Implementation of anesthesia quality indicators in Germany : A prospective, national, multicenter quality improvement study.

BACKGROUND: In 2016 the German Society of Anesthesiology and Intensive Care Medicine (DGAI) and the Association of German Anesthetists (BDA) published 10 quality indicators (QI) to compare and improve the quality of anesthesia care in Germany. So far, there is no evidence for the feasibility of implementation of these QI in hospitals. OBJECTIVE: This study tested the hypothesis that the implementation of the 10 QI is feasible in German hospitals. MATERIAL AND METHODS: This prospective three-phase national multicenter quality improvement study was conducted in 15 German hospitals and 1 outpatient anesthesia center from March 2017 to February 2018. The trial consisted of an initial evaluation of pre-existing structures and processes by the heads of the participating anesthesia departments, followed by a 6-month implementation phase of the QI as well as a final re-evaluation phase. The implementation procedure was supported by web-based implementation aids ( www.qi-an.org ) and internal quality management programs. The primary endpoint was the difference in the number of implemented QI per center before and after implementation. Secondary endpoints were the number of newly implemented QI per center, the overall number of successful implementations of each QI, the identification of problems during the implementation as well as the kind of impediments preventing the QI implementation. RESULTS: The average number of implemented QI increased from 5.8 to 6.8 (mean of the differences 1.1 ± 1.3; P < 0.01). Most frequently the QI perioperative morbidity and mortality report (5 centers) and the QI temperature management (4 centers) could be implemented. After the implementation phase, the QI incidence management and patient blood management were implemented in all 16 centers. Implementation of other quality indicators failed mainly due to a lack of time and lack of structural resources. CONCLUSION: In this study the implementation of QI was proven to be mostly feasible in the participating German hospitals. Although several QI could be implemented with minor effort, more time, financial and structural resources would be required for some QI, such as the QI postoperative visit.

[Implementation of anesthesia quality indicators in Germany : A prospective, national, multicenter quality improvement study]. / Implementierung anästhesiologischer Qualitätsindikatoren in Deutschland : Eine prospektive, nationale, multizentrische Qualitätssteigerungsstudie German version.

BACKGROUND: In 2016 the German Society of Anesthesiology and Intensive Care Medicine (DGAI) and the Association of German Anesthetists (BDA) published 10 quality indicators (QI) to compare and improve the quality of anesthesia care in Germany. So far, there is no evidence for the feasibility of implementation of these QI in hospitals. OBJECTIVE: This study tested the hypothesis that the implementation of the 10 QI is feasible in German hospitals. MATERIAL AND METHODS: This prospective three-phase national multicenter quality improvement study was conducted in 15 German hospitals and 1 outpatient anesthesia center from March 2017 to February 2018. The trial consisted of an initial evaluation of pre-existing structures and processes by the heads of the participating anesthesia departments, followed by a 6-month implementation phase of the QI as well as a final re-evaluation phase. The implementation procedure was supported by web-based implementation aids ( www.qi-an.org ) and internal quality management programs. The primary endpoint was the difference in the number of implemented QI per center before and after implementation. Secondary endpoints were the number of newly implemented QI per center, the overall number of successful implementations of each QI, the identification of problems during the implementation as well as the kind of impediments preventing the QI implementation. RESULTS: The average number of implemented QI increased from 5.8 to 6.8 (mean of the differences 1.1 ± 1.3; P < 0.01). Most frequently the QI perioperative morbidity and mortality report (5 centers) and the QI temperature management (4 centers) could be implemented. After the implementation phase, the QI incidence management and patient blood management were implemented in all 16 centers. Implementation of other quality indicators failed mainly due to a lack of time and lack of structural resources. CONCLUSION: In this study the implementation of QI was proven to be mostly feasible in the participating German hospitals. Although several QI could be implemented with minor effort, more time, financial and structural resources would be required for some QI, such as the QI postoperative visit.

Outcomes of Recipients With Pancreas Transplant Alone Who Develop End-Stage Renal Disease.

