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.

Detection of significant liver fibrosis in Chinese psoriasis patients receiving methotrexate: a comparison between transient elastography and liver histology.

INTRODUCTION: Methotrexate (MTX) is effective for treating psoriasis and psoriatic arthritis, but its potential hepatoxicity remains a concern. Liver biopsy, the gold standard for detecting MTX-induced liver injury, is invasive and carries considerable risk. Transient elastography (TE) offers a non-invasive alternative for detecting advanced liver fibrosis. This study investigated the performance of TE in detecting MTX-induced liver fibrosis among Chinese psoriasis patients, compared with liver biopsy. METHODS: This study included adult patients with clinical psoriasis. Liver stiffness measurement using TE was performed in patients receiving MTX. Exclusion criteria were known liver cirrhosis, positive viral hepatitis carrier status, or conditions influencing TE performance. Liver biopsy was performed when liver stiffness was ≥7.1 kilopascals (kPa) or when the total cumulative dose (TCD) of MTX was ≥3.5 g. RESULTS: A total of 228 patients were screened; among 34 patients who met the inclusion criteria, nine (26.5%) had significant liver fibrosis (Roenigk grade ≥3a). The area under the receiver operating characteristic curve was 0.76 (95% confidence interval=0.59-0.93; P=0.021), indicating that TE had satisfactory performance in detecting liver fibrosis. A cut-off value of 7.1 kPa of liver stiffness yielded 100% sensitivity and 68% specificity. Liver fibrosis was not correlated with the TCD of MTX or the duration of MTX use; it was significantly correlated with obesity and diabetes status (body mass index ≥30 kg/m2, waist circumference ≥138 cm, and glycated haemoglobin level ≥7.8%). CONCLUSION: Transient elastography is reliable and superior to the TCD for detecting liver fibrosis in Chinese psoriasis patients receiving MTX. Liver biopsy should be reserved for high-risk patients or patients with liver stiffness ≥11.7 kPa on TE.

Thermographic visualization of facial vasoconstriction is associated with 30-day all-cause mortality in medical patients; prospective observational two-site cohort study.

INTRODUCTION: Quick and reliable assessment of acute patients is required for accurate triage. The temperature gradient between core and peripheral temperature could possibly instantly provide information on circulatory status. METHODS: Adult medical patients, who did not receive supplementary oxygen, attending two emergency departments, had a thermographic image taken on arrival. The association between 30-day mortality and gradients was tested using logistic regression. RESULTS: 726 patients were studied, median age was 64 years and 14 (1.9%) died within 30 days. There was a significant association between mortality and temperature gradient, comparable to vital signs, age, and clinical intuition. CONCLUSION: Temperature gradient between nose and eye had an acceptable discriminatory power for 30-day all-cause mortality.

Rho-mediated signaling promotes BRAF inhibitor resistance in de-differentiated melanoma cells.

Over half of cutaneous melanoma tumors have BRAFV600E/K mutations. Acquired resistance to BRAF inhibitors (BRAFi) remains a major hurdle in attaining durable therapeutic responses. In this study we demonstrate that ~50-60% of melanoma cell lines with vemurafenib resistance acquired in vitro show activation of RhoA family GTPases. In BRAFi-resistant melanoma cell lines and tumors, activation of RhoA is correlated with decreased expression of melanocyte lineage genes. Using a machine learning approach, we built gene expression-based models to predict drug sensitivity for 265 common anticancer compounds. We then projected these signatures onto the collection of TCGA cutaneous melanoma and found that poorly differentiated tumors were predicted to have increased sensitivity to multiple Rho kinase (ROCK) inhibitors. Two transcriptional effectors downstream of Rho, MRTF and YAP1, are activated in the RhoHigh BRAFi-resistant cell lines, and resistant cells are more sensitive to inhibition of these transcriptional mechanisms. Taken together, these results support the concept of targeting Rho-regulated gene transcription pathways as a promising therapeutic approach to restore sensitivity to BRAFi-resistant tumors or as a combination therapy to prevent the onset of drug resistance.

Cross-sectional study on emergency department management of sepsis.

