Background
Liver transplantation is an established treatment option for end‐stage liver failure. Now that newer, more potent immunosuppressants have been developed, glucocorticosteroids may no longer ...be needed and their removal may prevent adverse effects.
Objectives
To assess the benefits and harms of glucocorticosteroid avoidance (excluding intra‐operative use or treatment of acute rejection) or withdrawal versus glucocorticosteroid‐containing immunosuppression following liver transplantation.
Search methods
We searched the Cochrane Hepato‐Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded and Conference Proceedings Citation Index ‐ Science, Literatura Americano e do Caribe em Ciencias da Saude (LILACS), World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, and The Transplant Library until May 2017.
Selection criteria
Randomised clinical trials assessing glucocorticosteroid avoidance or withdrawal versus glucocorticosteroid‐containing immunosuppression for liver transplanted people. Our inclusion criteria stated that participants should have received the same co‐interventions. We included trials that assessed complete glucocorticosteroid avoidance (excluding intra‐operative use or treatment of acute rejection) versus short‐term glucocorticosteroids, as well as trials that assessed short‐term glucocorticosteroids versus long‐term glucocorticosteroids.
Data collection and analysis
We used RevMan to conduct meta‐analyses, calculating risk ratio (RR) for dichotomous variables and mean difference (MD) for continuous variables, both with 95% confidence intervals (CIs). We used a random‐effects model and a fixed‐effect model and reported both results where a discrepancy existed; otherwise we reported only the results from the fixed‐effect model. We assessed the risk of systematic errors using 'Risk of bias' domains. We controlled for random errors by performing Trial Sequential Analysis. We presented our results in a 'Summary of findings' table.
Main results
We included 17 completed randomised clinical trials, but only 16 studies with 1347 participants provided data for the meta‐analyses. Ten of the 16 trials assessed complete postoperative glucocorticosteroid avoidance (excluding intra‐operative use or treatment of acute rejection) versus short‐term glucocorticosteroids (782 participants) and six trials assessed short‐term glucocorticosteroids versus long‐term glucocorticosteroids (565 participants). One additional study assessed complete post‐operative glucocorticosteroid avoidance but could only be incorporated into qualitative analysis of the results due to limited data published in an . All trials were at high risk of bias. Only eight trials reported on the type of donor used. Overall, we found no statistically significant difference for mortality (RR 1.15, 95% CI 0.93 to 1.44; low‐quality evidence), graft loss including death (RR 1.15, 95% CI 0.90 to 1.46; low‐quality evidence), or infection (RR 0.88, 95% CI 0.73 to 1.05; very low‐quality evidence) when glucocorticosteroid avoidance or withdrawal was compared with glucocorticosteroid‐containing immunosuppression. Acute rejection and glucocorticosteroid‐resistant rejection were statistically significantly more frequent when glucocorticosteroid avoidance or withdrawal was compared with glucocorticosteroid‐containing immunosuppression (RR 1.33, 95% CI 1.08 to 1.64; low‐quality evidence; and RR 2.14, 95% CI 1.13 to 4.02; very low‐quality evidence). Diabetes mellitus and hypertension were statistically significantly less frequent when glucocorticosteroid avoidance or withdrawal was compared with glucocorticosteroid‐containing immunosuppression (RR 0.81, 95% CI 0.66 to 0.99; low‐quality evidence; and RR 0.76, 95% CI 0.65 to 0.90; low‐quality evidence). We performed Trial Sequential Analysis for all outcomes. None of the outcomes crossed the monitoring boundaries or reached the required information size. Hence, we cannot exclude random errors from the results of the conventional meta‐analyses.
Authors' conclusions
Many of the benefits and harms of glucocorticosteroid avoidance or withdrawal remain uncertain because of the limited number of published randomised clinical trials, limited numbers of participants and outcomes, and high risk of bias in the trials. Glucocorticosteroid avoidance or withdrawal appears to reduce diabetes mellitus and hypertension whilst increasing acute rejection, glucocorticosteroid‐resistant rejection, and renal impairment. We could identify no other benefits or harms of glucocorticosteroid avoidance or withdrawal. Glucocorticosteroid avoidance or withdrawal may be of benefit in selected patients, especially those at low risk of rejection and high risk of hypertension or diabetes mellitus. The optimal duration of glucocorticosteroid administration remains unclear. More randomised clinical trials assessing glucocorticosteroid avoidance or withdrawal are needed. These should be large, high‐quality trials that minimise the risk of random and systematic error.
To identify whether socioeconomic deprivation is associated with worse health-related quality of life (HR-QoL), anxiety and depression following liver transplantation.