Recipients of pancreas transplant alone (PTA) may be at increased risk for developing end-stage renal disease (ESRD). The survival experience of PTA recipients developing ESRD has not been described. Furthermore, the relative survival of these patients as compared to diabetics on chronic dialysis is unknown. We studied all adult PTA recipients from January 1, 1990 to September 1, 2008 using the Scientific Registry of Transplant Recipients. Each PTA recipient developing ESRD was matched to 10 diabetics on chronic dialysis from the United States Renal Data System. Cox proportional hazards models were fitted to determine the relation between ESRD and mortality among PTA recipients, and the relation between PTA and mortality among diabetics on chronic dialysis. There were 1597 PTA recipients in the study, of which 207 developed ESRD. Those with ESRD had a threefold increase in mortality versus those without (adjusted hazard ratio 3.28 [95% confidence interval: 2.27, 4.76]). There was no significant difference in the risk of death among PTA recipients with ESRD versus diabetics on dialysis. PTA recipients developing ESRD are three times more likely to die than PTA recipients without ESRD; however, the risk of death in these patients was similar to diabetics on chronic dialysis without PTA.

Major incidents and complications in otherwise healthy patients undergoing elective procedures: results based on 1.37 million anaesthetic procedures.

BACKGROUND: Improved anaesthesia safety has made severe anaesthesia-related incidents, complications, and deaths rare events, but concern about morbidity and mortality in anaesthesia continues. This study examines possible severe adverse outcomes or death recorded in a large national surveillance system based on a core data set (CDS). METHODS: Cases from 1999 to 2010 were filtered from the CDS database. Cases were defined as elective patients classified as ASA physical status grades I and II (without relevant risk factors) resulting in death or serious complication. Four experts reviewed the cases to determine anaesthetic involvement. RESULTS: Of 1 374 678 otherwise healthy, ASA I and II patients in the CDS database, 36 met the study inclusion criteria resulting in a death or serious complication rate of 26.2 per million [95% confidence interval (CI), 19.4-34.6] procedures, and for those with possible direct anaesthetic involvement, 7.3 per million cases (95% CI, 3.9-12.3). CONCLUSIONS: This is the first study assessing severe incidents and complications from a national outcome-tracking database. Annual identification and review of cases, perhaps with standardized database queries in the respective departments, might provide more detailed information about the cascades that lead to unfortunate outcomes.

[Anesthesiological considerations for patients with trisomy 21 (Down syndrome)]. / Anästhesiologische Besonderheiten der Trisomie 21 (Down-Syndrom).

The most common chromosomal abnormality is trisomy 21 which is also known as Down syndrome and occurs in approximately 1 in 800 births. The majority of the resulting disabling conditions cannot be cured and affect people of all ages, ethnicity and economic levels. Life expectancy has increased with advances in medical care in the same way as in the rest of the population. One of the major tasks for health care professionals is to help these differently abled children and their families function in the most effective way possible as they learn to accept the limitations imposed by a persistent disability. Signs and symptoms of trisomy 21 are very variable based on the trias of mental retardation to a variable degree, hand anomalies and cardiac complications. Other abnormalities are atlantoaxial instability (AAI), tracheal stenosis, a predisposition to respiratory complications, chronic hypothyroidism, microgenia and macroglossia. These conditions are relevant to anesthetic procedures and patients with Down syndrome and their families have specific expectations and attitudes towards medical and anesthetic treatment.

Veno-venous extracorporeal membrane oxygenation (ECMO) support during anaesthesia for oesophagectomy.

The use of extracorporeal membrane oxygenation in adults has increased in popularity and importance for the support of patients with cardiac or pulmonary failure. Although it is now quite commonly used in the intensive care unit, its use has rarely been described as a means of support during anaesthesia and surgery. We report the case of a patient who required curative resection of the oesophagus following previous left pneumonectomy where veno-venous extracorporeal membrane oxygenation was required both during surgery and for the first three days postoperatively. We describe the anaesthetic management of this patient who only had a single lung, review other alternatives and discuss why extracorporeal membrane oxygenation was particularly suited to this case. To the best of our knowledge, the anaesthetic literature to date does not contain a case report of this type.

