Adjuvant chemotherapy for adenocarcinoma arising from intraductal papillary mucinous neoplasia: multicentre ADENO-IPMN study.

BACKGROUND: The clinical impact of adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia is unclear. The aim of this study was to identify factors related to receipt of adjuvant chemotherapy and its impact on recurrence and survival. METHODS: This was a multicentre retrospective study of patients undergoing pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia between January 2010 and December 2020 at 18 centres. Recurrence and survival outcomes for patients who did and did not receive adjuvant chemotherapy were compared using propensity score matching. RESULTS: Of 459 patients who underwent pancreatic resection, 275 (59.9%) received adjuvant chemotherapy (gemcitabine 51.3%, gemcitabine-capecitabine 21.8%, FOLFIRINOX 8.0%, other 18.9%). Median follow-up was 78 months. The overall recurrence rate was 45.5% and the median time to recurrence was 33 months. In univariable analysis in the matched cohort, adjuvant chemotherapy was not associated with reduced overall (P = 0.713), locoregional (P = 0.283) or systemic (P = 0.592) recurrence, disease-free survival (P = 0.284) or overall survival (P = 0.455). Adjuvant chemotherapy was not associated with reduced site-specific recurrence. In multivariable analysis, there was no association between adjuvant chemotherapy and overall recurrence (HR 0.89, 95% c.i. 0.57 to 1.40), disease-free survival (HR 0.86, 0.59 to 1.30) or overall survival (HR 0.77, 0.50 to 1.20). Adjuvant chemotherapy was not associated with reduced recurrence in any high-risk subgroup (for example, lymph node-positive, higher AJCC stage, poor differentiation). No particular chemotherapy regimen resulted in superior outcomes. CONCLUSION: Chemotherapy following resection of adenocarcinoma arising from intraductal papillary mucinous neoplasia does not appear to influence recurrence rates, recurrence patterns or survival.

Long-term Outcomes following Resection of Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasm (A-IPMN) versus Pancreatic Ductal Adenocarcinoma (PDAC): A Propensity-score Matched Analysis.

OBJECTIVE: The aim of the present study was to compare long-term post-resection oncological outcomes between A-IPMN and PDAC. SUMMARY BACKGROUND DATA: Knowledge of long term oncological outcomes (e.g recurrence and survival data) comparing between adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) and pancreatic ductal adenocarcinoma (PDAC) is scarce. METHODS: Patients undergoing pancreatic resection (2010-2020) for A-IPMN were identified retrospectively from 18 academic pancreatic centres and compared with PDAC patients from the same time-period. Propensity-score matching (PSM) was performed and survival and recurrence were compared between A-IPMN and PDAC. RESULTS: 459 A-IPMN patients (median age,70; M:F,250:209) were compared with 476 PDAC patients (median age,69; M:F,262:214). A-IPMN patients had lower T-stage, lymphovascular invasion (51.4%vs. 75.6%), perineural invasion (55.8%vs. 71.2%), lymph node positivity (47.3vs. 72.3%) and R1 resection (38.6%vs. 56.3%) compared to PDAC(P<0.001). The median survival and time-to-recurrence for A-IPMN versus PDAC were 39.0 versus19.5months (P<0.001) and 33.1 versus 14.8months (P<0.001), respectively (median follow-up,78 vs.73 months). Ten-year overall survival for A-IPMN was 34.6%(27/78) and PDAC was 9%(6/67). A-IPMN had higher rates of peritoneal (23.0 vs. 9.1%, P<0.001) and lung recurrence (27.8% vs. 15.6%, P<0.001) but lower rates of locoregional recurrence (39.7% vs. 57.8%; P<0.001). Matched analysis demonstrated inferior overall survival (P=0.005), inferior disease-free survival (P=0.003) and higher locoregional recurrence (P<0.001) in PDAC compared to A-IPMN but no significant difference in systemic recurrence rates (P=0.695). CONCLUSIONS: PDACs have inferior survival and higher recurrence rates compared to A-IPMN in matched cohorts. Locoregional recurrence is higher in PDAC but systemic recurrence rates are comparable and constituted by their own distinctive site-specific recurrence patterns.