INTRODUCTION: Emergency departments (EDs) play an important role in the early identification and management of sepsis. Little is known about local EDs' processes of care for sepsis, adoption of international recommendations, and the impact of the new Sepsis-3 definitions. METHODS: Structured telephone interviews based on the United Kingdom Sepsis Trust 'Exemplar Standards for the Emergency Management of Sepsis' were conducted from January to August 2017 with nominated representatives of all responding public hospital EDs in Hong Kong, followed by a review of hospital/departmental sepsis guidelines by the investigators. RESULTS: Sixteen of the 18 public EDs in Hong Kong participated in the study. Among various time-critical medical emergencies such as major trauma, sepsis was perceived by the interviewees to be the leading cause of in-hospital mortality and the second most important preventable cause of death. However, only seven EDs reported having departmental guidelines on sepsis care, with four adopting the Quick Sequential Organ Failure Assessment score or its modified versions. All responding EDs reported that antibiotics were stocked within their departments, and all EDs with sepsis guidelines mandated early intravenous antibiotic administration within 1 to 2 hours of detection. Reported major barriers to optimal sepsis care included lack of knowledge and experience, nursing human resources shortages, and difficulty identifying patients with sepsis in the ED setting. CONCLUSION: There are considerable variations in sepsis care among EDs in Hong Kong. More training, resources, and research efforts should be directed to early ED sepsis care, to improve patient outcomes.

Revitalizing the drug pipeline: AntibioticDB, an open access database to aid antibacterial research and development.

The current state of antibiotic discovery, research and development is insufficient to respond to the need for new treatments for drug-resistant bacterial infections. The process has changed over the last decade, with most new agents that are in Phases 1-3, or recently approved, having been discovered in small- and medium-sized enterprises or academia. These agents have then been licensed or sold to large companies for further development with the goal of taking them to market. However, early drug discovery and development, including the possibility of developing previously discontinued agents, would benefit from a database of antibacterial compounds for scrutiny by the developers. This article describes the first free, open-access searchable database of antibacterial compounds, including discontinued agents, drugs under pre-clinical development and those in clinical trials: AntibioticDB (AntibioticDB.com). Data were obtained from publicly available sources. This article summarizes the compounds and drugs in AntibioticDB, including their drug class, mode of action, development status and propensity to select drug-resistant bacteria. AntibioticDB includes compounds currently in pre-clinical development and 834 that have been discontinued and that reached varying stages of development. These may serve as starting points for future research and development.

Radioembolisation of hepatocellular carcinoma: a primer.

Transarterial radioembolisation (TARE) has gained increasing acceptance as an additional/alternative locoregional treatment option for hepatocellular carcinoma, and colorectal hepatic metastases that present beyond potentially curative options. This is a catheter-based transarterial selective internal brachytherapy that involves injection of radioactive microspheres (usually Y-90) that are delivered selectively to the liver tumours. Owing to the combined radioactive and microembolic effect, the findings at follow-up imaging are significantly different from that seen with other transarterial treatment options. Considering increasing confidence among clinicians, refinement in techniques and increasing number of ongoing trials, TARE is expected to gain further acceptance and become an important tool in the armamentarium for the treatment of liver malignancies. So it is imperative that all radiologists involved in the management of liver malignancies are well versed with TARE to facilitate appropriate discussion at multidisciplinary meetings to direct further management. In this article, we provide a comprehensive review on various aspects of radioembolisation with Y-90 for hepatocellular carcinoma including the patient selection, treatment planning, radiation dosimetry and treatment, side effects, follow-up imaging and future direction.

Predictors of Stroke, Myocardial Infarction or Death within 30 Days of Carotid Artery Stenting: Results from the International Carotid Stenting Study.

