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Biomedical subjects

M Golling

Publications and source records attributed to M Golling.

At least 19 recordsLinked to original sources

Evaluation of microperfusion disturbances in the transplanted liver after Kupffer cell destruction using GdCl3: an experimental porcine study.

BACKGROUND: Organ function after liver transplantation is determined by ischemia-reperfusion injury. Destruction of Kupffer cells with gadolinium chloride (GdCl3) has been shown to have a possible preventive effect on the extent of this injury, which can be extrapolated by analyzing the distribution of hepatic microperfusion. The aim of this study was to evaluate the protective effect of GdCl3 on disturbances of microperfusion in the transplanted liver. METHODS: Landrace pigs were randomly divided into three groups. In the control group (CG; n=6) a mapping of the native liver was conducted. For mapping, the four hepatic liver lobes were named from right to left with A to D and every lobe was divided into three vertical segments (cranial, medial, and caudal). In each of these 12 areas, microperfusion was quantified using a thermodiffusion probe (TD [mL/100 g/min]). The other two groups were considered as transplanted treated group (TTG; n=10) and transplanted nontreated group (TnTG; n=10). The TTG received an infusion of 20 mg/kg GdCl3 intravenously 24 hours before organ harvesting. Then standardized orthotopic liver transplantation was performed. In TnTG, standardized orthotopic liver transplantation was carried out without prior GdCl3 injection. In the recipients, the microperfusion of transplanted livers were mapped in both TnTG and TTG, in two different time points (1 hour [n=5] and 24 hours (n=5]) after reperfusion. RESULTS: A significant reduction of macrophages in the TTG livers in comparison to the CG and TnTG livers was observed (P<.05). However, the number of macrophages in CG and TnTG livers showed no significant difference (P>.05). Regarding liver microperfusion, in TnTG, a marked heterogeneity was detected in the livers after reperfusion. Significant differences between liver lobes (horizontal planes; P=.032) and vertical layers of intralobar liver parenchyma (P=.029) were observed. The same pattern was seen in TTG livers after reperfusion and a significant difference between horizontal (P=.024) and vertical layers (P=.018) of liver tissue were observed. Comparing intralobar regional flow data between vertical planes 24 hours after reperfusion still showed a prominent variation of hepatic tissue perfusion in TnTG livers (P=.028). Within the same horizontal layers, no significant differences between lobes were measured anymore (P=.16). Contrary to TnTG, in TTG, a homogenous pattern of regional liver tissue perfusion was recorded 24 hours after reperfusion. Comparison of TD data on the liver regions showed no significant microperfusion differences in either horizontal (P=.888) or vertical (P=.841) layers. CONCLUSIONS: Application of GdCl3 resulted in a significant reduction of Kupffer cells. Twenty four hours after transplantation microperfusion showed a homogeneous pattern, which constituted an earlier and better recovery of the transplanted liver. Therefore, destruction of Kupffer cells reduced ischemia-reperfusion injury and seemed to be responsible for the early recovery of microperfusion disturbances and thus for an improvement of graft function.

Animals↗

[Colorectal cancer liver metastases -- neoadjuvant concepts for preoperative down-sizing].

Liver resection for colorectal metastases disease can be performed with curative intent at low morbidity and mortality. Only 15-30 % of liver metastases are amenable to potentially curative resection. Five year survival following primary and repeat liver resection has consistently been reported as 25-40 %. Future strategies focus at widening the indication and extending therapeutic options. The aim of neoadjuvant treatment of irresectable liver metastasis is the conversion to secondary resectability either via increasing residual liver mass (portal vein embolisation/2-stage resection) and/or reducing tumor load via chemotherapy ("down-sizing"). Current data suggest resectability following neoadjuvant chemotherapy in around 8 % of cases but varying between 1-33 %.

Antineoplastic Combined Chemotherapy Protocols↗

Nutritional support after open liver resection: a systematic review.

