Modern diagnostic approach to patients with abdominal aortic aneurysm.

INTRODUCTION: Abdominal aortic aneurysm (AAA) is a relatively frequent and serious condition in vascular surgery. The diagnostic and indication process and its treatment are driven by the guidelines which dictate an intervention when the maximum AAA diameter is more than 55 mm. Nevertheless, this approach is not fully sufficient in all AAA cases and thus we have been seeking to develop a modern diagnostic tool using computer modeling and vascular wall stress analysis. METHODS: The project has been ongoing in cooperation with engineers from VUT Brno (Brno University of Technology) and VŠB Ostrava (Technical University of Ostrava) for ten years. The design of the analytical tool was created during the first, experimental period of the project; this tool is able to assess vascular wall stress from regular CT scans using the finite element method. This primary model was gradually altered and its precision was increased considerably in the course of the years using data from mechanical and histological tests of AAA wall specimens harvested during open repairs. Additionally, other patient specific data are included in the analysis such as blood pressure, gender and material characteristics. RESULTS: The effectiveness of the method was evaluated in a pseudo-prospective study, showing clear superiority of the vascular wall stress analysis over the maximum diameter approach. The method was used in clinical practice for the first time during restrictions due to the COVID-19 pandemic; based on the analysis we were able to assess which AAA cases can be postponed and which had a high risk of rupture and an intervention was required despite the restrictions. The method achieved 100% sensitivity, and its specificity was also much better compared to the maximum diameter approach. CONCLUSION: The vascular wall stress analysis of AAA seems to be much more precise than the classic indication approach based only on the maximum diameter, and it can be used to determine the therapy based on patient specific parameters.

A preliminary investigation on the effect of extracorporeal shock wave therapy as a treatment for neurogenic heterotopic ossification following traumatic brain injury. Part I: Effects on pain.

INTRODUCTION: Neurogenic heterotopic ossification (NHO) is a complication of a neurological injury following traumatic brain injury (TBI) and may be present around major synovial joints. It is often accompanied by severe pain, which may lead to limitation in activities of daily living. Currently, a common intervention for NHO is surgery, which has been reported to carry many additional risks. This study was designed to assess the effect of extracorporeal shock wave therapy (ESWT) on pain in patients with TBI with chronic NHO. METHODS: A series of single-case studies (n = 11) was undertaken with patients who had TBI and chronic NHO at the hip or knee. Each patient received four applications of high-energy EWST delivered to the affected joint over 8 weeks. Two-weekly follow-up assessments were carried out, and final assessments were made 3 and 6 months post-intervention. Pain was measured using the Faces Rating Scale, and X-rays were taken at baseline and 6-months post-intervention to physiologically measure the size of the NHO. RESULTS: The application of high-energy ESWT was associated with significant overall reduction of pain in patients with TBI and NHO (Tau-0.412, 95% confidence interval -0.672 to -0.159, p = 0.002). CONCLUSIONS: ESWT is a novel non-invasive intervention for reducing pain resulting from NHO in patients with TBI.

[Endoscopic harvest of great saphenous vein for infrainguinal arterial bypass: summary of our initial experience]. / Pouzití metody endoskopického odberu velké safény v periferní infrainguinální cévní chirurgii - zhodnocení iniciálních zkuseností.

