The value of "diaphragmatic relaxing incision" for the durability of the crural repair in patients with paraesophageal hernia: a double blind randomized clinical trial.

Background: Surgical repair of paraesophageal hernias (PEHs) is burdened with high recurrence rates, and hitherto various techniques explored to enforce the traditional crural repair have not been successful. The hiatal reconstruction in PEH is exposed to significant tension, which may be minimized by adding a diaphragmatic relaxing incision to enhance the durability of the crural repair. Patients and methods: All individuals undergoing elective laparoscopic repair of a large PEH, irrespective of age, were considered eligible. PEHs were classified into types II-IV. The preoperative work-up program included multidetector computed tomography and symptom assessment questionnaires, which will be repeated during the postoperative follow-up. Patients were randomly divided into a control group with crural repair alone and an intervention group with the addition of a left-sided diaphragmatic relaxing incision at the edge of the upper pole of the spleen. The diaphragmatic defect was then covered by a synthetic mesh. Results: The primary endpoint of this trial was the rate of anatomical PEH recurrence at 1 year. Secondary endpoints included symptomatic gastroesophageal reflux disease, dysphagia, odynophagia, gas bloat, regurgitation, chest pain, abdominal pain, nausea, vomiting, postprandial pain, cardiovascular and pulmonary symptoms, and patient satisfaction in the immediate postoperative course (3 months) and at 1 year. Postoperative complications, morbidity, and disease burden were recorded for each patient. This was a double-blind study, meaning that the operation report was filed in a locked archive to keep the patient, staff, and clinical assessors blinded to the study group allocation. Blinding must not be broken during the follow-up unless required by any emergencies in the clinical management of the patient. Likewise, the patients must not be informed about the details of the operation. Trial Registration: ClinicalTrials.gov, identification number NCT04179578.

The comparison of the effects of ketamine and etomidate on cardiodynamics, biochemical and oxidative stress parameters in Wistar male rats.

It is well known the use of ketamine and etomidate in clinical practice; however, the difference in the systemic effects of these two anesthetic agents is still debatable. Thus, in the present study we aimed to compare their effects on heart, and other organs through estimation of cardiodynamics, biochemical and hematological parameters. Male Wistar rats were divided in 2 groups containing of 2 subgroups (n = 7 in each subgroup, n = 28 in total): (1) bolus injection of anesthetic ketamine (40 mg/kg b.w., i.p. n = 14); (2) bolus injection of anesthetic etomidate (20 mg/kg b.w., i.p. n = 14). The experiments were done in vitro in one subgroup of each group: cardiodynamic variables (dp/dtmax, dp/dtmin, heart rate), coronary flow, oxidative stress in coronary effluent and cardiac tissue homogenate, and in vivo in another subgroup: biochemical and hematological parameters, and oxidative stress in haemolysate. Significantly increased left ventricular contractility (dp/dtmax) and relaxation (dp/dtmin) were noticed in etomidate group. Creatinine (CREA), HDL cholesterol and folate were significantly higher in etomidate group, whereas amylase (AMY) and eosinophils in ketamine group. Our results suggested that ketamine has more antioxidant potential compared to etomidate, and etomidate has more favorable effects regarding cardiac performance.

The effects of gasotransmitters inhibition on biochemical and haematological parameters and oxidative stress in propofol-anaesthetized Wistar male rats.

This study aimed to investigate the effects of propofol through evaluating its interaction with nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO). Wistar male rats were divided in 4 groups: (1) bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (2) Nω-nitro-l-arginine methyl ester (L-NAME; NO synthase inhibitor, 60 mg/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (3) DL-propargylglycine (DL-PAG; H2S synthase inhibitor, 50 mg/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (4) zinc protoporphyrin IX (ZnPPIX; CO synthase inhibitor, 50 µmol/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.). Increased levels of albumins, low-density lipoproteins, alkaline phosphatase, amylase, high-sensitivity Troponin T, and fibrinogen were found in L-NAME + propofol group. Platelet crit, platelet count, total cholesterol, and high-density lipoproteins were elevated in ZnPPIX + propofol group. Hydrogen peroxide was increased in all groups treated with gasotransmitters inhibitors. Reduced glutathione was reduced in all groups, superoxide dismutase activity only in L-NAME + propofol. The effect of propofol on various biochemical, haematological, and oxidative stress markers may be at least in part mediated through interaction with 3 estimated gasotransmitters.