OBJECTIVES: Stroke, myocardial infarction (MI), and death are complications of carotid artery stenting (CAS). The effect of baseline patient demographic factors, processes of care, and technical factors during CAS on the risk of stroke, MI, or death within 30 days of CAS in the International Carotid Stenting Study (ICSS) were investigated. METHODS: In ICSS, suitable patients with recently symptomatic carotid stenosis > 50% were randomly allocated to CAS or endarterectomy. Factors influencing the risk of stroke, MI, or death within 30 days of CAS were examined in a regression model for the 828 patients randomized to CAS in whom the procedure was initiated. RESULTS: Of the patients, 7.4% suffered stroke, MI, or death within 30 days of CAS. Independent predictors of risk were age (risk ratio [RR] 1.17 per 5 years of age, 95% CI 1.01-1.37), a right-sided procedure (RR 0.54, 95% CI 0.32-0.91), aspirin and clopidogrel in combination prior to CAS (compared with any other antiplatelet regimen, RR 0.59, 95% CI 0.36-0.98), smoking status, and the severity of index event. In patients in whom a stent was deployed, use of an open-cell stent conferred higher risk than use of a closed-cell stent (RR 1.92, 95% CI 1.11-3.33). Cerebral protection device (CPD) use did not modify the risk. CONCLUSIONS: Selection of patients for CAS should take into account symptoms, age, and side of the procedure. The results favour the use of closed-cell stents. CPDs in ICSS did not protect against stroke.

Rare cause of jaundice in a post liver transplant patient.

A hepatitis B virus carrier suffering from acute flare of chronic hepatitis B infection underwent deceased-donor liver transplantation. He was put on the immunosuppressive agent tacrolimus. On routine follow-up, he was found to have abnormal liver function. Computed tomography scan of the abdomen did not show any dilatation of the biliary system. Liver biopsy showed scattered microabscesses, and a microgranuloma was detected. Endoscopic retrograde cholangiography was performed and a biliary anastomotic stricture (BAS) was noted. In addition, the Chinese liver fluke, Clonorchis sinensis, was discovered. Balloon dilatation and stenting were performed. The patient was given a course of praziquantel. His liver function improved and normalized. We present the case of a liver transplant recipient with cholangitis caused by C. sinensis infestation and infection and biliary obstruction resulting from BAS.

Pilot study evaluating catheter-directed contrast-enhanced ultrasound compared to catheter-directed computed tomography arteriography as adjuncts to digital subtraction angiography to guide transarterial chemoembolization.

AIM: To investigate the feasibility and procedural value of catheter-directed contrast-enhanced ultrasound (CCEUS) compared with catheter-directed computed tomography arteriography (CCTA) in patients undergoing transarterial chemoembolization (TACE) guided by digital subtraction angiography (DSA). MATERIALS AND METHODS: From December 2010 to December 2011, a pilot study was conducted including nine patients (mean age 66.6 years; SD 8.3 years; seven men) undergoing TACE with drug-eluting beads for unresectable hepatocellular carcinoma (HCC). Both CCEUS and CCTA were performed in addition to DSA. Alterations of treatment plan based on CCEUS were recorded and compared with CCTA. RESULTS: CCEUS provided additional information to DSA altering the treatment plan in four out of nine patients (44.4%). In these four patients, CCEUS helped to identify additional tumour feeders (n = 2) or led to a change in catheter position (n = 2). The information provided by CCEUS was similar to that provided by CCTA. CONCLUSION: CCEUS is a potentially valuable imaging tool in adjunction to DSA when performing TACE and may provide similar information to CCTA.

Prolyl isomerase Pin1 and protein kinase HIPK2 cooperate to promote cortical neurogenesis by suppressing Groucho/TLE:Hes1-mediated inhibition of neuronal differentiation.

The Groucho/transducin-like Enhancer of split 1 (Gro/TLE1):Hes1 transcriptional repression complex acts in cerebral cortical neural progenitor cells to inhibit neuronal differentiation. The molecular mechanisms that regulate the anti-neurogenic function of the Gro/TLE1:Hes1 complex during cortical neurogenesis remain to be defined. Here we show that prolyl isomerase Pin1 (peptidyl-prolyl cis-trans isomerase NIMA-interacting 1) and homeodomain-interacting protein kinase 2 (HIPK2) are expressed in cortical neural progenitor cells and form a complex that interacts with the Gro/TLE1:Hes1 complex. This association depends on the enzymatic activities of both HIPK2 and Pin1, as well as on the association of Gro/TLE1 with Hes1, but is independent of the previously described Hes1-activated phosphorylation of Gro/TLE1. Interaction with the Pin1:HIPK2 complex results in Gro/TLE1 hyperphosphorylation and weakens both the transcriptional repression activity and the anti-neurogenic function of the Gro/TLE1:Hes1 complex. These results provide evidence that HIPK2 and Pin1 work together to promote cortical neurogenesis, at least in part, by suppressing Gro/TLE1:Hes1-mediated inhibition of neuronal differentiation.

