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.

Precursor Epithelial Subtypes of Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasms (A-IPMN): Clinicopathological Features, Recurrence and Response to Adjuvant Chemotherapy.

BACKGROUND: The clinico-oncological outcomes of precursor epithelial subtypes of adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) are limited to small cohort studies. Differences in recurrence patterns and response to adjuvant chemotherapy between A-IPMN subtypes are unknown. METHODS: Clincopathological features, recurrence patterns and long-term outcomes of patients undergoing pancreatic resection (2010-2020) for A-IPMN were reported from 18 academic pancreatic centres worldwide. Precursor epithelial subtype groups were compared using uni- and multivariate analysis. RESULTS: In total, 297 patients were included (median age, 70 years; male, 78.9%), including 54 (18.2%) gastric, 111 (37.3%) pancreatobiliary, 80 (26.9%) intestinal and 52 (17.5%) mixed subtypes. Gastric, pancreaticobiliary and mixed subtypes had comparable clinicopathological features, yet the outcomes were significantly less favourable than the intestinal subtype. The median time to recurrence in gastric, pancreatobiliary, intestinal and mixed subtypes were 32, 30, 61 and 33 months. Gastric and pancreatobiliary subtypes had worse overall recurrence (p = 0.048 and p = 0.049, respectively) compared with the intestinal subtype but gastric and pancreatobiliary subtypes had comparable outcomes. Adjuvant chemotherapy was associated with improved survival in the pancreatobiliary subtype (p = 0.049) but not gastric (p = 0.992), intestinal (p = 0.852) or mixed subtypes (p = 0.723). In multivariate survival analysis, adjuvant chemotherapy was associated with a lower likelihood of death in pancreatobiliary subtype, albeit with borderline significance [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.31-1.01; p = 0.058]. CONCLUSIONS: Gastric, pancreatobiliary and mixed subtypes have comparable recurrence and survival outcomes, which are inferior to the more indolent intestinal subtype. Pancreatobiliary subtype may respond to adjuvant chemotherapy and further research is warranted to determine the most appropriate adjuvant chemotherapy regimens for each subtype.

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.

The effects of previous abdominal surgery and the utilisation of modified access techniques on the operative difficulty and outcomes of laparoscopic cholecystectomy and bile duct exploration.

BACKGROUND: Early reports suggested that previous abdominal surgery was a relative contraindication to laparoscopic cholecystectomy (LC) on account of difficulty and potential access complications. This study analyses different types/systems of previous surgery and locations of scars and how they affect access difficulties. As modified access techniques to minimise risk of complications are under-reported the study details and evaluates them. METHOD: Prospectively collected data from consecutive LC and common bile duct explorations (LCBDE) performed by a single surgeon over 30 years was analysed. Previous abdominal surgery was documented and peri-operative outcomes were compared with patients who had no previous surgery using Chi-squared analysis. RESULTS: Of 5916 LC and LCBDE, 1846 patients (31.2%) had previous abdominal surgery. The median age was 60 years. Those with previous surgery required more frequent duodenal (RR 1.07; p = 0.023), hepatic flexure (RR 1.11; p = 0.043) and distal adhesiolysis (RR 3.57; p < 0.001) and had more access related bowel injuries (0.4% vs. 0.0%; p < 0.001). Previous upper gastrointestinal and biliary surgery had the highest rates of adhesiolysis (76.3%), difficult cystic pedicles (58.8%), fundus-first approach (7.2%), difficulty grades (64.9% Grades 3-5) and utilisation of abdominal drains (71.1%). Previous open surgery resulted in longer operative time compared to previous laparoscopic procedures (65vs.55 min; p < 0.001), increased difficulty of pedicle dissection (42.4% vs. 36.0%; p < 0.05) and required more duodenal, hepatic flexure and distant adhesiolysis (p < 0.05) and fundus-first dissection (4% vs 2%; p < 0.05). Epigastric and supraumbilical access and access through umbilical and other hernias were used in 163 patients (8.8%) with no bowel complications. CONCLUSION: The risks of access and adhesiolysis in patients with previous abdominal scars undergoing biliary surgery are dependent on the nature of previous surgery. Previous open, upper gastrointestinal and biliary surgery carried the most significant risks. Modified access techniques can be adopted to safely mitigate these risks.

