An association of the MCP-1 and CCR2 single nucleotide polymorphisms with colorectal cancer prevalence.

THE AIM OF THE STUDY: We evaluated the connection between the presence of the -2518 A/G MCP-1 as well as 190 G/A CCR2 polymorphic variants and colorectal cancer (CRC) occurrence. MATERIAL AND METHODS: Study group consisted of subjects with different stages of CRC as well as healthy controls. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: W observed an association between the colorectal cancer and the GG genotype of the -2518 A/G MCP-1 single nucleotide polymorphism. No statistically significant correlation was found between CRC and the 190 G/A CCR2 polymorphism. CONCLUSION: The results of this study support the hypothesis that polymorphism in the MCP-1 gene may contribute to the etiology of colorectal cancer.

Polymorphism within the distal RAD51 gene promoter is associated with colorectal cancer in a Polish population.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in developed countries. Annually, over one million of new cases in the world are recorded. Majority of CRCs occur sporadically with dominant phenotype of chromosomal instability (CIN). Permanent exposure to DNA damaging agents such as ionizing radiation result in DNA double-stranded breaks, which create favorable conditions for chromosomal aberration to arise. Homologous recombination repair (HRR) is the leading process engaged in maintaining of the genome integrity. RAD51 protein was recognized as crucial in HRR. Single nucleotide polymorphisms are the primary source of genetic variation which presence in the RAD51 promoter region can affect on its expression and consequently modulate HR efficiency. OBJECTIVES: The aim of this study was to analyze the distribution of genotypes and allele frequencies of -4791A/T and -4601A/G RAD51 gene polymorphisms, followed by an assessment of their relationship with the risk of CRC. MATERIAL AND METHODS: The study included 115 patients with confirmed CRC. Control group was consisted of 118 cancer-free individuals with a negative family history. The genotypes were identified by PCR-RFLP method. CONCLUSION: This study revealed statistically significant association between appearance of G/A genotype in position -4601 of RAD51 gene and CRC risk.

The -553 T/A polymorphism in the promoter region of the FGF2 gene is associated with increased breast cancer risk in Polish women.

INTRODUCTION: Fibroblast growth factor-2 (FGF2) is an important signalling molecule contributing to angiogenesis, tumour growth and progression and its expression is implicated in breast cancer (BC) development. We investigated whether -553 T/A FGF2 gene polymorphism is associated with the risk and progression of BC in Polish women. MATERIAL AND METHODS: The -553 T/A polymorphism was genotyped in 230 breast cancer patients and 245 control subjects, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. Moreover, FastQuant human angiogenesis array was used to measure FGF2 levels in tumour (n = 127) and serum (n = 76) samples. RESULTS: The T/A genotypes (OR = 2.12, 95% CI: 1.20-3.74) (p = 0.08) and the combined heterozygotes T/A and homozygote A/A (OR = 2.18, 95% CI: 1.24-3.83) (p = 0.006) had an increased risk of BC. The median FGF2 levels in the tumours of A allele carriers were significantly increased compared to T/T patients, whereas in serum FGF2 levels were hardly altered among different genotype carriers. Significantly higher frequency of A allele was found in patients with lymph node metastases (OR = 2.53; 95% CI: 1.23-5.17) (p = 0.009) and human epidermal growth factor receptor 2 positive tumour (OR = 3.22, 95% CI: 1.49-6.99) (p = 0.002). Furthermore, Kaplan-Meier survival analysis showed that the A allele predicted worse disease-free survival (DFS) in BC patients. CONCLUSIONS: Our study shows for the first time that the -553 T/A FGF2 gene polymorphism may be associated with a risk of BC developing and progression in Polish women and may have prognostic value for the assessment of BC high-risk groups.

Association of polymorphism of Lys589Glu Exo1 gene with the risk of colorectal cancer in the Polish population.