The impact of prehabilitation on outcomes in frail and high-risk patients undergoing major abdominal surgery: A systematic review and meta-analysis.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Do some patients receive unnecessary parenteral nutrition after pancreatoduodenectomy? Results from an international multicentre study.

Backgrounds/Aims: After pancreatoduodenectomy (PD), an early oral diet is recommended; however, the postoperative nutritional management of PD patients is known to be highly variable, with some centers still routinely providing parenteral nutrition (PN). Some patients who receive PN experience clinically significant complications, underscoring its judicious use. Using a large cohort, this study aimed to determine the proportion of PD patients who received postoperative nutritional support (NS), describe the nature of this support, and investigate whether receiving PN correlated with adverse perioperative outcomes. Methods: Data were extracted from the Recurrence After Whipple's study, a retrospective multicenter study of PD outcomes. Results: In total, 1,323 patients (89%) had data on their postoperative NS status available. Of these, 45% received postoperative NS, which was "enteral only," "parenteral only," and "enteral and parenteral" in 44%, 35%, and 21% of cases, respectively. Body mass index < 18.5 kg/m2 (p = 0.03), absence of preoperative biliary stenting (p = 0.009), and serum albumin < 36 g/L (p = 0.009) all correlated with receiving postoperative NS. Among those who did not develop a serious postoperative complication, i.e., those who had a relatively uneventful recovery, 20% received PN. Conclusions: A considerable number of patients who had an uneventful recovery received PN. PN is not without risk, and should be reserved for those who are unable to take an oral diet. PD patients should undergo pre- and postoperative assessment by nutrition professionals to ensure they are managed appropriately, and to optimize perioperative outcomes.

Preclinical evidence for anaplastic lymphoma kinase inhibitors as novel therapeutic treatments for cholangiocarcinoma.

Introduction: 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. Methods: 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. Results: 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 IC50 ranging from 1 to 9 µM and co-treatments with gemcitabine and cisplatin further sensitized cells, with IC50 ranging from IC50 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. Discussion: 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.

Postoperative complications after pancreatoduodenectomy for malignancy: results from the Recurrence After Whipple's (RAW) study.

BACKGROUND: Pancreatoduodenectomy (PD) is associated with significant postoperative morbidity. Surgeons should have a sound understanding of the potential complications for consenting and benchmarking purposes. Furthermore, preoperative identification of high-risk patients can guide patient selection and potentially allow for targeted prehabilitation and/or individualized treatment regimens. Using a large multicentre cohort, this study aimed to calculate the incidence of all PD complications and identify risk factors. METHOD: Data were extracted from the Recurrence After Whipple's (RAW) study, a retrospective cohort study of PD outcomes (29 centres from 8 countries, 2012-2015). The incidence and severity of all complications was recorded and potential risk factors for morbidity, major morbidity (Clavien-Dindo grade > IIIa), postoperative pancreatic fistula (POPF), post-pancreatectomy haemorrhage (PPH) and 90-day mortality were investigated. RESULTS: Among the 1348 included patients, overall morbidity, major morbidity, POPF, PPH and perioperative death affected 53 per cent (n = 720), 17 per cent (n = 228), 8 per cent (n = 108), 6 per cent (n = 84) and 4 per cent (n = 53), respectively. Following multivariable tests, a high BMI (P = 0.007), an ASA grade > II (P < 0.0001) and a classic Whipple approach (P = 0.005) were all associated with increased overall morbidity. In addition, ASA grade > II patients were at increased risk of major morbidity (P < 0.0001), and a raised BMI correlated with a greater risk of POPF (P = 0.001). CONCLUSION: In this multicentre study of PD outcomes, an ASA grade > II was a risk factor for major morbidity and a high BMI was a risk factor for POPF. Patients who are preoperatively identified to be high risk may benefit from targeted prehabilitation or individualized treatment regimens.

Risk of Recurrence after Surgical Resection for Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasia (IPMN) with Patterns of Distribution and Treatment: An International, Multicentre, Observational Study.