INTRODUCTION: This study was undertaken to determine the feasibility of endoscopic vein harvest (EVH) for infrainguinal arterial bypass surgery. We describe our initial experience and early results of bypasses done using this minimally invasive approach. METHOD: From April 2012 to March 2015, 16 patients underwent 16 femoropopliteal bypass operations with great saphenous vein (GSV) being harvested by endoscopic technique. The indication for intervention was critical limb ischemia (Rutherford category "5") in 7 patients (43.7%) and severe intermittent claudication (Rutherford category "3") in 9 patients (56.3%). There were 14 male (87.5%) and 2 female (12.5%) patients, with a mean age of 59.9 years. Selection of patients for EVH was based on clinical and duplex ultrasound appearance of GSV. Only patients with adequate GSV were considered for EVH. We collected data regarding patients demographics, history, clinical findings, operative procedures and postoperative recovery including complications. Patients were followed at 3, 6, 12, 18 and 24 months postoperatively and yearly thereafter. Patencies were analyzed by Kaplan-Meier method. Statistical analysis was performed using IBM SPSS Statistics 21.0 software (IBM Corp, Armonk, NY). RESULTS: Endoscopically harvested GSV was utilised for formation of proximal (10; 62.5%) or distal (6; 37.5%) femoropopliteal bypass. One patient underwent conversion to open harvest after endoscopic dissection of the vein. It occurred early in our experience. All other GSV harvests were accomplished endoscopically. 2 patients (12.5%) developed postoperative surgical site infection (SSI) Szilagyi gr. II (1 patient after successful EVH - location: groin; 1 patient after conversion of EVH to open vein harvest - location: groin and vein harvest incision). Mean follow-up was 10.2 months (range 0.3 to 27.0 months). At 1 and 2 years, primary patency was 82.0% and 82.0%, assisted primary patency was 93.8% and 93.8%, and secondary patency was 100.0% and 100.0%. At 1 and 2 years, amputation-free survival was 100.0% and 100.0%. No patient died within the study period (mortality 0.0%). CONCLUSIONS: Endoscopic harvest of GSV is a minimally invasive alternative to a standard open harvest of GSV. It is a feasible option for patients undergoing infrainguinal arterial bypass. In our early experience, patencies of EVH femoropopliteal bypasses are comparable to those achieved using traditional open vein harvest technique. Combination of endoscopic vein harvest with femoropopliteal bypass formation results in a low incidence of surgical site infections. KEY WORDS: endoscopic vein harvest - great saphenous vein - peripheral vascular surgery - femoropopliteal bypass - minimally invasive vascular surgery.

[The use of hybrid revascularization procedures for the therapy of multilevel lower extremity arterial disease--analysis of single center experience]. / Analýza výsledku hybridních revaskularizacních výkonu pro multietázové postizení tepenného systému dolních koncetin--výsledky jednoho centra.

