Assessing the Therapeutic Impacts of HAMLET and FOLFOX on BRAF-Mutated Colorectal Cancer: A Study of Cancer Cell Survival and Mitochondrial Dynamics In Vitro and Ex Vivo.

Background and Objectives: Colorectal cancer (CRC) is a major global health challenge. The BRAF V600E mutation, found in 8-12% of CRC patients, exacerbates this by conferring poor prognosis and resistance to therapy. Our study focuses on the efficacy of the HAMLET complex, a molecular substance derived from human breast milk, on CRC cell lines and ex vivo biopsies harboring this mutation, given its previously observed selective toxicity to cancer cells. Materials and Methods: we explored the effects of combining HAMLET with the FOLFOX chemotherapy regimen on CRC cell lines and ex vivo models. Key assessments included cell viability, apoptosis/necrosis induction, and mitochondrial function, aiming to understand the mutation-specific resistance or other cellular response mechanisms. Results: HAMLET and FOLFOX alone decreased viability in CRC explants, irrespective of the BRAF mutation status. Notably, their combination yielded a marked decrease in viability, particularly in the BRAF wild-type samples, suggesting a synergistic effect. While HAMLET showed a modest inhibitory effect on mitochondrial respiration across both mutant and wild-type samples, the response varied depending on the mutation status. Significant differences emerged in the responses of the HT-29 and WiDr cell lines to HAMLET, with WiDr cells showing greater resistance, pointing to factors beyond genetic mutations influencing drug responses. A slight synergy between HAMLET and FOLFOX was observed in WiDr cells, independent of the BRAF mutation. The bioenergetic analysis highlighted differences in mitochondrial respiration between HT-29 and WiDr cells, suggesting that bioenergetic profiles could be key in determining cellular responses to HAMLET. Conclusions: We highlight the potential of HAMLET and FOLFOX as a combined therapeutic approach in BRAF wild-type CRC, significantly reducing cancer cell viability. The varied responses in CRC cell lines, especially regarding bioenergetic and mitochondrial factors, emphasize the need for a comprehensive approach considering both genetic and metabolic aspects in CRC treatment strategies.

Predictors of Quality of Life Six Years after Curative Colorectal Cancer Surgery: Results of the Prospective Multicenter Study.

Background and objectives: Improving early diagnosis and advances in colorectal cancer (CRC) treatment leads to longer survival of these patients. The purpose of this study was to identify the main surgical factors affecting long-term Quality of life (QoL) among colorectal cancer patients after surgery. Materials and Methods: QoL was prospectively evaluated in patients undergoing elective colorectal cancer resection operations in three CRC surgery centers of Lithuania using EORTC generic (QLQC-30) and disease-specific (QLQ-CR29) questionnaires at the time of preoperative admission and 1, 24, and 72 months after surgery. QoL was evaluated among different patient groups, diagnostic and treatment modalities, disease, and postoperative complications. Non-parametric tests and multivariate logistic regression models were used for statistical analysis. Results: Eighty-eight consecutive CRC patients from three institutions were included in the study over a three-month inclusion period, 42 (47.73%) women and 46 (52.27%) men, mean age 64.2 ± 11.5 years. Most tumors were localized in the sigmoid colon and rectum. The largest number of patients had stage III cancer. Twenty-nine patients died-a 6-year survival rate was 67%. 50 of 59 live patients (84.8%) responded to the questionnaire 6 years after their operation. Evaluating changes in quality of life 72 months after surgery with assessments before surgery, both questionnaire responses revealed good long-term CRC surgical treatment results: improved general and functional scale estimates and decreased symptom scale ratings. The multivariate analysis found that age, stoma formation, and rectal cancer were independent risk factors for having worse QoL six years after surgical intervention. Conclusions: Six years after surgery, QoL returns to preoperative levels. Age, stoma formation, adjuvant treatment, and rectal cancer reduce long-term QoL.

The Role of VEGFA, COX2, HUR and CUGBP2 in Predicting the Response to Neoadjuvant Therapy in Rectal Cancer Patients.