Inhibition of gasotransmitters production and calcium influx affect cardiodynamic variables and cardiac oxidative stress in propofol-anesthetized male Wistar rats 1.

It has been assumed that the cardioprotective effects of propofol are due to its non-anesthetic pleiotropic cardiac and vasodilator effects, in which gasotransmitters (NO, H2S, and CO) as well as calcium influx could be involved. The study on isolated rat heart was performed using 4 experimental groups (n = 7 in each): (1) bolus injection of propofol (100 mg/kg body mass, i.p.); (2) L-NAME (NO synthase inhibitor, 60 mg/kg body mass, i.p.) + propofol; (3) DL-PAG (H2S synthase inhibitor, 50 mg/kg body mass, i.p.) + propofol; (4) ZnPPIX (CO synthase inhibitor, 50 µmol/kg body mass, i.p.) + propofol. Before and after the verapamil (3 µmol/L) administration, cardiodynamic parameters were recorded (dp/dtmax, dp/dtmin, systolic left ventricular pressure, diastolic left ventricular pressure, heart rate, coronary flow), as well as coronary and cardiac oxidative stress parameters. The results showed significant increases of diastolic left ventricular pressure following NO and CO inhibition, but also increases of coronary flow following H2S and CO inhibition. Following verapamil administration, significant decreases of dp/dtmax were noted after NO and CO inhibition, then increase of diastolic left ventricular pressure following CO inhibition, and increase of coronary flow following NO, H2S, or CO inhibition. Oxidative stress markers were increased but catalase activity was significantly decreased in cardiac tissue. Gasotransmitters and calcium influx are involved in pleiotropic cardiovascular effects of propofol in male Wistar rats.

Surgical treatment of obesity in DM1--a case report and a review of the literature.

In patients with myotonic dystrophy type 1 overweight and obesity are frequent. When present this has further negative effects on the patients' pulmonary and muscle function as well as social participation. Anesthesia in myotonic dystrophy type 1 patients is associated with increased risks, especially in those who are obese. We describe the outcome of the first patient reported who has undergone gastric bypass surgery. The operation went without complications. Within two years after surgery she has lost 56.5 kg corresponding to 44% of her preoperative body weight (128.5 kg). She has lost muscle mass and muscle strength, but has gained somewhat in functional tests including pulmonary function and has no longer any need for nocturnal ventilation. Surgical treatment of obesity may be feasible in selected myotonic dystrophy type 1 patients but further studies are needed to determine appropriate criteria for surgery including body mass index limits and how pre- and post-operative follow-up should best be made.

The muscular expression of RAS in patients with achalasia.

INTRODUCTION: Angiotensin II (AngII) elicits smooth muscle contractions via activation of AngII type 1 receptor (AT1R) in the intestinal wall and in sphincter regions in several species. Achalasia is a rare swallowing disorder and is characterized by a loss of the wave-like contraction that forces food through the oesophagus and a failure of the lower oesophageal sphincter to relax during swallowing. AIMS AND METHODS: The present study was undertaken to elucidate expression and distribution of a local renin-angiotensin system (RAS) in the muscular layer of distal normal human oesophagus as well as in patients with achalasia using western blot analysis, immunohistochemistry and polymerase chain reaction (PCR). RESULTS: AT1R, together with enzyme renin and cathepsin D expression were decreased in patients with achalasia. In contrast, the mast cells chymase, cathepsin G, neprilysin and the receptor for angiotensin 1-7 peptides, the MAS receptor, were increased in patients with achalasia. CONCLUSION: The results showed the existence of a local RAS in human oesophageal muscular layer. The enzymes responsible for AngII production are different and there has been a shift in receptor physiology from AT1R to MAS receptor in patients with achalasia. These changes in the RAS might play a significant role in the physiological motor control for patients with achalasia.

The effects of intraganglionic injection of calcium/calmodulin-dependent protein kinase II inhibitors on pain-related behavior in diabetic neuropathy.

