Management of the Hepatic Lymph Nodes during Resection of Liver Metastases from Colorectal Cancer: A Systematic Review

Background. Hepatic lymph node involvement is generally considered a contraindication for liver resection performed for colorectal liver metastases. However, some advocate hepatic lymphadenectomy in the presence of macroscopic involvement and others routine lymphadenectomy. The aim of this review is to assess the role of lymphadenectomy in resection of liver metastases from colorectal cancer. Methods. Medline, Embase and Central databases were searched using a formal search strategy. Trials with survival data with a minimum follow-up of 1 year were considered for inclusion. Meta-analysis was performed using Revman. Results. A total of 4230 references were identified. Ten reports of nine studies including 926 patients qualified for the review. The prevalence of nodal metastases after routine lymphadenectomy was 16.3%. The overall 3-year and 5-year survival rates in node-positive patients were 9/151 (11.3%) and 2/137 (1.5%), respectively, compared to 3-year and 5-year survival rates of 424/787 (53.9%) and 246/767 (32.1%) in node-negative patients. The odds ratios for 3-year and 5-year survivals in node positive disease compared to node-negative disease were 0.12 (95% CI 0.06 to 0.24) and 0.08 (95% CI 0.03 to 0.22). There was no randomized controlled trial which assessed the survival benefit of routine or “selective” lymphadenectomy. Conclusion. Currently, there is no evidence of survival benefit for routine or selective lymphadenectomy. Survival rates are low in patients with positive lymph nodes draining the liver irrespective of whether they are detected by routine lymphadenectomy or by macroscopic involvement. Further trials in this patient group are required

Integrating telehealth care-generated data with the family practice electronic medical record:qualitative exploration of the views of primary care staff

BACKGROUND: Telehealth care is increasingly being employed in the management of long-term illness. Current systems are largely managed via “stand-alone” websites, which require additional log-ons for clinicians to view their patients’ symptom records and physiological measurements leading to frustrating delays and sometimes failure to engage with the record. However, there are challenges to the full integration of patient-acquired data into family physicians’ electronic medical records (EMR) in terms of reliability, how such data can best be summarized and presented to avoid overload to the clinicians, and how clarity of responsibility is managed when multiple agencies are involved. OBJECTIVE: We aimed to explore the views of primary care clinicians on the acceptability, clinical utility, and, in particular, the benefits and risks of integrating patient-generated telehealth care data into the family practice EMR and to explore how these data should be summarized and presented in order to facilitate use in routine care. METHODS: In our qualitative study, we carried out semi-structured interviews with clinicians with experience of and naïve to telehealth care following demonstration of pilot software, which illustrated various methods by which data could be incorporated into the EMR. RESULTS: We interviewed 20 clinicians and found 2 overarching themes of “workload” and “safety”. Although clinicians were largely positive about integrating telehealth care data into the EMR, they were concerned about the potential increased workload and safety issues, particularly in respect to error due to data overload. They suggested these issues could be mitigated by good system design that summarized and presented data such that they facilitated seamless integration with clinicians’ current routine processes for managing data flows, and ensured clear lines of communication and responsibility between multiple professionals involved in patients’ care. CONCLUSIONS: Family physicians and their teams are likely to be receptive to and see the benefits of integrating telehealth-generated data into the EMR. Our study identified some of the key challenges that must be overcome to facilitate integration of telehealth care data. This work particularly underlines the importance of actively engaging with clinicians to ensure that systems are designed that align well with existing practice data-flow management systems and facilitate safe multiprofessional patient care

Rock Bass Learn to Associate Food with a Visual Cue and Remember the Association when Food is Absent

We explored the foraging ability of rock bass (Ambloplites rupestris) by testing three hypotheses consistent with the predictions of optimal foraging theory: 1) fish can learn to associate food with a visual cue; 2) trained fish will go to a visual cue faster than untrained fish; and 3) over time, without the reinforcement of food, trained fish will exhibit a diminished response to a visual cue. Our results supported each hypothesis. During the first 96 h of testing, 88 to 100% of trained fish went to the visual cue first; 50% of the trained fish went to the visual cue first after 312 h. None of the untrained fish went to the visual cue first. Trained fish went to the visual cue significantly faster (11.0 cm sec-1 ) than untrained (1.6 cm sec-1 ) fish. There were no significant differences in velocity to the visual cue among the times tested for control fish (0.8 to 2.6 cm sec-1 ). However, velocities of experimental fish were significantly higher from 0 to 24 h (16.7 cm sec-1 ) than from 48 to 312 h (6.7 cm sec-1 ), suggesting that they began extinguishing their responses as the time since the last food reward associated with the cue increased. If rock bass use these abilities in their natural habitats, they likely improve their foraging efficiency and, thus, their overall fitness. (No actual Publication Date listed on Report

Mirizzi syndrome associated with hepatic artery pseudoaneurysm: a case report.

