Efficacy and safety of regorafenib as a first-line agent alone or in combination with an immune checkpoint inhibitor for advanced hepatocellular carcinoma: a retrospective cohort study.

Background: The RESORCE-III trial demonstrated that advanced hepatocellular carcinoma (HCC) patients who progressed on sorafenib and had second-line therapy with regorafenib improved overall survival compared with placebo. Later, immunotherapy with immune checkpoint inhibitors (ICIs) combined with antiangiogenetic antibodies has evolved as the preferred first-line treatment for fit patients. We aimed to explore the efficacy and safety of regorafenib as a first-line agent alone or in combination with ICIs in patients with advanced HCC. Methods: We identified 50 patients with advanced HCC treated with regorafenib as a first-line agent. Two patients were lost to follow-up and excluded. Baseline factors, dosing, concomitant use of ICIs, toxicity and outcome of treatment were recorded from electronic medical records. Results: Twenty-six patients received regorafenib as monotherapy and twenty-two received regorafenib + ICI in combination. In the total cohort, the median progression-free survival (mPFS) was 7.7 months and the median overall survival (mOS) was 16.7 months (P=0.02). Objective response rate (ORR) and disease control rate (DCR) assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 were 21% and 73%. In the regorafenib monotherapy group, mPFS was 5.9 months, and mOS was 13.9 months; in the combination group, mPFS was 7.8 months, and mOS was 23.6 months. ORR and DCR were 15% and 65% in the monotherapy group, and 27% and 82% in the combined treatment group, respectively. Conclusions: Regorafenib used in combination with ICIs had a mild safety profile and resulted in improved response and an almost doubling of mOS compared to monotherapy, warranting further prospective evaluation in a randomized study.

Should Empiric Anti-Fungals Be Administered Routinely for All Patients with Perforated Peptic Ulcers? A Critical Review of the Existing Literature.

A perforated peptic ulcer (PPU) is a surgical emergency with a high mortality rate. PPUs cause secondary peritonitis due to bacterial and fungal peritoneal contamination. Surgery is the main treatment modality and patient's comorbidites impacts perioperative morbidity and surgical outcomes. Even after surgery, resuscitation efforts should continue. While empiric antibiotics are recommended, the role of empiric anti-fungal treatment is unclear due to a lack of scientific evidence. This literature review demonstrated a paucity of studies evaluating the role of empiric anti-fungals in PPUs, and with conflicting results. Studies were heterogeneous in terms of patient demographics and underlying surgical pathology (PPUs vs. any gastrointestinal perforation), type of anti-fungal agent, timing of administration and duration of use. Other considerations include the need to differentiate between fungal colonization vs. invasive fungal infection. Despite positive fungal isolates from fluid culture, it is important for clinical judgement to identify the right group of patients for anti-fungal administration. Biochemistry investigations including new fungal biomarkers may help to guide management. Multidisciplinary discussions may help in decision making for this conundrum. Moving forward, further research may be conducted to select the right group of patients who may benefit from empiric anti-fungal use.

Assessing the impact of frailty in elderly patients undergoing emergency laparotomies in Singapore.

Introduction: The global rise in ageing populations poses challenges for healthcare systems. By 2030, Singapore anticipates a quarter of its population to be aged 65 or older. This study addresses the dearth of research on frailty's impact on emergency laparotomy (EL) outcomes in this demographic, emphasising the growing significance of this surgical intervention. Method: Conducted at 2 tertiary centres in Singapore from January to December 2019, a retrospective cohort study examined EL outcomes in patients aged 65 or older. Frailty assessment, using the Clinical Frailty Scale (CFS), was integrated into demographic, diagnostic and procedural analyses. Patient data from Tan Tock Seng Hospital and Khoo Teck Puat Hospital provided a comprehensive view of frailty's role in EL. Results: Among 233 participants, 26% were frail, revealing a higher vulnerability in the geriatric population. Frail individuals exhibited elevated preoperative risk, prolonged ICU stays, and significantly higher 90-day mortality (21.3% versus 6.4%). The study illuminated a nuanced connection between frailty and adverse outcomes, underlining the critical need for robust predictive tools in this context. Conclusion: Frailty emerged as a pivotal factor influencing the postoperative trajectory of older adults undergoing EL in Singapore. The integration of frailty assessment, particularly when combined with established metrics like P-POSSUM, showcased enhanced predictive accuracy. This finding offers valuable insights for shared decision-making and acute surgical unit practices, emphasising the imperative of considering frailty in the management of older patients undergoing emergency laparotomy.