Clinical relevance of cranial nerve injury following carotid endarterectomy.

OBJECTIVES: The benefit of carotid endarterectomy (CEA) may be diminished by cranial nerve injury (CNI). Using a quality improvement registry, we aimed to identify the nerves affected, duration of symptoms (transient vs. persistent), and clinical predictors of CNI. METHODS: We identified all patients undergoing CEA in the Vascular Study Group of New England (VSGNE) between 2003 and 2011. Surgeon-observed CNI rate was determined at discharge (postoperative CNI) and at follow-up to determine persistent CNI (CNIs that persisted at routine follow-up visit). Hierarchical multivariable model controlling for surgeon and hospital was used to assess independent predictors for postoperative CNI. RESULTS: A total of 6,878 patients (33.8% symptomatic) were included for analyses. CNI rate at discharge was 5.6% (n = 382). Sixty patients (0.7%) had more than one nerve affected. The hypoglossal nerve was most frequently involved (n = 185, 2.7%), followed by the facial (n = 128, 1.9%), the vagus (n = 49, 0.7%), and the glossopharyngeal (n = 33, 0.5%) nerve. The vast majority of these CNIs were transient; only 47 patients (0.7%) had a persistent CNI at their follow-up visit (median 10.0 months, range 0.3-15.6 months). Patients with perioperative stroke (0.9%, n = 64) had significantly higher risk of CNI (n = 15, CNI risk 23.4%, p < .01). Predictors for CNI were urgent procedures (OR 1.6, 95% CI 1.2-2.1, p < .01), immediate re-exploration after closure under the same anesthetic (OR 2.0, 95% CI 1.3-3.0, p < .01), and return to the operating room for a neurologic event or bleeding (OR 2.3, 95% CI 1.4-3.8, p < .01), but not redo CEA (OR 1.0, 95% CI 0.5-1.9, p = .90) or prior cervical radiation (OR 0.9, 95% CI 0.3-2.5, p = .80). CONCLUSIONS: As patients are currently selected in the VSGNE, persistent CNI after CEA is rare. While conditions of urgency and (sub)acute reintervention carried increased risk for postoperative CNI, a history of prior ipsilateral CEA or cervical radiation was not associated with increased CNI rate.

Adjuvant hepatic intra-arterial iodine-131-lipiodol following curative resection of hepatocellular carcinoma: a prospective randomized trial.

BACKGROUND: The purpose of the present study was to determine whether intrahepatic injection of (131)I-lipiodol (Lipiodol) is effective against recurrence of surgically resected hepatocellular carcinoma (HCC). METHODS: From June 2001 through March 2007, this nationwide multi-center prospective randomized controlled trial enrolled 103 patients 4-6 weeks after curative resection of HCC with complete recovery (52: Lipiodol, 51: Control). Follow-up was every 3 months for 1 year, then every 6 months. Primary and secondary endpoints were recurrence-free survival (RFS) and overall survival (OS), respectively, both of which were evaluated by the Kaplan-Meier technique and summarized by the hazard ratio (HR). The design was based on information obtained from a similar trial that had been conducted in Hong Kong. RESULTS: The Lipiodol group showed a small, and nonsignificant, improvement over control in RFS (HR = 0.75; 95 % confidence interval [95 % CI] 0.46-1.23; p = 0.25) and OS (HR = 0.88; 95 % CI 0.51-1.51; p = 0.64). Only two serious adverse events were reported, both with hypothyroidism caused by (131)I-lipiodol and hepatic artery dissection during angiography. CONCLUSIONS: The randomized trial provides insufficient evidence to recommend the routine use of (131)I-lipiodol in these patients.

Computed tomography hepatic arteriography has a hepatic falciform artery detection rate that is much higher than that of digital subtraction angiography and 99mTc-MAA SPECT/CT: implications for planning 90Y radioembolization?

