Extracorporeal cardiopulmonary resuscitation-based approach to refractory out-of-hospital cardiac arrest: A focus on organ donation, a secondary analysis of a Prague OHCA randomized study.

BACKGROUND: Refractory out-of-hospital cardiac arrest (OHCA) has a poor outcome. In patients, who cannot be rescued despite using advanced techniques like extracorporeal cardiopulmonary resuscitation (ECPR), organ donation may be considered. This study aims to evaluate, in refractory OHCA, how ECPR versus a standard-based approach allows organ donorship. METHODS: The Prague OHCA trial randomized adults with a witnessed refractory OHCA of presumed cardiac origin to either an ECPR-based or standard approach. Patients who died of brain death or those who died of primary circulatory reasons and were not candidates for cardiac transplantation or durable ventricle assist device were evaluated as potential organ donors by a transplant center. In this post-hoc analysis, the effect on organ donation rates and one-year organ survival in recipients was examined. RESULTS: Out of 256 enrolled patients, 75 (29%) died prehospitally or within 1 hour after admission and 107 (42%) during the hospital stay. From a total of 24 considered donors, 21 and 3 (p = 0.01) were recruited from the ECPR vs standard approach arm, respectively. Fifteen brain-dead and none cardiac-dead subjects were ultimately accepted, 13 from the ECPR and two from the standard strategy group. A total of 36 organs were harvested. The organs were successfully transplanted into 34 recipients. All transplanted organs were fully functional, and none of the recipients died due to graft failure within the one-year period post-transplant. CONCLUSION: The ECPR-based approach in the refractory OHCA trial is associated with increased organ donorship and an excellent outcome of transplanted organs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01511666. Registered January 19, 2012.

Multilocular infection caused by hypervirulent Klebsiella pneumoniae.

Hypervirulent strains of Klebsiella pneumoniae (hvKP) can cause atypical multilocular infections in otherwise healthy patients. Diagnosis of infection caused by hvKP is based mainly on clinical findings and laboratory results, including detection of virulence genes. It typically manifests as hepatic abscess with metastatic spread. Treatment is based on surgical intervention in combination with targeted antimicrobial therapy. The occurrence of hvKP infection is relatively common in Asia, and while still rare in Europe, incidence is increasing. The article aims to provide a short overview of the issue and increase awareness of the possible occurrence of hvKP infections.

Circulating tumor DNA as a biomarker in metastatic colorectal carcinoma case report.

INTRODUCTION: Colorectal cancer (CRC) is the third most common malignant disease worldwide. The stage of the disease at the time of diagnosis and the capture of an early recurrence have a direct impact on long-term survival. Existing control screening methods often do not reflect real-time metastatic disease. In patients with detectable circulating tumor DNA (ctDNA), liquid biopsy can be an effective monitoring tool. CASE REPORT: In 2012, we performed sigmoid resection in a 57 years old patient for advanced CRC. The follow-up assessments included: blood samples for CA 19-9 and CEA, endoscopy and imaging methods. We also sampled peripheral blood to determine the level of ctDNA. Its value corresponded to the development of the disease throughout the period. Twice it outperformed imaging methods. CEA showed some degree of unreliability, especially after prolonged illness. CA 19-9 was in the normal range at all times. CONCLUSION: Circulating tumor DNA is an effective tool in the diagnosis of recurrent metastatic CRC. In patients with detectable ctDNA, its level correlates with the tumoral mass in real time. It has a predictive value in monitoring the treatment response. Its implementation in the follow-up of patients with CRC may have an impact on the choice of treatment strategy and consequently on patient survival.

Multidisciplinary team in colorectal cancer treatment - analysis of our patients in 2017.

