Lowered Immune Cell Function in Liver Recipients Recovered From Posttransplant Lymphoproliferative Disease Who Developed Graft Tolerance.

UNLABELLED: Tolerance after treatment and recovery from posttransplant lymphoproliferative disease (PTLD) have been described but little is known about the immunology. The objective of this study is to evaluate the immunity of pediatric recipients who recovered from PTLD. MATERIALS AND METHODS: Pediatric recipients who recovered from PTLD after liver transplant and twice the number of recipients who never had PTLD were recruited. Their immune statuses were measured by ImmuKnow (measurement of adenosine 5-triphospate level produced CD4+ T helper cells), and the results were divided into 3 groups, "low" (≤225 ng/mL), "moderate" (226 to 524 ng/mL), and "high" (≥525 ng/mL). The results of both groups were compared and analyzed. RESULTS: Nine PTLD recipients and 20 non-PTLD recipients were recruited. There were no significant differences in terms of sex and age between the 2 groups. The majority of PTLD recipients (88.9%) had "low" immune status responses, and none of them had "high" responses. For non-PTLD recipients, more than half (55%) had "moderate" immune status responses. The median value of adenosine 5-triphospate levels was significantly lower in the PTLD group (119 ng/mL vs 380.5 ng/mL P = 0.014), and their trough immunosuppressant level was also lower (3.8 µg/L vs 7.7 µg/L; P = 0.004). None of the patients in either group had abnormal liver enzymes (aspartate aminotransferase/alanine aminotransferase) to suggest graft rejection. CONCLUSIONS: Patients who recovered from PTLD have a lower CD4 T-cell activity compared with those who have not suffered from PTLD. Under careful monitoring, their immunosuppressant levels can be kept at low levels to prevent recurrence of PTLD.

Post-transplant lymphoproliferative disorders in liver transplant recipients: a clinicopathological study.

BACKGROUND AND AIMS: Complications after liver transplantation are major factors that determine the prognosis of patients. In this study, we aimed at investigating an important though less frequently occurring complication, post-transplant lymphoproliferative disorders (PTLD), in a single institution after liver transplantation. METHODS: 15 cases with a diagnosis of PTLD in post-liver transplant patients were retrieved from our archive and the clinicopathological features reviewed. RESULTS: The overall incidence of PTLD was 2.3% (n=15/658), and the incidence was much higher in the paediatric than the adult age groups, being 11.1% (9/81) and 1% (6/577), respectively. The median time of presentation was 16 months after transplantation (occurrence time ranging from 2 to 87 months after transplantation). Lymph nodes, gastrointestinal tract and graft liver were the commonest sites of involvement. 11 cases were classified as monomorphic PTLD according to WHO classification and the majority (n=10/11) of them were of B cell differentiation. 12 of the total 15 PTLD cases showed a positive result for Epstein-Barr virus-encoded RNAs with in situ hybridisation. Eight patients were alive at the time of review, and two of them suffered from recurrence of the PTLD. Among the seven patients who died, six succumbed within 1 year from the diagnosis of PTLD. CONCLUSIONS: Despite its relative rarity as a complication for liver transplantation, PTLD imposes significant effects on the morbidity, mortality and treatment implications in postliver transplant patients. The clinicopathological data would hopefully provide better insight into the surveillance and management for susceptible patients.

Bile duct anastomotic stricture after pediatric living donor liver transplantation.

BACKGROUND/PURPOSE: Hepaticojejunostomy is a well-accepted method, whereas duct-to-duct anastomosis is gaining popularity for bile duct reconstruction in pediatric living donor liver transplantation (LDLT). Biliary complications, especially biliary anastomotic stricture (BAS), are not clearly defined. The aim of the present study is to determine the rate of BAS and its associated risk factors. METHODS: The study included 78 pediatric patients (<18 years old) who underwent LDLT during the period from end of September 1993 to end of November 2010. The diagnosis of BAS was based on clinical, biochemical, histologic, and radiologic results. RESULTS: All patients received left-side grafts. Thirteen patients (16.7%) developed BAS after LDLT. Among them, 3 patients (23.1%) had duct-to-duct anastomosis during LDLT. The median follow-up period for the BAS group and the non-BAS group was 57.8 and 79.5 months, respectively (P = .683). Ten of the patients with BAS required percutaneous transhepatic biliary drainage with or without dilatation for treating the stricture. Multivariable analysis showed that hepatic artery thrombosis and duct-to-duct anastomosis were 2 risk factors associated with BAS. CONCLUSION: In pediatric LDLT, hepaticojejunostomy is the preferred method for bile duct reconstruction, but more large-scale research needs to be done to reconfirm this result.

