Outcomes after emergency appendicectomy in patients with liver cirrhosis: a population-based cohort study from England.

INTRODUCTION: The mortality risk after appendicectomy in patients with liver cirrhosis is predicted to be higher than in the general population given the associated risk of perioperative bleeding, infections and liver decompensation. This population-based cohort study aimed to determine the 90-day mortality risk following emergency appendicectomy in patients with cirrhosis. METHODS: Adult patients undergoing emergency appendicectomy in England between January 2001 and December 2018 were identified from two linked primary and secondary electronic healthcare databases, the clinical practice research datalink and hospital episode statistics data. Length of stay, re-admission, case fatality and the odds ratio of 90-day mortality were calculated for patients with and without cirrhosis, adjusting for age, sex and co-morbidity using logistic regression. RESULTS: A total of 40,353 patients underwent appendicectomy and of these 75 (0.19%) had cirrhosis. Patients with cirrhosis were more likely to be older (p < 0.0001) and have comorbidities (p < 0.0001). Proportionally, more patients with cirrhosis underwent an open appendicectomy (76%) compared with 64% of those without cirrhosis (p = 0.03). The 90-day case fatality rate was 6.67% in patients with cirrhosis compared with 0.56% in patients without cirrhosis. Patients with cirrhosis had longer hospital length of stay (4 (IQR 3-9) days versus 3 (IQR 2-4) days and higher readmission rates at 90 days (20% vs 11%, p = 0.019). Most importantly, their odds of death at 90 days were 3 times higher than patients without cirrhosis, adjusted odds ratio 3.75 (95% CI 1.35-10.49). CONCLUSION: Patients with cirrhosis have a threefold increased odds of 90-day mortality after emergency appendicectomy compared to those without cirrhosis.

Cholecystectomy in patients with cirrhosis: a population-based cohort study from England.

BACKGROUND: This population-based cohort study aimed to determine postoperative outcomes after emergency and elective cholecystectomy in patients with cirrhosis. METHODS: Linked electronic healthcare data from England were used to identify all patients undergoing cholecystectomy between January 2000 and December 2017. Length of stay (LOS), re-admission, case fatality and the odds ratio of 90-day mortality were calculated for patients with and without cirrhosis, adjusting for age, sex and co-morbidity using logistic regression. RESULTS: Of the total 69,141 eligible patients who underwent a cholecystectomy, 511 (0.74%) had cirrhosis. In patients without cirrhosis 86.55% underwent a laparoscopic procedure compared with 57.53% in patients with cirrhosis (p < 0.0001). LOS was longer in those with cirrhosis (3 IQR 1-8 vs 1 IQR 1-3 days,p < 0.0001). 90-day re-admission was greater in patients with cirrhosis, 36.79% compared with 14.95% in those without cirrhosis. 90-day case fatality after elective cholecystectomy in patients with and without cirrhosis was 2.79% and 0.43%; and 12.82% and 2.39% following emergency cholecystectomy. This equated to a 3-fold (OR 3.22, IQR 1.72-6.02) and a 4-fold (OR 4.52, IQR 2.46-8.33) increased odds of death at 90-days following elective and emergency cholecystectomy after adjusting for confounders. CONCLUSION: Patients with cirrhosis undergoing cholecystectomy have an increased 90-day risk of postoperative mortality, which is significantly worse after emergency procedures.

Mortality following elective and emergency colectomy in patients with cirrhosis: a population-based cohort study from England.

BACKGROUND: Patients with cirrhosis undergoing colectomy have a higher risk of postoperative mortality, but contemporary estimates are lacking and data on associated risk and longer term outcomes are limited. This study aimed to quantify the risk of mortality following colectomy by urgency of surgery and stage of cirrhosis. DATA SOURCES: Linked primary and secondary-care electronic healthcare data from England were used to identify all patients undergoing colectomy from January 2001 to December 2017. These patients were classified by the absence or presence of cirrhosis and severity. Case fatality rates at 90 days and 1 year were calculated, and cox regression was used to estimate the hazard ratio of postoperative mortality controlling for age, gender and co-morbidity. RESULTS: Of the total, 36,380 patients undergoing colectomy, 248 (0.7%) had liver cirrhosis, and 70% of those had compensated cirrhosis. Following elective colectomy, 90-day case fatality was 4% in those without cirrhosis, 7% in compensated cirrhosis and 10% in decompensated cirrhosis. Following emergency colectomy, 90-day case fatality was higher; it was 16% in those without cirrhosis, 35% in compensated cirrhosis and 41% in decompensated cirrhosis. This corresponded to an adjusted 2.57 fold (95% CI 1.75-3.76) and 3.43 fold (95% CI 2.02-5.83) increased mortality risk in those with compensated and decompensated cirrhosis, respectively. This higher case fatality in patients with cirrhosis persisted at 1 year. CONCLUSION: Patients with cirrhosis undergoing emergency colectomy have a higher mortality risk than those undergoing elective colectomy both at 90 days and 1 year. The greatest mortality risk at 90 days was in those with decompensation undergoing emergency surgery.