INTRODUCTION: Multidisciplinary teams (MDTs) have become a standard part of treating oncological patients. Based on the available data, they have lead to significantly higher survival rates in the treatment of colorectal cancer (CRC). Reported negatives include potentially longer times between diagnoses and the start of appropriate treatment, and the lack of quality controls over the MTDs actions. This report aims to assess the benefits of MDTs using our own data set for 2017. METHODS: Year 2010 saw the institution of an MDT at the Central Military University Hospital in Prague, with the obligation to refer CRC patients to the MDT before the start of treatment. Having standardized the registration, we have implemented a simple procedure to track the quality of our MDTs involvement and its patient benefits: number of patients, number of referrals with proposed diagnostic and therapeutic procedure, frequency and reason of changes to original strategies, and the frequency of variations from the MDTs conclusions. RESULTS: 405 CRC patients were referred to the MDT in 2017; we have found 499 referrals in this group. The data set was formed predominantly by men (61%), with the mean age of 63 (21-91), and the median age of 64.5 years. Surgical treatment was the most commonly proposed procedure (59%), followed by systemic treatment or, as the case may be, radiotherapy. In 24% of the cases, the conclusion did not match the originally proposed procedure. The decision not to go through with the proposed surgical treatment was the most common change (66 %). We have found a difference in the quality of referral in patients examined specifically by the referring doctor, as opposed to patients whose medical records have just been sent in. We have found therapeutic variation in the MTDs conclusions in less than 5% of patients. CONCLUSION: Having analyzed our data for CRC patients referred to the MDT in 2017, we have found out that in 24% of the patients, the MDT referral leads to a change in the originally proposed diagnostic and therapeutic procedure. Consensus among the MDTs members on the CRC patients treatment guarantees an optimum procedure. What is fundamental is that the referring doctor knows the patient. Constant tracking of the MDTs outputs forms a condition for sustaining the quality of its work and a base for assessing its benefits to the patients.

Portal vein ligation with alcohol injection - our first experiences.

INTRODUCTION: Surgical resection of colorectal liver metastases is a gold standard treatment. The indication criteria still continue expanding. The future liver remnant volume (FLRV) remains the only limiting factor of the resection. Many methods have been discussed to increase the FLRV. Injection of absolute alcohol into the portal vein seems to be one of the most effective. PATIENTS AND METHODS: In 2018 we perioperatively injected 25 ml of absolute alcohol into the ligated right portal branch in 3 patients with colorectal liver metastases at our department. All patients were indicated for second-stage right hemihepatectomy. RESULTS: The mean FLRV increase was 206.6 cm3 46 weeks after absolute alcohol injection. A transient elevation of transaminases was observed with spontaneous regression within 10 days from alcohol injection. There was no complication clearly associated with alcohol application. No liver failure was observed. No patient died. All three patients underwent second-stage right hemihepatectomy. CONCLUSION: Portal vein ligation with alcohol injection can be an uncomplicated and highly effective method to achieve FLRV hypertrophy.

[Bile leakage after liver resection: A retrospective cohort study]. / Biliární leak po jaterních resekcích: retrospektivní analýza vlastního souboru.

INTRODUCTION: Many previous reports have focused on bile leakage after liver resection. Despite the improvements in surgical techniques and perioperative care the incidence of this complication rather keeps increasing. A number of predictive factors have been analyzed. There is still no consensus regarding their influence on the formation of bile leakage. The objective of our analysis was to evaluate the incidence of bile leakage, its impact on mortality and duration of hospitalization at our department. At the same time, we conducted an analysis of known predictive factors. METHOD: The authors present a retrospective review of the set of 146 patients who underwent liver resection at the Department of Surgery of the 2nd Faculty of Medicine of the Charles University and Central Military Hospital Prague, performed between 20102013. We used the current ISGLS (International Study Group of Liver Surgery) classification to evaluate the bile leakage. The severity of this complication was determined according to the Clavien-Dindo classification system. Statistical significance of the predictive factors was determined using Fishers exact test and Students t-test. RESULTS: The incidence of bile leakage was 21%. According to ISGLS classification the A, B, and C rates were 6.5%, 61.2%, and 32.3%, respectively. The severity of bile leakage according to the Clavien-Dindo classification system - I-II, IIIa, IIIb, IV and V rates were 19.3%, 42%, 9.7%, 9.7%, and 19.3%, respectively. We determined the following predictive factors as statistically significant: surgery for malignancy (p<0.001), major hepatic resection (p=0.001), operative time (p<0.001), high intraoperative blood loss (p=0.02), construction of HJA (p=0.005), portal venous embolization/two-stage surgery (p=0.009) and ASA score (p=0.02). Bile leakage significantly prolonged hospitalization time (p<0.001). In the group of patients with bile leakage the perioperative mortality was 23 times higher (p<0.001) than in the group with no leakage. CONCLUSION: Bile leakage is one of the most serious complications of liver surgery. Most of the risk factors are not easily controllable and there is no clear consensus on their influence. Intraoperative leak tests could probably reduce the incidence of bile leakage. In the future, further studies will be required to improve the perioperative management and techniques to prevent such serious complications. Multidisciplinary approach is essential in the treatment.