INTRODUCTION: The goal of this study was to evaluate our experience and results of single staged hybrid procedures for revascularization of lower extremities affected by multilevel arterial occlusive disease. We analysed the effect of the indication and type of reconstruction on patency. METHOD: Patients were retrospectively reviewed. Data collection was conducted prospectively. Patients were divided into 5 groups based on the type of hybrid reconstruction. Group "1" included patients who underwent transluminal angioplasty (TA)±stenting of iliac arteries with endarterectomy (EA) and patch arterioplasty of the femoral bifurcation (35 patients; 27.6 %). Group "2" included patients who underwent TA±stenting of iliac arteries with infrainguinal bypass (15 patients; 11.8 %). Group "3" consisted of patients who underwent TA±stenting of outflow lower extremity arteries: superficial femoral artery±popliteal artery±crural arteries in combination with EA and patch arterioplasty of the femoral bifurcation (52 patients; 40.9 %). Group "4" represented patients who underwent infrainguinal bypass surgery in combination with TA distal to the site of open reconstruction (3 patients; 2.4%). Group "5" represented a heterogenous population of patients who underwent a hybrid reconstruction which did not belong to any of the 4 previously mentioned groups (22 patients; 17.3 %). The patients were divided into 3 groups based on the indication criteria of the intervention: Patients with acute limb ischemia (ALI) were put into group "ALI". Patients with critical limb ischemia (CLI) were put into group "CLI". Patients with claudications were put into group "II". Patency analyses were performed using Kaplan-Meier life tables. Differences in patency rates between the different groups of patients were determined using the log-rank test. Statistical analysis was performed using the software IBM SPSS Statistics 21.0. RESULTS: The study included 127 patients who underwent 127 hybrid arterial procedures. Technical and clinical success rates were 96.9% and 98.4%. 30-day perioperative mortality rate was 3.1%. The primary (PP), assisted-primary (APP) and secondary patency (SP) results at 2 years were the best amongst the patients from groups "1" and "3". These patients underwent patch arterioplasty±EA of the femoral bifurcation in combination with transluminal angioplasty of inflow or outflow arteries of the lower extremity. The resulting PP, APP and SP rates at 2 years in group "1" were 80.6%, 84.3% and 84.3%. Patency rates in group "3" in the same order at 2 years were 81.1 %, 82.8% and 86.3%. Significantly lower patency rates were achieved in patients from groups "2" and "5". The resulting PP, APP and SP rates in group "2" at 2 years were 39.4%, 59.1% and 59.1%; in group "5" at 2 years they were 30.4%, 49.2% and 70.7%. Taking into account the effect of the indication on patency rates, we found that patients from group "CLI" had the best APP and SP rates at 2 years: 81.6% and 86.2%. Only the PP rate at 2 years was the best in group "II" (patients with claudications): 71.1%. Patients who underwent their operations because of acute limb ischemia (group "ALI") achieved the worst results among these 3 groups. Their PP, APP and SP rates at 2 years were 33.7%, 46.2% and 45.5%. Patients from the group "CLI" had the best amputation-free survival at 2 years: 89.1% amongst the 3 groups subdivided according to the indication for the intervention ("II" 81.9%; "ALI" 61.4%). Overall survival and amputation-free survival at 2 years were 93.2% and 82.3%, respectively, for the whole studied population. CONCLUSION: The hybrid procedure is an intervention which combines endovascular and open reconstruction performed at the same time. Hybrid procedures provide effective therapy for patients with multilevel lower extremity arterial disease. They have low complication rates, periprocedural morbidity and mortality. Using these procedures, we are able to achieve good limb salvage rates and patency rates irrespective of the form of chronic limb ischemia (claudications, critical limb ischemia). Results for patients with acute limb ischemia are inferior. The combination of patch arterioplasty±endarterectomy of the femoral bifurcation with transluminal angioplasty of inflow or outflow limb arteries is our hybrid procedure of choice with the most favourable results.

Plasma Low-density Lipoprotein Receptor-related Protein 1 Concentration is not Associated with Human Abdominal Aortic Aneurysm Presence.

OBJECTIVE/BACKGROUND: Recent genetic data suggest that a polymorphism of LRP1 is an independent risk factor for abdominal aortic aneurysm (AAA). The aims of this study were to assess whether plasma and aortic concentrations of low-density lipoprotein receptor-related protein 1 (LRP1) are associated with AAA, and to investigate the possible relevance of LRP1 to AAA pathophysiology. METHODS: Three analyses were conducted. First, plasma LRP1 concentrations were measured in community-dwelling men with and without AAA (n = 189 and n = 309, respectively) using enzyme-linked immunosorbent assay. Second, Western blotting analyses were employed to compare the expression of LRP1 protein in aortic biopsies collected from patients with AAA and nonaneurysmal postmortem donors (n = 6/group). Finally, the effect of in vitro LRP1 blockade on matrix metalloprotease 9 (MMP9) clearance by vascular smooth muscle cells was assessed by zymography. RESULTS: Plasma LRP1 concentrations did not differ between groups of men with and without AAA (median concentration 4.56 µg/mL [interquartile range {IQR} (3.39-5.96)] and 4.43 µg/mL [IQR 3.44-5.84], respectively; p = .48), and were not associated with AAA after adjusting for other risk factors (odds ratio 1.10 [95% confidence interval: 0.91-1.32]; p = 0.35). In contrast, LRP1 expression was approximately 3.4-fold lower in aortic biopsies recovered from patients with AAA compared with controls (median [IQR] expression 1.72 [0.94-3.14] and 5.91 [4.63-6.94] relative density units, respectively; p < .01). In vitro LRP1 blockade significantly reduced the ability of vascular smooth muscle cells to internalize extracellular MMP9. CONCLUSIONS: These data suggest that aortic but not circulating LRP1 is downregulated in patients with AAA and indicates a possible role for this protein in clearing an aneurysm-relevant ligand.

