Peptic Ulcer Disease in Living Liver Donors: A Longitudinal Population-Based Study.

The objective of this nationwide cohort study was to investigate the risk of peptic ulcer disease (PUD) in living liver donors (LDs). A total of 1333 LDs and 5332 matched nondonors were identified during 2003-2011. Hospitalized patients identified as LDs were assigned to the LD cohort, and the non-LD comparison cohort comprised age- and sex-matched nondonors. Cumulative incidences and hazard ratios (HRs) were calculated. The overall incidence of PUD was 1.74-fold higher in the LD cohort than in the non-LD cohort (2.14 vs. 1.48 per 1000 person-years). After adjustment for age, sex, monthly income and comorbidities, we determined that the LD cohort exhibited a higher risk of PUD than did the non-LD cohort (adjusted HR 1.74, 95% confidence interval [CI] 1.45-2.09). The incidence of PUD increased with age; the risk of PUD was 2.53-fold higher in patients aged ≥35 years (95% CI 2.14-2.99) than in those aged ≤34 years. LDs with comorbidities of osteopathies, chondropathies and acquired musculoskeletal deformities exhibited a higher risk of PUD (adjusted HR 3.93, 95% CI 2.64-5.86) compared with those without these comorbidities. LDs are associated with an increased risk of PUD after hepatectomy.

Phenotypic spectrum associated with PTCHD1 deletions and truncating mutations includes intellectual disability and autism spectrum disorder.

Studies of genomic copy number variants (CNVs) have identified genes associated with autism spectrum disorder (ASD) and intellectual disability (ID) such as NRXN1, SHANK2, SHANK3 and PTCHD1. Deletions have been reported in PTCHD1 however there has been little information available regarding the clinical presentation of these individuals. Herein we present 23 individuals with PTCHD1 deletions or truncating mutations with detailed phenotypic descriptions. The results suggest that individuals with disruption of the PTCHD1 coding region may have subtle dysmorphic features including a long face, prominent forehead, puffy eyelids and a thin upper lip. They do not have a consistent pattern of associated congenital anomalies or growth abnormalities. They have mild to moderate global developmental delay, variable degrees of ID, and many have prominent behavioral issues. Over 40% of subjects have ASD or ASD-like behaviors. The only consistent neurological findings in our cohort are orofacial hypotonia and mild motor incoordination. Our findings suggest that hemizygous PTCHD1 loss of function causes an X-linked neurodevelopmental disorder with a strong propensity to autistic behaviors. Detailed neuropsychological studies are required to better define the cognitive and behavioral phenotype.

Congenital diaphragmatic hernia in Smith-Magenis syndrome: a possible locus at chromosome 17p11.2.

We report on a 7-month-old girl with Smith-Magenis syndrome (SMS) due to a 4.76-Mb deletion of 17p12-17p11.2 detected by array comparative genomic hybridization. She was also affected with a left-sided congenital diaphragmatic hernia (CDH) and cardiac anomalies including an atypical atrioventricular canal defect and a cleft mitral valve. To our knowledge, this is the first reported case of a patient with both SMS and CDH. There are numerous chromosomal regions in which duplications, deletions, inversions, or translocations have been associated with CDH, but none have previously been reported at or close to 17p11.2. We discuss candidate genes for the diaphragmatic defect in this patient. Our case demonstrates that it is important to consider the possibility of SMS in non-isolated cases of diaphragmatic hernia.

The reproducibility of the virtual organ computer-aided analysis program for evaluating 3-dimensional power Doppler ultrasonography of diffuse thyroid disorders.

AIM: The aim of this study was to evaluate the intra- observer and inter-observer reproducibility of 3-dimensional (3D) power Doppler ultrasonography with the virtual organ computer-aided analysis (VOCAL) program for measuring thyroid volume and vascular indices in patients with diffuse thyroid disorders. MATERIALS AND METHODS: Patients with diffuse goiters were examined by 3D ultrasonography from August 2005 to July 2006. The parameters for vascular assessment included the vascularization index (VI), flow index (FI), vascularization-flow index (VFI), and thyroid size, and were obtained using the VOCAL program. This program used plane A and a 30 degrees rotational step. Intra-observer and inter-observer repeatability are presented as intra-class correlation coefficient (intra-CC) and inter-class correlation coefficient (inter-CC), with values >0.70 being acceptable. RESULTS: Sixty-three patients in total were enrolled for this study, including 19 patients with simple goiter and 44 patients with autoimmune thyroid disease (AITD) (23 Graves' disease, 21 Hashimoto's thyroiditis). Thyroid volume and 3 vascular indices showed excellent reproducibility in the AITD group (intra- CC>0.9373 and inter-CC>0.8763) and its subgroups. The VI had excellent consistent reproducibility in the simple goiter group (intra-CC>0.8987 and inter-CC>0.8881), but the other parameters did not. CONCLUSIONS: Based on this study, 3D power Doppler ultrasonography with the VOCAL program is a reliable tool for evaluating diffuse thyroid disorders due to an autoimmune process. The VI is the most reliable parameter.