OBJECTIVE: This international multicentre cohort study aims to identify recurrence patterns and treatment of first and second recurrence in a large cohort of patients after pancreatic resection for adenocarcinoma arising from IPMN. SUMMARY BACKGROUND DATA: Recurrence patterns and treatment of recurrence post resection of adenocarcinoma arising from IPMN are poorly explored. METHOD: Patients undergoing pancreatic resection for adenocarcinoma from IPMN between January 2010 to December 2020 at 18 pancreatic centres were identified. Survival analysis was performed by the Kaplan-Meier log rank test and multivariable logistic regression by Cox-Proportional Hazards modelling. Endpoints were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided). RESULTS: Four hundred and fifty-nine patients were included (median, 70 y; IQR, 64-76; male, 54 percent) with a median follow-up of 26.3 months (IQR, 13.0-48.1 mo). Recurrence occurred in 209 patients (45.5 percent; median time to recurrence, 32.8 months, early recurrence [within 1 y], 23.2 percent). Eighty-three (18.1 percent) patients experienced a local regional recurrence and 164 (35.7 percent) patients experienced distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (HR 1.09;P=0.669) One hundred and twenty patients with recurrence received further treatment. The median survival with and without additional treatment was 27.0 and 14.6 months (P<0.001), with no significant difference between treatment modalities. There was no significant difference in survival between location of recurrence (P=0.401). CONCLUSION: Recurrence after pancreatic resection for adenocarcinoma arising from IPMN is frequent with a quarter of patients recurring within 12 months. Treatment of recurrence is associated with improved overall survival and should be considered.

Does an extensive diagnostic workup for upfront resectable pancreatic cancer result in a delay which affects survival? Results from an international multicentre study.

Backgrounds/Aims: Pancreatoduodenectomy (PD) is recommended in fit patients with a carcinoma (PDAC) of the pancreatic head, and a delayed resection may affect survival. This study aimed to correlate the time from staging to PD with long-term survival, and study the impact of preoperative investigations (if any) on the timing of surgery. Methods: Data were extracted from the Recurrence After Whipple's (RAW) study, a multicentre retrospective study of PD outcomes. Only PDAC patients who underwent an upfront resection were included. Patients who received neoadjuvant chemo-/radiotherapy were excluded. Group A (PD within 28 days of most recent preoperative computed tomography [CT]) was compared to group B (> 28 days). Results: A total of 595 patents were included. Compared to group A (median CT-PD time: 12.5 days, interquartile range: 6-21), group B (49 days, 39-64.5) had similar one-year survival (73% vs. 75%, p = 0.6), five-year survival (23% vs. 21%, p = 0.6) and median time-todeath (17 vs. 18 months, p = 0.8). Staging laparoscopy (43 vs. 29.5 days, p = 0.009) and preoperative biliary stenting (39 vs. 20 days, p < 0.001) were associated with a delay to PD, but magnetic resonance imaging (32 vs. 32 days, p = 0.5), positron emission tomography (40 vs. 31 days, p > 0.99) and endoscopic ultrasonography (28 vs. 32 days, p > 0.99) were not. Conclusions: Although a treatment delay may give rise to patient anxiety, our findings would suggest this does not correlate with worse survival. A delay may be necessary to obtain further information and minimize the number of PD patients diagnosed with early disease recurrence.

Serious complications of pancreatoduodenectomy correlate with lower rates of adjuvant chemotherapy: Results from the recurrence after Whipple's (RAW) study.

INTRODUCTION: Adjuvant chemotherapy (AC) can prolong overall survival (OS) after pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). However, fitness for AC may be influenced by postoperative recovery. We aimed to investigate if serious (Clavien-Dindo grade ≥ IIIa) postoperative complications affected AC rates, disease recurrence and OS. MATERIALS AND METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study (n = 1484), a retrospective study of PD outcomes (29 centres from eight countries). Patients who died within 90-days of PD were excluded. The Kaplan-Meier method was used to compare OS in those receiving or not receiving AC, and those with and without serious postoperative complications. The groups were then compared using univariable and multivariable tests. RESULTS: Patients who commenced AC (vs no AC) had improved OS (median difference: (MD): 201 days), as did those who completed their planned course of AC (MD: 291 days, p < 0.0001). Those who commenced AC were younger (mean difference: 2.7 years, p = 0.0002), more often (preoperative) American Society of Anesthesiologists (ASA) grade I-II (74% vs 63%, p = 0.004) and had less often experienced a serious postoperative complication (10% vs 18%, p = 0.002). Patients who developed a serious postoperative complication were less often ASA grade I-II (52% vs 73%, p = 0.0004) and less often commenced AC (58% vs 74%, p = 0.002). CONCLUSION: In our multicentre study of PD outcomes, PDAC patients who received AC had improved OS, and those who experienced a serious postoperative complication commenced AC less frequently. Selected high-risk patients may benefit from targeted preoperative optimisation and/or neoadjuvant chemotherapy.

