Pretransplant risk factors and optimal timing for living-related liver transplantation in biliary atresia: experience of one Japanese children's hospital and transplantation center

Background/Purpose

Although living-related liver transplantation (LRLT) is effective for patients with biliary atresia (BA) after a failed Kasai operation, the pretransplant factors affecting post-LRLT mortality and the optimal timing of the procedure remain unclear.

Method

A retrospective review of 27 patients with BA after a failed Kasai operation (median age, 22 months; range, 6-237 months) who received LRLT from 1994 to 2005 was done. The clinical characteristics at the time of the pre-LRLT assessment of those who did and did not survive were compared. A simple regression analysis and receiver operating characteristic analysis were done to correlate the clinical data.

Results

Among the 27 patients, 4 patients died within 1 year post-LRLT. The significant factors affecting posttransplant death were hepatopulmonary syndrome (HPS), age at LRLT, and graft-to-recipient weight ratio. The arterial blood gas analysis of HPS patients showed that there was a significant negative correlation between the Sao₂ value on room air and the intrapulmonary shunt ratio. The receiver operating characteristic analysis of age at LRLT showed that the optimal cutoff point was 103 months of age.

Conclusion

Older children with HPS or a lower graft-to-recipient weight ratio are not ideal candidates for LRLT. The correlation between the shunt ratio and Sao₂ suggests that HPS could be detected early using pulse oximetry.     

D-Ala2, D-Leu5] enkephalin (DADLE) protects liver against ischemia-reperfusion injury in the rat

BACKGROUND: [D-Ala(2), D-Leu(5)] enkephalin (DADLE) is a synthetic delta class of opioid and is reported to induce hibernation as well as hibernation induction trigger (HIT) in the serum of hibernating mammals. DADLE and HIT have been demonstrated to protect the heart, lung, and jejunum against ischemia-reperfusion (I-R) injury. In the present study, we examined the effect of DADLE on I-R injury of the liver in rats. METHODS: After administration of DADLE (DADLE group) or normal saline as a vehicle (Control group), partial hepatic ischemia was induced by occluding the vessels supplying 92% of the liver for 45 min, followed by declamping the vessels and resection of the non-ischemic lobe. After 120 min of reperfusion, serum glutamic-pyruvic transaminase (GPT), hyaluronic acid (HA) levels, and concentrations of malondialdehyde (MDA) of the liver tissue were measured. Additionally, bile output from the ischemic lobes was measured after reperfusion. RESULTS: GPT levels were significantly lower in the DADLE group as compared to those of the Control group (P < 0.05), but the serum levels of HA were not different between the two groups. The concentrations of MDA of the liver tissue were significantly lower in the DADLE group than in the Control group (P < 0.01). The bile output after reperfusion was not significantly different between the two groups. CONCLUSIONS: DADLE protects against I-R injury in hepatocytes, but not in the sinusoidal endothelial cells of the liver in rats. An anti-oxidative effect is suggested to be responsible for this effect.     

The Evaluation of Postdialysis l-Carnitine Administration and Its Effect on Weekly Requiring Doses of rHuEPO in Hemodialysis Patients

Background. In this study, our aim was to evaluate the effect of postdialysis administration of parenteral l-carnitine supplementations on hematological parameters and also on weekly requiring dose of the recombinant human erythropoietine (rHuEPO) in hemodialysis (HD) patients. Material and Methods. The stable 34 patients (17 male, 17 female) were enrolled in the study who were on rHuEPO therapy and a regular maintenance HD program at 5 h, three times a week with bicarbonate dialysate and with biocompatible membranes in HD Center of Medical Faculty Hospital in University of Dicle. rHuEPO was administered subcutanously at 80–120 U/kg/week. The patients were divided into two groups: Group 1, rHuEPO therapy (n = 17) and Group 2, rHuEPO therapy +l-carnitine (n = 17). l-carnitine (l-carnitine ampul, Santa Farma) 1 g was injected postdialysis intravenously via venous route of the dialytic set, three times a week. The patient's hemoglobin (Hgb), hematocrit (Hct), serum iron (Fe^{+ 2}), total iron-binding capacity (TIBC), transferrin saturation index (TSI), and serum ferritin (Fer) levels were followed during the 16-week period. The weekly requiring doses of rHuEPO and hematological parameters of patients were recorded at the beginning of the study, at 8 weeks, and at 16 weeks of the study period. Results. In group 1 (n = 17, 13 female, four male), the mean age was 38.8 ± 12.1 years, mean period time on HD therapy was 18.1 ± 14.9 months, and mean Kt/V value was 1.48 ± 0.28. In group 2 (n = 17, 13 male, four female), the mean age was 48.1 ± 15.4 years, mean period time on HD therapy was 34.4 ± 23.0 months, and mean Kt/V value was 1.29 ± 0.20. The hematological parameters of the groups were found as follows: in group 1, Hgb: 7.9–10.8 g/dl, Hct: 25.3–32.5%; in group 2, Hgb: 10.2–11.8 g/dl, Hct: 30.6–35.4%, respectively (p< 0.05). The target Hgb/Hct values were achieved at the end of the study in both groups. Both groups were the same according to their serum Fe^{+ 2} markers (p > 0.05). But unlike serum Fe^{+ 2} markers, there were significant differences on weekly requiring doses of rHuEPO therapy between groups. While in group 1, the mean weekly requiring dose of rHuEPO was 6529 U/week (120 U/kg/week) at the beginning of the study, and maintenance weekly requiring dose of rHuEPO was 3588 U/week (66 U/kg/week) at the end of the study, in group 2, they were 4882 U/week (80 U/kg/week), and 1705 U/week (28 U/kg/week), respectively. According to these values, the total reduction in weekly requiring dose of rHuEPO was 45% in group 1, and 65% in group 2; the net gain was 20% in group 2 (p< 0.05). Conclusions. If other factors related to anemia are excluded, the postdialysis parenteral l-carnitine therapy can be considered in selected stable patients, which may improve anemia and may reduce the weekly requiring dose of the rHuEPO and also be cost-effective.     