Calcium/calmodulin-dependent protein kinase II (CaMKII) has been implicated in the transmission of nociceptive input in diabetic neuropathy. The aim of this study was to test whether intraganglionic (i.g.) injection of CaMKII inhibitors may alleviate pain-related behavior in diabetic rats. Diabetes was induced in Sprague-Dawley rats using 55 mg/kg streptozotocin intraperitoneally. Two weeks after diabetes induction, CaMKII inhibitors myristoil-AIP and KN93 were injected directly into the right L5 dorsal root ganglion (DRG). Behavioral testing with mechanical and thermal stimuli was performed before induction of diabetes, the day preceding the injection, as well as 2 and 24h after the i.g. injection. The expression of total CaMKII and its alpha isoform in DRG neurons was analyzed using immunohistochemistry. CaMKII inhibitors attenuated pain-related behavior in a modality-specific fashion. Attenuation of nociceptive behavior was accompanied with a corresponding decrease of CaMKII alpha expression in DRG neurons on the side of injection. A significant decrease of CaMKII alpha expression was seen in small- and medium-sized neurons. In conclusion, our study provides evidence that CaMKII inhibitors are potential pharmacological agents that should be further explored for treatment of diabetic neuropathy symptoms.

Attenuation of pain-related behaviour evoked by carrageenan injection through blockade of neuropeptide Y Y1 and Y2 receptors.

BACKGROUND: It is well known that neuropeptide Y (NPY) participates in the modulation of chronic pain, but its exact role has not yet been fully explained. In this study, we explored whether targeted delivery of NPY and its antagonists into dorsal root ganglion (DRG) modulates pain-related behaviour in rats with experimentally induced inflammatory nociception. METHODS: Inflammatory nociception was induced by intraplantar carrageenan injection. Immediately after carrageenan injection, NPY or its antagonists were injected directly into DRG. Behavioural testing was performed on the day preceding the carrageenan injection and four times (5 h after, on the first, fifth and eighth days) following the injection. Immunohistochemical analysis was performed 8 days following the surgery. RESULTS: Our results showed that NPY, applied directly to DRG, induced cold allodynia in carrageenan inflammatory pain model. NPY in carrageenan-injected rats did not additionally exacerbate activation of satellite cells in DRG and astrocytes in dorsal horn caused by intraplantar carrageenan injection. However, application of NPY Y1 and Y2 antagonists directly into DRG reversed carrageenan proalgesic effects and reduced gliosis in DRG and dorsal horn. CONCLUSION: These findings indicate an important link between pain-related behaviour and neuroimmune actions of NPY Y1 and Y2 receptors.

Disconnection of chamber and catheter as a complication of central venous catheter type port-a-cath.

The use of a central vein catheter (CVC) type port-a-cath (VPS), apart from the comfort it provides to the patient undergoing chemotherapy, also carries certain complications. In this study, our patient was subjected to chemotherapy after a radical breast cancer operation and was given a CVC type VPS. After further care, a rare complication was verified--disconnection of the chamber and catheter, which one was visually identified in the right heart chamber. As the patient was vitally endangered, she was immediately hospitalized and the catheter was removed by catheterization of the right femoral vein, with scopic imaging. Early diagnosis and localization of the problem prevented more severe complications and mortality.

Evaluation of the response to treatment in patients with idiopathic achalasia by the timed barium esophagogram: results from a randomized clinical trial.

To choose which treatment would be most effective for the individual patient with newly diagnosed achalasia is difficult for the tending physician. A diagnostic tool that would allow prediction of the symptomatic and functional response after treatment for achalasia is therefore needed. The timed barium esophagogram (TBE) is a method that allows objective assessment of esophageal emptying, but the value of TBE in the clinical management of achalasia remains to be clarified. The aim of this study was first, to assess the ability of TBE to predict symptoms and treatment failure during post-treatment follow-up. Second, to determine whether esophageal emptying as assessed by TBE differs after treatment with pneumatic dilatation or laparoscopic myotomy. Fifty-one patients with newly diagnosed achalasia were prospectively randomized to pneumatic dilatation (n = 26) or laparoscopic myotomy (n = 25). Evaluation with TBE was performed before (n = 46) and after treatment (n = 43). The median interval between treatment and post-treatment TBE was 6 months, and the median follow-up time after the post-treatment TBE was 18 months. Following therapeutic intervention, TBE parameters did not differ significantly between treatment groups. However, significant correlations were found between the height of the barium column at 1 min and the symptom scores at the end of follow up for 'dysphagia for liquids' (P < 0.05, rho = 0.47), 'chest pain' (P < 0.05, rho = 0.42), and the 'Watson dysphagia score' (P < 0.05, rho = 0.46). Patients with less than 50% improvement in this TBE-parameter (height at 1 min) post-treatment had a 40% risk of treatment failure during follow-up. In summary, pneumatic balloon dilatation and laparoscopic myotomy similarly affected esophageal function as assessed by TBE-emptying. Lack of improvement in barium-column height post-treatment was associated with an increased risk of treatment failure which should motivate close surveillance in order to detect symptomatic recurrence at an early stage.