Sustained improved emergency laparotomy outcomes over 3 years after a transdisciplinary perioperative care pathway-A 1:1 propensity score matched study.

BACKGROUND: Emergency laparotomy is associated with high morbidity and significant global health burden. This study aims to compare postoperative outcomes of patients who underwent emergency laparotomy before and after implementation of a emergency laparotomy pathway. METHODS: This is a single-center study of all patients who presented with an acute abdomen and/or conditions requiring emergency laparotomy during pre-emergency laparotomy pathway (retrospective cohort from January 2016 to December 2018) and after the emergency laparotomy pathway (prospective cohort from January 2019 to December 2021). Patients who underwent emergency laparotomy for trauma or vascular surgery were excluded. A 1:1 propensity score matching was performed to address for confounding factors. RESULTS: There were 888 patients (emergency laparotomy pathway, n = 428, and pre-emergency laparotomy pathway, n = 460) in the unmatched cohort. The mean age was 63.0 ± 15.4 years, and 43.8% had predicted mortality >10% using Portsmouth-Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity. The most common indication for emergency laparotomy was intestinal obstruction (30.5%). Overall incidence rates of major morbidity and 30-day mortality were 16.2% and 3.5%, respectively. There were 736 patients (n = 368 patients per arm) after propensity score matching. Demographic characteristics were comparable after propensity score matching. The emergency laparotomy pathway was associated with more patients assessed by geriatric medicine (odds ratio = 15.22; P < .001), reduced major morbidity (odds ratio = 0.63; P = .024), reduced intra-abdominal collection (odds ratio = 0.39; P = .006), and need for unplanned radiological and/or surgical intervention after index emergency laparotomy (odds ratio = 0.63; P = .024). Length of stay and 30-day mortality were comparable between the emergency laparotomy pathway and pre-emergency laparotomy pathway in both the unmatched and propensity score matched cohort. CONCLUSION: Sustained improved postoperative outcomes were achieved 3 years postimplementation of the emergency laparotomy pathway .

The Ongoing Debate on the Use of Prophylactic Antibiotics in Acute Pancreatitis-Is There a Conclusion? A Comprehensive Narrative Review.

Acute pancreatitis (AP) is a common but often self-limiting disease in the majority of patients. However, in the minority, who may progress to moderately severe or severe AP, high mortality risk has been reported. Infected pancreatitis necrosis (IPN) in necrotising pancreatitis has been shown to result in more than twice the mortality rate compared with in sterile pancreatic necrosis. This raises the question on whether prophylactic antibiotics (PABs) should be given in subgroups of AP to prevent superimposed infection to improve survival outcomes. Despite numerous randomised controlled trials (RCTs), meta-analyses, and guidelines on the management of AP, there is a lack of strong evidence to suggest the use of PABs in AP. Additionally, use of PABs is associated with antimicrobial resistance. Considerable heterogeneity exists and limits the interpretation of results-subgroup of AP benefitting from PAB use, choice/class of PAB, and timing of administration from symptom onset and duration of PAB use. Only a minority of existing meta-analyses suggest mortality benefits and reduction in IPN. The majority of existing guidelines do not recommend the use of PABs in AP. More research is required to make more definitive conclusions. Currently, PAB should only be administered after multidisciplinary discussions led by pancreatology experts.

Outcomes of liver resection in hepatitis C virus-related intrahepatic cholangiocarcinoma: A systematic review and meta-analysis.