BACKGROUND: Perioperative nutrition in patients with limited liver function after partial hepatic resection is still controversial. In particular, the significance of perioperative total enteral nutrition remains unresolved. The aim of this review is to investigate the impact of early postoperative total enteral nutrition on convalescence after partial liver resection. MATERIALS AND METHODS: In an internet-based Medline-Search (time course: 1960-08/2005) a total of five prospective, randomized controlled trials were found comparing the impact of enteral and parenteral nutrition after liver resection. After study validity had been established, a systematic review was undertaken (odds ratio, 95% confidence interval, p < 0.05 level of significance; Review Manager 4.2, The Cochrane Collaboration). Primary endpoints were complication rate (infection, organ malfunction) and mortality. Standardized immune parameters were also surveyed. RESULTS: Statistical analysis showed that enteral nutrition resulted in a significantly lower rate (p = 0.04) of wound infection and catheter-related complications than parenteral nutrition did. No statistically significant differences in mortality due to enteral or parenteral nutrition could be found. Patients receiving enteral nutrition showed better postoperative immune competence. CONCLUSION: Early enteral nutrition after liver resection is a safe procedure. Compared to parenteral nutrition it is associated with a decreased incidence of postoperative complications. Facing the inhomogeneity of these trials, especially in nutrition protocols and end points, this first systematic review stresses the need for an update of the importance of early enteral nutrition after liver resection within randomized controlled multicenter trials.

Hepatectomy↗

Surgical resection of colorectal liver metastases--the current standard therapy (review).

Liver resection for colorectal metastases can be performed with curative intent in about 15-20% of patients. From a surgical point of view a radical (R0) resection is of paramount importance. Perioperative mortality is mainly linked to the extent of the liver resection (class I/II). Results of ischemic or drug induced preconditioning have been ambiguous and their clinical use is at most questionable. Five year survival following primary and repeat liver resection is consistently reported as 30-40%. Options for improvement of prognosis by purely technical means appear limited. Instead, future strategies aim at increasing the number of patients (with primarily irresectable and potentially respectable disease) amenable to curative liver resection. This could be achieved preoperatively via portal vein embolisation and neoadjuvant chemotherapy and surgically via sequential resection or a combination of surgery with local ablative therapy. All suggested modalities performed in primarily inoperable tumors should be systematically evaluated in clinical trials.

Colorectal Neoplasms↗

Passively mode-locked 914-nm Nd:YVO4 laser.

We demonstrate what is to our knowledge the first mode-locked Nd:YVO4 laser operating on the 4F3/2-4I9/2 transition at 914 nm. Using a semiconductor saturable-absorber mirror for passive mode locking, we have obtained 3-ps pulses at a repetition rate of 233.8 MHz. The laser is based on a standard delta cavity and is pumped by a Ti:sapphire laser. We obtained an average output power of 42 mW through one mirror and an accumulated output power of approximately 150 mW (through all cavity mirrors) at a pump power of 1.4 W.

Journal Article↗

[Standard surgical resection of colorectal liver metastases].

Liver resection for colorectal metastases can be performed with curative intent in about 15-20% of patients. From a surgical point of view, achieving a radical (R0) resection is of paramount importance. Perioperative mortality is mainly linked to the extent of the resection (class I/II). Results of ischemic or drug-induced preconditioning have been ambiguous, and their clinical use is at most questionable. Five-year survival following primary and repeated liver resection is consistently reported at 30-40%. The options for improving prognosis by purely technical means appear limited. Instead, future strategies must aim at the conversion of primarily irresectable and potentially resectable liver metastases into resectable tumors. This could be achieved preoperatively via portal vein embolisation and neoadjuvant chemotherapy and surgically via sequential resection or a combination of surgery with local ablative therapy. All suggested modalities for primarily inoperable tumors should be systematically evaluated in clinical trials.

Colorectal Neoplasms↗

Does the liver ever age? Results of liver transplantation with donors above 80 years of age.