INTRODUCTION: This is the first case report of Mirizzi syndrome associated with hepatic artery pseudoaneurysm. CASE PRESENTATION: A 54-year-old man presented with painful obstructive jaundice and weight loss. Computed tomography showed a hilar mass in the liver. Following an episode of haemobilia, angiography demonstrated a pseudoaneurysm of a branch of the right hepatic artery that was embolised. At surgery, a gallstone causing Mirizzi type II syndrome was found to be responsible for the biliary obstruction and a necrotic inflammatory mass and haematoma were found to be extending into the liver. The mass was debrided and drained, the obstructing stones removed and the bile duct drained with a t-tube. The patient made a full recovery. CONCLUSION: This case highlights another situation where there may be difficulty in differentiating Mirizzi syndrome from biliary tract cancer.Published versio

A mechanistic evaluation of human beta defensin 2 mediated protection of human skin barrier in vitro

The human skin barrier, a biological imperative, is impaired in inflammatory skin diseases such as atopic dermatitis (AD). Staphylococcus aureus is associated with AD lesions and contributes to pathological inflammation and further barrier impairment. S. aureus secretes extracellular proteases, such as V8 (or 'SspA'), which cleave extracellular proteins to reduce skin barrier. Previous studies demonstrated that the host defence peptide human beta-defensin 2 (HBD2) prevented V8-mediated damage. Here, the mechanism of HBD2-mediated barrier protection in vitro is examined. Application of exogenous HBD2 provided protection against V8, irrespective of timeline of application or native peptide folding, raising the prospect of simple peptide analogues as therapeutics. HBD2 treatment, in context of V8-mediated damage, modulated the proteomic/secretomic profiles of HaCaT cells, altering levels of specific extracellular matrix proteins, potentially recovering V8 damage. However, HBD2 alone did not substantially modulate cellular proteomic/secretomics profiles in the absence of damage, suggesting possible therapeutic targeting of lesion damage sites only. HBD2 did not show any direct protease inhibition or induce expression of known antiproteases, did not alter keratinocyte migration or proliferation, or form protective nanonet structures. These data validate the barrier-protective properties of HBD2 in vitro and establish key protein datasets for further targeted mechanistic analyses.</p

Pharmacological interventions for primary sclerosing cholangitis: an attempted network meta-analysis.

