Biomedical subjects

Thomas M van Gulik

Publications and source records attributed to Thomas M van Gulik.

At least 19 recordsLinked to original sources

PubMed2006

Improved outcome of resection of hilar cholangiocarcinoma (Klatskin tumor).

BACKGROUND: Treatment of hilar cholangiocarcinoma (Klatskin tumors) has changed in many aspects. A more extensive surgical approach, as proposed by Japanese surgeons, has been applied in our center over the last 5 years; it combines hilar resection with partial hepatectomy for most tumors. The aim of this study was to assess the outcome of a 15-year evolution in the surgical treatment of Klatskin tumors. METHODS: A total of 99 consecutive patients underwent resection for hilar cholangiocarcinoma in three 5-year time periods: periods 1 (1988-1993; n=45), 2 (1993-1998; n=25), and 3 (1998-2003; n=29). Outcome was evaluated by assessment of completeness of resection, postoperative morbidity and mortality, and survival. RESULTS: The proportion of margin negative resections increased significantly from 13% in period 1 to 59% in period 3 (P<.05). Two-year survival increased significantly from 33%+/-7% and 39%+/-10% in periods 1 and 2 to 60%+/-11% in period 3 (P<.05). Postoperative morbidity and mortality were considerable but did not increase with this changed surgical strategy (68% and 10%, respectively, in period 3). Lymph node metastasis was, next to period of resection, also associated with survival in univariate analysis. CONCLUSIONS: Mainly in the last 5-year period (1998-2003), when the Japanese surgical approach was followed, more hilar resections were combined with partial liver resections that included segments 1 and 4, thus leading to more R0 resections. This, together with a decrease in lymph node metastases, resulted in improved survival without significantly affecting postoperative morbidity or mortality.

Adult↗

PubMed2006

Factors influencing the local failure rate of radiofrequency ablation of colorectal liver metastases.

BACKGROUND: The prognosis of patients with colorectal cancer is poor, especially when there is distant metastatic disease. Local ablation of tumor by radiofrequency ablation (RFA) has emerged as a safe and effective new treatment modality, but its long-term efficacy may be hindered by renewed local tumor growth at the site of RFA. The objectives of this study were to identify risk factors for local RFA failure and to define exclusion criteria for RFA treatment of colorectal liver metastases. METHODS: A total of 199 lesions in 87 patients were ablated with RFA. Factors influencing local failure rates were identified and compared with data from the literature. RESULTS: The local failure rate was 47.2%, and the average time to local disease progression was 6.5 months. Factors that significantly correlated with increased failure rates were metachronous occurrence of liver metastases, large mean lesion size, and central tumor location. CONCLUSIONS: Because accurate electrode placement is pivotal in achieving adequate tumor necrosis, RFA should not be performed percutaneously when electrode placement is impaired. We suggest that lesions >5 cm and lesions located near great vessels or adjacent organs should be treated with open RFA, thus allowing vascular inflow occlusion and complete mobilization of the liver. Lesions that are difficult to reach by electrodes should be approached by an open procedure.

Adult↗

PubMed2006

Hepatobiliary function assessed by 99mTc-mebrofenin cholescintigraphy in the evaluation of severity of steatosis in a rat model.

PURPOSE: This study evaluated the utility of non-invasive assessment of hepatobiliary function by 99mTc-mebrofenin cholescintigraphy in a rat model of diet-induced steatosis. METHODS: Male Wistar rats (250-300 g) were fed a standard methionine- and choline-deficient (MCD) diet for up to 5 weeks, thereby inducing hepatic fat accumulation, progressive inflammation and fibrogenesis corresponding with clinical steatosis. 99mTc-mebrofenin pinhole scintigraphy was used to evaluate the hepatocyte mebrofenin uptake rate, the time of maximum hepatic uptake (T(peak)) and the time required for peak activity to decrease by 50% (T(1/2peak)). Scintigraphic parameters were correlated with biochemical and serological parameters and with liver histopathology. RESULTS: MCD diet induced mild steatosis after 1 week and severe steatosis with prominent inflammation after 5 weeks. T(peak), T(1/2peak) prolonged and the uptake rate decreased significantly, while the severity of steatosis increased (p<0.05). There was a strong, significant correlation between the severity of steatosis (histopathology, hepatic triglyceride content) and the 99mTc-mebrofenin uptake rate (r2=0.83, p<0.0001 and r2=0.82, p<0.0001, respectively). In addition, the uptake rate correlated significantly with the increased inflammation (plasma and hepatic TNF-alpha, r2=0.72, p<0.0001 and r2=0.52, p=0.001, respectively). The correlation of the uptake rate with hepatocellular damage was weak (AST and ALT, r2=0.29 and 0.32, respectively), but correlation with synthetic function was strong (prothrombin time, r2=0.70, p<0.001). CONCLUSION: Hepatobiliary function assessed by 99mTc-mebrofenin scintigraphy correlates with the extent and progression of steatosis. These results suggest a potential role for mebrofenin scintigraphy as a non-invasive functional follow-up method for disease progression in steatotic patients.