[Incidence and risk factors of ischemic colitis after AAA repair in our cohort of patients from 2005 through 2009]. / Incidence a rizikové faktory vzniku strevní ischemie u pacientu po resekci AAA v nasem souboru z let 2005-2009.

INTRODUCTION: Using retrospective analysis, we sought to investigate the incidence, risk factors and therapeutic outcomes of ischemic colitis in patients after surgical and endovascular repair of abdominal aortic aneurysms (AAA). MATERIAL AND METHODS: The complete inpatient and outpatient medical records of all patients undergoing surgical or endovascular AAA repair in our Department from January 2005 to December 2009 were retrospectively reviewed. We selected all patients who had developed an acute or chronic form of postoperative large or small bowel ischemia. We carried out data analysis and focused on determining the incidence and risk factors of this complication and the outcomes of its treatment. RESULTS: Two hundred and seven AAA repairs were performed in the 2nd Department of Surgery of St. Anne's University Hospital in Brno and the Faculty of Medicine of Masaryk University in Brno during the studied period. This number includes endovascular AAA repairs (13 patients; 6.3%) as well as one robot-assisted operation, and also the whole clinical spectrum of AAA manifestations, from non-symptomatic forms to ruptured aneurysm forms. The rest of the patients underwent open operation. Bowel ischemia developed in a total of 11 patients (5.3 %), who all underwent open AAA repair. Six of these patients presented with non-ruptured AAA and the remaining 5 with ruptured AAA. In 3 patients, bowel ischemia was diagnosed with a delay of several months from the original revascularization operation in the clinical form of postischemic stricture of the large bowel (2 patients) or postischemic colitis (1 patient). 8 patients were diagnosed with acute ischemic colitis affecting an isolated segment of the small bowel in one patient, extended segments of the large bowel (descending colon + sigmoid colon + rectum) in 2 patients, and typically the descending and sigmoid colon in 5 patients. None of the three patients with late manifestation of ischemic colitis died. Of the 8 patients with acute presentation, resection of the ischemic bowel +/- the rectum was performed in 6 patients. 3 of them died and 3 survived the operation and have been followed up in our outpatient department. 2 patients with acute manifestation did not undergo bowel resection. Both of them died. The overall mortality of all patients with ischemic colitis was 45.5% (5 patients out of 11 died) in our study. When considering only patients suffering from the acute form of ischemic colitis, the mortality rate in our studied cohort amounts to 62.5% (5 patients out of 8 died). CONCLUSION: Bowel ischemia after AAA repair remains to be a serious complication. Besides the acute form of ischemic colitis, its possible late clinical manifestation in the form of postischemic stricture of the large bowel or postischemic large bowel colitis must also be kept in mind when following up patients. The analysis of our patient's data shows that conditions requiring the use of vasopressors and an increased need of transfusions (more than 7 units of packed red blood cells) intraoperatively represent important predictors of colon ischemia after AAA repair.

[Infected brachial artery pseudoaneurysm--infrequent complication secondary to parenteral drug abuse]. / Infikovaná pseudoaneuryzma a. brachialis--raritní kazuistika u dlouholetého intravenózního narkomana.

INTRODUCTION: Intravenous drug abuse brings many infectious and surgical complications. Considering the duration of a drug scene in Czech Republic, pseudoaneurysms are not frequent complications, but we can expect their increased frequency with time. METHODS: A 27-year-old patient with known history of parenteral drug abuse (heroin, pervitin) was treated at our department during the autumn of 2006. He had self-injected heroin into an armpit four days before his appearance in our outpatient department. An abscess of his left arm and armpit resulting from cellulitis was his admission diagnosis based on a clinical ground. We did not validate that diagnosis with any radiology test. The operation made clear that pseudoaneurysm in a proximal part of brachial artery was a correct diagnosis. Because of severe inflammation of his left upper extremity, the pseudoaneurysm was dealt with resection, ligation of the brachial artery above and below the defect and leaving the incision to heal by secondary intention. RESULTS AND CONCLUSIONS: The pseudoaneurysm was treated with excision, tying the proximal and distal ends of brachial artery without urgent revascularization, extensive debridement of all necrotic tissues and leaving the incision to heal by secondary intention. Our approach did not threaten viability of the limb, which did not show any signs of ischemia during close postoperative monitoring. Our way seems to be appropriate and in agreement with current literature. The peroperative finding stresses the necessity of standard and Doppler ultrasound in every intravenous drug abuser with clinical picture of "a typical abscess" located in groin, elbow and armpit.