Portal venous versus systemic venous drainage of pancreas grafts: impact on long-term results.

Portal venous (PV) and systemic venous (SV) drainage methods are used in pancreas transplantation. The impact of the reconstruction technique on long-term outcome remains unclear. We compared the efficacy and side effects of both methods in 192 recipients who received synchronous pancreas kidney transplants between November 1995 and November 2007. SV and PV drainage were used in 147 and 45 cases, respectively. Pancreas function was determined by hemoglobin A1c levels and annual oral glucose tolerance test. Serum creatinine assessed kidney function. Serum lipid (low-density lipoprotein, high-density lipoprotein and cholesterol) levels and body mass index were measured annually. Patient and graft survival were calculated by log-rank analysis. Pancreas survival for SV versus PV patients was similar after 5 years (81.8% vs. 75.5%) and 10 years (65.1% vs. 60%; p = NS). Similarly, no difference was detected between the groups regarding kidney survival after 5 years (92.9% vs. 84.4%) and 10 years (81.6% vs. 75.5%; p = NS). Patient survival did not differ at 5 years (94.3% vs. 88.8%) and 10 years (85.1% vs. 84.4%; p = NS). Pancreas and kidney function and the lipid profiles were similar in both groups. SV and PV drainage of pancreas grafts offer similar long-term graft survival and function and choice of method should remain the preference of the surgeon.

Paediatric Perianesthesia questionnaire: development and data from eight hospitals across Germany.

BACKGROUND: Opinions about satisfaction with care are rarely obtained from children and few studies of this type exist in the area of paediatric anaesthesia. In this study, we developed a comprehensive self-administered questionnaire to measure the level of paediatric and, as a substitute in younger children, parental satisfaction with anaesthesia. In addition, we aimed to identify factors influencing satisfaction and compare results between hospitals. METHODS: We followed a rigorous protocol including construction of a pilot questionnaire and qualitative and quantitative analysis. The questionnaire was adapted for confounding variables. We analysed satisfied and dissatisfied groups and compared satisfaction scores between participating hospitals. RESULTS: A questionnaire was developed which comprised 37 questions assessed on a five-point Likert scale. With a response rate of 71%, a total of 1052 patients completed the questionnaire. In the final analysis, 760 questionnaires (72%) were included. Most questionnaires were answered by the parents [705 (92.8%)]. The mean age of children was 6.7 (4.97) yr. Multivariate analysis found a history of previous anaesthetic problems and the identity of the person answering the questionnaire as influencing factors on the sum score. The most important differences between satisfied and dissatisfied children were found for the dimensions 'privacy and waiting', 'information giving', and 'discomfort'. Scores differed between hospitals. CONCLUSIONS: Our psychometric questionnaire provides a novel approach to paediatric patient satisfaction with anaesthesia care and covers areas deemed important by children, parents, and carers. Significant differences between satisfied and dissatisfied groups and between participating hospitals were found.

The Anesthesia Preoperative Evaluation Clinic (APEC): a prospective randomized controlled trial assessing impact on consultation time, direct costs, patient education and satisfaction with anesthesia care.

