Background
The laparoscopic approach in distal pancreatectomy is associated with higher rates of splenic preservation compared to open surgery. Although favorable postoperative short-term outcomes ...have been reported in open spleen-preserving distal pancreatectomy when compared to distal pancreatectomy with splenectomy, it is unclear whether this observation applies to the laparoscopic approach. The aim of this study is to compare laparoscopic spleen-preserving distal pancreatectomy (LSPDP) with laparoscopic distal pancreatectomy with splenectomy (LDPS).
Study design
This is a UK wide, propensity score-matched study, including patients who underwent LSPDP or LDPS between 2006 and 2016. Short-term outcomes were compared between LSPDP and LDPS according to intention to treat. Additionally, risk factors for unplanned splenectomy were explored.
Results
A total of 456 patients were included from eleven centers (229 LSPDP and 227 LDPS). We were able to match 173 LSPDP cases to 173 LDPS cases, according to intention to treat. No differences were seen in postoperative morbidity between the groups. The only identified risk factor for unplanned splenectomy was tumor size ≥ 30 mm.
Conclusions
Preserving the spleen during laparoscopic distal pancreatectomy is not associated with a lower postoperative morbidity compared to sacrificing the spleen. Tumor size is a risk factor for unplanned splenectomy.
Non-alcoholic fatty liver disease (NAFLD) begins with lipid accumulation within hepatocytes, but the relative contributions of different macronutrients is still unclear. We investigated the impact of ...fatty acids, glucose and fructose on lipid accumulation in primary human hepatocytes (PHH) and three different cell lines: HepG2 (human hepatoblastoma−derived cell line), Huh7 (human hepatocellular carcinoma cell line) and McA-RH7777 (McA, rat hepatocellular carcinoma cell line). Cells were treated for 48 h with fatty acids (0 or 200 μM), glucose (5 mM or 11 mM) and fructose (0 mM, 2 mM or 8 mM). Lipid accumulation was measured via Nile Red staining. All cell types accumulated lipid in response to fatty acids (p < 0.001). PHH and McA, but not HepG2 or Huh7 cells, accumulated more lipid with 11 mM glucose plus fatty acids (p = 0.004, fatty acid × glucose interaction, for both), but only PHH increased lipid accumulation in response to fructose (p < 0.001). Considerable variation was observed between PHH cells from different individuals. Lipid accumulation in PHH was increased by insulin (p = 0.003) with inter-individual variability. Similarly, insulin increased lipid accumulation in both HepG2 and McA cells, with a bigger response in McA in the presence of fatty acids (p < 0.001 for fatty acid × insulin). McA were more insulin sensitive than either HepG2 or Huh7 cells in terms of AKT phosphorylation (p < 0.001 insulin × cell type interaction). Hence, glucose and fructose can contribute to the accumulation of lipid in PHH with considerable inter-individual variation, but hepatoma cell lines are not good models of PHH.
Bile duct cancer (cholangiocarcinoma, CCA) has a poor prognosis for patients, and despite recent advances in targeted therapies for other cancer types, it is still treated with standard chemotherapy. ...Anaplastic lymphoma kinase (ALK) has been shown to be a primary driver of disease progression in lung cancer, and ALK inhibitors are effective therapeutics in aberrant ALK-expressing tumors. Aberrant ALK expression has been documented in CCA, but the use of ALK inhibitors has not been investigated. Using CCA cell lines and close-to-patient primary cholangiocarcinoma cells, we investigated the potential for ALK inhibitors in CCA.
ALK, cMET, and ROS1 expression was determined in CCA patient tissue by immunohistochemistry and digital droplet polymerase chain reaction, and that in cell lines was determined by immunoblot and immunofluorescence. The effect on cell viability and mechanism of action of ALK, cMet, and ROS1 inhibitors was determined in CCA cell lines. To determine whether ceritinib could affect primary CCA cells, tissue was taken from four patients with biliary tract cancer, without ALK rearrangement, mutation, or overexpression, and grown in three-dimensional tumor growth assays in the presence or absence of humanized mesenchymal cells.