Predictors of actual five-year survival and recurrence after pancreatoduodenectomy for ampullary adenocarcinoma: results from an international multicentre retrospective cohort study.

BACKGROUND: Pancreatoduodenectomy (PD) is recommended in fit patients with a resectable ampullary adenocarcinoma (AA). We aimed to identify predictors of five-year recurrence/survival. METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study, a multicentre retrospective study of PD patients with a confirmed head of pancreas or periampullary malignancy (June 1st, 2012-May 31st, 2015). Patients with AA who developed recurrence/died within five-years were compared to those who did not. RESULTS: 394 patients were included and actual five-year survival was 54%. Recurrence affected 45% and the median time-to-recurrence was 14 months. Local only, local and distant, and distant only recurrence affected 34, 41 and 94 patients, respectively (site unknown: 7). Among those with recurrence, the most common sites were the liver (32%), local lymph nodes (14%) and lung/pleura (13%). Following multivariable tests, number of resected nodes, histological T stage > II, lymphatic invasion, perineural invasion (PNI), peripancreatic fat invasion (PPFI) and ≥1 positive resection margin correlated with increased recurrence and reduced survival. Furthermore, ≥1 positive margin, PPFI and PNI were all associated with reduced time-to-recurrence. CONCLUSIONS: This multicentre retrospective study of PD outcomes identified numerous histopathological predictors of AA recurrence. Patients with these high-risk features might benefit from adjuvant therapy.

A Comparison of Primary Human Hepatocytes and Hepatoma Cell Lines to Model the Effects of Fatty Acids, Fructose and Glucose on Liver Cell Lipid Accumulation.

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.

Poor anaerobic threshold and VO2 max recorded during cardiopulmonary exercise testing (CPET) prior to cytoreductive surgery in advanced (stage 3/4) ovarian cancer (AOC) is associated with suboptimal cytoreduction but does not preclude maximum effort cytoreduction.

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 VO2 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 VO2 ≥15 group (p = .0006). No other correlations were seen between AT or VO2 max and complications or readmissions. No difference in overall survival was seen if R0 resection was achieved.IMPACT STATEMENTWhat 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.

Systematic Review of Treatments for Colorectal Metastases in Elderly Patients to Guide Surveillance Cessation Following Hepatic Resection for Colorectal Liver Metastases.

BACKGROUND: Although included in surveillance programmes for colorectal cancer (CRC) metastases, elderly patients are susceptible to declines in health and quality of life that may render them unsuitable for further surveillance. Deciding when to cease surveillance is challenging. METHODS: There are no publications focused on surveillance of elderly patients for CRC metastases. A systematic review of studies reporting treatment outcomes for CRC metastases in elderly patients was performed to assess the risk-benefit balance of the key objectives of surveillance; detecting and treating CRC metastases. RESULTS: Sixty-eight eligible studies reported outcomes for surgery and chemotherapy in the elderly. Liver resections and use of chemotherapy, including biologics, are more conservative and have poorer outcomes in the elderly compared with younger patients. Selected studies demonstrated poorer quality-of-life (QoL) following surgery and chemotherapy. Studies of ablation in elderly patients are limited. DISCUSSION: The survival benefit of treating CRC metastases with surgery or chemotherapy decreases with advancing age and QoL may decline in the elderly. The relatively lower efficacy and detrimental QoL impact of multimodal therapy options for detected CRC metastases in the elderly questions the benefit of surveillance in some elderly patients. Care of elderly patients should thus be customized based on their preference, formal geriatric assessment, natural life-expectancy, and the perceived risk-benefit balance of treating recurrent CRC metastases. Clinicians may consider surveillance cessation in patients aged 75 years and above if geriatric assessment is unsatisfactory, patients decline surveillance, or patient fitness deteriorates catastrophically.

