A profile of spatial abilities in people with Down syndrome.

BACKGROUND: Spatial abilities are fundamental cognitive abilities, have direct applications in daily life, serve as a cognitive foundation for many other complex skills and are used in many specialty jobs. The current study aimed to systematically and comprehensively evaluate the spatial abilities of individuals with Down syndrome (DS) relative to mental ability-matched typically developing (TD) children based on Newcombe and Shipley's double-dimension theoretical framework for classifying spatial abilities. METHODS: Forty adolescents and young adults with DS and 40 TD children completed a nonverbal intelligence test (Raven's), two measures of static-extrinsic skills (water-level task and cart task), two measures of static-intrinsic skills (figure ground and form completion), two measures of dynamic-extrinsic skills (three mountains task and dog task) and two measures of dynamic-intrinsic spatial skills (mental rotation task and block design task). RESULTS: Participants with DS showed reduced performance on two dynamic-intrinsic tasks and one static-extrinsic task (i.e. cart task) relative to TD children. Performances were similar in two dynamic-extrinsic tasks and two static-intrinsic tasks. Analyses of composite accuracy for each spatial category further confirmed deficits in dynamic-intrinsic and static-extrinsic categories for people with DS relative to TD children. CONCLUSIONS: Our results showed an uneven profile of spatial abilities in people with DS relative to ability-matched TD children with particular weaknesses in comprehending and manipulating dynamic-intrinsic and static-extrinsic spatial relations. Furthermore, our research has important clinical implications for more targeted interventions to improve spatial abilities in people with DS.

[Pharmaceutical care in a visceral surgical ward]. / Pharmazeutische Betreuung einer viszeralchirurgischen Station.

BACKGROUND: Medication errors and subsequent drug-related problems (DRPs) result from lack of sufficient information during the prescribing step. The objectives of this study were to evaluate the contribution of having a pharmacist participate in clinical routine on a surgical unit by studying DRPs, and the classification of DRPs in the Pharmaceutical Care Network Europe (PCNE) system. MATERIALS AND METHODS: The pharmacotherapy of all patients of a visceral surgical ward was evaluated by a pharmacist in a prospective study design over a six-month period. The identified DRPs were classified using the PCNE system. RESULTS: In 29 131 prescription lines, 697 DRPs were registered. This corresponds to a mean intervention rate of 2.4 %. All DRPs were classified into the modified PCNE system with 910 causes and 1 148 interventions. The most frequent DRPs were "lack of home medication" (35.6 %), drug dosing problems (18.6 %), the inappropriate duplication of drugs of the same therapeutic group (6.7 %) and drug interactions (6.5 %). 78.6 % vs. 3.7 % of all registered DRPs were completely vs. near completely resolved by pharmacist. CONCLUSIONS: We consider the PCNE system with the four-level of classification to be a practical and easy-to-use tool in the daily hospital setting. Although we did not notice clinically relevant impairments of patient safety, a pharmacist may support the drug therapy and improve patient safety in clinics supporting the free choice of the drug therapy by the physician.

Age- and sex-standardised prevalence rates of fatigue in a large hospital-based sample of cancer patients.

BACKGROUND: The aim of this longitudinal study was to determine age- and sex-standardised prevalence rates of cancer-related fatigue in different groups of patients. METHODS: This was a prospective study in a cohort of N=1494 cancer patients investigating fatigue at three time points t1-t3 (t1: admission to hospital, t2: discharge, t3: half a year after t1). Fatigue was measured with the Multidimensional Fatigue Inventory. Age- and sex-adjusted norms were derived from a representative community sample of N=2037, using a cutoff at the 75th percentile. RESULTS: At admission to the hospital, 32% of the patients were classified as fatigued. At discharge, the overall prevalence rate was 40%, and at half a year after t1, prevalence was 34%. Fatigue prevalence rates differed according to tumour stage, site, age, and sex of the patients. CONCLUSION: The prevalence rates provided by this study can be used for the planning of research and clinical routine.