BACKGROUND: Primary sclerosing cholangitis is a chronic cholestatic liver disease that is associated with both hepatobiliary and colorectal malignancies, which can result in liver cirrhosis and its complications. The optimal pharmacological treatment for patients with primary sclerosing cholangitis remains controversial. OBJECTIVES: To assess the comparative benefits and harms of different pharmacological interventions in people with primary sclerosing cholangitis by performing a network meta-analysis, and to generate rankings of available pharmacological interventions according to their safety and efficacy. Given that it was not possible to assess whether potential effect modifiers were similar across comparisons, we did not perform the network meta-analysis but instead used standard Cochrane methods.When trials begin to provide an adequate description of potential effect modifiers, we will attempt to conduct network meta-analysis. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Science Citation Index - Expanded, the WHO International Clinical Trials Registry Platform, and randomised controlled trials registers until February 2017 to identify randomised clinical trials (RCT) on pharmacological interventions for primary sclerosing cholangitis. SELECTION CRITERIA: We included only RCTs, irrespective of language, blinding, or publication status, in which participants were given a diagnosis of primary sclerosing cholangitis. We excluded trials that included previously liver-transplanted participants. We considered any of various pharmacological interventions compared with one other or with placebo. We excluded trials that compared different doses of various pharmacological interventions or that reported different treatment durations, except for ursodeoxycholic acid (UDCA). As UDCA is the drug most commonly investigated for primary sclerosing cholangitis, we performed a second analysis in which we stratified the dose of UDCA. DATA COLLECTION AND ANALYSIS: We calculated the odds ratio and the rate ratio with 95% confidence intervals (CIs) using both fixed-effect and random-effects models based on available-participant analysis with Review Manager. We assessed risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE. MAIN RESULTS: We identified 22 RCTs in which 1211 participants were randomised to 13 different interventions. Most were placebo-controlled trials. Trials had few restrictions apart from an established diagnosis of primary sclerosing cholangitis, evidence of cholestasis, absence of decompensated liver disease, and absence of malignancy. However, some trials included symptomatic participants only, and others included both symptomatic and asymptomatic participants. A total of 11 RCTs (706 participants) provided data for one or more outcomes. The period of follow-up ranged from three months to three years in most trials. Only three trials reported follow-up longer than three years. Investigators found no evidence of differences in important clinical benefits such as reduction in mortality at maximal follow-up and improvement in health-related quality of life. Primary outcomes Mortality: Effect estimates: colchicine versus placebo: odds ratio 0.44, 95% CI 0.04 to 5.07, participants = 84, one trial; penicillamine versus placebo: odds ratio 1.18, 95% CI 0.39 to 3.58, participants = 70, one trial; steroids versus placebo: odds ratio 3.00, 95% CI 0.10 to 90.96, participants = 11, one trial; ursodeoxycholic acid versus placebo: odds ratio 1.51, 95% CI 0.63 to 3.63, participants = 348, two trials, I2 = 0%; vancomycin versus placebo: not estimable because no events in either group, participants = 29, one trial. Serious adverse events (proportion): Effect estimates: infliximab versus placebo: odds ratio not estimable (because of zero events in both arms), participants = 7, one trial; steroids versus placebo: odds ratio 20.00, 95% CI 0.93 to 429.90, participants = 11, one trial; vancomycin versus placebo: not estimable because no events in either group, participants = 29, one trial. Serious adverse events (number): Effect estimates: infliximab versus placebo: rate ratio 0.80, 95% CI 0.02 to 40.44, participants = 7, one trial; penicillamine versus placebo: rate ratio 13.60, 95% CI 0.78 to 237.83, participants = 70, one trial; steroids versus placebo: rate ratio 3.32, 95% CI 0.71 to 15.62, participants = 11, one trial. Adverse events (proportion): Effect estimates: steroids versus placebo: odds ratio 20.00, 95% CI 0.93 to 429.90, participants = 11, one trial; ursodeoxycholic acid versus placebo: odds ratio 1.22, 95% CI 0.68 to 2.17, participants = 198, one trial; vancomycin versus placebo: not estimable because no events in either group, participants = 29, one trial. Adverse events (number): Effect estimates: cyclosporin versus placebo: rate ratio 2.64, 95% CI 0.99 to 7.03, participants = 26, one trial; steroids versus placebo: rate ratio 3.32, 95% CI 0.71 to 15.62, participants = 11, one trial; ursodeoxycholic acid plus metronidazole versus ursodeoxycholic acid: rate ratio 2.36, 95% CI 0.98 to 5.71, participants = 71, one trial. Health-related quality of life: ursodeoxycholic acid versus placebo: mean difference 1.30, 95% CI -5.61 to 8.21, participants = 198, one trial (Short Form (SF)-36 General Health Scale). Secondary outcomes Studies provided no evidence of differences in clinical benefits such as a reduction in the requirement for liver transplantation or a reduction in the incidence proportion of cholangiocarcinoma. One small trial (29 participants) comparing vancomycin versus placebo reported no malignancies, no liver decompensation, and no liver transplantation in either group after a very short follow-up period of 12 weeks after treatment. None of the remaining trials clearly reported other clinical benefits such as decreased development of all malignancies, colorectal cancer, liver decompensation, time to liver decompensation, time to liver transplantation, or requirement for cholecystectomy to allow comparisons between different interventions. SOURCE OF FUNDING: Fifteen trials reported the source of funding; three were funded by parties without vested interest in results of the trial, and 12 were funded in part or in full by drug companies. AUTHORS' CONCLUSIONS: Evidence is currently insufficient to show differences in effectiveness measures such as mortality, health-related quality of life, cirrhosis, or liver transplantation between any active pharmacological intervention and no intervention. However, trials were at high risk of bias and included small numbers of participants, had short follow-up periods, and reported few clinical outcomes. An urgent need exists to identify an effective medical treatment for primary sclerosing cholangitis through well-designed RCTs with adequate follow-up that aim to identify differences in outcomes important to people with primary sclerosing cholangitis