BACKGROUND: Cholangiocarcinoma is the second most common primary liver malignancy. Its incidence and mortality rates have been increasing in recent years. Hepatitis C virus (HCV) infection is a risk factor for development of cirrhosis and cholangiocarcinoma. Currently, surgical resection remains the only curative treatment option for cholangiocarcinoma. We aim to study the impact of HCV infection on outcomes of liver resection (LR) in intrahepatic cholangiocarcinoma (ICC). AIM: To study the outcomes of curative resection of ICC in patients with HCV (i.e., HCV+) compared to patients without HCV (i.e., HCV-). METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies to assess the outcomes of LR in ICC in HCV+ patients compared to HCV- patients in tertiary care hospitals. PubMed, EMBASE, The Cochrane Library and Scopus were systematically searched from inception till August 2023. Included studies were RCTs and non-RCTs on patients ≥ 18 years old with a diagnosis of ICC who underwent LR, and compared outcomes between patients with HCV+ vs HCV-. The primary outcomes were overall survival (OS) and recurrence-free survival. Secondary outcomes include perioperative mortality, operation duration, blood loss, intrahepatic and extrahepatic recurrence. RESULTS: Seven articles, published between 2004 and 2021, fulfilled the selection criteria. All of the studies were retrospective studies. Age, incidence of male patients, albumin, bilirubin, platelets, tumor size, incidence of multiple tumors, vascular invasion, bile duct invasion, lymph node metastases, and stage 4 disease were comparable between HCV+ and HCV- group. Alanine transaminase [MD 22.20, 95%confidence interval (CI): 13.75, 30.65, P < 0.00001] and aspartate transaminase levels (MD 27.27, 95%CI: 20.20, 34.34, P < 0.00001) were significantly higher in HCV+ group compared to HCV- group. Incidence of cirrhosis was significantly higher in HCV+ group [odds ratio (OR) 5.78, 95%CI: 1.38, 24.14, P = 0.02] compared to HCV- group. Incidence of poorly differentiated disease was significantly higher in HCV+ group (OR 2.55, 95%CI: 1.34, 4.82, P = 0.004) compared to HCV- group. Incidence of simultaneous hepatocellular carcinoma lesions was significantly higher in HCV+ group (OR 8.31, 95%CI: 2.36, 29.26, P = 0.001) compared to HCV- group. OS was significantly worse in the HCV+ group (hazard ratio 2.05, 95%CI: 1.46, 2.88, P < 0.0001) compared to HCV- group. CONCLUSION: This meta-analysis demonstrated significantly worse OS in HCV+ patients with ICC who underwent curative resection compared to HCV- patients.

Feasibility and safety of minimally invasive multivisceral resection for T4b rectal cancer: A 9-year review.

BACKGROUND: Colorectal cancer is the third most common cancer and the second highest cause of cancer-related mortality worldwide. About 5%-10% of patients are diagnosed with locally advanced rectal cancer (LARC) on presentation. For LARC invading into other structures (i.e. T4b), multivisceral resection (MVR) and/or pelvic exenteration (PE) remains the only potential curative surgical treatment. MVR and/or PE is a major and complex surgery with high post-operative morbidity. Minimally invasive surgery (MIS) has been shown to improve short-term post-operative outcomes in other gastrointestinal malignancies, but there is little evidence on its use in MVR, especially so for robotic MVR. AIM: To assess the feasibility and safety of minimally invasive MVR (miMVR), and compare post-operative outcomes between robotic and laparoscopic MVR. METHODS: This is a single-center retrospective cohort study from 1st January 2015 to 31st March 2023. Inclusion criteria were patients diagnosed with cT4b rectal cancer and underwent MVR, or stage 4 disease with resectable systemic metastases. Patients who underwent curative MVR for locally recurrent rectal cancer, or metachronous rectal cancer were also included. Exclusion criteria were patients with systemic metastases with non-resectable disease. All patients planned for elective surgery were enrolled into the standard enhanced recovery after surgery pathway with standard peri-operative management for colorectal surgery. Complex surgery was defined based on technical difficulty of surgery (i.e. total PE, bladder-sparing prostatectomy, pelvic lymph node dissection or need for flap creation). Our primary outcomes were the margin status, and complication rates. Categorical values were described as percentages and analysed by the chi-square test. Continuous variables were expressed as median (range) and analysed by Mann-Whitney U test. Cumulative overall survival (OS) and recurrence-free survival (RFS) were analysed using Kaplan-Meier estimates with life table analysis. Log-rank test was performed to determine statistical significance between cumulative estimates. Statistical significance was defined as P < 0.05. RESULTS: A total of 46 patients were included in this study [open MVR (oMVR): 12 (26.1%), miMVR: 36 (73.9%)]. Patients' American Society of Anesthesiologists score, body mass index and co-morbidities were comparable between oMVR and miMVR. There is an increasing trend towards robotic MVR from 2015 to 2023. MiMVR was associated with lower estimated blood loss (EBL) (median 450 vs 1200 mL, P = 0.008), major morbidity (14.7% vs 50.0%, P = 0.014), post-operative intra-abdominal collections (11.8% vs 50.0%, P = 0.006), post-operative ileus (32.4% vs 66.7%, P = 0.04) and surgical site infection (11.8% vs 50.0%, P = 0.006) compared with oMVR. Length of stay was also shorter for miMVR compared with oMVR (median 10 vs 30 d, P = 0.001). Oncological outcomes-R0 resection, recurrence, OS and RFS were comparable between miMVR and oMVR. There was no 30-d mortality. More patients underwent robotic compared with laparoscopic MVR for complex cases (robotic 57.1% vs laparoscopic 7.7%, P = 0.004). The operating time was longer for robotic compared with laparoscopic MVR [robotic: 602 (400-900) min, laparoscopic: Median 455 (275-675) min, P < 0.001]. Incidence of R0 resection was similar (laparoscopic: 84.6% vs robotic: 76.2%, P = 0.555). Overall complication rates, major morbidity rates and 30-d readmission rates were similar between laparoscopic and robotic MVR. Interestingly, 3-year OS (robotic 83.1% vs 58.6%, P = 0.008) and RFS (robotic 72.9% vs 34.3%, P = 0.002) was superior for robotic compared with laparoscopic MVR. CONCLUSION: MiMVR had lower post-operative complications compared to oMVR. Robotic MVR was also safe, with acceptable post-operative complication rates. Prospective studies should be conducted to compare short-term and long-term outcomes between robotic vs laparoscopic MVR.

