforated Jejunal GIST: A Rare Case Report and Review of Molecular and Clinical Literature.

This case report details a rare instance of a perforated jejunal gastrointestinal stromal tumor (GIST) in a 76-year-old female patient. The patient presented with acute abdominal pain and distension without any changes in bowel habits or episodes of nausea and vomiting. Initial diagnostics, including abdominal plain radiography and ultrasonography, were inconclusive; however, a computed tomography (CT) scan revealed pneumoperitoneum and an irregular fluid collection suggestive of small intestine perforations. Surgical intervention uncovered a 35 mm jejunal GIST with a 10 mm perforation. Histopathological examination confirmed a mixed cell type GIST with high malignancy potential, further substantiated by immunohistochemistry markers CD117, DOG1, and vimentin. Molecular analysis illuminated the role of key oncogenes, primarily KIT and PDGFRA mutations, emphasizing the importance of molecular diagnostics in GIST management. Despite the severity of the presentation, the patient's postoperative recovery was favorable, highlighting the effectiveness of prompt surgical and multidisciplinary approaches in managing complex GIST cases.

Metastatic Breast Cancer Presenting as Acute Appendicitis: A Rare Case Study and Review of Current Knowledge.

This manuscript discusses a rare case of acute appendicitis caused by metastasis from invasive breast carcinoma of no special type in a 70-year-old female previously diagnosed with breast cancer. It delves into the diagnostic challenges and management complexities of such unusual clinical presentations. The paper includes an analysis of 19 documented cases, enriching the understanding of metastatic patterns and treatment strategies in breast cancer. It underlines the importance of considering a history of malignancy when diagnosing acute abdominal conditions and emphasizes a comprehensive approach in interpreting diagnostic imaging in patients with past oncological issues to effectively manage metastatic breast cancer exhibiting atypical manifestations.

Association of Periodontal Disease with Activity of Crohn's Disease.

INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory granulomatous disease that can affect the entire gastrointestinal tract. It is characterized by various extraintestinal manifestations (EIMs), of which oral manifestations (OMs) are often possible. One of the possible OMs is periodontal disease (PD), a chronic inflammatory condition of the supporting tissues of the teeth. This study aimed to show the existence of a mutual relationship between the clinical activity of PD and the clinical and endoscopic activity of CD. MATERIALS AND METHODS: One clinical and two endoscopic indexes were used for the assessment of CD activity and clinical attachment loss (CAL), bleeding on probing (BOP), pocket probing depth (PPD), and radiographic bone loss (RBL) in a dental panoramic tomogram to assess PD in CD patients. RESULTS: A total of 38 patients underwent the entire study process, of which 20 patients had CD and 18 patients had CD and PD. Considering all CD activity scores, there were 26 patients with active disease; half of them had PD, and 85.7% of operated patients had active CD. The values of CAL, PPD, BOP, and RBL were higher in active CD patients than those in remission, except for BOP when comparing to the CDAI score, which was higher in those in remission of CD. CONCLUSION: The results of this study indicate that there is a connection between the activity of CD and worse conditions of the supporting tissues of the gums in the oral cavity, so it is important to keep in mind the necessity of referring patients with CD to a dentist for timely and adequate therapeutic measures.

Physical Exercise of Patients on Hemodialysis, Optimistic or Pessimistic.

Chronic kidney disease leads to significant functional limitations and severe disability, which requires the application of an appropriate physical rehabilitation strategy that helps patients achieve social well-being and significant health benefits. Data sources MEDLINE, PubMed, Google Scholar and Web of Science were electronically searched, by using search terms: physical exercise, hemodialysis, barriers, risks of exercise, expected benefits. The contraindications for exercise are recent myocardial infarction, uncontrolled arrhythmia and hypertension, unstable angina pectoris, unregulated diabetes mellitus, the presence of neurological and muscular dysfunctions, malignancies, and pregnancy. The implementation of the physical exercise program for hemodialysis patients confirmed all the expected benefits: improvement of cardiovascular functions, stabilization of blood pressure, increased muscle strength, improvement of nutritional status and quality of dialysis, reduction of negative emotions, anxiety and depression, as well as social interaction of patients and their families. Despite the fact that a large number of studies have proven the beneficial effects of exercise during hemodialysis, a physical rehabilitation program as a standard form of treatment has not yet been introduced. Although there is no doubt that the effects of physical activity on the survival and the quality of life of patients on hemodialysis are positive, rehabilitation program still falls under the routine practice program in a small number of dialysis centers. One of the biggest obstacles to the implementation of the physical therapy program in hemodialysis patients is the lack of a clearly defined program that defines all the needs of dialysis patients.  DOI: 10.52547/ijkd.7570.

Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp - The cross-sectional clinical study.

The aim of this study was to evaluate the efficacy of endoscopic polypectomy as a therapeutic treatment for malignant alteration of colorectal polyps. In a 5-year research, 89 patients were included, who were tested and treated at the University Clinical Center Kragujevac, Kragujevac, Serbia, with the confirmed presence of malignant alteration polyps of the colon by colonoscopy, which were removed using the method of endoscopic polypectomy and confirmed by the histopathological examination of the entire polyp. After that, the same group of patients was monitored endoscopically within a certain period, controlling polypectomy locations and the occurrence of a possible remnant of the polyp, in the period of up to 2 years of polypectomy. We observed that, with an increasing size of polyps, there is also an increase in the percentage of the complexity of endoscopic resection and the appearance of remnant with histological characteristics of the invasive cancer. The highest percentage of incomplete endoscopic resection and the appearance of remnant with histological characteristics of the invasive cancer were shown at malignant altered polyps in the field of tubulovillous adenoma. Eighteen patients in total underwent the surgical intervention. In conclusion, our data support the high efficacy of endoscopic polypectomy for the removal of the altered malignant polyp.

The Enigma of Mammaglobin: Redefining the Biomarker Paradigm in Breast Carcinoma.

The continuous evolution of cancer biology has led to the discovery of mammaglobin, a potential novel biomarker for breast carcinoma. This review aims to unravel the enigmatic aspects of mammaglobin and elucidate its potential role in redefining the paradigm of breast carcinoma biomarkers. We will thoroughly examine its expression in tumoral and peritumoral tissues and its circulating levels in the blood, thereby providing insights into its possible function in cancer progression and metastasis. Furthermore, the potential application of mammaglobin as a non-invasive diagnostic tool and a target for personalized treatment strategies will be discussed. Given the increasing incidence of breast carcinoma worldwide, the exploration of novel biomarkers such as mammaglobin is crucial in advancing our diagnostic capabilities and treatment modalities, ultimately contributing to improved patient outcomes.

Treatment of Ulcerative Colitis: Impact on Platelet Aggregation.

Background and Objectives: Ulcerative colitis is chronic and/or progressive inflammation of the colorectal mucosa and submucosa and represents one of two major inflammatory bowel diseases. Ulcerative colitis has been associated with increased risk of arteriosus and venous thrombosis. There are numerous factors responsible for this; one of them is platelet activation and aggregation. The objective of our study was to determine if different treatment options for ulcerative colitis have an impact on platelet aggregation. Materials and Methods: This research was a prospective, observational study and included 94 newly diagnosed patients with UC divided into four treatment groups. For all patients, we measured platelet aggregability by using an impedance aggregometry method with a multiplate analyzer before and after treatment with infliximab, adalimumab, vedolizumab and azathioprine. A Paired Samples t test was performed in order to determine the difference in platelet aggregability before and after a certain therapy, since the data followed a normal distribution. Taking into account the impact of some clinical characteristics, multiple linear regression was conducted for the purpose of estimating the effect of therapy on the level of reduction in platelet aggregability. Results: All four drugs significantly reduced platelet aggregability. After we excluded the influence of clinical and endoscopic scores and disease localization on the results, we found that infliximab had the greatest anti-platelet activity. Conclusions: In addition to the well-known traditional risk factors for atherosclerosis, activation and aggregation of platelets play a significant role in the development of arterial thrombosis, and our results suggested that therapy use for the treatment of UC, especially infliximab, can have a great impact on cardiovascular morbidity and mortality by decreasing platelet aggregability.

Atherosclerotic Cardiovascular Disease in Inflammatory Bowel Disease: The Role of Chronic Inflammation and Platelet Aggregation.