Intensive pre-operative information course (IPIC) and pre-operative weight loss results in long-term sustained weight loss following bariatric surgery: 11 years results from a tertiary referral centre.

INTRODUCTION: Outcomes of long-term (5-10-year) weight loss have not been investigated thoroughly and the role of pre-operative weight loss on long-term weight loss, among other factors, are unknown. Our regional bariatric service introduced a 12 week intensive pre-operative information course (IPIC) to optimise pre-operative weight loss and provide education prior to bariatric surgery. The present study determines the effect of pre-operative weight loss and an intense pre-operative information course (IPIC), on long-term weight outcomes and sustained weight loss post-bariatric surgery. METHODS: Data were collected prospectively from a bariatric center (2008-2022). Excess weight loss (EWL) ≥ 50% and ≥ 70% were considered outcome measures. Survival analysis and logistic regression identified variables associated with overall and sustained EWL ≥ 50% and ≥ 70%. RESULTS: Three hundred thirty-nine patients (median age, 49 years; median follow-up, 7 years [0.5-11 years]; median EWL%, 49.6%.) were evaluated, including 158 gastric sleeve and 161 gastric bypass. During follow-up 273 patients (80.5%) and 196 patients (53.1%) achieved EWL ≥ 50% and ≥ 70%, respectively. In multivariate survival analyses, pre-operative weight loss through IPIC, both < 10.5% and > 10.5% EWL, were positively associated with EWL ≥ 50% (HR 2.23, p < 0.001) and EWL ≥ 70% (HR 3.24, p < 0.001), respectively. After a median of 6.5 years after achieving EWL50% or EWL70%, 56.8% (154/271) had sustained EWL50% and 50.6% (85/168) sustained EWL70%. Higher pre-operative weight loss through IPIC increased the likelihood of sustained EWL ≥ 50% (OR, 2.36; p = 0.013) and EWL ≥ 70% (OR, 2.03; p = 0.011) at the end of follow-up. CONCLUSIONS: IPIC and higher pre-operative weight loss improve weight loss post-bariatric surgery and reduce the likelihood of weight regain during long-term follow-up.

Optimising the use of colonoscopy to improve risk stratification for colorectal cancer in symptomatic patients: A decision-curve analysis.

OBJECTIVES: Pressured healthcare resources make risk stratification and patient prioritisation fundamental issues for the investigation of colorectal cancer (CRC) in symptomatic patients. The present study uses machine learning algorithms and decision strategies to improve the appropriate use of colonoscopy. DESIGN: All symptomatic patients in a single health board (2018-2021) proceeding to colonoscopy to investigate for CRC were included. Machine learning algorithms (NeuralNetwork, randomForest, Logistic regression, Naïve-Bayes and Adaboost) were used to risk-stratify patients for CRC using demographics, symptoms, quantitative faecal immunochemical test (qFIT) and haematological tests. Decision curve analyses were performed to determine the optimal decision strategies. RESULTS: 3776 patients were included (median age, 65; M:F,0.9:1.0) and CRC was identified in 217 patients (5.7%). qFIT > 400 µg Hb/g was the most important variable (%IncMSE = 78.5). RandomForrest had the highest area under curve (0.91) and accuracy (0.80) for CRC. When utilising decision curve analysis (DCA), 30%, 46% and 54% of colonoscopies were saved at accepted CRC probabilities of 1%, 2% and 3%, respectively. RandomForrest modelling had superior net clinical benefit compared to default colonoscopy strategies. CONCLUSIONS: MLA-derived decision strategies that account for patient and referrer risk preference reduce colonoscopy demand and carry net clinical benefit compared to default colonoscopy strategies.

Validation of the updated Bosniak classification (2019) in pathologically confirmed CT-categorised cysts.