Expression of MDR proteins in breast cancer and its correlation with some clinical and pathological parameters.

The aim of this work was to determine the expression of the multidrug resistance (MDR) proteins, namely MDR1 (P-glycoprotein), MRP1 (multidrug resistance-related protein) and LRP (lung resistance-related protein), in 87 samples of breast carcinoma. Detection of these proteins was provided by using indirect enzymatic immunohistochemistry. Our findings were compared with the other clinical and pathological parameters: expression of Her2/neu, estrogen receptor status (ER), progesteron receptor status (PR), histological grade and regional lymph node status. For statistical analysis, non-parametric two sided Mann-Whitney-U test was used. Majority of breast carcinoma specimens show positivity for these proteins. The MDR1 and MRP1 signal was found in the cytoplasm of cancer cells. The expression of LRP was detected in the cytoplasm close to the nuclear membrane. The samples were positive for MDR1 protein in 57%, for MRP1 in 84% and for LRP in 79%. Comparing our results with other clinical and pathological parameters, negative correlation between ER, PR and MDR1 expressions and histological grading status was found. No associations were observed between the MRP1 and LRP proteins and histological grading, as well as between the expression of three MDR proteins and the other clinically relevant parameters. In conclusion, high frequency of expression of MDR proteins in breast carcinoma cells suggests, that these proteins might be an important factor of drug resistance in breast carcinoma. Nevertheless, the negative correlation between the histological grade of malignancy of tumor and the expression of ER, PR and MDR1 indicates possible influence of progressive tumor cell de-differentiation. However, this finding has to be confirmed in additional evaluations.

[Results of the large intestine resection in elderly patients]. / Výsledky resekce tlustého streva u nemocných ve vysokém véku.

The colorectal carcinoma incidence increases with age. The radical resection procedure significantly extends the survival period, when compared with other therapeutic approaches. The tissue damage may exceed the organ reserve capacity in cases of the elderly patients and may result in higher postoperative morbidity and mortality rates. The aim of this study was to compare the results and the surgical risks of the large intestine carcinoma resection procedure in elderly patients, compared to younger patients with the same diagnosis. THE PATIENT GROUP AND METHODOLOGY: The retrospective study summons up the clinical results of 3778 patients from all over the Czech Republic, who underwent primeoperations for the following diagnoses: C18--a malignant neoplasm of the large intestine, and C19--a malignant neoplasm of the rectosigmoideal junction, in 2001. The results are compared with our own patient group in the same time-period. The results were assessed according to the following age-group criteria: 21-59 yrs., 60-69 yrs. and over 70 yrs. of age. We assessed the following factors: age, diagnosis, incidence of early postoperative complications and duration of patients hospitalization. RESULTS: The patients in the 21-59 year-group and in the group over 70 years of age, had significantly different rates of early postoperative complications (12.3% vs 17.6%, p < 0.001). The rate of complications was twice as high in urgent procedures compared to planned procedures in all age groups (p < 0.001). The average hospitalization lasted 14.8 +/- 10.9 days. We discovered statistically significant differences in the duration of hospitalization among all three age groups respectively (p < 0.01). CONCLUSION: Based on our results, we believe the age itself not be an indication-limiting factor for the radical resection procedure for the large intestine carcinoma. The elderly patients benefit from its oncological radicality with acceptable rates of the postoperative complications risks. We believe even extensive surgical procedures to be feasible in cases of appropriately indicated elderly patients, and their surgical risks to be acceptable considering the expected benefits for the respective patient.