Background and Objectives: Atherosclerosis is one of inflammatory bowel disease's most significant cardiovascular manifestations. This research aimed to examine the relationship between biochemical, haemostatic, and immune parameters of atherosclerosis and ulcerative colitis patients and its relationship to platelet aggregation. Materials and Methods: A clinical, observational cross-sectional study was performed, during which the tested parameters were compared in the experimental and control groups. The patients were divided into four groups. The first group had 25 patients who had ulcerative colitis and atherosclerosis. The second group included 39 patients with ulcerative colitis without atherosclerosis. The third group comprised 31 patients suffering from atherosclerosis without ulcerative colitis, and the fourth group comprised 25 healthy subjects. Results: In our study, we registered statistically higher levels of inflammatory markers like SE, CRP, Le, fecal calprotectin, TNF-α, and IL-6, as well as the higher value of thrombocytes and thrombocyte aggregation in the group of patients with ulcerative colitis compared to the control group. Lower levels of total cholesterol and LDL were also recorded in patients with ulcerative colitis and atherosclerosis and ulcerative colitis without atherosclerosis compared to healthy control. Triglyceride and remnant cholesterol were higher in patients with ulcerative colitis and atherosclerosis when compared to patients with ulcerative colitis and healthy control but lower than in patients with atherosclerosis only. Conclusions: Several inflammatory markers and platelet aggregation could be good discrimination markers for subjects with ulcerative colitis with the highest risk of atherosclerosis.

Ascites as First Atypical and Only Clinical Manifestation of De Novo Follicular Lymphoma.

Follicular lymphoma is the most common indolent non-Hodgkin's lymphoma and is usually initially detected in lymph nodes. Primary extranodal NHL is most commonly primarily localized in the gastrointestinal tract. We present one unusual case of ileum FL with ascites as the first clinical sign. The 73-year-old female patient was presented to the emergency department for evaluation of mild abdominal pain and abdominal swelling that had been going on for three days followed by bloating and occasional pain in the spine. The abdominal contrast-enhanced CT revealed the contrast stagnation in the distal part of the ileum. The ileum wall about 11 cm in length was thickened up to 2.9 cm and the tumor mass infiltrated all layers of ileum mesenteric lymphadenopathy up to 2 cm in diameter and significant ascites. On the upper ileum wall, the vegetative mass was described 3 cm in diameter. The patient had an emergent laparotomy with the ileocolic resection and latero-lateral ileocolic anastomosis. The microscopy finding of terminal ileum and the regional lymph nodes showed domination of cleaved cells with irregular nuclei which correspond to centrocytes. There were 0-15 large non-cleaved cells corresponding to centroblast in the microscopy high-power field. The final diagnosis was follicular lymphoma, the clinical stage 2E and histological grade by Berard and Mann criteria 1-2.

CAR T Cell Therapy for Chronic Lymphocytic Leukemia: Successes and Shortcomings.

Chimeric antigen receptor T (CAR T) cell therapy achieved remarkable success in B-cell leukemia and lymphoma which led to its incorporation in treatment protocols for these diseases. CAR T cell therapy for chronic lymphocytic leukemia (CLL) patients showed less success compared to other malignant tumors. In this review, we discuss the published results regarding CAR T cell therapy of CLL, possible mechanisms of failures and expected developments.

Anemia of inflammation in patients with colorectal cancer: Correlation with interleukin-1, interleukin-33 and galectin-1.

Background: Patients with colorectal cancer (CRC) have anemia often present as a consequence of chronic bleeding from tumor. The exact role of lL-33, Galectin-l and IL-l in the pathological genesis of anemia in colorectal cancer patients has not been elucidated yet. The main goal of this research was to analyze Gal-l, IL-l and lL-33 systemic values in anemic and non-anemic CRC patients. Methods: Concentrations of IL-33, Galectin-1 and IL-1 have been studied in blood samples of 55 CRC patients (27 without anemia and 28 with anemia). Results: CRC patients with anemia had more severe and local advanced disease compared to CRC non-anemic patients. Anemia positively correlated with higher nuclear grade, lymph and blood vessel invasion, as well as with higher TNM stage, detectable metastatic lesions in lung and liver and peritoneal carcinomatosis. Significantly higher IL-33, Gal-1 and IL-1 concentration have been found in sera of patients with CRC and detected anemia. CRC patients mostly had microcytic anemia, while ferritin values were in normal range. Analysis revealed positive mutual correlation between serum values of galectin-1, IL-1 and IL-33 in CRC patients. Level of hemoglobin negatively correlated with serum IL-33, Gal-1 and IL-1. We have analyzed the Receiver Operating Characteristic (ROC) curves of serum IL-33, Gal-1 and IL-1 showed that these cytokines can be treated as additional markers for anemia of inflammation in CRC patients. Conclusions: Predomination of Galectin-1, IL-1 and IL-33 in anemic CRC patients implicates on their potential role in anemia genesis and further development.

