Algimantas Tamelis

Initial results of a randomized controlled trial comparing clinical and pathological downstaging of rectal cancer after preoperative short-course radiotherapy or long-term chemoradiotherapy, both with delayed surgery.

Aim  The aim of this study was to compare the downstaging achieved after long‐course chemoradiotherapy (chRT) and short‐term radiotherapy (sRT) followed by delayed surgery.

Microvessel density as new prognostic marker after radiotherapy in rectal cancer

BackgroundThe extent of angiogenesis is an important prognostic factor for colorectal carcinoma, however, there are few studies concerning changes in angiogenesis with radiotherapy (RTX). Our aim was to investigate changes in tumor angiogenesis influenced by radiotherapy to assess the prognostic value of angiogenesis the microvessel density (MVD) in overall survival after radiotherapy.MethodsTumor specimens were taken from 101 patients resected for rectal cancer. The patients were divided into three groups according to the treatment they received before surgery (not treated, a short course, or long course of RTX). Tumor specimens were paraffin-embedded and immunohistochemistry was performed with primary antibody against CD-34 to count MVD.ResultsMVD was significantly lower in the group of patients treated with a long course of RTX (p <0.025). The mean MVD for the long RTX group was 134.8; for the short RTX group – 192.5; and for those not treated with RTX – 193.0. There were no significant statistical correlations between MVD and age, sex, grade of tumor differentiation (G) and tumor size (T) in those untreated with RTX. In long RTX group we found a significant prognostic rate for MVD when the density cut off was near 130 with 92.3% sensitivity and 64.7% specificity. When the MVD was lower than a cut off of 130, the survival period significantly increased (p = 0.001), the mortality rate is significantly higher if the MVD is higher than 130 (microvessel/mm2) (1953.047; p = 0.002), if the histological grade is moderate/poor (127.407; p = 0.013), if the tumor is T3/T4 (111.618; p = 0.014), and if the patient is male (17.92; p = 0.034) adjusted by other variable in model.ConclusionOur results show that a long course of radiotherapy significantly decreased angiogenesis in rectal cancer tissue. MVD was found to be a favourable marker for tumor behaviour during RTX and a predictor of overall survival after long course of RTX. Further investigations are now needed to determine the changes in angiogenesis during a shorter course of RTX.

The impact of age on post-operative outcomes of colorectal cancer patients undergoing surgical treatment

Backgroundthe purpose of study was to evaluate the impact of age on outcomes in colorectal cancer surgery.Methodspatients on hospital database treated for colorectal cancer during the period 1995 – 2002 were divided into two groups: Group 1 – patients of 75 years or older (n = 154), and Group 2 – those younger than 75 years (n = 532).ResultsIn Group 1, for colon cancers, proximal tumors were significantly more common (23% vs. 13.5%, p < 0.05), complicated cases were more frequent (46 % vs. 33%, p = 0.002), bowel obstruction more common at presentation (40% vs. 26.5%, p = 0.001), and more frequent emergency surgery required (24% vs. 14%, p = 0.003). Postoperative overall morbidity was higher in the elderly group, but with no differences in surgical complications rate. Overall 5 year survival was 39% vs. 55% (p = 0.0006) and cancer related 5 year survival was 44% vs. 62% (p = 0.0006). Multivariate Cox analysis showed that age was not an independent risk factor for postoperative mortality.ConclusionPreoperative complications and co-morbidities, more advanced disease, and higher postoperative nonsurgical complication rates adversely affect postoperative outcomes after surgery for colorectal cancer in the elderly.

