Hong Kong consensus recommendations on the management of pancreatic ductal adenocarcinoma.

This project was undertaken to develop the first set of consensus statements regarding the management of pancreatic ductal adenocarcinoma (PDAC) in Hong Kong, with the goal of providing guidance to local clinicians. A multidisciplinary panel of experts discussed issues surrounding current PDAC management and reviewed evidence gathered in the local context to propose treatment recommendations. The experts used the Delphi approach to finalise management recommendations. Consensus was defined as ≥80% acceptance among all expert panel members. Thirty-nine consensus statements were established. These statements cover all aspects of PDAC management, including diagnosis, resectability criteria, treatment modalities according to resectability, personalised management based on molecular profiling, palliative care, and supportive care. This project fulfils the need for guidance regarding PDAC management in Hong Kong. To assist clinicians with treatment decisions based on varying levels of evidence and clinical experience, treatment options are listed in several consensus statements.

Acute kidney injury following hepatectomy and its impact on long-term survival for patients with hepatocellular carcinoma.

BACKGROUND: Acute kidney injury (AKI) is increasingly being recognized after hepatectomy. This study aimed to identify factors predicting its occurrence and its impact on long-term outcome among patients with hepatocellular carcinoma (HCC). METHODS: This was a retrospective analysis of the incidence of AKI, factors predicting its occurrence, and its impact on patients undergoing hepatectomy between September 2007 and December 2018. A subgroup analysis included patients with histologically proven HCC. RESULTS: The incidence of AKI was 9.2 per cent in 930 patients. AKI was associated with increased mortality, morbidity, posthepatectomy liver failure (PHLF), and a longer hospital stay. On multivariable analysis, study period December 2013 to December 2018, diabetes mellitus, mean intraoperative BP below 72.1 mmHg, operative blood loss exceeding 377ml, high Model for End-Stage Liver Disease (MELD) score, and PHLF were predictive factors for AKI. Among 560 patients with HCC, hypertension, BP below 76.9 mmHg, blood loss greater than 378ml, MELD score, and PHLF were predictive factors. The 1-, 3-, and 5-year overall survival rates were 74.1, 59.2, and 51.6 per cent respectively for patients with AKI, and 91.8, 77.9, and 67.3 per cent for those without AKI. Corresponding 1-, 3-, and 5-year disease-free survival rates were 56.9, 42.3, and 35.4 per cent respectively in the AKI group, and 71.7, 54.5, and 46.2 per cent in the no-AKI group. AKI was an independent predictor of survival in multivariable analysis. CONCLUSION: AKI is associated with longer hospital stay, and higher morbidity and mortality rates. It is also associated with shorter long-term survival among patients with HCC. To avoid AKI, control of blood loss and maintaining a reasonable BP (72-77 mmHg) during hepatectomy is important.

All-optical serrodyne frequency shifter.

We describe and demonstrate a method to induce a single-sideband serrodyne-like optical frequency shift in an all-fiber device. The time-varying phase-shift is generated by cross-phase modulation in a nonlinear fiber. Unlike electro-optic based serrodyne methods, which require a high-fidelity and high-bandwidth analog electrical ramp modulation signal, the proposed optical method uses a simple pulsed pump and can be made simultaneously both low-loss and polarization-independent. We demonstrate the technique by shifting a 1550 nm optical signal 150 MHz in a 1.5 dB insertion-loss polarization-independent frequency shifter and show a pathway to multi-GHz shifting frequencies.

Robotic versus laparoscopic hepatectomy: application of the difficulty scoring system.