Aniline Compounds↗

PubMed2006

Hypoxia/reoxygenation impairs glucose absorption and cAMP-mediated secretion more profoundly than glutamine absorption and Ca2+/PKC-mediated secretion in rat ileum in vitro.

BACKGROUND: Intestinal ischemia and reperfusion may lead to profuse secretion of water and electrolytes. The underlying mechanisms have been related to increased hydrostatic pressure, to denudation of intestinal villi, and, recently, to adenosine-mediated enhancement of chloride secretion. METHODS: We studied the effects of hypoxia and reoxygenation on baseline electrophysiologic parameters; on glucose- and glutamine-induced absorption; on secretion induced by carbachol, histamine, and forskolin; and on epithelial barrier function to disodium-fluorescein and horseradish peroxidase in rat ileum mounted in Ussing chambers. RESULTS: We observed that 30 minutes of hypoxia followed by 60 minutes of reoxygenation differentially affected glucose and glutamine absorption to 11% and 42%, respectively, of control values. Cyclic adenosine monophosphate-mediated secretion induced by forskolin was reduced to 9% of controls. In contrast, Ca(2+)/protein kinase C-mediated secretion induced by carbachol or histamine was reduced only to 35% to 48% of controls. Furthermore, the epithelium fully was capable of maintaining its barrier function to small and large permeability probes, even after 90 minutes of hypoxia. CONCLUSIONS: We conclude that hypoxia and reoxygenation differentially impair nutrient absorption, corroborating recent absorption data in in vivo models of ischemia, and that it differentially affects secretory capacity in crypts, dependent on the intracellular messenger pathway. The relative persistence of Ca(2+)/protein kinase C-mediated secretion to hypoxia and reoxygenation indicates that secretagogues that activate this pathway play a significant role in the intraluminal fluid sequestration and diarrhea observed after intestinal ischemia and reperfusion.

Absorption↗

PubMed2006

Management of spontaneous haemorrhage and rupture of hepatocellular adenomas. A single centre experience.

BACKGROUND: Hepatocellular adenomas (HCA) may present with spontaneous haemorrhage and rupture. The aim of this study was to assess management in 22 patients treated for haemorrhage and/or rupture of HCA. PATIENTS AND METHODS: Between May 1990 and July 2005, 22 female patients were diagnosed with acute haemorrhage and/or rupture of lesions highly suspicious of HCA. Preoperative imaging diagnostics and pathologic specimens were reviewed. RESULTS: Twelve haemodynamically stable and four unstable patients could be treated conservatively. One patient underwent acute partial liver resection, whereas four patients underwent laparotomy with initial packing of the liver. In one patient, selective embolisation of the left hepatic artery was performed. Fifteen patients eventually underwent resection after a mean time of 8 months after initial treatment. Six patients did not undergo resection and showed no complications or rebleeding after a mean follow-up of 24.6 months. Only in seven patients, histopathological examination showed HCA, and in one patient, HCA with focal nodular hyperplasia. CONCLUSION: HCA with haemorrhage and/or rupture does not necessarily require immediate liver resection. Conservative treatment is justified in stable patients. In case of an instable patient with or without hemoperitoneum, laparotomy with packing or selective embolisation can stop the bleeding.