ALK and cMet but not ROS were both upregulated in CCA tissues and cell lines. Cell survival was inhibited by crizotinib, a c-met/ALK/ROS inhibitor. To determine the mechanism of this effect, we tested c-Met-specific and ALK/ROS-specific inhibitors, capmatinib and ceritinib, respectively. Whereas capmatinib did not affect cell survival, ceritinib dose-dependently inhibited survival in all cell lines, with IC
ranging from 1 to 9 µM and co-treatments with gemcitabine and cisplatin further sensitized cells, with IC
ranging from IC
0.60 to 2.32 µM. Ceritinib did not inhibit cMet phosphorylation but did inhibit ALK phosphorylation. ALK was not mutated in any of these cell lines. Only ceritinib inhibited 3D growth of all four patient samples below mean peak serum concentration, in the presence and absence of mesenchymal cells, whereas crizotinib and capmatinib failed to do this. Ceritinib appeared to exert its effect more through autophagy than apoptosis.
These results indicate that ceritinib or other ALK/ROS inhibitors could be therapeutically useful in cholangiocarcinoma even in the absence of aberrant ALK/ROS1 expression.
AIM To evaluate the outcome of patients with bilobar colorectal liver metastases(CRLM) and identify clinicopathological variables that influenced survival.METHODS Patients with bilobar CRLM were ...identified from a prospectively maintained hepatobiliary database during the study period(January 2010-June 2014). Collated data included demographics, primary tumour treatment, surgical data, histopathology analysis and clinical outcome. Down-staging therapy included Oxaliplatinor Irinotecan- based regimens, and Cetuximab was also used in patients that were K-RAS wild-type. Response to neo-adjuvant therapy was assessed at the multidisciplinary team meeting and considered for surgery if all macroscopic CRLM were resectable with a clear margin while preserving sufficient liver parenchyma.RESULTS Of the 136 patients included, thirty-two(23.5%) patients were considered inoperable and referred for palliative chemotherapy, and thirty-four(25%) patients underwent liver resection. Seventy(51.4%) patients underwent down-staging therapy, of which 37(52.8%) patients responded sufficiently to undergo liver resection. Patients that failed to respond to down-staging therapy(n = 33, 47.1%) were referred for palliative therapy. There was a significant difference in overall survival between the three groups(surgery vs down-staging therapy vs inoperable disease, P < 0.001). All patients that underwent hepatic resection, including patients that had down-staging therapy, had a significantly better overall survival compared to patients that were inoperable(P < 0.001). On univariate analysis, only resection margin significantly influenced disease-free survival(P = 0.017). On multi-variate analysis, R0 resection(P = 0.030) and female(P = 0.036) gender significantly influenced overall survival. CONCLUSION Patients undergoing liver resection with bilobar CRLM have a significantly better survival outcome. R0 resection is associated with improved disease-free and overall survival in this patient group.
Background
N‐acetylcysteine (NAC) has many uses in medicine; notable in the management of paracetamol toxicity, acute liver failure and liver surgery. The aim of this review was to critically ...appraise the published literature for the routine use of NAC in liver resection surgery.
Methods
An electronic search was performed of EBSCOhost (Medline and CINAHL database), PubMed and the Cochrane Library for the period 1990–2016. MeSH headings: ‘acetyl‐cysteine’, ‘liver resection’ and ‘hepatectomy’ were used to identify all relevant articles published in English.
Results
Following the search criteria used, three articles were included. Two of these studies were randomized controlled trials. All the studies collated data on morbidity and mortality. All three studies did not show a significant difference in overall complications rates in patients that underwent hepatic resection that had NAC infusion compared with patients that did not. In one study, NAC administration was associated with a higher frequency of grade A post‐hepatectomy liver failure. In another study, a significantly higher incidence of delirium was observed in the NAC group, which led to the trial to be terminated early.
Conclusion
The current published data do not support the routine use of NAC following liver resection.
There is emerging evidence that the pancreas may be a target organ of SARS-CoV-2 infection. This aim of this study was to investigate the outcome of patients with acute pancreatitis (AP) and ...coexistent SARS-CoV-2 infection.
A prospective international multicentre cohort study including consecutive patients admitted with AP during the current pandemic was undertaken. Primary outcome measure was severity of AP. Secondary outcome measures were aetiology of AP, intensive care unit (ICU) admission, length of hospital stay, local complications, acute respiratory distress syndrome (ARDS), persistent organ failure and 30-day mortality. Multilevel logistic regression was used to compare the two groups.