BACKGROUND: The development of robotic system may help to relieve the difficulties encountered during laparoscopic hepatectomy. A difficulty scoring system (DSS) was developed to assess the difficulty of various laparoscopic liver resection procedures. The aim of this study is to explore if the DSS is applicable in robotic hepatectomy and to compare the outcomes of robotic hepatectomy and laparoscopic hepatectomy among different difficulty levels. METHODS: Clinical data from all consecutive patients who underwent robotic and conventional laparoscopic hepatectomy at the Prince of Wales Hospital, Hong Kong, were prospectively collected and reviewed. The difficulty level of operations was graded using the DSS. Perioperative outcomes of robotic and conventional laparoscopic hepatectomy were compared at each difficulty level. RESULTS: A total of 107 and 94 patients underwent robotic and laparoscopic hepatectomy during the study period, respectively. Among them, 16 and 2 patients were operated for recurrent pyogenic cholangitis, respectively, and were excluded because no mark for tumour location can be assigned. For robotic hepatectomy, a higher DSS was significantly correlated with higher minor complication rate (p = 0.001), more intraoperative blood loss (p = 0.002), longer operation time (p < 0.001) and longer post-operative hospital stay (p < 0.001). The mean DSS scores of robotic and laparoscopic hepatectomy were 4.5 and 3.6, respectively. (p = 0.004). For cases with low (DSS 1-3) and intermediate (DSS 4-6) difficulty level, there was no significant difference in operative blood loss, operation time and overall complications rate. Only 2 cases (2.2%) with high difficulty level were operated with laparoscopic approach while 20% of patients operated with robotic approach had DSS > 6. CONCLUSIONS: DSS significantly correlated with surgical outcomes in patient who underwent robotic hepatectomy. Perioperative outcomes following robotic and conventional laparoscopic hepatectomy were similar in cases with low and intermediate difficulty. However, robotic system allowed minimally invasive approach in cases with higher difficulty level.

Enhanced recovery after surgery for liver resection.

INTRODUCTION: Enhanced recovery after surgery (ERAS) reduces postoperative length of hospital stay and patient stress response to liver surgery. The aim of the present study was to evaluate the efficacy and feasibility of an ERAS programme for liver resection. METHODS: A multidisciplinary ERAS protocol was implemented for both open and laparoscopic liver resection in a tertiary hospital in Hong Kong. The clinical outcomes of patients who underwent liver resection and underwent the ERAS perioperative programme were compared with those who received a conventional perioperative programme between September 2015 and July 2016. Propensity score matching analysis was used to minimise background differences. RESULTS: A total of 20 patients who underwent liver resection were recruited to the ERAS programme. Their clinical outcomes were compared with another 20 patients who received hepatectomy under a conventional perioperative programme after propensity score matching. The ERAS programme was associated with a significantly shorter length of hospital stay (P=0.033) without an increase in complication rates in patients who underwent open liver resection. There was no such significant association in patients who underwent laparoscopic liver resection. No patients required readmission in this cohort. CONCLUSIONS: The ERAS perioperative programme for liver resection is safe and feasible. It significantly shortened the hospital stay after open liver resection but not after laparoscopic liver resection.

Human Endothelial Protein C Receptor Overexpression Protects Intraportal Islet Grafts in Mice.

Islet transplantation can potentially cure type 1 diabetes mellitus, but it is limited by a shortage of human donors as well as by islet graft destruction by inflammatory and thrombotic mechanisms. A possible solution to these problems is to use genetically modified pig islets. Endothelial protein C receptor (EPCR) enhances protein C activation and regulates coagulation, inflammation, and apoptosis. We hypothesized that human EPCR (hEPCR) expression on donor islets would improve graft survival and function. Islets from an hEPCR transgenic mouse line strongly expressed the transgene, and hEPCR expression was maintained after islet isolation. Islets were transplanted from hEPCR mice and wild-type (WT) littermates into diabetic mice in a marginal-dose syngeneic intraportal islet transplantation model. The blood glucose level normalized within 5 days in 5 of 7 recipients of hEPCR islets, compared with only 2 of 7 recipients of WT islets (P < .05). Transplanted hEPCR islets had better preserved morphology and more intense insulin staining than WT grafts, and they retained transgene expression. The improved engraftment compared with WT islets suggests that inflammation and coagulation associated with the transplant process can be reduced by hEPCR expression on donor tissue.

Comparative Analysis of Proteins with Stimulating Activity on Ovarian Estradiol Biosynthesis from Four Different Dioscorea Species in vitro Using Both Phenotypic and Target-based Approaches: Implication for Treating Menopause.