Periodontal regeneration using ex vivo autologous stem cells engineered to express the BMP-2 gene: an alternative to alveolaplasty.

The regeneration of the periodontal attachment apparatus remains clinically challenging because of the involvement of three tissue types and the complexity of their relationship. Human recombinant bone morphogenic protein-2 (rhBMP-2) can accelerate the regeneration of bone and cementum and the insertion of periodontal ligament fibers but may lead to a deranged periodontal relationship, ankylosis and root resorption.This study evaluated a novel approach to regeneration of the periodontal attachment apparatus using a combination of ex vivo autologous bone marrow mesenchymal stem cells (MSCs) engineered by replication-defective adenovirus to express the BMP-2 gene and Pluronic F127 (PF127). Twenty-four periodontal defects were surgically created in 12 New Zealand white rabbits and randomly assigned to three experimental groups with MSCs: the advBMP-2 group; the advbetagal group; the MSC group and one control group: PF127 only. The regenerated periodontal attachment apparatus was assessed histologically and the total regenerated bone volume was calculated from three-dimensional computed tomography analysis.This approach regenerated not only cementum with Sharpey's fiber insertion, but also statistically significant quantities of bone, re-establishing a more normal relationship among the components of the regenerated periodontal attachment apparatus, which is beneficial for the maintenance of periodontal health.Ex vivo gene transfer using stem cells as vectors may provide an advantage of slower BMP-2 release, increasing cementogenesis. There is regeneration of the periodontal attachment apparatus, whereas direct usage of the protein (rhBMP-2) yields unhinged periodontal relationship. Thus, this approach may represent an alternative means for periodontal alveolar bone graft in clinical settings.

Persistent dizziness and nausea in patients receiving postoperative epidural pain control after living donor liver transplantation: case reports.

Dizziness and nausea are frequent problems among patients receiving patient-controlled epidural analgesia (PCEA) after major surgery. It is important to consider the various etiologies that might cause these adverse events, especially among patients who have undergone massive hepatic resection for living donor liver transplantation (LDLT). We have described 2 LDLT cases with persistent dizziness and nausea postoperatively despite several adjustments in PCEA management. Their symptoms were quickly relieved after suspension of PCEA medication. Our 2 cases of LDLT represented a unique setting for this type of complication.

Artificial vascular graft for inferior vena cava reconstruction in living donor liver transplantation: a case report.

Artificial grafts are not recommended because of the high incidence of thrombogenic effects. However, in some situations, such as emergency or when no vascular bank is available, an artificial graft must be used. We present a case in which a polytetrafluoroethyline graft was used as a conduit to reconstruct the retrohepatic vena cava severed during living donor liver transplantation (LDLT). A 48-year-old woman had end-stage primary biliary cirrhosis for 5 years received a right lobe liver graft from her son. The retrohepatic vena cava was divided and ligated in several sequences. The upper end of the severed retrohepatic vena cava retracted into the liver parenchyma. The lower end of the severed vena cava was distended, with multiple stitches. A 16-mm artificial graft was used as a conduit to replace the inferin vena cava for outflow reconstruction. The patient tolerated the complicated procedure well. No anticoagulant was used throughout the entire course. The patient has been well with excellent liver function after follow-up for more than 5 years. Magnetic resonance imaging and Doppler ultrasonographic studies showed good patency of the cava with no evidence of thrombosis. We suggest use of an artificial graft in living donor liver transplantation, in particular in urgent situations when autologous or allogeneic vessels are not available.

Fatal duodenal hemorrhage complicated after living donor liver transplantation: case report.

Fatal hemorrhage caused by duodenal ulcer is rarely seen after liver transplantation. We report a case with penetrating duodenal ulcer resulting in massive gastrointestinal tract hemorrhage from a ruptured pseudoaneurysm of the hepatic artery. The patient, a 54-year-old man, had undergone living donor liver transplantation with a graft from his son. Massive hematelnesis occurred 7 days after transplantation. Endoscopy revealed a penetrating duodenal ulcer. Repeated episodes of hemorrhage resulted in shock. Angiography showed a ruptured pseudoaneurysm of the proper hepatic artery. Embolization controlled the bleeding; however, the grafted liver became ischemic. The patient subsequently developed ischemic cholangitis, which was treated with percutaneous transhepatic cholangial drainage. Repeat transplantation was performed 30 months later. The patient was doing well at 10-month follow-up.