The effects of respiratory exercises on partial pressures of gases and anxiety in the acute phase of COVID-19 infection.

INTRODUCTION: Respiratory exercise in post-COVID-19 significantly improves pulmonary function, exercise capacity and quality of life. Our study aimed to investigate the effect of respiratory exercise on partial pressures of oxygen, carbon dioxide and oxygen saturation in arterial blood and anxiety assessed by the GAD-7 scale in the acute phase of COVID-19 infection. METHODS: The study was conducted at the Clinical Center, Kragujevac, from June to July 2020. The study was a prospective clinical trial and included 62 patients with the acute-phase of COVID-19 infection (61.3% males, mean age 60.82 ± 11.72). The duration of the comprehensive pulmonary rehabilitation program was 14 days ± 2.28 days. Oxygen saturation and heart rate were determined by using the pulse oximeter, oxygen flow, and arterial blood gas analysis values by using the gas analyzer. The anxiety assessment was measured using the Generalized Anxiety Disorder (GAD-7). RESULTS: The values of oxygen saturation significantly differed before and after the respiratory exercise sessions (95.77 vs 98.02, respectively; p < .001). After the respiratory exercise program, significantly lower values of the GAD-7 scale were observed compared to the values before the respiratory exercise program (p = .049). A significant negative correlation was observed between oxygen saturation after respiratory exercise and age and presence of chronic obstructive pulmonary disease (ρ = -0.329; p = .013; ρ = -0.334; p = .009, respectively). GAD-7 score after respiratory exercise negatively correlated with chronic obstructive pulmonary disease and malignancy (ρ = -0.285; p = .025; ρ = -0.350; p = .005, respectively). CONCLUSION: The respiratory exercise program significantly improves oxygen saturation and anxiety levels in COVID-19 patients.

Increased Severity of Ulcerative Colitis in the Terminal Phase of the Metabolic Syndrome.

Ulcerative colitis is chronic immune-mediated disorder that affects primarily colonic mucosa. The metabolic syndrome has increasing global prevalence with a significant impact on biology of chronic diseases, such as ulcerative colitis. Today it is known that the metabolic syndrome attenuates severity of ulcerative colitis. Still, there is no evidence that different stages of metabolic syndrome alter the course of the ulcerative colitis. The aim of this study was to dissect out how progression of the metabolic syndrome impacted the biology of ulcerative colitis and severity of clinical presentation. Seventy-two patients (41 men and 31 women, 22-81 years old) were enrolled in this observational cross-sectional study. Concentrations of pro- and anti-inflammatory cytokines in serum and feces samples were measured and phenotype of colon infiltrating cells was analyzed. Patients in the terminal phase of the metabolic syndrome have clinically and pathohistologically more severe form of ulcerative colitis, which is followed by decreased concentrations of systemic galectin-1, increased values of systemic pro-inflammatory mediators and increased influx of lymphocytes in affected colon tissue. Our data suggest that reduced concentrations of galectin-1 and predomination of the pro-inflammatory mediators in patients with terminal stage of the metabolic syndrome enhance local chronic inflammatory response and subsequent tissue damage, and together point on important role of galectin-1 in immune response in ulcerative colitis patients with the metabolic syndrome.

Metabolic syndrome attenuates ulcerative colitis: Correlation with interleukin-10 and galectin-3 expression.

BACKGROUND: Ulcerative colitis (UC) is a chronic disease characterized by inflammation of intestinal epithelium, primarily of the colon. An increasing prevalence of metabolic syndrome (MetS) in patients with UC has been documented recently. Still, there is no evidence that MetS alters the course of the UC. AIM: To test the influence of the MetS on the severity of UC and the local and systemic immune status. METHODS: Eighty nine patients with de novo histologically confirmed UC were divided in two groups, according to ATP III criteria: Group without MetS (no MetS) and group with MetS. RESULTS: Clinically and histologically milder disease with higher serum level of immunosuppressive cytokine interleukin-10 (IL-10) and fecal content of Galectin-3 (Gal-3) was observed in subjects with UC and MetS, compared to subjects suffering from UC only. This was accompanied with predomination of IL-10 over pro-inflammatory cytokines tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-17 (IL-17) in the sera as well as Gal-3 over TNF-α and IL-17 in feces of UC patients with MetS. Further, the patients with both conditions (UC and MetS) had higher percentage of IL-10 producing and Gal-3 expressing innate and acquired immune cells in lamina propria. CONCLUSION: Local dominance of Gal-3 and IL-10 over pro-inflammatory mediators in patients with MetS may present a mechanism for limiting the inflammatory process and subsequent tissue damage in UC.