Adenoma, Liver Cell↗

PubMed2006

Liver protection by hypothermic perfusion at different temperatures during total vascular exclusion.

INTRODUCTION: In situ hypothermic perfusion (HP) can be applied to attenuate ischemia and reperfusion (I/R) injury during liver resection under total vascular exclusion (TVE). This study examines the protective effect of cooling by HP at 20 and 28 degrees C as compared with no HP during TVE in a porcine liver I/R model. METHODS: Twenty-one pigs underwent 60 min TVE of the liver followed by 24 h reperfusion. HP was performed via the portal vein using ringerlactate solution of 4 degrees C. Pigs were assigned to three groups: TVE without HP (no-HP, n=9), TVE with HP at 28 degrees C (HP-28, n=6) and TVE with HP at 20 degrees C (HP-20, n=6). RESULTS: Perfusion volumes during TVE were 5.1+/-0.5 and 17.3+/-1.7 l in HP-28 and HP-20, respectively (P<0.05). Aspartate aminotransferase (AST) after 24 h reperfusion was 1172+/-440 U/l in no-HP as compared with 223+/-69 and 180+/-22 U/l in HP-28 and HP-20, respectively (P<0.05). No differences in liver function or histopathology were found between the HP-28 and HP-20 groups. CONCLUSIONS: HP at 20 degrees C is equally effective in preserving liver function and preventing hepatocellular injury under TVE as compared with HP at 28 degrees C. HP at 28 degrees C is advised, because of the lesser perfusion volume necessary for cooling of the liver.

Animals↗

PubMed2005

Mild hypothermic preservation for transport purposes of the AMC bioartificial liver charged with porcine hepatocytes.

BACKGROUND: Preservation conditions play a crucial role during transport of a bioartificial liver (BAL) from the laboratory to the hospital. We assessed the possibility to preserve the AMC-BAL loaded with freshly isolated porcine hepatocytes at mild hypothermic temperatures. METHODS: Two laboratory-scale AMC-bioreactors were loaded with 1 billion freshly isolated porcine hepatocytes per experiment (n=6). Bioreactors in the control group were kept for three days at 37 degrees C. Bioreactors in the transport group were kept at 37 degrees C during day 1, at 15 degrees C during day 2, and again at 37 degrees C during day 3. In addition, long-term mild hypothermic preservation periods of 45 and 110 hr at 15 degrees C and 26 degrees C, respectively, were assessed. The effect of mild hypothermic preservation on hepatocytes inside the bioreactors was tested by determination of cell damage parameters, as well as metabolic and hepatocyte-specific functions. RESULTS: A 24-hour period of mild hypothermic preservation did not reduce any hepatocyte-specific function. LDH release was significantly higher only at day 2. Albumin production at day 2 and lidocaine elimination at day 3 were significantly higher with glucose consumption and lactate production being significantly lower at both test days. Long-term mild hypothermic preservation had a drastic negative effect on cellular viability and hepatocyte-specific function. CONCLUSIONS: Mild hypothermic preservation at temperatures as low as 15 degrees C and for a duration of 24 hr is a feasible method to preserve BAL systems loaded with freshly isolated porcine liver cells and will simplify the logistics of BAL transport from the laboratory to the hospital.

Albumins↗

PubMed2005

Evidence for Galalpha(1-3)Gal expression on primary porcine hepatocytes: implications for bioartificial liver systems.

BACKGROUND/AIMS: To bridge acute liver failure (ALF) patients to orthotopic liver transplantation, several bioartificial liver (BAL) systems have been developed. The bio-component of most BAL systems consists mainly of porcine hepatocytes. Plasma or blood of ALF patients is perfused through the BAL thereby contacting porcine hepatocytes. Xenogeneic BAL systems may suffer from hyperacute rejection similar to whole-organ xenotransplants. Hyperacute rejection is mediated by antibodies directed against Galalpha(1-3)Gal, a carbohydrate structure present on most mammalian cells. Galalpha(1-3)Gal is produced by the enzyme alpha1,3-galactosyltansferase (alphaGal-T). Conflicting data have been published concerning Galalpha(1-3)Gal expression on hepatocytes in intact porcine liver. We investigated whether isolated porcine hepatocytes express Galalpha(1-3)Gal. METHODS: Immunofluorescence, flow cytometry, RT-PCR and enzyme activity assays were performed on freshly isolated and cultured porcine hepatocytes and liver biopsies. Anti-Galalpha(1-3)Gal antibodies were measured in plasma from patients treated with BAL by ELISA. RESULTS: Isolated porcine hepatocytes express (alphaGal-T) at low levels and Galalpha(1-3)Gal is present in low quantities on these cells, in contrast to hepatocytes in situ. Furthermore, IgG and IgM anti-Galalpha(1-3)Gal are depleted from the plasma of ALF patients during BAL treatment. CONCLUSIONS: Isolation and culture of porcine hepatocytes induce Galalpha(1-3)Gal expression, which may elicit immunological responses potentially compromising BAL functionality.