Rhizomes of Dioscorea species are traditionally used for relieving menopausal syndromes in Chinese medicine. The estrogen-stimulating bioactive principles have been demonstrated in our previous study. In this study, the estrogen-stimulating effects of proteins isolated from four Dioscorea species [D. alata L. (DA), D. zingiberensis C.H. Wright (DH), D. collettii var. hypoglauca (Palib.) S.J. Pei & C.T. Ting (DH), and D. oppositifolia L. (DO)] have been investigated and compared. Microscopic authentication of four Dioscorea species was performed by using paraffin and powder sections of the rhizomes. The potential bioactive proteins of four Dioscorea species have been rapidly isolated by using a DOI-antibody affinity column chromatography on immobilized antibodies against on estradiol-stimulating protein from DO (DOI), and their bioactivity has been rapidly confirmed and compared by phenotypic (i.e., estradiol-stimulating effect) and target-based (i.e., STAR, aromatase, estrogen receptors) screening approaches. The estrogen-stimulating activity of bioactive proteins from DO is the highest. In addition, bioactive proteins from DO upregulated the estradiol-metabolizing enzymes (aromatase and steroidogenic acute regulatory protein). Meanwhile, bioactive proteins from DA, DH and DO upregulated estrogen receptor ß (ERß). All bioactive proteins did not change the expression of estrogen receptor ß (ERα). The estrogen-stimulating bioactive proteins isolated from DO increased biosynthesis of estradiol and upregulated the protein expression of aromatase, steroidogenic acute regulatory protein, and ERß. The results scientifically support the traditional use of DO in Chinese medicine for relieving menopausal syndrome. Besides, proteins from DA and DZ could also upregulate the translational levels of ERß, and potentially reducing the risk of ovarian cancer, which also support the clinical use of them for treating female aging disorder. Graphical Abstract Comparative Analysis of DOI-like Proteins with Stimulating Activity on Ovarian Estradiol Biosynthesis from Four Different Dioscorea Species in vitro.

Simultaneous multi-frequency topological edge modes between one-dimensional photonic crystals.

We show theoretically that, in the limit of weak dispersion, one-dimensional binary centrosymmetric photonic crystals can support topological edge modes in all photonic bandgaps. By analyzing their bulk band topology, these "harmonic" topological edge modes can be designed in a way that they exist at all photonic bandgaps opened at the center of the Brillouin zone, at all gaps opened at the zone boundaries, or both. The results may suggest a new approach to achieve robust multi-frequency coupled modes for applications in nonlinear photonics, such as frequency upconversion.

HLA-B*38:02:01 predicts carbimazole/methimazole-induced agranulocytosis.

Thioamides antithyroid-drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD-induced agranulocytosis is important for clinical management. We performed a genome-wide association study (GWAS) involving 20 patients with ATD-induced agranulocytosis and 775 healthy controls. The top finding was further replicated. A single-nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD-induced agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8-103.7; P = 1.3 × 10(-24)) and replication (OR = 37; 95% CI = 3.7-367.4; P = 9.6 × 10(-7)). HLA-B*38:02:01 was in complete linkage disequilibrium with rs185386680. High-resolution HLA typing confirmed that HLA-B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)-induced agranulocytosis (OR = 265.5; 95% CI = 27.9-2528.0; P = 2.5 × 10(-14)), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA-B*38:02:01 in predicting CMZ/MMI-induced agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing agranulocytosis in populations in which the frequency of the risk allele is high.

Antiviral therapy improves post-hepatectomy survival in patients with hepatitis B virus-related hepatocellular carcinoma: a prospective-retrospective study.