Cross-sectional study.
Liver ...transplant recipients within a national transplantation programme.
Participants completed the condition-specific 'Short Form of Liver Disease Quality of Life' Questionnaire, the Generalised Anxiety Disorder-7 (GAD-7) Questionnaire and the Patient Health Questionnaire-9 (PHQ-9). The aggregate HR-QoL Score (range 0-100) was derived, and multivariable linear regression was performed based on sociodemographic and clinical variables to estimate its independent association with Scottish Index of Multiple Deprivation (SIMD) quintiles. The GAD-7 Questionnaire and PHQ-9 were used to screen respondents for anxiety and depression, and multivariable logistic regression was performed to estimate their independent association with SIMD quintiles.
Some 331 patients completed the questionnaires. Quintiles were equally distributed in the cohort, with no significant differences observed in underlying patient characteristics. Following multivariable adjustment, greater socioeconomic deprivation was associated with lower post-transplantation HR-QoL scores, with a difference of 9.7 points (95% CI: 4.6 to 14.9, p<0.001) between the most and least deprived quintiles. Recipients living in areas of least deprivation were less likely to suffer from anxiety (OR 0.05, 95% CI: 0.00 to 0.28, p=0.003) or depression (OR 0.13, 95% CI: 0.02 to 0.56, p=0.009).
Despite the highly selected nature of liver transplant recipients, those living in the most deprived areas have a significantly lower HR-QoL and are more likely to suffer from anxiety and depression.
Duplicate publication can introduce significant bias into a meta-analysis if studies are inadvertently included more than once. Many studies are published in more than one journal to maximize ...readership and impact of the study findings. Inclusion of multiple publications of the same study within a meta-analysis affords inappropriate weight to the duplicated data if reports of the same study are not linked together. As studies which have positive findings are more likely to be published in multiple journals this leads to a potential overestimate of the benefits of an intervention. Recent advances in immunosuppression strategies following liver transplantation have led to many studies investigating immunosuppressive regimes including immunosuppression monotherapy. In this letter we focus on a recently published meta-analysis by Lan et al investigating studies assessing immunosuppression monotherapy for liver transplantation. The authors claim to have identified fourteen separate randomised studies investigating immunosuppression monotherapy. Seven of the references appear to relate to only three studies which have been subject to duplicate publication. Several similarities can be identified in each of the duplicate publications including similar authorship, identical immunosuppression regimes, identical dates of enrolment and citation of the original publication in the subsequent manuscripts. We discuss the evidence of the duplicate publication inclusion in the meta-analysis.
Abstract
Background
Cancer cachexia is not purely an end-stage phenomenon and can influence the outcomes of patients with potentially curable disease. This review examines the effect of pre-treatment ...cachexia on overall survival, in patients undergoing surgical resection of oesophagogastric cancer.
Methods
A systematic literature search of MEDLINE, EMBASE and Cochrane Library databases was conducted, from January 2000 to May 2022, to identify studies reporting the influence of cachexia on patients undergoing an oesophagogastric resection for cancer with curative intent. Meta-analyses of the primary (overall survival) and secondary (disease-free survival and postoperative mortality) outcomes were performed using random-effects modelling. Meta-regression was used to examine disease stage as a potential confounder.
Results
Ten non-randomized studies, comprising 7186 patients, were eligible for inclusion. The prevalence of pre-treatment cachexia was 35 per cent (95 per cent c.i.: 24–47 per cent). Pooled adjusted hazard ratios showed that cachexia was adversely associated with overall survival (HR 1.46, 95 per cent c.i.: 1.31–1.60, P < 0.001). Meta-analysis of proportions identified decreased overall survival at 1-, 3- and 5-years in cachectic cohorts. Pre-treatment cachexia was not a predictor of disease-free survival and further data are required to establish its influence on postoperative mortality. The proportion of patients with stage III/IV disease was a significant moderator of between-study heterogeneity. Cachexia may have a greater influence on overall survival in studies where more patients have a locally advanced malignancy.
Conclusion
Pre-treatment cachexia adversely influences overall survival following resection of an oesophagogastric malignancy.
Cancer cachexia is not purely an end-stage phenomenon and can even influence the outcomes of patients with potentially curable disease. In patients undergoing surgical resection of an oesophagogastric cancer, cachexia is adversely associated with overall survival (HR 1.46, 95 per cent c.i.: 1.31–1.60, P < 0.001). Consideration of cachexia, during the shared decision-making process, may improve risk stratification and facilitate targeted interventions.