Can Computerized Simulation be Used to Assess Surgical Proficiency in Laparoscopic Colorectal Surgeries? A Systematic Review.

INTRODUCTION: Computerized simulation (CS) of surgery in virtual reality (VR), augmented reality (AR) and mixed reality (MR) settings are used to teach foundational skills, but its applicability in advanced training is to be determined. This review aims to summarize the types of CS available for laparoscopic colorectal surgery (CRS) and its utility in assessment of proficiency. METHODS: A systematic review of CS in laparoscopic CRS was done on PubMed, Embase, Scopus and Cochrane Library databases. RESULTS: Eleven relevant observational studies were identified. The most common procedure simulated was laparoscopic colectomy. Assessment using performance metrics measured by the simulator such as path length moved by laparoscopic tools, procedure time and number of discrete movements had the most consistent differentiating ability between expert and non-expert cohorts. Surgeons fared similarly in proficiency scores in assessment with CS compared to assessment with traditional cadaveric or porcine models. CONCLUSION: CS of laparoscopic CRS may be used in assessment of proficiency using performance metrics measuring economy of movement. CS may be a viable assessment tool in advanced surgical training, but further studies should assess utility of incorporating it as a formal assessment tool in training programs.

A 10-year review on older patients undergoing colorectal cancer surgery: surgeon-led geriatric service and good quality surgery are drivers of good outcomes.

BACKGROUND: Older age and frailty are associated with worse postoperative outcomes and prolonged length of stay (LOS). In this study, we aimed to analyze the long-term outcomes after the implementation of our geriatric surgical service (GSS). METHODS: This was a single-center retrospective study from July 2010 to December 2021 on patients aged ≥75 years or patients aged ≥65 years with frailty. Our GSS includes multidisciplinary assessment and optimization by specialized nurses, physiotherapists, anesthetists, dietitians, and geriatricians. Cumulative sum (CUSUM) analysis was used to assess the performance of our GSS. Our primary outcome was defined as the presence of 30-day mortality, prolonged LOS ≥ 14 days, and/or >10% decrease in the modified Barthel Index at 6 weeks, which depicts the failure of GSS. A downsloping CUSUM curve implies consecutive cases of success. RESULTS: There were 233 patients with a mean age of 79.0 ± 4.9 years; of these, 73 patients (31.3%) were frail. The overall 30-day mortality (1.7%), Clavien-Dindo ≥ grade IIIA complications (12.0%), and LOS (median, 7.0 days) were low. The CUSUM analysis showed 3 phases with overall sustained improvement in outcomes. Transient inconsistency in the second phase (during midimplementation of GSS) may be due to the early adoption of laparoscopic surgery (44.6% vs 24.1%; adjusted P =.031) and expansion of service to include patients with higher perioperative risks (weighted Charlson Comorbidity Index score ≥4: 64.9% vs 38.0%; adjusted P =.002) in the second period compared with the first period. The outcomes subsequently improved in the third phase after overcoming the learning curve. CONCLUSION: Our GSS showed sustained performance over the past decade. Good quality surgery and surgeon-led geriatric service are paramount for good postoperative outcomes.

Evaluating a Single Surgeon's Learning Curve for Laparoscopic Totally Extraperitoneal Repair of Inguinal Hernia with Telescopic Dissection: A Cumulative Sum Control Chart Analysis.

