Is suturing of the bladder defect in benign Enterovesical fistula necessary?

BACKGROUND: Enterovesical fistula (EVF) is a abnormal connection between the intestine and the bladder. The aim of the study was to analyze whether closure of the defect in the bladder wall during surgery is always necessary. METHODS: Fifty-nine patients with benign EVF undergoing surgical treatment were enrolled. A one-stage surgical procedure was performed in all patients. After the separation of the diseased bowel segment, methylene blue was introduced. Through a catheter into the bladder. Only patients with urinary bladder leakage were sutured. RESULTS: The most common intestinal fistula involving the urinary bladder was colovesical fistula, observed in 53% of cases. Two-thirds of patients had diverticular disease as the underlying pathology. There was no relationship between suturing of the bladder and perioperative complications. Recurrent EVF was observed in one patient with bladder suturing and in two patients without suture. CONCLUSIONS: These findings suggest that closure of the bladder defect is not necessary in cases where a leak is not demonstrated from the bladder intraoperatively. This study is limited by its retrospective design and small numbers and a randomized controlled trial is recommended to answer this question definitively.

Expression of vascular endothelial growth factor and its correlation with clinical symptoms and endoscopic findings in patients with chronic radiation proctitis.

AIM: The aim of this study was to assess the expression of vascular endothelial growth factor (VEGF) as a key proangiogenic factor and determine whether there is any correlation between its expression and clinical symptoms or endoscopic changes in patients with chronic radiation proctitis (ChRP). METHOD: Fifty patients who had all undergone radiotherapy for prostate, cervical or uterine cancer were included in the study (37 women, 13 men). There was a control group of 20 patients (9 women, 11 men). The Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scoring system was used for grading the severity of the proctitis. Endoscopic scoring of late rectal mucosal damage was performed using Gilinsky's classification. Serum levels of VEGF were analysed by the enzyme-linked immunosorbent assay method. RESULTS: Most patients presented with Grade 1 symptoms. Endoscopic assessment showed that most patients had Grade 1 late rectal mucosal damage. The predominant endoscopic finding was the presence of telangiectasia. Assessment of VEGF correlation between the control group and the degrees of endoscopic changes showed statistically significant differences for all three degrees (P < 0.0001, P = 0.0251 and P = 0.0005, respectively). Due to the small numbers of patients with Grades 2 and 3 symptoms using the RTOG/EORTC scoring system, they were grouped with Grades 1 and 4 respectively forming two groups for statistical purposes. VEGF expression differed significantly between controls and group I and between controls and group II (P = 0.0001, P = 0.0009, respectively). CONCLUSION: A significant increase in VEGF expression was found to correlate with clinical symptoms and endoscopic rectal mucosa changes in patients with ChRP, suggesting that it may play an important role in pathological angiogenesis.

Modulation of Colorectal Cancer Risk by Polymorphisms in 51Gln/His, 64Ile/Val, and 148Asp/Glu of APEX Gene; 23Gly/Ala of XPA Gene; and 689Ser/Arg of ERCC4 Gene.

Polymorphisms in DNA repair genes may affect the activity of the BER (base excision repair) and NER (nucleotide excision repair) systems. Using DNA isolated from blood taken from patients (n = 312) and a control group (n = 320) with CRC, we have analyzed the polymorphisms of selected DNA repair genes and we have demonstrated that genotypes 51Gln/His and 148Asp/Glu of APEX gene and 23Gly/Ala of XPA gene may increase the risk of colorectal cancer. At the same time analyzing the gene-gene interactions, we suggest the thesis that the main factor to be considered when analyzing the impact of polymorphisms on the risk of malignant transformation should be intergenic interactions. Moreover, we are suggesting that some polymorphisms may have impact not only on the malignant transformation but also on the stage of the tumor.

Does C-reactive protein monitoring after colorectal resection with anastomosis give any practical benefit for patients with intra-abdominal septic complications?