Kidney transplant from the same donor without maintenance immunosuppression after previous hematopoietic stem cell transplant.

In January 2005, an 18-year-old male patient with acute myeloid leukemia (AML) received a haploidentical hematopoietic stem cell transplantation (HSCT) from his father. He developed hemolytic uremic syndrome and end-stage renal disease (ESRD) requiring hemodialysis on day 357 after HSCT. On day 1020 after HSCT, a living kidney donation from the stem cell donor was carried out. The creatinine before kidney transplantation (KT) was ≈450 µmol/L, 268 µmol/L on day 2 after KT, 88 µM on day 38 and 89 µmol/L on day 960 (day 1980 after HSCT). Immunosuppression was gradually discontinued: cortisone on day 28, tacrolimus on day 32 and MMF on day 100 after KT (day 1120 after HSCT). As of June 2010, 66 months after HSCT and 32 months after KT, the patient has had neither rejection episodes nor clinical manifestations of transplantation-related complications. The patient reached 100% hematopoietic donor chimerism prekidney transplant and retained this state postkidney transplant. This unique case is the first report of a successful kidney transplant without immunosuppression after HSCT from the same haploidentical donor.

Anxiety and depression in cancer patients compared with the general population.

The objective of this study was to compare the prevalence of anxiety and depression in cancer patients with the prevalence found in the general population, using the Hospital Anxiety and Depression Scale (HADS). Participants were 1529 cancer patients treated between 2002 and 2004 in Germany and 2037 persons from the German general population. In the cancer patients, the risk of psychiatric distress was nearly twice that of the general population. While for older age groups (61 years and above) there were only small differences between cancer patients and the general population, the differences in both scales were high for young persons. There were differences between the HADS mean scores of the patients with different tumour localisations, with high values for brain cancer and low scores for prostate cancer. The influence of the tumour stage on anxiety and depression was weak. However, depression scores of patients with a survival time less than 1 year were elevated. The results show that large sample sizes are necessary to evaluate the psychological situation of cancer patients, and that age and gender differences must be taken into account when several samples are compared.

Hospital anxiety and depression scale cutoff scores for cancer patients in acute care.

The aim of this study was to determine optimal cutoff scores for the Hospital Anxiety and Depression Scale (HADS) when used in evaluating cancer patients in acute care. A total of 689 cancer patients were assessed during their first days of in-patient treatment, using the structured clinical interview for DSM and the HADS. Statistical analysis was performed using ROC curves. A total of 222 patients (32%) had a mental disorder. The area under the curve was the best in the total scale of the HADS, namely 0.73. With a score of > or =13, it is possible to detect 76% of the cases with a specificity of .60, whereas 95% of the cases can be detected with a score of > or =6 (specificity 0.21). With scores of > or =16 and > or =22, recommended by the test authors for primary care, only 59 and 30% of the comorbid cancer patients are indicated. Lower HADS cutoff scores when preferable when evaluating cancer patients than are recommended for use in primary care. When using HADS in clinical practice and epidemiological studies, it is important to decide whether, for the task at hand, high detection rates of affected patients or low misclassification rates are more important.

Quality of care and emotional support from the inpatient cancer patient's perspective.

BACKGROUND: Patient satisfaction and emotional support are crucial elements of cancer care. Little is known, however, about which areas of care are important from the patient's perspective and the roles emotional distress and support play in this context. METHODS: Multicenter prospective study was conducted (n = 396 cancer patients; t1 = after admission to hospital, t2 = before discharge). Quality of care was measured with the quality of care from the patient's perspective questionnaire, and emotional distress was measured with the hospital anxiety and depression scale. Additional questions regarding emotional support wished (at t1) and provided (at t2) were administered. RESULTS: The patients reported that the domains of care most important to them were as follows: respect and commitment of the physicians, information before procedures, care equipment, and medical care. The areas where improvements are most obviously needed were nutrition, participation, clarity about who is responsible for personal care, and having the possibility of speaking in private with nurses and psycho-oncologists. Fifty-six percent of the patients were highly emotionally distressed, 84% wanted support from physicians, 76% from nurses, 33% from psychologists, and 7% from a pastor. CONCLUSION: Emotional support is a crucial part of patient satisfaction and should be provided by several members of the oncological team, especially the patients' physicians. In turn, it is crucial that medical professionals be equipped with good communication skills.