Background: Laparoscopic totally extraperitoneal (TEP) inguinal hernia repair (IHR) reduces risk of injury to intraperitoneal structures. Balloon dissection is more costly and has theoretical risk of injury to the surrounding structures compared with telescopic dissection (TD). This study aims to evaluate the learning curve (LC) for TEP IHR with TD of a single surgeon. Methods: This is a 3-year retrospective cohort study from January 2020 to December 2022 on patients who underwent elective laparoscopic TEP unilateral IHR with TD. Exclusion criteria were recurrent inguinal hernia. Cumulative sum (CUSUM) analysis was performed to evaluate the number of cases required to surmount the LC, that is, NLC for operating time (OT) and open conversion. One way analysis of variance was used to perform groupwise comparison. Results: There were 69 patients who underwent laparoscopic TEP unilateral IHR with TD. The median age was 58.0 years (range 24.0-80.0) and body mass index was 23.0 (range 18.6-30.0). Majority of the hernia was indirect (n = 48, 69.6%). The median OT was 70 minutes (range 35-210). Three cases (4.3%) had open conversion. One-year recurrence was 4.2% (n = 1/24). CUSUM analysis showed improvement in OT after the eighth case. However, this was followed by multiple inflection points with no apparent stabilization in OT. Pairwise comparison showed a decrease in OT between cases 18-36 and cases 37-54. There was no incidence of open conversion until the 56th case. Conclusion: Laparoscopic TEP IHR using TD is safe in the absence of a practor. A minimum of 36 cases is required to surmount the initial LC.

The impact of waiting time and delayed treatment on the outcomes of patients with hepatocellular carcinoma: A systematic review and meta-analysis.

Hepatocellular carcinoma (HCC) is the sixth most diagnosed cancer worldwide. Healthcare resource constraints may predispose treatment delays. We aim to review existing literature on whether delayed treatment results in worse outcomes in HCC. PubMed, Embase, The Cochrane Library, and Scopus were systematically searched from inception till December 2022. Primary outcomes were overall survival (OS) and disease-free survival (DFS). Secondary outcomes included post-treatment mortality, readmission rates, and complications. Fourteen studies with a total of 135,389 patients (delayed n = 25,516, no delay n = 109,873) were included. Age, incidence of male patients, Child-Pugh B cirrhosis, and Barcelona Clinic Liver Cancer Stage 0/A HCC were comparable between delayed and no delay groups. Tumor size was significantly smaller in delayed versus no delay group (mean difference, -0.70 cm; 95% confidence interval [CI]: -1.14, 0.26; p = 0.002). More patients received radiofrequency ablation in delayed versus no delay group (OR, 1.22; 95% CI: 1.16, 1.27; p < 0.0001). OS was comparable between delayed and no delay in HCC treatment (hazard ratio [HR], 1.13; 95% CI: 0.99, 1.29; p = 0.07). Comparable DFS between delayed and no delay groups (HR, 0.99; 95% CI: 0.75, 1.30; p = 0.95) was observed. Subgroup analysis of studies that defined treatment delay as > 90 days showed comparable OS in the delayed group (HR, 1.04; 95% CI: 0.93, 1.16; p = 0.51). OS and DFS for delayed treatment were non-inferior compared to no delay, but might be due to better tumor biology/smaller tumor size in the delayed group.

Establishing the Learning Curve of Laparoscopic and Robotic Distal Gastrectomy: a Systematic Review and Meta-Regression Analysis.

BACKGROUND: Minimally invasive distal gastrectomy (MIDG) is non-inferior compared with open distal gastrectomy for gastric cancer. However, MIDG bears a learning curve (LC). This study aims to evaluate the number of cases required to surmount the LC (i.e. NLC) in MIDG. METHODS: PubMed, Embase, Scopus, and the Cochrane Library were systematically searched from inception to August 2022 for studies which reported NLC in MIDG. NLC on reduced-port/single-port MIDG only were separately analysed. Poisson mean (95% confidence interval (CI)) was used to determine NLC. Negative binomial regression was used to compare NLC between laparoscopic distal gastrectomy (LDG) and robotic distal gastrectomy (RDG). RESULTS: A total of 45 articles with 71 data sets (LDG n=47, RDG n=24) were analysed. There were 7776 patients in total (LDG n=5516, RDG n=2260). Majority of studies were conducted in East Asia (n=68/71). Majority (76.1%) of data sets used non-arbitrary methods of analyses. The overall NLC for RDG was significantly lower compared to LDG (RDG 22.4 (95% CI: 20.4-24.5); LDG 46.7 (95% CI: 44.1-49.4); incidence rate ratio 0.48, p<0.001). The median number of laparoscopic gastrectomy (LG) cases prior was 0 (interquartile range (IQR) 0-105) for LDG and 159 (IQR 101-305.3) for RDG. Meta-regression analysis did not show a significant impact prior experience in LG, extent of lymphadenectomy and intracorporeal vs extracorporeal anastomosis had on overall NLC for LDG and RDG. CONCLUSION: NLC for RDG is shorter compared to LDG, but this may be due to prior experience in LG and ergonomic advantages of RDG.

