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.

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.

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.

Opioid analgesia and severity of acute pancreatitis: An international multicentre cohort study on pain management in acute pancreatitis.

BACKGROUND: The effect of analgesic modalities on short-term outcomes in acute pancreatitis remains unknown. However, preclinical models have raised safety concerns regarding opioid use in patients with acute pancreatitis. OBJECTIVE: This study aimed to assess the association between analgesics, particularly opioids, and severity and mortality in hospitalised patients with acute pancreatitis. METHODS: This prospective multicentre cohort study recruited consecutive patients admitted with a first episode of acute pancreatitis between April 1 and 30 June 2022, with a 1-month follow-up. Data on aetiology, clinical course, and analgesic treatment were collected. The primary outcome was the association between opioid analgesia and acute pancreatitis severity, which was analysed using univariate and multivariate analyses. RESULTS: Among a total of 1768 patients, included from 118 centres across 27 countries, 1036 (59%) had opioids administered on admission day, and 167 (9%) received opioids after admission day. On univariate analysis, moderately severe or severe acute pancreatitis was associated with male sex, Asian ethnicity, alcohol aetiology, comorbidity, predicted severe acute pancreatitis, higher pain scores, longer pain duration and opioid treatment (all p < 0.001). On multivariate analysis, comorbidity, alcohol aetiology, longer pain duration and higher pain scores increased the risk of moderately severe or severe acute pancreatitis (all p < 0.001). Furthermore, opioids administered after admission day (but not on admission day) doubled the risk of moderately severe or severe disease (OR 2.07 (95% CI, 1.29-3.33); p = 0.003). Opioid treatment for 6 days or more was an independent risk factor for moderately severe or severe acute pancreatitis (OR 3.21 (95% CI, 2.16-4.79; p < 0.001). On univariate analysis, longer opioid duration was associated with mortality. CONCLUSION: Opioid treatment increased the risk of more severe acute pancreatitis only when administered after admission day or for 6 days or more. Future randomised studies should re-evaluate whether opioids might be safe in acute pancreatitis.

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.

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.

Biogenesis, inheritance, and 3D ultrastructure of the microsporidian mitosome.

During the reductive evolution of obligate intracellular parasites called microsporidia, a tiny remnant mitochondrion (mitosome) lost its typical cristae, organellar genome, and most canonical functions. Here, we combine electron tomography, stereology, immunofluorescence microscopy, and bioinformatics to characterise mechanisms of growth, division, and inheritance of this minimal mitochondrion in two microsporidia species (grown within a mammalian RK13 culture-cell host). Mitosomes of Encephalitozoon cuniculi (2-12/cell) and Trachipleistophora hominis (14-18/nucleus) displayed incremental/non-phasic growth and division and were closely associated with an organelle identified as equivalent to the fungal microtubule-organising centre (microsporidian spindle pole body; mSPB). The mitosome-mSPB association was resistant to treatment with microtubule-depolymerising drugs nocodazole and albendazole. Dynamin inhibitors (dynasore and Mdivi-1) arrested mitosome division but not growth, whereas bioinformatics revealed putative dynamins Drp-1 and Vps-1, of which, Vps-1 rescued mitochondrial constriction in dynamin-deficient yeast (Schizosaccharomyces pombe). Thus, microsporidian mitosomes undergo incremental growth and dynamin-mediated division and are maintained through ordered inheritance, likely mediated via binding to the microsporidian centrosome (mSPB).

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.

The impact of surgical set-up of endoscopic two surgeon four hand anterior skull base surgeries on surgeons' ergonomics.

BACKGROUND: The impact of different surgical set-ups of endoscopic two surgeon four hand anterior skull base surgeries on surgeons' ergonomics remain unclear. This study aims to explore the effect of surgeon, patient and surgical screen positioning on surgeons' ergonomics using the Rapid Entire Body Assessment (REBA) tool. METHODS: A total of 20 different surgical positions of anterior skull base surgery were simulated and the ergonomic impact on surgeons' neck, truck, leg and wrist were measured using the validated Rapid Entire Body Assessment (REBA) tool. To investigate the ergonomic effect of different surgical setups, the operating surgeon, assisting surgeon, patient head, camera and screen positions were positioned differently in each surgical position. RESULTS: The lowest REBA Score recorded is 3 whereas the highest score is 8. The REBA scores for the majority of positions are 3 highlighting that these positions are ergonomically favorable. Position 12 is the least ergonomically favorable position with a total REBA score of 19. In this position, operating surgeon is positioned to the right of the patient, assisting surgeon to the left of patient, patient head in central position with camera held by operating surgeon and one screen is placed to the right of patient. Positions 13 and 17 are the most ergonomically favorable positions with a total REBA score of 12. In these positions, the patient's head is positioned to the center, two screens were utilized, and the surgeons were positioned on either side of the patient. The utilization of 2 screens with a central patient head position with the surgeons placed on either side of the patient contribute towards a more ergonomically state in these positions. CONCLUSIONS: Certain positional behaviors are better at reducing musculoskeletal injury risk when compared to other. Positions with two screens and central head positions are more favourable ergonomically and surgeons should consider this set-up to reduce musculoskeletal injuries during anterior skull base surgery.