Galectin-3 Regulates Indoleamine-2,3-dioxygenase-Dependent Cross-Talk between Colon-Infiltrating Dendritic Cells and T Regulatory Cells and May Represent a Valuable Biomarker for Monitoring the Progression of Ulcerative Colitis.

Galectin-3 regulates numerous biological processes in the gut. We investigated molecular mechanisms responsible for the Galectin-3-dependent regulation of colon inflammation and evaluated whether Galectin-3 may be used as biomarker for monitoring the progression of ulcerative colitis (UC). The differences in disease progression between dextran sodium sulphate-treated wild type and Galectin-3-deficient mice were investigated and confirmed in clinical settings, in 65 patients suffering from mild, moderate, and severe colitis. During the induction phase of colitis, Galectin-3 promoted interleukin-1ß-induced polarization of colonic macrophages towards inflammatory phenotype. In the recovery phase of colitis, Galectin-3 was required for the immunosuppressive function of regulatory dendritic cells (DCs). Regulatory DCs in Galectin-3:Toll-like receptor-4:Kynurenine-dependent manner promoted the expansion of colon-infiltrated T regulatory cells (Tregs) and suppressed Th1 and Th17 cell-driven colon inflammation. Concentration of Galectin-3 in serum and stool samples of UC patients negatively correlated with clinical, endoscopic, and histological parameters of colitis. The cutoff serum values of Galectin-3 that allowed the discrimination of mild from moderate and moderate from severe colitis were 954 pg/mL and 580 pg/mL, respectively. Fecal levels of Galectin-3 higher than 553.44 pg/mL indicated attenuation of UC. In summing up, Galectin-3 regulates the cross-talk between colon-infiltrating DCs and Tregs and represents a new biomarker for monitoring the progression of UC.

Indoleamine 2,3-dioxygenase-dependent expansion of T-regulatory cells maintains mucosal healing in ulcerative colitis.

BACKGROUND: Dendritic cell (DC)-derived indolamine 2,3-dioxygenase (IDO) degrades tryptophan to kynurenine, which promotes conversion of inflammatory T cells in immunosuppressive regulatory T cells (Tregs). We analyzed the significance of the IDO:Treg axis for inducing and maintaining mucosal healing in ulcerative colitis (UC). METHODS: Dextran sodium sulphate (DSS)-induced colitis in BALB/c mice (model for mucosal healing) and C57BL/6 mice (model for persistent disease) was used. Serum, fecal samples and colon-infiltrating immune cells of 65 patients with UC with mucosal healing or persistent colitis were analyzed. RESULTS: Significantly higher serum levels of kynurenine and downregulated inflammatory cytokines were noticed in DSS-treated BALB/c mice compared with C57BL/6 mice. Increased IDO activity and attenuated capacity for antigen presentation and production of inflammatory cytokines, observed in BALB/c DCs, was followed by a significantly lower number of inflammatory T helper 1 (Th1) and Th17 cells and a notably increased number of Tregs in the colons of DSS-treated BALB/c mice. DCs and Tregs were crucially important for the maintenance of mucosal healing since their depletion aggravated colitis. Mucosal healing, followed by an increase in kynurenine and intestinal Tregs, was re-established when BALB/c DCs were transferred into DC-depleted or Treg-depleted DSS-treated BALB/c mice. This phenomenon was completely abrogated by the IDO inhibitor. Significantly higher serum and fecal levels of kynurenine, accompanied by an increased presence of intestinal Tregs, were noticed in patients with UC with mucosal healing and negatively correlated with disease severity, fecal calprotectin, colon-infiltrating interferon γ and interleukin-17-producing cells, serum and fecal levels of inflammatory cytokines. CONCLUSION: IDO-dependent expansion of endogenous Tregs should be further explored as a new approach for the induction and maintenance of mucosal healing in patients with UC.

Fecal Galectin-3: A New Promising Biomarker for Severity and Progression of Colorectal Carcinoma.

