Saturable elimination of piperacillin in critically ill patients: implications for continuous infusion.

The study aimed to evaluate saturation of piperacillin elimination in critically ill adult patients. Seventeen critically ill adult patients received continuous and intermittent infusion of piperacillin/tazobactam. Piperacillin plasma concentrations (n = 217) were analysed using population pharmacokinetic (PopPK) modelling. Post-hoc simulations were performed to evaluate the type I error rate associated with the study. Unseen data were used to validate the final model. The mean error (ME) and root mean square error (RMSE) were calculated as a measure of bias and imprecision, respectively. A PopPK model with parallel linear and non-linear elimination best fitted the data. The median and 95% confidence interval (CI) for the model parameters drug clearance (CL), volume of central compartment (V), volume of peripheral compartment (Vp) and intercompartmental clearance (Q) were 9 (7.69-11) L/h, 6.18 (4.93-11.2) L, 11.17 (7.26-12) L and 15.61 (12.66-23.8) L/h, respectively. The Michaelis-Menten constant (Km) and the maximum elimination rate for Michaelis-Menten elimination (Vmax) were estimated without population variability in the model to avoid overfitting and inflation of the type I error rate. The population estimates for Km and Vmax were 37.09 mg/L and 353.57 mg/h, respectively. The bias (ME) was -20.8 (95% CI -26.2 to -15.4) mg/L, whilst imprecision (RMSE) was 49.2 (95% CI 41.2-56) mg/L. In conclusion, piperacillin elimination is (partially) saturable. Moreover, the population estimate for Km lies within the therapeutic window and therefore saturation of elimination should be accounted for when defining optimum dosing regimens for piperacillin in critically ill patients.

Measuring antibiotics in exhaled air in critically ill, non-ventilated patients: A feasibility and proof of concept study.

PURPOSE: Measurement of antibiotic concentrations is increasingly used to optimize antibiotic therapy. Plasma samples are typically used for this, but other matrices such as exhaled air could be an alternative. MATERIALS AND METHODS: We studied 11 spontaneously breathing intensive care unit patients receiving either piperacillin/tazobactam or meropenem. Patients exhaled in the ExaBreath® device, from which the antibiotic was extracted. The presence of antibiotics was also determined in the condensate found in the device and in the plasma. RESULTS: Piperacillin or meropenem could be detected in the filter in 9 patients and in the condensate in 10. Seven patients completed the procedure as prescribed. In these patients the median quantity of piperacillin in the filter was 3083 pg/filter (range 988-203,895 pg/filter), and 45 pg (range 6-126 pg) in the condensate; meropenem quantity was 21,168 pg/filter, but the quantity in the condensate was below the lower limit of quantification. There was no correlation between the concentrations in the plasma and quantities detected in the filter or condensate. CONCLUSIONS: Piperacillin and meropenem can be detected and quantified in exhaled air of non-ventilated intensive care unit patients; these quantities did not correlate with plasma concentrations of these drugs.

[A rare cause of cryptorchidism, the persistence of müllerian ducts syndrome]. / Une cause rare de cryptorchidie le syndrome de persistance des structures müllériennes.

The Persistent Müllerian Ducts Syndrome (PMDS) is a rare congenital syndrome. It is one of abnormalities of genito-sexual development that is found on the normally virilized boy (46XY). It is characterized by the development of both Wolf structures and Müller duct. The pathophysiology can be explained by an action deficit of the anti-müllerian hormone (AMH). Its clinical presentations vary depending on the localization of the testis and the associated symptoms. Its discovery is mostly fortuitous and generally made in per-operative surgery of cryptorchidism or inguinal hernia. Treatment should be surgical. It relies on two aspects : ensuring the testicular descent and performing the excision of the müllerian duct. The follow-up is identical to the cryptorchid testes and the fertility problems will be influenced by the surgical procedure as well as the timing of the treatment.

Le syndrome de persistance des canaux mullériens (PMDS) est un syndrome congénital rare donnant des anomalies du développement génito-sexuel chez le garçon normalement virilisé (46XY). Il se caractérise par le développement à la fois des structures de Wolf et des canaux de Müller. Sa physiopathologie s'explique par un défaut d'action de l'hormone anti-müllérienne (AMH). Il existe différentes présentations cliniques qui varient en fonction de la localisation du testicule et des symptômes associés. Sa découverte est fortuite et généralement faite en per-opératoire d'une chirurgie de cryptorchidie ou d'hernie inguinale. Le traitement doit être chirurgical. Il repose sur deux aspects : assurer la descente testiculaire et réaliser l'exérèse des canaux müllériens. Le suivi est identique à celui d'un testicule cryptorchide et le risque de trouble de la fertilité varie en fonction de l'âge de prise en charge et du geste chirurgical.