Animals↗

PubMed2005

Anastomosis of Riolan revisited: the meandering mesenteric artery.

The eponym anastomosis of Riolan suggests that Jean Riolan (1580-1657), a famous 17th century French anatomist, was the first to describe this mesenteric arterial connection between the superior and inferior mesenteric arteries. Riolan was a strong defender of traditional Galenic doctrine in medicine and proved a vigorous opponent of the new concept of the circulation of blood as exposed by William Harvey (1578-1657). As confirmed by examining his anatomy book published in 1649, it is unlikely that Riolan would have conceived an arterial collateral pathway in the mesocolon. He probably had observed vascular arcades running along the inner border of the colon. It was not until 1743 that Albrecht von Haller (1708-1777) gave a detailed description of the anatomy of the mesenteric arteries, referring to the arterial collateral connection between the superior and inferior mesenteric arteries as the Arcus Riolani in honor of an old master of anatomy.

Collateral Circulation↗

PubMed2005

Improved rat liver preservation by hypothermic continuous machine perfusion using polysol, a new, enriched preservation solution.

For experimental machine perfusion (MP) of the liver, the modified University of Wisconsin solution (UW-G) is most often used. In our search for an enriched MP preservation solution, Polysol was developed. Polysol is enriched with various amino acids, vitamins, and other nutrients for the liver metabolism. The aim of this study was to compare Polysol with UW-G for MP preservation of the liver. Rat livers were preserved during 24 hours with hypothermic MP using UW-G (n = 5) or Polysol (n = 5). Hepatocellular damage (aspartate aminotransferase [AST], alanine aminotransferase [ALT], lactate dehydrogenase [LDH], alpha-glutathione-S-transferase [alpha-GST]) and bile production were measured during 60 minutes of reperfusion (37 degrees C) with Krebs-Henseleit buffer. Control livers were reperfused after 24 hours of cold storage in UW (n = 5). MP using UW-G or Polysol showed less liver damage when compared with controls. Livers machine perfused with Polysol showed less enzyme release when compared to UW-G. Bile production was higher after MP using either UW-G or Polysol compared with controls. In conclusion, machine perfusion using Polysol results in better quality liver preservation than cold storage with UW and machine perfusion using UW-G.

Adenosine↗

PubMed2005

Improved machine perfusion preservation of the non-heart-beating donor rat liver using Polysol: a new machine perfusion preservation solution.

Waiting lists for transplantation have stimulated interest in the use of non-heart-beating donor (NHBD) organs. Recent studies on organ preservation have shown advantages of machine perfusion (MP) over cold storage (CS). To supply the liver with specific nutrients during MP, the preservation solution Polysol was developed. The aim of our study was to compare CS in University of Wisconsin solution (UW) with MP using UW-gluconate (UW-G) or Polysol in an NHBD model. After 30 minutes of warm ischemia, livers were harvested from rats for preservation by either CS, MP-UW-G, or MP-Polysol. After 24 hours of preservation, livers were reperfused with Krebs-Henseleit buffer (KHB). Perfusate samples were analyzed for liver damage and function. Biopsies were examined by hematoxylin and eosin staining and transmission electron microscopy. Liver damage was highest after CS compared with the MP groups. MP using Polysol compared with UW-G resulted in less aspartate aminotransferase (AST) and alanine aminotransferase (ALT) release. Perfusate flow, bile production, and ammonia clearance were highest after MP-Polysol compared with CS and MP-UW-G. Tissue edema was least after MP-Polysol compared with CS and MP-UW-G. In conclusion, preservation of the NHBD rat liver by hypothermic MP is superior to CS. Furthermore, MP using Polysol results in better-quality liver preservation compared with using UW-G.