Gastric pneumatosis in a premature neonate.

Gastric pneumatosis is extremely rare during infancy. It has been reported in association with necrotizing enterocolitis or congenital abnormalities such as pyloric stenosis. Here, we report a case of gastric pneumatosis in a premature neonate on synchronized nasal intermittent positive pressure ventilation. No pneumatosis was noted in the rest of the bowel or esophagus. There could have been mild damage in the gastric mucosa, either related to the placement of the feeding tube or secondary to the use of indomethacin or both. The condition was further aggravated by noninvasive ventilation. An increase in intragastric pressure resulted in the submucosal dissection of air followed by the development of gastric pneumatosis. Conservative management strategies, including the use of a nasogastric tube for decompression and the withholding of feeding, successfully managed the gastric pneumatosis in our patient. An uneventful recovery was made after conservative management. Prompt recognition and evaluation of this condition were essential for making the diagnosis.

Pediatric liver transplantation in Hong Kong-a domain with scarce deceased donors.

AIM: The study aimed to assess the outcome of live-donor liver transplantation for pediatric patients in a region with limited access to deceased donors. PATIENTS AND METHODS: From September 1993 to September 2008, 78 pediatric patients aged between 73 days and 17 years (mean, 40 months) received 83 liver transplants. Sixty-two were living-related liver transplantations (LRLTs), and 21 were deceased-donor liver transplantations (DDLTs). The mean follow-up period was 6.5 years. The prospectively collected data of these patients were analyzed retrospectively. RESULTS: The 1-, 2-, and 5-year survival rates of patients and grafts were 91%, 90%, 88% and 87%, 86%, 83%, respectively. The survival rates of LRLT patients and DDLT patients were 89%, 89%, 87%, and 90%, 86%, 86%, respectively (P = .58). The survival rates of patients aged 12 months or younger and patients older than 12 months were 95%, 92%, 90% and 90%, 90%, 87%, respectively (P = .65). One live donor developed temporary peroneal palsy, and another developed lung collapse (3%, 2/62). All live donors resumed their normal activities with no difficulty. CONCLUSION: With meticulous surgical techniques and postoperative care, it is justifiable to accept donated livers from voluntary live donors for transplantation to save pediatric patients in a place with scarce deceased donors.

Laparoscopic surgery induced interleukin-6 levels in serum and gut mucosa: implications of peritoneum integrity and gas factors.

BACKGROUND: The peritoneum serves as an integral part of host immunity, and the homeostasis of intraperitoneal environment is held to be beneficial for patient recovery after abdominal surgery. How minimal invasive access to the abdomen by laparoscopy and incisions would alter the intraperitoneal immune response is not fully defined. This study examined the levels of IL-6 in serum and gut mucosa following laparoscopic surgery with reference to the peritoneum integrity and gas factors. METHODS: BALB/c mice were divided into three groups (ten animals in each group) that underwent different abdominal surgical treatments: laparotomy (open group), laparoscopy with atmospheric air (air group) or carbon dioxide pneumoperitoneum (CO(2) group). A 3-cm incision of the skin and muscle was made in all animals except the peritoneum was left intact in the latter two animal groups in order to cancel out the incisional tissue injury present in laparotomy. Four hours after surgery, serum, and jejunal mucosa were extracted for IL-6 measurement by enzyme-linked immunosorbent assay (ELISA). RESULTS: Open laparotomy resulted in significant elevation of serum IL-6 level when compared to the laparoscopic procedures in the descending order of open > air > CO(2) groups. For the mucosal IL-6 level, both the open and air groups were significantly higher than the CO(2) group. Data from multivariate analysis revealed that breaching or incision of the peritoneum was an important factor for the elevated levels of IL-6 in serum (p < 0.001) and jejunal mucosa (p = 0.032). CONCLUSION: The present study suggests that laparoscopic techniques to minimize the size of the peritoneal incision as well as exposure to atmospheric air can potentially reduce postoperative stress responses associated with abdominal surgery and prompt early recovery.