Prehabilitation prior to surgery for pancreatic cancer: A systematic review.

INTRODUCTION: Prehabilitation aims to improve fitness and outcomes of patients undergoing major surgery. This systematic review aimed to appraise current available evidence regarding the role of prehabilitation in patients undergoing oncological pancreatic resection. METHODS: A systematic literature search of PUBMED, MEDLINE, EMBASE databases identified articles describing prehabilitation programmes before pancreatic resection for malignancy. Data collected included timing of prehabilitation, programme type, duration, adherence and post-operative outcome reporting. RESULTS: Six studies, including 193 patients were included in the final analysis. Three studies included patients undergoing neoadjuvant therapy followed by resection and 3 studies included patients undergoing upfront resection. Time from diagnosis to surgery ranged between 2 and 22 weeks across all studies. Two studies reported a professionally supervised exercise programme, and four described unsupervised programmes. Exercise programmes varied from 5 days to 6 months in duration. Adherence to exercise programmes was better with supervised programmes (99% reaching weekly activity goal vs 85%) and patients not undergoing neoadjuvant therapy (90% reaching weekly activity goal vs 82%). All studies reported improvement in muscle mass or markers of muscle function following prehabilitation. Two studies reported the impact of Prehabilitation on postoperative outcomes and Prehabilitation was associated with lower delayed gastric emptying and a shorter hospital stay with no impact on other postoperative outcomes. CONCLUSION: Early evidence demonstrates that Prehabilitation programmes may improve postoperative outcomes following pancreatic surgery. However current Prehabilitaton programmes for patients undergoing pancreatic resection report diverse exercise regimens with no consensus regarding timing or length of Prehabilitation, warranting a need for standardisation of Prehabilitation programmes in pancreatic surgery.

Meta-Analysis and Meta-Regression of Risk Factors for Surgical Site Infections in Hepatic and Pancreatic Resection.

BACKGROUND: The risk factors for surgical site infection (SSI) after HPB surgery are poorly defined. This meta-analysis aimed to quantify the SSI rates and risk factors for SSI after pancreas and liver resection. METHODS: The PUBMED, MEDLINE and EMBASE databases were systematically searched using the PRISMA framework. The primary outcome measure was pooled SSI rates. The secondary outcome measure was risk factor profile determination for SSI. RESULTS: The overall rate of SSI after pancreatic and liver resection was 25.1 and 10.4%, respectively (p < 0.001). 32% of pancreaticoduodenectomies developed SSI vs 23% after distal pancreatectomy (p < 0.001). The rate of incisional SSI in the pancreatic group was 9% and organ/space SSI 16.5%. Biliary resection during liver surgery was a risk factor for SSI (25.0 vs 15.7%, p = 0.002). After liver resection, the incisional SSI rate was 7.6% and the organ space SSI rate was 10.2%. Pancreas-specific SSI risk factors were pre-operative biliary drainage (p < 0.001), chemotherapy (p < 0.001) and radiotherapy (p = 0.007). Liver-specific SSI risk factors were smoking (p = 0.046), low albumin (p < 0.001) and significant blood loss (p < 0.001). The rate of organ/space SSI in patients with POPF was 47.7% and in patients without POPF 7.3% (p < 0.001). Organ/space SSI rate was 43% in patients with bile leak and 10% in those without (p < 0.001). CONCLUSIONS: The risk factors for SSI following pancreatic and liver resections are distinct from each other, with higher SSI rates after pancreatic resection. Pancreaticoduodenectomy has increased risk of SSI compared to distal pancreatectomy. Similarly, biliary resections during liver surgery increase the rates of SSI.

Haemostatic Efficacy of Topical Agents During Liver Resection: A Network Meta-Analysis of Randomised Trials.