BACKGROUND AND OBJECTIVES: The aim of the study was to determine systemic and fecal values of galectin-3 and pro- and anti-inflammatory cytokines in patients with CRC and the relationship with clinicopathological aspects. METHODS: Concentrations of galectin-3, TNF-α, TGF-ß, IL-10, and IL-1ß were analyzed in samples of blood and stool of 60 patients with CRC. RESULTS: Systemic concentration of TNF-α was significantly lower in patients with severe diseases (advanced TNM stage, nuclear grade, and poor histological differentiation) as in patients with more progressive CRC (lymph and blood vessel invasion, presence of metastasis). Fecal values of anti-inflammatory cytokines TGF-ß and IL-10 were increased in patients with severe stadium of CRC. Fecal concentration of Gal-3 was enhanced in CRC patients with higher nuclear grade, poor tumor tissue differentiation, advanced TNM stage, and metastatic disease. Gal-3/TNF-α ratio in sera and feces had a higher trend in patients with severe and advanced diseases. Positive correlation between fecal Gal-3 and disease severity, tumor progression, and biomarkers AFP and CEA, respectively, was also observed. CONCLUSIONS: Predomination of Gal-3 in patients with advanced diseases may implicate on its role in limiting ongoing proinflammatory processes. The fecal values of Gal-3 can be used as a valuable marker for CRC severity and progression.

Deletion of Galectin-3 Enhances Xenobiotic Induced Murine Primary Biliary Cholangitis by Facilitating Apoptosis of BECs and Release of Autoantigens.

Galectin-3 (Gal-3) is a carbohydrate binding lectin, with multiple roles in inflammatory diseases and autoimmunity including its antiapoptotic effect on epithelial cells. In particular, increased expression of Gal-3 in epithelial cells is protective from apoptosis. Based on the thesis that apoptosis of biliary epithelial cells (BECs) is critical to the pathogenesis of Primary Biliary Cholangitis (PBC), we have analyzed the role of Gal-3 in the murine model of autoimmune cholangitis. We took advantage of Gal-3 knockout mice and immunized them with a mimotope of the major mitochondrial autoantigen of PBC, 2-octynoic acid (2-OA) coupled to BSA (2OA-BSA) and evaluated the natural history of subsequent disease, compared to control wild-type mice, by measuring levels of antibodies to PDC-E2, immunohistology of liver, and expression of Gal-3. We report herein that deletion of Gal-3 significantly exacerbates autoimmune cholangitis in these mice. This is manifested by increased periportal infiltrations, bile duct damage, granulomas and fibrosis. Interestingly, the BECs of Gal-3 knockout mice had a higher response to apoptotic stimuli and there were more pro-inflammatory lymphocytes and dendritic cells (DCs) in the livers of Gal-3 knockout mice. In conclusion, Gal-3 plays a protective role in the pathways that lead to the inflammatory destruction of biliary epithelial cells.

Potential dual immunomodulatory role of VEGF in ulcerative colitis and colorectal carcinoma.

OBJECTIVE: Progression from ulcerative colitis (UC) toward colorectal carcinoma (CRC) is multistep process that includes gene alterations of tumor suppressor genes, such as p53 and p16. The aim of this study was to investigate the expression patterns of p16, p53 and VEGF in affected tissue and serum levels of cytokines TNF-α, IFN-γ, IL-4, IL-6, IL-10 and IL-17 in patients with UC and CRC, respectively. MATHERIALS AND METHODS. Serum levels of cytokine in patients with UC (n=24) and CRC (n=75) and in a healthy group (n=37) were analyzed by ELISA. Endoscopic biopsies specimens of UC and CRC were studied by immunohistochemical staining for p16, p53 and VEGF. RESULTS: Patients with UC with presence of extraintestinal manifestations, complications, and positive staining of p16, p53 and VEGF respectively had higher serum levels of pro-inflammatory cytokines. Higher percentage of CRC patients had positive staining of p16, p53 and VEGF. CRC patients with positive staining of VEGF had decreased systemic values of pro-inflammatory IFN-γ and increased values of immunosuppressive IL-10. CONCLUSIONS: Relatively low IL-10 in patients with severe UC is insufficient to compensate IL-6 secretion and subsequently enhanced type 1/17 immune response. In UC patients, p16 and p53 induce enhanced VEGF expression and subsequent production of pro-inflammatory TNF-α and IL-6. In CRC patients VEGF seems to have immunosuppressive role. It appears that tumor suppressor gene-VEGF axis have dual role on immune response in inflammation of UC and tumor growth and progression of CRC.