UNLABELLED: The incidence of colorectal cancer (CRC) is increasing from year to year. Despite intensive research CRC etiology remains unknown. Studies suggest that at the basis of the process of carcinogenesis can lie reduced efficiency of DNA repair mechanisms, often caused by polymorphisms in DNA repair genes. The aim of the study was to determine the relationship between gene polymorphism Lys589Glu of EXO1 gene and modulation of the risk of colorectal cancer in the Polish population. Determination of the molecular basis of carcinogenesis process and predicting increased risk will allow qualifying patients to increased risk group and including them in preventive program. MATERIAL AND METHODS: The material used in study was blood collected from 130 patients diagnosed with colorectal cancer. The control group consisted of 135 healthy people. Genotyping was performed by TaqMan method. RESULTS: The results obtained indicate that the genotype Lys/Glu is associated with an increased risk of colorectal cancer (OR 1.811, 95% Cl 1.031-3.181, p = 0.038). CONCLUSION: On the basis of these results, we conclude that Exo1 gene polymorphism Lys589Glu may be associated with an increased risk of colorectal cancer.

The role of polymorphisms of genes CXCL12/CXCR4 and MIF in the risk development IBD the Polish population.

Inflammatory bowel disease (IBD) are characterized recurrent inflammation of gastrointestinal tract. The etiology and pathogenesis this disease is currently unclear, but it has become evident that immune and genetic factors are involved in this process. The aim of this study was to determine whether gene polymorphisms: MIF-173 G/C; CXCL12-801 G/A and CXCR4 C/T exon 2 position of rs2228014 is associated with susceptibility to IBD. A total of 286 patients were examined with IBD, including 152 patients with ulcerative colitis and 134 with Crohn's disease (CD) and 220 healthy subjects were recruited from the Polish population. Genotyping for polymorphisms in CXCL12/CXCR4 and MIF was performed by RFLP-PCR. Statistical significance was found for polymorphisms CXCR4, a receptor gene for CXCL12 genotypes and alleles in CD and for genotype C/T and T allele in ulcerative colitis with respect to control. This confirms the effect of CXCL12 gene. The interplay between CXCL12 and its receptor CXCR4 affects homeostasis and inflammation in the intestinal mucosa. Three-gene analysis in CD confirmed the association of genotype GGGGCT. Statistical analysis of clinical data of patients with ulcerative colitis showed significant differences in the distribution of genotype C/T and T allele for CXCR4 in the left-side colitis. Having CXCR4/CXCL12 chemokine axis polymorphisms may predispose to the development of IBD. Activation can also be their defensive reaction to the long-lasting inflammation.

Alterations in expression profile of iron-related genes in colorectal cancer.

Iron can play a role in colorectal cancer (CRC) development. The expression of genes involved in iron metabolism and its regulation in CRC has not been investigated well. Also the correlation between the level of iron-related genes expression and cancer progression is not known. In this study we collected paired samples of primary adenocarcinoma and adjacent normal mucosa from 73 patients. We assessed the mRNA or miRNA levels of 21 genes and verify their association with clinicopathological characteristics of CRC patients. Our experiments revealed, that the level of divalent metal transporter 1 transcript is well correlated with mRNA levels of iron regulatory proteins (IRPs) in tumor specimens. We have shown, that IRP2 can also be engaged in the mRNA stabilization of other iron transporter-transferrin receptor 1 (TfR1) in early stage of disease, however, in more advanced stages of CRC, mRNA level of TfR1 is related to miR-31 level. For the first time we have shown, that ferroportin concentration is significantly associated with miR-194 level, causing the reduction of this transporter amount in tumor tissues of patients with more advanced stages of CRC. We have also shown the alterations in expressing profile of miR-31, miR-133a, miR-141, miR-145, miR-149, miR-182 and miR-194, which were observed even in the early stage of disease, and identified a set of genes, which take place in correct assigning of patients in dependence of CRC stage. These iron-related genes could become potential diagnostic or prognostic indicators for patients with CRC.

Association of Thr241Met polymorphism of XRCC3 gene with risk of colorectal cancer in the Polish population.