BACKGROUND: Hepatic resection carries a high risk of parenchymal bleeding both intra- and post-operatively. Topical haemostatic agents are frequently used to control bleeding during hepatectomy, with multiple products currently available. However, it remains unknown which of these is most effective for achieving haemostasis and improving peri-operative outcomes. METHODS: A systematic review and random-effects Bayesian network meta-analysis of randomised trials investigating topical haemostatic agents in hepatic resection was performed. Interventions were analysed by grouping into similar products; fibrin patch, fibrin glue, collagen products, and control. Primary outcomes were the rate of haemostasis at 4 and 10 min. RESULTS: Twenty randomized controlled trials were included in the network meta-analysis, including a total of 3267 patients and 7 different interventions. Fibrin glue and fibrin patch were the most effective interventions for achieving haemostasis at both 4 and 10 min. There were no significant differences between haemostatic agents with respect to blood loss, transfusion requirements, bile leak, post-operative complications, reoperation, or mortality. CONCLUSIONS: Amongst the haemostatic agents currently available, fibrin patch and fibrin glue are the most effective methods for reducing time to haemostasis during liver resection, but have no effect on other peri-operative outcomes. Topical haemostatic agents should not be used routinely, but may be a useful adjunct to achieve haemostasis when needed.

A systematic review of the impact of portal vein pressure changes on clinical outcomes following hepatic resection.

BACKGROUND: There are evolving data correlating elevated post-hepatic resection portal vein pressure (PVP) with risk of developing post-resection liver failure (PLF) and other complications. As a consequence, modulation of PVP presents a potential strategy to improve outcomes following liver resection (LR). The primary aim of this study was to review the existing evidence regarding the impact of post-resection PVP on clinical outcomes in patients undergoing a LR. METHODS: Systematic literature searches of electronic databases in accordance with PRISMA were conducted. Changes in PVP and clinical outcomes following liver resection were defined according to the existing literature. RESULTS: Ten studies, consisting of 712 patients with a median age 61 (52-68) years, were identified that met the inclusion criteria. Of those, 77% (n = 550) underwent a major LR and 27% (n = 195) of patients had cirrhosis. Following LR, the median (range) PVP increased from 11.4 mmHg (median baseline, range 7.3-16.4) to 15.9 mmHg (7.9-19). The overall median incidence of PLF was 19%. Six of the ten studies found an elevated PVP after LR predicted PLF. One study found elevated PVP after LR predicted mortality after LR. CONCLUSION: Elevated PVP following hepatic resection was associated with increased rates of PLF. It was not possible to define a specific threshold PVP for predicting PLF. Modulation of PVP therefore presents a potential strategy to mitigate the incidence of LR. Future studies should standardize on reporting liver remnant and haemodynamics to better characterize clinical outcomes following LR.

A systematic review and network meta-analysis of parenchymal transection techniques during hepatectomy: an appraisal of current randomised controlled trials.

BACKGROUND: Major liver resection can lead to significant morbidity and mortality. Blood loss is one of the most important factors predicting a good outcome. Although various transection methods have been reported, there is no consensus on the best technique. This systematic review and network meta-analysis aims to characterise and identify the best reported technique for elective parenchymal liver transection based on published randomised controlled trials (RCT's). METHODS: A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Central to identify RCT's up to 5th June 2019 that examined parenchymal transection for liver resection. Data including study characteristics and outcomes including intraoperative (blood loss, operating time) and postoperative measures (overall and major complications, bile leaks) were extracted. Indirect comparisons of all regimens were simultaneously compared using random-effects network meta-analyses (NMA) which maintains randomisation within trials. RESULTS: This study identified 22 RCT's involving 2360 patients reporting ten parenchymal transection techniques. Bipolar cautery has lower blood loss and shorter operating time than stapler (mean difference: 85 mL; 22min) and Tissue Link (mean difference: 66 mL; 29min). Bipolar cautery was ranked first for blood loss and operating time followed by stapler and TissueLink. Harmonic scalpel is associated with lower overall complications than Hydrojet (Odds ratio (OR): 0.48), BiClamp forceps (OR: 0.46) and clamp crushing (OR: 0.41). CONCLUSION: Bipolar cautery techniques appear to best at reducing blood loss and associated with shortest operating time. In contrast, Harmonic scalpel appears best for overall and major complications. Given the paucity of data and selective outcome reporting, it is still hard to identify what is the best technique for liver resection. Therefore, further high-quality large-scale RCT's are still needed.