AIM: Anesthetic preoperative evaluation clinics (APECs) are relatively new institutions. Although cost effective, APECs have not been universally adopted in Europe. The aim of this study was to compare preoperative anesthetic assessment in wards with an APEC, assessing time, information gain, patient satisfaction and secondary costs. METHODS: Two hundred and seven inpatients were randomized to be assessed at the APEC or on the ward by the same two senior anesthetists. The outcomes measured were the length of time for each consultation, the amount of information passed on to patients and the level of patient satisfaction. The consultation time was used to calculate impact on direct costs. A multivariate analysis was conducted to detect confounding variables. RESULTS: Ninety-four patients were seen in the APEC, and 78 were seen on the ward. The total time for the consultation was shorter for the APEC (mean 8.4 minutes [P<0.01]), and we calculated savings of 6.4 Euro per patient. More information was passed on to the patients seen in the APEC (P<0.01). The general satisfaction scores were comparable between groups. A multivariate analysis found that the consultation time was significantly influenced by the type of anesthesia, the magnitude of the operation and the location of the consultation. Gain in information was significantly influenced by age, education and the location of the visit. CONCLUSION: The APEC reduced consultation times and costs and had a positive impact on patient education. The cost savings are related to personnel costs and, therefore, are independent of other potential savings of an APEC, whereas global patient satisfaction remains unaltered.

The Heidelberg Peri-anaesthetic Questionnaire--development of a new refined psychometric questionnaire.

We have developed a questionnaire to assess patients' peri-anaesthetic satisfaction. We recruited 1398 patients and 59 health care professionals for construction and validation. Relevant items were rated for preferences. The resulting questions underwent a cognitive and a standard pretest. The resultant Heidelberg Peri-anaesthetic Questionnaire consists of 38 questions about five identified themes: trust and atmosphere; fear; discomfort; treatment by personnel; and information and waiting. Internal consistency was demonstrated for the sum score (Cronbach's alpha = 0.79) and the five factors (Cronbach's alpha = 0.42-0.79). Multivariate analysis found significant influences of age, school education, marital status and duration of anaesthesia. Dissatisfied patients had a median (IQR [range]) of 73% (66-76% [35-83]), and satisfied patients 92% (90-94% [88-100]) of the sum score. The Heidelberg Peri-anaesthetic Questionnaire offers a valid and reliable way to identify dissatisfied patients and generate quality improvement and also has use as a benchmark tool.

Renal safety of CT angiography and perfusion imaging in the emergency evaluation of acute stroke.

BACKGROUND AND PURPOSE: Multimodal CT imaging with contrast-enhanced CT angiography (CTA) and CT perfusion (CTP) is increasingly being used to guide emergency management of acute stroke. However, little has been reported about the safety of intravenous contrast administration associated with these studies in the acute stroke population, including cases in which baseline creatinine values are unknown. We investigated the incidence of contrast-induced nephropathy (CIN), defined as a 25% or more increase in baseline creatinine levels within 72 hours of contrast administration and chronic kidney disease in patients receiving CTA+/-CTP at our regional stroke center. MATERIALS AND METHODS: We analyzed 198 patients who underwent contrast CT studies for evaluation of acute ischemic or hemorrhagic stroke at our center (2003-2007). Through retrospective chart abstraction, we analyzed serial creatinine levels (baseline to day 3) and later values (>/=day 4) where available. The incidences of CIN and/or chronic kidney disease were documented. After power analysis, CIN and non-CIN groups were compared by using the unpaired t test, Wilcoxon rank sum test, or Fisher exact test. RESULTS: None of the 198 patients developed chronic kidney disease or required dialysis. Of 175 patients with serial creatinine measurements between baseline and day 3, 5 (2.9%) developed CIN. The incidence of CIN was 2% in patients who were scanned before a baseline creatinine level was available. CONCLUSION: The incidence of renal sequelae is relatively low in acute stroke patients undergoing emergent multimodal CT scanning. Prompt CTA/CTP imaging of acute stroke, if indicated, need not be delayed in those with no history of renal impairment.

The effectiveness of renal transplantation as a treatment for recurrent uremic cardiomyopathy.

Congestive heart failure is more prevalent in patients with end-stage renal disease than in the general population. Although optimal treatment has yet to be defined, these patients are considered to be at high risk for renal transplantation. The present report of a 27-year-old man describes a full recovery from uremic cardiomyopathy following a renal transplant. Despite the patient developing recurrent cardiac dysfunction following graft failure, a second transplant was successful, which, again, resulted in complete resolution of the cardiomyopathy. Patients with recurrent uremic cardiomyopathy following failed kidney transplantation should be considered for a second kidney transplant.

