Identification of a lactylation-related gene signature to characterize subtypes of hepatocellular carcinoma using bulk sequencing data.

Background: Prior studies indicate that lactylation regulates various biological mechanisms within cancer. However, lactylation-related genes (LRGs) have been found to have limited value in predicting the prognosis of hepatocellular carcinoma (HCC). The aim of this study was to review HCC LRGs using data from The Cancer Genome Atlas (TCGA). Methods: The RNA sequencing data and related clinical information of patients with HCC patients were collected from the TCGA database. A total of 20 LRGs were selected and bioinformatics analysis was performed. A consistency cluster analysis was conducted to classify the HCC tumors. Using a lactylation-related model of HCC, prognosis, immune cell infiltration, and immunotherapy was evaluated. Results: A total of 4,378 genes were associated with prognosis. Twenty LRGs (i.e., ACIN1, RAN, PPP1CB, ALDOB, SUMO2, THOC2, HDAC1, SF3A1, SF3B1, HNRNPM, PPP1CC, SRRM1, PRPF6, HDAC2, H2AFV, ALYREF, H2AFZ, H2AFX, HNRNPK, and MAGOH) were identified. The 20 LRGs were used to divide TCGA-HCC patients into low-risk (G1) and high-risk (G2) categories. The upregulated genes in the G1 group primarily participate in the p53 signaling pathway, focal adhesion, extracellular matrix (ECM)-receptor interaction, and cell cycle, while the downregulated genes primarily participate in the glycolysis/gluconeogenesis, carbon metabolism, and biosynthesis of amino acids. The box plots showed a significant difference in the immune cell populations, with a higher abundance of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and myeloid dendritic cells in the G1 than the G2 HCC samples. Further, the box plots showed higher expression levels of seven of the eight immune checkpoint inhibitor (ICI)-related genes in the G1 HCC samples than the G2 samples. There was a significant disparity in the cancer stem cell (CSC) scores between the G1 and G2 TCGA-HCC patients. Additionally, the G1 TCGA-HCC patients had higher tumor immune dysfunction and exclusion (TIDE) scores than the G2 TCGA-HCC patients. The prognosis of the HCC patients was also predicted using a six-LRG model, comprising HDAC2, SRRM1, SF3B1, HDAC1, THOC2, and PPP1CB. Conclusions: Strong correlation between LRGs and tumor classification as well as immunity in patients with HCC was identified. LRG signatures serve as reliable prognostic markers for HCC.

Pancreatic pseudocyst: The past, the present, and the future.

A pancreatic pseudocyst is defined as an encapsulated fluid collection with a well-defined inflammatory wall with minimal or no necrosis. The diagnosis cannot be made prior to 4 wk after the onset of pancreatitis. The clinical presentation is often nonspecific, with abdominal pain being the most common symptom. If a diagnosis is suspected, contrast-enhanced computed tomography and/or magnetic resonance imaging are performed to confirm the diagnosis and assess the characteristics of the pseudocyst. Endoscopic ultrasound with cyst fluid analysis can be performed in cases of diagnostic uncertainty. Pseudocyst of the pancreas can lead to complications such as hemorrhage, infection, and rupture. The management of pancreatic pseudocysts depends on the presence of symptoms and the development of complications, such as biliary or gastric outlet obstruction. Management options include endoscopic or surgical drainage. The aim of this review was to summarize the current literature on pancreatic pseudocysts and discuss the evolution of the definitions, diagnosis, and management of this condition.

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.

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.

The 2023 WSES guidelines on the management of trauma in elderly and frail patients

The trauma mortality rate is higher in the elderly compared with younger patients. Ageing is associated with physiological changes in multiple systems and correlated with frailty. Frailty is a risk factor for mortality in elderly trauma patients. We aim to provide evidence-based guidelines for the management of geriatric trauma patients to improve it and reduce futile procedures. Six working groups of expert acute care and trauma surgeons reviewed extensively the literature according to the topic and the PICO question assigned. Statements and recommendations were assessed according to the GRADE methodology and approved by a consensus of experts in the field at the 10th international congress of the WSES in 2023. The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage, including drug history, frailty assessment, nutritional status, and early activation of trauma protocol to improve outcomes. Acute trauma pain in the elderly has to be managed in a multimodal analgesic approach, to avoid side effects of opioid use. Antibiotic prophylaxis is recommended in penetrating (abdominal, thoracic) trauma, in severely burned and in open fractures elderly patients to decrease septic complications. Antibiotics are not recommended in blunt trauma in the absence of signs of sepsis and septic shock. Venous thromboembolism prophylaxis with LMWH or UFH should be administrated as soon as possible in high and moderate-risk elderly trauma patients according to the renal function, weight of the patient and bleeding risk. A palliative care team should be involved as soon as possible to discuss the end of life in a multidisciplinary approach considering the patient's directives, family feelings and representatives' desires, and all decisions should be shared. The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage based on assessing frailty and early activation of trauma protocol to improve outcomes. Geriatric Intensive Care Units are needed to care for elderly and frail trauma patients in a multidisciplinary approach to decrease mortality and improve outcomes.