Should open Kasai portoenterostomy be performed for biliary atresia in the era of laparoscopy?

Kasai portoenterostomy has been the treatment of choice for neonates with biliary atresia since its introduction. With the advance in laparoscopic techniques, a few centers have reported the feasibility of performing laparoscopic Kasai portoenterostomy. However, the outcome of this new technique is not known. Here, we aim to evaluate, as the only referral center for liver transplantation, our experience with patients referred for transplantation after failed Kasai portoenterostomy. A retrospective study was carried out between October 1996 and September 2005. The records of all patients with the diagnosis of biliary atresia were retrieved. The type of procedure and clinical outcome of the patients were noted. Early failure of Kasai enterostomy was defined as the need for liver transplantation within 1-year post-Kasai operation. For the period studied, a total of 72 patients with biliary atresia were identified. Sixty-three of the 72 patients had their Kasai portoenterostomies performed openly while nine patients underwent laparoscopic Kasai portoenterostomy in a center experienced in laparoscopic surgery. Six of these patients were referred for transplantation within 1 year, giving the early failure rate of 66.6%. In comparison, the early failure rate for open Kasai procedure was 38.5%. Regarding post-operative complications, one patient who underwent laparoscopic Kasai procedure also suffered intestinal volvulus after initial surgery and another was found to have internal herniation of the Roux loop. Laparoscopic Kasai portoenterostomy seems to be associated with more post-operative complications and worse early clinical outcome. As a result, we remain guarded about the present-day technique of laparoscopy for biliary atresia.

Immunochemical characterization of the functional constituents of Tripterygium wilfordii contributing to its anti-inflammatory property.

1. Tripterygium wilfordii (TW) contains bioactive compounds that possess immunosuppressive properties. These compounds are considered to be potential drugs in the treatment of acute graft rejections. However, their structure-activity relationships remain unknown. 2. The aim of the present study was to delineate the molecular moieties of triptolide that could account for its ability to inhibit inflammatory responses. In this context, purified TW active compounds (triptolide and triptonide) and synthetic triptolide derivatives were prepared to investigate the structure-activity relationships of triptolide. To this end, rat splenocytes were treated with increasing concentrations of the compounds and then allogenically stimulated using a mixed lymphocyte reaction to determine their antiproliferative activities. From the results, the IC50 value of each compound was calculated. 3. Modification of the beta-hydroxyl group at the C-14 position of the triptolide molecule significantly affected the immunosuppressive activity of T59, as demonstrated by a sevenfold increase of the IC50. Conversely, reduction of the gamma-butyrolactone group in T60 and T61 completely abrogated the antiproliferative effect. Alterations in the C-14 beta-hydroxyl and gamma-butyrolactone groups also resulted in reduced cytotoxicity. 4. The present findings demonstrate that the C-14 beta-hydroxyl and gamma-butyrolactone moieties of the triptolide molecule are crucial for its anti-inflammatory properties and cytotoxicity and are responsible for the compound's antiproliferative activity.

Towards a near-zero recurrence rate in laparoscopic inguinal hernia repair for pediatric patients of all ages.

BACKGROUND/PURPOSE: The recurrence rate in laparoscopic inguinal hernia (LIH) repair remains high. The aim of this study was to assess whether the introduction of technical improvements, including (1) decreasing tension on the purse-string knot when closing the internal hernia opening by injecting normal saline extraperitoneally, (2) using an airtight knot, and (3) stress-testing the airtightness of the knot by increasing intraperitoneal gas pressure, could eliminate recurrence in LIH repair in pediatric patients of all ages. METHODS: A retrospective review was performed of the prospectively collected data of 451 LIH repairs in 314 children of various ages in our institution from September 2002 to September 2006. The technical improvements mentioned above to prevent recurrence were introduced in the second half of the series of operations (tensionless repair [TL]). The data on both groups of operations were then compared. RESULTS: A total of 225 hernias were repaired in the first group (164 patients), compared with 226 in the TL group (150 patients). The differences between the ratio of boys to girls (129:35 vs 112:38) and the mean ages (50.84 +/- 48.15 vs 45.59 +/- 47.95 m) in the 2 groups were not statistically significant. The recurrence rate in the TL group was much lower than in the first group (0.4% vs 4.88%, P = .003). There was no postoperative testicular atrophy in either group of patients. CONCLUSION: It is possible to achieve a near-zero recurrence rate in laparoscopic hernia repair in pediatric patients of all ages.