Expression of the multidrug resistance-associated protein 1 (MRP1) and the lung resistance-related protein (LRP) in human lung cancer.

Fifty lung cancer samples (41 non-small cell lung cancer-NSCLC and 9 small cell lung cancer-SCLC) were immunohistochemically analyzed for lung resistance-related protein (LRP) and multidrug resistance-associated protein 1 (MRP1) expressions which were then correlated with histopathological subtype of the tumor. To detect these proteins, monoclonal antibodies LRP-56 and MRPm6 were used. NSCLC samples were divided into two groups, adenocarcinomas (17 samples) and squamous cell carcinomas (24 samples). Four categories of LRP and MRP1 quantity were distinguished: +++ = high level--90--100% of positive cells, ++ = lower level--10--90% of positive cells, + = low level--up to 10% of positive cells, - = negative cells--0% of positive cells. Within the NSCLC group the most samples (36/41) had the similar level of LRP and MRP1. Significantly higher expression of both proteins was observed in the adenocarcinomas in comparison with squamous cell carcinomas. The lowest positive staining for LRP and MRP1 proteins has been found in SCLC. It is suggested that our finding can confirm the overall empirical clinical knowledge about much higher chemosensitivity of untreated SCLC comparing to NSCLC.

Allelic and haplotype frequencies of the p53 polymorphisms in brain tumor patients.

The polymorphisms of the tumor suppressor gene p53 in exon 4 (p53 BstUI) and in intron 6 (p53 MspI) have been suggested to be associated with the genetically determined susceptibility in diverse types of human cancer. In our hospital-based case-control study, we examined the allele and genotype incidence of these polymorphisms as well as their haplotype combinations in 60 brain tumor patients (27 males and 33 females) and 183 controls without malignancies. The genotype characteristics were determined by the PCR-based RFLP method using DNA extracted from peripheral blood. In this study we show that the p53 BstUI and the p53 MspI polymorphisms are not associated with increased risk of brain tumors. Thus, we conclude that the p53 BstUI and the p53 MspI polymorphic sites within the tumor suppressor gene p53 do not represent genetic determinants of susceptibility to brain tumors.

Occurrence and genetic association of selected virulence factors in clinical Escherichia coli isolates.

Occurrence of cnf1+ E. coli pathogenic strains among extraintestinal E. coli isolates was evaluated to explain an impact of cytotoxic necrotizing factor type 1 (CNF1) in human infections. A total of 120 E. coli isolates were characterized for presence of virulence factors cnf1- and pap--specific sequences by PCR, and the production of alpha-hemolysin using blood agar-plate test. Different association patterns among the detected virulence factors were obtained by comparison of various groups of clinical E. coli isolates. These differences probably reflect a potential impact of CNF1 in the colonization of vaginal environment.

Detection of pap-, sfa- and afa-specific DNA sequences in Escherichia coli strains isolated from extraintestinal material.

P-fimbriae, S-fimbriae and AFA-adhesins are virulence factors responsible for adherence of Escherichia coli strains to extraintestinal host-cell surface. Detection of pap-, sfa- and afa-specific sequences performed by PCR revealed 74% pap+, 65% sfa+, and 8.3% afa+ strains in a group of 84 extraintestinal E. coli isolates. Detection in a group of fecal strains showed 29% pap+, 21% sfa+ and 4% afa+ strains. pap together with sfa were found as the most frequent combination (56%) among extraintestinal isolates probably due to localization of pap- and sfa-operons on a common pathogenicity island. The occurrence of afa-specific sequence among 56 urine strains was 11%, although no afa+ strain was detected among 28 gynecological isolates. No strains with detected adhesin operons were found among twenty (24%) extraintestinal E. coli strains.

[Laparoscopic splenectomy--personal experience]. / Laparoskopická splenektomie--vlastní zkusenosti.