The effects of terlipressin and direct portacaval shunting on liver hemodynamics following 80% hepatectomy in the pig.

Liver failure is the major cause of death following liver resection. Post-resection portal venous pressure (PVP) predicts liver failure, is implicated in its pathogenesis, and when PVP is reduced, rates of liver dysfunction decrease. The aim of the present study was to characterize the hemodynamic, biochemical, and histological changes induced by 80% hepatectomy in non-cirrhotic pigs and determine if terlipressin or direct portacaval shunting can modulate these effects. Pigs were randomized (n=8/group) to undergo 80% hepatectomy alone (control); terlipressin (2 mg bolus + 0.5-1 mg/h) + 80% hepatectomy; or portacaval shunt (PCS) + 80% hepatectomy, and were maintained under terminal anesthesia for 8 h. The primary outcome was changed in PVP. Secondary outcomes included portal venous flow (PVF), hepatic arterial flow (HAF), and biochemical and histological markers of liver injury. Hepatectomy increased PVP (9.3 ± 0.4 mmHg pre-hepatectomy compared with 13.0 ± 0.8 mmHg post-hepatectomy, P<0.0001) and PVF/g liver (1.2 ± 0.2 compared with 6.0 ± 0.6 ml/min/g, P<0.0001) and decreased HAF (70.8 ± 5.0 compared with 41.8 ± 5.7 ml/min, P=0.002). Terlipressin and PCS reduced PVP (terlipressin = 10.4 ± 0.8 mmHg, P=0.046 and PCS = 8.3 ± 1.2 mmHg, P=0.025) and PVF (control = 869.0 ± 36.1 ml/min compared with terlipressin = 565.6 ± 25.7 ml/min, P<0.0001 and PCS = 488.4 ± 106.4 ml/min, P=0.002) compared with control. Treatment with terlipressin increased HAF (73.2 ± 11.3 ml/min) compared with control (40.3 ± 6.3 ml/min, P=0.026). The results of the present study suggest that terlipressin and PCS may have a role in the prevention and treatment of post-resection liver failure.

The Composition of Poly(Ethylene Terephthalate) (PET) Surface Precipitates Determined at High Resolving Power by Tandem Mass Spectrometry Imaging.

We present the first demonstration of a general method for the chemical characterization of small surface features at high magnification via simultaneous collection of mass spectrometry (MS) imaging and tandem MS imaging data. High lateral resolution tandem secondary ion MS imaging is employed to determine the composition of surface features on poly(ethylene terephthalate) (PET) that precipitate during heat treatment. The surface features, probed at a lateral resolving power of<200 nm using a surface-sensitive ion beam, are found to be comprised of ethylene terephthalate trimer at a greater abundance than is observed in the surrounding polymer matrix. This is the first chemical identification of PET surface precipitates made without either an extraction step or the use of a reference material. The new capability employed for this study achieves the highest practical lateral resolution ever reported for tandem MS imaging.

A New Method and Mass Spectrometer Design for TOF-SIMS Parallel Imaging MS/MS.

We report a method for the unambiguous identification of molecules in biological and materials specimens at high practical lateral resolution using a new TOF-SIMS parallel imaging MS/MS spectrometer. The tandem mass spectrometry imaging reported here is based on the precise monoisotopic selection of precursor ions from a TOF-SIMS secondary ion stream followed by the parallel and synchronous collection of the product ion data. Thus, our new method enables simultaneous surface screening of a complex matrix chemistry with TOF-SIMS (MS(1)) imaging and targeted identification of matrix components with MS/MS (MS(2)) imaging. This approach takes optimal advantage of all ions produced from a multicomponent sample, compared to classical tandem mass spectrometric methods that discard all ions with the exception of specific ions of interest. We have applied this approach for molecular surface analysis and molecular identification on the nanometer scale. High abundance sensitivity is achieved at low primary ion dose density; therefore, one-of-a-kind samples may be relentlessly probed before ion-beam-induced molecular damage is observed.

Adherence to enhanced recovery after surgery protocols across a high-volume gastrointestinal surgical service.