Indication for splenectomy in the era of living-donor liver transplantation.

Although end-stage liver disease (ESLD) is often associated with splenomegaly and thrombocytopenia, splenectomy is not necessary in liver transplantation (OLT) except in special situations. In this paper, we examined the indications for splenectomy in the era of living-donor living transplantation. Six of 46 patients underwent splenectomies. Among them, one received a cadaveric graft. Three splenectomies were performed at 6, 7, and 44 days after OLT because of a huge spleen, massive ascites, or impaired liver function. The other two patients received simultaneous splenectomy during OLT to prevent rejection of ABO-incompatible grafts with a positive anti-T-cell test; and one, for postoperative therapy of hepatitis C. All six patients had a good response to splenectomy. We concluded that splenectomy may be indicated for recipients with severe thrombocytopenia, small-for-size syndrome, ABO incompatibility with positive anti-T/B-cell tests and post-OLT therapy for hepatitis C.

Innovative technique to reconstruct two branches of the right hepatic artery in living donor liver transplantation.

Hepatic arterial thrombosis is a critical complication in living donor liver transplantation (LDLT). Two separate branches of the right hepatic artery (RHA) are sometimes observed and addressed by anastomosis of the larger branch first, then checking backflow from the smaller branch. If not good, the smaller branch must be reconstructed. We used the cystic artery as a conduit for the reconstruction. Meticulous dissection was performed to identify all branches of the hepatic artery in the donor operation. The length of cystic artery preserved was as long as possible. The cystic arterial stump was anastomosed to the stump of the posterior branch the of RHA under microscopic guidance on the back table. Patency was checked through the stump of the anterior branch of the RHA. With this technique, only one orifice, the stump of right anterior hepatic artery, was used for hepatic artery reconstruction. We have performed this technique in two patients. Both had good arterial flow after living donor liver transplantation. This innovative technique is easy and safe, and requires only one anastomosis, which, in theory, decreases the adds of developing hepatic arterial thrombosis.

Polytetrafluoroethylene patch venoplasty for outflow reconstruction in living donor liver transplantation: two case reports.

Outflow obstruction may lead to liver congestion and eventual graft failure after living donor liver transplantation. Various methods of venoplasty provide wider outflow tracts. Most series have suggested use of autologous or allogenic grafts for patch venoplasty. We used a polytetrafluorethylene patch in two patients. Both showed good patency of the outflow tract at Doppler ultrasonography at 7 months and 4 months posttransplantation. A polytetrafluoroethylene patch may be a good alternative when no other autologous or allogeneic vascular patch is available or when the situation is critical.

Urgent laparoscopic cholecystectomy in the management of acute cholecystitis: timing does not influence conversion rate.

BACKGROUND: The optimal treatment of acute cholecystitis is urgent laparoscopic cholecystectomy. Most reports suggest that a delay of 72 or 96 h from onset of symptoms leads to a higher conversion rate. This study assessed the conversion rate in relation to the timing of urgent laparoscopic cholecystectomy for acute cholecystitis. METHODS: During a 12 month period, 112 patients received laparoscopic cholecystectomy for acute cholecystitis at a tertiary care university hospital in central Taiwan. Data were collected prospectively. RESULTS: The overall conversion rate was 3.6% (4/112). Of 62 procedures performed within 72 h from onset of symptoms, 2 were converted, as compared with 2 of 50 procedures after 72 h. Of 76 procedures performed within 96 h from onset of symptoms, 3 were converted, as compared with 1 of 36 procedures after 96 h. There were no mortalities or common bile duct injuries. CONCLUSIONS: The conversion rate for urgent laparoscopic cholecystectomy among patients with acute cholecystitis can be as low as 3.6%. The timing of urgent laparoscopic cholecystectomy has no impact on the conversion rate.

Laparoscopic appendectomy in the elderly.

