Percutaneous drainage versus emergency cholecystectomy for the treatment of acute cholecystitis in critically ill patients : does it matter ?

RESUME DE THESEContexte de l'étudeLe but de cette étude est de comparer le drainage percutané (DP) et la chirurgie d'urgence (CU) de la vésicule biliaire (VB) pour le traitement de la cholécystite aiguë lithiasique/alithiasique dans un groupe homogène de patients gravement malades et hospitalisés aux soins intensifs (SI).Patients et méthodeEntre les années 2001 et 2007, tous les patients successivement traités par DP ou CU pour cholécystite aiguë aux SI ont été rétrospectivement analysés. Les cas ont été collectés à partir d'une base de données prospective. Le DP était effectué par voie trans-hépatique et la chirurgie par voie ouverte ou laparoscopique. L'état général des patients et la dysfonction des organes étaient évalués par deux scores validés (SAPS Π et SOFA, respectivement). L'analyse des données s'est portée sur les complications à court terme (morbidité, mortalité hospitalière) et à long terme (récurrence des symptômes) après drainage ou chirurgie en urgence.RésultatsQuarante-deux patients (âge médian 65 ans, 32-94 ans) ont été inclus dans l'étude ; 45% ont eu une CU (10 laparoscopics, 9 voies ouvertes) et 55% un DP (n=23) de la vésicule biliaire. Le DP et la CU ont eu des taux de succès respectifs de 91 et 100% pour la résolution du sepsis lié à la cholécystite aigiie. Après drainage et chirurgie de la VB, la dysfonction des organes secondaire au sepsis s'est résolue dans les 3 jours. Malgré le drainage, deux patients ont nécessité une cholécystectomie en urgence pour cholécystite gangréneuse. Le taux de conversion de la laparoscopic à la voie ouverte était de 20%. La morbidité majeure était de 0% après drainage et 21% après chirurgie en urgence (p=0.034). Finalement, la mortalité hospitalière était similaire (13% après DP vs. 16% après CU, p=1.0) et uniquement liée aux co-morbidités des patients. La récurrence des symptômes liés à la VB n'est apparue que chez des patients initialement drainés pour cholécystite lithiasique.ConclusionsChez les patients gravement malades des soins intensifs, le drainage percutané et la chirurgie en urgence de la VB sont tous deux efficaces pour la résolution d'un sepsis lié à une cholécystite aigiie. Cependant, la chirurgie d'urgence est associée à une morbidité majeure accrue et l'approche par laparoscopic n'est pas toujours réalisable. Le drainage percutané de la VB est donc une modalité de traitement valable, mais nécessite à distance de l'épisode aigu une cholécystectomie par laparoscopic, surtout après une cholécystite lithiasique.

Population-based analysis of 4113 patients with acute cholecystitis: defining the optimal time-point for laparoscopic cholecystectomy

Objective: To compare clinical outcomes after laparoscopic cholecystectomy (LC) for acute cholecystitis performed at various time-points after hospital admission. Background: Symptomatic gallstones represent an important public health problem with LC the treatment of choice. LC is increasingly offered for acute cholecystitis, however, the optimal time-point for LC in this setting remains a matter of debate. Methods: Analysis was based on the prospective database of the Swiss Association of Laparoscopic and Thoracoscopic Surgery and included patients undergoing emergency LC for acute cholecystitis between 1995 and 2006, grouped according to the time-points of LC since hospital admission (admission day (d0), d1, d2, d3, d4/5, d ≥6). Linear and generalized linear regression models assessed the effect of timing of LC on intra- or postoperative complications, conversion and reoperation rates and length of postoperative hospital stay. Results: Of 4113 patients, 52.8% were female, median age was 59.8 years. Delaying LC resulted in significantly higher conversion rates (from 11.9% at d0 to 27.9% at d ≥6 days after admission, P < 0.001), surgical postoperative complications (5.7% to 13%, P < 0.001) and re-operation rates (0.9% to 3%, P = 0.007), with a significantly longer postoperative hospital stay (P < 0.001). Conclusions: Delaying LC for acute cholecystitis has no advantages, resulting in significantly increased conversion/re-operation rate, postoperative complications and longer postoperative hospital stay. This investigation—one of the largest in the literature—provides compelling evidence that acute cholecystitis merits surgery within 48 hours of hospital admission if impact on the patient and health care system is to be minimized.

