Jouni Lauronen

High survival rates after liver transplantation for hepatoblastoma and hepatocellular carcinoma

Kosola S, Lauronen J, Sairanen H, Heikinheimo M, Jalanko H, Pakarinen M. High survival rates after liver transplantation for hepatoblastoma and hepatocellular carcinoma.
Pediatr Transplantation 2010: 14:646–650.

Endoscopic surveillance and primary prophylaxis sclerotherapy of esophageal varices in biliary atresia.

Objectives: Evidence-based recommendations on endoscopic screening and prophylactic treatment of esophageal varices in patients with biliary atresia (BA) are scarce. We assessed the efficiency of endoscopic surveillance and risk factors of esophageal varices and associated upper gastrointestinal bleeding. Methods: A total of 47 consecutive children with BA and portoenterostomy underwent yearly endoscopies and prophylactic injection sclerotherapy of esophageal varices between 1987 and 2009. The median follow-up was 1.7 years (range 0.5–18.9) and overall 2-year survival 71%. Disease characteristics, clearance of jaundice, laboratory tests reflecting liver function and hypersplenism, as well as sonographic signs of portal hypertension were related to endoscopic findings and bleeding episodes. Results: Grade 2 to 3 varices developed with similar frequency after failed (18/28, 64%) and successful portoenterostomy (10/19, 53%) in 28 patients. Following failed portoenterostomy, esophageal varices were encountered significantly earlier (8 [4–23] vs 19 [4–165] months, P = 0.004), and they reappeared after eradication more often (16/16 vs 4/10, P = 0.001). Varices bled only after failed portoenterostomy (13/28 vs 0/19, P < 0.001). Increased serum bilirubin concentration >40 &mgr;mol/L at 3 months after portoenterostomy was a risk factor of upper gastrointestinal bleeding (odds ratio [OR] 17, 95% confidence interval [CI] 1.7–175, P = 0.017). Conclusions: In future studies as well as clinical surveillance of BA patients’ varices, successful and failed portoenterostomy patients should be approached as separate groups with divergent prognoses. After failed portoenterostomy, surveillance should start early, for example, at 6 months.

General health, health-related quality of life and sexual health after pediatric liver transplantation: a nationwide study.

The long‐term impact of pediatric liver transplantation (LT) and its complications on general health, health‐related quality of life (HRQoL) and sexual health were assessed. We conducted a national cross‐sectional study of all pediatric recipients who underwent LT between 1987 and 2007. Of 66 survivors, 57 participants (86%) were compared to randomly chosen healthy controls (n = 141) at 10.7 ± 6.6 years posttransplant. PedsQL4.0, SF‐36, DISF‐SR and AUDIT questionnaires for appropriate age groups were used. Patients and controls <7 years had similar HRQoL and 54% of patients aged over 7 scored within the controls’ normal range on all HRQoL domains. In adult survivors, physical functioning and general health were decreased (p < 0.05). Biliary complications, reoperations and obesity were independently associated with reduced HRQoL (p < 0.05 for all). Still 64% of adult survivors considered their health excellent. Sexual health was similar to controls but LT recipients may experience problems with their orgasm strength (p = 0.050) and condom‐based contraception was more common after LT than among controls (58% and 12%, p < 0.001). In conclusion, normal HRQoL and sexual health are achievable post‐LT.

COMORBIDITIES IN CHRONIC PEDIATRIC PERITONEAL DIALYSIS PATIENTS: A REPORT OF THE INTERNATIONAL PEDIATRIC PERITONEAL DIALYSIS NETWORK

♦ Background, Objectives, and Methods: Hospitalization and mortality rates in pediatric dialysis patients remain unacceptably high. Although studies have associated the presence of comorbidities with an increased risk for death in a relatively small number of pediatric dialysis patients, no large-scale study had set out to describe the comorbidities seen in pediatric dialysis patients or to evaluate the impact of those comorbidities on outcomes beyond the newborn period. In the present study, we evaluated the prevalence of comorbidities in a large international cohort of pediatric chronic peritoneal dialysis (CPD) patients from the International Pediatric Peritoneal Dialysis Network registry and began to assess potential associations between those comorbidities and hospitalization rates and mortality. ♦ Results: Information on comorbidities was available for 1830 patients 0 - 19 years of age at dialysis initiation. Median age at dialysis initiation was 9.1 years [interquartile range (IQR): 10.9], median follow-up for calculation of hospitalization rates was 15.2 months (range: 0.2 - 80.9 months), and total follow-up time in the registry was 2095 patient-years. At least 1 comorbidity had been reported for 602 of the patients (32.9%), with 283 (15.5%) having cognitive impairment; 230 (12.6%), motor impairment; 167 (9.1%), cardiac abnormality; 76 (4.2%), pulmonary abnormality; 212 (11.6%), ocular abnormality; and 101 (5.5%), hearing impairment. Of the 150 patients (8.2%) that had a defined syndrome, 85% had at least 1 nonrenal comorbidity, and 64% had multiple comorbidities. The presence of at least 1 comorbidity was associated with a higher hospitalization rate [hospital days per 100 observation days: 1.7 (IQR: 5.8) vs 1.2 (IQR: 3.9), p = 0.001] and decreased patient survival (4-year survival rate: 73% vs 90%, p < 0.0001). ♦ Conclusions: Nearly one third of pediatric CPD patients in a large international cohort had at least 1 comorbidity, and multiple comorbidities were frequently reported among patients with a defined syndrome. Preliminary analysis suggests an association between comorbidity and poor outcome in those patients. As this powerful international registry matures, further multivariate analyses will be important to more clearly define the impact of comorbidities on hospitalization rates and mortality in pediatric CPD patients.