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.

Doctor, let us not tell her about the porcine implant.

With the proliferation of pharmaceuticals and advances in innovative medical technologies, use of animal-derived products is widespread in the healthcare industry. The use of these products sometimes conflicts with the religious beliefs of patients. I was involved in an ethical dilemma during reoperative abdominal hernia surgery. I engaged with the patient's next-of-kin via an intraoperative phone discussion regarding the possible use of a porcine-derived biological mesh implant. Here, I reflect on the experience to help clinicians who seek ethical competence alongside clinical competence.

Chemical composition and biological activities of Lonicera caprifolium L. (Caprifoliaceae) essential oil.

This work aimed to investigate the chemical composition, antioxidant activity, antinociceptive effect, and wound healing activity of the Lonicera caprifolium L. flower essential oil (LCEO). Linalool (16.42%), d-limonene (9.99%), and α-cadinol (10.65%) were the most prevalent components of the LCEO. The LCEO revealed moderate DPPH and ABTS radical-scavenging activity. LCEO exhibited potent antinociceptive activity in acetic acid-induced writhing and hot plate-induced pain model; LCEO reduced 73.88 ± 2.78% of writhing and significantly increased pain withdrawal latency in the mice, respectively. The LCEO also presented a potent wound healing effect, with 98.08 ± 1.37% wound closure on the 12th day of treatment. The results of the study demonstrate antioxidant and wound healing potential with antinociceptive effect. To the best of our knowledge, this is the first report on the bioactivities of L. caprifolium L. essential oil.

Effect of perioperative branched chain amino acids supplementation in liver cancer patients undergoing surgical intervention: A systematic review.

BACKGROUND: Branched chain amino acid (BCAA) supplementation has been associated with favourable outcomes in liver malignancies requiring definitive resection or liver transplantation. Currently, there are no updated systematic reviews evaluating the efficacy of perioperative BCAA supplementation in patients undergoing surgery for liver cancer. AIM: To evaluate the efficacy of perioperative BCAA supplementation in patients undergoing surgery for liver cancer. METHODS: A systematic review of randomized control trials and observational studies was conducted on PubMed, Embase, Cochrane Library, Scopus, and Web of Science to evaluate the effect of perioperative BCAA supplementation compared to standard in-hospital diet, in liver cancer patients undergoing surgery. Clinical outcomes were extracted, and a meta-analysis was performed on relevant outcomes. RESULTS: 16 studies including 1389 patients were included. Perioperative BCAA administration was associated with reduced postoperative infection [risk ratio (RR) = 0.58 95% confidence intervals (CI): 0.39 to 0.84, P = 0.005] and ascites [RR = 0.57 (95%CI: 0.38 to 0.85), P = 0.005]. There was also a reduction in length of hospital stay (LOS) [weighted mean difference (WMD) = -3.03 d (95%CI: -5.49 to -0.57), P = 0.02] and increase in body weight [WMD = 1.98 kg (95%CI: 0.35 to 3.61, P = 0.02]. No significant differences were found in mortality, cancer recurrence and overall survival. No significant safety concerns were identified. CONCLUSION: Perioperative BCAA administration is efficacious in reducing postoperative infection, ascites, LOS, and increases body weight in liver cancer patients undergoing surgical resection.

Transmembrane serine protease 2, a SARS-CoV-2 internalization protease, correlates with clinical outcome, molecular features, and immunotherapy response in colorectal cancer.