Acute Acalculous Cholecystitis as a Presenting Manifestation in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is known to involve the gastrointestinal tract, but gallbladder involvement is rare. The authors report the case of a 26-year-old postpartum female who presented with acute right upper quadrant abdominal pain and was diagnosed with acute acalculous cholecystitis (AAC). In the presence of concomitant features of nephritis, pericardial effusion, anaemia and positive ANA titre, the diagnosis of SLE was confirmed during hospitalisation. Histopathological analysis of the gall bladder revealed evidence of vasculitis. Although rare, AAC can be the first presentation of patients diagnosed with SLE. Prompt diagnosis and management results in a better patient outcome.

Acute Cholecystitis as a Complication After Colonoscopy: A Case Report and Literature Review

Acute cholecystitis after colonoscopy is a rare event, with less than 10 cases described in the literature. We report the case of a male patient with silent gallstones who underwent colonoscopy for follow-up of his Crohn’s disease. The colonoscopy revealed erosions in the terminal ileum, from which biopsies were taken. A sessile polyp 4 mm in diameter at the recto-sigmoid junction was also removed. Less than 24 h after the colonoscopy, the patient complained of upper right quadrant pain, nausea and vomiting. Based on the clinical findings, laboratory data and ultrasonography, we diagnosed acute cholecystitis and excluded any complication after the colonoscopy. Laparoscopic cholecystectomy was performed and the patient was discharged.

Pathogenicity of Plesiomonas shigelloides : interactions with eukaryotic host cells in vitro