PURPOSE: To compare the hepatic falciform artery (HFA) detection rates of digital subtraction angiography (DSA), computed tomography hepatic arteriography (CTHA) and 99mTc-macroaggregated albumin (99mTc-MAA) single photon emission computed tomography with integrated CT (SPECT/CT) and to correlate HFA patency with complication rates of yttrium-90 (90Y) radioembolization. MATERIAL AND METHODS: From August 2008 to November 2010, 79 patients (range 23-83 years, mean 62.3 years; 67 male) underwent pre-treatment DSA, CTHA and 99mTc-MAA scintigraphy (planar/SPECT/CT) to assess suitability for radioembolization with 90Y resin microspheres. Thirty-seven patients were excluded from the study, because CTHA was performed with a catheter position that did not result in opacification of the liver parenchyma adjacent to the falciform ligament. DSA, CTHA and 99mTc-MAA SPECT/CT images and medical records were retrospectively reviewed. RESULTS: A patent HFA was detected in 22 of 42 patients (52.3%). The HFA detection rates of DSA, CTHA and 99mTc-MAA SPECT/CT were 11.9%, 52.3% and 13.3%, respectively (p<0.0001). An origin from the segment 4 artery was seen in 51.7% of HFAs. Prophylactic HFA coil-embolization prior to 90Y microspheres infusion was performed in 2 patients. Of the patients who underwent radioembolization with a patent HFA, none developed supra-umbilical radiation dermatitis. One patient experienced epigastric pain attributed to post-embolization syndrome and was managed conservatively. CONCLUSION: The HFA detection rate of CTHA is superior to that of DSA and 99mTc-MAA SPECT/CT. Complications related to non-target radiation of the HFA vascular territory rarely occur, even in patients undergoing radioembolization with a patent HFA.

Autoimmune pancreatitis presenting as a pancreatic mass mimicking malignancy.

Autoimmune pancreatitis is a rare cause of chronic pancreatitis and pancreatic mass. We describe a case of focal autoimmune pancreatitis in a 51-year-old man presenting with obstructive jaundice and pancreatic mass, mimicking malignancy. The immunological test was suggestive of autoimmune pancreatitis, and the patient responded well to a course of steroids, with complete resolution of the pancreatic mass. Autoimmune pancreatitis, therefore, must be kept in mind as a differential diagnosis of pancreatic mass. Recognition of this disease by its typical radiological and serological findings may help to avoid unnecessary surgical resection.

Cholestasis and biliary dilatation associated with chronic ketamine abuse: a case series.

Ketamine is a dissociative anaesthetic agent that is still widely used in veterinary and human medicine. It is increasingly being used as a recreational hallucinogenic drug. Chronic ketamine abuse is known to account for lower urinary tract symptoms and urinary bladder dysfunction. There is now emerging evidence that ketamine misuse is also associated with abnormal liver function tests and biliary tract abnormality. We report three cases of chronic ketamine misuse in three young men who all presented with obstructive jaundice and biliary tract abnormality. We also describe the clinical features, radiological findings and potential underlying mechanisms for this new entity.

Can continuous pump feeding reduce the incidence of pneumonia in nasogastric tube-fed patients? A randomized controlled trial.

BACKGROUND & AIMS: Continuous pump feeding is often used to reduce aspiration risk in older patients on tube feeding, but its effectiveness in preventing aspiration pneumonia is unproven. A randomized controlled trial was therefore performed to examine the effectiveness of continuous pump feeding in decreasing the incidence of pneumonia in tube-fed older hospital patients. METHODS: One hundred and seventy eight elderly patients from three convalescence hospitals and one infirmary, on nasogastric tube feeding, were randomly assigned to have intermittent bolus (bolus) or continuous pump (pump) feeding for 4weeks. The primary outcome was the incidence of pneumonia. The secondary outcome was mortality. RESULTS: Eighty five subjects were randomized into the pump group and 93 in the bolus group. The groups were comparable in age, nutritional and functional status, co-morbidities and history of pneumonia, except that there were more women in the pump group. Within 4weeks, 15 subjects (17.6%) in the pump group and 18 (19.4%) in the bolus group developed pneumonia. Seven subjects (8.2%) in pump group and 13 subjects (14.0%) in bolus group died. There was no significant difference in either pneumonia or death rates between the two groups. CONCLUSION: Continuous pump feeding did not significantly affect the rates of pneumonia or mortality in tube-fed older hospital patients when compared with intermittent bolus feeding.