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Heikki Mäkisalo

Publications and source records attributed to Heikki Mäkisalo.

16 recordsLinked to original sources
PubMed2006

Graft protein C entrapment is associated with reduced phagocyte activation during reperfusion in human liver transplantation.

OBJECTIVE: To explore the potential anti-inflammatory role of protein C pathway in ischemia-reperfusion injury during liver transplantation. DESIGN: Prospective, observational clinical study. SETTING: Tertiary teaching hospital. PATIENTS: Fifty adult patients undergoing liver transplantation for acute liver failure or chronic liver disease. INTERVENTIONS: To assess changes occurring across the transplanted liver, samples of blood entering and leaving the graft were obtained simultaneously from portal and hepatic veins. Plasma protein C and activated protein C levels, neutrophil and monocyte CD11b and L-selectin expression, and leukocyte differential counts were measured. Postoperative liver function and outcome of transplantation were recorded. MEASUREMENTS AND MAIN RESULTS: During reperfusion, protein C became entrapped within the graft (portal vein 49% [20-96%]; graft caval effluent 25% [12-76%], p < .001), without concomitant activated protein C outflow from the graft. Simultaneously, marked neutrophil and monocyte activation occurred within the graft. Enhanced hepatic protein C entrapment was associated with reduced neutrophil and monocyte activation (R = .377, p = .011; R = .389, p = .008, respectively) during reperfusion. CONCLUSIONS: Protein C entrapment occurs immediately during reperfusion in the graft without concomitant activated protein C release, suggesting a shortage of activated protein C in the reperfused graft. The ongoing inflammatory response during reperfusion may lead to protein C and activated protein C utilization within the graft. Indeed, hepatic protein C entrapment is associated with reduced hepatic phagocyte activation, suggesting a regulatory role for protein C pathway in hepatic reperfusion in human liver transplantation.

Adult↗
PubMed2006

A prospective, randomized, multi-centre trial of systemic adjuvant chemotherapy versus no additional treatment in liver transplantation for hepatocellular carcinoma.

The role of adjuvant systemic chemotherapy in liver transplantation (LT) for hepatocellular carcinoma (HCC) is controversial. Here, we report the results of a Nordic prospective, randomized, multi-centre trial of systemic low-dose doxorubicin in patients with HCC. Between February 1996 and April 2004, 46 patients were randomized to receive either neoadjuvant doxorubicin in combination with LT (chemo group; n = 19) or LT alone (control group; n = 27). In the chemo group, doxorubicin was administered intravenously, 10 mg/m(2) weekly, starting from acceptance onto the waiting list for LT. One intraoperative dose of 15 mg/m(2) was given, and postoperatively doxorubicin was given weekly at a dose of 10 mg/m(2), depending on the clinical course, up to a cumulative dose of 400 mg/m(2). Actuarial, 3-year overall survival (OS) and disease-free survival (DFS) in the control group were 70% and 50%, respectively. In the chemo group, both OS and DFS were 63%. Freedom from recurrence at 3 years was 55% in the control group and 74% in the chemo group. None of the differences was statistically significant. Neoadjuvant treatment with systemic low-dose doxorubicin seems not to improve either survival or freedom from recurrence in patients with HCC undergoing LT.

Aged↗
PubMed2005

Spontaneous rupture of a hepatic cystadenoma and cystadenocarcinoma: report of two cases.

Hepatobiliary cystadenomas and cystadenocarcinomas are rare tumors. Differentiating between these tumors and benign hepatic cysts may be difficult. Because of their rarity, diagnosis is often delayed and may result in inaccurate treatment, resulting in unnecessary morbidity and mortality. The purpose of this report is to draw attention to these entities and their complications. We report on two cases with spontaneous rupture of hepatobiliary cystadenoma and cystadenocarcinoma cysts, initially treated as simple hepatic cysts by aspiration, or by aspiration combined with sclerotherapy. The spontaneous rupture of the cysts appeared years after the initial treatment of the cysts, leading in one case to a prolonged stay in an intensive care unit. In both cases, a formal liver resection was carried out and microscopic investigations revealed a mucinous cystadenocarcinoma and cystadenoma. In conclusion, although hepatobiliary cystadenomas and cystadenocarcinomas are rare findings, they should not be forgotten in the diagnostic workshop when examining patients with hepatic cysts. If hepatobiliary cystadenomas and cystadenocarcinomas cannot be excluded following radiological imaging, surgery is recommended.

Adult↗
PubMed2005

Preoperative hepatic 3D models: virtual liver resection using three-dimensional imaging technique.

Emerging new techniques for liver resections set new requirements for the preoperative imaging and planning. Open surgery is a three-dimensional procedure and planning of the resection line may be difficult when basing on conventional two-dimensional CTs or MRIs, although all the information is there. With multidetector-row CT (MDCT), thin slices can be obtained with excellent temporal resolution, and precise three-dimensional (3D) models can be created. We regard 3D imaging technique useful in most liver resections. It improves the surgeon's knowledge of liver anatomy and makes even more complicated liver resections safe. Better knowledge of three-dimensional appearances of liver structures may further improve the results of curative liver surgery. However, before becoming a routine clinical procedure, research and development are still needed. Also, careful testing and evaluation of the methods have to be performed. In the future, 3D models will probably play an important role in the preoperative planning of liver resections.