Management of combined hepatocellular and cholangiocarcinoma.

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare primary liver malignancy composed of cells with histopathological features of both cholangiocarcinoma (CC) and hepatocellular carcinoma (HCC). It reportedly accounts for 0.4-14.2% of all primary liver carcinomas, with incidence varying in different regions. The clinical features are similar to those of either HCC or CC. Preoperative noninvasive diagnosis of cHCC-CC with conventional radiography is difficult. Because the origin of cHCC-CC is from two different tumour entities, despite intensive preoperative imaging studies, most studied patients were misdiagnosed either as HCC or CC. Accurate preoperative diagnosis is important because the most appropriate treatment depends on the major component of the tumour (HCC or CC). A high index of suspicion, imaging studies (ultrasound, computed tomography, positron emission tomography), levels of serum tumour markers (alpha-fetoprotein, carbohydrate antigen 19-9), and histology assist case detection and treatment choice. Patients who qualify for surgery should have a partial hepatectomy with hilar lymph node dissection, which can result in 5-year survival rates exceeding 50%. The role of liver transplantation is not yet known.

Comparison of histidine-tryptophan-ketoglutarate solution and University of Wisconsin solution in adult liver transplantation.

BACKGROUND: A safe and effective preservation solution is a precondition for successful orthotopic liver transplantation (OLT). This study compared University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions in OLT. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 137 primary cadaveric. OLT performed between January 2003 and December 2006 at our institution. Sixty-eight grafts were harvested using UW and 69 using HTK. Recipients were managed similarly in regard to operative techniques and immunosuppression. We collected donor data including serum transaminases, serum sodium, ICU stay and assessed macroscopic liver quality. Recipient serum transaminases were collected on postoperative days 1, 7, 14, and 30. We compared biliary and vascular complications, as well as patient and graft survivals. RESULTS: Mean serum bilirubin levels were slightly higher in the HTK group at 1,7,14, and 30 days after transplantation, whereas transaminases were higher in the UW group. Primary nonfunction occurred in 1 patient in each group. Retransplantation was performed in 5 patients in the UW and in 9 patients in the HTK group. Biliary complication rates were similar in the UW and HTK groups (22% and 17%, respectively). Six arterial complications occurred in the HTK (8.7%) and 2 in the UW group (2.9%; P < .05). Mean follow-up was 25 months. Graft survival at 1, 12, and 36 months was 90%, 78%, and 75% versus 90%, 71%, and 71% in the UW versus HTK groups, respectively. One-, 12-, and 36-month patient survival rates were 93%, 78%, and 75% versus 93%, 78%, and 78% in the UW versus HTK groups, respectively. CONCLUSIONS: There were no significant differences in graft and patient survivals between the 2 groups. Whereas the biliary complication rates were comparable in both groups, the arterial complications were clearly higher in the UW group (8.7% vs 2.9%; P < .05%). UW and HTK solutions seemed to be equally safe and effective in the preservation of liver grafts. The high incidence of arterial complications in the UW group requires further prospective studies.