Preoperative transarterial chemoembolization (TACE) + liver resection versus upfront liver resection for large hepatocellular carcinoma (≥5 cm): a systematic review and meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) accounts for majority of primary liver cancer. Use of preoperative neoadjuvant transarterial chemoembolization (PN-TACE) may result in tumor shrinkage and improve resectability. This study aims to summarize the outcomes of PN-TACE versus upfront liver resection (Up-LR) in large HCC (≥5 cm). METHODS: PubMed, Embase, The Cochrane Library, and Scopus were systematically searched till September 2022 for studies comparing PN-TACE versus Up-LR. The primary study outcomes were overall survival (OS), disease-free survival (DFS), and recurrence. Our secondary outcomes were postoperative morbidity and mortality. RESULTS: There were 12 studies with 15 data sets including 3960 patients (PN-TACE n = 2447, Up-LR n = 1513). Majority (89.5%, n = 1250/1397) of patients had Child's A liver cirrhosis. Incidence of Child's B cirrhosis was higher in PN-TACE compared to Up-LR (Odds ratio (OR) 1.69, 95% CI: 1.18, 2.41, p = 0.004). Pooled hazard ratio (HR) for OS showed no significant difference between PN-TACE and Up-LR (HR 0.87, 95% CI: 0.64, 1.18, p = 0.37), but DFS was superior in PN-TACE (HR 0.79, 95% CI: 0.63, 0.99, p = 0.04). Subgroup analysis based on study design failed to show any significant effect in randomized controlled trials (n = 2/15 data sets). However, operating time (mean difference (MD) 31.94 min, 95% CI: 2.42, 61.45, p = 0.03) and blood loss (MD 190.93 ml, 95% CI: 10.22, 317.65, p = 0.04) were higher in PN-TACE. Intrahepatic and extrahepatic recurrence, post-operative morbidity and in-hospital mortality were comparable between PN-TACE and Up-LR. CONCLUSION: In retrospective studies, PN-TACE resulted in superior DFS compared to Up-LR. However, this may be confounded by selection bias.

A prospective study on the efficacy of sequential treatment of technology Lipido-Colloid Impregnated with Silver and Technology Lipido-Colloid Nano-Oligosaccharide Factor in the management of venous leg ulcers.

Background and Aims: Venous leg ulcers (VLUs) are associated with significant morbidity and poor quality of life (QOL). Compression therapy and wound dressing are the mainstay treatment options. Technology Lipido-Colloid Impregnated with Silver (TLC-Ag) reduces bacterial load and Technology Lipido-Colloid Nano-Oligosaccharide Factor (TLC-NOSF) reduces elevated matrix metalloproteinases and improve wound healing. However, evidence is scarce on the role of sequential therapy. This study aims to evaluate if sequential treatment with TLC-Ag and TLC-NOSF improves VLU wound healing and QOL. Methods: This is a prospective cohort study from May 2020 to October 2021 on patients with VLUs who received sequential therapy, consisting of 2 weeks of TLC-Ag followed by two-layer compression bandage (2LB) with TLC-NOSF until complete wound healing. Participants were followed-up with weekly dressing changes. Our primary outcomes were wound area reduction (WAR) and Pressure Ulcer Scale of Healing (PUSH) score. Our secondary outcomes were QOL measures. Results: There were 28 patients with 57.1% males (n = 16) with a mean age of 65.3 years. Mean duration of VLU was 13.9 ± 11.7 weeks before the initiation of sequential therapy. Mean baseline wound area was 8.44 cm2. Median time to wound healing was 10 weeks. 57.1% of patients achieved complete wound closure at 3 months. There was significant WAR after 1 month (mean area 8.44-5.81 cm2, 31.2% decrease) and after 3 months (mean area 8.44-2.53 cm2, 70.0% decrease). Mean monthly WAR was 28.9%. PUSH score also decreased at 1 month (16.5% decrease, p < 0.001) and 3 months (63.3% decrease, p < 0.001) marks following the sequential therapy. EuroQol Visual Analog Scale (EQ-VAS) improved following sequential therapy (baseline: 69.0 ± 15.0, week 13: 80.2 ± 13.2, p < 0.001). Conclusion: Sequential therapy with TLC-Ag followed by TLC-NOSF and 2LB is feasible, with good wound healing and improvement in QOL of patients with VLUs.