INTRODUCTION: Facing an increasing shortage of donor organs, donor criteria become more extended and so-called marginal organs are accepted for transplantation. For liver donation donor age above 70 years is accepted as a risk factor concerning primary dysfunction or nonfunction. Therefore, the aim of this study was to compare the early outcome of grafts older versus younger than 80 years of age. PATIENTS AND METHOD: Between August 2002 and February 2004, 40 adult liver transplants were performed using triple immunosuppression with tacrolimus, MMF, and low-dose corticosteroids. Recipients with HCC received low-dose rapamycin after postoperative day 14. The outcome of grafts from donors under 80 years of age (n=35) was compared with those from donors 80 years old or more (n=5). For statistical analysis Mann-Whitney-U-Test and Fisher's Exact Test were used with P < .05 considered statistically significant. RESULTS: The average donor age of our population was 54.4 +/- 17.3 years with five donors older than 80 years (80-83 years). These donors all had additional risk factors. The recipients of the latter grafts suffered from HCC and liver cirrhosis Child A (n=2) or from viral hepatitis (n=3). One recipient had advanced cirrhosis with severe complications. The outcomes of both groups were comparable concerning intraoperative and postoperative courses. All recipients of old liver grafts left the hospital with stable graft function. CONCLUSION: Liver grafts over 80 years can be transplanted with good results, especially if given to recipients with malignancy and otherwise stable liver function.

Age Factors↗

Influence of methicillin-resistant Staphylococcus aureus carrier status in liver transplant recipients.

The prevalence of methicillin-resistant Staphylococus aureus (MRSA) has increased worldwide and MRSA has emerged as an important cause of sepsis in cirrhotic patients and liver transplant recipients. In this retrospective study, the prevalence of MRSA colonization and its influence on infections following orthotopic liver transplantation (OLT) was investigated. From August, 2002 until November, 2004, 66 primary cadaver OLT were performed for adult recipients. Antibody induction used Daclizumab (n = 49) or ATG (n = 14). Maintenance immunosuppression consisted of tacrolimus and steroids, with 30 patients receiving mycophenolate mofetil and 4, rapamune. For perioperative anti-infectious prophylaxis cefotaxime, metronidazole, and tobramycin were administered for 48 hours. The preoperatively performed routine swabs revealed MRSA colonization in 12 of 66 (18.2%) patients. The stage of cirrhosis was equivalent for MRSA(-) patients according to Child score. The mean MELD score was significantly higher for MRSA(+) patients (24.3 versus 18.7, P = .036). More MRSA(+) patients were hospitalized at the time of transplantation (14/54 versus 8/12, P = .018). The incidence of posttransplant infections was not significantly different among the two groups. Within the first year 7 of 66 (10.6%) patients died: 3 of 12 (25%) MRSA(+) and 4 of 54 (7.4%) MRSA(-). The 1-year survival was lower in the MRSA(+) group (74.1% versus 94.1%). In conclusion, this study did not show that an MRSA-positive carrier status implies an increased risk for septic complications following OLT. Mortality was increased for MRSA(+), but failed to show a significant difference. A significantly higher MELD score and pretransplant hospitalization for MRSA(+) patients may contribute to the higher mortality and reflect sicker patients.

Carrier State↗

Compact 10-GHz Nd:GdVO4 laser with 0.5-W average output power and low timing jitter.

We demonstrate a compact, diode-pumped Nd:GdVO4 laser with a repetition rate of 9.66 GHz and 0.5-W average output power. The laser is passively mode locked with a semiconductor saturable absorber mirror (SESAM), yielding 12-ps-long sech2-shaped pulses. For synchronization of the pulse train to an external reference clock, the SESAM is mounted on a piezoelectric transducer. With an electronic feedback loop of only a few kilohertz loop bandwidth we achieved a rms timing jitter of 146 fs (integrated from 10 Hz to 10 MHz). This is an upper limit because it is mostly limited by the measurement system. The laser setup with a simple linear cavity has a footprint of only 130 mm x 30 mm.

Journal Article↗

Predicting creatinine clearance by a simple formula following live-donor kidney transplantation.