AIM: This study aimed to assess the influence of the C-reactive protein (CRP) level on the early outcome after elective colorectal resection. METHOD: Patients with colorectal cancer operated on between 2006 and 2013 were identified retrospectively. They were divided into a study group operated on between 2010 and 2013 when CRP was measured routinely on the fourth postoperative day and a control group operated on between 2006 and 2009 when the CRP level was not measured routinely. Mortality, intra-abdominal septic complications (IASC), abscesses and anastomotic leakage (AL), the need for reoperation, the interval from index surgery to relaparotomy, length of hospital stay and imaging studies were compared by multivariate analysis. RESULTS: A total of 1189 patients were assessed, including 598 (50.3%) in the study group (mean age 61.3 ± 13 years; 282 female) and 591 (49.7%) in the control group (mean age 61.8 ± 11 years; 267 female). There were seven (1.2%) postoperative deaths in the study group and nine (1.5%) in the control group (P = 0.598). Abdominal ultrasound (US) was performed more often in the study group [97 (16.2%) vs 71 (12.0%); P = 0.037]. In the study group the interval to diagnosis of IASC was shorter than in the control group (5.7 ± 1.5 days vs 7.3 ± 1.3 days; P = 0.029). The decision to reoperate was also made earlier in the study group (6.2 ± 1.7 days vs 7.4 ± 2.8 days; P = 0.043). CONCLUSION: Routine measurement of CRP can help to make an earlier diagnosis of IASC and earlier decision for relaparotomy, without any influence on mortality or length of hospital stay.

Efficiency of Base Excision Repair of Oxidative DNA Damage and Its Impact on the Risk of Colorectal Cancer in the Polish Population.

DNA oxidative lesions are widely considered as a potential risk factor for colorectal cancer development. The aim of this work was to determine the role of the efficiency of base excision repair, both in lymphocytes and in epithelial tissue, in patients with CRC and healthy subjects. SNPs were identified within genes responsible for steps following glycosylase action in BER, and patients and healthy subjects were genotyped. A radioisotopic BER assay was used for assessing repair efficiency and TaqMan for genotyping. Decreased BER activity was observed in lymphocyte extract from CRC patients and in cancer tissue extract, compared to healthy subjects. In addition, polymorphisms of EXO1, LIG3, and PolB may modulate the risk of colorectal cancer by decreasing (PolB) or increasing (LIG3 and EXO1) the chance of malignant transformation.

Role of base-excision repair in the treatment of childhood acute lymphoblastic leukaemia with 6-mercaptopurine and high doses of methotrexate.

Methotrexate (MTX) and 6-mercaptopurine (6MP) are the most commonly used drugs in the therapy of childhood acute lymphoblastic leukaemia (ALL). The main genotoxic effect of MTX resulting from inhibition of thymidylate synthase is mis-incorporation of uracil into DNA, which is considered essential for the effectiveness of the Protocol M in ALL IC BFM 2002/EURO LB 2002 regimens. In this study, we investigated the level of basal and induced DNA damage as well as the effectiveness of DNA repair in lymphocytes of children with ALL at four time-points during therapy with MTX and 6MP. To assess DNA damage and the efficacy of DNA repair we used the modified alkaline comet assay with uracil DNA glycosylase (Udg) and endonuclease III (EndoIII). In addition, we examined the induction of apoptosis in the lymphocytes of the patients during treatment. Finally, we compared the activity of base-excision repair (BER), involved in removal of both uracil and oxidized bases from DNA in lymphocytes of children with ALL and lymphocytes of healthy children. BER efficiency was estimated in an in vitro assay with cellular extracts and plasmid substrates of heteroduplex DNA with an AP-site. Our results indicate that there is a significant decrease in the efficacy of DNA repair associated with an increased level of uracil in DNA and induction of apoptosis during therapy. Moreover, it was found that the BER capacity was decreased in the lymphocytes of ALL patients in contrast to that in lymphocytes of healthy children. Thus, we suggest that an impairment of the BER pathway may play a role in the pathogenesis and therapy of childhood ALL.

Impaired nucleotide excision repair pathway as a possible factor in pathogenesis of head and neck cancer.