Animals↗

PubMed2005

Dutch surgery in Japan.

An isolation policy was adopted in feudal Japan from 1639 to 1853 owing to the fear of foreign influence. During those 200 years of isolation, all foreigners were withheld from the country with the exception of the Dutch, who were permitted to establish a trading post on a small island in the Bay of Nagasaki, called Decima. Western culture and science reached the Japanese exclusively through the Dutch on Decima. Health care on Decima was provided by Dutch barber-surgeons, who introduced Western surgical practice in Japan. Official interpreters were the only Japanese allowed on Decima. It was from among these interpreters that the first Japanese surgeons arose who, having mastered the Dutch language, translated several Dutch anatomic and surgical texts. Genpaku Sugita translated a Dutch anatomy textbook into Japanese, which was completed in 1774. This book, entitled Kaitai Shinsho [New Book on Anatomy], was the first Western scientific monograph to be translated entirely into Japanese. Several Dutch surgical schools were founded through which Dutch surgery, known in Japan as "surgery of the red-haired" was propagated. According to the custom of the surgical guilds in Holland, certificates were granted to Japanese apprentices who had completed their training in Dutch surgery. About 60 Dutch surgeons had served on Decima up to 1850, providing the basis for surgery to develop in Japan. Among them, Philipp Franz von Siebold was an exceptional scholar who also had a great impact in making Japanese culture known to the Western world.

Anatomy↗

PubMed2005

Incidence and management of biliary leakage after hepaticojejunostomy.

This study analyzes the change in the management of biliary leakage after hepaticojejunostomy. Between 1993 and 2003 all patients (n = 1033) were studied with a hepaticojejunostomy as part of a pancreatoduodenectomy (n = 486), proximal bile duct resection (without liver resection) (n = 35), and biliodigestive bypass for malignant (n = 302) and benign (n = 210) disease. Biliary leakage was defined as the presence of bile-stained fluid (>50 mL) in the abdominal drain more than 24 hours after surgery, proven radiologically or at relaparotomy. The studied patients were divided into two equal periods to analyze the change in management. Overall, 24 of 1033 patients (2.3%) had biliary leakage. In multivariate analysis, a body mass index greater than 35 kg/m2 (P = .012), endoscopic biliary drainage (P = .044), and an anastomosis on the segmental bile ducts (P < .001) were independent predictors of leakage. Management in the first half of the study period (1993-1998) versus the second half (1999-2003) was maintenance of operatively placed drains (18% vs. 15%, respectively, P = 1.000), percutaneous transhepatic biliary drainage (18% vs. 69%, respectively, P = .012), surgical drainage (55% vs. 8%, respectively, P = .023), and re-hepaticojejunostomy (9% vs. 8%, respectively, P = 1.000). There was no mortality in the patients with biliary leakage. Leakage after a hepaticojejunostomy is a relatively rare complication without mortality and can safely be managed with percutaneous transhepatic biliary drainage.

Biliary Tract Diseases↗

PubMed2005

Imaging of liver function with dedicated animal dynamic pinhole scintigraphy in rats.

BACKGROUND: Non-invasive evaluation of liver function in small animal models remains a challenge. Hepatobiliary scintigraphy (HBS) enables the assessment of total and regional liver function for both uptake and excretion in larger species. AIM: To validate quantitative liver function assessment with dedicated pinhole HBS in rats. To illustrate an application of this technique, liver function was assessed in two surgical models of liver regeneration. METHODS: HBS was performed in 12 rats with 99mTc-mebrofenin on a dedicated animal pinhole gamma camera. The hepatic uptake rate was calculated twice by different observers to establish a normal range and the reproducibility of processing. The degree of hepatocellular injury and synthesis function were assessed by serum liver tests. Liver function was compared with liver weight. Subsequently, three groups of three rats were scanned on three separate days to assess the reproducibility of HBS. Finally, to illustrate an application of this technique, liver function was assessed in two surgical models of liver regeneration. RESULTS: HBS in rats was feasible without mortality. The mean liver uptake rate was 77.29+/-1.29% . min(-1). Calculation of the liver uptake (% . min(-1)) was highly reproducible (r=0.95, P<0.001). There was a good correlation between liver weight and function measured by HBS at baseline and after partial resection (r=0.94, P<0.001). CONCLUSION: HBS offers a unique combination of functional liver uptake and excretion assessment with the ability to determine the liver function reserve before and after an intervention in rats.