Computer Simulation↗
PubMed2005

Activated protein C reduces graft neutrophil activation in clinical renal transplantation.

We studied the role of endogenous activated protein C (APC), the major physiological anti-coagulant with concomitant anti-inflammatory properties, on ischemia/reperfusion (I/R) in 45 patients participating in a larger trial comparing three immunosuppressive protocols in cadaveric renal transplantation: perioperative anti-thymocyte globulin (ATG, Fresenius AG, Bad Homburg, Germany), perioperative basiliximab and conventional triple therapy. Blood samples for assessing plasma APC, protein C, and lactoferrin concentrations, neutrophil CD11b and L-selectin expressions and blood leukocyte differential counts were obtained preoperatively and before reperfusion from central venous cannula, complemented with simultaneous samples from iliac artery and graft vein for calculation of transrenal differences (Delta) of study parameters at 1 and 5 min after reperfusion. Unlike basiliximab or conventional therapy groups, ATG infusion induced a substantial increase in plasma APC concentration (119 [88-144]% before infusion vs. 232 [85-1246]% after infusion, p<0.001), resulting in renal graft sequestration of APC at 1 min after reperfusion (Delta=-72 [-567 to 12]%, p<0.001). Graft APC consumption was associated with transrenal reduction of neutrophil activation markers (L-selectin r=0.7, p=0.01; lactoferrin r=-0.6, p=0.02; CD11b r=-0.8, p=0.001), and with both warm (r=0.6, p=0.01) and cold ischemia time (r=0.6, p=0.02) and donor age (r=0.6, p=0.01). These findings suggest that APC has an anti-inflammatory role in I/R injury in clinical renal transplantation.

Anti-Inflammatory Agents↗
PubMed2004

Association of graft neutrophil sequestration with delayed graft function in clinical renal transplantation.

BACKGROUND: The authors studied the impact of neutrophil activation, detected in experimental models, on reperfusion injury in clinical renal transplantation. METHODS: Forty-five patients from a larger trial comparing three immunosuppressive protocols were recruited: perioperative antithymocyte globulin (ATG) with low initial cyclosporine A (CsA) triple therapy (group A, n=15); two-dose basiliximab with low initial CsA triple therapy (group B, n=16); and conventional triple therapy (group C, n=14). Blood samples were obtained preoperatively, before reperfusion, and at 1 and 5 min after reperfusion. During reperfusion, samples were collected from the iliac artery and the graft vein for calculation of transrenal differences (Delta) of study parameters. Leukocyte differential counts, plasma lactoferrin concentration, and neutrophil CD11b and L-selectin expressions were assessed. Graft blood flow was measured at 2 and 30 min after reperfusion. RESULTS: ATG induced neutrophil activation already before reperfusion. Thus, group A was excluded, but groups B and C were pooled for analysis of reperfusion-induced neutrophil activation. At 1 min after reperfusion, lactoferrin concentration was higher in graft vein than iliac artery, yielding Delta=15 microg/L (P<0.05). Concomitantly, Delta neutrophil count correlated with both Delta L-selectin expression (R=0.49, P=0.012) and graft blood flow at 2 min (R=0.51, P=0.007). At 5 min after reperfusion, 0.17 (-1.0-0.24)x10 cells/L neutrophils were sequestered in the graft (P<0.001). This sequestration correlated with graft blood flow at 30 min (R=0.53, P=0.005) and was stronger in patients with delayed graft function (DGF) (Delta = -0.38 [-1.45 to -0.2]) than those without (Delta = -0.12 [-0.41-0.24], P<0.001). In multiple regression analysis, sequestration was the most important parameter associated with DGF. CONCLUSIONS: Neutrophils are activated and sequestered in the reperfused graft during clinical renal transplantation. Neutrophil sequestration is a powerful independent factor explaining the incidence of DGF.

Adolescent↗
PubMed2004

Liver transplantation for primary sclerosing cholangitis; predictors and consequences of hepatobiliary malignancy.