DNA double strand breaks (DSBs) are the most dangerous lesions which can lead to carcinogenesis. Homologous recombination (HR) is an important pathway responsible for maintaining genome integrity through repair of DSBs. Single nucleotide polymorphism (SNP) is an essential source of genetic variation whose presence in genes involved in HR may have a crucial role in modulation of DNA repair capacity. This case-control study was designed to evaluate the influence of XRCC3 gene Thr241Met polymorphism on CRC risk and progression among Polish population. Genotyping was performed by RFLP-PCR (restriction length fragment polymorphism). The subject of our study was consist of 194 patients with CRC and 204 cancer-free individuals who were age and sex-matched as a control group. Obtained genotype distributions in controls as well as patients fit to the Hardy-Weinberg expectations. Odd ratio analysis indicates diminished risk for heterozygous model and Met allele. Comparison of patients with noninvasive and advanced stage of CRC did not imply any statistical significance. Our results suggest that Thr241Met XRCC3 gene polymorphism might be regarded as CRC potential molecular marker. Nevertheless, that hypothesis needs to be confirmed by subsequent studies.

An association selected polymorphisms of XRCC1, OGG1 and MUTYH gene and the level of efficiency oxidative DNA damage repair with a risk of colorectal cancer.

Oxidative damage has been implicated in the pathogenesis of colorectal cancer (CRC). The base excision repair (BER) pathway is the major DNA repair pathway for oxidative DNA damage and genetic variation associated with impaired BER might thus increase a risk of CRC. In this work, we evaluated associations between the repair efficiency of oxidative DNA lesions and single-nucleotide polymorphisms of BER genes: the 194Trp/Arg and the 399Arg/Gln XRCC1, the 326Ser/Cys OGG1 and the 324Gln/His MUTYH and CRC occurrence in a Polish population. These polymorphisms were genotyped in 182 CRC patients and 245 control subjects, using a PCR-RFLP approach. The level of oxidative damage and DNA repair capacity in lymphocytes and CRC tissue samples was evaluated by comet assay using FPG and Nth glycosidases. The 326Ser/Cys OGG1 and the 324Gln/His as well as the 324His/His MUTYH genotypes were found to be associated with an increased CRC risk, while no association was found for the XRCC1 gene polymorphisms. It was also demonstrated the reduced capacity of oxidative damage repair in CRC patients in comparison to healthy controls. Moreover, the decrease efficiency of DNA repair were correlated with the 399Gln/Gln XRCC1 and the 324His/His MUTYH genotypes occurrence in CRC patients. The results obtained in our study indicated an association of OGG1 and MUTYH genes polymorphisms involved in oxidative DNA lesions repair with the risk occurrence of colorectal cancer in Polish patients. It was also found that studied polymorphisms might affect DNA repair capacity suggesting their role in CRC pathogenesis. Finally, we conclude that BER pathway may be an important target for the diagnosis and treatment of colorectal patients.

Lack of association between the 135G/C RAD51 gene polymorphism and the risk of colorectal cancer among Polish population.

One of the major causes of carcinogenesis is loss of genome stability. RAD51 in process of homologous recombination (HR) played crucial role in maintenance integrity of genome through initiate of DNA double strand breaks repair. Presence of single nucleotide polymorphism (SNP) in RAD51 gene could change the capacity of DNA repair and altered the response to damaging agents. Research on potential impact of genetic variability on development and progression CRC may contribute to setting new genetic markers or/and determined individual susceptibility to CRC.The aim of the study. This study was designed to evaluate the effect of 135 G/C (rs1801320) RAD51 polymorphism located in the 5' untraslated region on the risk and progression of CRC.Material and methods. The subjects consisted of histologically confirmed colorectal cancer (n = 200) and controls (n = 200) with lack of previous history of cancer. The distribution of genotypes was determined by restriction fragment length polymorphism PCR (RFLP - PCR). Statistical analysis was based on multivariate regression model.Results and conclusion. Our study reveal no significance association of 135 G/C RAD51 polymorphism with occurrence and progression of colorectal cancer.

The -2518 A/G MCP-1 polymorphism as a risk factor of inflammatory bowel disease.