Background and objectives: The effectiveness of neoadjuvant therapy, which is commonly used for stage II-III rectal cancer (RC) treatment, is limited. Genes associated with the pathogenesis of RC could determine response to this treatment. Therefore, the aim of this study was to investigate the potential predictive value of VEGFA, COX2, HUR and CUGBP2 genes and the associations between post-treatment changes in gene expression and the efficacy of neoadjuvant therapy. Materials and Methods: Biopsies from RC and healthy rectal tissue of 28 RC patients were collected before neoadjuvant therapy and 6-8 weeks after neoadjuvant therapy. The expression levels of VEGFA, COX2, HUR, CUGBP2 genes were evaluated using a quantitative real-time polymerase chain reaction. Results: The results reveal a significantly higher expression of VEGFA, COX2 and HUR mRNA in RC tissue compared to healthy rectal tissue (p < 0.05), and elevated VEGFA gene expression in pre-treatment tissues was associated with a better response to neoadjuvant therapy based on T-stage downstaging (p < 0.05). The expression of VEGFA, HUR and CUGBP2 genes significantly decreased after neoadjuvant therapy (p < 0.05). Responders to treatment demonstrated a significantly stronger decrease of VEGFA and COX2 expression after neoadjuvant therapy than non-responders (p < 0.05). Conclusions: The findings of this study suggest that the pre-treatment VEGFA gene expression might have predictive value for the response to neoadjuvant therapy, while the post-treatment decrease in VEGFA and COX2 gene expression could indicate the effectiveness of neoadjuvant therapy in RC patients.

A Variant of COL3A1 (rs3134646) Is Associated With Risk of Developing Diverticulosis in White Men.

BACKGROUND: Colonic diverticulosis is one of the most common gastroenterological disorders. Although diverticulosis is typically benign, many individuals develop diverticulitis or other aspects of diverticular disease. Diverticulosis is thought to stem from a complex interaction of environmental, dietary, and genetic factors; however, the contributing genetic factors remain unknown. OBJECTIVE: The aim of our present study was to determine the role of genetic variants within genes encoding for collagens of the connective tissue in diverticulosis. DESIGN: This was a transsectional genetic association study. SETTINGS: This study was conducted at three tertiary referral centers in Germany and Lithuania. PATIENTS: Single-nucleotide polymorphisms in COL3A1 (rs3134646, rs1800255) and COL1A1 (rs1800012) were genotyped in 422 patients with diverticulosis and 285 controls of white descent by using TaqMan assays. MAIN OUTCOME MEASURES: The association of colonoscopy-proven diverticulosis with genetic polymorphisms with herniations was assessed in multivariate models. RESULTS: The rs3134646, rs1800255, and rs1800012 variants were significantly associated with the risk of developing diverticulosis in the univariate model; however, these associations were not significant in the multivariate logistic regression analysis including additional nongenetic variables. When selectively analyzing sexes, the genotype AA (AA) in rs3134646 remained significantly associated with diverticulosis in men (OR, 1.82; 95% CI, 1.04-3.20; p = 0.04). LIMITATIONS: Because a candidate approach was used, additional relevant variants could be missed. Within our cohort of patients with diverticulosis, only a small proportion had diverticular disease and thus, we could not examine the variants in these subgroups. Functional studies, including the analysis of the involved collagens, are also warranted. CONCLUSIONS: Our study shows that a variant of COL3A1 (rs3134646) is associated with the risk of developing colonic diverticulosis in white men, whereas rs1800255 (COL3A1) and rs1800012 (COL1A1) were not associated with this condition after adjusting for confounding factors. Our data provide novel valuable insights in the genetic susceptibility to diverticulosis. See Video Abstract at http://links.lww.com/DCR/A504.

Improved perioperative care is associated with improved long-term survival in colorectal cancer.

PURPOSE: To compare perioperative colorectal cancer care and survival in patient cohorts operated in 2005 and in 2010 in Lithuania. METHODS: Comparative observational cohort study was performed. The study was conducted in the three Lithuanian cancer hospitals. Patients, who underwent curative surgery for colorectal cancer in 2005 and 2010, were included. Demographic characteristics, distribution of the tumors, preoperative diagnostics and staging, surgical treatment, the quality of pathological examination, morbidity, and mortality were analyzed. One- and 5-year overall survival data were compared between the groups. RESULTS: Colorectal cancer diagnostics and treatment improved from 2005 to 2010 significantly. The disease was identified as stage III-IV for 45 vs. 48% of the patients; however, computed tomography staging scan was performed only for 5.9 vs. 17.8% in 2005 and 2010, respectively. Laparoscopic operations were performed 1.5 vs. 10.5% and abdominoperineal resections-42.7 vs. 31.7% in 2005 and 2010, respectively. The number of harvested lymph nodes was mentioned in 55.8 vs. 97.7% of the cases, whereas more than 12 lymph nodes were examined in 18 vs. 66.6% of cases after histological examination. The overall 5-year survival was 52.1 vs. 63.1% (p < 0.0001), while the 5-year survival of the patients with stage IV of disease was 4.2 vs. 17.8% in 2005 and 2010, respectively. CONCLUSION: Preoperative investigation, surgical treatment, pathological examination, and postoperative course are associated with improved overall survival in colorectal cancer patients, undergoing curative surgery in the resource-limited settings.