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.

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.

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.

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.

Anastomotic Leak in Ovarian Cancer Cytoreduction Surgery: A Systematic Review and Meta-Analysis.

INTRODUCTION: Anastomotic leaks (AL) following ovarian cytoreduction surgery could be detrimental, leading to significant delays in commencing adjuvant chemotherapy, prolonged hospital stays and increased morbidity. The aim of this study was to investigate risk factors associated with anastomotic leaks after ovarian cytoreduction surgery. MATERIAL AND METHODS: The MEDLINE (via PubMed), Cochrane Library, EMBASE and Scopus bibliographical databases were searched. Original clinical studies investigating risk factors for AL in ovarian cytoreduction surgery were included. RESULTS: Eighteen studies with non-overlapping populations reporting on patients undergoing cytoreduction surgery for ovarian cancer (n = 4622, including 344 cases complicated by AL) were included in our analysis. Patients undergoing ovarian cytoreduction surgery complicated by AL had a significantly higher rate of 30-day mortality but no difference in 60-day mortality. Multiple bowel resections were associated with an increased risk of postoperative AL, while no association was observed with body mass index (BMI), American Society of Anesthesiologists (ASA) score, age, smoking, operative approach (primary versus interval cytoreductive, stapled versus hand-sewn anastomoses and formation of diverting stoma), neoadjuvant chemotherapy and use of hyperthermic intraperitoneal chemotherapy (HIPEC). DISCUSSION: Multiple bowel resections were the only clinical risk factor associated with increased risk for AL after bowel surgery in the ovarian cancer population. The increased 30-day mortality rate in patients undergoing ovarian cytoreduction complicated by AL highlights the need to minimize the number of bowel resections in this population. Further studies are required to clarify any association between neoadjuvant chemotherapy and decreased AL rates.

The Variation in Outcomes of Septic Patients: A Dual-Centre Comparative Study.

Introduction Despite significant advances in the field of medicine, sepsis is constantly growing as a major public health concern. The global epidemic of sepsis imposes a significant economic burden on healthcare systems world-over. Furthermore, its high prevalence in society is inevitably paralleled by an excessive mortality rate, with approximately six million deaths reported every year. The primary aim of this study was to evaluate and compare, the management of acutely septic patients against outcomes in a tertiary teaching institution in Pakistan versus a similar one in the United Kingdom. Methods This study was a dual-centred, retrospective comparative analysis comparing all patients admitted through the emergency department at the respective tertiary centres. Patient details were collected and compared across the two sites to evaluate the effect of individual characteristics on prognosis. The outcomes of these presentations were analysed by comparing rates of in-hospital mortality, admission to the ICU or discharge. Results The total number of patients identified as having sepsis was 60 in the Pakistan cohort, and 92 in the Aberdeen cohort. No significant difference was found when comparing genders, and the results of basic observations were largely similar at presentation. Twenty-five per cent (25%) (n=38) of the total study population were deemed to have a poor outcome at 3 days, but 50% of the Pakistan cohort was deemed to have a poor outcome. Conclusion Managing sepsis has developed significantly in recent years, but most of this development was implemented in high-income countries. There was a significant delay in time to resuscitate septic patients in Pakistan, with significantly raised three-day morbidity and mortality. There is a need for further comparative studies of the management of sepsis in Pakistan and other low-income countries to identify the problems and tackle obstacles on every level of the healthcare system.

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.

Evaluation of Textbook Outcome as a Composite Quality Measure of Elective Laparoscopic Cholecystectomy.

Importance: A textbook outcome (TO) is a composite quality measure that incorporates multiple perioperative events to reflect the most desirable outcome. The use of TO increases the event rate, captures more outcomes to reflect patient experience, and can be used as a benchmark for quality improvement. Objectives: To introduce the concept of TO to elective laparoscopic cholecystectomy (LC), propose the TO criteria, and identify characteristics associated with TO failure. Design, Setting, and Participants: This retrospective cohort study was performed at 3 surgical units in a single health board in the United Kingdom. Participants included all patients undergoing elective LC between January 1, 2015, and January 1, 2020. Data were analyzed from January 1, 2015, to January 1, 2020. Main Outcomes and Measures: The TO criteria were defined based on review of existing TO metrics in the literature for other surgical procedures. A TO was defined as an unremarkable elective LC without conversion to open cholecystectomy, subtotal cholecystectomy, intraoperative complication, postoperative complications (Clavien-Dindo classification ≥2), postoperative imaging, postoperative intervention, prolonged length of stay (>2 days), readmission within 100 days, or mortality. The rate of TOs was reported. Reasons for TO failure were reported, and preoperative characteristics were compared between TO and TO failure groups using both univariate analysis and multivariable logistic regressions. Results: A total of 2166 patients underwent elective LC (median age, 54 [range, 13-92] years; 1579 [72.9%] female). One thousand eight hundred fifty-one patients (85.5%) achieved a TO with an unremarkable perioperative course. Reasons for TO failure (315 patients [14.5%]) included conversion to open procedure (25 [7.9%]), subtotal cholecystectomy (59 [18.7%]), intraoperative complications (40 [12.7%]), postoperative complications (Clavien-Dindo classification ≥2; 92 [29.2%]), postoperative imaging (182 [57.8%]), postoperative intervention (57 [18.1%]), prolonged length of stay (>2 days; 142 [45.1%]), readmission (130 [41.3%]), and mortality (1 [0.3%]). Variables associated with TO failure included increasing American Society of Anesthesiologists score (odds ratio [OR], 2.55 [95 CI, 1.69-3.85]; P < .001), increasing number of prior biliary-related admissions (OR, 2.68 [95% CI, 1.36-5.27]; P = .004), acute cholecystitis (OR, 1.42 [95% CI, 1.08-1.85]; P = .01), preoperative endoscopic retrograde cholangiopancreatography (OR, 2.07 [95% CI, 1.46-2.92]; P < .001), and preoperative cholecystostomy (OR, 3.22 [95% CI, 1.54-6.76]; P = .002). Conclusions and Relevance: These findings suggest that applying the concept of TO to elective LC provides a benchmark to identify suboptimal patterns of care and enables institutions to identify strategies for quality improvement.