BACKGROUND: This study aimed to compare the outcomes of laparoscopic and open appendectomy among the elderly. METHODS: Data on 53 elderly patients with a diagnosis of suspected appendicitis were prospectively collected and retrospectively reviewed. Among these patients, 24 had undergone laparoscopic appendectomy (LA) and 29 had undergone open appendectomy (OA). The indications for either method were based on the patient's choice. RESULTS: No statistically significant difference in operative time was found between the LA (70 +/- 28 min) and OA (60 +/- 22 min) groups. There was no statistically significant difference in lengths of hospital stay between the LA (4.8 +/- 3.0 days) and OA (5.0 +/- 3.1 days) groups, and there was a statistically significant difference in the postoperative analgesic doses between the LA (0.5 +/- 0.3 doses) and OA (1.7 +/- 1.5 doses) groups. No conversion of laparoscopic to open surgery was necessary, and no intraabdominal abscesses developed. CONCLUSION: According to this study, LA is as safe and effective as OA for the elderly. Furthermore, it significantly reduces postoperative wound pain.

Contraction of collagen gels seeded with tendon cells.

Knowledge of the adaptation of the soft tissue to mechanical factors and biomolecules would be essential to better understand the mechanism of tendon injury and to improve the outcome of tendon repair. The responses to these factors could be different for the distinct types of cells in the tendon: cells from the tendon sheath, fibroblasts from the epitenon surface, or fibroblasts from the internal endotenon. In this study, we examined the mechanical and histological characteristics of the rate of contraction of the collagen gel seeded with epitenon and endotenon fibroblasts. The rate of contraction and the mechanical property of the contracted construct depend on the gel concentration and also the treatment of TGF-beta1.

Association of genetic polymorphisms of MK, IL-4, p16, p21, p53 genes and human gastric cancer in Taiwan.

AIMS: To assess gastric cancer risk and clinical-pathological factors associated with genetic polymorphisms of MK, IL-4, p16, p21 and p53 genes. METHODS: A retrospective study was conducted for 123 patients who had recently developed primary gastric cancer. Clinical data and pathological findings were collected, genetic polymorphisms of MK, IL-4, p16, p21 and p53 genes were analysed, and the associations of genetic polymorphisms with gastric cancer carcinogenesis were evaluated. RESULTS: There was significant association of genetic polymorphisms between gastric cancer and control groups in p53 genes. After further stratification of the cancer group into different clinical-pathologic parameters, there were significant associations in the sex and LN involvement groups in MK gene; alcohol consumption group in p16 gene; age and cell differentiation groups in p21 gene; age and tumour location groups in p53 gene; but we fail to find any significant association with IL-4 gene polymorphisms. CONCLUSIONS: Genetic susceptibility testing is a tool to evaluate the association of genetic polymorphisms with gastric cancer carcinogenesis.

Frequent allelic loss on chromosomes 4q and 16q associated with human hepatocellular carcinoma in Taiwan.

To define the critical region of liver-specific tumor suppressor genes in human hepatocellular carcinoma (HCC), we analyzed 30 cases of hepatocellular carcinoma using nine 4q and six 16q microsatellite polymorphic DNA markers. We observed one major common deleted region which was flanked by D4S175-D4S1625 and there may be two tumor suppressor genes on chromosome 16q associated with HCC. An extensive study of allelotyping of human HCC was therefore carried out in the candidate region on arms of chromosome 4q with additional tumor tissues and more informative microsatellite DNA markers. These data imply that at least one putative tumor suppressor gene is located in the human chromosome 4q26-q27 region and provides very useful information for further construction of a long-range physical restriction map and thereafter cloning of the putative tumor suppressor gene.

Absence of APC gene mutation in the mutation cluster region in hepatocellular carcinoma.

APC gene mutations have been demonstrated not only in colorectal carcinoma but also in a variety of human cancers. To define the possible role of mutations of the APC gene in hepatocarcinogenesis, we examined 46 pairs of hepatocellular carcinomas and corresponding non-tumorous liver tissue by polymerase chain reaction and single strand conformation polymorphism. All 46 hepatocellular carcinomas had no altered electrophoretic mobility to suggest the presence of APC gene mutation in the mutation cluster region. We also examined the possible loss of heterozygosity of APC and MCC gene loci by fragment length polymorphism analysis and by polymerase chain reaction. None of the cases showed a loss of heterozygosity at the APC and MCC gene loci. The results suggested that the possibility of APC and MCC as the gene defect in the genesis of human hepatocellular carcinoma may be very rare.