Evaluation of clinical teaching quality in competency-based residency training in Lithuania.

BACKGROUND AND AIM: In 2013, all residency programs at the Lithuanian University of Health Sciences were renewed into the competency-based medical education curriculum (CBME). In 2015, we implemented the validated EFFECT questionnaire together with the EFFECT-System for quality assessment of clinical teaching in residency training. The aim of this study was to investigate the influence of characteristics of the resident (year of training) and clinical teacher (gender, age, and type of academic position) on teaching quality, as well as to assess areas for teaching quality improvement. MATERIALS AND METHODS: Residents from 7 different residency study programs filled out 333 EFFECT questionnaires evaluating 146 clinical teachers. We received 143 self-evaluations of clinical teachers using the same questionnaire. Items were scored on a 6-point Likert scale. Main outcome measures were residents' mean overall (MOS), mean subdomain (MSS) and clinical teachers' self-evaluation scores. The overall comparisons of MOS and MSS across study groups and subgroups were done using Student's t test and ANOVA for trend. The intraclass correlation coefficient (ICC) was calculated in order to see how residents' evaluations match with self-evaluations for every particular teacher. To indicate areas for quality improvement items were analyzed subtracting their mean score from the respective (sub)domain score. RESULTS: MOS for domains of "role modeling", "task allocation", "feedback", "teaching methodology" and "assessment" valued by residents were significantly higher than those valued by teachers (P<0.01). Teachers who filled out self-evaluation questionnaires were rated significantly higher by residents in role modeling subdomains (P<0.05). Male teachers in (sub)domains "role modeling: CanMEDS roles and reflection", "task allocation", "planning" and "personal support" were rated significantly higher than the female teachers (P<0.05). Teachers aged 40 years or younger were rated higher (P<0.01). Residents ratings by type of teachers' academic position almost in all (sub)domains differed significantly (P<0.05). No correlation observed between MOS of a particular teacher and MOS as rated by residents (ICC=0.055, P=0.399). The main areas for improvement were "feedback" and "assessment". CONCLUSIONS: Resident evaluations of clinical teachers are influenced by teachers' age, gender, year of residency training, type of teachers' academic position and whether or not a clinical teacher performed self-evaluation. Development of CBME should be focused on the continuous evaluation of quality, clinical teachers educational support and the implementation of e-portfolio.

Validation of the EFFECT questionnaire for competence-based clinical teaching in residency training in Lithuania.

BACKGROUND AND AIM: In 2013, all residency programs at the Lithuanian University of Health Sciences were renewed into a competency-based medical education curriculum. To assess the quality of clinical teaching in residency training, we chose the EFFECT (evaluation and feedback for effective clinical teaching) questionnaire designed and validated at the Radboud University Medical Centre in the Netherlands. The aim of this study was to validate the EFFECT questionnaire for quality assessment of clinical teaching in residency training. MATERIALS AND METHODS: The research was conducted as an online survey using the questionnaire containing 58 items in 7 domains. The questionnaire was double-translated into Lithuanian. It was sent to 182 residents of 7 residency programs (anesthesiology reanimathology, cardiology, dermatovenerology, emergency medicine, neurology, obstetrics and gynecology, physical medicine and rehabilitation). Overall, 333 questionnaires about 146 clinical teachers were filled in. To determine the item characteristics and internal consistency (Cronbach's α), the item and reliability analyses were performed. Furthermore, confirmatory factor analysis (CFI) was performed using a model for maximum-likelihood estimation. RESULTS: Cronbach's α within different domains ranged between 0.91 and 0.97 and was comparable with the original version of the questionnaire. Confirmatory factor analysis demonstrated satisfactory model-fit with CFI of 0.841 and absolute model-fit RMSEA of 0.098. CONCLUSIONS: The results suggest that the Lithuanian version of the EFFECT maintains its original validity and may serve as a valid instrument for quality assessment of clinical teaching in competency-based residency training in Lithuania.

Preoperative long-course chemoradiotherapy plus adjuvant chemotherapy versus short-course radiotherapy without adjuvant chemotherapy both with delayed surgery for stage II-III resectable rectal cancer: 5-Year survival data of a randomized controlled trial.