Results of resection and transplantation for hepatocellular carcinoma in cirrhosis and noncirrhosis.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Both liver resection (LR) and orthotopic liver transplantation (OLT) are surgical treatment options depending on the size of the tumor and the presence of cirrhosis. Liver cirrhosis is the main reason for the high early postoperative mortality after resection. Even in the Child A stage, extensive resections are not recommended. This study presented the results of surgical treatment (LR or OLT) for HCC in cirrhotic and noncirrhotic livers. We analyzed the data of 76 patients who underwent LR or OLT for HCC from January 2001 to December 2006. In noncirrhotic livers the following resections were performed: 30 right and extended right hemihepatectomies (54.5%); 11 left hemihepatectomies (20%); and 14 mono- or bisegmentectomies (25.5%). In cirrhotic livers the following procedures were performed: in Child A stage 1 right hemihepatectomy, 1 extended right hemihepatectomy, 1 extended left hemihepatectomy, and 4 mono- or bisegmentectomies; and in Child B stage, 3 mono- or bisegmentectomies. Among 11 patients who underwent transplantation, tumors in 2 patients exceeded the Milan criteria. Five patients in the LR group were treated with transarterial chemoembolization before transplantation. LR for HCC in cirrhosis should be performed with caution; there were no long-term survivors in our data. Our study confirmed that OLT shows good long-term survival in early HCC stages. However, this may also be true for stages above the Milan criteria. For HCC in noncirrhotic livers, LR remains the treatment of choice, justifying an extensive surgical approach. Such an approach achieved favorable long term survivals.

Liver transplantation for hilar cholangiocarcinoma: a German survey.

BACKGROUND: The present study reports a German survey addressing outcomes in nonselected historical series of liver transplantation (OLT) for hilar cholangiocarcinoma (HL). PATIENTS AND METHODS: We sent to all 25 German transplant centers performing OLT a survey that addressed (1) the number of OLTs for HL and the period during which they were performed; (2) the incidence of HL diagnosed prior to OLT/rate of incidental HL (for example, in primary sclerosing cholangitis); (3) tumor stages according to Union Internationale Centre le Cancer; (4) patient survival; and (5) tumor recurrence rate. RESULTS: Eighty percent of centers responded, reporting 47 patients who were transplanted for HL. Tumors were classified as pT2 (25%), pT3 (73%), or pT4 (2%). HL was diagnosed incidentally in 10% of cases. A primary diagnosis of PSC was observed in 16% of patients. Overall median survival was 35.5 months. When in-hospital mortality (n = 12) was excluded, the median survival was 45.4 months, corresponding to 3- and 5-year survival rates of 42% and 31%, versus 31% and 22% when in-hospital mortality was included. HL recurred in 34% of cases. Three- and 5-year survivals for the 15 patients transplanted since 1998 was 57% and 48%, respectively. Median survival ranged from 20 to 42 months based on the time period (P = .014). CONCLUSIONS: The acceptable overall survival, the improved results after careful patient selection since 1998, and the encouraging outcomes from recent studies all suggest that OLT may be a potential treatment for selected cases of HL. Prospective multicenter randomized studies with strict selection criteria and multimodal treatments seem necessary.

Histopathological outcome of 597 isolated soft tissue tumors suspected of soft tissue sarcoma: a single-center 12-year experience.

BACKGROUND: The aim of this present report was to analyze the patients referred to us with the presumptive diagnosis of soft tissue sarcoma (STS). METHODS: We reviewed all patients referred to us with suspected soft tissue sarcoma (STS) of the extremities or trunk over a 12-year period. RESULTS: We treated 597 patients with soft tissue tumors. Open biopsy revealed soft tissue sarcoma in 318 cases, benign mesenchymal tumor in 124 cases and isolated metastases (ISTM) from carcinomas in 98 patients; other pathologies were found in 57 patients. The primary carcinomas were lung cancer in 26 patients, breast cancer in 19 patients, renal carcinoma in 16 patients, carcinoma of the esophagus in 12 patients, colonic carcinoma in 5 patients, thyroid gland cancer in 6 patients, and in 14 patients carcinoma of unknown primary was diagnosed. CONCLUSIONS: In our collective with soft tissue tumor, 50% of the patients had the diagnosis of soft tissue sarcoma, 20% presented with a metastasis of carcinoma and 20% had a benign tumor. Referring to our results, in patients with the presumptive diagnosis of soft tissue sarcomas, soft tissue metastasis of a primary carcinoma was unexpectedly common, indicating that greater consideration should be given to this differential diagnosis.