Tobacco smoking is one of the major risk factors in pathogenesis of head and neck squamous cell carcinomas (HNSCC). Many of the chemical compounds present in tobacco are well-known carcinogens which form adducts with DNA. Cells remove these adducts mainly by the nucleotide excision repair pathway (NER). NER also eliminates a broad spectrum of pyrimidine dimers (CPD) and photo-products (6-4PP) induced by UV-radiation or DNA cross-links after cisplatin anti-cancer treatment. In this study DNA damage and repair was examined in peripheral blood lymphocytes obtained from 20 HNSCC patients and 20 healthy controls as well as HTB-43 larynx and SSC-25 tongue cancer cell lines. DNA repair kinetics in the examined cells after cisplatin or UV-radiation treatment were investigated using alkaline comet assay during 240min of post-treatment incubation. MTT assay was used to analyse cell viability and the Annexin V-FITC kit specific for kinase-3 was employed to determine apoptosis after treating the cells with UV-radiation at dose range from 0.5 to 60J/m(2). NER capability was assessed in vitro with cell extracts by the use of a bacterial plasmid irradiated with UV-light as a substrate for the repair. The results show that lymphocytes from HNSCC patients and HTB-43 or SSC-25 cancer cells were more sensitive to genotoxic treatment with UV-radiation and displayed impaired DNA repair. Also evidenced was a higher rate of apoptosis induction after UV-radiation treatment of lymphocytes from the HNSCC patients and the HTB-43 cancer cells than after treatment of those from healthy donors. Finally, our results showed that there was a significant decrease in NER capacity in HTB-43 or SSC-25 cancer cells as well as in peripheral blood lymphocytes of HNSCC patients compared to controls. In conclusion, we suggest that the impaired NER pathway might be a critical factor in pathogenesis of head and neck cancer.

Resection of the primary tumour or other palliative procedures in incurable stage IV colorectal cancer patients?

OBJECTIVE: The aims of the study were to analyse the early and late results of surgical treatment in patients with stage IV colorectal cancer (CRC) and to evaluate the effect of primary tumour resection and other clinical factors on survival. METHOD: A group of 134 patients with stage IV CRC was electively operated on between 1996 and 2000. The first group underwent resection of the primary tumour (52 patients; mean age 63.4 +/- 10.3) and the second group of patients underwent procedures without resection (82 patients; mean age 62.6 +/- 10.6). RESULTS: Postoperative morbidity occurred significantly more often (P = 0.041) in the first group--in 26 patients (50%) than in the second group - 19 patients (23.1%). The resection of the primary tumour increased the survival probability; hazard ratio (HR): 1.78; 95% confidence interval (CI): 1.21-2.78%; P = 0.004. Bi-lobar metastases increased mortality risk compared with uni-lobar; HR 2.32; 95% CI: 1.47-3.68; P = 0.0003. The 2-year survival rate in patients with uni-lobar metastases in the first group was 44.2%, in the second group: 30.7%; P = 0.023. CONCLUSION: Primary tumour resection in stage IV CRC increases the risk of postoperative complications. In the given setting, however, it results in an increased 2-year survival rate but it may not influence the 5-year survival rate. In patients with bi-lobar liver metastases resection of the primary tumour does not prolong survival time.

Chemoprevention of colorectal cancer - a new target needed?

OBJECTIVE: Novel treatments for colorectal cancer (CRC) include chemoprevention. Nonsteroidal anti-inflammatory drugs (NSAIDs) were the first to be studied and an inverse association was proven between their use and the development of invasive CRC. The numerous side effects of NSAIDs led, however, to the search for safer drugs. These have included Coxibs (selective COX-2 inhibitors). In this study, the role of coxibs in the chemoprevention of CRC is reviewed. RESULTS: Numerous in-vitro and in-vivo experiments have shown the effectiveness of coxibs in the chemoprevention of CRC. These have led to the registration of celecoxib by the USA Food and Drug Administration for the treatment of familial adenomatous polyposis. Further studies of coxibs have revealed an increased risk of serious cardiovascular events when compared with placebo. This finding has considerably decreased the opportunities for chemoprevention of CRC. CONCLUSION: The multi-directional activity of coxibs, which was the reason for their effectiveness against CRC development may be the key to proposing a new target area for chemoprevention. It has been shown that celecoxib partly inhibits the activity of NF-kappaB, transcription factor involved in inflammation and carcinogenesis pathways. Modulation of its activation may be the future of effective CRC chemoprevention.