Management of malignant Gastric Outlet Obstruction (mGOO) due to pancreatic cancer in the era of EUS-Gastrojejunostomy: an international practice survey and case vignette study by Pancreas 2000 from the European Pancreatic Club.

BACKGROUND: Malignant Gastric Outlet Obstruction (mGOO) has been standardly treated by surgical Gastrojejunostomy (S-GJ) or Endoscopic Stenting (ES). Recently, EUS-Gastrojejunostomy (EUS-GJ) has emerged as an alternative, despite its worldwide diffusion is heterogeneous. The aim of this survey was to assess clinical decision-making around mGOO and to explore current opinions regarding EUS-GJ. METHODS: An online survey, spread through social networks and EPC newsletter, was created exploring opinions regarding indications, contraindications, benefits/risks, availability of mGOO treatments; 2 case vignettes explored clinical decision-making in different scenarios. RESULTS: Overall, 290 pancreatologists from 44 countries responded, of whom 35% surgeons and 65% gastroenterologists. The most common treatment for mGOO was ES (86%), followed by laparoscopic GJ (76%). EUS-GJ was accessible to 59% of respondents, with 10% proficient in this technique. Gold-standard treatment for mGOO varied by specialty; 45% of gastroenterologists preferred ES, 20% EUS-GJ, and 10% surgical GJ, while among surgeons, these were 24%, 8%, and 25%, respectively. A higher annual volume of mGOO treated correlated with increased EUS-GJ adoption and reduced surgical advice. For 51%, EUS-GJ will become the primary treatment for mGOO, notably higher among gastroenterologists and high-volume centers. For 14%, EUS-GJ spread will be limited in the future, or used only when ES fails (19%). Life expectancy, disease stage and patient's frailty are the main decision driver in therapeutic choice, whereas future surgical resectability does not contraindicate any treatment for 75%. EUS-GJ's main advantages were its minimally invasive nature and clinical efficacy, offset by its steep learning curve. CONCLUSIONS: This survey revealed significant differences in the management of mGOO, depending on specialties, local expertise and treatment volume, suggesting the lack of standardized algorithms. Life expectancy and patients' frailty are the main decision drivers. Regarding EUS-GJ, its availability remains suboptimal, with learning curve as the main perceived barrier.

Epigenetic mechanisms and metabolic reprogramming in fibrogenesis: dual targeting of G9a and DNMT1 for the inhibition of liver fibrosis.

OBJECTIVE: Hepatic stellate cells (HSC) transdifferentiation into myofibroblasts is central to fibrogenesis. Epigenetic mechanisms, including histone and DNA methylation, play a key role in this process. Concerted action between histone and DNA-mehyltransferases like G9a and DNMT1 is a common theme in gene expression regulation. We aimed to study the efficacy of CM272, a first-in-class dual and reversible G9a/DNMT1 inhibitor, in halting fibrogenesis. DESIGN: G9a and DNMT1 were analysed in cirrhotic human livers, mouse models of liver fibrosis and cultured mouse HSC. G9a and DNMT1 expression was knocked down or inhibited with CM272 in human HSC (hHSC), and transcriptomic responses to transforming growth factor-ß1 (TGFß1) were examined. Glycolytic metabolism and mitochondrial function were analysed with Seahorse-XF technology. Gene expression regulation was analysed by chromatin immunoprecipitation and methylation-specific PCR. Antifibrogenic activity and safety of CM272 were studied in mouse chronic CCl4 administration and bile duct ligation (BDL), and in human precision-cut liver slices (PCLSs) in a new bioreactor technology. RESULTS: G9a and DNMT1 were detected in stromal cells in areas of active fibrosis in human and mouse livers. G9a and DNMT1 expression was induced during mouse HSC activation, and TGFß1 triggered their chromatin recruitment in hHSC. G9a/DNMT1 knockdown and CM272 inhibited TGFß1 fibrogenic responses in hHSC. TGFß1-mediated profibrogenic metabolic reprogramming was abrogated by CM272, which restored gluconeogenic gene expression and mitochondrial function through on-target epigenetic effects. CM272 inhibited fibrogenesis in mice and PCLSs without toxicity. CONCLUSIONS: Dual G9a/DNMT1 inhibition by compounds like CM272 may be a novel therapeutic strategy for treating liver fibrosis.