Aniline Compounds↗

PubMed2005

Thrombolytic therapy for acute superior mesenteric artery occlusion.

The aim of this review is to evaluate thrombolytic therapy for acute superior mesenteric artery occlusion as an alternative or adjunctive treatment modality to surgical therapy and to provide current knowledge for timely and informed decisions regarding treatment of acute mesenteric ischemia. A systematic analysis of the available literature from 1966 to 2003 regarding thrombolytic therapy for superior mesenteric artery thromboembolism was performed. A total of 20 case reports and seven small series covered 48 patients with acute superior mesenteric artery thromboembolism. In the herein reviewed series, thrombolytic therapy of acute superior mesenteric artery thromboembolism resulted in angiographic resolution of the thromboembolism in 43 patients, in clinical success without requiring additional surgical intervention in 30 patients, and in survival in 43 patients, with similar complication rates as in thrombolytic treatment of peripheral vascular occlusions. Remission of abdominal pain during the first few hours of treatment formed the most important indicator of therapeutic success. Insufficient evidence from reviewed literature is available to determine the relative effectiveness and safety of thrombolytic treatment for acute superior mesenteric artery thromboembolism; however, initial results appear to be promising. Thrombolytic therapy can be effective relatively quickly, may obviate surgery, and has the potential to resolve the clot completely. In some cases it can be used as an alternative or neo-adjunctive treatment modality to surgery. A treatment guideline for thrombolysis of acute superior mesenteric artery thromboembolism should be developed.

Algorithms↗

PubMed2005

Delayed massive hemorrhage after pancreatic and biliary surgery: embolization or surgery?

OBJECTIVE: To analyze the management of delayed massive hemorrhage (DMH) after major pancreatic and biliary surgery. SUMMARY BACKGROUND DATA: Despite a decreased mortality rate for pancreatic and biliary surgery, DMH is still an important cause of postoperative mortality. The aim of the present study was to analyze the management of DMH after pancreatic and biliary surgery, and specifically to assess the role of embolization and surgical intervention. METHODS: The study group (SG) consisted of 1010 patients from 1994 to 2002 who underwent pancreatic or biliary surgery (cholecystectomy excluded). Patients from a previous study (1983-1993, n = 686) were used as a historical control group (HCG). RESULTS: The incidence of DMH (SG 2.3% vs. HCG 3.2%) declined somewhat but did not differ significantly between both periods. The number of patients with a septic complication (SG 74% vs. HCG 50%) and a sentinel bleed (SG 78% vs. HCG 100%) before the onset of DMH did not differ significantly. Embolization (SG 2 of 2 patients vs. HCG 0 of 2 patients) was not used frequently. Successful outcome after surgical intervention (SG 14 of 16 patients vs. HCG 8 of 14 patients) and the surgical procedures performed to obtain hemostasis were comparable and overall mortality (SG 22% vs. HCG 29%) was comparable. CONCLUSIONS: The incidence of DMH declined somewhat from 3.2% to 2.3% over the past years. Most patients present with septic complications and a sentinel bleed before onset of DMH. Despite general acceptance of embolization in our unit, it was used infrequently in patients with DMH. Aggressive surgical intervention was the treatment of choice in patients with DMH after pancreatic or biliary surgery.

Adult↗

PubMed2005

Hospital volume and mortality after pancreatic resection: a systematic review and an evaluation of intervention in the Netherlands.