INTRODUCTION: The updated Bosniak classification in 2019 (v2019) addresses vague imaging terms and revises the criteria with the intent to categorise a higher proportion of cysts in lower-risk groups and reduce benign cyst resections. The aim of the present study was to compare the diagnostic accuracy and inter-observer agreement rate of the original (v2005) and updated classifications (v2019). METHOD: Resected/biopsied cysts were categorised according to Bosniak classifications (v2005 and v2019) and the diagnostic accuracy was assessed with reference to histopathological analysis. The inter-observer agreement of v2005 and v2019 was determined. RESULTS: The malignancy rate of the cohort was 83.6% (51/61). Using v2019, a higher proportion of malignant cysts were categorised as Bosniak ≥ III (88.2% vs 84.3%) and a significantly higher percentage were categorised as Bosniak IV (68.9% vs 47.1%; p = 0.049) in comparison to v2005. v2019 would have resulted in less benign cyst resections (13.5% vs 15.7%). Calcified versus non-calcified cysts had lower rates of malignancy (57.1% vs 91.5%; RR,0.62; p = 0.002). The inter-observer agreement of v2005 was higher than that of v2019 (kappa, 0.70 vs kappa, 0.43). DISCUSSION: The updated classification improves the categorisation of malignant cysts and reduces benign cyst resection. The low inter-observer agreement remains a challenge to the updated classification system.

A multicentre prospective evaluation of health-related quality of life and patient related outcomes in pancreatic and peripancreatic cancer: PROMCAN study.

BACKGROUND: The temporal evolution of HRQoL and the importance of other PROs to patients, following resection for pancreatic and peripancreatic malignancy remains unexplored. METHODS: Patients undergoing pancreatic resection between 2021 and 2022 were enrolled from 2 UK HPB centres. Patients completed the EORTC QLQ-C30, QLQ-PAN26 tools and rated 56 PROs preoperatively (T1), at discharge (T2), 6-weeks (T3), 3-months (T4) and 6-months (T5) postoperatively. ANOVA followed by post-hoc analysis was used to examine patterns in HRQoL through time. Multivariable ANOVA was used to identify impact of clinical factors on HRQoL. RESULTS: 63 patients were recruited [median age, 72 (IQR 41-85); 39/63 male]. Physical functioning declined from 70.4 (26.2) at T1 to 53.5 (20.9) at T2 (p = 0.016). Global QoL score increased significantly from 41.0 (23.0) at T2 to 60.0 (26.1) at T5 (p = 0.007), as did role functioning [21.1 (27.9) at T2 to 59.4 (32.8) at T5, p < 0.001]. Chemotherapy status and the postoperative complications did not significantly change HRQoL. General QoL and health were the only PROs rated as 'very important' (scores 7-9) by more than 80 % of participants at five time-points. CONCLUSION: Recuperation of HRQoL measures is seen at 6-months postoperative and was not affected by chemotherapy or postoperative complications. Notably, PROs important to patients varied over time.

Defining Prolonged Length of Stay (PLOS) Following Elective Laparoscopic Cholecystectomy and Derivation of a Preoperative Risk Score to Inform Resource Utilization, Risk Stratification, and Patient Consent.

OBJECTIVE: The present study defines prolonged length of stay (PLOS) following elective laparoscopic cholecystectomy (LC) and its relationship with perioperative morbidity. A preoperative risk tool to predict PLOS is derived to inform resource utilization, risk stratification and patient consent. BACKGROUND: Surgical candidates for elective LC are a heterogeneous group at risk of various perioperative adverse outcomes. Preoperative recognition of high-risk patients for PLOS has implications on feasibility for day surgery, resource utilization, preoperative risk stratification, and patient consent. METHODS: Data for all patients who underwent elective LC between January 2015 and January 2020 across 3 surgical centers (1 tertiary referral center and 2 satellite units) in 1 health board were collected retrospectively (n=2166). The optimal cut-off of PLOS as a proxy for operation-related adverse outcomes was found using receiver operating characteristic curves. Multivariate logistic regression was conducted on a derivation subcohort to derive a preoperative model predicting PLOS. Receiver operating characteristic curves were performed to validate the model. Patients were stratified by the risk tool and the risks of PLOS were determined. RESULTS: A LOS of ≥3 days following elective LC demonstrated the best diagnostic ability for operation-related adverse outcomes [area under curve (AUC)=0.87] and defined the PLOS cut-off. The rate of PLOS was 6.6% (144/2166), 86.1% of which had a perioperative adverse outcome. PLOS was strongly associated with all adverse outcomes (subtotal, conversion-to-open, intraoperative complications, postoperative complication/imaging/intervention) ( P <0.001). The preoperative model demonstrated good diagnostic ability for PLOS in the derivation (AUC=0.81) and validation cohorts (AUC=0.80) and stratified patients appropriately. CONCLUSIONS: Morbidity in PLOS patients is significant and pragmatic patient selection in accordance with the risk tool may help centers improve resource utilization, risk stratification, and their consent process. The risk tool may help select candidates for cholecystectomy in a strictly ambulatory/outpatient center.