SARS-CoV-2 infection in acute pancreatitis increases disease severity and 30-day mortality: COVID PAN collaborative study.

OBJECTIVE: 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. DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

ACE Inhibitor Therapy Does Not Influence the Survival Outcomes of Patients with Colorectal Liver Metastases Following Liver Resection.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors have been shown to possibly influence the survival outcomes in certain cancers. The aim of this study was to evaluate the impact of ACE inhibitors on the outcomes of patients undergoing liver resection for colorectal liver metastases (CRLM). The secondary aim was to determine whether ACE inhibitors influenced histopathological changes in CRLM. METHODS: Patients treated with liver resection for CRLM over a 13-year period were identified from a prospectively maintained database. Data including demographics, primary tumour treatment, surgical data, histopathology analysis and clinical outcome were collated and analysed. RESULTS: A total of 586 patients underwent primary hepatic resections for CRLM during this period including 100 patients on ACE inhibitors. The median follow-up period was 23 (range: 12-96) months, in which 267 patients developed recurrent disease and 131 patients died. Independent predictors of disease-free survival on multivariate analysis included synchronous presentation, neoadjuvant chemotherapy, major liver resection, tumour size and number, extent of hepatic steatosis, R0 resection and presence of perineural invasion. Poorer overall survival was associated with neoadjuvant treatment, major liver resection, presence of multiple metastases, perineural invasion and positive resection margins on multivariate analysis. ACE inhibitors did not influence the survival outcome or histological presentation in CRLM. CONCLUSION: The use of ACE inhibitors did not affect the survival outcome or tumour biology in patients with CRLM following liver resection.

Retrospective cohort study of statin therapy effect on resected colorectal liver metastases.

BACKGROUND: Above and beyond their role in cardiovascular risk reduction, statins appear to have a chemopreventive role in some gastro-intestinal cancers. In the quest for new chemopreventive agents, some existing established drugs such as statins have shown potential for re-purposing as chemoprevention. Probing existing drugs, whose pharmacodynamics are familiar, for novel beneficial effects offers a more cost-effective and less time-consuming strategy than establishing brand new drugs whose pharmacodynamic profile is unfamiliar. Observational studies show statins decrease the risk of developing colorectal cancer but there are no published studies exploring the potential impact of statins on carcinogenesis in colorectal liver metastases (CRLM). AIM: To evaluate impact of statins on outcomes of CRLM resection, and secondarily to assess if statins influence CRLM histo-pathology. METHODS: We conducted a retrospective cohort study of patients operated for CRLM over a 13-year period from 2005 to 2017. Patients were identified from a prospective database maintained in our Tertiary care hospital. All 586 patients included the study had undergone resection of CRLM following discussion at multidisclipinary team meeting, some patients requiring neoadjuvant chemotherapy to downstage CRLM prior to surgery. We analysed patient demographics, operative details, CRLM histopathology, Index of Deprivation, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and chemotherapy use in relation to clinical outcome. Statistics were performed using SPSS version 16.0; significance taken at 5%. RESULTS: Liver resection for CRLM was undertaken in 586 patients at a median age of 68 (range 19 to 88) years. Statin therapy was used by 181 patients. Median follow-up time was 23 (range 12-96) mo and further colorectal cancer metastases developed in 267 patients. A total of 131 patients died. Multi-variate analysis identified 6 independent predictors of poorer disease-free survival: Synchronous presentation, multiple tumours, tumour size ≥ 5 cm, moderate-severe steatosis, peri-neural invasion, and R1-resection margin. Poorer overall survival was significantly associated with neo-adjuvant chemotherapy, major hepatectomy, peri-neural invasion and R1-resection margin. Neither histo-pathological nor radiological traits of CRLM were affected by statins, and, there was no demonstrable effect of statin therapy on patient outcomes. CONCLUSION: Statin therapy does not affect patient survival following liver resection for CRLM. We postulate the reason for this key finding is that statins do not modulate tumour biology of CRLM.

Splenic preservation versus splenectomy in laparoscopic distal pancreatectomy: a propensity score-matched study.

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.