Neuroprotective effects of L-carnitine and vitamin E alone or in combination against ischemia-reperfusion injury in rats

BACKGROUND: Neurological injury because of transient cerebral ischemia is a potential complication of cardiovascular surgery. In this study, the neuroprotective effects of L-carnitine, vitamin E, and the combination of these agents on ischemia/reperfusion (I/R) injury were determined in a rat model of transient global cerebral I/R. METHODS: Rats were pretreated with L-carnitine (100 mg/kg, i.v.) and vitamin E (50 mg/kg, i. v.), alone or in combination and then subjected to cerebral I/R induced by a four-vessel-occlusion technique for a duration of 15 min followed by 15 min of reperfusion. Malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, and glutathione (GSH) levels were measured in the cerebral tissues. Histopathological examinations were also carried out under light and electron microscopy. RESULTS: The results showed that I/R elevated MDA levels, which were accompanied by a reduction in SOD activities and GSH levels. Surviving neurons was markedly decreased in CA1 and CA3 subfield of hippocampus in I/R animals. L-carnitine, vitamin E, and their combination restored MDA levels and SOD activities, with a tendency to increase surviving neurons in CA1 and CA3 subfield. Combined treatment of L-carnitine and vitamin E had better GSH levels than individual treatment of these agents. CONCLUSIONS: The results suggest that L-carnitine has a potent neuroprotective effect against cerebral-I/R-induced injury in rat brain that is comparable to that of vitamin E. However, the combined use of L-carnitine and vitamin E does not further protect from neuronal injury, although it provides an increase in GSH levels.     

L-arginine impacts pulmonary vascular structure in rats with an aortocaval shunt

BACKGROUND: The present study was designed to explore the therapeutic effect of L-arginine on the proliferation and apoptosis of pulmonary artery smooth muscle cells (SMCs) in high pulmonary blood flow-induced pulmonary hypertension and therefore to provide a basis for the mechanism by which L-arginine regulated pulmonary hypertension. MATERIALS AND METHODS: Twenty-one male SD rats were randomly divided into shunting group, shunting with L-arginine group, and control group. Abdominal aorta and inferior vena cava shunting was produced in rats of the shunting group and the shunting with L-arginine group. Pulmonary artery mean pressure (mPAP) and pulmonary vascular microstructure were analyzed. Immunohistochemistry for proliferative cell nuclear antigen (PCNA) and Fas expressions and TdT-mediated dUTP-biotin nick-end labeling (TUNEL) were used to detect cell proliferation and apoptosis, respectively. RESULTS: mPAP, RV/BW, and RV/LV + S were significantly increased in shunted rats compared to normal controls (P < 0.01, respectively). Pulmonary vascular structural remodeling developed in shunted rats. Proliferative index (PI), apoptotic index (AI), and the ratio of PI/AI of pulmonary artery SMCs in the rats of shunting group were elevated obviously (P < 0.01). Meanwhile, the expressing integral score of Fas was elevated in the shunting group (P < 0.01). However, L-arginine significantly attenuated pulmonary artery pressure and ameliorated pulmonary vascular structural remodeling. Also, it reduced PI and again augmented AI of pulmonary artery SMCs. The ratio of PI/AI was significantly reduced (P < 0.01). The expressing integral score of Fas was again augmented by L-arginine (P < 0.01). CONCLUSIONS: L-Arginine could inhibit proliferation and promote apoptosis of pulmonary artery SMCs in shunted rats.     