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.

Laparoscopic Lumen-guided cholecystectomy in face of the difficult gallbladder.

BACKGROUND: Where the critical view of safety cannot be established during cholecystectomy, certain salvage techniques are indicated to reduce the likelihood of bile duct injury. The present study describes a salvage technique termed the "laparoscopic lumen-guided cholecystectomy" (LLC) and reports its peri-operative outcomes. METHOD: A summary of the technique is as follows: (1) Hartmann's pouch is incised and stones are evacuated; (2) the cystic anatomy is inspected from the inside of the gallbladder; (3) the lumen is used to guide retrograde dissection towards the cystic pedicle; (4) cystic duct control is achieved if deemed safe. LLC cases performed between June 2020 and January 2022 in a single health board were included. The operative details and peri-operative outcomes of the technique are reported and compared to cases of similar difficulty where the LLC was not attempted. RESULTS: LLC was performed in 4.6% (27/587) of cases. In all 27 cases, LLC was performed for a "frozen" cholecystohepatic triangle. Hartmann's pouch was completely excised in all cases (27/27) and cystic duct control was achieved in 85.2% of cases (23/27). No cases of bile leak or ductal injury were reported. Rates of bile leak, post-operative complications and ERCP were lower following LLC compared to the group where LLC was not attempted (p < 0.01). CONCLUSION: LLC is a safe salvage technique and should be considered in cases where the critical view of safety cannot be established. The technique achieves cystic duct control in the majority of cases and favourable outcomes in the face of a difficult cholecystectomy.

Index Admission Cholecystectomy for Biliary Colic Precludes the Risk of Readmissions with Biliary Complications and should be Standard Treatment.

BACKGROUND: Emergency biliary colic admissions can be managed with an index or elective laparoscopic cholecystectomy (LC). Opting to perform an elective LC may have significant repercussions such as the risk of readmissions before operation with further attacks or with biliary complications (e.g. cholecystitis, pancreatitis, choledocholithiasis). The risk of readmission and biliary complications in patients admitted with biliary colic but scheduled for elective surgery has never been investigated. The secondary aim was to compare rates of peri-operative morbidity between the index admission, elective and readmission LC cohorts. METHOD: All patients admitted with a diagnosis of biliary colic over a 5-year period and proceeding to LC were included in the study (n = 441). The risk of being readmitted and suffering further morbidity whilst awaiting elective LC was investigated. Peri-operative morbidity was compared between the index admission, elective and readmitted LC groups using univariate and multivariate analysis. RESULTS: Following a biliary colic admission, the risk of readmission whilst awaiting elective LC is significant (2 months-25%; 10 months-48%). In this group, the risks of subsequent biliary complications (18.0%) and the requirement for ERCP (6.5%) were significant. Patients who are readmitted before LC, suffer a more complicated peri-operative course (longer total length of stay, higher post-operative complications, imaging and readmission). DISCUSSION: Index admission LC for biliary colic avoids the significant risk of readmission and biliary complications before surgery and should be the gold standard. Readmitted patients are likely to have higher rates of peri-operative adverse outcomes. Patients should be counselled about these risks.

The impact on complication rates of delayed routine pessary reviews during the COVID-19 pandemic.