Hair cortisol in relation to job stress and depressive symptoms.

BACKGROUND: Measurement of hair cortisol concentration (HCC) may be used as a biomarker for chronic stress. However, the association between stress and HCC has rarely been investigated in a working population. AIMS: To explore associations between (i) HCC and various stress measures and (ii) HCC and symptoms of depression in Belgian workers. METHODS: Hair samples were collected from workers in two production companies and cortisol content was determined by liquid chromatography tandem mass spectrometry. Participants completed a questionnaire including socio-demographics, health behaviours and standardized measures for assessing stress. RESULTS: After excluding those workers suffering from a psychiatric or neuroendocrine disease and those treated with glucocorticoids, there were a total of 102 workers with both questionnaire, cortisol results and anthropometric measures. Median HCC was 5.73 pg/mg hair (interquartile range = 4.52-9.06). No significant associations were found between cortisol and the standardized measures related to several work psychosocial risk factors. A significantly lower mean HCC was found in shift workers compared with dayworkers, adjusted for age. Additionally, a significant higher mean HCC was found in workers with symptoms of depression compared with those without symptoms of depression, after adjustment for age. CONCLUSIONS: HCC showed a limited applicability as a biomarker for job stress in this sample, although the results suggest this method may be a suitable marker for detecting early symptoms of depression. Further research is needed to investigate the applicability of HCC in the working environment and within job stress research.

How appropriate is therapeutic drug monitoring for lithium? Data from the Belgian external quality assessment scheme.

BACKGROUND: Lithium remains a mainstay in the management of mood disorders. As with many psychotropic drugs, lithium treatment requires continuous observation for adverse effects and strict monitoring of serum concentrations. The present study aimed to assess the appropriateness of lithium assays used by Belgian laboratories, and to evaluate acceptability of their clinical interpretations. METHODS: Nine in-house serum samples spiked with predetermined concentrations of lithium were distributed to 114 participants in the Belgian external quality assessment scheme. Laboratories were requested to report the assay technique, lithium measurements and interpretations with regard to measured concentrations. Inter/intramethod imprecision and bias were reported and acceptability of clinical interpretations was assessed. The intramethod variability was evaluated by selecting methods used by 6 laboratories or more. Flame photometry (IL 943) was considered as the reference method. RESULTS: Laboratories returned assay results using colorimetry (69.3%), ion selective electrode (15.8%), flame photometry (8.8%), atomic absorption spectroscopy (5.2%) or mass spectrometry (0.9%). Lithium concentrations were systematically higher when measured with the Vitros assay (median bias: 4.0%), and were associated with consecutive biased interpretations. In contrast, the Thermo Scientific Infinity assay showed a significant negative bias (median bias: 9.4%). 36.0% of laboratories reported numerical values below their manufacturer cut-off for the blank sample; 16.6% of these laboratories detected residual lithium concentrations. CONCLUSIONS: The present study revealed assay-related differences in lithium measurements and their interpretations. Overall, there appeared to be a need to continue EQA of therapeutic drug monitoring for lithium in Belgium.

Roadside drug testing: comparison of two legal approaches in Belgium.

BACKGROUND: Internationally, urine on-site testing has been used for detecting drivers under the influence of drugs (DUID) but more and more countries, such as Belgium, are switching to oral fluid screening. OBJECTIVE: To compare the previous (published in 1999) and current (published 2009) enforcement procedures of DUID in Belgium. The two evaluated procedures differ in the way the drivers are screened by the police (signs of impairment versus signs of recent drug use), the matrix for screening (urine versus oral fluid) and the analytical cut-off concentrations in plasma. METHODS: Data on positive screening and confirmation results were gathered from 1st April 2008 to 30th September 2010, when urine screening (Dipro Druglab panels test) was performed; and from 1st October 2010 to 31st March 2013, when an on-site oral fluid test (Securetec Drugwipe 5(+)) was used. RESULTS: Approximately 4100 data sets related to urine screening and 3900 data sets related to oral fluid screening were studied. Eighty-eight percent of positive urine on-site tests yielded positive results in plasma for cannabis, 21% for cocaine, 20% for amphetamines and 7% for opiates. Sixty-six percent of the positive oral fluid on-site tests yielded positive results in plasma for cannabis, 30% for cocaine, 28% for amphetamines and 8% for opiates. For cannabis, opiates and amphetamines more negative results in plasma were observed in the period of urine screening. CONCLUSIONS: The percentage of plasma samples of tested drivers, in which none of the positive screened target drugs were present in a concentration above the legal cut-off value, has decreased from 17% to 8% since the introduction of the current legislation involving oral fluid screening.