Histopathologic Predictors of Survival and Recurrence in Resected Ampullary Adenocarcinoma: International Multicenter Cohort Study.

OBJECTIVE: The aim of the study was to define histopathologic characteristics that independently predict overall survival (OS) and disease-free survival (DFS), in patients who underwent resection of an ampullary adenocarcinoma with curative intent. SUMMARY BACKGROUND DATA: A broad range of survival rates have been described for adenocarcinoma of the ampulla of Vater, presumably due to morphological heterogeneity which is a result of the different epitheliums ampullary adenocarcinoma can arise from (intestinal or pancreaticobiliary). Large series with homogenous patient selection are scarce. METHODS: A retrospective multicenter cohort analysis of patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma in 9 European tertiary referral centers between February 2006 and December 2017 was performed. Collected data included demographics, histopathologic details, survival, and recurrence. OS and DFS analyses were performed using Kaplan-Meier curves and Cox proportional hazard models. RESULTS: Overall, 887 patients were included, with a mean age of 66 ±â€Š10 years. The median OS was 64 months with 1-, 3-, 5-, and 10-year OS rates of 89%, 63%, 52%, and 37%, respectively. Histopathologic subtype, differentiation grade, lymphovascular invasion, perineural invasion, T-stage, N-stage, resection margin, and adjuvant chemotherapy were correlated with OS and DFS. N-stage (HR = 3.30 [2.09-5.21]), perineural invasion (HR = 1.50 [1.01-2.23]), and adjuvant chemotherapy (HR = 0.69 [0.48-0.97]) were independent predictors of OS in multivariable analysis, whereas DFS was only adversely predicted by N-stage (HR = 2.65 [1.65-4.27]). CONCLUSIONS: Independent predictors of OS in resected ampullary cancer were N-stage, perineural invasion, and adjuvant chemotherapy. N-stage was the only predictor of DFS. These findings improve predicting survival and recurrence after resection of ampullary adenocarcinoma.

A Bioreactor Technology for Modeling Fibrosis in Human and Rodent Precision-Cut Liver Slices.

Precision cut liver slices (PCLSs) retain the structure and cellular composition of the native liver and represent an improved system to study liver fibrosis compared to two-dimensional mono- or co-cultures. The aim of this study was to develop a bioreactor system to increase the healthy life span of PCLSs and model fibrogenesis. PCLSs were generated from normal rat or human liver, or fibrotic rat liver, and cultured in our bioreactor. PCLS function was quantified by albumin enzyme-linked immunosorbent assay (ELISA). Fibrosis was induced in PCLSs by transforming growth factor beta 1 (TGFß1) and platelet-derived growth factor (PDGFßß) stimulation ± therapy. Fibrosis was assessed by gene expression, picrosirius red, and α-smooth muscle actin staining, hydroxyproline assay, and soluble ELISAs. Bioreactor-cultured PCLSs are viable, maintaining tissue structure, metabolic activity, and stable albumin secretion for up to 6 days under normoxic culture conditions. Conversely, standard static transwell-cultured PCLSs rapidly deteriorate, and albumin secretion is significantly impaired by 48 hours. TGFß1/PDGFßß stimulation of rat or human PCLSs induced fibrogenic gene expression, release of extracellular matrix proteins, activation of hepatic myofibroblasts, and histological fibrosis. Fibrogenesis slowly progresses over 6 days in cultured fibrotic rat PCLSs without exogenous challenge. Activin receptor-like kinase 5 (Alk5) inhibitor (Alk5i), nintedanib, and obeticholic acid therapy limited fibrogenesis in TGFß1/PDGFßß-stimulated PCLSs, and Alk5i blunted progression of fibrosis in fibrotic PCLS. Conclusion: We describe a bioreactor technology that maintains functional PCLS cultures for 6 days. Bioreactor-cultured PCLSs can be successfully used to model fibrogenesis and demonstrate efficacy of antifibrotic therapies.

A Systematic Review and Network-Meta-Analysis of Gastro-Enteric Reconstruction Techniques Following Pancreatoduodenectomy to Reduce Delayed Gastric Emptying.