The authors present an account on their own experience with laparoscopic splenectomy which is used at the First Surgical Clinic, First Medical Faculty and General Faculty Hospital in Prague since 1996. In 1996 to 2002 the authors performed at the Surgical Clinic a total of 66 splenectomies. This number included on account of injury of the spleen, tumour or cyst 12 splenectomies by the open route. The remaining ones were indicated for haematological reasons in collaboration with the haematological department of the First Medical Clinic of the First Medical Faculty and General Faculty Hospital in Prague and the Institute of Haematology and Blood Transfusion in Prague. 23 splenectomies for haematological reasons were made by the classical open route. In 31 patients the splenectomy was performed by the laparoscopic route. In all haematological reasons were involved. In the group operated at the First Surgical Clinic LSE was indicated because of ITP 15x, for spherocytosis 8x, for haemolytic anaemia 7x, for eliptocytosis 1x. In eight patients at the same time laparoscopic cholecystectomy was performed. In the group subjected to classical splenectomy infection in the surgical wound was recorded in 11%, re-operations on account of a suppurative complications in the abdominal cavity were made in 13% and on account of haemorrhage in 11%. In the group of laparoscopic splenectomies the authors did not record infection at the site of the inserted trocars, there were no suppurative complications in the abdominal cavity. In four laparoscopic operations the authors converted the operation on account of haemorrhage four times (11%), once on account of major adiposity of the omentum, in five postoperative revision on account of haemorrhage was necessary (16%), incl. one case of profuse haemorrhage. Therefore the authors sought a way how to prevent haemorrhage. Based on their own experience they recommend to apply clamps to the trunk of the lienal artery. The time of operation was reduced by the application of clamps to the lienal artery to 60-80 mins. and the peroperative blood losses dropped to 20-30 ml. The morbidity declined and the patients are discharged into domiciliary care on the 4th day after operation, to be on the safe side. No late complications of the operation were recorded.

Germ line polymorphisms of the tumor suppressor gene p53 and lung cancer.

Two p53 variable sites (BstUI and MspI SNPs in exon 4 and intron 6, respectively) and their haplotype combinations were studied in 109 patients (84 males and 25 females) with lung cancer and 113 healthy controls from the region of Eastern Slovakia. There were no differences found between lung cancer patients and controls carrying the distribution of p53 BstUI and MspI alleles. However, the genotype distribution showed a significantly higher proportion of MspI heterozygotes in lung cancer patients (P=0.048, OR 1.83, 95% CI 1.00-3.34) than in controls. The analysis based on haplotype frequencies showed the presence of BstUI-MspI 2-1 haplotype in cancer patients (5.4%) in contrast to the absence of this haplotype in healthy controls. The results of this study suggest that the p53 MspI polymorphism may modify the susceptibility to lung cancer as a single factor rather than in combination with BstUI polymorphism.

Polymorphism of the p53 gene within the codon 72 in lung cancer patients.

We tested the codon 72 single nucleotide polymorphism (SNP) of the tumor suppressor gene p53 for association with lung cancer. In our hospital-based case-control study, 168 lung cancer patients (134 males and 34 females) and 148 controls without malignant diseases were recruited. The genotype characteristics were determined by PCR-based RFLP method using DNA extracted from peripheral blood. Only in lung cancer patients but not in the controls we found both significant decrease of A1 allele of the p53 codon 72 (p=0.024, OR 0.56, 95% CI 0.43-0.72) and A1/A1 homozygous genotype (p=0.006, OR 0.27,95% CI 0.15-0.51). The results of this study suggest a protective effect of A1 allele against lung cancer.

p53 single nucleotide polymorphisms and bladder cancer.

Two p53 germline polymorphisms, a BstUI in exon 4 and a MspI in intron 6 were studied using polymerase chain reaction (PCR) based methods in 50 patients with bladder cancer and 145 healthy controls. Increased frequencies of the BstUI and MspI A2 alleles were found to be associated with statistically non-significant (p = 0.2308 and p = 0.5959) but increased odd ratios for bladder cancer (OR 1.44, 95% CI 0.82-2.27 and OR 1.20, 95% CI 0.61-2.33). Statistically significant difference between patients with bladder cancer and controls was found in the distribution of MspI genotypes. There was a significantly lower proportion of the heterozygous A1A2 genotype in all patients but not in controls (p = 0.0354). The results of this study suggest that BstUI and Msp1 germ line polymorphisms of the tumor suppressor gene p53 marginally modify the risk of bladder cancer.