A pregnant woman with acute myocardial infarction due to coronary artery dissection: pre-hospital and in-hospital management.

A young pregnant woman (32nd week of gestation) presented with acute chest pain due to right coronary artery dissection (CAD) in a pre-hospital setting. The pre-hospital diagnosis by the ambulance staff of an acute myocardial infarction in the antenatal period based on a 12-lead ECG combined with successful treatment by percutaneous coronary intervention with stenting is novel.

[Acute coronary syndrome in the prehospital phase]. / Das akute Koronarsyndrom in der Prähospitalphase.

Cardiovascular diseases are the number one cause of death in Germany. In 2002 about 70,000 people died of acute myocardial infarction (AMI) and of these 37% died before arrival at hospital which underlines the relevance of adequate prehospital care. The generic term acute coronary syndrome (ACS) was introduced because a single pathomechanism accounts for the different forms and comprises unstable angina pectoris (iAP), non-ST-elevation myocardial infarction (NSTEMI), ST-elevation myocardial infarction (STEMI) and sudden cardiac death (SCD). Characteristic features are retrosternal pain, vegetative symptoms and radiation of pain into the adjoining regions. Further differentiation can only be achieved by the 12-lead ECG, as cardiac-specific enzymes do not play a role in prehospital decisions. Prehospital delays should be avoided, history and physical examination should be brief but focused, vital parameters should be assessed and monitored. Basic treatment for ACS should comprise inhalative oxygen, nitrates, morphine, aspirin and beta-blockers. If STEMI is diagnosed, patients with symptoms <12 h should undergo fibrinolytic therapy unless there is primary percutaneous coronary intervention (PCI) available within 90 min or if contraindicated. Heparin should be given to patients with STEMI depending on the choice of fibrinolytic agent, it otherwise results in a higher risk of bleeding, but in patients with iAP or NSTEMI it reduces mortality. All patients must be accompanied by the emergency physician during transportation and should be brought to a hospital with primary PCI, especially those with complicated ACS. Treatment of complications depends largely on the type, persistence and severity.

Laparoscopic cholecystectomy in cirrhotic patients.

BACKGROUND: Due to unacceptable increases in intra- and postoperative complications and associated morbidity, cirrhosis of the liver is often considered to be a contraindication for laparoscopic cholecystectomy (LC). However, recent advances have now made it increasingly possible for experienced surgeons to perform LC on this high-risk population. The aim of this study was to evaluate the impact of the coagulopathy associated with cirrhosis on the performance and results of LC. We hypothesized that the factors leading to hemorrhage, rather than Child's classification, would drive operating time and resource utilization. METHODS: Between 1 July 1996 and 30 June 2003, 1,285 cholecystectomies were performed. Thirty one of these patients had evidence of cirrhosis at the time of operation. The 31 patients were divided into high, (low platelets, prolonged International Normalized Ratio) (n = 18), intermediate, (abnormal liver function tests, normal clotting) (n = 5), and low, (normal platelets, normal clotting, and normal liver function tests) (n = 8) surgical risk categories for further analysis. Based on the Child-Turcotte-Pugh (CTP) classification of cirrhosis, there were three grade C and 28 grade A or grade B patients. RESULTS: There were 24 LC, three of which were started laparoscopically and then converted to open, and four open cholecystectomies. Operating room time ranged from 79 to 450 min, with the extent of coagulopathy correlating with the length of time needed to achieve satisfactory hemostasis. Median length of stay postoperatively in the high-risk group was 2 days (range, 0-20). Nine of the cholecystectomies were performed on an outpatient basis. One patient received a liver transplantation 5 months post-LC. There were no operative deaths, bile duct injuries, or returns to the operating room for bleeding. Blood product usage correlated with preexisting coagulopathy. CONCLUSIONS: Currently, the classification of cirrhotic patients is normally done using the CTP score. However, preoperative platelet levels and INR more accurately predict the difficulty of cholecystectomy than CTP score, because intraoperative hemorrhage is the primary concern in these patients. This study demonstrates that preoperative degree of coagulopathy, and not Child's class, should guide the surgeon's approach and expectations when LC is performed in a cirrhotic patient.