Evaluation of VEGF A expression and microvascular density as prognostic factors in extrahepatic cholangiocarcinoma.

OBJECTIVES: Angiogenesis is essential for tumor growth and metastasis. An association between microvessel density, a measure of tumor angiogenesis, and conventional prognostic variables has been shown for many different tumor entities. In extrahepatic cholangiocarcinoma, the VEGF expression and microvessel density have rarely been investigated. METHODS: Paraffin-embedded specimens from 51 resected adenocarcinomas of the extrahepatic bile duct were immunostained for vascular endothelial growth factor A (VEGF A) and CD 34 to evaluate the microvessel density (MVD). VEGF A staining was evaluated by combining intensity and percentage of positive tumor cells, as low (expression equal or below the median), or high (above the median). Microvessel density was assessed using a method published by Weidner et al. RESULTS: Median disease free survival (DFS) of the study group was 12.5 months (range, 1-66.3 months). DFS was calculated in the 39 patients with complete resection. It was significantly better in patients with low microvessel density than DFS in patients with high microvessel density (33 months (range, 3-66.3 months) vs. 21.8 months (range, 1.6-31.6 months); p=0.022). In contrast, VEGF A expression did not correlate with survival. There was a trend toward a higher VEGF A expression in highly vascularized tumors (p=0.08), but failed to reach statistic significance. CONCLUSIONS: The present study indicates, that vascularisation has an important impact on survival of extrahepatic cholangiocarcinoma patients. Other molecules than VEGF A are probably involved in neovascularization in extrahepatic cholangiocarcinoma.

Laparoscopic spray application of fibrin sealant effects on hemodynamics and spray efficiency at various application pressures and distances.

BACKGROUND: Laparoscopic resections of parenchymal organs are increasingly performed. However, little is known about the effects of laparoscopic fibrin sealant spray applications on intraabdominal pressure (IAP) and hemodynamics. METHODS: Cardiac and pulmonary monitoring was performed via two central venous pressure lines in the thoracic and abdominal vena cava, a pulmonary artery catheter, and a peripheral artery line. Air was sprayed into the abdomen at pressures of 2, 3, and 4 bar for 30 s. According to the group, a valve on a trocar was open or closed. To optimize fibrin sealant application, the sealant was sprayed at three different application pressures (2, 2.5, and 3 bar) and distances (2, 3.5, and 5 cm). RESULTS: All spray simulations caused a significant increase in the IAP. During the first 10 s of spraying, the IAP increase was 5 mmHg or less, but rose rapidly during the last 20 s of spraying. The IAP increase resulted in decreased pulmonary compliance. Pulmonary resistance and the central venous pressures of both the thoracic and abdominal vena cava increased. At application pressures of 3 and 4 bar, the IAP increase was greater than 2 bar of pressure, reaching IAP values exceeding 35 mmHg. Spray mist formation was primarily dependent on application pressure, whereas clot formation and surface coverage depended on both application pressure and distance. The best results were achieved with an application pressure of 2.5 bar and a distance of 5 cm from the surface. CONCLUSIONS: This study shows that fibrin sealants can be used safely in laparoscopic procedures. Keeping the spray periods short and allowing air to escape from the abdomen can minimize the IAP increase. According to our results, a laparoscopic spray application of fibrin sealant should start with an insufflation pressure of 10 mmHg, an application pressure of 2.5 bar, and an application distance of 5 cm with a valve on the trocar left open.

Overview of the MELD score and the UNOS adult liver allocation system.