Adaptive lipid metabolism after ileal autotransplantation in pigs with proximal gut resection

BACKGROUND Transplantation of the small intestine impairs intestinal absorptive function, but the adaptive response of a segmental graft is unknown. The aim of this study was to investigate the effects of ileal autotransplantation on the adaptive absorption and metabolism of lipids in pigs that had undergone proximal gut resection. METHODS Serum lipids, plasma vitamins A and E, absorption and excretion of cholesterol, bile acids and fat, plasma cholesterol precursor and plant sterol proportions to cholesterol (respective markers of cholesterol synthesis and absorption), enteric structure, and transit were determined 4, 8, and 14 weeks after 75% proximal resection with (n = 15) or without (n = 15) autotransplantation of the remaining ileum. RESULTS As compared with pigs that underwent proximal gut resection, the additional autotransplantation reduced the adaptive increase in total serum and high-density lipoprotein cholesterol, plasma plant sterol proportions and vitamin E concentrations, cholesterol and fat absorption efficiency, and villus height (p < 0.05 for all) during the 14 postoperative weeks and resulted in increases of up to 4.6, 2.7, 1.3, and 2.1 times the plasma cholesterol precursors (p < 0.005), fecal excretion of bile acids (p < 0.0005), neutral steroids (p < 0.005), and net elimination of cholesterol (p < 0.0005), respectively. Cholesterol and fat absorption and plasma plant sterols were significantly enhanced between 8 and 14 weeks after autotransplantation (p < 0.05, p < 0.005, and p < 0.05, respectively), whereas fecal elimination of cholesterol remained increased until the end of the follow-up. CONCLUSIONS Autotransplantation of the ileum in pigs that have undergone proximal small bowel resection disturbs the adaptive absorption of cholesterol, bile acids, fat, and fat-soluble vitamins, resulting, through increased fecal elimination of cholesterol, in decreased serum cholesterol despite a marked compensatory increase in cholesterol synthesis.

Synchronous ileal autotransplantation impairs adaptation of remaining gut in pigs with proximal small bowel resection.

This study investigates the effects of ilealautotransplantation on morphology, crypt cellproliferation, and brush border disaccharidases of theremaining jejunoileum and colon in growing pigs with 75% proximal small bowel resection. Resection wasperformed on 30 pigs, of which 15 underwent anautotransplantation of the remaining ileum. Theautotransplanted pigs showed reduced weight gain andremnant ileal length when compared to the resectedcontrols. In the autotransplanted pigs, small boweldiameter and weight, mucosal weight and protein content,villus height and surface area, crypt depth, and the number of proliferating crypt cells werereduced similarly both in the intact jejunum and in theautotransplanted ileal remnant. Autotransplantation alsodecreased the number of proliferative crypt cells of the colon. Specific activities of maltaseand sucrase tended to increase in the autotransplantedileal remnant, whereas the total enzyme activitiesdecreased. These results suggest that ilealautotransplantation disturbs postresectional adaptation of theremaining gut.

Effects of transection and extrinsic denervation and a model of autotransplantation of the porcine jejunoileum on cholesterol biodynamics.