1777 patients with AP were included during the study period from 1 March to 23 July 2020. 149 patients (8.3%) had concomitant SARS-CoV-2 infection. Overall, SARS-CoV-2-positive patients were older male patients and more likely to develop severe AP and ARDS (p<0.001). Unadjusted analysis showed that SARS-CoV-2-positive patients with AP were more likely to require ICU admission (OR 5.21, p<0.001), local complications (OR 2.91, p<0.001), persistent organ failure (OR 7.32, p<0.001), prolonged hospital stay (OR 1.89, p<0.001) and a higher 30-day mortality (OR 6.56, p<0.001). Adjusted analysis showed length of stay (OR 1.32, p<0.001), persistent organ failure (OR 2.77, p<0.003) and 30-day mortality (OR 2.41, p<0.04) were significantly higher in SARS-CoV-2 co-infection.
Patients with AP and coexistent SARS-CoV-2 infection are at increased risk of severe AP, worse clinical outcomes, prolonged length of hospital stay and high 30-day mortality.
Prehabilitation comprises multidisciplinary preoperative interventions including exercise, nutritional optimisation and psychological preparation aimed at improving surgical outcomes. The aim of this ...systematic review and meta-analysis was to determine the impact of prehabilitation on postoperative outcomes in frail and high-risk patients undergoing major abdominal surgery.
Embase, Medline, CINAHAL and Cochrane databases were searched from January 2010 to January 2023 for randomised clinical trials (RCTs) and observational studies evaluating unimodal (exercise) or multimodal prehabilitation programmes. Meta-analysis was limited to length of stay (primary end point), severe postoperative complications (Clavien-Dindo Classification ≥ Grade 3) and the 6-minute walk test (6MWT). The analysis was performed using RevMan v5.4 software.
Sixteen studies (6 RCTs, 10 observational) reporting on 3339 patients (1468 prehabilitation group, 1871 control group) were included. The median (interquartile range) age was 74.0 (71.0–78.4) years. Multimodal prehabilitation was applied in fifteen studies and unimodal in one. Meta-analysis of nine studies showed a reduction in hospital length of stay (weighted mean difference −1.07 days, 95 % CI −1.60 to −0.53 days, P < 0.0001, I2 = 19 %). Ten studies addressed severe complications and a meta-analysis suggested a decline in occurrence by up to 44 % (odds ratio 0.56, 95 % CI 0.37 to 0.82, P < 0.004, I2 = 51 %). Four studies provided data on preoperative 6MWT. The pooled weighted mean difference was 40.1 m (95 % CI 32.7 to 47.6 m, P < 0.00001, I2 = 24 %), favouring prehabilitation.
Given the significant impact on shortening length of stay and reducing severe complications, prehabilitation should be encouraged in frail, older and high-risk adult patients undergoing major abdominal surgery.
This study assessed Cardiopulmonary Exercise Testing (CPET) in predicting oncological outcomes, post-operative recovery and complications in advanced ovarian cancer (AOC) cytoreductive surgery. We ...reviewed all patients who had CPET prior to AOC cytoreductive surgery with evidence of upper abdominal disease on preoperative imaging at the University Hospitals of Derby and Burton (UHDB) between August 2016 and July 2019. Patients were stratified by AT and maximum VO
2
levels. 43 patients were identified. AT showed no relationship with major complications. 100% of patients in the AT ≥11 group received R0 (n = 21, 91.30%), or R1 (n = 2, 8.70%) cytoreduction, whereas in the AT <11 group, only 75.00% achieved and R0 or R1 resection (p = .02). Surgical complexity was higher in the AT ≥11 group (p = .001) and the VO
2
≥15 group (p = .0006). No other correlations were seen between AT or VO
2
max and complications or readmissions. No difference in overall survival was seen if R0 resection was achieved.
IMPACT STATEMENT
What is already known on this subject? CPET testing allows pre-operative assessment of functional capacity to generate variables that can be used as a risk-stratification tool for major surgery. Whilst CPET testing has been shown to predict morbidity in non-gynaecological surgery, it remains unproven in cytoreductive surgery for ovarian cancer surgery despite being increasingly utilised.
What do the results of study add? Our data suggest that CPET testing does not predict complication rates or survival in AOC. Patients with poor CPET performance are more likely to receive suboptimal cytoreductive outcomes from surgery.
What are the implications of these findings for clinical practice and/or further research? CPET results should not be used to discount patients from cytoreductive surgery further research should address the interplay with nutrition, haematological markers, neoadjuvant chemotherapy and CPET performance.
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