["Liver fist approach" in the management of synchronous liver metastases from colorectal cancer: Preliminary non-randomized study results]. / "Liver first approach" u synchronních metastáz kolorektálního karcinomu: Predbezné výsledky nerandomizované studie.

INTRODUCTION: Liver metastases are diagnosed in 60% of patients with colorectal cancer, both at the time of diagnosis or later in the course of their management. Surgical treatment is the sole potentially curable method with 5-year overall survival of approximately 50%. However, only less than 20% of patients underwent liver resection. A joint effort of medical oncologists and surgeons is to increase the numbers of resected patients. The "liver first approach" (LFA) is one of approaches aimed at increasing resecability. The authors present their preliminary results using this method. METHODS: 102 patients were included in the multicentre study supported by the grant IGA NT 13660 Evaluation of quality of multimodal treatment for patients with colorectal cancer liver metastases - conducted at the Central Military Hospital between September 2012 and January 2015. We used LFA in 12 patients (12%). Patients were indicated for liver resection based on good response to neoadjuvant systemic therapy. Multiple bilobar liver involvement (>4 metastases) was present in 11 cases and one large solitary metastasis in the right liver lobe in one case. The primary tumor was located in the rectum in 9 patients, in the rectosigmoid in 3 patients; 3 patients had a colostomy. Others showed no signs of bowel obstruction. RESULTS: We have performed R0 resections in 11 cases, and two-stage hepatectomy with portal vein embolisation was indicated 3 times (in one case we did not finish the second stage due to quick progression after PVE). We performed major resections 7 times, along with sever extraanatomic resections, incl. 11 RFA (6 times in combination with major resections). Perioperative mortality was 0%, morbidity 33% (Dindo-Clavien >2). Ten patients underwent adjuvant chemotherapy, in 7 cases including radiotherapy of the small pelvis due to a local advanced primary tumor. Resection of the primary tumor was done in 7 patients (58%). Two patients died recently because of disease progression (17%); progression was observed in 6 patients (50%). CONCLUSION: We deem the LFA suitable especially for patients with metastatic rectal tumors where adjuvant systemic therapy can be combined with radiotherapy. The timing of the resection of the primary tumor still remains a question: it is necessary to rule out potential recurrence of liver metastases, which affected more than 50% of the patients. The benefit of LFA must be confimed by randomised studies.

[Da Vinci assisted surgery for rectal cancer - preliminary results of nonrandomized trial]. / Da Vinci asistovaná lécba karcinomu rekta - prubezné výsledky nerandomizované studie.

INTRODUCTION: The incidence of colorectal cancer (CRC) in the Czech Republic is reported to be one of the highest on the global scale. Radical tumor removal has been observed to be the most effective part in the context of current multimodal therapy. The authors present their preliminary results of robotic assisted treatment of rectal carcinoma (RC). METHOD: The observed group includes 61 patients who underwent robotic assisted treatment for rectal cancer. The data were collected prospectively in the last 31 patients. Analyses were conducted on epidemiological data, perioperative outcomes, complications and oncological results. RESULTS: Robotic assisted treatment of RC was performed in 61 patients: 34 men and 27 women, mean age of 62 years (33-80). Neoadjuvant oncological treatment was indicated in 46% of the patients. Average blood loss was 187 ml, transfusions were administered in three cases. Conversion to open procedure was performed 6 times, and 16 patients had postoperative complications. Anastomotic leak was observed in 10% of the patients, and 4 patients undewent surgical treatment. No patient died. Local recurrence of the cancer was diagnosed in 3 (5%) patients. The quality of mesorectal excision (ME) and the circumferential resection margin [(y)pCRM] have been determined in 27 patients since 2013. Positive (y)pCRM was recorded in two cases and incomplete ME was observed in 25.8% of the patients. CONCLUSION: Surgical treatment for RC is pivotal in multimodal therapy. Our preliminary results are similar to the conclusions in other published studies. The da Vinci robotic system is a safe manipulator in the treatment of RC and provides indisputable benefits to the surgeon when operating in the narrow pelvic space. However, the benefits of robotic treatment in abdominal surgery are yet to be evaluated in patients (with respect to long-term results, sufficient number of patients or a high EBM level of evidence). The high purchase price of the robotic device, individual instruments with equipment and non-systemic compensation constitute a significant hindrance that prevents wider use of the robotic system in the treatment of RC and other abdominal malignancies in the Czech Republic.

Pylephlebitis in patient with covered perforated rectosigmoid cancer.