Laparoscopic cholecystectomy after the learning curve: what should we expect?

BACKGROUND: The introduction of laparoscopic cholecystectomy (LC) in the late 1980s was accompanied an increase in common bile duct (CBD) injuries. This retrospective analysis of 2,005 cholecystectomies performed at a single institution investigates the factors that have contributed to a record of zero CBD injuries in 1,674 consecutive LC. METHODS: The medical records of 1,285 consecutive patients operated on from 7 July 1996 to 6 June 2003 were obtained. We also examined the peer review records of an additional 720 LC performed between 1 January 1990 and 7 July 1996. RESULTS: There were no CBD injuries among 1,674 consecutive LC patients spanning the period since 1990. Of the 954 patients who underwent LC since 1996, six had a cystic duct leak and five had a duct of Luschka leak. Intraoperative cholangiography (IOC) was performed in 20.2% of cases (n = 193/954). Seventy of 157 patients who underwent cholangiography alone demonstrated one or more stones in the CBD (44.6%). In 40 patients (58.0%), endoscopic retrograde cholangio pancreatography (ERCP) was uniformly successful in clearing intraoperatively identified stones. In36.2% of cases, the stones were removed via laparoscopic CBD exploration (CBDE) (n = 25). In 5.8% of positive cases, the stones were removed via open CBDE (n = 4). Among 761 patients who did not undergo IOC, seven patients (0.92%) returned to the hospital for retained stones. Three of these patients had elevated liver function tests (LFT) preoperatively (1.3%) and four had normal LFT (1.1%). CONCLUSIONS: Injuries of the CBD can be avoided by performing an extensive dissection of the triangle of Calot and by developing a critical view of the operative field to ensure the patient's safety during LC. If all LFT are normal and IOC is not performed, the occurrence of clinically significant stones postoperatively is minimal; in this group, only four patients had retained stones. Thus, in the face of normal LFT, routine IOC is unnecessary for a low CBD injury rate, and a return to the hospital for retained bile duct stones is rarely required, regardless of the number of times ductal stones are found on routine cholangiography. This implies that the significance of the stones discovered at IOC is questionable in most cases, thereby providing an argument against routine cholangiography. Most discovered CBD stones can be treated by ERCP, thus obviating the need for the T-tube drainage associated with CBDE. The 21st century finds LC to be a mature and safe surgical procedure.

Robotic microsurgical vasovasostomy and vasoepididymostomy in rats.

Robotic and robotic assisted procedures are rapidly increasing in popularity amongst practicing surgeons and urologists. Robotic techniques are now commonly used to perform radical prostatectomies for prostate cancer and pyeloplasties for uretero-pelvic junction obstruction. Other robotic procedures include robotic assisted coronary artery bypass and partial nephrectomies. We initially studied the da Vinci surgical robot in order to determine the feasibility of adapting the robot to microsurgical vasovasostomy and vasoepididymostomy. In this paper, we describe our experience in developing a set of practice exercises using the da Vinci robot to prepare for these microsurgical procedures. We also review the design and results of our studies of robotic microsurgical vasovasostomy and vasoepididymostomy in rats.Finally, we discuss the potential future roles of robotic microsurgery in urology and surgery.

Correlation of ultrasonographic and orchidometer measurements of testis volume in adults.