Stability of generic brands of meropenem reconstituted in isotonic saline.

BACKGROUND: Meropenem is a relatively unstable compound when dissolved. Currently, all available data have been derived from tests on the original product from Astrazeneca, and it is unsure if these data can be extrapolated to the stability of other commercially available vials. The aim of this study was therefore to assess the stability of four different brands of meropenem to be used as a prolonged or continuous infusion. METHODS: Commercially available meropenem vials were reconstituted and mixed with 0.9% sodium chloride to produce solutions with concentrations of 10.20 and 40 mg/mL in polypropylene syringes, which were kept at 25 °C. Samples were taken immediately after preparation and up to 12 hours. Solutions retaining >90% of the initial concentration were considered stable. RESULTS: The stability was concentration-dependent. At 25 °C, all 10 and 20 mg/mL solutions were stable for 12 hours in 0.9% sodium chloride, while the 40 mg/mL solutions were stable for a maximum of 8 hours. Stability of the different vials of meropenem was comparable for the time period tested (related samples Friedman's two way of analysis of variance by ranks, P=0.282). CONCLUSION: All tested commercially available vials of meropenem in a concentration of 10 and 20 mg/mL were stable for 12 hours at 25 °C when diluted in 0.9% sodium chloride. The 40 mg/mL solutions were stable for a maximum of 8 hours. This report is the first to show equivalent stability between different commercially available vials of meropenem.

Investigation of urinary excretion of hydroxyethyl starch and dextran by uhplc-hrms in different acquisition modes.

Plasma volume expanders (PVEs) such as hydroxyethyl starch (HES) and dextran are misused in sports because they can prevent dehydration and reduce haematocrit values to mask erythropoietin abuse. Endogenous hydrolysis generates multiple HES and dextran oligosaccharides which are excreted in urine. Composition of the urinary metabolic profiles of PVEs varies depending on post-administration time and can have an impact on their detectability. In this work, different mass spectrometry data acquisition modes (full scan with and without in-source collision-induced dissociation) were used to study urinary excretion profiles of HES and dextran, particularly by investigating time-dependent detectability of HES and dextran urinary oligosaccharide metabolites in post-administration samples. In-source fragmentation yielded the best results in terms of limit of detection (LOD) and detection times, whereas detection of HES and dextran metabolites in full scan mode with no in-source fragmentation is related to recent administration (< 24 hours). Urinary excretion studies showed detection windows for HES and dextran respectively of 72 and 48 hours after administration. Dextran concentrations were above the previously proposed threshold of 500 µg · mL(-1) for 12 hours. A "dilute-and-shoot" method for the detection of HES and dextran in human urine by ultra-high-pressure liquid chromatography-electrospray ionization-high resolution Orbitrap™ mass spectrometry was developed for this study. Validation of the method showed an LOD in the range of 10-500 µg · mL(-1) for the most significant HES and dextran metabolites in the different modes. The method allows retrospective data analysis and can be implemented in existing high-resolution mass spectrometry-based doping control screening analysis.

Therapeutic drug monitoring-based dose optimisation of piperacillin and meropenem: a randomised controlled trial.