Health economic evaluation of therapeutic strategies in patients with idiopathic achalasia: results of a randomized trial comparing pneumatic dilatation with laparoscopic cardiomyotomy.

BACKGROUND: We have prospectively collected information concerning the costs incurred during the management of patients allocated to either forceful dilatation or to an immediate laparoscopic operation because of newly diagnosed achalasia. METHODS: Fifty-one patients with newly diagnosed achalasia were randomized to either pneumatic dilatation to a diameter of 30-40 mm or to a laparoscopic myotomy to which was added a posterior partial fundoplication. Follow-ups were scheduled at 1, 3, 6, and 12 months after inclusion. At each follow-up visit a study nurse interviewed the patients regarding symptoms and their quality of life (QoL) and a health economic questionnaire was completed. In the latter questionnaire, patients were asked to report the presence and character of contacts with the healthcare system since the last visit. RESULTS: In the dilatation group six patients (23%), including the patient who was operated on because of perforation, were classified as failures during the first 12 months of follow-up compared to one (4%) in the myotomy group (p = 0.047). Five of those classified as failures in the dilatation group subsequently had a surgical myotomy and the sixth patient was treated with repeated dilatations. The patient classified as failure in the myotomy group was treated with endoscopic dilatation. The initial treatment cost and the total costs were significantly higher for laparoscopic myotomy compared to a pneumatic dilatation-based strategy (p = 0.0002 and p = 0.0019, respectively). When the total costs were subdivided into the different resources used, we found that the single largest cost item for pneumatic dilatation was that for hospital stay and that for laparoscopic myotomy was the actual operative treatment (operating room time). The cost-effectiveness analysis, relating to the actual treatment failures, revealed that the cost to avoid one treatment failure (incremental cost-effectiveness ratio) amounted to 9239 euros. CONCLUSION: The current prospective, controlled clinical trial shows that despite a higher level of clinical efficacy of laparoscopic myotomy to prevent treatment failure in newly diagnosed achalasia, the cost effectiveness of pneumatic dilatation is superior, at least when a reasonable time horizon is applied.

Pneumatic dilatation or laparoscopic cardiomyotomy in the management of newly diagnosed idiopathic achalasia. Results of a randomized controlled trial.

BACKGROUND: The most effective therapeutic strategy in newly diagnosed achalasia is yet to be established. Therefore we designed a study in which pneumatic dilatation was compared to laparoscopic cardiomyotomy to which was added a partial posterior fundoplication. PATIENTS AND RESULTS: A series of 51 patients (24 males, mean age 44 years) were randomly allocated to the therapeutic modalities (dilatation = 26, surgery = 25). All patients were followed for at least 12 months, and during that period the pneumatic dilatations strategy had significantly more treatment failures (P = 0.04). Only minor differences emerged between the study groups when symptoms, dysphagia scorings, and quality-of-life assessments were evaluated 12 months after initiation of therapy. CONCLUSIONS: Laparoscopic myotomy was found to be superior to an endoscopic balloon dilatation strategy in the treatment of achalasia when studied during the first 12 months after treatment.

Is there such thing as "reversible dementia" (RD)?

RD is an extremely important problem for the practice of geriatricians. Rationale for this review had come from our question: could we increase and improve the cognitive function of our patients by treating some of "internal medicine" diseases at our hospital. Our clinical experience is telling us that it might be so. We administered the mini mental state examination (MMSE) test on 77 patients to check, if there is a relation between mental state and physical health. Patients were treated with appropriate cardiological, pulmonological and other needed therapies. Results indicate that recovering from the main disease increases the MMSE scores. This leads to the conclusion that successful treatment of patients can be followed and also confirmed by the results of the MMSE test. We have also observed that damaged physical health can inflict cognitive functions, no matter how old a person is.