BACKGROUND AND OBJECTIVE: At present, there are common recommendations for treatment for stage II-III resectable rectal cancer patients: preoperative conventional chemoradiotherapy (CRT) with delayed surgery in 6-8 weeks or preoperative short-course radiotherapy (SCRT) followed by immediate surgery. The aim of this study was to compare overall survival (OS) and disease-free survival (DFS) in two treatment groups: preoperative SCRT and CRT both with delayed surgery plus adjuvant chemotherapy in CRT arm. MATERIALS AND METHODS: A total of 150 patients were randomly assigned to two groups: 75 to CRT (preoperative conventional CRT, 50Gy/25 fr with fluorouracil and leucovorin on the 1st and the 5th week of RT followed by TME surgery in 6-8 weeks and 4 cycles of adjuvant fluorouracil/leucovorin every 4 weeks; then follow-up) and 75 to SCRT (preoperative short-course RT, 25Gy/5 fr followed by TME surgery in 6-8 weeks; then follow-up). The data of 140 patients (72 in CRT and 68 in SCRT group) were included in statistical analysis. Primary end points were OS and DFS. RESULTS: Median follow-up was 60.5 (range, 5-108) months. The 5-year DFS was 67% in the CRT group (n=72) and 45% in the SCRT group (n=68) (P=0.013; HR=1.88; 95% CI, 1.13-3.12; P=0.015). The 5-year OS was 79% and 62% in the CRT and SCRT groups, respectively (P=0.015; HR=2.05; 95% CI, 1.13-3.70; P=0.017). The 5-year OS for intent-to-treat (ITT) population (n=150) was 78% in the CRT and 58% in the SCRT group (P=0.003; HR=2.28; 95% CI, 1.30-4.00; P=0.004). CONCLUSIONS: The 5-year DFS and OS were significantly better in the CRT than the SCRT group. For ITT population, OS was also significantly better after CRT versus SCRT.

Epigenetic silencing of miR-137 is a frequent event in gastric carcinogenesis.

MicroRNAs (miRNA) are involved in posttranscriptional regulation of gene expression and are dysregulated during carcinogenesis. CpG island methylation of miR-137 is a common event in different cancers; however, the role of miR-137 in gastric cancer (GC) remains largely unexplored. In this study we aimed to characterize the epigenetic alterations of miR-137 in gastric carcinogenesis. We analyzed total 295 tissues including paired primary gastric cancer (T-GC) with corresponding adjacent gastric mucosa (N-GC), paired primary colorectal cancer (CRC) tissues with corresponding non-tumorous mucosa, gastric tissues from controls (N), and patients with chronic/atrophic gastritis (CG) with and without Helicobacter pylori infection. Bisulfite pyrosequencing and TaqMan RT-PCR were used to analyze miR-137 methylation and expression, respectively. Survival differences were evaluated using Kaplan-Meier analyses. miR-137 CpG island methylation was more frequent in tumorous compared to non-tumorous conditions and higher in CRC than in GC. In comparison to N-GC, miR 137 methylation level was lower in N and CG tissues, which correlates with Correas cascade. MiR-137 methylation inversely correlates with global LINE-1 methylation and miR-137 expression. miR-137 methylation was higher in intestinal type GC compared to diffuse one, and higher in antrum compared to cardia and corpus, however, miR-137 methylation was associated with worse prognosis in diffuse, but not in intestinal type of GC. The expression in colon was significantly higher compared to any gastric tissues suggesting functional difference. In summary, miR-137 methylation is a frequent event in gastrointestinal cancers which occurs early in stepwise manner during gastric carcinogenesis and inversely correlates with global methylation. © 2015 Wiley Periodicals, Inc.

Preoperative conventional chemoradiotherapy versus short-course radiotherapy with delayed surgery for rectal cancer: results of a randomized controlled trial.