INTRODUCTION: This network meta-analysis aimed to identify the reconstruction technique associated with lowest rates of DGE following pancreatoduodenectomy (PD) from randomised controlled trials (RCTs). METHODS: A systematic literature search of PubMed, Embase and MEDLINE databases was carried out using the PRISMA framework to identify all RCTs comparing reconstruction techniques of gastrojejunostomy after PD, with overall DGE as the primary endpoint. The primary outcome measure was overall DGE. Secondary outcomes were grade B/C DGE, duration of nasogastric tube, time to solid food intake, overall and grade B/C pancreatic fistula, bile leaks, reoperation, length of hospital stay and in-hospital mortality. RESULTS: The search strategy identified eight RCTs including 761 patients. Six RCTs compared antecolic (n = 291 patients) and retrocolic Billroth II (n = 289 patients) reconstruction (n = 6 studies), and two RCTs compared antecolic Billroth II (n = 92 patients) and Roux-en-Y (n = 89 patients) reconstruction. Overall, antecolic Billroth II ranked best for overall and grade B/C DGE, bile leak, surgical site infection, length of stay and in-hospital mortality. Roux-en-Y was best for overall and grade B/C pancreatic fistula. CONCLUSION: Antecolic Billroth II gastroenteric reconstruction is associated with the lowest rates of delayed gastric emptying after PD amongst the currently available techniques of gastrojejunostomy reconstructions.

Robotic versus conventional laparoscopic distal pancreatic resection: a systematic review and meta-analysis.

BACKGROUND: Robotic surgery offers theoretical advantages to conventional laparoscopic surgery including improved instrument dexterity, 3D visualization and better ergonomics. This review aimed to determine if these theoretical advantages translate into improved patient outcomes in patients undergoing distal pancreatectomy through laparoscopic (LDP) or robotic (RDP) approaches. METHOD: A systematic literature search was conducted for studies reporting minimally invasive surgery for distal pancreatectomy. Meta-analysis of intraoperative (blood loss, operating times, conversion and R0 resections) and postoperative outcomes (overall complications, pancreatic fistula, length of hospital stay) was performed using random effects models. RESULT: Twenty non-randomised studies including 3112 patients (793 robotic and 2319 laparoscopic) were considered appropriate for inclusion. LDP had significantly shorter operating time than RDP (mean: 28, p < 0.001) but no significant difference in blood loss (mean: 52 mL, p = 0.07). RDP was associated with significantly lower conversion rates than LDP (OR 0.48, p < 0.001), but no difference in spleen preservation rate and R0 resection. There were no significant differences in overall and major complications, overall and high-grade pancreatic fistula. However, RDP was associated with a shorter length of hospital stay (mean: 1, p < 0.001). CONCLUSION: Robotic distal pancreatectomy appears to offer some advantages compared to conventional laparoscopic surgery, although both techniques appear equivalent. Importantly, the quality of evidence is generally limited to cohort studies and a high-quality randomised trial comparing both techniques are needed.

Prognosis of sporadic resected small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors - a multi-institutional study.

BACKGROUND: Malignant potential of small (≤20 mm) nonfunctional pancreatic neuroendocrine tumors (sNF-PNET) is difficult to predict and management remain controversial. The aim of this study was to assess the prognosis of sporadic nonmetastatic sNF-PNETs. METHODS: Patients were identified from databases of 16 centers. Outcomes and risk factors for recurrence were identified by uni- and multivariate analyses. RESULTS: sNF-PNET was resected in 210 patients, and 66% (n = 138) were asymptomatic. Median age was 60 years, median tumor size was 15 mm, parenchyma-sparing surgery was performed in 42%. Postoperative mortality was 0.5% (n = 1), severe morbidity rate was 14.3% (n = 30), and 14 of 132 patients (10.6%) with harvested lymph nodes had metastatic lymph nodes. Tumor size, presence of biliary or pancreatic duct dilatation, and WHO grade 2-3 were independently associated with recurrence. Patients with tumors sized ≤10 mm were disease free at last follow-up. The 1-, 3- and 5-year disease-free survival rates for patients with tumors sized 11-20 mm on preoperative imaging were 95.1%, 91.0%, and 87.3%, respectively. CONCLUSIONS: In sNF-PNETs, the presence of biliary or pancreatic duct dilatation or WHO grade 2-3 advocate for surgical treatment. In the remaining patients, a wait-and-see policy might be considered.

Chronic pancreatitis: Do serum biomarkers provide an association with an inflammageing phenotype?