Midterm evaluation of cardiopulmonary effects of closed repair for pectus excavatum

Background/Purpose

Since the introduction of the closed technique for repair of pectus excavatum, increasing numbers of patients are presenting for surgery. However, controversy exists regarding the effects of repair on long-term cardiopulmonary outcome. This report details the effects over time of closed repair of pectus excavatum on pulmonary function, cardiac function, exercise tolerance, and the patient's perception of appearance and subjective ability to exercise.

Methods

All patients undergoing closed repair of pectus excavatum were evaluated prospectively. Preoperative computed tomography scan, static pulmonary function studies, exercise tolerance, and echocardiographic evaluation of cardiac function were done. Studies were repeated at 3 and 21 months post-bar placement, and then 3 months after bar removal.

Results

Pre- and postoperative data were available for an initial 48 patients, with 11 patients completing the full evaluation after bar removal. All measures of pulmonary function including forced expiratory volume in 1 second and forced vital capacity were reduced at 3 months postoperation, with a gradual increase during follow-up; however, pulmonary function remained below normative values for patients without pectus excavatum of similar age. Cardiac function as measured by cardiac output and index was increased at 3 months postoperation and maintained thereafter. Exercise tolerance declined initially and then increased by the 21-month evaluation point and after bar removal. Patients reported a subjective improvement in the ability to exercise immediately after bar insertion.

Conclusions

These results corroborate previous studies which suggested that after closed repair of pectus excavatum there is an immediate subjective improvement in the ability to exercise which is paralleled by an improvement in cardiac output. However, there is an early postoperative decline in pulmonary function which does improve over time; however, this does not reach normal values for similar weight. Further studies are needed to determine whether these results are maintained, or whether after bar removal there is a further improvement in pulmonary status. These results do support the use of the closed repair of pectus excavatum for maintaining and possibly improving cardiopulmonary function in this patient population.     

Percutaneous endoscopic gastrostomy tube removal and replacement after “buried bumper syndrome”: the simple way

Background  Percutaneous endoscopic gastrostomy (PEG) feeding tubes are required for an increasing number of patients with long-term nutritional requirements. “Buried bumper syndrome” (BBS) occurs in 2–6% of PEG placements. In the past, this has been a difficult problem to resolve. The authors aimed to design a safe and simple method of dealing with BBS that can be performed by any endoscopist on a routine endoscopic list with the patient under sedation. Methods  For 6 years, the authors have used a minimally invasive way to deal with BBS. They have successfully treated 20 BBS patients on a routine endoscopy list with the patient under sedation. The existing PEG is divided 5 cm from the skin. A pair of stent-grasping forceps is inserted via the tube. A snare then is passed via the gastroscope, caught in the stent-grasping forceps, and brought out via the PEG tube. Next, the tube is split as deeply as possible into the PEG exit site, and the snare is closed around the tube. Gentle traction is applied along the endoscope, allowing the internal bumper to concertina and pop through the mucosa. Another PEG can now be placed at a separate site, although the authors have successfully used the same tract. Results  All the patients were followed up, with no further problems related to BBS. Conclusions  The authors’ method is a simple way of addressing the difficult BBS problem. It can be used to remove and replace a PEG with a buried bumper on a routine endoscopy list with the patient under sedation.     

Operative innovation to the “Nuss” procedure for pectus excavatum: operative and functional effects

Background

The “Nuss” procedure for repair of pectus excavatum is performed with increasing frequency worldwide. We describe a technique of performing relaxing or “kerf” incisions along the cartilaginous ribs at the point of maximal chest wall concavity to facilitate retrosternal dissection and to reduce chest wall tension. The effects on operative parameters and long-term changes in cardiopulmonary function and appearance were evaluated prospectively.

Methods

Thirty patients underwent a Nuss procedure for the period from 2001 to 2004. Fifteen patients underwent a modified Nuss (MN) with sternocostal “relaxing” incisions, and these were compared to 15 patients undergoing a standard Nuss (SN). Data were prospectively gathered and included the number of relaxing incisions, bar number, blood loss, duration of epidural analgesia, number of days to discharge, and preoperative and postoperative cardiopulmonary function measures.

Results

The average Haller index of the SN group was 3.9 ± 0.7 vs MN group index of 4.6 ± 1.6 (P < .05). The median number of relaxing incisions in the study group was 4.0 ± 0.7 (range 3 - 8). There were no significant differences between the study groups in any of the operative parameters analyzed, including blood loss, days of epidural requirements or days to reach functional independence. Nor were there differences in the improvement in subjective appearance, complications, pulmonary function, cardiac output at rest, oxygen transport or minute ventilation at maximal exercise. Subjectively, bar positioning and the intraoperative visualization was easier with the relaxing incisions.

Conclusions

The addition of sternocostal relaxing incisions to the standard Nuss procedure appears to facilitate retrosternal dissection and bar placement, but no changes in long-term function or cosmesis were noted. The use of relaxing incisions appears to be safe and may facilitate operative visualization of retrosternal structures.