BACKGROUND: There still is no evidence which neoadjuvant therapy regimen for stage II-III rectal cancer is superior. The aim of this study was to compare results achieved after long-course chemoradiotherapy (CRT) with short-term radiotherapy (RT) followed by delayed surgery. METHODS: A randomized trial was carried out between 2007-2013. One hundred fifty patients diagnosed with stage II-III rectal cancer were randomized into one of two neoadjuvant treatment arms: conventional chemoradiotherapy (CRT) and short-term radiotherapy (RT) followed by surgery after 6-8 weeks. Primary endpoints of this trial were downstaging and pathological complete response rate. Secondary endpoints were local recurrence rate and overall survival. RESULTS: The pathological complete response was found in 3 (4.4%) cases after RT and 8 (11.1%) after CRT (P = 0.112). Downstaging (stage 0 and I) was observed in 21 (30.9%) cases in RT group vs. 27 (37.5%) cases in CRT group (P = 0.409). Median follow-up time was 39.7 (range 4.9-79.7) months. 3-years overall survival (OS) was 78% in RT group vs. 82.4% in CRT group (P = 0.145), while disease-free survival (DFS) differed significantly - 59% in RT group vs. 75.1% in CRT group (P = 0,022). Hazard ratio of cancer progression for RT patients was 1.93 (95% CI: 1.08-3.43) compared to CRT patients. CONCLUSION: Three-years disease-free survival was better in CRT group comparing with RT group with no difference in overall survival. TRIAL REGISTRATION: http://clinicaltrials.gov identifier NCT00597311. January 2008.

Short-term results of quality of life for curatively treated colorectal cancer patients in Lithuania.

BACKGROUND AND OBJECTIVE: Treatment options for colorectal cancer patients create the need to assess the quality of life (QoL) of colorectal cancer patients in the early postoperative period when changes are potentially greatest. The aim of the current study was to assess the QoL of colorectal cancer patients following open and laparoscopic colorectal surgery. MATERIALS AND METHODS: A total of 82 consecutive patients requiring elective open or laparoscopic colorectal surgery were recruited to the study for 3 months in the three colorectal surgery centers of Lithuania. Patients completed the EORTC QLQ-C30 (version 3.0) questionnaire before surgery, 2 and 5 days, 1 and 3 months after operation. The EORTC QLQ-CR29 questionnaire was completed before surgery and at 1 and 3 months after operation. Analysis was done according to the manual for each instrument. RESULTS: EORTC QLQ-C30 reflected the postoperative recovery of QoL. The global health status, cognitive and emotional functioning came back to the preoperative level in one month after operation. Physical and role functioning for laparoscopic group was significantly improved in 1 month after operation and in 3 months for open surgery group respectively. Colorectal module EORTC-QLQ-CR29 found that future perspective increased significantly in laparoscopic group 1 month after operation. CONCLUSIONS: The present study showed that majority of functional scale scores came back to the preoperative level during the first 3 months after colorectal cancer surgery. Differences in QoL according to surgical approach are mostly expressed on this period.

Influence of NADPH oxidase on inflammatory response in primary intestinal epithelial cells in patients with ulcerative colitis.

BACKGROUND: The aim of this study is to evaluate the role of NADPH oxidase in primary intestinal epithelial cells during the active phase of UC. METHODS: The primary human colonic epithelial cells were isolated from 19 patients with mild to moderate inflammatory activity of UC and 14 controls using chelation method. The cells were cultivated under the effect of mediators. Viability of cells was assessed by fluorescent microscopy. Production of reactive oxygen species (ROS) by the cells was measured fluorimetrically using Amplex Red. Production of TNF-α cytokine by the colonic epithelial cells was analysed by ELISA. RESULTS: The results of our study showed that unstimulated cells of UC patients had a decreased viability, increased ROS production, but similar TNF-α level when compared to the controls. Stimulation with LPS increased hydrogen peroxide and TNF-α level in the UC group. Treatment of colonic epithelial cells with NADPH oxidase inhibitor increased cell viability decreased the levels of ROS and TNF-α in the LPS-treated cells isolated from UC patients. CONCLUSIONS: Our study showed that bacterial endotoxins induced NADPH oxidase activation in the colonic epithelial cells. Moreover, we revealed that treatment with NADPH oxidase inhibitors had a protective effect against pro-inflammatory action of LPS in human colonic epithelium cells during inflammation.

The pattern of colorectal cancer surgery in Lithuania in 2005: do results meet expectations?