BACKGROUND: Chronic pancreatitis is an inflammatory disorder of the pancreas that is associated with accelerated mortality for patients suffering from this disease. The association between chronic inflammation and accelerated biological ageing has been well described and is often referred to as "inflammageing". In this review we seek to determine how systemic inflammation in chronic pancreatitis may contribute to an accelerated ageing phenotype. METHODS: A systematic literature search with a predefined search protocol was performed on Medline, Embase and Cochrane libraries according to the PRISMA guidelines. RESULTS: The initial search identified 499 studies. After title, abstract and full text screen of the search results, 20 were included for further evaluation. In the 20 remaining articles 41 inflammatory mediators were identified - mainly involved in chronic inflammation, fibrosis and particularly cardinal features of inflammageing such as sarcopenia and osteoporosis. CONCLUSION: Chronic pancreatitis is associated with elevated levels of inflammatory mediators many of which are associated with an accelerated ageing phenotype and may explain some of the clinical sequelae of this disease.

Histone methyltransferase ASH1 orchestrates fibrogenic gene transcription during myofibroblast transdifferentiation.

UNLABELLED: Transdifferentiation of hepatic stellate cells (HSCs) to a myofibroblast-like phenotype is the pivotal event in liver fibrosis. The dramatic change in phenotype associated with transdifferentiation is underpinned by a global change in gene expression. Orchestrated changes in gene expression take place at the level of chromatin packaging which is regulated by enzymatic activity of epigenetic regulators that in turn affect histone modifications. Using expression profiling of epigenetic regulators in quiescent and activated primary HSCs we found a number of histone methyltransferases including MLL1, MLL5, Set1 and ASH1 to be highly up-regulated during transdifferentiation of HSCs. All of these histone methyltransferases regulate methylation of lysine 4 of histone H3, which is a signature of actively transcribed genes. We therefore postulated that one or more of these enzymes may be involved in positively influencing expression of profibrogenic genes. CONCLUSION: We find that ASH1 directly binds to the regulatory regions of alpha smooth muscle actin (αSMA), collagen I, tissue inhibitor of metalloproteinase-1 (TIMP1) and transforming growth factor beta1 (TGFß1) in activated HSCs while depletion of ASH1 caused broad suppression of fibrogenic gene expression. We also discovered that MeCP2 positively regulates ASH1 expression and therefore identify ASH1 as a key transcriptional activator component of the MeCP2 epigenetic relay pathway that orchestrates coordinated induction of multiple profibrogenic genes.

An experimental study to identify the potential role of pharmacogenomics in determining the occurrence of oxaliplatin-induced liver injury.

BACKGROUND: Oxaliplatin-based chemotherapy has been linked to the development of sinusoidal obstruction syndrome (SOS), which is detrimental to outcome after liver resection for colorectal liver metastases (CLM). The aim of this study was to determine how the expression of genes involved in the transport and metabolism of FOLFOX chemotherapy impacts on tissue injury in a murine model of CLM. METHODS: Experimental CLM was established in C57/B16 mice and treated with FOLFOX chemotherapy. After 3 weeks, the animals were killed and RNA extracted from liver, spleen and tumour tissue. DNA damage was assessed by immunohistochemistry for γH2AX. Gene expression was determined by reverse transcriptase polymerase chain reaction. RESULTS: FOLFOX treatment was associated with an increase in the number of γH2AX-positive cells in both the spleen (P < 0.01) and tumour tissue (P < 0.01), but not the liver. Tissue resistance to injury following FOLFOX was associated with high expression of the copper transporter ATP7B. Differences in the expression of genes related to 5-fluorouracil metabolism or DNA repair did not correlate with the severity of tissue injury. CONCLUSIONS: High levels of expression of ATP7B are associated with resistance to tissue injury following FOLFOX chemotherapy. Polymorphisms in the ATP7B gene may explain varying susceptibility to SOS among patients following oxaliplatin-based chemotherapy.

N-acetylcysteine administration does not improve patient outcome after liver resection.

