Liver transplantation for iatrogenic bile duct injury: a systematic review.

BACKGROUND: Bile duct injury (BDI) is an infrequent but serious complication of cholecystectomy, often with life-changing consequences. Liver transplantation (LT) may be required following severe BDI, however given the rarity, few large studies exist to guide management for complex BDI. METHODS: A systematic review was performed to assess post-operative complications, 30-day mortality, retransplant rate and 1-year and 5-year survival following LT for BDI in Medline, EMBASE, Web of Science or Cochrane Clinical Trials Database. RESULTS: Seven articles met inclusion criteria, describing 179 patients that underwent LT for BDI. Secondary biliary cirrhosis (SBC) was the main indication for LT (82.2% of patients). Median model for end-stage liver disease (MELD) scores at time of LT ranged from 16 to 20.5. Median 30-day mortality was 20.0%. The 1-year and 5-year survival ranges were 55.0-84.3% and 30.0-83.3% respectively, and the overall retransplant rate was 11.5%. CONCLUSION: BDI is rarely indicated for LT, predominantly for SBC following multiple prior interventions. MELD scores poorly reflect underlying morbidity, and exception criteria for waitlisting may avoid prolonged LT waiting times. 30-day mortality was higher than for non-BDI indications, with comparable long term survival, suggesting that LT remains a viable but high risk salvage option for severe BDI.

Long-term survival outcome of laparoscopic liver resection for hepatocellular carcinoma.

Long-term survival is the most important outcome measurement of a curative oncological treatment. For hepatocellular carcinoma (HCC), the long-term disease-free and overall survival of laparoscopic liver resection (LLR) is shown to be non-inferior to the current standard of open liver resection (OLR). Some studies have reported a superior long-term oncological outcome in LLR when compared to OLR. It has been argued that improvement of visualization and instrumentation and reduced operative blood loss and perioperative blood transfusion may contribute to reduced risk of postoperative tumor recurrence. On the other hand, since most of the comparative studies of the oncological outcomes of LLR and OLR for HCC are non-randomized, it remained inconclusive as to whether LLR confers additional survival benefit compared to OLR. Despite the paucity of level 1 evidence, the practice of LLR for HCC has gained wide-spread acceptance due to the reproducible improvements in the perioperative outcomes and non-inferior oncological outcomes demonstrated by large-scaled, matched comparative studies. Meta-analyses of the outcomes of these studies by multiple systematic reviews have also returned noncontradictory conclusions. On the basis of a theoretical advantage of LLR over OLR in preventing tumor recurrence, the current review aims to dissect from the current meta-analyses and comparative studies any evidence of such superiority.

Vocal Cord Palsies Missed by Transcutaneous Laryngeal Ultrasound (TLUSG): Do They Experience Worse Outcomes?

INTRODUCTION: Transcutaneous laryngeal ultrasound (TLUSG) is an innovative, non-invasive tool in detecting post-thyroidectomy vocal cord palsy (VCP). However, TLUSG failed to detect about 6-15% laryngoscopic examination (LE)-confirmed VCP. It is unclear whether the outcome of patients with VCP missed by TLUSG [false negative (FN)] is different from those with VCP diagnosed by TLUSG [true positive (TP)]. Therefore, this study aimed to compare the clinical outcome and prognosis between patients with FN results and TP results. METHODS: Over 46 months, all consecutive patients undergoing thyroidectomy or endocrine-related neck procedure were recruited. They underwent pre-operative and post-operative voice assessments on symptoms, voice-specific questionnaire [voice handicap index questionnaire (VHI-30)], TLUSG and LE. For patients with post-operative vocal cord palsy, reassessment LE would be arranged at second, fourth, sixth and twelfth months post-operatively until VCP recovered. RESULTS: In total, 1196 patients, including 74 post-thyroidectomy VCP, were recruited. For those with assessable vocal cords (VC), 58 VCP were correctly diagnosed by TLUSG (TP) and 10 VCP were missed by TLUSG (FN). Sensitivity and specificity of detecting a VCP by TLUSG were 85.3% and 94.7%, respectively. VHI-30 score was significantly increased after operation in TP group [31 (range - 6-105), p < 0.001] but not in FN group [20 (14-99), p = 0.089]. Comparing to TP group, VCP recovered earlier (69 vs. 125 days, p < 0.001) and less patients suffered from permanent VCP in patients with FN results. (34.5% vs. 0.0%, p = 0.027). CONCLUSION: The VCP missed by TLUSG had a milder course of disease. Early recovery of VC function and non-permanent palsy were expected.