Are outcomes for emergency index-admission laparoscopic cholecystectomy performed by hepatopancreatobiliary surgeons better compared to non-hepatopancreatobiliary surgeons? A 10-year audit using 1:1 propensity score matching.

BACKGROUND: Emergency index-admission cholecystectomy (EIC) is recommended for acute cholecystitis in most cases. General surgeons have less exposure in managing "difficult" cholecystectomies. This study aimed to compare the outcomes of EIC between hepatopancreatobiliary (HPB) versus non-HPB surgeons. METHODS: This is a 10-year retrospective audit on patients who underwent EIC from December 2011 to March 2022. Patients who underwent open cholecystectomy, had previous cholecystitis, previous endoscopic retrograde cholangiopancreatography or cholecystostomy were excluded. A 1:1 propensity score matching (PSM) was performed to adjust for confounding variables (e.g. age ≥ 75 years, history of abdominal surgery, presence of dense adhesions). RESULTS: There were 1409 patients (684 HPB cases, 725 non-HPB cases) in the unmatched cohort. Majority (52.3%) of them were males with a mean age of 59.2 ± 14.9 years. Among 472 (33.5%) patients with EIC performed ≥ 72 hours after presentation, 40.1% had dense adhesion. The incidence of any morbidity, open conversion, subtotal cholecystectomy and bile duct injury were 12.4%, 5.0%, 14.6% and 0.1%, respectively. There was one mortality within 30 days from EIC. PSM resulted in 1166 patients (583 per group). Operative time was shorter when EIC was performed by HPB surgeons (115.5 min vs. 133.4 min, P < 0.001). The mean length of hospital stay was comparable. EIC performed by HPB surgeons was independently associated with lower open conversion [odds ratio (OR)=  0.24, 95% confidence interval (CI): 0.12-0.49, P < 0.001], lower fundus-first cholecystectomy (OR=  0.58, 95% CI: 0.35-0.95, P=  0.032), but higher subtotal cholecystectomy (OR=  4.19, 95% CI: 2.24-7.84, P < 0.001). Any morbidity, bile duct injury and mortality were comparable between the two groups. CONCLUSION: EIC performed by HPB surgeons were associated with shorter operative time and reduced risk of open conversion. However, the incidence of subtotal cholecystectomy was higher.

Carbon footprints in minimally invasive surgery: Good patient outcomes, but costly for the environment.

Advancements in technology and surgical training programs have increased the adaptability of minimally invasive surgery (MIS). Gastrointestinal MIS is superior to its open counterparts regarding post-operative morbidity and mortality. MIS has become the first-line surgical intervention for some types of gastrointestinal surgery, such as laparoscopic cholecystectomy and appendicectomy. Carbon dioxide (CO2) is the main gas used for insufflation in MIS. CO2 contributes 9%-26% of the greenhouse effect, resulting in global warming. The rise in global CO2 concentration since 2000 is about 20 ppm per decade, up to 10 times faster than any sustained rise in CO2 during the past 800000 years. Since 1970, there has been a steady yet worrying increase in average global temperature by 1.7 °C per century. A recent systematic review of the carbon footprint in MIS showed a range of 6-814 kg of CO2 emission per surgery, with higher CO2 emission following robotic compared to laparoscopic surgery. However, with superior benefits of MIS over open surgery, this poses an ethical dilemma to surgeons. A recent survey in the United Kingdom of 130 surgeons showed that the majority (94%) were concerned with climate change but felt that the lack of leadership was a barrier to improving environmental sustainability. Given the deleterious environmental effects of MIS, this study aims to summarize the trends of MIS and its carbon footprint, awareness and attitudes towards this issue, and efforts and challenges to ensuring environmental sustainability.