UNLABELLED: The aim of this study was to expose the pattern of the surgical treatment of colorectal cancer in Lithuania in 2005. MATERIAL AND METHODS: A retrospective analysis of 590 patients treated for colorectal cancer in the surgical departments of the Hospital of Lithuanian University of Health Sciences, the Institute of Oncology of Vilnius University, and Vilnius University Hospital Santariskiu Klinikos in 2005 was performed. Demographic data, preoperative evaluation, postoperative complications assessed according to the Clavien-Dindo classification, the quality of pathological examination, and survival rates were analyzed. RESULTS: A total of 590 patients, 269 women (45.6%) and 321 men (54.4%), were included in this study; the mean age was 68.3 years (SD, 11.2). Tumors were found in the colon of 274 patients (46.4%) and in the rectum of 316 patients (53.6%). An abdominal ultrasound scan was preoperatively performed in 516 patients (87.5%) and a chest x-ray in 316 patients (53.6%); 35 patients (5.9%) underwent abdominal computed tomography. Endorectal ultrasound was done in 99 (31.7%) cases. Neoadjuvant radiotherapy for T3 and T4 rectal tumors was applied in 42 cases (18.1%). Besides, 211 patients (35.8%) developed postoperative complications with an anastomotic leak emerging in 20 cases (3.4%). Death occurred in 7 patients (1.18%). On the average, 11.15 lymph nodes (SD, 6.02) were found in pathological specimens. Circumferential resection margins were assessed in 58 cases (18.4%). The overall 5-year survival rate was 52.06%. CONCLUSIONS: The preoperative evaluation and the treatment of patients with colorectal cancer were not sufficiently consistent in Lithuania in 2005. In order to improve the treatment of colorectal cancer, standardization or the national database of colorectal cancer is necessary.

HAMLET effect on cell death and mitochondrial respiration in colorectal cancer cell lines with KRAS/BRAF mutations.

PURPOSE: Treatment of advanced colorectal cancer (CRC) depends on the correct selection of personalized strategies. HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a natural proteolipid milk compound that might serve as a novel cancer prevention and therapy candidate. Our purpose was to investigate HAMLET effect on viability, death pathway and mitochondrial bioenergetics of CRC cells with different KRAS/BRAF mutational status in vitro. METHODS: We treated three cell lines (Caco-2, LoVo, WiDr) with HAMLET to evaluate cell metabolic activity and viability, flow cytometry of apoptotic and necrotic cells, pro- and anti-apoptotic genes, and protein expressions. Mitochondrial respiration (oxygen consumption) rate was recorded by high-resolution respirometry system Oxygraph-2 k. RESULTS: The HAMLET complex was cytotoxic to all investigated CRC cell lines and this effect is irreversible. Flow cytometry revealed that HAMLET induces necrotic cell death with a slight increase in an apoptotic cell population. WiDr cell metabolism, clonogenicity, necrosis/apoptosis level, and mitochondrial respiration were affected significantly less than other cells. CONCLUSION: HAMLET exhibits irreversible cytotoxicity on human CRC cells in a dose-dependent manner, leading to necrotic cell death and inhibiting the extrinsic apoptosis pathway. BRAF-mutant cell line is more resistant than other type lines. HAMLET decreased mitochondrial respiration and ATP synthesis in CaCo-2 and LoVo cell lines but did not affect WiDr cells' respiration. Pretreatment of cancer cells with HAMLET has no impact on mitochondrial outer and inner membrane permeability.

Incidence of inflammatory bowel disease in Kaunas region, Lithuania.

OBJECTIVE: The aim of this study was to evaluate the incidence of inflammatory bowel disease in Kaunas and its region during a 3-year period. MATERIAL AND METHODS: The study was conducted during the 3-year period (2007-2009) and enrolled the patients from Kaunas with its region, which has a population of 381,300 inhabitants. The data were collected from all practices in the area where the diagnosis of inflammatory bowel disease was made by practicing gastroenterologists and consulting pediatricians along with endoscopists. Only new cases of inflammatory bowel disease were included into analysis. The diagnosis of ulcerative colitis and Crohn's disease was strictly made according to the Copenhagen criteria. Age- and sex-standardized incidence was calculated for each year of the study period. RESULTS: A total of 108 new inflammatory bowel disease cases were diagnosed during the study period: 87 had ulcerative colitis, 16 Crohn's disease, and 5 indeterminate colitis. The incidence of ulcerative colitis, Crohn's disease, and indeterminate colitis for each study year was 6.85, 5.33, and 7.38 per 100,000; 0.95, 1.11, and 1.57 per 100,000; and 0.47, 0.21, and 0.42 per 100,000, respectively. The average 3-year standardized incidence of ulcerative colitis, Crohn's disease, and indeterminate colitis was 6.52, 1.21, and 0.37 per 100,000, respectively. The mean patients' age at onset of ulcerative colitis, indeterminate colitis, and Crohn's disease was 49.95 (SD, 17.03), 49.80 (SD, 17.71), and 34.94 years (SD, 0.37), respectively. CONCLUSIONS: The average 3-year incidence of ulcerative colitis in Kaunas region was found to be lower as compared with that in many parts of Central and Western Europe. The incidence of Crohn's disease was low and very similar to other countries of Eastern Europe. Age at onset of the diseases appeared to be older than that reported in the Western industrialized countries.