Lessons Learned After 1000 Cases of Transcutaneous Laryngeal Ultrasound (TLUSG) with Laryngoscopic Validation: Is There a Role of TLUSG in Patients Indicated for Laryngoscopic Examination Before Thyroidectomy?

INTRODUCTION: Patients with hoarseness of voice, previous neck operation, or suspicion of malignancy are at high risk of having pre-thyroidectomy vocal cord (VCP) palsy. Therefore, vocal cord (VC) functions should be evaluated before surgery. This study aimed to evaluate the accuracy of hoarseness, a voice-related questionnaire (Voice Handicap Index [VHI]-30), and transcutaneous laryngeal ultrasound (TLUSG) in diagnosing VCP, as well as the role of TLUSG in the evaluation of high-risk patients. METHODS: A total of 1000 patients undergoing thyroidectomy or other endocrine-related neck procedures were prospectively included. Symptoms of hoarseness, the VHI-30 score, and TLUSG were evaluated. Validation laryngoscopies were performed by a separate endoscopist after performing TLUSG. All the assessments were performed one to seven days before surgery. The findings of hoarseness, the VHI-30 score, and TLUSG were correlated with laryngoscopic findings to evaluate the diagnostic accuracy. RESULTS: Of 1000 patients, nine preoperative VCP were diagnosed with laryngoscopy. Sensitivity in detecting VCP by hoarseness, the VHI-30 score, and TLUSG were 33.3%, 62.5%, and 88.9%, respectively. A total of 342 patients were considered as high risk, and eight preoperative VCP were confirmed with laryngoscopy. Despite it not being possible to visualize the VCs in 26 (7.7%) patients, TLUSG had a higher accuracy in detecting VCP than the VHI-30 did (96.8% vs. 74.2%; p < 0.001). If patients had been selected who were unassessable or who had had VCP on assessment for confirmatory laryngoscopy, TLUSG saved more patients from laryngoscopic examinations than the VHI-30 did (87.7% vs. 71.3%; p < 0.001). A history of neck operation and suspicion of malignancy did not affect the assessment by TLUSG (p > 0.05). CONCLUSION: TLUSG is a feasible, non-invasive, and sensitive tool in detecting VCP in high-risk patients. It has safely precluded 87.7% high-risk patients from laryngoscopy. TLUSG should be incorporated as a part of the ultrasound examination of the thyroid.

Determining the Learning Curve of Transcutaneous Laryngeal Ultrasound in Vocal Cord Assessment by CUSUM Analysis of Eight Surgical Residents: When to Abandon Laryngoscopy.

Transcutaneous laryngeal ultrasonography (TLUSG) is a promising alternative to laryngoscopy in vocal cords (VCs) assessment which might be challenging in the beginning. However, it remains unclear when an assessor can provide proficient TLUSG enough to abandon direct laryngoscopy . Eight surgical residents (SRs) without prior USG experience were recruited to determine the learning curve. After a standardized training program, SRs would perform 80 consecutive peri-operative VCs assessment using TLUSG. Performances of SRs were quantitatively evaluated by a composite performance score (lower score representing better performance) which comprised total examination time (in seconds), VCs visualization, and assessment accuracy. Cumulative sum (CUSUM) chart was then used to evaluate learning curve. Diagnostic accuracy and demographic data between every twentieth TLUSG were compared. 640 TLUSG examinations had been performed by 8 residents. 95.1% of VCs could be assessed by SRs. The CUSUM curve showed a rising pattern (learning phase) until 7th TLUSG and then flattened. The curve declined continuously after 42nd TLUSG (after reaching a plateau). Rates of assessable VCs were comparable in every twentieth cases performed. It took a longer time to complete TLUSG in 1st-20th than 21st-40th examinations. (45 vs. 32s, p = 0.001). Although statistically not significant, proportion of false-negative results was higher in 21st-40th (2.5%) than 1(st)-20th (0.6%), 41(st)-60th (0.7%), and 61(st)-80th (0.7%) TLUSG performed. After a short formal training, surgeons could master skill in TLUSG after seven examination and assess vocal cord function consistently and accurately after 40 TLUSG.

A rabbit model of age-dependant ocular hypertensive response to topical corticosteroids.