INTRODUCTION AND HYPOTHESIS: During the COVID-19 pandemic, guidance was issued in the United Kingdom advising a delay in routine pessary reviews. The impact of this has not been fully explored. The null hypothesis for this study is that delayed routine pessary reviews during the COVID-19 pandemic did not result in a statistically significant increase in complication rate. METHODS: A retrospective comparative cohort study was conducted in NHS Tayside, Scotland, involving 150 patients pre-pandemic and 150 patients during the COVID-19 pandemic (before exclusions). Their notes were reviewed identifying age, care provider, pessary type, length of pessary usage, review date, time elapsed since the previous review, bleeding/infection/ulceration, removal issues, pessary replacement and outcome. Patients excluded were those with no pessary in situ at review, reviews at ≤4 months and >8 months (pre-pandemic) and reviews at ≤8 months (COVID-19 pandemic). RESULTS: The pre-pandemic group (n=106) had average review times of 10.1,6.2 and 6.2 months for cubes, rings and all others. Overall rates of bleeding/infection/ulceration; reported removal issues; and pessary subsequently not replaced were 9.4%, 11.3% and 5.7% respectively. The COVID-19 pandemic group (n=125) had average review times of 14.7, 10.8 and 11.4 months for cubes, rings and all others. Overall rates of bleeding/infection/ulceration; reported removal issues; and pessary subsequently not replaced were 21.6%, 16.0%, and 12.0% respectively. CONCLUSIONS: Overall, there was a significant increase in rates of bleeding/ulceration/infection (p=0.01). When individual pessaries were considered, this only remained true for rings (p=0.02). Our data would suggest that routine ring pessary reviews should not be extended beyond 6 months or risk bleeding/ulceration/infection.

Morbidity following emergency and elective cholecystectomy: a retrospective comparative cohort study.

INTRODUCTION: An emergency laparoscopic cholecystectomy (EMLC) is commonly performed for all biliary pathology, yet EMLC can be challenging due to acute inflammation. Understanding the risks of EMLC is necessary before patients can make an informed decision regarding operative management. The aim of the present study was to compare rates of operative and post-operative outcomes between EMLC and elective LC (ELLC) using a large contemporary cohort, to inform the consent process and influence surgical decision making. METHODS: All patients who underwent EMLC and ELLC in one UK health board between January 2015 and December 2019 were considered for inclusion. Data were collected retrospectively from multiple regional databases using a deterministic records-linkage methodology. Patients were followed up for 100 days post-operatively for adverse outcomes and outcomes were compared between groups using both univariate and multivariate analysis adjusting for pre-operative factors. RESULTS: A total of 2768 LCs were performed [age (range), 52(13-92); M:F, 1:2.7]. In both the univariate and multivariate analysis, EMLC was positively associated with subtotal cholecystectomy (RR 2.0; p < 0.001), post-operative complication (RR 2.8; p < 0.001), post-operative imaging (RR 2.0; p < 0.001), post-operative intervention (RR 2.3; p < 0.001), prolonged post-operative hospitalisation (RR 3.8; p < 0.001) and readmission (RR 2.2; p < 0.001). EMLC had higher rates of post-operative mortality in univariate analysis (RR 10.8; p = 0.01). DISCUSSION: EMLC is positively associated with adverse outcomes versus ELLC. Of course this study does not focus on a specific biliary pathology; nevertheless, it illustrates the additional risk associated with EMLC. This should be clearly outlined during the consent process but should be balanced with the risk of further biliary attacks. Further studies are required to identify particular patient groups who benefit from elective surgery.

Elective laparoscopic cholecystectomy: recurrent biliary admissions predispose to difficult cholecystectomy.

INTRODUCTION: Patients undergoing elective laparoscopic cholecystectomy (ELLC) represent a heterogeneous group making it challenging to stratify risk. The aim of this paper is to identify pre-operative factors associated with adverse peri- and post-operative outcomes in patients undergoing ELLC. This knowledge will help stratify risk, guide surgical decision making and better inform the consent process. METHODS: All patients who underwent ELLC between January 2015 and December 2019 were included in the study. Pre-operative data and both peri- and post-operative outcomes were collected retrospectively from multiple databases using a deterministic records-linkage methodology. Patients were divided into groups based on clinical indication (i.e. biliary colic versus cholecystitis) and adverse outcomes were compared. Multivariate regression models were generated for each adverse outcome using pre-operative independent variables. RESULTS: Two-thousand one hundred and sixty-six ELLC were identified. Rates of peri- and post-operative adverse outcomes were significantly higher in the cholecystitis versus biliary colic group and increased with number of admissions of cholecystitis (p < 0.05). Rates of subtotal (29.5%), intra-operative complication (9.8%), post-operative complications (19.6%), prolonged post-operative stay (45.9%) and re-admission (16.4%) were significant in the group of patients with ≥ 2 admissions with cholecystitis. CONCLUSION: Our data demonstrate that patients with repeated biliary admission (particularly cholecystitis) ultimately face an increased risk of a difficult ELLC with associated complications, prolonged post-operative stay and readmissions. These data provide robust evidence that individualised risk assessment and consent are necessary before ELLC. Strategies to minimise recurrent biliary admissions prior to LC should be implemented.