Diarrhoea is one of the leading causes of morbidity and mortality in populations in developing countries and is a significant health issue throughout the world. Despite the frequency and the severity of the diarrhoeal disease, mechanisms of pathogenesis for many of the causative agents have been poorly characterised. Although implicated in a number of intestinal and extra-intestinal infections in humans, Plesiomonas shigelloides generally has been dismissed as an enteropathogen due to the lack of clearly demonstrated virulence-associated properties such as production of cytotoxins and enterotoxins or invasive abilities. However, evidence from a number of sources has indicated that this species may be the cause of a number of clinical infections. The work described in this thesis seeks to resolve this discrepancy by investigating the pathogenic potential of P. shigelloides using in vitro cell models. The focus of this research centres on how this organism interacts with human host cells in an experimental model. Very little is known about the pathogenic potential of P. shigel/oides and its mechanisms in human infections and disease. However, disease manifestations mimic those of other related microorganisms. Chapter 2 reviews microbial pathogenesis in general, with an emphasis on understanding the mechanisms resulting from infection with bacterial pathogens and the alterations in host cell biology. In addition, this review analyses the pathogenic status of a poorly-defined enteropathogen, P. shigelloides. Key stages of pathogenicity must occur in order for a bacterial pathogen to cause disease. Such stages include bacterial adherence to host tissue, bacterial entry into host tissues (usually required), multiplication within host tissues, evasion of host defence mechanisms and the causation of damage. In this study, these key strategies in infection and disease were sought to help assess the pathogenic potential of P. shigelloides (Chapter 3). Twelve isolates of P. shigelloides, obtained from clinical cases of gastroenteritis, were used to infect monolayers of human intestinal epithelial cells in vitro. Ultrastructural analysis demonstrated that P. shigelloides was able to adhere to the microvilli at the apical surface of the epithelial cells and also to the plasma membranes of both apical and basal surfaces. Furthermore, it was demonstrated that these isolates were able to enter intestinal epithelial cells. Internalised bacteria often were confined within vacuoles surrounded by single or multiple membranes. Observation of bacteria within membranebound vacuoles suggests that uptake of P. shigelloides into intestinal epithelial cells occurs via a process morphologically comparable to phagocytosis. Bacterial cells also were observed free in the host cell cytoplasm, indicating that P. shige/loides is able to escape from the surrounding vacuolar membrane and exist within the cytosol of the host. Plesiomonas shigelloides has not only been implicated in gastrointestinal infections, but also in a range of non-intestinal infections such as cholecystitis, proctitis, septicaemia and meningitis. The mechanisms by which P. shigelloides causes these infections are not understood. Previous research was unable to ascertain the pathogenic potential of P. shigel/oides using cells of non-intestinal origin (HEp-2 cells derived from a human larynx carcinoma and Hela cells derived from a cervical carcinoma). However, with the recent findings (from this study) that P. shigelloides can adhere to and enter intestinal cells, it was hypothesised, that P. shigel/oides would be able to enter Hela and HEp-2 cells. Six clinical isolates of P. shigelloides, which previously have been shown to be invasive to intestinally derived Caco-2 cells (Chapter 3) were used to study interactions with Hela and HEp-2 cells (Chapter 4). These isolates were shown to adhere to and enter both nonintestinal host cell lines. Plesiomonas shigelloides were observed within vacuoles surrounded by single and multiple membranes, as well as free in the host cell cytosol, similar to infection by P. shigelloides of Caco-2 cells. Comparisons of the number of bacteria adhered to and present intracellularly within Hela, HEp-2 and Caco-2 cells revealed a preference of P. shigelloides for Caco-2 cells. This study conclusively showed for the first time that P. shigelloides is able to enter HEp-2 and Hela cells, demonstrating the potential ability to cause an infection and/or disease of extra-intestinal sites in humans. Further high resolution ultrastructural analysis of the mechanisms involved in P. shigelloides adherence to intestinal epithelial cells (Chapter 5) revealed numerous prominent surface features which appeared to be involved in the binding of P. shige/loides to host cells. These surface structures varied in morphology from small bumps across the bacterial cell surface to much longer filaments. Evidence that flagella might play a role in bacterial adherence also was found. The hypothesis that filamentous appendages are morphologically expressed when in contact with host cells also was tested. Observations of bacteria free in the host cell cytosol suggests that P. shigelloides is able to lyse free from the initial vacuolar compartment. The vacuoles containing P. shigel/oides within host cells have not been characterised and the point at which P. shigelloides escapes from the surrounding vacuolar compartment has not been determined. A cytochemical detection assay for acid phosphatase, an enzymatic marker for lysosomes, was used to analyse the co-localisation of bacteria-containing vacuoles and acid phosphatase activity (Chapter 6). Acid phosphatase activity was not detected in these bacteria-containing vacuoles. However, the surface of many intracellular and extracellular bacteria demonstrated high levels of acid phosphatase activity, leading to the proposal of a new virulence factor for P. shigelloides. For many pathogens, the efficiency with which they adhere to and enter host cells is dependant upon the bacterial phase of growth. Such dependency reflects the timing of expression of particular virulence factors important for bacterial pathogenesis. In previous studies (Chapter 3 to Chapter 6), an overnight culture of P. shigelloides was used to investigate a number of interactions, however, it was unknown whether this allowed expression of bacterial factors to permit efficient P. shigelloides attachment and entry into human cells. In this study (Chapter 7), a number of clinical and environmental P. shigelloides isolates were investigated to determine whether adherence and entry into host cells in vitro was more efficient during exponential-phase or stationary-phase bacterial growth. An increase in the number of adherent and intracellular bacteria was demonstrated when bacteria were inoculated into host cell cultures in exponential phase cultures. This was demonstrated clearly for 3 out of 4 isolates examined. In addition, an increase in the morphological expression of filamentous appendages, a suggested virulence factor for P. shigel/oides, was observed for bacteria in exponential growth phase. These observations suggest that virulence determinants for P. shigel/oides may be more efficiently expressed when bacteria are in exponential growth phase. This study demonstrated also, for the first time, that environmental water isolates of P. shigelloides were able to adhere to and enter human intestinal cells in vitro. These isolates were seen to enter Caco-2 host cells through a process comparable to the clinical isolates examined. These findings support the hypothesis of a water transmission route for P. shigelloides infections. The results presented in this thesis contribute significantly to our understanding of the pathogenic mechanisms involved in P. shigelloides infections and disease. Several of the factors involved in P. shigelloides pathogenesis have homologues in other pathogens of the human intestine, namely Vibrio, Aeromonas, Salmonella, Shigella species and diarrhoeaassociated strains of Escherichia coli. This study emphasises the relevance of research into Plesiomonas as a means of furthering our understanding of bacterial virulence in general. As well it provides tantalising clues on normal and pathogenic host cell mechanisms.