BACKGROUND AND AIMS: Enhanced recovery after surgery (ERAS) has been shown to improve outcomes for patients following gastrointestinal surgery. Data on protocol adherence and how this impacts on outcome are limited. This study examines how protocol adherence changes over time and determines how this impacts on outcome across a large-volume gastrointestinal surgical service. MATERIALS AND METHODS: A prospective review of patients eligible for colorectal, liver and oesophagogastric ERAS over two 3-month periods in 2010 and 2011 was performed. End points included: length of stay (LOS), overall protocol adherence, individual modality adherence, reason for pathway deviation and patient outcomes. RESULTS: 172 patients (110 colorectal, 31 liver and 31 oesophagogastric) were evaluated. For each sub-speciality, the introduction of ERAS led to significant reductions in LOS that were sustained for the duration of the study. Adherence was achieved across 60% (colorectal), 75% (liver) and 88% (oesophagogastric) of individual pathway modalities. The major causes of pathway deviation were: post-operative nausea and vomiting (colorectal), pain (liver) and pulmonary complications (oesophagogastric). CONCLUSIONS: Large-scale implementation of ERAS at a high-volume centre is feasible and offers many of the benefits demonstrated in controlled trials, but adherence may diminish over time.

Gemcitabine transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma.

BACKGROUND/AIMS: Transcatheter arterial chemoembolization (TACE) has been shown to increase survival in patients with unresectable hepatocellular carcinoma (HCC), however toxicity from commonly used agents limits its use in unresectable disease. Gemcitabine is a well tolerated chemotherapeutic agent with a high first pass clearance. In this study we evaluated a cohort of patients with unresectable HCC treated with gemcitabine-TACE alone. METHODOLOGY: A review of all patients that underwent gemcitabine-TACE for unresectable HCC from 2002 to 2006 was performed. No patients were eligible for resection, liver transplantation or ablation. All patients received gemcitabine-TACE alone. The primary outcome measure was survival from first treatment. Secondary outcome measures included radiological response and toxicity. RESULTS: 55 patients underwent a total of 172 gemcitabine-TACE treatments for unresectable HCC. Median age was 64.7 years. All patients had Barcelona-Clinic Liver Cancer (BCLC) stage B (44%) or C (56%) disease. Median survival following gemcitabine-TACE was 8.8 months. 22% demonstrated a partial response and 61% had stable disease. 6% experienced grade 3/4 adverse events. There was 1 treatment related death. CONCLUSIONS: Gemcitabine-TACE is well tolerated and appears to provide an alternative agent for patients with unresectable HCC undergoing chemoembolization.

Spatially resolved correlation of active and total doping concentrations in VLS grown nanowires.

Controlling axial and radial dopant profiles in nanowires is of utmost importance for NW-based devices, as the formation of tightly controlled electrical junctions is crucial for optimization of device performance. Recently, inhomogeneous dopant profiles have been observed in vapor­liquid­solid grown nanowires, but the underlying mechanisms that produce these inhomogeneities have not been completely characterized. In this work, P-doping profiles of axially modulation-doped Si nanowires were studied using nanoprobe scanning Auger microscopy and Kelvin probe force microscopy in order to distinguish between vapor­liquid­solid doping and the vapor­solid doping. We find that both mechanisms result in radially inhomogeneous doping, specifically, a lightly doped core surrounded by a heavily doped shell structure. Careful design of dopant modulation enables the contributions of the two mechanisms to be distinguished, revealing a surprisingly strong reservoir effect that significantly broadens the axial doping junctions.

UCHL1-dependent control of hypoxia-inducible factor transcriptional activity during liver fibrosis.

Liver fibrosis is the excessive accumulation of extracellular matrix proteins that occurs in most types of chronic liver disease. At the cellular level, liver fibrosis is associated with the activation of hepatic stellate cells (HSCs) which transdifferentiate into a myofibroblast-like phenotype that is contractile, proliferative and profibrogenic. HSC transdifferentiation induces genome-wide changes in gene expression that enable the cell to adopt its profibrogenic functions. We have previously identified that the deubiquitinase ubiquitin C-terminal hydrolase 1 (UCHL1) is highly induced following HSC activation; however, the cellular targets of its deubiquitinating activity are poorly defined. Here, we describe a role for UCHL1 in regulating the levels and activity of hypoxia-inducible factor 1 (HIF1), an oxygen-sensitive transcription factor, during HSC activation and liver fibrosis. HIF1 is elevated during HSC activation and promotes the expression of profibrotic mediator HIF target genes. Increased HIF1α expression correlated with induction of UCHL1 mRNA and protein with HSC activation. Genetic deletion or chemical inhibition of UCHL1 impaired HIF activity through reduction of HIF1α levels. Furthermore, our mechanistic studies have shown that UCHL1 elevates HIF activity through specific cleavage of degradative ubiquitin chains, elevates levels of pro-fibrotic gene expression and increases proliferation rates. As we also show that UCHL1 inhibition blunts fibrogenesis in a pre-clinical 3D human liver slice model of fibrosis, these results demonstrate how small molecule inhibitors of DUBs can exert therapeutic effects through modulation of HIF transcription factors in liver disease. Furthermore, inhibition of HIF activity using UCHL1 inhibitors may represent a therapeutic opportunity with other HIF-related pathologies.