Matrix metalloproteinase-9 is a prognostic marker to predict survival of patients who underwent surgery due to rectal carcinoma.

Common prognostic factors do not fully predict clinical outcomes in colorectal cancer, one of the most common malignancies in developed countries. Therefore, biological prognostic markers are under investigation. We investigated the prognostic value of expression of matrix metalloproteinases (MMP-2 and MMP-9) and their inhibitors (TIMP-2 and TIMP-3) in rectal carcinoma to predict survival of the patients. Retrospective analysis of clinicopathological findings of 64 patients who underwent rectal resection due to carcinoma and were followed-up from 2 to 96 months (median 48) was performed. Semi-quantitative scoring was used to assess the expression levels of MMP-2, MMP-9, TIMP-2 and TIMP-3 in rectal carcinoma. During the follow-up, 28 patients died. The deceased patients demonstrated significantly higher expression of MMP-9 and lower expression of TIMP-3 in parenchyma of carcinoma and lower expression of TIMP-2 in stroma of carcinoma, compared to survivors. Moreover, the deceased patients were associated with advanced tumor, metastases in lymph nodes and distant metastases. According to univariate analysis longer survival was predicted by lower expression of MMP-9 in parenchymal cells (p = 0.03), tumor size (early tumor) (p = 0.026), absence of metastases in lymph nodes (p = 0.02) or distant metastases (p = 0.04). Multivariate analysis revealed that metastases in lymph nodes, higher expression of MMP-9 in parenchyma, and lower expression of MMP-9 in stromal cells significantly increased mortality. Expression of MMP-9 in rectal carcinoma is a prognostic marker for overall survival. It is important to identify the origin of MMP-9 to predict better overall survival of the patients.

Environmental and Dietary Risk Factors for Colonic Diverticulosis and Diverticulitis.

BACKGROUND AND AIMS: Colonic diverticulosis (CD) is among the most common conditions of the large bowel. Several factors have been associated with an increased risk of CD and its complications, including advanced age, obesity, physical inactivity, and a low-fiber diet. Available data is conflicting and a comprehensive analysis of different bowel, dietary and environmental habits linked with CD is lacking. We aimed to investigate the relationship between potential risk factors and CD prevalence using full data from a colonoscopy-based cross-sectional study in Europe. METHODS: The study was conducted at three tertiary referral centers in Germany and Lithuania. It included consecutive adult patients referred for routine colonoscopy who completed a detailed questionnaire on our considered multiple risk factors for diverticulosis and diverticulitis, including dietary and environmental factors, and bowel habits. RESULTS: The study included 1,333 patients, 696 women and 635 men. Colonic diverticulosis was diagnosed in 858 (64%) of patients. Multivariate analysis revealed that age (OR: 1.08, 95%CI: 1.06-1.10, p<0.001) and obesity (OR: 1.05, 95%CI: 1.02-1.09, p=0.004) were associated with CD. We also revealed new risk factors for CD: increased frequency of bowel movements (OR: 0.10, 95%CI: 0.03-0.33, p<0.001) and feeling of incomplete bowel emptying (OR: 2.05, 95%CI: 1.47-2.87, p<0.001). Older participants had reduced odds (OR: 0.921, 95 CI: 0.89-0.95, p<0.05) of diverticulitis compared to younger subjects. Feeling of incomplete bowel emptying after defecation was associated with increased odds (OR: 2.769, 95% CI 1.35-5.7, p<0.006) for diverticulitis. Moreover, participants with a higher educational status had increased odds (OR: 2.453, 95%CI: 1.31-4.59, p=0.005) for diverticulitis compared to the lower education group. CONCLUSIONS:  Study shows that older age, obesity, frequency of bowel movements, and feeling of incomplete bowel emptying are associated with the risk of CD. Furthermore, older age, feeling of incomplete bowel emptying, and higher education were associated with the risk of diverticulitis among CD patients.

Lymph node retrieval after resection of rectal cancer following preoperative chemoradiotherapy.