Gastrointestinal complications after kidney transplantation

The aim of the study was to evaluate gastrointestinal (GI) complications after kidney transplantation in the Finnish population. The adult patients included underwent kidney transplantation at Helsinki University Central Hospital in 1990-2000. Data on GI complications were collected from the Finnish Kidney Transplantation Registry, patient records and from questionnaires sent to patients. Helicobacter pylori IgG and IgA antibodies were measured from 500 patients before kidney transplantation and after a median 6.8-year follow up. Oesophagogastroduodenoscopy with biopsies was performed on 46 kidney transplantation patients suffering from gastroduodenal symptoms and 43 dyspeptic controls for studies of gastroduodenal cytomegalovirus (CMV) infection. Gallbladder ultrasound was performed on 304 patients after a median of 7.4 years post transplantation. Data from these 304 patients were also collected on serum lipids, body mass index and the use of statin medication. Severe GI complications occurred in 147 (10%) of 1515 kidney transplantations, 6% of them fatal after a median of 0.93 years. 51% of the complications occurred during the first post transplantation year, with highest incidence in gastroduodenal ulcers and complications of the colon. Patients with GI complications were older and had more delayed graft function and patients with polycystic kidney disease had more GI complications than the other patients. H.pylori seropositivity rate was 31% and this had no influence on graft or patient survival. 29% of the H.pylori seropositive patients seroreverted without eradication therapy. 74% of kidney transplantation patients had CMV specific matrix protein pp65 or delayed early protein p52 positive findings in the gastroduodenal mucosa, and 53% of the pp65 or p52 positive patients had gastroduodenal erosions without H.pylori findings. After the transplantation 165 (11%) patients developed gallstones. A biliary complication including 1 fatal cholecystitis developed in 15% of the patients with gallstones. 13 (0.9%) patients had pancreatitis. Colon perforations, 31% of them fatal, occurred in 16 (1%) patients. 13 (0.9%) developed a GI malignancy during the follow up. 2 H.pylori seropositive patients developed gastroduodenal malignancies during the follow up. In conclusion, severe GI complications usually occur early after kidney transplantation. Colon perforations are especially serious in kidney transplantation patients and colon diverticulosis and gallstones should be screened and treated before transplantation. When found, H.pylori infection should also be treated in these patients.

Intrahepatic cholestasis of pregnancy : genetic background, epidemiology and hepatobiliary consequences

Intrahepatic cholestasis of pregnancy (ICP) is the most common cholestatic liver disease during pregnancy. The reported incidence varies from 0.4 to 15% of full-term pregnancies. The etiology is heterogeneous but familial clustering is known to occur. Here we have studied the genetic background, epidemiology, and long-term hepatobiliary consequences of ICP. In a register-based nation-wide study (n=1 080 310) the incidence of ICP was 0.94% during 1987-2004. A slightly higher incidence, 1.3%, was found in a hospital-based series (n=5304) among women attending the University Hospital of Helsinki in 1992-1993. Of these 16% (11/69) were familial and showed a higher (92%) recurrence rate than the sporadic (40%) cases. In the register-based epidemiological study, advanced maternal age and, to a lesser degree, parity were identified as new risk factors for ICP. The risk was 3-fold higher in women >39 years of age compared to women <30 years. Multiple pregnancy also associated with an elevated risk. In a genetic study we found no association of ICP with the genes regulating bile salt transport (ABCB4, ABCB11 and ATP8B1). The livers of postmenopausal women with a history of ICP tolerated well the short-term exposure to oral and transdermal estradiol, although the doses used were higher than those in routine clinical use. The response of serum levels of sex hormone-binding globulin (SHBG) to oral estradiol was slightly reduced in the ICP group. Transdermal estradiol had no effect on C-reactive protein (CRP) or SHBG. A number of liver and biliary diseases were found to be associated with ICP. Women with a history of ICP showed elevated risks for non-alcoholic liver cirrhosis (8.2 CI 1.9-36), cholelithiasis and cholecystitis (3.7 CI 3.2-4.2), hepatitis C (3.5 CI 1.6-7.6) and non-alcoholic pancreatitis (3.2 CI 1.7-5.7). In conclusion, ICP complicates around 1% of all full-term pregnancies in Finland and its incidence has remained unchanged since 1987. It is familial in 16% of cases with a higher recurrence rate. Although the cause remains unknown, several risk factors, namely advanced maternal age, parity and multiple pregnancies, can be identified. Both oral and transdermal regimens of postmenopausal hormone therapy (HT) are safe for women with a history of ICP when liver function is considered. Some ICP patients are at risk of other liver and biliary diseases and, contrary to what has been thought, a follow-up is warranted.