Acute portal vein thrombosis and septic thrombophlebitis of the portal vein represent serious, although rare cases in the non-cirrhotic population. The authors present a case report, in which nonspecific clinical and CT scan findings led to the difficult diagnosis of pylephlebitis due to perforated rectosigmoid cancer.

[The benefit of the da Vinci robotic system in abdominal oncosurgery - our preliminary results]. / Prínos robotického systému da Vinci v abdominální onkochirurgii - nase predbezné výsledky.

INTRODUCTION: The robotization of minimally invasive treatment in surgery has been evident since the beginning of the third Millennium. The authors present their current evaluation of the benefits of the da Vinci robotic system in the treatment of abdominal malignancy. MATERIAL AND METHODS: The authors summarize published studies in the Medline and Pubmed databases that compare robotic, laparoscopic and open approaches in the treatment of abdominal malignancy. Epidemiological data, intraoperative blood loss, complications and oncological outcomes are monitored in a group of 30 patients with carcinoma of rectum. RESULTS: The results measured in the evaluated parameters (open conversion, perioperative and non - surgery complications, intraoperative blood loss, histological findings, lethality) are similar in the published studies, i.e. without significant differences in both groups subject to the robotic and laparoscopic treatment. The operative time in the group of robotic surgery has been is slightly longer (a non-significant difference) in most of published studies. 30 patients underwent the robotic assisted treatment of the carcinoma of the rectum (14 men and 16 women, average age of 60 years (33-80). Neoadjuvant treatment was indicated in 50% of the patients. Average blood loss was 260 ml, transfusion was administered in one case. Conversion to laparotomic treatment was performed twice, four patients had post-operative complications, no patient has died. We have not found any relapse of oncological disease in the observed set to this date. CONCLUSION: The Da Vinci robotic system is a safe manipulator in the treatment of abdominal malignancy (including HPB surgery). Randomized clinical trials (RCT) have confirmed (short-term clinical and oncological) results comparable to the laparoscopic or open approach treatment. The benefits of robotic surgery for patients in abdominal surgery (long-term results, sufficient number of patients and high-grade EBM) are yet to be evaluated, however. It is necessary to implement more randomized clinical trials going forward. Our preliminary results are similar to the results reached in other, published studies.

[Biliary complications after major liver resection]. / Biliární komplikace po velkých resekcích jater.

INTRODUCTION: Major liver resection involves operations where three or more liver segments are resected. The decrease of perioperative and early lethality enlarged indicator conditions, especially in patients with colorectal cancer liver metastasis. Bile leakage belongs to major postoperative complications. AIM: Authors present literary experience and retrospective analysis of patients with emphasis on biliary complications and their treatment. RESULTS: 96 patients underwent major hepatic resections between April 2004 and December 2009 at the Surgery Department of the Central Military Hospital in Prague. The average age of patients was 61 (25-84). Patients with an oncology disease dominated the set, representing 78% of all the patients. One half of the patients were formed by patients with colorectal cancer liver metastasis. Fourteen patients (14.6%) suffered from postoperative biliary complications. Non-surgical treatment was successful in nine cases. Surgical treatment was necessary in five cases. Combinations of these methods were essential in half of the patients. Two patients died (2.1%). CONCLUSION: Bile leakage after major liver resection is a quite common and serious postoperative complication. Conservative treatment (ERCP, CT - navigated drainage) is the method of choice. Surgical treatment is necessary where conservative management fails or where the size of the bile leakage is large. Multidisciplinary approach to treatment of these patients is essential.

[Multidisciplinary cooperation in the management of serious bleedings complicating necrotizing pancreatitis--a case review]. / Multioborová spolupráce pri osetrení závazného krvácení komplikující prubeh nekrotizující pankreatitidy--kazuistika.

Acute necrotising pancreatitis is connected with a high complication rate. The most serious ones are hemorrhagic complications with bleeding from vascular structures erosions. Authors report a case of endovascular treatment of surgically untreatable lesion of portal vein. In this case stentgraft was successfully implanted to cover the erosion and stop the bleeding. Percutaneous transhepatic route was used.

[Treatment of hepatocellular carcinoma and current situation in the Czech Republic]. / Lécba hepatocelulárního karcinomu a soucasný stav v Ceské republice.