BACKGROUND: Post-operative hepatic dysfunction is a major cause of concern when undertaking a liver resection. The generation of reactive oxygen species (ROS) as a result of hepatic ischaemia/reperfusion (I/R) injury can result in hepatocellular injury. Experimental evidence suggests that N-acetylcysteine may ameliorate ROS-mediated liver injury. METHODS: A cohort of 44 patients who had undergone a liver resection and receiving peri-operative N-acetylcysteine (NAC) were compared with a further cohort of 44 patients who did not. Liver function tests were compared on post-operative days 1, 3 and 5. Peri-operative outcome data were retrieved from a prospectively maintained database within our unit. RESULTS: Administration of NAC was associated with a prolonged prothrombin time on the third post-operative day (18.4 versus 16.4 s; P = 0.002). The incidence of grades B and C liver failure was lower in the NAC group although this difference did not reach statistical significance (6.9% versus 14%; P = 0.287). The overall complication rate was similar between groups (32% versus 25%; P = ns). There were two peri-operative deaths in the NAC group and one in the control group (P = NS). CONCLUSION: In spite of promising experimental evidence, this study was not able to demonstrate any advantage in the routine administration of peri-operative NAC in patients undergoing a liver resection.

Is aggressive intravenous fluid prescription the answer to reduce mortality in severe pancreatitis? The FLIP study: Fluid resuscitation in pancreatitis.

Backgrounds/Aims: Acute pancreatitis is an emergency presentation, which can range from mild to life threatening. Intravenous fluids are the cornerstone of management. Although the WATERFALL trial described the optimal fluid rate in mild/moderate pancreatitis, this trial excluded patients with moderate-severe/severe pancreatitis. The aim of this study was to establish clinical practice regarding intravenous fluid administration in acute pancreatitis and assess its effect on mortality. Methods: Prospective multi-centre audit of patients with acute pancreatitis was conducted. Data were collected regarding intravenous fluid administration within 72 hours of admission. The primary outcome was 30-day mortality. Multivariable logistic regression was used to identify predictors of 30-day mortality. Results: Those with severe pancreatitis received more fluid; median 5.7 L versus 4 L in 72 hours (p = 0.003). Participants with severe pancreatitis who died within 30 days received a median of 2,750 mL in the first 24 hours, compared to 4,000 mL in those who survived. The following factors were significant predictors of 30-day mortality: age, Glasgow score, C-reactive protein, ischaemic heart disease, and pancreatitis aetiology. Overall, volume of intravenous fluid was not associated with mortality. However, the effect of intravenous fluid volume on mortality differed significantly depending on pancreatitis severity. In severe pancreatitis, increased volume of intravenous fluid was associated with significant reductions in mortality (odds ratio = 0.655; 0.459-0.936; p = 0.020). Conclusions: In severe pancreatitis, more aggressive fluid prescription was associated with decreased mortality; however, this was not the case in milder disease. Further prospective trials guiding fluid resuscitation in severe pancreatitis are needed, as the impact of fluid on this population appears to differ from that in those with milder disease.

Chemotherapy-associated liver injury in patients with colorectal liver metastases: a systematic review and meta-analysis.

BACKGROUND: Chemotherapy-associated liver injury is a major cause for concern when treating patients with colorectal liver metastases. The aim of this review was to determine the pathological effect of specific chemotherapy regimens on the hepatic parenchyma as well as on surgical morbidity, mortality and overall survival. METHODS: A systematic review of the published literature and a meta-analysis were performed. For each of the variables under consideration, the effects of different chemotherapy regimens were determined by calculation of relative risks by a random-effects model. RESULTS: Hepatic parenchymal injury is regimen specific, with oxaliplatin-based regimens being associated with grade 2 or greater sinusoidal injury (number needed to harm 8; 95 % confidence interval [CI] 6.4-13.6), whereas irinotecan-based regimens associated with steatohepatitis (number needed to harm 12; 95 % CI 7.8-26). The use of bevacizumab alongside FOLFOX reduces the risk of grade 2 or greater sinusoidal injury (relative risk 0.34; 95 % CI 0.15-0.75). CONCLUSIONS: Chemotherapy before resection of colorectal liver metastases is associated with an increased risk of regimen-specific liver injury. This liver injury may have implications for the functional reserve of the liver for patients undergoing major hepatectomy for colorectal liver metastases.

Laparoscopic liver resection: is there a learning curve?