BACKGROUND: The effect of antiviral therapy on the post-hepatectomy long-term survival in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains uncertain. AIM: To evaluate the effect of antiviral therapy on post-hepatectomy survival and recurrence in patients with HBV-related HCC. METHODS: This was a prospective-retrospective study of a total of 404 patients who underwent hepatectomy for HBV-related HCC in a tertiary academic hospital. Data on patient and tumour characteristics, tumour recurrence, treatment for recurrence and survival were compared between antiviral and no antiviral groups. RESULTS: Patient's and tumour characteristics were comparable between the two groups, except a higher proportion of patients with cirrhosis in the antiviral group. With a mean follow-up time of 52.4 months, antiviral group had a better 5-year overall survival (66.7% vs. 56.0%, P = 0.001) while there was no significant difference in the 5-year disease-free survival (44.7% vs. 38.1%, P = 0.166). Use of antiviral therapy was associated with better liver function reserve at the time of recurrence and a greater proportion of patients could receive curative treatment for recurrence (38.5% vs. 24.3%, P = 0.041). There was no significant different in the hazard ratios of patients who started antiviral therapy before or after operation (P = 0.054). CONCLUSIONS: Use of antiviral therapy improves the long-term post-hepatectomy survival in patients with HBV-related HCC. With a better liver function reserve at the time of recurrence, a greater proportion of patients in antiviral group could receive curative treatment for recurrence.

An uncommon cause of Cushing's syndrome in a 70-year-old man.

Cushing's syndrome due to exogenous steroids is common, as about 1% of the general populations use exogenous steroids for various indications. Although endogenous Cushing's syndrome due to ectopic adrenocorticotropic hormone from a pancreatic neuroendocrine tumour is rare, a correct and early diagnosis is important. The diagnosis and management require high clinical acumen and collaboration between different specialists. We report a case of ectopic adrenocorticotropic hormone Cushing's syndrome due to pancreatic neuroendocrine tumour with liver metastasis. Early recognition by endocrinologists with timely surgical resection followed by referral to oncologists led to a favourable outcome for the patient up to 12 months after initial presentation.

Alignment dependent enhancement of the photoelectron cutoff for multiphoton ionization of molecules.

The multiphoton ionization rate of molecules depends on the alignment of the molecular axis with respect to the ionizing laser polarization. By studying molecular frame photoelectron angular distributions from N(2), O(2), and benzene, we illustrate how the angle-dependent ionization rate affects the photoelectron cutoff energy. We find alignment can enhance the high energy cutoff of the photoelectron spectrum when probing along a nodal plane or when ionization is otherwise suppressed. This is supported by calculations using a tunneling model with a single ion state.

The status of heart transplantation in Taiwan, 2005-2010.

Heart transplantation (HT) is the standard therapy used to treat end-stage heart disease. Taiwan Organ Registry and Sharing Center (TORSC) is a registry and database of organ donations and transplantations. To understand the profiles of heart donors and recipients is crucial for efficient utilization. Data was provided by the TORSC and 487 HT were performed from 2005 to 2010. The main causes of donor brain death were head injury (n = 243; 51.1%) and cerebrovascular accidents/strokes (n = 147; 30.9%). The mean age of the recipients was 46.3 ± 14.6 years, and 80.3% were men (n = 391). Physicians and nurses were responsible for most organ procurement. In multivariate analysis, considering donor and recipient gender, donor and recipient age, and donor-to-recipient weight ratio as independent variables, factors that were significantly predictive of graft survival were donor age (hazard rate [HR], 1.02; 95% confidence interval [CI], 1.00-1.03; P = .01) and recipient age (HR, 1.03; 95% CI, 1.01-1.04; P < .01). Our results showed that age is a determinant of allograft survival and healthcare professionals are the primary impetus for obtaining consent for organ donation.

Late presentation of simple virilising 21-hydroxylase deficiency in a Chinese woman with Turner's syndrome.

Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency is a well-known disorder of sexual development (previously known as ambiguous genitalia) in genotypic female neonates. We report on a 66-year-old Chinese, brought up as male, with a simple virilising form of congenital adrenal hyperplasia associated with Turner's syndrome (karyotype 45,X/47,XXX/46,XX). His late presentation was recognised due to his exceptionally short stature and persistent sexual ambiguity. His condition was only brought to medical attention as he developed a huge abdominal mass, which later turned out to be a benign ovarian mucinous cyst. It is therefore important to look out for co-existing congenital adrenal hyperplasia in patients with Turner's syndrome and virilisation, after the presence of Y chromosome material has been excluded.

Mid-infrared supercontinuum generation in As2S3-silica "nano-spike" step-index waveguide.