Occam's razor or Hickam's dictum-COVID-19 is not a textbook aetiology of acute pancreatitis: A modified Naranjo Score appraisal.

BACKGROUND: Acute pancreatitis (AP) is a disease spectrum ranging from mild to severe disease. During the coronavirus disease 2019 (COVID-19) pandemic, numerous reports of AP have been published, with most authors concluding a causal relationship between COVID-19 and AP. Retrospective case reports or small case series are unable to accurately determine the cause-effect relationship between COVID-19 and AP. AIM: To establish whether COVID-19 is a cause of AP using the modified Naranjo scoring system. METHODS: A systematic review was conducted on PubMed, World of Science and Embase for articles reporting COVID-19 and AP from inception to August 2021. Exclusion criteria were cases of AP which were not reported to be due to COVID-19 infection, age < 18 years old, review articles and retrospective cohort studies. The original 10-item Naranjo scoring system (total score 13) was devised to approximate the likelihood of a clinical presentation to be secondary to an adverse drug reaction. We modified the original scoring system into a 8-item modified Naranjo scoring system (total score 9) to determine the cause-effect relationship between COVID-19 and AP. A cumulative score was decided for each case presented in the included articles. Interpretation of the modified Naranjo scoring system is as follows: ≤ 3: Doubtful, 4-6: Possible, ≥ 7: Probable cause. RESULTS: The initial search resulted in 909 articles, with 740 articles after removal of duplicates. A total of 67 articles were included in the final analysis, with 76 patients which had AP reported to be due to COVID-19. The mean age was 47.8 (range 18-94) years. Majority of patients (73.3%) had ≤ 7 d between onset of COVID-19 infection and diagnosis of AP. There were only 45 (59.2%) patients who had adequate investigations to rule out common aetiologies (gallstones, choledocholithiasis, alcohol, hypertriglyceridemia, hypercalcemia and trauma) of AP. Immunoglobulin G4 testing was conducted in 9 (13.5%) patients to rule out autoimmune AP. Only 5 (6.6%) patients underwent endoscopic ultrasound and/or magnetic resonance cholangiopancreatogram to rule out occult microlithiasis, pancreatic malignancy and pancreas divisum. None of the patients had other recently diagnosed viral infections apart from COVID-19 infection, or underwent genetic testing to rule out hereditary AP. There were 32 (42.1%), 39 (51.3%) and 5 (6.6%) patients with doubtful, possible, and probable cause-effect relationship respectively between COVID-19 and AP. CONCLUSION: Current evidence is weak to establish a strong link between COVID-19 and AP. Investigations should be performed to rule out other causes of AP before establishing COVID-19 as an aetiology.

Use of preinjury antiplatelet and oral anticoagulant agents on outcomes following blunt trauma in an Asian population: a 1:2 propensity score matched study.

BACKGROUND: Bleeding is a feared complication of antiplatelets (APTs) and oral anti-coagulants (OACs) use. Asians are at higher risk of bleeding from APT/OAC compared to Western population. Our study aims to investigate the impact of preinjury APT/OAC use on outcomes of moderate to severe blunt trauma. METHODS: This is a retrospective cohort study from Jan 2017 - Dec 2019 of all patients with moderate to severe blunt trauma. A 1:2 propensity score matching (PSM) analysis was performed to address for confounding factors. Our primary outcome was in-hospital mortality. Our secondary outcomes were severity of head injury and need for emergency surgery within the first 24 hours. RESULTS: There were 592 patients (APT/OAC n=72, no APT/OAC n=520) included in our study. The median age was 74 years in APT/OAC and 58 years in no APT/OAC. PSM resulted in 150 patients (APT/OAC n=50, no APT/OAC n=100). In the PSM cohort, more patients with APT/OAC use had ischemic heart disease (76% vs 0%, P<0.001). APT/OAC use was independently associated with higher in-hospital mortality (22.0% vs 9.0%, Odds ratio (OR) 3.00, 95% Confidence interval (CI): 1.05, 8.56, P=0.040) Severity of head injury (abbreviated injury scale in APT/OAC: 3.33 ± 1.53, vs 2.97 ± 1.43, P=0.380) and need for emergency surgery (APT/OAC 16.2% vs 11.0%, P=0.434) was comparable between APT/OAC and no APT/OAC. CONCLUSIONS: Preinjury APT/OAC use was associated with higher in-hospital mortality. Severity of head injury and need for emergency surgery within 24 hours from admission were comparable between APT/OAC use and no APT/OAC use.