PURPOSE: There is variability in the pharmacokinetics (PK) of antibiotics (AB) in critically ill patients. Therapeutic drug monitoring (TDM) could overcome this variability and increase PK target attainment. The objective of this study was to analyse the effect of a dose-adaption strategy based on daily TDM on target attainment. METHODS: This was a prospective, partially blinded, and randomised controlled trial in patients with normal kidney function treated with meropenem (MEM) or piperacillin/tazobactam (PTZ). The intervention group underwent daily TDM, with dose adjustment when necessary. The predefined PK/pharmacodynamic (PK/PD) target was 100% fT>4MIC [percentage of time during a dosing interval that the free (f) drug concentration exceeded 4 times the MIC]. The control group received conventional treatment. The primary endpoint was the proportion of patients that reached 100% fT>4MIC and 100 % fT>MIC at 72 h. RESULTS: Forty-one patients (median age 56 years) were included in the study. Pneumonia was the primary infectious diagnosis. At baseline, 100% fT>4MIC was achieved in 21% of the PTZ patients and in none of the MEM patients; 100% fT>MIC was achieved in 71% of the PTZ patients and 46 % of the MEM patients. Of the patients in the intervention group, 76 % needed dose adaptation, and five required an additional increase. At 72 h, target attainment rates for 100% fT>4MIC and 100% fT>MIC were higher in the intervention group: 58 vs. 16%, p = 0.007 and 95 vs. 68%, p = 0.045, respectively. CONCLUSIONS: Among critically ill patients with normal kidney function, a strategy of dose adaptation based on daily TDM led to an increase in PK/PD target attainment compared to conventional dosing.

Methadone-related fatalities: review in the Ghent district between 1978-2008.

Previous research demonstrated that Methadone Maintenance Programs (MMP) and Methadone Maintenance Treatment/Therapy (MMT) could significantly reduce the mortality risk. However, in current forensic practice, methadone ingestion can still directly or indirectly be involved in fatalities. The objectives of this study were twofold. Firstly, referring to the wide range of blood levels reported in methadone-related fatalities, we aimed to provide insight into the interpretation of a quantitative post-mortem blood concentration. Secondly, to examine and discuss possible causes, mechanisms and manners of death. During a 30-year-period, all medico-legal files at the Department of Forensic Medicine (Ghent University) were searched through, to investigate whether methadone was involved in the fatal outcome. A significant increase in the methadone-related fatalities was found since 1995, which has also been noticed in other studies. In our study (n=48), the most frequent cause of death was intoxication: only one was due to a pure methadone intoxication, whereas in all other fatal intoxications, a poly-drug intoxication was found. In this study, cardiopulmonary failure, induced by depression of the vital centres in the brainstem, was--as expected--the most important mechanism of death. When we considered the post-mortem blood levels in our study group, we observed a wide range, namely between 0.10 and 4.13 microg/ml (median: 0.54 microg/ml, mean: 0.81 microg/ml, SD: 0.14). This was in line with previous reports, although the extreme values differed. We conclude that the interpretation of post-mortem methadone blood levels is still hazardous due to e.g. difficulties to assess the individual tolerance level, the variety of surviving periods after ingestion, interfering post-mortem redistribution and the combined ingestion of methadone with other drugs. Therefore, a close collaboration between the forensic pathologist and toxicologist is recommended in order to provide a well-grounded conclusion.

[Illicit drugs, medications and traffic accidents]. / Drogues, médicaments et accidentologie.

The European Union (EU) has 25 member-states and 455 million inhabitants. Statistics on traffic accidents in the EU show that more than 45,000 people are killed annually, including 5200 in France. At the same time, nearly two million persons in the EU require medical treatment for traffic-accident-related injuries, including 109,000 in France. In addition, traffic accidents are the major cause of death of those individuals aged 15 to 24 years. One third of the EU inhabitants will be hospitalized during their life due to a traffic accident with a cost over 160 billion euro (2-3% of the Gross Domestic Product). An important contributing factor to crashes is the use of alcohol and/or illicit drugs or medication when driving, as they exert negative effects on cognition and psychomotor functions. For illicit drugs, abuse of cannabis with or without alcohol is a major concern for the EU. In fact, three million Europeans use cannabis daily and 80% of them drive after use. A number of French studies since 1999 have underlined the high prevalence of cannabis found in the blood of injured or killed drivers. From medical or judicial observations, it is clear that cannabis use increases the risk of traffic accidents. Many groups outside Europe have also shown the association between drug abuse and crashes. The number of casualties related to certain medicines, especially benzodiazepines remains at a high level, particularly in the elderly. In many countries the prevalence of medicinal drugs associated with car accidents is higher than with cannabis. Annex III of the European Union Council Directive of July the 29th 1991 in fact states that a driving license should not be issued to or renewed for applicants or drivers who are dependent on psychotropic substances or use them regularly. Recently, France has categorized the medicinal drugs available in the country by using three pictograms: level one yellow, "be careful"; level two orange, "be very careful"; level three red, "don't drive". It is an important campaign that increases awareness among the public and the medical professionals about the potential dangerous effects of medicinal drugs when driving. The EU objective of reducing the number of fatalities to 25,000 by 2010 will require strengthening measures against the use of alcohol, illicit and medicinal drugs by not well-informed drivers. It is not only a really great challenge, but also a significant investment towards improving public health in France as well as in Europe.