OBJECTIVE: To investigate the ocular hypertensive response to topical dexamethasone (DEX), rimexolone (RIM), loteprednol etabonate (LOT) and fluorometholone (FML) in rabbits of different ages. METHODS: Seventy-five rabbits of three age groups (7 weeks, 6 months and 1-year old) received topical administration of 0.1% DEX, 1% RIM, 0.5% LOT, 0.1% FML or balanced salt solution four times daily for 1 month. Intraocular pressure (IOP) was monitored at regular time intervals. After a month, eyes were harvested for histological study with haematoxylin and eosin (H&E), periodic acid Schiff and Masson trichrome staining. Trabecular meshwork changes were graded by masked ocular pathologists. RESULTS: Topical DEX caused the greatest increase in IOP, followed by RIM and FML. LOT caused the least IOP increase. Similar pattern of IOP response to the four corticosteroids was observed in the three studied age groups. Young rabbits (7 week) were the most responsive to corticosteroids among the age groups. Extracellular matrix thickening in the trabecular meshwork region and loss of trabecular meshwork cells were observed after DEX, FML or RIM treatments. CONCLUSION: Young rabbits are more susceptible to steroid induced increase in IOP, even for milder steroids such as fluorometholone and rimexolone.

Comparison of standard automated perimetry, frequency-doubling technology perimetry, and short-wavelength automated perimetry for detection of glaucoma.

PURPOSE: To compare the performance of standard automated perimetry (SAP), frequency-doubling technology (FDT) perimetry, and short-wavelength automated perimetry (SWAP) in detecting glaucoma. METHODS: One hundred thirty-two eyes of 95 glaucoma patients and 37 normal subjects had retinal nerve fiber layer (RNFL) imaging and visual field testing by SAP, Matrix FDT perimetry, and Swedish interactive thresholding algorithm (SITA) SWAP at the same visit (all perimeters by Carl Zeiss Meditec, Inc., Dublin, CA). Visual field defects were confirmed with two or more consecutive examinations by the same types of perimetry. Glaucoma was defined with the reference to the RNFL thickness deviation map score (≥ 4, glaucomatous; ≤ 2, normal). The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of MD (mean deviation) and PSD (pattern standard deviation) of the perimetries were compared. RESULTS: Taking all glaucoma patients into consideration, the sensitivity was highest for Matrix FDT perimetry (69%), followed by SAP (68%), and then SITA SWAP (59%). When the analysis included only patients with early glaucoma, the sensitivity decreased to 52%, 46%, and 34%, respectively, with a significant difference detected between Matrix FDT perimetry and SITA SWAP (P = 0.034). The specificity was ≥ 97% for all perimetries. The AUCs of MD and PSD followed a similar order, with Matrix FDT perimetry having the greatest AUC (0.89-0.94), followed by SAP (0.87-0.94), and then SITA SWAP (0.69-0.90). There were significant differences in sensitivities at 90% specificity between Matrix FDT perimetry and SITA SWAP (P ≤ 0.005 for MD; P ≤ 0.039 for PSD). CONCLUSIONS: The performance for glaucoma detection was comparable between FDT perimetry and SAP. FDT perimetry had a higher sensitivity for detecting glaucoma than did SWAP at a comparable level of specificity.

Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography: analysis of the retinal nerve fiber layer map for glaucoma detection.