BACKGROUND/AIMS: Hepatobiliary malignancies are frequently seen in primary sclerosing cholangitis (PSC) and they complicate the evaluation of patients and timing of liver transplantation. METHODS: Data from all Nordic PSC patients listed for liver transplantation during 1990-2001 were recorded prospectively. Predictors of hepatobiliary malignancy and patient survival rates have been analysed. RESULTS: Hepatobiliary malignancy was found in 52/255 (20%) patients accepted to the waiting list. Recent diagnosis of PSC, no ursodeoxycholic acid (UDCA) treatment, clinical suspicion and previous colorectal-cancer were predictors of malignancy. Among 89 patients with a strong suspicion of malignancy prior to acceptance, 35 (39%) had confirmed malignancy. A clinical suspicion had been raised in 35/52 (67%) patients with malignancy. Malignancy was found in 31/223 patients who received a liver allograft. The 1-, 3- and 5-year patient survival rates following transplantation for patients with PSC and cholangiocarcinoma were 65, 35 and 35%, respectively. CONCLUSIONS: Hepatobiliary malignancy is suspected in 1/3 of the PSC patients and found in 1/5. Although cholangiocarcinoma is regarded as a contraindication to liver transplantation (LTX), PSC patients with cholangiocarcinoma had a 35% 5-year survival following transplantation.

Adult↗
PubMed2003

Activation of protein C during reperfusion in clinical liver transplantation.

BACKGROUND: Activated protein C (APC) exhibits anticoagulant and antiinflammatory properties. We studied the kinetics and magnitude of protein C activation in clinical liver transplantation and the interaction of this activation with neutrophil and monocyte activation. METHODS: In 10 patients undergoing liver transplantation, we measured plasma protein C and APC levels, neutrophil and monocyte CD11b and L-selectin expression, and leukocyte differential counts pre-, intra-, and postoperatively. Samples of blood entering and leaving the liver were obtained simultaneously to assess changes across the liver. RESULTS: Protein C level was low preoperatively (65%, range 39%-141%) and remained low throughout surgery. Compared with the preoperative level (107%, range 78%-161%), APC level increased during liver reperfusion (471%, range 183%-917%, P=0.05). A transhepatic decrease in protein C level (-16%, range -45%-5%, P=0.007), but not in APC level, occurred during initial liver reperfusion. At the same time, neutrophil and monocyte activation took place in the liver. CONCLUSIONS: Despite protein C deficiency, patients with liver insufficiency are able to maintain normal APC levels. During reperfusion, protein C consumption occurs in the liver without concomitant hepatic release of APC, indicating a shortage of APC in the reperfused liver. The process consuming protein C and APC may be related to the simultaneous ongoing neutrophil and monocyte activation within the liver graft, indicating a regulatory role for APC in inflammation.

Adult↗
PubMed2003

Liver transplantation for primary sclerosing cholangitis in the Nordic countries: outcome after acceptance to the waiting list.

Primary sclerosing cholangitis (PSC) is a common indication for liver transplantation, but evaluation of patients and timing of liver transplantation remain as major problems. Data from PSC and control patients listed for liver transplantation from 1990 through 2000 in the Nordic countries were recorded prospectively. Outcomes from the waiting list and after transplantation have been recorded for both groups. For PSC patients, regression analyses have been performed to analyze predictors of outcome. A total of 255 PSC and 610 control patients were accepted on the liver transplantation waiting list from 1990 to 2000. In the PSC group, 223 patients (87%) received a first liver allograft, and 32 patients (13%) died without transplantation. The corresponding figures for the control group were 89% and 10%. For PSC patients, the 5- and 10-year survival from the time of acceptance was 68% and 58%, respectively. A higher Model for End-Stage Liver Disease score and a shorter duration of PSC predicted death on the waiting list for PSC patients. PSC is a frequent indication for liver transplantation. In our material, serum bilirubin or Model for End-Stage Liver Disease score and PSC duration are predictors of outcome including survival of the waiting list.

Adolescent↗
PubMed2002

Management and outcome of major bile duct injuries after laparoscopic cholecystectomy: from therapeutic endoscopy to liver transplantation.

Laparoscopic cholecystectomy is associated with a higher rate of bile duct injuries than an open cholecystectomy. The annual incidence of bile duct injuries has remained almost constant and these injuries tend to be more serious, making demands on the method of repair. We wanted to report the management and outcome of major bile duct injuries after laparoscopic cholecystectomy in patients referred to a hepatobiliary and liver transplantation unit. Eighteen patients (14 women), with a median age of 53.5 years were referred to the liver surgery unit with a major bile duct injury after laparoscopic cholecystectomy. The injury was identified after a median of 3 days (range, 0 to 25 days) after operation and the median time interval to referral was 79 days (0 to 2270 days). Fourteen patients had undergone surgery before referral. By the time of referral, four patients had developed end-stage cirrhosis, necessitating liver transplantation. Three of them had undergone bilioenteric drainage operations at the referring institute. Of the remaining 14 patients, three were managed by therapeutic endoscopic procedures. Ten patients were managed with Roux-en-Y hepaticojejunostomy. One died of septic complications before the repair. A median time for hospitalization in our unit was 33 days (range, 10 to 164 days). At present, 16 patients are alive. One patient died of Kaposi's sarcoma 7 months after liver transplantation. A long interval between bile duct injury and referral was associated with the development of end-stage liver disease. Surgery of biliary lesions is demanding, and surgical experience with multidisciplinary approach, including therapeutic endoscopy and liver transplantation, is necessary for successful outcome.

Adult↗