UNLABELLED: Inflammatory bowel diseases (IBD) are disorders originated from immune disturbances. The AIM OF THE STUDY was to evaluate the association between the -2518 A/G MCP-1 polymorphism and the risk of IBD development. MATERIAL AND METHODS: Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Study group consisted of 197 subjects with IBD (120 with ulcerative colitis and 77 with Crohn's disease) as well as 210 healthy controls. RESULTS: The presence of the -2518 G/G MCP-1 genotype in the investigated groups seems to be connected with higher risk of inflammatory bowel disease as well as Crohn's disease only (OR 2.26; 95% CI 1.44-3.54 and OR 2.08; 95% CI 1.21-3.46, respectively). CONCLUSIONS: Our data showed that the -2518 A/G MCP-1 polymorphism might be associated with the IBD occurrence and might be used as predictive factor of these diseases in a Polish population.

The lL-8 and IL-13 gene polymorphisms in inflammatory bowel disease and colorectal cancer.

Inflammatory bowel diseases (IBD) and colorectal cancer (CRC) are disorders that originate from immune disturbances. In our study, we evaluated the association between the -251 T/A interleukin (IL)-8 and the -1112 C/T IL-13 polymorphisms, the risk of IBD, and CRC development. Genotypes were determined by PCR-restriction fragment length polymorphism in 191 patients with CRC, 150 subjects with IBD, and 205 healthy controls. We found an association between CRC and the presence of the -251 TA genotype and A allele of the IL-8 gene (odds ratios [ORs] 2.28 and 1.65). A similar relationship was observed between these polymorphic variants and ulcerative colitis (OR 2.05 for the -251 TA genotype and OR 1.47 for the -251 A allele) as well as Crohn's disease (ORs 3.11 and 1.56, respectively). Our research also revealed that the CT and TT genotypes of the IL-13 -1112 C/T polymorphism may be connected with a higher risk of CRC (ORs 2.28 and 1.65). The same genotypes affected the susceptibility of IBD (ORs 2.26 and 3.72). Our data showed that the IL-8 -251 T/A and IL-13 -1112 C/T polymorphisms might be associated with the IBD and CRC occurrence and might be used as predictive factors of these diseases in a Polish population.

Genetic variations of the CTNNA1 and the CTNNB1 genes in sporadic colorectal cancer in Polish population.

UNLABELLED: Experimental as well as clinical observations have demonstrated that the E-cadherin/catenin complex is a powerful inhibitor of invasion. Abrogation of this pathway is implicated in the carcinogenesis of several malignancies, especially colorectal cancer. The aim of the study was to determine the CTNNA1 and the CTNNB1 mutations and its relationship to clinical and pathological features of sporadic colorectal cancer (CRC) in Polish patients. MATERIAL AND METHODS: Paired tumor and normal tissue samples from 110 sporadic CRC patients undergoing resective surgery were prospectively studied for the alpha catenin (CTNNA1) gene and beta catenin (CTNNB1)gene mutations by PCR/single strand conformation polymorphism (SSCP). RESULTS: The CTNNA1 gene alteration in exon 7 were detected in 4 samples and in exon 3 of CTNNB1 gene were found in 3 samples. There was a trend at the limit of statistical significance associating younger age at diagnosis (<50) with CTNNA1 and the CTNNB1 mutations. The mutation of CTNNB1 seemed to occur more frequently in the proximal colon than distal. The CRC patients with CTNNA1 mutation had a significantly increased lymph node metastasis. On the other hand, there was no correlation between mutations and the other clinical variables (e.g. sex, grade and depth of invasion). CONCLUSION: Although we found a low frequency of mutations in the CTNNA1 and the CTNNB1 genes, but the analysis the relationship with clinical and pathological features of CRC patients may indicated an association of these mutations with the risk and progression of CRC.

Large colorectal polyps--endoscopic polypectomy as an alternative to surgery.