Subtotal Cholecystectomy Results in High Peri-operative Morbidity and Its Risk-Profile Should be Emphasised During Consent.

BACKGROUND: Subtotal cholecystectomy aims to reduce the likelihood of bile duct injury but risks a multitude of less severe, yet significant complications. The primary aim of the present study was to report peri-operative outcomes of subtotal laparoscopic cholecystectomy (SLC) relative to total laparoscopic cholecystectomy (TLC) to inform the consent process. METHOD: All laparoscopic cholecystectomies between 2015 and 2020 in one health board were included. The peri-operative outcomes of SLC (n = 87) and TLC (n = 2650) were reported. Pre-operative variables were compared between the two groups to identify risk factors for SLC. The outcomes between the SLC and TLC were compared using univariate, multivariate and propensity analysis. RESULTS: Risk factors for SLC included higher age, male gender, cholecystitis, increased biliary admissions, ERCP, cholecystostomy and emergency cholecystectomy. Following SLC, rates of post-operative complication (45.9%), imaging (37.9%) intervention (28.7%) and readmission (29.9%) were significant. The risk profile was vastly heightened compared to that of TLC: intra-operative complications (RR 9.0; p < 0.001), post-operative complications [bile leak (RR 58.9; p < 0.001), collection (RR 12.2; p < 0.001), retained stones (RR 7.2; p < 0.001) and pneumonia (RR 5.4; p < 0.001)], post-operative imaging (RR 4.4; p < 0.001), post-operative intervention (RR 12.3; p < 0.001), prolonged PLOS (RR 11.3; p < 0.001) and readmission (RR 4.5; p < 0.001). The findings were consistent using multivariate logistic regression and propensity analysis. CONCLUSION: The relative morbidity associated with SLC is significant and high-risk patients should be counselled for the peri-operative morbidity of subtotal cholecystectomy.

Patient and physician positioning during anterior skull base surgery impacts physician ergonomics.

BACKGROUND: The effects of anterior skull base surgery on surgeon's ergonomics remain unclear and this study explores the impact of patient, surgeon and screen positioning on surgeon's ergonomics during anterior skull base surgery using the Rapid Upper Limb Assessment (RULA) tool. METHOD: A total of 20 different surgical positions involving the operating surgeon, assisting surgeon, patient head position, camera position and screen position/number were simulated. For each position, the ergonomic effects on the upper limb, neck, trunk and lower limb of surgeons were analysed using the Rapid Upper Limb Assessment (RULA) tool. RESULTS: The lowest RULA score is 2 and the maximum score is 6. The majority of scores ranged from 2 to 3 suggesting the majority of positions have acceptable postures. The average RULA score of the right side of operating surgeon was 2.8 versus 2.95 on the left-side (p = 0.297). For the assisting surgeon, the average RULA score of the right side was 3.65 versus 3.25 for the left side (p = 0.053). The average combined (left and right) RULA score for the operating surgeon was 5.76 versus 6.9 for the assisting surgeon (p < 0.001). Position 17 (operating surgeon to the right of patient, assisting surgeon to the left of patient, central patient head position and two screens) is the most ergonomically favourable position. Position 2 (operating and assisting surgeon to the right of patient, patient head position to the right and one screen position to the left of patient) is the least favourable position. CONCLUSION: This simulation raises awareness of risk of musculoskeletal injury in anterior skull base surgery and highlights that certain positional behaviours are better for reducing injury risk than others. Two screens should be considered when performing a two-surgeon, four-hand anterior skull base surgery and surgeons should consider applying this to their own ergonomic environment in theatre.

Does non-visible haematuria require urgent assessment? A retrospective cohort study from a university teaching hospital.