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BFBNIB, FZAB, GIS, IJS, KILJ, NUK, OILJ, SBCE, SBMB, UL, UPUK
Objectives To define associations between hospital volume and outcomes following cholecystectomy, after adjustment for case mix using a national database.Design Retrospective, national population ...based study using multilevel modelling and simulation.Setting Locally validated administrative dataset covering all NHS hospitals in Scotland.Participants All patients undergoing cholecystectomy between 1 January 1998 and 31 December 2007.Main outcome measures Mortality, 30 day reoperation rate, 30 day readmission rate, and length of stay.Results We identified 59 918 patients who had a cholecystectomy in one of 37 hospitals: five hospitals had high volumes (>244 cholecystectomies/year), 10 had medium volumes (173-244), and 22 had low volumes (<173). Compared with low and medium volume hospitals, high volume hospitals performed more procedures non-electively (17.1% and 19.5% v 32.8%), completed more procedures laparoscopically (64.7% and 73.8% v 80.9%), and used more operative cholangiography (11.2% and 6.3% v 21.2%; χ2 test, all P<0.001). In a well performing multivariable analysis with bias correction for a low event rate, the odds ratio for death was greater in both the low volume (odds ratio 1.45, 95% confidence interval 1.06 to 2.00, P=0.022) and medium volume (1.52, 1.11 to 2.08, P=0.010) groups than in the high volume group. However, in simulation studies, absolute risk differences between volume groups were clinically negligible for patients with average risk (number needed to treat to harm, low v high volume, 3871, 1963 to 17 118), but were significant in patients with higher risk. In models accounting for the hierarchical structure of patients in hospitals, those in medium volume hospitals were more likely to undergo reoperation (odds ratio 1.74, 1.31 to 2.30, P<0.001) or be readmitted (1.17, 1.04 to 1.31, P=0.008) after cholecystectomy than those in high volume hospitals. Length of stay was shorter in high volume hospitals than in low (hazard ratio for discharge 0.78, 0.76 to 0.79, P<0.001) or medium volume hospitals (0.75, 0.74 to 0.77, P<0.001). These differences were also only of clinical significance in patients at higher risk.Conclusions There is wide variation among hospitals in the management of gallstone disease and an association between higher hospital volume and better outcome after a cholecystectomy. The relative risk of death is lower in high volume centres, and although absolute risk differences between volume groups are significant for elderly patients and patients with comorbidity, they are clinically negligible for those at average risk.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Bile duct injury (BDI) after cholecystectomy can lead to recurrent cholangitis, even after biliary reconstruction. This necessitates hepatectomy in a minority of patients. A systematic review was ...conducted, summarizing the pattern of biliary injury sustained in this group and their outcomes after hepatectomy.
A literature search included the MEDLINE, EMBASE, PubMed and Cochrane libraries. Retrospective cohort studies describing outcomes for hepatectomy after BDI, and the nature of the antecedent BDI, published between 1999 and 2019, were selected.
Eight articles described a cohort of 2110 patients with BDI. Of these, 84 underwent hepatectomy. Complex vasculo-biliary injuries had been sustained in most cases. The mean time to hepatectomy was between 26 and 224 months after BDI. A right hepatectomy was performed in 67–89% of cases. Post hepatectomy, intra-abdominal infection (range 0–50%) and bile leaks (range 0–45%) occurred variably. Mortality occurred in three series. Nineteen percent of patients (16 of 84) developed recurrent symptoms at follow up.
Hepatectomy after bile duct injury is an uncommon procedure and represents a salvage strategy when vasculo-biliary injury happens. Liver resection leads to resolution of symptoms in the majority of the cases however postoperative bile leaks and intra-abdominal infection are common.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Social media has an increasingly important role in scientific communication, clinical discussions and knowledge distribution. While several surgical disciplines have taken to internet for increased ...connectivity, there is currently little knowledge about the social media activity in the field of hepatopancreatobiliary surgery. We aimed to evaluate the implementation and use of a specific HPB hashtag and Twitter handle.
The hashtag and Twitter handle (#SoMe4HPB; @hpb_so) were initiated on February 2019. We evaluated the response during the initial 15 months by applying NodeXL to trace activity.
The Twitter handle had 1388 followers (by May 7, 2020) and had generated 855 tweets and retweets. A total of 1120 mentions of 182 accounts were recorded in original tweets by @hpb_so. The largest global reach was recorded in December 2019 (254.000 people). Pancreatic cancer was the subject of 15% of all posts, liver malignancies of 12% of all posts and minimally invasive surgery of 8%.