On February 27, 2002, the United Network for Organ Sharing (UNOS) introduced a new allocation policy for cadaveric liver transplants, based on the Model for End-Stage Liver Disease (MELD) score. This new policy stratifies the patients based on their risk of death while on the waiting list. We analyzed the background and main features of this new allocation policy to evaluate the effects on waiting list dynamics as well as the accuracy of MELD as a predictor of pretransplantation mortality and posttransplantation outcome. MELD has proved to be accurate as a predictor of waiting list mortality, but seems to be less accurate to predict posttransplantation outcome. Immediate effects of the new policy were a reduction in the waiting list, while organs were primarily directed to sicker patients with reduced waiting times. There was a statistically but not significantly reduced number of patients removed from the list due to death or severity of sickness. The balance between medical urgency and transplant benefit is still to be defined as is the relationship between pretransplantation criteria and posttransplantation outcomes, and the way this relationship should be included in the allocation policy.

Successful staged kidney and liver transplantation for glycogen storage disease type Ib: A case report.

Glycogen storage disease type Ib is a rare metabolic disease caused by a defect of the G6P transporter. Patients suffer from hypoglycemic episodes; growth and developmental delay; osteoporosis; neutropenia; and tendency to infections, ovarian cysts, and liver adenomas. Terminal kidney disease is a rare complication. Liver transplantation has been performed to prevent malignant transformation of hepatic adenomas. We present the case of a female patient with glycogenosis type Ib who had severe hypoglycemic episodes and recurrent infections since early childhood. She became dialysis dependent at the age of 24 years. Kidney transplantation was performed at age 30, and liver transplantation 2 years later. The main indication for liver transplantation were the persistent, therapy-refractory hypoglycemic episodes. The transplanted kidney function is stable. The liver transplantation resulted in the disappearance of hypoglycemic episodes, with the patient leading a normal life and eating a normal diet. The neutropenia did not recover, but there were no more significant infectious episodes after liver transplantation. This is, to the best of our knowledge, the first communication of a dual kidney and liver transplant performed in a patient with glycogenosis type Ib. It confirmed the beneficial effect of liver transplantation on the quality of life of patients with severe hypoglycemia. The transplantation should be attempted earlier in the course of the disease to reduce complications and allow catch-up growth. Hepatocyte transplantation may be considered; however, long-term results seem to be rather poor in the few documented cases.

Expression of p73 and its relation to histopathology and prognosis in hepatocellular carcinoma.

BACKGROUND: The protein p73, the first identified homologue of the tumor suppressor gene p53 (also known as TP53), has been shown to induce apoptosis (programmed cell death), but its function in tumor development has not been established. This study was undertaken to investigate the expression of p73 in liver tissue of patients with hepatocellular carcinoma (HCC) and to determine whether this expression has any impact on prognosis. METHODS: In situ hybridization and immunohistochemistry for the detection of p73 RNA transcripts and protein, respectively, were performed in tissues from 193 patients with curatively (R0-) resected HCC. Patients receiving liver transplantation were excluded. The results obtained were analyzed with respect to their association with pathohistologic stage, Edmondson grade, p53 expression status and several histopathologic factors of possible prognostic value, and, finally, with patient survival. RESULTS: RNA transcripts encoding p73 were detected by in situ hybridization in tumor cells but not in stromal, endothelial, or inflammatory cells or in cholangiocytes. Transcripts were also found occasionally in non-neoplastic hepatocytes. By immunohistochemistry, we detected p73 protein in 61 (32%) of the 193 carcinomas examined. Positive immunohistochemical staining was confined to the cell nucleus. Univariate survival analysis showed that p73 expression status was statistically significantly related to prognosis (two-sided P<.0001). Patients with p73-positive tumors had a poorer prognosis than those with p73-negative carcinomas. Multivariate Cox survival analysis identified the age of the patient, p73 expression status, co-existing cirrhosis, and Edmondson grade as independent prognostic factors. CONCLUSION: The protein p73 is overexpressed by a subset of HCCs and could serve as a useful indicator of prognosis in patients with this disease.