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.

Scaffolds containing growth factors and extracellular matrix induce hepatocyte proliferation and cell migration in normal and regenerating rat liver.

BACKGROUND & AIMS: Intrahepatic drug delivery from implantable scaffolds is being developed as a strategy to modulate growth and enhance regeneration at the time of liver resection. In this study we examine the effects of scaffolds containing hepatocyte growth factor, epidermal growth factor, fibroblast growth factor 1, fibroblast growth factor 2, and liver-derived extracellular matrix (L-ECM) when implanted into normal and partially hepatectomized rat livers. METHODS: Scaffolds loaded with combinations of growth factors and L-ECM were implanted into normal livers (controls=L-ECM, polymer or sham) and livers following partial hepatectomy (controls=partial hepatectomy or sham). The primary end points were hepatocyte DNA synthesis and liver tissue penetration into scaffolds. Secondary end points included non-parenchymal cell DNA synthesis, liver weight analysis, liver function, and histological characterisation of the peri-implant parenchyma. RESULTS: Four days after implantation in normal livers, there was significantly more hepatocyte proliferation around growth factor scaffolds than controls. Seven days after implantation, there was significantly more tissue penetration into growth factor scaffolds than control scaffolds. ED-1 and desmin positive cells were present in the pores of scaffolds. Two days after partial hepatectomy, there was significantly more hepatocyte proliferation around scaffold implanted livers than after partial hepatectomy alone. CONCLUSIONS: Growth factors and L-ECM accelerated non-parenchymal cell migration into scaffolds and increased hepatocyte and non-parenchymal cell proliferation around them. These results demonstrate the potential for intrahepatic implantation of scaffolds containing growth factors and L-ECM to modulate growth in the normal and regenerating liver.

Meta-analysis of survival outcomes following surgical and non surgical treatments for colorectal cancer metastasis to the lung.

BACKGROUND: Controversy exists regarding the optimal management of colorectal lung metastases (CRLM). This meta-analysis compared surgical (Surg) versus interventional (chemotherapy and/or radiotherapy) and observational non-surgical (NSurg) management of CRLM. METHODS: A systematic review of the major databases including Medline, Embase, SCOPUS and the Cochrane library was performed. RESULTS: One randomized and nine observational studies including 2232 patients: 1551 (69%) comprised the Surg cohort, 521 (23%) the interventional NSurg group and 160 (7%) the observational NSurg group. A significantly higher overall survival (OS) was observed when Surg was compared to interventional NSurg at 1 year (Surg 88%, 310/352; interventional NSurg 64%, 245/383; odds ratio (OR) 2.77 (confidence interval (CI) 1.94-3.97), P = 0.001), at 3 years (Surg 59%, 857/1444; interventional NSurg 26%, 138/521; OR 2.61 (CI 1.65-4.15), P = 0.002), at 5 years (Surg 47%, 533/1144; interventional NSurg 23%, 45/196; OR 3.24 (CI 1.42-7.39), P = 0.009) and at 10 years (Surg 27%, 306/1122; interventional NSurg 1%, 2/168; OR 15.64 (CI 1.87-130.76), P = 0.031). Surg was associated with a greater OS than observational NSurg at only 1 year (Surg 92%, 98/107; observational NSurg 83%, 133/160; OR 6.69 (CI 1.33-33.58), P = 0.037) and was similar to observational NSurg at all other OS time points. Comparable survival was observed among Surg and overall NSurg cohorts at 3- and 5-year survival in articles published within the last 3 years. CONCLUSIONS: Recent evidence suggests comparable survival with Surg and NSurg modalities for CRLM, contrasting to early evidence where Surg had an improved survival. Significant selection bias contributes to this finding, prompting the need for high powered randomized controlled trials and registry data.