The outcome after live-donor kidney transplantation is influenced by many parameters. The aim of our study was to establish a multivariate prognostic model for calculating the recipient's creatinine clearance after transplantation. Basic immunological, donor-, recipient- and process-related variables were assessed in a series of 18 live-donor kidney transplant patients with an uncomplicated postoperative course. Multivariate analysis was carried out with automated forward and backward selection. The following four parameters were included in the predictive model: recipient age, recipient BMI, graft clearance and degree of relationship. The coefficient of determination (R(2)) was 0.67. It could be shown that a significant prediction of creatinine clearance after living related kidney transplantation can be made, based on simple variables. Therefore, this formula could help to detect early complications in the post-transplantation course if the recipient's creatinine clearance drops below the predicted result.

Adolescent↗

[Locally recurrent rectal carcinoma].

There is no doubt that surgical treatment with curative intent is warranted in patients with recurrent colorectal cancer. This is also true for locally recurrent rectal cancer. Operative procedures are demanding but may be curative if complete excision can be achieved. Preoperative radiochemotherapy has helped to improve resectability, but operative morbidity is still high. Procedure-related mortality on the other hand is low, at around 3%, and 25% 5-year survival can be expected after complete excision.

Combined Modality Therapy↗

[Consensus-recommendations for sirolimus in liver transplantation].

Sirolimus is an m-TOR inhibitor without renal side effects and potentially protects against the development of malignancy. Due to a higher incidence of complications in two trials and an official warning in the drug information, the use of Sirolimus in liver transplantation is limited. The participants of this consensus meeting had to analyse and evaluate the literature with respect to the potential role of Sirolimus in liver transplantation. This consensus statement follows the scheme normally employed for the presentation of guidelines including the grading of evidence (1a-5) and the extent of recommendation (A-C). Moreover, the consensus included the experience of the authors with respect to the handling of Sirolimus after liver transplantation.

Drug Therapy, Combination↗

Characterization of hepatic parenchymous perfusion heterogeneity and regional flow kinetics after porcine liver transplantation.

BACKGROUND: In clinical practice, a heterogeneous hepatic tissue microperfusion (MC) is often observed after liver resection or transplantation (LTx). Nevertheless this hepatic perfusion phenomenon has never been really quantified with respect to its anatomic distribution and time course in detail. The aim of the study was to characterize liver perfusion heterogeneity and local flow kinetics both in the physiological situation and after standardized ischemia and reperfusion using an established model of porcine LTx. METHODS: Regional distribution of hepatic MC in healthy native porcine livers (control group; n = 8) was analyzed in comparison with data derived 60 min, 24 h, and 72 h after porcine LTx (transplantation group; n = 8 each subgroup; cold ischemia time: 5.7 +/- 1.2 h). MC was measured with implanted thermal diffusion electrodes (TD). Flow in hepatic artery and portal vein was continuously detected by ultrasonic probes. For standardization of measurement localizations, porcine liver lobes were divided anatomically into three horizontal layers (cranial, medial, caudal), defining 12 distinct hepatic measurement regions. RESULTS: In the control group, a homogenous liver MC with a mean flow of 81.6 +/- 13.9 ml/100 g/min was detected in all regions. After LTx, a marked MC heterogeneity was noted 60 min after reperfusion. MC rehomogenization was first documented within horizontal liver planes 24 h later. Comparison of MC between planes showed persisting heterogeneity with a significant intralober drop of mean MC in the cranio-caudal direction. Complete MC rehomogenization (both between horizontal and vertical liver planes) was detected 72 h after reperfusion. Still, an overall reduction of mean liver perfusion by about 15% was existent. CONCLUSIONS: A homogenous tissue perfusion was observed in healthy porcine livers. In contrast, marked heterogeneity of hepatic MC was detected after LTx. Heterogeneity presents as a very dynamic and temporary phenomenon. Early horizontal flow rehomogenization and reconstitution of normal blood flow, particularly primarily in the cranial liver layers, appear to be characteristic features during early flow reconstitution after postischemic reperfusion. Due to heterogeneity and time-dependent flow dynamics, measurement of MC volumes at single hepatic regions may not always allow a valid characterization of liver perfusion quality during the first 24 h after postischemic reperfusion.