Mutational analysis of the p27(kip1) gene in hepatocellular carcinoma.

p27(Kip1) is an inhibitor of cyclin-dependent kinase. It has been reported that reduced p27(Kip1) expression is present in human hepatocellular carcinoma. To determine the role of p27(Kip1) in hepatocarcinogenesis, 46 cases with hepatocellular carcinomas were studied. p27(Kip1) mutation was first screened by single strand conformation polymorphism, and direct DNA sequencing was then performed on those cases with mobility shifts. Two polymorphism sites were found. One is a previously described polymorphism at codon 109 (GTC-->GGC) which was found in two cases. The second polymorphism was identified at codon 55 (GCG-->GCA) in six of the 46 cases. However, the polymorphism at codon 55 was also present in seven of 93 healthy controls (7.5%), indicating that it is not associated with a predisposition for development of hepatocellular carcinoma (Fisher's exact test, 0.05). These results show that p27(Kip1) mutation is not a frequent event in human hepatocellular carcinoma, and suggest that it may be inactivated predominantly by transcriptional and/or posttranscriptional regulation rather than genomic aberrations.

Is the process of beta-cell destruction in type 1 diabetes at time of diagnosis more extensive in females than in males?

OBJECTIVE: To evaluate sex differences in patients with insulin-dependent diabetes mellitus (type 1 diabetes) by comparing the integrated parameters of metabolic control at the time of clinical diagnosis and 3 months after intensive insulin therapy in pre-pubertal, pubertal and post-pubertal patients. DESIGN: A total of 331 consecutive patients with newly diagnosed type 1 diabetes were studied. The mean age of the group was 15 years (s.d. 8.1; range 5-23 years). Patients were stratified into three groups according to their age at disease onset: pre-pubertal (ages 5-9 years), pubertal (ages 10-18 years) and post-pubertal (ages 19-23 years). METHODS: Glycated haemoglobin (HbA(1c)), insulin dose and both basal and glucagon-stimulated C-peptide were evaluated at diagnosis and after 3 months of insulin therapy. RESULTS: We found that females diagnosed after puberty were those with the lowest basal C-peptide compared with males (P=0.005). No statistically significant differences were observed for other metabolic parameters. When the entire group was evaluated, females at the time of diagnosis showed significant lower body mass index (P=0.001), lower basal C-peptide (P=0.021) and higher HbA(1c) (P=0.023) and required more insulin than males (P<0.001). After 3 months of therapy, only a significantly greater dose of insulin was observed in females compared with males (P=0.001), with similar good metabolic control as assessed by HbA(1c). CONCLUSIONS: We conclude that the process of beta-cell destruction at diagnosis may be more extensive in post-pubertal females than in males. Moreover, after the introduction of insulin therapy, females and males show similar metabolic parameters, although females still require significantly more insulin than males to achieve good metabolic control, 3 months after diagnosis.

Correlation of fine needle aspiration cytology and frozen section biopsies in the diagnosis of thyroid nodules.

AIMS: To evaluate the correlation of fine needle aspiration (FNA) cytology and frozen section biopsy in the diagnosis of thyroid nodules. METHODS: The medical records of 662 patients who underwent FNA cytology of the thyroid and thyroid surgery were analysed. Frozen section biopsies were taken from 586 of the 662 patients. The diagnostic correlations of FNA cytology, frozen section, and both FNA cytology and frozen section with definitive histological assessment were evaluated. RESULTS: Among the 662 patients who received FNA cytology, there were 356 cases (53.8%) diagnosed as benign, 114 cases (17.2%) as malignant, 148 cases (22.4%) as indeterminate, and 44 cases (6.6%) as unsatisfactory. The positive predictive value for the detection of malignancy by FNA cytology was 92.1% and the negative predictive value was 95.2%. The incidence of malignancy in the indeterminate cytological diagnosis was 23%. The diagnosis from frozen sections was benign in 445 cases (75.9%), malignant in 134 cases (22.9%), and deferred in 7 cases (1.2%). By frozen section, the positive and negative predictive values were 97% and 95.5%, respectively. Diagnostic accuracy up to 98% was achieved when FNA cytology and frozen section diagnoses were in agreement. No false positives were observed when FNA cytology and frozen sections were both positive for malignancy. When FNA cytology and frozen section diagnoses were discordant, frozen section showed a higher accuracy (78.9%) than FNA cytology (21.1%). In the face of an indeterminate or unsatisfactory cytological diagnosis, the diagnostic accuracy of frozen sections reached 92.6%. CONCLUSIONS: The results confirm that FNA cytology is a useful tool in the initial evaluation of thyroid nodules. Intraoperative frozen section is a valuable procedure to confirm the cytological diagnosis and identify malignancy in patients with indeterminate or unsatisfactory cytological diagnosis. With reliance on frozen sections as an intraoperative guide of thyroid surgery, the possibility of unnecessary extensive surgery and the need for the second operation are considerably lower.