UNLABELLED: Endoscopic polypectomy of colorectal polyps is a common procedure. However, endoscopic treatment of large polyps (those with a diameter exceeding 2 cm) remains questionable. There is a serious risk of colorectal carcinoma presence inside these lesions, which eventually would require surgical intervention. Apart from this fact endoscopic polypectomy of large polyps is connected with substantial risk of complications, such as perforation and bleeding. Many patients with large colorectal polyps are qualified for surgical intervention. THE AIM OF THE STUDY was to determine the efficacy and safety of polypectomy of large colorectal polyps. MATERIAL AND METHODS: The study presented results of endoscopic treatment in case of patients with large colorectal polyps at the Department of General and Colorectal Surgery, Medical University in Lódz. Patients were admitted to the hospital during the period between January, 2008 and January, 2010. The following parameters were analysed: location of polyps, percentage of high grade dysplasia, complete excision rate, and complications connected with polypectomy procedures. RESULTS: During the analyzed period of time 488 endoscopic polypectomies were performed. Forty-three large colorectal polyps were removed (8.8%). Seven (16.3%) of them were classified as flat polyps. Out of 488 removed polyps, 39 were classified as adenomas with high grade dysplasia (7.9%), while 16 were large-exceeding 2 cm (37.2%). Considering the group of large polyps no invasive carcinoma case was detected. The radical excision rate for large pedunculated polyps was obtained in 88.8% (32/36) of cases. In case of flat adenomas the above-mentioned parameter was lower--57.1% (4/7). During polypectomy of large colorectal polyps one perforation was observed during the excision of a flat cecal polyp. In two cases immediate bleeding occurred (2/43). In both cases endoscopic treatment of bleeding proved sufficient. CONCLUSIONS: Endoscopic polypectomy of large pedunculated polyps is a safe and efficient method, which makes it a rationale alternative for surgery. Polypectomy of flat adenomas is connected with a lower radical excision rate and higher risk of perforation.

Association of -1112 c/t promoter region polymorphism of the interleukin 13 gene with occurrence of colorectal cancer.

Colorectal carcinoma is one of the leading causes of death from cancer amongst adults. Considering its molecular background, cytokines are the key component of the inflammatory microenvironment of these tumors. Investigations that enable better understanding of colorectal cancer concerning the molecular level, may provide important tools for genetic screening of disease high-risk groups, as well as molecular diagnostics for the non-invasive detection of cancer in its early stages.THE AIM OF THE STUDY was to evaluate the association between colorectal cancer and the -1112 C/T single nucleotide polymorphism (SNP) of the interleukin-13 gene. MATERIAL AND METHODS. The study group comprised 150 cancer patients and 170 healthy subject genotypes from the Polish population. Analysis was performed by PCR-restriction fragment length polymorphism (PCR-RFLP). RESULTS. We showed that the CT genotype is connected with a higher risk of colon cancer occurrence (OR 2.51; 95% CI 1.57-4.02; p < 0.0001). We also correlated the polymorphic variants of the IL-13 gene with the clinical characteristics of colorectal cancer patients. We observed no association between the investigated polymorphism and colorectal cancer progression, evaluated by tumor stage, as well as lymph node metastasis. CONCLUSIONS. The presented study suggested the possibility of a connection between the IL-13 gene polymorphism (-1112 C/T) and colorectal cancer risk in the Polish population.

Contribution of the -173 G/C polymorphism of macrophage migration inhibitory factor gene to the risk of inflammatory bowel diseases.