Animals↗

Experimental monitoring of hepatic glucose, lactate, and glutamate metabolism by microdialysis during surgical preparation of the liver hilus.

Mechanical liver manipulation can lead to hepatic microcirculation (MC) impairment. The pathobiochemical relevance of this phenomenon is not fully understood. Microdialysis (MD) allows a quantification of metabolic products in interstitial fluid, thus enabling analysis of the hepatic metabolic state during changes of liver perfusion. The aim of the study was to quantify the functional effects of standardized surgical liver preparation both on liver metabolism and microperfusion. Two groups of animals (pigs, n = 25) were formed: In the trial group (TG; n = 13) the liver was mobilized, followed by hilar preparation. In the control group (CG; n = 12) mobilization of the liver without hilar dissection was performed. Surgical manipulation was followed by an observation in both groups. Hepatic interstitial glucose, lactate, and glutamate concentrations were detected by MD and liver MC by thermodiffusion. During liver mobilization MC decreased significantly in both groups (TG; 86.7 +/- 2.0 to 73.4 +/- 2.3 ml/100 g min; and CG; 88.3 +/- 3.1 to 71.9 +/- 2.2 ml/100 g/min). In the trial group levels decreased further during hilar preparation reaching minimal values of 65.6 +/- 2.8. After preparation MC recovered to baseline. Glucose, lactate, and glutamate concentrations increased significantly during liver mobilization in the trial (glucose; 0.52 +/- 0.13 to 0.88 +/- 0.19 mmol/L; lactate; 0.34 +/- 0.07 to 0.54 +/- 0.07 mmol/L; glutamate; 34.5 +/- 3.6 to 52.6 +/- 8.0 micromol/L) and control group (glucose; 0.58 +/- 0.06 to 0.95 +/- 0.13 mmol/L; lactate; 0.30 +/- 0.06 to 0.49 +/- 0.07 mmol/L; glutamate; 32.9 +/- 2.36 to 56.1 +/- 5.12 micromol/L). Throughout hilus preparation maximum values could be measured in TG (glucose; 1.69 +/- 0.34; lactate; 0.90 +/- 0.18; glutamate; 63.5 +/- 7.2). After termination of mobilization or preparation baseline concentrations were reached again. MD allows monitoring of metabolic changes in hepatic parenchyma. Surgical liver preparation leads to changes of intrahepatic glucose, lactate, and glutamate levels (without alterations of parameters in systemic plasma) along with hepatic MC impairment. Reconstitution of hepatic MC was accompanied by rapid normalization of metabolic parameters. By measuring specific parameters, MD could prove to be of use for functional assessment of metabolic effects due to MC disturbances.

Animals↗

Surgical therapy for loco-regional recurrence and distant metastasis of gastric cancer.

The appearence of distant metastases or local recurrence is assumed to render gastric cancer incurable. However, experience with colorectal cancer has shown that patients with recurrent disease may have a chance for cure, if recurrent or metastatic disease can be completely resected. Since improved imaging allows detection of ever smaller tumour deposits, we have reviewed the pertinent literature to determine the current surgical options for recurrent or metastatic gastric cancer. Metastatic disease or local recurrence is rarely resectable. Tumour recurrence in the remnant stomach after partial gastrectomy can be treated by secondary total gastrectomy and may occasionally result in long-term survival. Other types of local recurrence are generally not amenable to complete resection. The same is true for distant metastases. If, however, distant metasases are technically resectable, 5 year survival of approximately 20% has been documented. Solitary and late appearing metachronous tumours are associated with an improved prognosis. As a consequence resection of distant metastases should be considered, because the risk of metastasectomy is generally low and there is no alternative treatment with a chance for cure.

Adult↗