BACKGROUND: Laparoscopic liver resection (LLR) is becoming an accepted treatment option for resecting both benign and malignant tumours. However, it is critical that the laparoscopic approach does not compromise the technical quality of the liver resection. The aim of this paper was to review the learning curve of LLR in a specialist HPB unit. METHODS: A prospective database was searched to identify patients undergoing LLR over a 4-year period. To assess the effect of the learning curve on outcome, the series was evaluated during two eras--early versus late. RESULTS: Fifty-one (27 males, median age 68 years) patients were identified with 37 having LLR. The most common indication was for colorectal liver metastases, and the most common procedure was a non-anatomical metastectomy. Changes in management decisions (n = 14) occurred more frequently during the first era (9 vs. 5; p > 0.05). More patients underwent right hepatectomy in the late group (3 vs. 1; p < 0.05). There did not appear to be any difference in duration of surgery for laparoscopic left lateral resection between the eras (200 vs. 240 min; p > 0.05) which probably reflected trainees performing more operations during the late era. Left hepatectomy was most commonly performed in the early era compared to more right hepatectomies during the late era. CONCLUSION: LLR is associated with a learning curve, but once this has been overcome it can be safely utilised in the management of malignant liver lesions even for major resections, surgical training and simultaneous resections.

Risk factors for decompensation and death following umbilical hernia repair in patients with end-stage liver disease.

INTRODUCTION: Symptomatic umbilical hernias are a common cause of morbidity and mortality in patients with cirrhosis and end-stage liver disease (ESLD). This study set out to characterise the factors predicting outcome following repair of symptomatic umbilical hernias in ESLD at a single institution. METHODS: A retrospective review was performed of all patients with ESLD who underwent repair of a symptomatic umbilical hernia between 1998 and 2020. Overall survival was predicted using the Kaplan-Meier method. Logistic regression was used to determine predictors of decompensation and 30-day, 90-day and 1-year mortality. RESULTS: One-hundred-and-eight patients with ESLD underwent umbilical hernia repair (emergency n = 78, 72.2%). Transjugular shunting was performed in 29 patients (26.9%). Decompensation occurred in 44 patients (40.7%) and was predicted by emergency surgery (OR, 13.29; P = 0.001). Length of stay was shorter in elective patients compared to emergency patients (3-days vs. 7-days; P = 0.003). Thirty-day, 90-day and 1-year survival was 95.2, 93.2 and 85.4%, respectively. Model for ESLD score >15 predicted 90-day mortality (OR, 18.48; P = 0.030) and hyponatraemia predicted 1-year mortality (OR, 5.31; P = 0.047). Transjugular shunting predicted survival at 1 year (OR, 0.15; P = 0.038). CONCLUSIONS: Repair of symptomatic umbilical hernias in patients with ESLD can be undertaken with acceptable outcomes in a specialist centre, however, this remains a high-risk intervention. Patients undergoing emergency repair are more likely to decompensate postoperatively, develop wound-related problems and have a longer length of stay. Transjugular shunting may confer a benefit to survival, but further prospective trials are warranted.

COVID-19 and liver cancer: lost patients and larger tumours.

BACKGROUND: Northern England has been experiencing a persistent rise in the number of primary liver cancers, largely driven by an increasing incidence of hepatocellular carcinoma (HCC) secondary to alcohol-related liver disease and non-alcoholic fatty liver disease. Here we review the effect of the COVID-19 pandemic on primary liver cancer services and patients in our region. OBJECTIVE: To assess the impact of the COVID-19 pandemic on patients with newly diagnosed liver cancer in our region. DESIGN: We prospectively audited our service for the first year of the pandemic (March 2020-February 2021), comparing mode of presentation, disease stage, treatments and outcomes to a retrospective observational consecutive cohort immediately prepandemic (March 2019-February 2020). RESULTS: We observed a marked decrease in HCC referrals compared with previous years, falling from 190 confirmed new cases to 120 (37%). Symptomatic became the the most common mode of presentation, with fewer tumours detected by surveillance or incidentally (% surveillance/incidental/symptomatic; 34/42/24 prepandemic vs 27/33/40 in the pandemic, p=0.013). HCC tumour size was larger in the pandemic year (60±4.6 mm vs 48±2.6 mm, p=0.017), with a higher incidence of spontaneous tumour haemorrhage. The number of new cases of intrahepatic cholangiocarcinoma (ICC) fell only slightly, with symptomatic presentation typical. Patients received treatment appropriate for their cancer stage, with waiting times shorter for patients with HCC and unchanged for patients with ICC. Survival was associated with stage both before and during the pandemic. 9% acquired COVID-19 infection. CONCLUSION: The pandemic-associated reduction in referred patients in our region was attributed to the disruption of routine healthcare. For those referred, treatments and survival were appropriate for their stage at presentation. Non-referred or missing patients are expected to present with more advanced disease, with poorer outcomes. While protective measures are necessary during the pandemic, we recommend routine healthcare services continue, with patients encouraged to engage.