The role of human glutathione S-transferases M1 and T1 in individual susceptibility to bladder cancer.

Several genes involved in the metabolism of carcinogens have been found to be polymorphic in the human population, and specific alleles are associated with increased risk of cancer at various sites. This study is focused on the polymorphic enzymes glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) that are involved in the detoxification of many xenobiotics involved in the etiology of bladder cancer. To investigate the role of GSTM1 and GSTT1 in bladder carcinogenesis, the polymerase chain reaction was used to determine GSTM1 and GSTT1 genotypes of cancer patients (n = 76) and controls (n = 248). The proportion of putative risk GSTM1 null genotype in the case group was 52.6%, compared to 49.6% in the control group, but the GSTT1 0/0 frequency in the bladder cancer group was significantly higher (P = 0.04) in comparison with the control group (27.6 vs 16.9%). Individuals lacking the GSTT1 gene are at an approximately 1.9-fold higher risk (OR = 1.87, C.I. 95% = 1.03-3.42) of developing bladder cancer in comparison with individuals with at least one active allele in the GSTT1 locus. A significantly higher incidence of GSTM1 deletion genotype (P = 0.02) was found in smokers with bladder cancer compared to the controls (70.6 vs 49.6%). Smokers lacking the GSTM1 gene are at an approximately 2.4-fold higher risk of bladder cancer (OR = 2.44, C.I. 95% = 1.10-5.30). The effect of smoking associated with the GSTT1 0/0 genotype was not found to affect the risk of bladder cancer.

Genetic polymorphism of glutathione S-transferases M1 and T1 as a risk factor in lung and bladder cancers.

A combined analysis of two polymorphic enzymes, glutathione S-transferase mu (GST M1) and q (GST T1) and their implication as cancer risk factors was performed in a case-control study of lung and bladder cancers. Using a multiplex polymerase chain reaction (PCR) based method, the frequency of the homozygous deleted GSTM1 and GSTT1 genotypes was examined in 117 lung cancer patients, 67 urinary bladder cancer patients, and in a community-based sample of 248 healthy, unrelated individuals. In both cancer groups the frequency of the GSTM1 null genotype was higher in comparison with that of the control group (59% and 59.7% vs. 49.6%), but this increase did not reach statistical significance (p > 0.05). After grouping by the smoking status, among smokers in both cancer groups (62.1% in lung cancer and 71.4% in the bladder cancer group, respectively) there were statistically significantly (p < 0.05) increased frequencies of the GSTM1 deletion genotype as compared to the control group (49.6%). Smokers with absence of the GSTM1 gene were at an approximately 1.7-fold higher risk for lung cancer (odds ratio--OR = 1.67, 95% confidence interval--CI 95% = 1.0-2.7, p = 0.04) and an approximately 2.5-fold higher risk for bladder cancer (OR = 2.54, CI 95% = 1.2-5.5, p = 0.02). As related to GSTT1, our study demonstrated an overall GSTT1 effect on bladder cancer risk. Individuals with absence of the GSTT1 gene were at an approximately 2.5-fold higher risk of developing bladder cancer. In the lung cancer cases, the frequency of the putatively high risk GSTT1 null genotype was not increased as compared with controls. No effect of smoking was found on risk of lung and bladder cancer associated with the GSTT1 0/0 genotype. In combined analysis, the obtained results suggested that individuals who were both GSTM1 null and GSTT1 null may be at increased risk because they lack both enzymes. The findings suggest that the GSTM1 null genotype may be associated with susceptibility to lung and urinary bladder cancer in dependence on the exposure to carcinogens in cigarette smoke and that the GSTT1 null genotype is not a critical factor in mediating the risk of lung cancer, but may be associated with an increased susceptibility to bladder cancer.