[Cannabis and driving: the situation in Europe]. / Cannabis et conduite automobile: la situation en Europe.

In Europe, three million people consume cannabis every day. Investigations showed that more than two thirds of drug users drive after having smoked cannabis. Epidemiological studies show that between 0.5% and 8.2% of the general driving population is positive for cannabis. For drivers wounded or deceased as a result of an accident, the percentage varies respectively from 3.3% to 10% and from 2.2% to 8.4%. Finally, very high percentages are found in the studies which analysed the presence of drugs in drivers suspected of driving under the influence of drugs: more than 50% in Austria, Belgium, Germany, Switzerland and the United Kingdom. Six European countries adopted an analytical or 'per se' legislation and the cut-offs vary between 0.3 and 2 ng/mL THC. In the Netherlands, experimental studies carried out after administration of cannabis clearly showed the impairing effects, in particular in the event of simultaneous consumption of cannabis and alcohol. Various research projects financed by the European Union studied the epidemiologic aspects (IMMORTAL), detection by psychotechnical tests (CERTIFIED) and roadside drug detection (ROSITA and ROSITA-2).

[Use of gamma-hydroxybutyric acid (GHB) at rave parties and in date rape in France: myth of reality?]. / Utilisation de l'acide gamma-hydroxybutyrique (GHB) dans les rave-parties et pour la soumission chimique en France: mythe ou réalité?

Since many years gamma-hydroxybutyric acid (GHB) is presented as very popular in rave-parties and for bodybuilders. It seems to be a controversy between media coverage and the results of toxicological analysis done in high-level laboratories. In order to clarify this problem, we compiled the data of 6 laboratories. They used the same analytical method by GC/MS. Depending the laboratory, the limit of detection was 1-2 micrograms/mL and the limit of quantification was 2.5-5 micrograms/mL. Two labs where looking for GHB in each forensic case (100 and 150 cases a year). Others labs performed GHB analysis only on specific request (each 10 cases a year). Mean time between ingestion of GHB and blood/urine sampling was 12-48 h. Mean time between sampling and analysis was much higher (a few hours to a few month. All samples were stored at +4 degrees C. Only 3 cases were considered as positive (blood GHB: 165, 132 and 114 micrograms/mL, urine GHB: 7450 and 436 micrograms/mL) They were admitted in an hospital EU. Interpreting results remains very difficult because GHB is endogenous, present in blood and urine, and its half-life is very short. One has to report only "positive" GHB results when amounts are higher than 5 micrograms/mL in blood and 10 micrograms/mL in urine. Obviously, forensic toxicologists have to play a very important part in diagnosis of GHB intoxications and estimating its frequency. Actually, because the lack of data in France, it is not possible to answer the question asked in the title of this paper.

Utilisation de l'acide gamma-hydroxybutyrique (ghb) dans les rave-parties et pour la soumission chimique en france : mythe ou réalité?

Since many years gamma-hydroxybutyric acid (GHB) is presented as very popular in rave-parties and for bodybuilders. It seems to be a controversy between media coverage and the results of toxicological analysis done in high-level laboratories. In order to clarify this problem, we compiled the data of 6 laboratories. They used the same analytical method by GC/MS. Depending the laboratory, the limit of detection was 1-2 µg/mL and the limit of quantification was 2.5-5 µg/ mL. Two labs where looking for GHB in each forensic case (100 and 150 cases a year). Others labs performed GHB analysis only on specific request (each 10 cases a year). Mean time between ingestion of GHB and blood/urine sampling was 12-48 h. Mean time between sampling and analysis was much higher (a few hours to a few month. All samples were stored at +4°C. Only 3 cases were considered as positive (blood GHB : 165, 132 and 114 µg/mL, urine GHB : 7450 and 436 µg/ mL) They were admitted in an hospital EU. Interpreting results remains very difficult because GHB is endogenous, present in blood and urine, and its half-life is very short. One has to report only « positive ¼ GHB results when amounts are higher than 5 µg/mL in blood and 10 µg/mL in urine. Obviously, forensic toxicologists have to play a very important part in diagnosis of GHB intoxications and estimating its frequency. Actually, because the lack of data in France, it is not possible to answer the question asked in the title of this paper.