Laparoscopic Pringle's manoeuvre for liver resection?: how I do it.

Although experience with the laparoscopic approach for liver resection has increased in recent years, it still remains a challenging procedure. One of the manoeuvres to reduce catastrophic haemorrhage is occlusion of hepatic inflow by compression of the hepato-duodenal ligament, the so-called Pringle's manoeuvre. One of the limitations of laparoscopic liver resection is the safe placement of a tape around the hepato-duodenal ligament to facilitate intermittent clamping of the porta-hepatis (Pringle's manoeuvre) prior to hepatic transection. We present a novel, safe and efficient technique that has evolved during this series of laparoscopic liver resections.

Surgical adjuncts to laparoscopic distal pancreatectomy.

Abstract Laparoscopic distal pancreatectomy (LDP) has emerged as an alternative approach to traditional open surgery for managing isolated pathology in the body and tail of the pancreas. Experience with this technique to date is limited with only small series reported in the literature. Common difficulties with this operation are related to dissection of the pancreas from the portal vein and management of the pancreatic stump. In this paper we describe our single centre experience to date and describe strategies we have developed which we believe facilitate safe and effective laparoscopic distal pancreatectomy.

Non-invasive synchronous monitoring of neutrophil migration using whole body near-infrared fluorescence-based imaging.

Advances in fluorescence imaging coupled with the generation of near infrared probes have significantly improved the capabilities of non-invasive, real-time imaging in whole animals. In this study we were able to overcome a limitation of in vivo fluorescence imaging and have established a dual cell tracking method where two different cell types can be monitored according to the spectral signature of the cell labelling fluorophore. Using a mouse model of acute liver injury, we have characterised the in vivo migration patterns of wild type and transgenic neutrophils with impaired chemotaxis. Here, we were able to demonstrate that IVIS provides a sensitive multiplexing technology to differentiate two different cell populations based on the spectral signature of the cell labelling fluorophores. This spectral unmixing methodology has the potential to uncover multidimensional cellular interactions involved in many diseases such as fibrosis and cancer. In vivo spectral un-mixing provides a useful tool for monitoring multiple biological process in real-time in the same animal.

Impact of routine nasogastric decompression versus no nasogastric decompression after pancreaticoduodenectomy on perioperative outcomes: meta-analysis.

BACKGROUND: Consensus on the use of nasogastric decompression (NGD) after pancreaticoduodenectomy (PD) is lacking. This meta-analysis reviewed current evidence on the impact of routine NGD versus no NGD after PD on perioperative outcomes. METHODS: PubMed, Medline, Scopus, Embase and Cochrane databases were searched for studies reporting on the role of NGD after PD on perioperative outcomes. Data up to January 2021were retrieved and analysed. RESULTS: Eight studies were included, with a total of 1301 patients enrolled, of whom 668 had routine NGD. Routine NGD was associated with a higher incidence of overall delayed gastric emptying (DGE) (odds ratio (OR) 2.51, 95 per cent c.i. 1.12 to 5.63, I2 = 83 per cent; P = 0.03) and clinically relevant DGE (OR 3.64, 95 per cent c.i. 1.83 to 7.25, I2 = 54 per cent; P < 0.01), a higher rate of Clavien-Dindo grade II or higher complications (OR 3.12, 95 per cent c.i. 1.05 to 9.28, I2 = 88 per cent; P = 0.04) and increased length of hospital stay (mean difference 2.67, 95 per cent c.i. 0.60 to 4.75, I2 = 97 per cent; P = 0.02). There were no significant differences in overall complications (OR 1.07, 95 per cent c.i. 0.79 to 1.46, I2 = 0 per cent; P = 0.66) or postoperative pancreatic fistula (OR 1.21, 95 per cent c.i. 0.86 to 1.72, I2 = 0 per cent; P = 0.28) between patients with or those without routine NGD. CONCLUSION: Routine NGD was associated with increased rates of DGE, major complications and longer length of stay after PD.