BACKGROUND/PURPOSE Small bowel transplantation impairs enteric function, necessitating transection, extrinsic denervation, and ischemia-reperfusion of the small intestine. The authors investigated how each of these nonimmunologic insides of the transplantation procedure modulates biodynamics of cholesterol and absorption of lipids. METHODS Twenty-three pigs with similar food, cholesterol, and fat intake underwent sham laparotomy (group 1), transection (group 2), extrinsic jejunoileal denervation (group 3), or a model of autotransplantation, including extrinsic jejunoileal denervation with in situ ischemia-reperfusion (group 4). Serum lipids, absorption, and excretion of cholesterol, bile acids, and fat were determined after 8 weeks. Plasma cholesterol precursors and plant sterols, respective markers of cholesterol synthesis, and absorption, were measured after 2 and 8 weeks. RESULTS When compared with sham laparotomy and transection groups, denervation and autotransplantation significantly decreased weight gain and increased plasma cholesterol precursors and fecal excretion of bile acids. In relation to sham operated animals, transection alone modestly increased plasma plant sterols at 2 weeks and biliary secretion and mass absorption of cholesterol. The latter changes were not observed after denervation or autotransplantation, ie, fractional and total absorption of cholesterol were significantly decreased in autotransplanted pigs when compared with transected controls. As compared with all the other groups, autotransplantation significantly increased bacterial metabolites of neutral sterols in feces and net fecal elimination of cholesterol, mainly as bile acids. CONCLUSIONS Extrinsic autonomic denervation of the jejunoileum, with or without synchronous ischemia-reperfusion, results in increased cholesterol synthesis, bile acid malabsorption, and decreased weight gain. Cholesterol malabsorption may develop gradually after intestinal autotransplantation, and even a short period of ischemia further impairs absorptive function of the denervated jejunoileum, resulting in increased fecal elimination of cholesterol mainly as bile acids.

Cholesterol metabolism altered and FGF21 levels high after pediatric liver transplantation despite normal serum lipids.

Liver transplantation (LT) predisposes to metabolic derangements and increases the risk for cardiovascular disease. We conducted a national cross‐sectional study of all pediatric recipients who underwent LT between 1987 and 2007. We measured serum levels of noncholesterol sterols (surrogate markers of cholesterol synthesis and intestinal absorption) and fibroblast growth factor 21 (FGF21) in 49 patients (74% of survivors) at a median of 10 years posttransplant and in 93 controls matched for age and gender. Although serum cholesterol levels were similar in patients and controls, patients displayed increased whole‐body synthesis and decreased intestinal absorption of cholesterol compared with controls (lathosterol to cholesterol ratio 129 ± 55 vs. 96 ± 41, respectively, p < 0.001; campesterol to cholesterol ratio 233 ± 91 vs. 316 ± 107, respectively; p < 0.001). Azathioprine (r =–0.383, p = 0.007) and low‐dose methylpredisolone (r =–0.492, p < 0.001) were negatively associated with lathosterol/sitosterol ratio reflecting a favorable effect on cholesterol metabolism. FGF21 levels were higher in patients than in controls (248 pg/mL vs. 77 pg/mL, p < 0.001). In healthy controls, FGF21 was associated with cholesterol metabolism, an association missing in LT recipients. Normal serum lipids are achievable in long‐term survivors of pediatric LT, but changes in cholesterol metabolism and increased FGF21 levels may explicate later cardiovascular risk.

Antithrombin reduces pulmonary hypertension during reperfusion after cardiopulmonary bypass in a pig

Background:  Antithrombin (AT) may alleviate many cardiopulmonary bypass (CPB) and ischemia‐reperfusion (I/R)‐related adverse effects. Using a porcine model of clinical cardiac surgery on CPB, we tested the effects of supplementary AT on myocardial and lung I/R injury.

Effects of Extrinsic Denervation With or Without Ischemia-Reperfusion Injury on Constitutional Mucosal Characteristics in Porcine Jejunoileum

We investigated the effects of jejunoileal denervation with or without ischemia–reperfusion on mucosal characteristics and small intestinal structure. Growing pigs underwent sham laparotomy, jejunal transection, or extrinsic jejunoileal denervation with or without in situ ischemia–reperfusion. Small intestinal morphology, crypt cell proliferation, enterocyte ultrastructure, and disaccharidase activities were analyzed from jejunum and ileum after eight weeks. Immunohistological analysis of the ileum showed no staining of catecholaminergic neurons after extrinsic denervation. Neural isolation of the jejunoileum with or without ischemia–reperfusion injury reduced weight gain and villous enterocyte density in the ileum, abolished the proximodistal gradient of sucrase activity, and increased mucosal thickness, villus height, and villus surface area in the ileum. However, gross jejunoileal morphology, crypt cell proliferation, and enterocyte ultrastructure remained unchanged. In conclusion, jejunoileal denervation in growing pigs selectively modulates constitutional mucosal characteristics in the ileum, presumably due to altered enterocyte turnover, without a decrease in small intestinal absorptive surface area. These changes are independent of short ischemia and subsequent reperfusion.