OBJECTIVE: To evaluate the diagnostic performance of the retinal nerve fiber layer (RNFL) thickness deviation map imaged by a spectral-domain optical coherence tomography (OCT; Cirrus HD-OCT, Carl Zeiss Meditec Inc, Dublin, CA) and compare its sensitivity and specificity for glaucoma detection with circumpapillary RNFL measurement derived from the standard 3.46 mm diameter circle scan. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: We included 102 normal subjects and 121 glaucoma patients. METHODS: One eye from each individual was imaged with Cirrus HD-OCT and Stratus OCT (Carl Zeiss Meditec Inc.). Glaucoma was defined based on the presence of visual field defects with the Humphrey visual field analyzer (Carl Zeiss Meditec Inc.). A scoring system (0-5) was developed to analyze the RNFL thickness deviation map taking the defect size, shape, depth, location, and distance from the disc margin into consideration. Each of these features was scored independently by a masked observer with a highest total score of 5 (glaucomatous RNFL defect) and a lowest score of 0 (no RNFL defect). Sensitivity and specificity were computed with a score of > or =3, > or =4, or =5. The diagnostic performance of circumpapillary RNFL measurement was analyzed with clock-hour and average RNFL thickness categorical classification. MAIN OUTCOME MEASURES: Diagnostic sensitivity and specificity. RESULTS: The sensitivities of the RNFL thickness deviation map ranged between 95.0% and 97.5%. There were significant differences in specificity between a map score of 5, a map score of > or =4 (87.3%), and a map score > or =3 (72.5%; P< or =0.014). A map score of 5 attained a significantly higher sensitivity (95.0%) compared with clock-hour or average RNFL thickness categorical classification by Stratus OCT or Cirrus HD-OCT (46.3%-88.4%; P< or =0.033) at a comparable level of specificity (95.1%), except when glaucoma was detected as having > or =1 clock-hour at the < or =5% level by Cirrus HD-OCT in which an equally high sensitivity (93.4%) was found but at the expense of a significantly lower specificity (83.3%; P<0.001). CONCLUSIONS: Analysis of the RNFL thickness deviation map provides additional spatial and morphologic information of RNFL damage and significantly improves the diagnostic sensitivity for glaucoma detection compared with conventional circumpapillary RNFL measurement.

Compound heterozygosity of two novel truncation mutations in RP1 causing autosomal recessive retinitis pigmentosa.

Purpose. To evaluate the phenotypic effects of two novel frameshift mutations in the RP1 gene in a Chinese pedigree of autosomal recessive retinitis pigmentosa (ARRP). Methods. Family members of a proband with ARRP were screened for RP1, RHO, NR2E3, and NRL mutations by direct sequencing. Detected RP1 mutations were genotyped in 225 control subjects. Since one family member with the RP1 deletion mutation in exon 2 was found to have age-related macular degeneration (AMD) but not RP, exons 2 and 3 of RP1 were screened in 120 patients with exudative AMD. Major AMD-associated SNPs in the HTRA1 and CFH genes were also investigated. Results. Two novel frameshift mutations in RP1, c.5_6delGT and c.4941_4942insT, were identified in the pedigree. They were absent in 225 control subjects. Family members who were compound heterozygous for the nonsense mutations had early-onset and severe RP, whereas those with only one mutation did not have RP. No mutations in RHO, NR2E3, and NRL were identified in the pedigree. Subject I:2 with AMD carried both at-risk genotypes at HTRA1 rs11200638 and CFH rs800292. No mutation in RP1 exons 2 and 3 was identified in 120 AMD patients. Conclusions. This report is the first to associate ARRP with compound heterozygous nonsense mutations in RP1. Identification of the nonsense-mediated mRNA decay (NMD)-sensitive mutation c.5_6delGT provided further genetic evidence that haploinsufficiency of RP1 is not responsible for RP. The authors propose four classes of truncation mutations in the RP1 gene with different effects on the etiology of RP.

In silico experimentation with a model of hepatic mitochondrial folate metabolism.

BACKGROUND: In eukaryotes, folate metabolism is compartmentalized and occurs in both the cytosol and the mitochondria. The function of this compartmentalization and the great changes that occur in the mitochondrial compartment during embryonic development and in rapidly growing cancer cells are gradually becoming understood, though many aspects remain puzzling and controversial. APPROACH: We explore the properties of cytosolic and mitochondrial folate metabolism by experimenting with a mathematical model of hepatic one-carbon metabolism. The model is based on known biochemical properties of mitochondrial and cytosolic enzymes. We use the model to study questions about the relative roles of the cytosolic and mitochondrial folate cycles posed in the experimental literature. We investigate: the control of the direction of the mitochondrial and cytosolic serine hydroxymethyltransferase (SHMT) reactions, the role of the mitochondrial bifunctional enzyme, the role of the glycine cleavage system, the effects of variations in serine and glycine inputs, and the effects of methionine and protein loading. CONCLUSION: The model reproduces many experimental findings and gives new insights into the underlying properties of mitochondrial folate metabolism. Particularly interesting is the remarkable stability of formate production in the mitochondria in the face of large changes in serine and glycine input. The model shows that in the presence of the bifunctional enzyme (as in embryonic tissues and cancer cells), the mitochondria primarily support cytosolic purine and pyrimidine synthesis via the export of formate, while in adult tissues the mitochondria produce serine for gluconeogenesis.