Workplace drug testing in Europe.

Not much information is available on workplace drug testing (WDT) in Europe. There is no specific legislation and there are no generally accepted guidelines. Many companies establish a drug policy with little or no provisions for drug testing. Often, testing is performed on-site by occupational physicians, with little or no quality control, no systematic confirmation of positives, no chain of custody and no adulteration testing. In some parts of Europe, e.g. in the United Kingdom and some Scandinavian countries, WDT is increasing in importance, but it is not as widespread as in USA. The most frequently performed tests are amphetamines, cannabinoids, cocaine, opiates and alcohol. The percentage of positives is variable, but seems to decrease with the years following the introduction of WDT. Cannabis is the drug that is most frequently found.Recently, the European Workplace Drug Testing Society (EWDTS) was founded, with the aims to ensure that WDT in Europe is performed to a defined quality standard and in a legally secured way and to provide an independent forum for all aspects of WDT.A working group in the United Kingdom has recently finalised the United Kingdom laboratory guidelines for legally defensible WDT and discussions are under way with the EWDTS to establish common guidelines. Many efforts will be needed to establish WDT as an accepted part of a company policy on drugs: establishing and maintaining the confidence in the results of the laboratory, establishing the legal status of WDT, preserving the privacy and rights of the employees, proving the cost-effectiveness of WDT in a European context, finding a balance between strict guidelines and enough flexibility to tailor testing to the changing needs. It is hoped that the exchange of experience between different countries will contribute to reaching these goals.

Quantification of the size of primary spontaneous pneumothorax: accuracy of the Light index.

BACKGROUND: The size of a pneumothorax (PTX) is usually estimated by the Light index. Treatment strategies of (primary, spontaneous) PTX partially depend upon the size of the PTX. To our knowledge, the Light index has not yet been correlated with the actual volume of the PTX. OBJECTIVES: To correlate the estimated size of a primary spontaneous PTX by means of the Light index, with the actual amount of air present in the pleural space. METHODS: Actual PTX volumes were measured by means of manual aspiration of air present in the pleural space in 18 patients with primary spontaneous PTX and correlated with the size estimation obtained by the Light index. RESULTS: Light index and volume measurements were strongly correlated (r = 0.84, p < 0.0001). CONCLUSIONS: The Light index is a good estimate of the actual size of a (primary spontaneous) PTX.

Influence of preoperative combined radiochemotherapy on surgical outcome and colonic anastomotic healing: experimental study in the rat.

PURPOSE: To study the influence of combined preoperative hyperfractionated irradiation with intraperitoneal 5-fluorouracil (5-FU) on surgical outcome and colonic anastomotic healing in a rat model. METHODS: Male Wistar rats were given 41.6 Gy of preoperative radiotherapy (RT) or sham irradiation, with intraperitoneal 5-FU at low dose (10 mg/kg) or high dose (20 mg/kg). Animals were arranged in 6 groups: RT + low-dose 5-FU (RCT-L), RT + high-dose 5-FU (RCT-H), sham RT + low-dose 5-FU (CT-L), sham RT + high-dose 5-FU (CT-H), RT alone (R), and a control group (sham RT + intraperitoneal saline). Side-to-side colonic anastomoses were constructed from one irradiated and one nonirradiated limb 4 days after radiochemotherapy. Animals were sacrificed 10 days after surgery. RESULTS: Compared to controls, more complications occurred in group RCT-H (50% versus 0%, p = 0.01). Adhesion formation was more intense in groups RCT-H and CT-H (p < 0.001 and p = 0.001, respectively). After therapy, white blood cell counts dropped significantly in all irradiated animals (p < 0.01), and platelet counts decreased significantly in group RCT-H (p = 0.01). No significant differences were noticed in anastomotic bursting pressure when the treated groups were compared to each other or to the control group. CONCLUSIONS: Neoadjuvant radiochemotherapy has no adverse effect on the strength of colonic anastomosis in this rat model. However, the combined RT with high-dose 5-FU does increase operative morbidity and adhesion formation.