The Social Media for the Hepato-Pancreato-Biliary community (#SoMe4HPB) and its associated Twitter handle @hpb_so had a well-built inception followed by a progressive development connecting individuals interested in HPB Surgery internationally. The involvement of more actors is required in order to fully attain its scientific dissemination role.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
48.
Equality, diversity and inclusion in HPB surgery Wigmore, Stephen J.; Kokudo, Norihiro; Smith, Martin J.
HPB (Oxford, England),
June 2021, 2021-06-00, 20210601, Volume:
23, Issue:
6
Journal Article
Peer reviewed
Open access
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: Resting energy expenditure (REE) is the major component of total energy expenditure. REE is traditionally performed by indirect calorimetry (IC) and is not well investigated after liver ...surgery. A mobile device (SenseWear Armband SWA) has been validated when estimating REE in other clinical settings but not liver resection. The aims of this study are to validate SWA vs IC, quantify REE change following liver resection, and determine factors associated with REE change. Materials and Methods: Patients listed for open liver resection prospectively underwent IC and SWA REE recordings pre- and postoperatively. In addition, the SWA was worn continuously postoperatively to estimate daily REE for the first 5 postoperative days. To determine acceptability of the SWA, validation analysis was performed. To assess REE change, peak postoperative REE was compared with preoperative levels. Factors associated with REE change were also analyzed. Results: SWA showed satisfactory validity compared with IC when estimating REE, although postoperatively, the 95% levels of agreement (–5.56 to 3.18 kcal/kg/d) may introduce error. Postoperative REE (median, 23.5 kcal/kg/d; interquartile range IQR, 22.6–25.7 kcal/kg/d) was significantly higher than predicted REE (median, 19.7 kcal/kg/d; IQR, 19.1–21.0 kcal/kg/d; P < .0001). Median REE rise was 11% (IQR, –1% to 25%). Factors associated with REE rise of >11% were age (P = .017) and length of operation (P = .03). Conclusions: SWA offers a suitable alternative to IC when estimating postoperative REE, but the magnitude of the error (8.74 kcal/kg/d) could hinder its accuracy. REE quantification after liver resection is important to identify patients who could be prone to energy imbalance and therefore malnutrition.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK, VSZLJ
Background
Cancer cachexia is a poorly understood metabolic consequence of cancer. During cachexia, different adipose depots demonstrate differential wasting rates. Animal models suggest adipose ...tissue may be a key driver of muscle wasting through fat–muscle crosstalk, but human studies in this area are lacking. We performed global gene expression profiling of visceral (VAT) and subcutaneous (SAT) adipose from weight stable and cachectic cancer patients and healthy controls.
Methods
Cachexia was defined as >2% weight loss plus low computed tomography‐muscularity. Biopsies of SAT and VAT were taken from patients undergoing resection for oesophago‐gastric cancer, and healthy controls (n = 16 and 8 respectively). RNA was isolated and reverse transcribed. cDNA was hybridised to the Affymetrix Clariom S microarray and data analysed using R/Bioconductor. Differential expression of genes was assessed using empirical Bayes and moderated‐t‐statistic approaches. Category enrichment analysis was used with a tissue‐specific background to examine the biological context of differentially expressed genes. Selected differentially regulated genes were validated by qPCR. Enzyme‐linked immunosorbent assay (ELISA) for intelectin‐1 was performed on all VAT samples. The previously‐described cohort plus 12 additional patients from each group also had plasma I = intelectin‐1 ELISA carried out.
Results
In VAT vs. SAT comparisons, there were 2101, 1722, and 1659 significantly regulated genes in the cachectic, weight stable, and control groups, respectively. There were 2200 significantly regulated genes from VAT in cachectic patients compared with controls. Genes involving inflammation were enriched in cancer and control VAT vs. SAT, although different genes contributed to enrichment in each group. Energy metabolism, fat browning (e.g. uncoupling protein 1), and adipogenesis genes were down‐regulated in cancer VAT (P = 0.043, P = 5.4 × 10−6 and P = 1 × 10−6 respectively). The gene showing the largest difference in expression was ITLN1, the gene that encodes for intelectin‐1 (false discovery rate‐corrected P = 0.0001), a novel adipocytokine associated with weight loss in other contexts.
Conclusions
SAT and VAT have unique gene expression signatures in cancer and cachexia. VAT is metabolically active in cancer, and intelectin‐1 may be a target for therapeutic manipulation. VAT may play a fundamental role in cachexia, but the down‐regulation of energy metabolism genes implies a limited role for fat browning in cachectic patients, in contrast to pre‐clinical models.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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