Hepatocelullar carcinoma (HCC) is the commonest primary liver malignacy. Its incidence is increasing worldwide. In the Czech Republic, about 250 new cases are reported per year. The patient's prognosis depends on early diagnosis and initiation of a correct therapeutical procedure. During the decision making process, tumor staging, as well as the chronic liver disease stage, must be considered. Surgery, i.e. liver resection or transplantation, is the only potentially curable method. Other treatment options include chemoembolization, radiofrequency ablation, alcoholization and, currently poorly effective systemic chemotherapy. Current monitoring of the radical procedures in the Czech Republic is unsatisfactory. Although surgical treatment has been performed by many clinics, based on the available data, none of the following could be assessed: the number of surgically managed HCC patients in the Czech Republic per year, disease staging in these patients and their short-term and long-term treatment outcomes. In the Czech Republic, 45 liver transplantations have been performed, data on resection procedures are not available. The aim of the authors is to support the Central HCC Patient Registry, presented at the following website: www.koc.cz.

[Atypically localised hepatic haemangioma as a cause of dyspeptic syndrome]. / Atypicky lokalizovaný hemangiom jater jako prícina dyspeptického syndromu.

INTRODUCTION: Haemangioma is a benign mesenchymal tumor growing from the endothehum of blood vessels. Most hepatic haemangiomas are asymptomatic while symptomatic haemangioma are usually manifested by non-specific pain dyspeptic syndrome, quite rarely also by hemorrhage, or icterus Symptomatic haemangiomas or large haemangiomas with fast growth, are indicated for surgical treatment. CASE REPORT: The authors present a 50-year-old patient with chronic dyspeptic condition and pressure pain in the epigastria. USG, CT, MR, CT angiography and EUS have all shown two lesiones (haemangioma of the left hepatic lobe, a tumor in the left subphrenic area of uncertain origin). We proposed an operational solution, and, surprisingly, the finding was a single haemangioma (2 parts-- intra- and extraparenchymatous--connected by a vascular bridge). We then performed left lobectomy. DISCUSSION: In the diagnosis of haemangioma, MR is a method of choice with high specificity and sensitivity. Why did not it yield the correct diagnosis? The structure, the signal and the type of postcontrast enhancement of the second lesion corresponded to a haemangioma, but the extraparenchymatous location and also the considerable remoteness from the liver invalidated this possibility before operation. Regarding to the differential diagnostics of the lesiones in the subphrenic area, which according to the imaging techniques are not related to the hepatic parenchyma, it is advisable to consider the possibility of the incidence of pedunculated hepatic haemangioma.

[Manual and robotic laparoscopic liver resection. Two case-reviews]. / Manuální a robotická laparoskopická resekce jater. Dve kazuistiky.

INTRODUCTION: Laparoscopic resection of the liver, compared to other laparoscopic procedures of the abdominal cavity, have become used in a clinical practice only in recent years. No literature data on robotic liver resections are available. METHODS: The authors completed 2 laparoscopic resections of the liver. The first case included a 61-year old male indicated for the procedure with a low differenciated hepatocellular carcinoma lesion in SII and SIII segments, measuring 6 cm in a diameter, in a Child A cirrhotic remodellation terrain. In-line RFA-assisted and HandPort-assisted manual laparoscopic left-sided lobectomy was completed. Histological findings confirmed the diagnosis and the R0 resection. Robotic laparoscopic resection of the focal nodular hyperplasia (FNH) lesion, growing from SII and SIII segments and measuring 7x7x5 cm was completed in the other case of a 29-year old female patient. RESULTS AND CONCLUSION: Both patients healed without complications, the hospitalization lasted 8 and 7 days, respectively. HandPort-assisted manual laparoscopic resections of the left liver lobe appears a safe method. The patient may benefit from a smaller entrance into the abdominal cavity, compared with open abdominal procedures. Experience in liver and laparoscopic surgery is a prerequisite, which is also supported by literature data. A pilot study must be conducted in order to assess benefits of robotic laparoscopic liver resections.

[Robotic laparoscopic cholecystectomy]. / Robotickái laparoskopická cholecystektomie.