Characteristics of timed barium esophagogram in newly diagnosed idiopathic achalasia: clinical and manometric correlates.

PURPOSE: To describe timed barium esophagogram (TBE) characteristics in patients with newly diagnosed idiopathic achalasia, and to correlate these with clinical and manometric variables. MATERIAL AND METHODS: Forty-six consecutive patients with newly diagnosed achalasia were examined with TBE. Esophageal emptying was assessed using the height, area, and volume of the barium column. Subjective evaluation was performed according to a standardized protocol in all patients. Objective diagnostic evaluation included manometry. RESULTS: At the 1-min time point after contrast ingestion, the static parameters median height, maximum, and mean width of the barium column were 16.0, 4.4, and 3.3 cm, respectively. Emptying, expressed as volume of barium, showed significant inverse correlation with the resting and the maximal relaxing pressure of the lower esophageal sphincter (LES) (R = -0.34 and R = -0.54, respectively). There was also an inverse correlation between emptied volume at TBE and the duration of symptoms (R = -0.36), and between barium column width and postprandial chest pain (R = -0.44). CONCLUSION: All patients with newly diagnosed achalasia presented with delayed emptying of barium the esophagus at TBE. The estimated emptied volume of barium (related to the ingested volume) correlated inversely with the basal tone and the relaxation pressure of the LES. Including estimation of the volume of emptied barium at TBE resulted in closer correlation with manometric values of LES tone than using the parameters traditionally recorded.

Timed barium esophagogram in the assessment of patients with achalasia: reproducibility and observer variation.

SUMMARY. The timed barium esophagogram (TBE) is a further development of the barium swallow, introducing functional and dynamic dimensions to the assessment. The purpose of our study was to assess the day to day variability of TBE parameters when scored in healthy subjects, in untreated and in previously treated patients with confirmed diagnoses of achalasia and to assess the intra- and interobserver agreement. After fasting, the subjects drank 250 mL of low-density barium sulfate suspension. Radiographs of the esophagus were exposed at 1, 2 and 5 min after the start of the barium ingestion. The heights and widths of the barium column and changes in these parameters over time (esophageal emptying) were assessed. Each subject was re-tested after a median time interval of 8 days. Healthy individuals emptied their esophagi effectively and promptly with no significant amount of contrast remaining in the lumen after 2 min. In the achalasia patients all TBE variables differed profoundly compared to the controls. There was an excellent intra- and interobserver agreement for all measured variables. The reproducibility of the static TBE variables from day-to-day was good, but not so for the functional assessment of esophageal emptying, having a correlation coefficient of only 0.50. The usefulness of TBE as a clinical and research tool in achalasia patients requires further evaluation.

MRI combined with MR cholangiopancreatography versus helical CT in the evaluation of patients with suspected periampullary tumors: a prospective comparative study.

PURPOSE: To establish the diagnostic accuracy of MRI including MR cholangiopancreatography (MRCP) compared with helical CT in the differentiation of malignant and benign lesions in the periampullary region. MATERIAL AND METHODS: Fifty-one patients (27 M, 24 F, mean age 66 years, range 39-86 years) with obstructive jaundice and sonographic evidence of intra- and extrahepatic bile duct dilatation (n=31) or suspicion of periampullary tumor, based on previously performed ultrasound and/or CT examination (n=20), were studied. MRI with MRCP and helical CT were reviewed blindly under standardized conditions. Lesion status (differentiation of malignant versus benign) was rated on a 5-point diagnostic confidence scale. Reference standards for comparison were findings at surgery or laparoscopy and/ or the clinical outcome. The predictive value of imaging findings was determined with multivariate logistic regression analysis. RESULTS: The areas under the receiver operating characteristic curve were 0.96 for MRI with MRCP and 0.81 for CT (P <0.05). Multivariate analysis of eight imaging variables at MRI indicated that a stricture with malignant characteristics at MRCP was the best predictor of malignancy. CONCLUSION: MRI with MRCP was significantly more accurate than CT in differentiating between malignant and benign lesions in patients with suspected periampullary tumors, mainly due to the information obtained on the MRCP images of the biliary and pancreatic duct anatomy.