UNLABELLED: Inflammatory bowel disease (IBD) represents a heterogeneous group of chronic disorders characterized by inflammation of gastrointestinal tract, typically with a relapsing and remitting clinical course of unknown etiology. Presumably, IBD develops with response exogenous environmental factors only in persons with genetic predisposition. This predisposition was suggested to be associated with polymorphism and mutations in genes encoding proinflammatory immune system proteins. Enhanced production of macrophage migration inhibitory factor (MIF) was found in patients with inflammatory bowel disease (IBD) and mice with experimental colitis. These results suggest that MIF plays a critical role in etiology of the colitis.The aim of the study was determine whether the MIF -173 G/C gene polymorphism is associated with the susceptibility to inflammatory bowel disease (IBD). MATERIAL AND METHODS: A total of 99 IBD patients, including 58 patients with ulcerative colitis (UC) and 41 with Crohn's disease (CD) and 436 healthy controls recruited from the Polish population, were genotyped for MIF polymorphisms. Genotyping of MIF gene polymorphism was performed by a RFLP-PCR. RESULTS: We found an increased risk of UC for the C allele of the MIF-173 G/C polymorphism. The distribution of the genotypes was not significantly different in the CD group compared with the controls. CONCLUSIONS: We demonstrated that the C allele is associated with an increased risk for development of UC. This suggests that the G/C polymorphism in the MIF gene promoter may be a potential risk factor for UC in Polish population.

Association of the-801G/A polymorphism of CXCL12 gene with the risk of inflammatory bowel diseases development in a Polish population.

UNLABELLED: Inflammatory bowel diseases (IBDs), mainly ulcerative colitis (UC) and Crohn's disease (CD), are characterized by chronic and idiopathic inflammatory conditions of gastrointestinal tract that are immunologically mediated. Stromal cell-derived factor 1 (CXCL12) has been demonstrated to be involved in the pathophysiology of IBD.The aim of the study was to investigate whether the CXCL12 -G/A polymorphism (rs1801157) is associated to IBD in a sample of Polish population. MATERIAL AND METHODS: A total of 188 patients with IBD including 103 patients with CU and 72 patients with CD and 184 controls were enrolled in the study. Both groups came from the Polish population. The G/A polymorphism of CXCL12 was determined by PCR-RFLP analysis. RESULTS: There was no association between G/A polymorphism at position -801 promoter region of CXCL12 gene and increased risk of IBD. The study population was not found a difference in genotype distribution between the control group and with both CD and CU patients. CONCLUSIONS: These results suggest that G/A polymorphism at position -801 promoter region of CXCL12 gene relates neither to the risk of the development of inflammatory bowel disease nor to the clinical subtypes of IBD in the Polish population. Whether this polymorphism truly contributes to disease susceptibility needs to be further addressed, and should stimulate additional studies in other populations.

Angiogenesis markers quantification in breast cancer and their correlation with clinicopathological prognostic variables.

Tumoural angiogenesis is essential for the growth and spread of breast cancer cells. Therefore the aim of this study was to assess the diagnostic performance of angiogenesis markers in tumours and there reflecting levels in serum of breast cancer patients. Angiogenin, Ang2, fibroblast growth factor basic, intercellular adhesion molecule (ICAM)-1, keratinocyte growth factor (KGF), platelet-derived growth factor-BB, and VEGF-A were measured using a FASTQuant angiogenic growth factor multiplex protein assay. We observed that breast cancer tumours exhibited high levels of PDGF-BB, bFGF and VEGF, and extremely high levels of TIMP-1 and Ang-2, whereas in serum we found significantly higher levels of Ang-2, PDGF-BB, bFGF, ICAM-1 and VEGF in patients with breast cancer compared to the benign breast diseases patients. Moreover, some of these angiogenesis markers evaluated in tumour and serum of breast cancer patients exhibited association with standard clinical parameters, ER status as well as MVD of tumours. Angiogenesis markers play important roles in tumour growth, invasion and metastasis. Our results suggest that analysis of angiogenesis markers in tumour and serum of breast cancer patients using multiplex protein assay can improve diagnosis and prognosis in this diseases.

A/G Polymorphism of the MMP-7 Gene Promoter Region in Colorectal Cancer.