OBJECTIVES: To evaluate the best available evidence on volume-outcome effect of pancreatic surgery by a systematic review of the existing data and to determine the impact of the ongoing plea for centralization in The Netherlands. SUMMARY BACKGROUND DATA: Centralization of pancreatic resection (PR) is still under debate. The reported impact of hospital volume on the mortality rate after PR varies. Since 1994, there has been a continuous plea for centralization of PR in The Netherlands, based on repetitive analysis of the volume-outcome effect. METHODS: A systematic search for studies comparing hospital mortality rates after PR between high- and low-volume hospitals was used. Studies were reviewed independently for design features, inclusion and exclusion criteria, cutoff values for high and low volume, and outcome. Primary outcome measure was hospital or 30-day mortality. Data were obtained from the Dutch nationwide registry on the outcome of PR from 1994 to 2004. Hospitals were divided into 4 volume categories based on the number of PRs performed per year. Interventions and their effect on mortality rates and centralization were analyzed. RESULTS: Twelve observational studies with a total of 19,688 patients were included. The studies were too heterogeneous to allow a meta-analysis; therefore, a qualitative analysis was performed. The relative risk of dying in a high-volume hospital compared with a low-volume hospital was between 0.07 and 0.76, and was inversely proportional to the volume cutoff values arbitrarily defined. In 5 evaluations within a decade, hospital mortality rates were between 13.8% and 16.5% in hospitals with less than 5 PRs per year, whereas hospital mortality rates were between 0% and 3.5% in hospitals with more than 24 PRs per year. Despite the repetitive plea for centralization, no effect was seen. During 2001, 2002, and 2003, 454 of 792 (57.3%) patients underwent surgery in hospitals with a volume of less than 10 PRs per year, compared with 280 of 428 (65.4%) patients between 1994 and 1996. CONCLUSIONS: The data on hospital volume and mortality after PR are too heterogeneous to perform a meta-analysis, but a systematic review shows convincing evidence of an inverse relation between hospital volume and mortality and enforces the plea for centralization. The 10-year lasting plea for centralization among the surgical community did not result in a reduction of the mortality rate after PR or change in the referral pattern in The Netherlands.

Chi-Square Distribution↗

PubMed2005

Bovine intestinal alkaline phosphatase attenuates the inflammatory response in secondary peritonitis in mice.

Lipopolysaccharide (LPS) contributes importantly to morbidity and mortality in sepsis. Bovine intestinal alkaline phosphatase (BIAP) was demonstrated to detoxify LPS through dephosphorylation. LPS injection combined with BIAP reduced inflammation and improved survival in various experimental settings. In this study, single-dose intravenous administration of BIAP (0.15 IU/g) was applied in a murine cecal ligation and puncture (CLP) model of polymicrobial sepsis. Saline was given as control (S group). Treatment with BIAP prior to CLP (prophylaxis; BIAP-P group) or shortly after (early treatment; BIAP-ET group) reduced cytokine concentrations in plasma and peritoneal lavage fluid (PLF). Tumor necrosis factor-alpha peak levels decreased from 170 pg/ml (S) to 57.5 (BIAP-P) and 82.5 (BIAP-ET) in plasma and in PLF from 57.5 pg/ml (S) to 35.3 (BIAP-P) and 16.8 (BIAP-ET) (all, P < 0.05). Peak interleukin-6 levels in plasma decreased from 19.3 ng/ml (S) to 3.4 (BIAP-P) and 11.5 (BIAP-ET) and in PLF from 32.6 ng/ml (S) to 13.4 (BIAP-P) and 10.9 (BIAP-ET) (all, P < 0.05). Macrophage chemoattractant protein 1 peak levels in plasma decreased from 2.0 ng/ml (S) to 1.0 (BIAP-P) and 0.7 (BIAP-ET) and in PLF from 6.4 (S) to 2.3 (BIAP-P) and 1.3 ng/ml (BIAP-ET) (all, P < 0.05). BIAP-treated groups showed decreased transaminase activity in plasma and decreased myeloperoxidase activity in the lung, indicating reduced associated hepatocellular and pulmonary damage. Survival was not significantly altered by BIAP in this single-dose regimen. In polymicrobial secondary peritonitis, both prophylactic and early BIAP treatment attenuates the inflammatory response both locally and systemically and reduces associated liver and lung damage.

Alanine Transaminase↗