Timed barium esophagogram: A simple physiologic assessment for achalasia.

OBJECTIVE: Success of achalasia therapy is difficult to determine because repeated physiologic study is impractical and symptoms are subjective. Timed barium esophagography directly measures esophageal emptying and is simple to perform. This study (1) evaluates the assessment of myotomy by timed barium esophagography and (2) compares it with premyotomy and postmyotomy symptoms. METHODS: Fifty patients ingested 250 mL low-density barium and had upright films at 1, 2, and 5 minutes premyotomy. Forty-five underwent repeat timed barium esophagography 8 weeks (median) postmyotomy. Premyotomy and postmyotomy height and width of the barium column were compared and related to symptoms. RESULTS: At 1, 2, and 5 minutes premyotomy, median barium column height was 19, 17, and 15 cm, and width was 5.2, 4.8, and 4.5 cm, respectively. Surgery reduced these to 7.0, 5.0, and 1.0 cm and to 3.5, 3.0, and 1.0 cm, respectively (P <.001). Postmyotomy complete esophageal emptying was seen in 29%, 36%, and 49% at 1, 2, and 5 minutes. Postmyotomy height was unrelated (r approximately 0.2) to premyotomy height but was directly related to premyotomy width (r = 0.3-0.5; P <.05); postmyotomy width was directly related to premyotomy width (r approximately 0.6; P <.001). Premyotomy dysphagia was more severe when little change in width occurred from 1 to 5 minutes (r = 0.26, P =.07). Premyotomy regurgitation was more severe the higher the barium column (r approximately 0.4, P <.007). Surgery relieved symptoms in the majority of patients (grade 2-5 dysphagia from 72% to 4%, grade 2-5 regurgitation from 79% to 4%). Postmyotomy symptoms were unrelated to the timed barium esophagogram. CONCLUSIONS: (1) The timed barium esophagogram gives objective confirmation of successful myotomy. (2) Symptoms are unreliable in assessing esophageal emptying.

Analyses of bronchial bulky DNA adduct levels and CYP2C9, GSTP1 and NQO1 genotypes in a Hungarian study population with pulmonary diseases.

Carcinogen-DNA adducts may represent an intermediate end-point in the carcinogenic cascade and may reflect exposure to chemical carcinogens, as well as susceptibility and, ultimately, cancer risk. Interindividual variability in activity of enzymes involved in the metabolism of polycyclic aromatic hydrocarbons to mutagenic diol epoxides may predict adduct levels and, indirectly, lung cancer risk. Using 32P-postlabeling methods, the levels of bulky DNA adducts were determined in macroscopically normal bronchial tissues obtained from resected lobes of 143 Hungarian patients with lung malignancy and other pulmonary conditions. DNA from normal tissue was also evaluated for polymorphisms in cytochrome P450 2C9 (CYP2C9) at two sites, codons 144 (Arg/Cys) and 359 (Ile/Leu), for glutathione S-transferase P1 (GSTP1) at codon 105 and for NAD(P)H:quinone oxidoreductase (NQO1) at codon 187 (Pro/Ser). Using the Mann-Whitney U-test and analysis of variance, levels of adducts were evaluated in relation to variant genotypes, separately for smokers and non-smokers. As previously reported, bulky DNA adduct levels in smokers (n = 104) were estimated to be 54% higher than in non-smokers (n = 39) (8.6 +/- 4.2 versus 5.6 +/- 3.3 per 10(8) nucleotides, respectively, P < 0.01). Adduct levels were 16-29% higher in individuals with the homozygous Ile359/Ile359 CYP2C9 allele than in those heterozygous for the variant allele (Ile359/Leu359) [8.8 +/- 4.3 (n = 84) versus 7.6 +/- 3.5 (n = 20) for smokers and 5.8 +/- 3.5 (n = 32) versus 4.5 +/- 1.3 (n = 7) for non-smokers], although differences were not statistically significant. There were no clear differences in adduct levels in relation to genotypes of NQO1 or GSTP1. Although numbers of patients in this study are large in relation to many studies of carcinogen-DNA adducts, it is still possible that significant differences were not noted for polymorphisms in xenobiotic metabolizing enzymes due to relatively small numbers in stratified data.