Traditional Chinese herbal medicines for treatment of liver fibrosis and cancer: from laboratory discovery to clinical evaluation.

Liver disease afflicts over 10% of the world population. This includes chronic hepatitis, alcoholic steatosis, fibrosis, cirrhosis and hepatocellular carcinoma (HCC), which are the most health-threatening conditions drawing considerable attention from medical professionals and scientists. Patients with alcoholism or viral hepatitis are much more likely to have liver cell damage and cirrhosis, and some may eventually develop HCC, which is unfortunately, and very often, a fatal malignancy without cure. While liver surgery is not suitable in many of the HCC cases, patients are mostly given palliative support cares or transarterial chemoembolization or systemic chemotherapies. However, HCC is well known to be a highly chemoresistant tumour, and the response rate is <10-20%. To this end, alternative medicines are being actively sought from other sources with hopes to halt the disease's progression or even eliminate the tumours. Traditional Chinese herbal medicine has begun to gain popularity worldwide for promoting healthcare as well as disease prevention, and been used as conventional or complementary medicines for both treatable and incurable diseases in Asia and the West. In this article, we discuss the laboratory findings and clinical trial studies of Chinese herbal medicines (particularly small molecule compounds) for the treatment of liver disease ranging from fibrosis to liver cancer.

Fetus in fetu--from prenatal ultrasound and MRI diagnosis to postnatal confirmation.

We report a case of fetus in fetu presented as a complex intra-abdominal heterogeneous cystic lesion during ultrasound examination of the fetus at 25 weeks of gestation. Progressive growth of this mass was noted in the prenatal period. Fetal magnetic resonance imaging provided additional information to aid in the prenatal diagnosis. This allows proper counselling for the parents and helps to plan the postnatal management. Surgical excision was carried out in the early neonatal period and the diagnosis of fetus in fetu was confirmed.

Prenatal surgery for congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) has a mortality rate of up to 77% despite optimal pre- and postnatal care. Fetuses with liver herniation, a low lung-to-head ratio, and an early diagnosis before 24 weeks have a particularly poor prognosis. In utero open repair of these fetuses does not improve patient survival. The PLUG (Plug the Lung Until it Grows) technique was reported to be able to reverse pulmonary hypoplasia in CDH. A foam plug or a titanium clip is used and the trachea can be unplugged using Ex Utero Intrapartum Tracheoplasty (EXIT) at birth. Since hysterotomy causes premature labour, a video-fetoscopic intrauterine technique of tracheal occlusion called Fetendo-PLUG was developed. Compared to those who receive standard postnatal care or fetal tracheal occlusion via open hysterotomy, patients who undergo Fetendo-PLUG are reported to have a higher survival rate of 75% and fewer fetal and maternal complications. A recent refinement is to use a detachable balloon for intratracheal occlusion through a single 5 mm port under real-time ultrasound guidance. Without the need for neck dissection, injury to the recurrent laryngeal nerves and trachea and vocal cord paresis can be minimized. The result of this form of treatment for CDH is promising, but further refinement of fetal instrumentation and development of effective tocolytic drugs are still required.

Transverse testicular ectopia detected by MR imaging and MR venography.

Crossed testicular ectopia is a rare anomaly, characterised by migration of one testis towards the opposite inguinal canal. In most reported cases, the correct diagnosis was not made pre-operatively. We report a case of transverse testicular ectopia diagnosed pre-operatively with MRI. MRI and MR venography demonstrated unilateral location of both testes in the right inguinal canal, which was confirmed by surgery. We provide a brief literature review of transverse testicular ectopia and the imaging of undescended testis.