Donor-recipient HLA-A mismatching is associated with hepatic artery thrombosis, sepsis, graft loss and reduced survival after liver transplantation

HLA matching is not routinely performed for liver transplantation as there is no consistent evidence of benefit, however the impact of HLA mismatching remains uncertain. We explored the effect of class I and II HLA mismatching on graft failure and mortality. 1042 liver transplants performed at a single centre, between 1999 and 2016 with available HLA typing data were included. Median follow up period was 9.38 years (IQR 4.9-14) and 350/1042 (33.6%) transplants resulted in graft loss and 280/1042 (26.9%) in death. Graft loss and mortality were not associated with the overall number of mismatches at HLA-A, -B, -C, -DR and -DQ loci. However, graft failure and mortality were both increased in the presence of one (p = 0.004 and p = 0.01) and two (p = 0.01 and p = 0.04) HLA-A mismatches. Elevated hazard ratios for graft failure and death were observed with HLA-A mismatches in univariate and multivariate Cox proportional hazard models. Excess graft loss with HLA-A mismatch (138/940 (14.7%) of mismatched compared to 6/102 (5.9%) matched transplants) occurred within the first-year following transplantation (OR 2.75, p = 0.02). Strikingly, all grafts lost due to hepatic artery thrombosis were in HLA-A mismatched transplants (31/940 vs. 0/102), as were those lost due to sepsis (35/940 vs. 0/102). In conclusion, HLA-A mismatching was associated with increased graft loss and mortality. The poorer outcome for The HLA mismatched group was due to hepatic artery thrombosis and sepsis and these complications occurred exclusively with HLA-A mismatched transplants. This suggests that HLA-A mismatching is important for post-transplant outcomes and knowledge of HLA-A status may enable enhanced surveillance and interventions to reduce risk of complications or stratified HLA-A matching in high-risk recipients

Ex Vivo Perfusion of Porcine Pancreas and Liver Sourced from Commercial Abattoirs after Circulatory Death as a Research Resource: A Methodological Study

Background: Machine perfusion (MP) is increasingly used for human transplant organ preservation. The use of MP for research purposes is another opportunity for this technology. The porcine pancreas and liver are similar in anatomical size and function to their human counterparts, making them an excellent resource for research, but they have some important differences from human organs which can influence their research use. In this paper, we describe a technique developed and tested for the retrieval of porcine organs for use in research on perfused viable organs. Methods: Whole-organ porcine pancreata and livers were harvested at a commercial abattoir, following standard slaughterhouse processes. The standard slaughterhouse process involved a thoracotomy and mid-line laparotomy, and all the thoracoabdominal organs were removed. The pancreas, fixed in the retroperitoneum, was carefully dissected from its attachments to the surrounding structures, and tissue planes between the pancreas, spleen, duodenum, and colon were meticulously identified and dissected. Vessel exposure and division: The aorta, portal vein (PV), hepatic vein (HV), and hepatic artery (HA) were dissected and isolated, preserving the input and output channels for the liver and pancreas. A distal 3 cm of the aorta was preserved and divided and served as the input for the pancreas perfusions. The liver, PV, HV, and HA were preserved and divided to preserve the physiological channels of the input (PV and HA) and output (HV) for the liver perfusions. The porcine hepatic and pancreas anatomy shares significant resemblance with the gross anatomy found in humans, and this was taken into consideration when designing the perfusion circuitry. The porcine pancreas and spleen shared a common blood supply, with branches arising from the splenic artery. The organs were flushed with cold, heparinised normal saline and transported in a temperature-regulated receptacle maintained at a core temperature between 4 and 8 °C, in line with the standards of static cold storage (SCS), to a dedicated perfusion lab and perfused using our novel perfusion machine with autologous, heparinised porcine blood, also collected at the abattoir