Background: Transmembrane serine protease 2 (TMPRSS2) mediates the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells. The relevant research indicates the intestine to be a target of SARS-CoV-2 infection, and thus we aimed to investigate the correlation between TMPRSS2 expression and the prognosis, molecular features, and immunotherapy response in patients with colorectal cancer (CRC). Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used in this study and a total of 1,385 patients were identified. The CIBERSORT algorithms were used to evaluate the relative infiltration levels of immune cell types in the tumor microenvironment (TME). The correlation between TMPRSS2 expression and immunotherapy response rate was assessed in another 2 independent cohorts. Results: TMPRSS2 expression was significantly downregulated in cancer tissue compared to the adjacent normal tissue, and patients with CRC with lower TMPRSS2 expression showed notably poorer prognosis. Functional enrichment analysis found that low TMPRSS2 expression was significantly associated with cancer metastasis-related pathways. Further analysis based on the miRWalk tool and JASPAR database identified a list of microRNAs (miRNAs) and transcriptional factors targeting TMPRSS2. Distinct differences in immune cell infiltration and tumor purity reflected by estimate and mutant-allele tumor heterogeneity score were observed between patients with low and high TMPRSS2 expression levels. Interestingly, patients with a low TMPRSS2 expression level showed a higher response rate to immunotherapy. Conclusions: CRC cells may be more resistant to SARS-CoV-2 infection due to the decreased expression of TMPRSS2, which could be a newly identified biomarker for prognosis and immunotherapy response prediction in patients with CRC.

Indocyanine green dye and its application in gastrointestinal surgery: The future is bright green.

Indocyanine green (ICG) is a water-soluble fluorescent dye that is minimally toxic and widely used in gastrointestinal surgery. ICG facilitates anatomical identification of structures (e.g., ureters), assessment of lymph nodes, biliary mapping, organ perfusion and anastomosis assessment, and aids in determining the adequacy of oncological margins. In addition, ICG can be conjugated to artificially created antibodies for tumour markers, such as carcinoembryonic antigen for colorectal, breast, lung, and gastric cancer, prostate-specific antigen for prostate cancer, and cancer antigen 125 for ovarian cancer. Although ICG has shown promising results, the optimization of patient factors, dye factors, equipment, and the method of assessing fluorescence intensity could further enhance its utility. This review summarizes the clinical application of ICG in gastrointestinal surgery and discusses the emergence of novel dyes such as ZW-800 and VM678 that have demonstrated appropriate pharmacokinetic properties and improved target-to-background ratios in animal studies. With the emergence of robotic technology and the increasing reporting of ICG utility, a comprehensive review of clinical application of ICG in gastrointestinal surgery is timely and this review serves that aim.

Enhanced perioperative care in emergency general surgery: the WSES position paper.

Enhanced perioperative care protocols become the standard of care in elective surgery with a significant improvement in patients' outcome. The key element of the enhanced perioperative care protocol is the multimodal and interdisciplinary approach targeted to the patient, focused on a holistic approach to reduce surgical stress and improve perioperative recovery. Enhanced perioperative care in emergency general surgery is still a debated topic with little evidence available. The present position paper illustrates the existing evidence about perioperative care in emergency surgery patients with a focus on each perioperative intervention in the preoperative, intraoperative and postoperative phase. For each item was proposed and approved a statement by the WSES collaborative group.

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.

Biliary fistula and late recurrence of liver hydatid cyst: Role of cysto-biliary communication: A prospective multicenter study.

BACKGROUND: Hydatid cyst disease (HCD) is common in certain locations. Surgery is associated with postoperative biliary fistula (POBF) and recurrence. The primary aim of this study was to identify whether occult cysto-biliary communication (CBC) can predict recurrent HCD. The secondary aim was to assess the role of cystic fluid bilirubin and alkaline phosphatase (ALP) levels in predicting POBF and recurrent HCD. AIM: To identify whether occult CBC can predict recurrent HCD. The secondary aim was to assess the role of cystic fluid bilirubin and ALP levels in predicting POBF and recurrent HCD. METHODS: From September 2010 to September 2016, a prospective multicenter study was undertaken involving 244 patients with solitary primary superficial stage cystic echinococcosis 2 and cystic echinococcosis 3b HCD who underwent laparoscopic partial cystectomy with omentoplasty. Univariable logistic regression analysis assessed independent factors determining biliary complications and recurrence. RESULTS: There was a highly statistically significant association (P ≤ 0.001) between cystic fluid biochemical indices and the development of biliary complications (of 16 patients with POBF, 15 patients had high cyst fluid bilirubin and ALP levels), where patients with high bilirubin-ALP levels were 3405 times more likely to have biliary complications. There was a highly statistically significant association (P ≤ 0.001) between biliary complications, biochemical indices, and the occurrence of recurrent HCD (of 30 patients with recurrent HCD, 15 patients had high cyst fluid bilirubin and ALP; all 16 patients who had POBF later developed recurrent HCD), where patients who developed biliary complications and high bilirubin-ALP were 244.6 and 214 times more likely to have recurrent hydatid cysts, respectively. CONCLUSION: Occult CBC can predict recurrent HCD. Elevated cyst fluid bilirubin and ALP levels predicted POBF and recurrent HCD.

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.

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.