Lack of association between miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608 gene polymorphisms and colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers worldwide with high mortality rates. MicroRNAs (miRNAs) have an established role in the development of different cancers. Single nucleotide polymorphisms (SNPs) in miRNA related genes were linked with various gastrointestinal malignancies. However, the data on association between miRNA SNPs and CRC development are inconsistent. The aim of the present study was to evaluate the association between miRNA-related gene polymorphisms (miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608) and the presence of CRC in European population. Gene polymorphisms were analyzed in 621 subjects (controls: n = 428; CRC: n = 193). MiR-27a T>C (rs895819), miR-146a G>C (rs2910164), miR-196a-2 C>T (rs11614913), miR-492 G>C (rs2289030) and miR-608 C>G (rs4919510) SNPs were genotyped by RT-PCR. Overall, all genotypes and alleles of miRNA SNPs were distributed equally between control and CRC groups. We observed a tendency for miR-146a C allele to be associated with lower risk of CRC when compared to G allele, however, the difference did not reach the adjusted P-value (odds ratio (OR) = 0.68, 95% confidence interval (CI) 0.49–0.95, P = 0.025). In conclusion, gene polymorphisms of miR-27a, miR-146a, miR-196a-2, miR-492, miR-492a and miR-608 were not associated with the presence of CRC in European subjects.

Morphologic pattern of myenteric neural plexus in colonic diverticular disease. A whole-mount study employing histochemical staining for acetylcholinesterase

BACKGROUND Diverticular disease (DD) of the colon is a frequent clinical problem because 30-50% of the population over the age of 60 years in western communities are affected by DD. Although certain clinical, physiological and biochemical studies have shown that the origin of DD may be neurogenic, the mechanism of DD pathogenesis is still not clear. METHODS The aim of the present study has been to assess the morphologic pattern of the myenteric nerve plexus (MNP) in diverticulous sigmoid colon (DSC) comparing the structural organization in DSC (n=10) to relatively normal sigmoid colon (rNSC) that had been resected from patients for rectal tumors (n=10). The histochemical method for acetylcholinesterase was utilized to visualize the MNP on pressure bloated, non-sectioned gut preparations. RESULTS The study revealed that the MNP of DSC was degenerated, as its interganglionic nerves were periodically interrupted and thinner than in rNSC. The number of myenteric ganglia in same-sized areas (125 mm(2)) as well as the average area of myenteric plexus was significantly higher in controls compared with the DD patients, (respectively, ganglion number: 163 +/- 12 and 149 +/- 12, p<0.02; MN-plexal area: 8.1 +/- 0.3 mm(2) and 7.2 +/- 0.2 mm(2), p<0.001). CONCLUSION The occurrence of DD in sigmoid colon is associated with morphologic alterations in MNP (i.e. the number of ganglia and plexus rarefaction, ganglion size and plexal area involution), which presumably demonstrate the failure of MNP in DD patients.

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

BackgroundThe aim of this study is to evaluate the role of NADPH oxidase in primary intestinal epithelial cells during the active phase of UC.MethodsThe 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.ResultsThe 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.ConclusionsOur 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.

Low-dose spinal hyperbaric bupivacaine for adult anorectal surgery: a double-blinded, randomized, controlled study ☆

BACKGROUND AND OBJECTIVE To produce selective spinal anesthesia for adult anorectal surgery. STUDY DESIGN Double-blinded, randomized, controlled trial. SETTING Operating room and postoperative recovery area. PATIENTS 152 adult, consecutive ASA physical status I, II, and III patients. INTERVENTIONS After patients underwent dural puncture in the sitting position at L3-L4 or L4-L5, 0.5% hyperbaric bupivacaine was injected over two minutes: Group S7.5 received 1.5 mL, Group S5 received 1.0 mL, and Group S4 0.8 mL. After sitting for 10 minutes, patients were positioned for surgery. MEASUREMENTS Rate of success, level and duration of sensory and motor block, time to voiding and ambulation, complications, and quality of anesthesia according to the patient and medical staff, were recorded. RESULTS Spinal block had a 98% rate of success. Mean level of sensory block was 10.4 +/- 1.7, 7.4 +/- 2.2, and 7.0 +/- 1.8 dermatomes in Groups S7.5, S5, and S4 (P < 0.01 S7.5 vs S5, and S7.5 vs S4). Mean duration of sensory block was 310.5 +/- 42.6, 255.9 +/- 43.7, and 228.8 +/- 34.8 min in Groups S7.5, S5, and S4 (P < 0.01 S7.5 vs S5, S7.5 vs S4, and S5 vs S4). Motor block was Bromage score 2-3 in 70.5% of Group S7.5 patients versus Bromage score 0-1 in 97.3% of Group S5 and 92.1% of Group S4 patients (P < 0.05). CONCLUSION A dose of 4 mg of hyperbaric bupivacaine produces a similar level of sensory and motor block as a 5 mg dose but with shorter duration and faster recovery.