BACKGROUND: According to the current guidelines of proper TNM staging, 12 lymph nodes per specimen are crucial. This study assessed the role of preoperative radiochemotherapy on the number of lymph nodes detected in the tumor-bearing specimen. MATERIAL AND METHODS: Retrospective data of 138 patients who underwent surgery for stage II and III rectal cancer without preoperative radiochemotherapy during the period of 2004-2006 (control group) were compared with prospective data of 38 patients who received preoperative radiochemotherapy during the period of 2007-2008 (study group). The number of patients with metastatic lymph nodes, number of lymph nodes per specimen, number of metastatic lymph nodes per specimen, and the size of the tumor between the groups were compared. RESULTS: Positive lymph nodes were detected in 88 (64%) patients in the control group as compared with 9 (21%) patients in the study group (P<0.05). The mean number of lymph nodes per specimen in the control group was 13.5, while in the study group, the mean number of lymph nodes per specimen was 6.29 (P<0.05). There was a significant difference in the mean number of metastatic lymph nodes per specimen between the groups (5.12 in the control group versus 2.11 in the study group; P<0.05). The mean size of the tumor was 4.37 cm in the control group and 2.45 cm in the study group (P<0.01). CONCLUSIONS: Preoperative radiochemotherapy for advanced rectal cancer significantly decreased the number of lymph nodes detected in the tumor-bearing specimen. This also resulted in a significant decrease in the number of metastatic lymph nodes detected in the specimen, and fewer patients with stage III (N+) cancer were diagnosed. Preoperative radiochemotherapy could induce a significant downsizing and downstaging of advanced rectal cancer, but great care in operative and pathologic examination techniques must be taken to ensure appropriate staging.

Colonic intussusception caused by colonic lipoma: a case report.

Intussusception is a pediatric condition that rarely presents in adults. Colonic lipomas 4 cm and more in diameter can cause colonic intussusception leading to emergency operation. Surgical resection of the involved segment must be the procedure of choice. We report a case of colonic intussusception caused by colonic lipoma in an adult. The patient underwent operation, and histopathological examination of the specimen confirmed the diagnosis of colonic submucosal lipoma.

Comparison of Changes in Disease-Free and Overall Survival of Resectable Rectal Adenocarcinoma between 2010 and 2015.

BACKGROUND: Management of rectal cancer (RC) has undergone many changes in recent decades. A multidisciplinary approach to this complex disease is essential, ensuring high-quality diagnostic, treatment, and outcomes. We aimed to compare treatment results of RC in a single-centre setting between 2010 and 2015. METHODS: A retrospective comparative study included patients with newly diagnosed and operated resectable RC. Patients' diagnostic and treatment data were analysed. Postoperative morbidity was measured according to the Clavien-Dindo classification. Survival data were received from the Lithuanian Cancer Registry. Continuous variables were expressed as mean and SD. Student t test and one-way ANOVA were used for parametric data and the Mann-Whitney test for non-parametric. A multivariate logistic regression analysis was used to identify independent factors for increased survival. Association between categorical variables was verified using Pearson χ2. RESULTS: The study included 179 patients: 80 from 2010 and 99 from 2015. Mean sample age was 67.1 ± 10.7 years. There was no significant difference regarding age, gender, median ASA (3 in both groups), but mean hospital stay was 2 days shorter (8 vs. 10 days) in 2015 (p = 0.002). There were only 8 patients (4%) admitted to the hospital on an emergency basis. Pelvis MRI and abdominal CT were performed more often in 2015: from 37.5 to 77.8% (p < 0.001) and from 52.5 to 97% in 2015, respectively. Circumferential margin evaluation increased from 13.8 to 36.4% (p = 0.001). Neoadjuvant therapy increased from 20% in 2010 to 44.9% in 2015 (p = 0.01). The overall postoperative Clavien-Dindo complication rate was higher in 2015 (13.8 vs. 20.2%, p = 0.596), but in-hospital mortality was lower (1 vs. 0 patients). Comparison of radiological TNM and pathological TNM with one-way ANOVA showed a significant difference staging between 2010 (p = 0.002) and 2015 (p = 0.001). The 2-year overall survival (OS) increased from 76.3 to 86.9% (p = 0.046) and the median disease-free survival from 27 (range 0-35) months to 28 (range 0-35) months (72.5-83.5%, p = 0.077). Multivariate logistic regression analysis determined that availability and performance of MRI were associated with an increased OS (OR = 1.529, 95% CI 0.916-2.554, p = 0.020). CONCLUSIONS: The expanded quantity of preoperative imaging, an improved radiological staging, and compulsory multidisciplinary team board discussions have led to selective neoadjuvant treatment decision followed by surgery which can positively affect the 2-year OS rate.