OBJECTIVE: To determine the correlation between testicular volume measured with an orchidometer or high-resolution scrotal ultrasonography (US) with colour-flow Doppler analysis. PATIENTS AND METHODS: In all, 159 men (mean age 36.6 years) presenting for infertility evaluation underwent both a physical examination by a one experienced examiner and high-resolution US with colour-flow Doppler analysis. An orchidometer was also used to measure testicular volume after stretching the scrotal skin tightly over the testis and after warming with a heating pad. The US was interpreted by a radiologist who had no knowledge of the orchidometer estimates. The volume was calculated as 0.71 x length x width x height. RESULTS: For the right testes the mean orchidometer and US estimates were 18.4 and 18.3 mL, yielding a correlation coefficient of 0.72 (r (2) = 0.52, P < 0.01). On the left the respective values were 17.1 and 16.9 mL, with a correlation coefficient of 0.69 (r (2) = 0.48, P < 0.01). CONCLUSION: Orchidometer estimates of testicular volume correlate closely and very significantly with US estimates in adults. In the hands of an experienced examiner orchidometer measurements provide an accurate, rapid and inexpensive assessment of testicular volume.

p16/p14(ARF) cell cycle regulatory pathways in primary neuroblastoma: p16 expression is associated with advanced stage disease.

p16 regulates the G(1)-S cell cycle transition by inhibiting the cyclin D-cyclin-dependent kinase (CDK)4/CDK6-mediated phosphorylation of retinoblastoma protein (pRb). We examined the possible derangement of the p16-CDK/cyclin D-pRb pathway in 40 primary neuroblastomas including 18 samples in the unfavorable stages (C and D) and 22 in the favorable stages (A, B, and Ds) by PCR, reverse transcription-PCR, Western blot, and immunohistochemistry and correlated the results with clinical outcome. No samples harbored alterations of the p16 gene. Interestingly, the samples in the unfavorable stages exhibited expression of p16 mRNA and protein more frequently than those in the favorable stages [mRNA, 9 of 18 (50%) versus 2 of 22 (9%), P = 0.006; protein, 5 of 16 (31%) versus 0 of 18 (0%), P = 0.013]. Alterations of the downstream components of the pathway were infrequent. pRb was deregulated in the majority of samples investigated [27 of 33 (82%), 24 with hyperphosphorylated pRb and 3 with no pRb protein]. The phosphorylation status of pRb did not correlate with p16 protein expression, suggesting that the elevated p16 protein may not be functioning properly to regulate the pathway. Among patients of all stages, p16 expression was significantly associated with a lower overall survival. There was no overexpression of MDM2, and loss of p14(ARF) expression and p53 mutation were infrequent events. Taken together, these findings suggest that up-regulated p16 expression may represent a unique feature of aggressive neuroblastoma.

Loss of CD95 expression is linked to most but not all p53 mutants in European hepatocellular carcinoma.

Experimental data have shown p53-dependent CD95 induction to be associated with increased levels of apoptosis after cytostatic treatment in hepatoma cells. A study of Japanese hepatocellular carcinoma (HCC) has reported an inverse correlation between CD95 and p53 expression. To examine the interaction of p53 and CD95 in tumors we investigated which alterations in p53 can be linked to loss of CD95 expression in European HCC. In 39 tumors we analyzed CD95 by immunohistochemistry and assessed the correlation between the findings of the p53 status as determined by immunohistochemistry and single-strand conformation polymorphism with polymerase chain reaction sequencing. In 10 of 14 tumors with evidence of p53 aberration there was also loss of CD95 expression, compared to 6 of 25 samples with apparent wild-type p53 (P<0.01). Three tumors with p53 mutations but sustained CD95 expression showed single base substitutions mapping to a narrow region of 20 codons in p53. A significant correlation with differentiation status of the tumor was found for the p53 aberration but not for CD95 expression. This is the first study to link loss of CD95 expression to specific p53 alterations in HCC. Functional p53 appears to be a major factor for CD95 expression in hepatocytes, the loss of which could contribute to chemoresistance and possibly immune evasion in hepatocellular carcinoma. Sustained CD95 expression in tumors with certain p53 aberrations may indicate functional heterogeneity of p53 mutants.