Análisis de la calidad en la atención del paciente de cirugía general de urgencia

Objetivo: proponer un instrumento para el seguimiento de la calidad de la atención de pacientes con patologías quirúrgicas abdominales urgentes. Métodos: se revisaron restropectivamente historias clínicas de pacientes quienes requirieron cirugía general de urgencia (CGU) en agosto de 2013. Se analizaron variables demográficas, factores de riesgo, severidad y desenlace hasta el día 30 postoperatorio. Se incluyeron los indicadores de calidad del National Surgical Quality Improvement Program (NSQIP) y el National Trauma Data Bank, y se adicionaron otros. Resultados: Se intervinieron 231 pacientes de 261 procedimientos de CGU. La edad promedio fue 49 años. Los procedimientos más comunes fueron la colecistectomía laparoscópica (37.2%), la apendicectomía (35.6%), la laparotomía exploratoria (12.6%), el drenaje de colección abdominal (9.1%) y la liberación de adherencias (6.9%). La mortalidad fue de 3.46% (n=8), la morbilidad severa fue de 8.04%. La duración de la hospitalización fue de 6.54 días +/- 5.180 y la de hospitalización en Unidad de Cuidado Intensivo fue de 5.7 días +/- 4.42. La oportunidad de salas de cirugía para la apendicetomía fue de 5 horas para las apendicitis con peritonitis generalizada, y de 8 horas para las apendicitis localizadas, 37 horas para colecistitis, 7.48 horas para colangitis y 2.42 horas para diverticulitis. Conclusiones: Crear de un instrumento para la medición de la calidad de la atención de los pacientes en CGU, es necesario para la autoevaluación institucional y para definir planes de mejoramiento y distribución de los recursos.

Curva de aprendizaje para ventana ecográfica de la vena cava inferior, en residentes de medicina de emergencias

INTRODUCCIÓN. El ultrasonido es fundamental en la medicina de emergencias, no se conoce cual debería ser la curva de aprendizaje para obtener las competencias técnicas y operativas; ACEP recomienda por cada ventana ecográfica realizar 25 repeticiones. No existe una curva de aprendizaje para ventana de VCI en la población de residentes colombianos. OBJETIVO: Determinar la curva de aprendizaje necesaria para obtener una proporción mayor al 80% de éxitos en la toma de la ventana ecográfica de la VCI, usando la escala de calificación para el aseguramiento de la calidad sugerida por ACEP, en residentes de I a III año de medicina de emergencias. METODOLOGÍA: Estudio experimental no comparativo, que evaluó la proporción de éxito en función del las tomas repetidas de la VCI por ultrasonido, mediciones que se tomaron luego de participar en una capacitación teórica y demostrativa de la técnica propuesta; se calificaron los videos según la escala publicada por ACEP. El análisis estadístico se realizó con un modelo logístico multinivel para la proporción del éxito, agrupado por repetición y agrupado por sujeto. RESULTADOS: Se obtuvo información de 8 residentes, cada uno realizo 25 repeticiones a 3 modelos sanos con asignación aleatoria. Se realizó la curva de aprendizaje obteniendo en 11 repeticiones una proporción de 0.80 (rango 0.54 a 0.92) y en 21 repeticiones una proporción de 0.9 (rango 0.75 a 0.96), datos ajustados por numero de repetición y residente. CONCLUSIÓN: La curva de aprendizaje para la ventana ecográfica de la VCI es de 11 y 21 repeticiones para obtener el 80% y 90% de éxito en residentes de medicina de emergencias de I a III año de la universidad del rosario.

Agonists of protease-activated receptors 1 and 2 stimulate electrolyte secretion from mouse gallbladder

Cholecystitis is one of the most common gastrointestinal diseases. Inflammation induces the activation of proteases that can signal to cells by cleaving protease-activated receptors (PARs) to induce hemostasis, inflammation, pain, and repair. However, the distribution of PARs in the gallbladder is unknown, and their effects on gallbladder function have not been fully investigated. We localized immunoreactive PAR(1) and PAR(2) to the epithelium, muscle, and serosa of mouse gallbladder. mRNA transcripts corresponding to PAR(1) and PAR(2), but not PAR(4), were detected by RT-PCR and sequencing. Addition of thrombin and a PAR(1)-selective activating peptide (TFLLRN-NH(2)) to the serosal surface of mouse gallbladder mounted in an Ussing chamber stimulated an increase in short-circuit current in wild-type but not PAR(1) knockout mice. Similarly, serosally applied trypsin and PAR(2) activating peptide (SLIGRL-NH(2)) increased short-circuit current in wild-type but not PAR(2) knockout mice. Proteases and activating peptides strongly inhibited electrogenic responses to subsequent stimulation with the same agonist, indicating homologous desensitization. Removal of HCO(3)(-) ions from the serosal buffer reduced responses to thrombin and trypsin by >80%. Agonists of PAR(1) and PAR(2) increase intracellular Ca(2+) concentration in isolated and cultured gallbladder epithelial cells. The COX-2 inhibitor meloxicam and an inhibitor of CFTR prevented the stimulatory effect of PAR(1) but not PAR(2). Thus PAR(1) and PAR(2) are expressed in the epithelium of the mouse gallbladder, and serosally applied proteases cause a HCO(3)(-) secretion. The effects of PAR(1) but not PAR(2) depend on generation of prostaglandins and activation of CFTR. These mechanisms may markedly influence fluid and electrolyte secretion of the inflamed gallbladder when multiple proteases are generated.