INK4a-ARF alterations and p53 mutations in hepatocellular carcinomas.

The INK4a-ARF (CDKN2A)- locus on chromosome 9p21 encodes for two tumour suppressor proteins, p16(INK4a) and p14(ARF), that act as upstream regulators of the Rb-CDK4 and p53 pathways. To study the contribution of each pathway in tumorigenesis of hepatocellular carcinoma (HCC), we analysed the alterations of p14(ARF), p16(INC4a) and p53. After microdissection, DNA of 71 hepatocellular carcinomas was analysed for INK4-ARF inactivation and p53 mutation by DNA sequence analysis, methylation-specific PCR (MSP), restriction-enzyme related polymerase chain reaction (RE-PCR), mRNA expression and immunohistochemistry. In addition, microdeletion of p14(ARF) and p16(INC4a) were assessed by differential PCR. Inactivation of p14(ARF) was found in 11/71 cases (15%), alterations of p16(INK4a) occurred in 47/71 carcinomas (66%), which correlated with loss of mRNA transcription. Five tumours (7%) had homozygous deletions of the INK4a-ARF locus. We failed to detect specific mutations of both exons. P16(INK4a) methylation with an unmethylated p14(ARF) promotor appeared in 39 cases. Mutations of p53 were found in 30 of 71 HCC (42%), and only one of them harboured p14(ARF) inactivation. We failed to establish alterations of the INK4a-ARF locus or p53 status as independent prognostic factor in these tumours. Our data indicate, that p14(ARF) methylation occurs independently of p16(INK4a) alterations in a subset of HCC together with wild type p53. The INK4a-ARF-/p53-pathway was disrupted in 86% of HCC, either by p53 mutations or by INK4a-ARF inactivation, and may have co-operative effects in hepatocarcinogenesis.

Alpha1-and beta2-adrenoceptors in the human liver with mass-forming intrahepatic cholangiocarcinoma: density and coupling to adenylate cyclase and phospholipase C.

Besides the regulation of hepatic metabolic pathways in which adrenoceptors are mainly involved, their effect on the second messenger cAMP is thought to be related to the growth and differentiation of neoplastic cells. However, few studies have been done on the status of these structures in the human liver affected by cholangiocarcinoma (CC). Thus, in this study, changes in densities of alpha1- and beta2-adrenoceptors (alpha1-and beta2-ARs) were investigated in membranes of human liver with cholangiocarcinoma, and for comparison, in membranes of non-adjacent non-tumour liver using the potent antagonists [3H]-prazosin and [1I]-iodocyanopindolol (ICYP) respectively. In addition, the activity of membrane-bound phospholipase C (PLC) and adenylate cyclase (AC) was also studied. In CC liver, the density of alpha1-and beta2-ARs was significantly reduced, compared with non-tumour liver tissues (alpha1-ARs: 23.38+/-4.69 vs 80.35+/-10.52, P=0.0002 beta2-ARs: 14.27+/-2.93 vs 33.22+/-4.32 fmol/mg protein, P=0.03), whereas the ligand affinities (KD) remained unchanged. The beta2-selective antagonist ICI 118,551 was about 100 times more potent in inhibiting ICYP binding than the beta1-selective antagonist CGP 20712A; thus, more than 98% of the beta-ARs were of the beta2-subtypes. The AC activity upon stimulants acting on beta-AR (isoprenaline), G-protein (GTP, NaF) and AC (forskolin) was decreased in CC liver. Similarly, noradrenaline-stimulated PLC activity was significantly reduced in tumour tissues. In conclusion, in CC liver the alpha1- and beta2-ARs density was down-regulated and the neoplastic invasion blunted AC and PLC activity. These quantitative changes may help to elucidate not fully understood pathogenetic mechanisms of disturbed hepatic metabolic processes, such as hypoglycemia during cancer in human liver.