INTRODUCTION: Laparoscopic approach profusely utilized in many surgical fields was enhanced by da Vinci robotic surgical system in range of surgery wards, imprimis in the United States today. There was multispecialized robotic centre program initiated in the Central Military Hospital in Prague in December 2005. Within the scope of implementing the da Vinci robotic system to clinical practice we executed robotic-assisted laparoscopic cholecystectomy. METHODS: We have accomplished elective laparoscopic cholecystectomy using the da Vinci robotic surgical system. Operating working group (two doctors, two scrub nurses) had completed certificated foreign training. Both of the surgeons have many years experience of laparoscopic cholecystectomy. Operator controlled instruments from the surgeon's console, assistant placed clips on ends of cystic duct and cystic artery from auxiliary port after capnoperitoneum installation. We evacuated gallbladder in plastic bag from abdominal cavity in place of original paraumbilical port. We were exploiting three working arms in all our cases, holding surgical camera, electrocautery hook and Cadiere forceps. We had been observing procedure time, technical complications connected with robotic system, length of hospital stay and complication incidence rate. RESULTS: We managed to finish all operations in laparoscopic way. Group of our patients formed 11 male patients (35.5%) and 20 women (64.5%), mean aged 52.5 years in range of 27 77 years. The average operation procedure lasted 100 minutes, in the group of last 11 patients only 69 minutes. We recorded paraumbilical wound infections in 3 (9.7 %) patients. We had not experienced any technical problems with robotic surgical system. Length of hospital stay was 3 days. CONCLUSIONS: Considering our initial experience with robotic lasparoscopic cholecystectomy we evaluate da Vinci robotic surgical system to be safe and sophisticated operating manipulator which however does not substitute the surgeon key-role of controlling position and decision competences. Presented results of our group are comparable to conclusions of abroad published works.

1-Hydroxymethylpyrene and its sulfuric acid ester: toxicological effects in vitro and in vivo, and metabolic aspects.

1-Hydroxymethylpyrene (HMP) is activated to a potent mutagen, detectable in Salmonella typhimurium, in the presence of hepatic cytosol, cofactor for sulfotransferases, and chloride anions. The number of induced mutations is linear to the amount of cytosol used over a wide range, allowing for the quantification of this activity. The activity is expressed with high selectivity in certain tissues and cell types. In adult rats, the highest level is found in the liver, the activity in females exceeding that in males about threefold. About half of the activity in the liver of females is provided by hydroxysteroid sulfotransferase a (STa), whereas other enzymes may be more important in males on account of their very low level of STa. The expression of STa is decreased in ATPase-negative, presumably preneoplastic, hepatic foci in female rats. In contrast to its high mutagenicity in bacteria, SMP shows only weak mutagenic activity in mammalian cells (Chinese hamster V79 cells), independently of whether it is externally added, or generated from HMP within the cells by heterologously expressed STa. Sulfation, however, strongly enhances the cytotoxicity of HMP in mammalian cells. The high cytotoxicity and low mutagenicity in mammalian cells in culture have possible correlates in vivo: while HMP is only a weak initiator of ATPase-negative hepatic foci in newborn rats, it shows substantial promoting activity with regard to such foci in female, but not in male rats. We postulate that this promotion results from selective toxification by STa in the normal hepatic parenchyma of female rats, and resistance of ATPase/STa-negative foci.

Some substrates and inhibitors of cytosolic epoxide hydrolase induce sister-chromatid exchanges in mammalian cells, but do not induce gene mutations in Salmonella typhimurium and V79 cells.

Trans-stilbene oxide, trans-beta-methylstyrene 7,8-oxide, trans-beta-ethylstyrene 7,8-oxide, trans-beta-propylstyrene 7,8-oxide and 4-fluorochalcone oxide were investigated for genotoxic activity in bacterial and mammalian cells, in the absence of external xenobiotic-metabolising systems. All compounds strongly enhanced the frequency of sister-chromatid exchanges (SCE) in cultured human lymphocytes. None of them was mutagenic in Salmonella typhimurium (reversion of the his- strains TA98, TA100 and TA104). The limit of detection was 1/20,000 to 1/10(6) of the activity of the positive control, benzo[a]pyrene 4,5-oxide, depending on the compound and the bacterial strain. Trans-beta-methylstyrene 7,8-oxide and 4-fluorochalcone oxide were additionally tested for induction of SCE and gene mutations in the same target cells, namely Chinese hamster V79 cells. Their influence on the level of SCE was similar to that observed in human lymphocytes, whilst gene mutations (at the hprt locus) were not induced. The four investigated styrene oxide derivatives are known to be excellent substrates for a mammalian enzyme, cytosolic epoxide hydrolase (cEH). 4-Fluorochalcone oxide is a potent selective inhibitor of this enzyme and is structurally similar to the investigated styrene oxide derivatives. These properties of the test compounds however cannot explain the observed discrepancies in the results, since the genetic end point (SCE versus gene mutations) was decisive, and SCE were induced in cEH-proficient human lymphocytes as well as in cEH-deficient V79 cells.