In gastrointestinal malignancies increased expression of matrilysin - MMP-7 - is often observed. Its high level positively correlates with clinical stage of malignancy and is a negative prognostic factor. This suggests a possible relationship between functional polymorphisms of the MMP-7 gene and susceptibility to development of colorectal cancer and an aggressive course of the disease.The aim of the study was to assess the effects of A/G functional polymorphism at -181 site of the MMP-7 gene promoter region on development and progression of colorectal cancer.Material and methods. In total, 184 patients treated surgically for colorectal cancer at the Department of General and Colorectal Surgery of the Medical University in Lódz in the years 2006-2009 and a control group of 205 cancer-free individuals with a negative family history for malignancy have been investigated. Polymorphic variants of the MMP-7 gene promoter region have been analysed using the RFLP-PCR method.Results. A statistically significant difference in distribution of genotypes has been found between the investigated group and the control group, and the OR analysis confirmed a relationship between the A/G [1.67 (1.03-2.72); p= 0.038] and G/G [2.12 (1.34-3.38); p = 0.018] genotypes and an increased risk of colorectal cancer. The risk of lymph node involvement was more than twice higher for the G/G genotype (OR = 2.83 (1.18-6.79); P = 0.017). In addition, the analysis of genotype distribution in patients divided into groups according to the T parameter of the TNM classification revealed a relationship between the G/G genotype and advanced tumour infiltration. No relationship between the investigated A/G polymorphism and the presence of distant metastases has been found.Conclusions. Obtained results indicate a possible relationship between -181 A/G polymorphism of the MMP-7 gene and malignant transformation of colorectal epithelial cells and progression of colorectal cancer. This suggests applicability of this polymorphism as a predisposing factor for the disease and a prognostic factor, which in the future may be useful in the management algorithm for colorectal cancer.

Malignant melanoma of the anorectum--a rare entity.

OBJECTIVE: Primary anorectal melanoma is a rare entity with a poor prognosis accounting for approximately 0.1-4.6% of anal tumours and 0.5-1.6% of all melanomas. Almost 60% of patients have already disseminated disease at initial diagnosis. METHOD: We report four cases of anorectal melanoma treated at our department from November 2006 to September 2008, as well as a review of the literature. RESULTS: There were two females and two males, of median age 69 years (range: 59-81 years). Most frequent complaints were rectal bleeding and/or anorectal pain. Three of our four patients had amelanotic melanomas. We found the positive expression of S-100 protein and HMB-45 in two patients and melanin A cells in one case. Abdominoperineal resection was performed in two patients, colostomy in one patient and a wide local excision also in one case. Three patients died on account of dissemination of melanoma, one patient is still alive. CONCLUSION: Anal melanoma remains a deadly problem. Clear guidelines for the therapy of anorectal melanoma have not been established. This mainly results from the rarity of this tumour. Treatment is based on retrospective studies, which report a limited number of cases.

How the location of the internal opening of anal fistulas affect the treatment results of primary transsphincteric fistulas.

PURPOSE: The purpose of this study was to assess the influence of identification of the location of the internal opening of anal fistula on the recurrence rate after surgical treatment in patients with primary transsphincteric anal fistulas. The influence of preoperative rectal ultrasound on the treatment results was studied. METHODS: One hundred thirty-one patients operated in the period February 1992 to July 2005 were analyzed. Endorectal ultrasound (ERUS) was not performed (till February 2004) on 103 out of the 131 patients, while the other 28 received ERUS (from March 2004). We performed either cutting seton technique or fistulectomy according to the course of fistulous tract (high or low transsphincteric fistulas). The recurrence rate of anal fistula was assessed after the complete healing of the anal fistula after 6 months. RESULTS: In patients in whom ERUS was not performed, the internal opening was identified by endoscopy in 41.7% and in 47.6% intraoperatively. In patients in whom ERUS was preoperatively performed, the internal opening was identified in 85.8%. In all the studied groups, the internal opening of anal fistula was not localized in 13 patients (9.9%). Recurrence of the fistulas occurred in ten patients (7.6%); in seven out of 13 patients, the internal opening was not found (53.85%), and in three out of 118, the internal opening was identified (2.54%). CONCLUSIONS: Relative risk of anal fistula recurrence was 20-fold higher in patients in whom the internal opening was not identified than in those with the internal opening identified. Preoperative ERUS doubled the identification rate and thus decreased the risk of recurrence.