Efficient generation of a broad-band mid-infrared supercontinuum spectrum is reported in an arsenic trisulphide waveguide embedded in silica. A chalcogenide "nano-spike", designed to transform the incident light adiabatically into the fundamental mode of a 2-mm-long uniform section 1 µm in diameter, is used to achieve high launch efficiencies. The nano-spike is fully encapsulated in a fused silica cladding, protecting it from the environment. Nano-spikes provide a convenient means of launching light into sub-wavelength scale waveguides. Ultrashort (65 fs, repetition rate 100 MHz) pulses at wavelength 2 µm, delivered from a Tm-doped fiber laser, are launched with an efficiency ~12% into the sub-wavelength chalcogenide waveguide. Soliton fission and dispersive wave generation along the uniform section result in spectral broadening out to almost 4 µm for launched energies of only 18 pJ. The spectrum generated will have immediate uses in metrology and infrared spectroscopy.

Ultrasonographic findings in eyes with retinopathy of prematurity in malaysia.

RetCam is an excellent screening tool for the detection of retinopathy of prematurity (ROP). However, affordability is a barrier when adopting the use of RetCam in developing countries. We aimed to describe different stages of ROP using ultrasonographic B-scan and to evaluate the association between funduscopic examinations and ultrasonographic B-scan findings in premature neonates with ROP in Malaysia. A descriptive cross sectional study was conducted in 90 eyes of 47 premature neonates with different stages of ROP in three tertiary hospitals in Malaysia. Experienced ophthalmologists performed detailed funduscopic examinations using binocular indirect ophthalmoscopy (BIO). A masked examiner performed a 10 MHz ultrasonographic B-scan evaluation with 12 meridian position images within 48 hours of clinical diagnosis. Data from the clinical examination and ultrasonographic findings were collected and analysed. We recruited 37 eyes (41.1%) with stage 1 ROP, 29 eyes (32.3%) with stage 2, 18 eyes (20.0%) with stage 3, and 3 eyes (3.3%) with stages 4 and 5 based on the clinical assessment. Ultrasonography correctly identified 3 (8.1%) stage 1 eyes, 17 (58.6%) stage 2 eyes, 13 (72.2%) stage 3 eyes, and 3 each (100%) of the stage 4 and 5 eyes. There was a significant association between the funduscopic signs and the ultrasound findings for stage 2 ROP and above (Fisher's exact test, p <0.001). In conclusion, all stages of ROP were detected and described with a 10 MHz ultrasonic B-scan system. A significant association was observed between funduscopic signs and ultrasonographic findings in premature Malaysian neonates with stage 2 ROP and above.

Randomized clinical trial of open hepatectomy with or without intermittent Pringle manoeuvre.

BACKGROUND: The intermittent Pringle manoeuvre (IPM) is commonly applied during liver resection. Few randomized trials have addressed its effectiveness in reducing blood loss and the results have been conflicting. The present study investigated the hypothesis that IPM could reduce blood loss during liver resection by 50 per cent. METHODS: Between May 2008 and April 2011, patients who underwent elective open hepatectomy were randomized into an IPM or no Pringle manoeuvre (NPM) group and stratified according to the presence or absence of cirrhosis. Data on demographics, type of hepatectomy, operative blood loss, duration of operation, mortality, morbidity and postoperative liver function were recorded and analysed. The primary endpoint was operative blood loss. RESULTS: There were 63 patients in each group. Median (range) operative blood loss was 370 (50-3600) ml in the IPM group versus 335 (40-3160) ml in the NPM group (P = 1·000). There were no differences in blood loss in different phases of the operation, blood loss per area of liver transected or blood transfusion rate, nor in total duration of operation or liver transection time. Postoperative serum alanine aminotransferase levels were higher in the IPM group (P < 0·001). There were more postoperative complications in the IPM group (41 versus 24 per cent; P = 0·036). CONCLUSION: The IPM did not reduce blood loss, but was associated with raised levels of postoperative liver parenchymal enzymes and more complications. REGISTRATION NUMBER: NCT00730743 (http://www.clinicaltrials.gov).