Preoperative chemoradiation vs radiation alone for stage II and III resectable rectal cancer: a meta‐analysis

Aim  The aim of this systematic literature review and meta‐analysis was to compare preoperative radiotherapy (RT) with preoperative chemoradiotherapy (ChRT) in patients with stage II and III resectable rectal cancer.

Replication study of ulcerative colitis risk loci in a Lithuanian-Latvian case-control sample

Background:Differences between populations might be reflected in their different genetic risk maps to complex diseases, for example, inflammatory bowel disease. We here investigated the role of known inflammatory bowel disease–associated single nucleotide polymorphisms (SNPs) in a subset of patients with ulcerative colitis (UC) from the Northeastern European countries Lithuania and Latvia and evaluated possible epistatic interactions between these genetic variants. Methods:We investigated 77 SNPs derived from 5 previously published genome-wide association studies for Crohns disease and UC. Our study panel comprised 444 Lithuanian and Latvian patients with UC and 1154 healthy controls. Single marker case–control association and SNP-SNP epistasis analyses were performed. Results:We found 14 SNPs tagging 9 loci, including 21q21.1, NKX2-3, MST1, the HLA region, 1p36.13, IL10, JAK2, ORMDL3, and IL23R, to be associated with UC. Interestingly, the association of UC with previously identified variants in the HLA region was not the strongest association in our study (P = 4.34 × 10−3, odds ratio [OR] = 1.25), which is in contrast to all previously published studies. No association with any disease subphenotype was found. SNP-SNP interaction analysis showed significant epistasis between SNPs in the PTPN22 (rs2476601) and C13orf31 (rs3764147) genes and increased risk for UC (P = 1.64 × 10−6, OR = 2.44). The association has been confirmed in the Danish study group (P = 0.04, OR = 3.25). Conclusions:We confirmed the association of the 9 loci (21q21.1, 1p36.13, NKX2-3, MST1, the HLA region, IL10, JAK2, ORMDL3, and IL23R) with UC in the Lithuanian–Latvian population. SNP-SNP interaction analyses showed that the combination of SNPs in the PTPN22 (rs2476601) and C13orf31 (rs3764147) genes increase the risk for UC.

Common Genetic Variants of PSCA, MUC1 and PLCE1 Genes are not Associated with Colorectal Cancer

BACKGROUND Polymorphisms of genes encoding PSCA, PLCE1 and MUC1 have been associated with the risk of different cancers in genome wide association studies (GWAS). Up to date there are limited data on the role of these genetic alterations in colorectal cancer (CRC) development. The aim of this study was to evaluate potential associations between single nucleotide polymorphisms (SNPs) of genes encoding PSCA, PLCE1 and MUC1 and the presence of CRC in European populations. MATERIALS AND METHODS Gene polymorphisms were analyzed in 574 European subjects (controls: n=382; CRC: n=192). PSCA C>T (rs2294008), PSCA G>A (rs2976392), MUC1 A>G (rs4072037) and PLCE1 A>G (rs2274223) SNPs were genotyped by RT-PCR. RESULTS The distribution of genotypes for all four SNPs was in line with the Hardy-Weinberg equilibrium (rs2294008, P=0.153; rs2976392, P=0.269; rs4072037, P=0.609; rs2274223, P=0.858). The distribution of genotypes and alleles of PSCA C>T, PSCA G>A, MUC1 A>G and PLCE1 A>G SNPs was similar among controls and CRC patient groups (P>0.05). GG genotype of MUC1 SNP was more frequent in CRC patients (24.0%) than in controls (20.2%); however, this association failed to reach significance (OR-1.45, P=0.15). Overall, in the present study SNPs of PSCA (rs2294008, rs2976392), MUC1 (rs4072037) and PLCE1 (rs2274223) genes were not associated with the presence of CRC. CONCLUSIONS Gene polymorphisms of PSCA, PLCE1 and MUC1 genes are not associated with the presence of CRC in European subjects.