Management of gallstone disease in children: a new protocol based on the experience of a single center

Background/purpose: Gallstones and cholelithiasis are being increasingly diagnosed in children owing to the widespread use of ultrasonography. The treatment of choice is cholecystectomy, and routine intraoperative cholangiography is recommended to explore the common bile duct. The objectives of this study were to describe our experience with the management of gallstone disease in childhood over the last 18 years and to propose an algorithm to guide the approach to cholelithiasis in children based on clinical and ultrasonographic findings. Methods: The data for this study were obtained by reviewing the records of all patients with gallstone disease treated between January 1994 and October 2011. The patients were divided into the following 5 groups based on their symptoms: group 1, asymptomatic; group 2, nonbiliary obstructive symptoms; group 3, acute cholecystitis symptoms; group 4, a history of biliary obstructive symptoms that were completely resolved by the time of surgery; and group 5, ongoing biliary obstructive symptoms. Patients were treated according to an algorithm based on their clinical, ultrasonographic, and endoscopic retrograde cholangiopancreatography (ERCP) findings. Results: A total of 223 patients were diagnosed with cholelithiasis, and comorbidities were present in 177 patients (79.3%). The most common comorbidities were hemolytic disorders in 139 patients (62.3%) and previous bariatric surgery in 16 (7.1%). Although symptoms were present in 134 patients (60.0%), cholecystectomy was performed for all patients with cholelithiasis, even if they were asymptomatic; the surgery was laparoscopic in 204 patients and open in 19. Fifty-six patients (25.1%) presented with complications as the first sign of cholelithiasis (eg, pancreatitis, choledocolithiasis, or acute calculous cholecystitis). Intraoperative cholangiography was indicated in 15 children, and it was positive in only 1 (0.4%) for whom ERCP was necessary to extract the stone after a laparoscopic cholecystectomy (LC). Preoperative ERCP was performed in 11 patients to extract the stones, and a hepaticojejunostomy was indicated in 2 patients. There were no injuries to the hepatic artery or common bile duct in our series. Conclusions: Based on our experience, we can propose an algorithm to guide the approach to cholelithiasis in the pediatric population. The final conclusion is that LC results in limited postoperative complications in children with gallstones. When a diagnosis of choledocolithiasis or dilation of the choledocus is made, ERCP is necessary if obstructive symptoms persist either before or after an LC. Intraoperative cholangiography and laparoscopic common bile duct exploration are not mandatory. Published by Elsevier Inc.

Biliary diseases in heart transplanted patients: a comparison between cyclosporine A versus tacrolimus-based immunosuppression

A cyclosporine (CsA)-based immunosuppression is associated with an increased incidence of cholelithiasis after heart transplantation. It is not known if tacrolimus (Tac) has comparable biliary side effects in humans. We evaluated the incidence of gallbladder sludge and cholelithiasis under Tac-based immunosuppression by ultrasound examinations in 31 cardiac transplants (25 male, 6 female, mean age: 59 ' 11 years). Data were compared to 57 patients (47 male, 10 female, mean age: 58 ' 11 years) who received CsA-based immunosuppression. 6 patients receiving Tac and 6 patients receiving CsA had already gallstones prior to transplantation so that finally 25 patients of the Tac group and 51 patients of the CsA group could be evaluated. In the Tac group the incidence of biliary sludge was 4% (1 of 25), of gallstones 28% (7 of 25). In comparison, patients receiving CsA developed biliary sludge in also 4% (2 of 51) and gallstones in 25% (13 of 51). Nine of 42 males in the CsA group (21%) and eight of 20 males in the Tac group (40%) developed either gallstones or sludge (n.s). Six of nine females in the CsA group (67%), but none of five females in the Tac group (0%) developed either gallstones or sludge (p = 0.01). In summary, the incidence of biliary disease in patients with Tac is comparable with CsA-based immunosuppression. We recommend regular sonographical examinations to detect biliary diseases as early as possible. In cases of clinically, laboratory and sonographical signs of cholecystitis cholecystectomy is indicated. It seems that towards lithogenicity female patients benefit more from a Tac-based treatment because the occurrence of gallstones is rare.