OBJECTIVES: It is not certain from current evidence which patient groups with non-visible haematuria (NVH) require urgent investigation and which investigations are sufficient. We report referral outcomes data from Scotland to identify patient groups who will benefit from urgent assessment to rule out urological cancer (UC) and whether full set of investigations are necessary in all referred patients. MATERIALS AND METHODS: Data were collected from electronic patient records for patients referred with NVH to secondary care urology services between July 2017 and May 2020. The correlations between risk factors and final diagnosis were assessed using categorical variables in a multivariate logistic regression analysis and using chi-squared models. Statistical analysis was performed using IBM SPSS data editor version 25. RESULTS: Our study cohort comprised 525 patients (43.4% males; median age 66 years), in which UC was diagnosed in 25 patients (4.8%). Age > 60 years had sensitivity and NPV for UC of 92% and 99%, respectively. Univariate and multivariate analysis showed male sex, age ≥ 60 years and smoking were significant predictors of UC in patients with NVH (p < 0.05). There was no significant difference in UC in patients with history of LUTS, anticoagulation and previous UC. CONCLUSION: The risk of urologic cancer in NVH patients is significant and male gender, age ≥ 60 years and smoking are significant predictors of UC. Patients with risk factors of UC require complete assessment of both the upper and lower urinary tract; however, in the absence of risk factors, patients do not require urgent or complete assessment.

Complex renal cysts (Bosniak ≥IIF): interobserver agreement, progression and malignancy rates.

OBJECTIVE: The objective was to assess the interobserver agreement rate, progression rates and malignancy rates in the assessment of complex renal cysts (≥ Bosniak IIF) using a population-based database. METHODS: A regional database identified 452 complex renal cysts in 415 patients between 2009 and 2019. Each patient was tracked and followed up using a unique identifier and deterministic linkage methodology. The interobserver agreement rate between radiologists was calculated using a weighted kappa statistic. Progression and malignancy rates of cysts (Bosniak ≥IIF) over the 11-year period were calculated. RESULTS: The linear-weighted kappa value was 0.69 for all complex cysts. The rate of progression and regression of Bosniak IIF cysts was 4.6% (7/151) and 3.3% (5/151), respectively. All malignant IIF cysts progressed within 16 months of diagnosis. The malignancy rate of surgically resected Bosniak III and IV cysts was 79.3% (23/29) and 84.5% (39/46), respectively. Of all malignant tumours, 73.8% and 93.7% were of low ISUP grade and low stage, respectively. CONCLUSIONS: This study further confirms that there is a good degree of agreement between radiologists in classifying complex renal masses using the Bosniak classification. The progression rate of Bosniak IIF cysts is low, but the malignancy rates of surgically resected Bosniak IIF, III and IV cysts are high. Benign cysts are frequently resected, and a very high proportion of histopathologically confirmed cancers in complex renal cysts are of low grade and stage. KEY POINTS: • There is a good degree of agreement between radiologists in classifying complex renal masses using the Bosniak classification. • The rate of progression of Bosniak IIF cysts is low, and malignant cysts progress early during surveillance. Although the malignancy rates of resected Bosniak IIF, III and IV cysts are high, the rate of benign cyst resection is significant.

Developing Electron Microscopy Tools for Profiling Plasma Lipoproteins Using Methyl Cellulose Embedment, Machine Learning and Immunodetection of Apolipoprotein B and Apolipoprotein(a).

Plasma lipoproteins are important carriers of cholesterol and have been linked strongly to cardiovascular disease (CVD). Our study aimed to achieve fine-grained measurements of lipoprotein subpopulations such as low-density lipoprotein (LDL), lipoprotein(a) (Lp(a), or remnant lipoproteins (RLP) using electron microscopy combined with machine learning tools from microliter samples of human plasma. In the reported method, lipoproteins were absorbed onto electron microscopy (EM) support films from diluted plasma and embedded in thin films of methyl cellulose (MC) containing mixed metal stains, providing intense edge contrast. The results show that LPs have a continuous frequency distribution of sizes, extending from LDL (> 15 nm) to intermediate density lipoprotein (IDL) and very low-density lipoproteins (VLDL). Furthermore, mixed metal staining produces striking "positive" contrast of specific antibodies attached to lipoproteins providing quantitative data on apolipoprotein(a)-positive Lp(a) or apolipoprotein B (ApoB)-positive particles. To enable automatic particle characterization, we also demonstrated efficient segmentation of lipoprotein particles using deep learning software characterized by a Mask Region-based Convolutional Neural Networks (R-CNN) architecture with transfer learning. In future, EM and machine learning could be combined with microarray deposition and automated imaging for higher throughput quantitation of lipoproteins associated with CVD risk.