The Effect of Platelet-Rich Plasma on Healing Time in Patients Following Pilonidal Sinus Surgery: A Systematic Review.

BACKGROUND:  Pilonidal disease (PD) is a debilitating condition characterised by the infection of subcutaneous tissue in the sacrococcygeal area. It is associated with a high risk of recurrence, pain, infection, and purulent discharge. The two main surgical methods of pilonidal sinus disease include excision with primary closure/flap repair or excision of the sinus with healing by secondary intent. Wounds left open to heal by secondary intent remain extremely common due to their association with reduced risk of recurrence, however, it is associated with prolonged healing times. This study aims to determine whether platelet-rich plasma (PRP) reduces healing time in patients post pilonidal sinus surgery with healing by secondary intent compared to simple wound dressings. METHOD:  Six databases were searched from their date of origin to May 30, 2022 for randomised control trials using predetermined inclusion and exclusion criteria. Only four papers were selected for review as per the Population, Intervention, Comparison, Outcomes and Study design (PICOS) criteria. Critical appraisal was carried out according to the Scottish Intercollegiate Guidelines Network Methodology Checklist for Randomised Control Trials and was assessed for risk of bias according to the Cochrane Handbook for Systematic Review of Interventions. The pooled effect size was calculated using the fixed-effect model. A homogeneity of pooled effect size for the studies was also found (Cochrane Q test, p-value = 0.97 I-square = 0.0%). RESULT:  Four studies (n = 336) were included in this review. Three of the four studies reported a statistically significant reduction in time taken in healing the wound. The mean difference between the intervention (PRP group) and the control group was 13.01 days, (95% CI 12.15-13.86 days, p < 0.00001). All of the included studies also reported a statistically significant reduction in time taken to return to work/activities of daily living in the treatment group compared to the control group (MD 9.68 days, 95% CI 9.16-10.21 days, p < 0.00001). CONCLUSION:  This study shows that PRP is effective in reducing healing time and is associated with a significantly shorter period taken to return to work/activities of daily living in patients post pilonidal sinus surgery, which was the primary and secondary outcome investigated in this systematic review, respectively. PRP should routinely be offered to patients undergoing excisional pilonidal sinus surgery for the aforementioned benefits.

Negative Appendicectomy Rates in Females of Childbearing Age: A Retrospective Analysis and Literature Review.

Introduction A negative appendicectomy rate (NAR) is defined as the portion of pathologically normal appendices removed surgically in patients suspected of having acute appendicitis. The lifetime risk of acute appendicitis is 8.6% for males and 6.7% for females; contrarily, the lifetime risk of appendicectomy is 12% for males and 23.1% for females. This study aims primarily to evaluate the true NAR in females of childbearing age to offer insight into potential strategies to reduce the number of unnecessary operative procedures carried out, along with their associated morbidity and mortality. Methods All emergency appendicectomies over a one-year period were retrospectively identified and collected from a single tertiary care centre. Preoperative clinical, laboratory and postoperative histopathological data were collected. The negative appendicectomy rate in subgroups divided by biomarkers and radiological imaging findings were analysed. The diagnostic value of these modalities in the context of acute appendicitis was found by calculating the sensitivity, specificity, positive predictive values, and negative predictive values. Results A total of 417 patients were included (median age 26; M:F, 0.7:1.0). The overall negative appendicectomy rate was 35.0% (146/417). Two-hundred sixty-one patients underwent an appendicectomy in the child-bearing age group. The NAR was significantly higher in those females with raised WBC and C-reactive protein (CRP) compared to their male counterparts (p-value -<0.001). Conclusion Women of childbearing age have a higher NAR of 43% when compared to the general population of 35%. Preoperative tests, including ultrasound scans, computed tomography and inflammatory markers in blood tests, help direct those who would benefit from surgery to the operating theatre, however, no test alone is suitably sensitive or specific. To reduce the NAR, management options include a return to observation and serial examination, increased use of low-dose CT or a commitment to improving the performance of ultrasonography.

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.