Metaverse and Telementoring: From Surgery to Workshop.

BACKGROUND: The Coronavirus 2019 (COVID-19) pandemic has favored the growth of telemedicine systems and in this context the idea of Metaverse was born and developed. A 3D reality in which people can interact with each other through digital reproductions of themselves. Metaverse has already been tested in numerous medical fields due to its ability to combine visual and auditory information with tactile sensations. The purpose of this study is to highlight its potential also in its ability to be used as a telementoring place where the skills and knowledge of surgeons from all over the world can be combined. MATERIAL AND METHODS: The first HPB Surgery Workshop was held at the "Metaverse Surgical Hospital, USA". During the workshop, surgeons located in various parts of the world reported on hepatic, pancreatic and biliary tract surgery and remotely supported the execution of a robotic liver resection. RESULTS: The Metaverse gave the opportunity for surgeons to meet and discuss HPB pathologies and its surgical strategies and for surgeons in training to interface with experts by participating in a moment of advanced training. CONCLUSION: In the Metaverse, telementoring can be used at very low cost to improve clinical and surgical practice.

Laparoscopic versus robotic abdominal and pelvic surgery: a systematic review of randomised controlled trials.

BACKGROUND: The current evidence is inconclusive on whether robotic or laparoscopic surgery is the optimal platform for minimally invasive surgery. Existing comparisons techniques focus on short-term outcomes only, while potentially being confounded by a lack of standardisation in robotic procedures. There is a pertinent need for an up-to-date comparison between minimally invasive surgical techniques. We aimed to systematically review randomised controlled trials comparing robotic and laparoscopic techniques in major surgery. METHODS: Embase, Medline and Cochrane Library were searched from their inception to 13th September 2022. Included studies were randomised controlled trials comparing robotic and laparoscopic techniques in abdominal and pelvic surgery. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Short-term, health-related quality of life, and long-term, outcomes were analysed. RESULTS: Forty-five studies, across thirteen procedures, involving 7364 patients were included. All of the studies reported non-significant differences in mortality between robotic and laparoscopic surgery. In majority of studies, there was no significant difference in complication rate (n = 31/35, 85.6%), length of postoperative stay (n = 27/32, 84.4%), and conversion rate (n = 15/18, 83.3%). Laparoscopic surgery was associated with shorter operative time (n = 16/31, 51.6%) and lower total cost (n = 11/13, 84.6%). Twenty three studies reported on quality of life outcomes; majority (n = 14/23, 60.9%) found no significant differences. CONCLUSION: There were no significant differences between robotic surgery and laparoscopic surgery with regards to mortality and morbidity outcomes in the majority of studies. Robotic surgery was frequently associated with longer operative times and higher overall cost. Selected studies found potential benefits in post-operative recovery time, and patient-reported outcomes; however, these were not consistent across procedures and trials, with most studies being underpowered to detect differences in secondary outcomes. Future research should focus on assessing quality of life, and long-term outcomes to further elucidate where the robotic platform could lead to patient benefits, as the technology evolves.

The influence of procedural volume on short-term outcomes for robotic pancreatoduodenectomy-a cohort study and a learning curve analysis.

BACKGROUND: An increasing number of robotic pancreatoduodenectomies (RPD) are reported, however, questions remain on the number of procedures needed for gaining technical proficiency in RPD. Therefore, we aimed to assess the influence of procedure volume on short-term RPD outcomes and assess the learning curve effect. METHODS: A retrospective review of consecutive RPD cases was undertaken. Non-adjusted cumulative sum (CUSUM) analysis was performed to identify the procedure volume threshold, following which before-threshold and after-threshold outcomes were compared. RESULTS: Since May 2017, 60 patients had undergone an RPD at our institution. The median operative time was 360 min (IQR 302.25-442 min). CUSUM analysis of operative time identified 21 cases as proficiency threshold, indicated by curve inflexion. Median operative time was significantly shorter after the threshold of 21 cases (470 vs 320 min, p < 0.001). No significant difference was found between before- and after-threshold groups in major Clavien-Dindo complications (23.8 vs 25.6%, p = 0.876). CONCLUSIONS: A decrease in operative time after 21 RPD cases suggests a threshold of technical proficiency potentially associated with an initial adjustment to new instrumentation, port placement and standardisation of operative step sequence. RPD can be safely performed by surgeons with prior laparoscopic surgery experience.

Circulating Tumor Cells and Cell-Free DNA in Pancreatic Ductal Adenocarcinoma.

Pancreatic cancer is detected late in the disease process and has an extremely poor prognosis. A blood-based biomarker that can enable early detection of disease, monitor response to treatment, and potentially allow for personalized treatment would be of great benefit. This review analyzes the literature regarding two potential biomarkers, circulating tumor cells (CTCs) and cell-free DNA (cfDNA), with regard to pancreatic ductal adenocarcinoma. The origin of CTCs and the methods of detection are discussed and a decade of research examining CTCs in pancreatic cancer is summarized, including both levels of CTCs and analyzing their molecular characteristics and how they may affect survival in both advanced and early disease and allow for treatment monitoring. The origin of cfDNA is discussed, and the literature over the past 15 years is summarized. This includes analyzing cfDNA for genetic mutations and methylation abnormalities, which have the potential to be used for the detection and prognosis of pancreatic ductal adenocarcinoma. However, the research certainly remains in the experimental stage, warranting future large trials in these areas.

Integrated molecular analysis to investigate the role of microRNAs in pancreatic tumour growth and progression.

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs involved in the post-transcriptional regulation of mRNAs and are aberrantly expressed in cancer with important roles in tumorigenesis. A broad analysis of the combined effects of altered activities of miRNAs in pancreatic ductal adenocarcinoma (PDAC) has not been done, and how miRNAs might affect tumour progression or patient outcomes is unclear. METHODS: We combined data from miRNA and mRNA expression profiles from PDAC and normal pancreas samples (each n=9) and used bioinformatic analyses to identify a miRNA-mRNA regulatory network in PDAC. We validated our findings in PDAC cell-lines (PANC-1, MIA PaCa-2, LPc006, and LPc167), subcutaneous PDAC xenografts in mice, and laser capture microdissected PDACs from patients (n=91). We used this information to identify miRNAs that contributed most to tumorigenesis. FINDINGS: We identified three miRNAs (miR-21, miR-23a, and miR-27a) that acted as cooperative repressors of a network of tumour suppressor genes that included PDCD4, BTG2, and NEDD4L. Inhibition of miR-21, miR-23a, and miR-27a had synergistic effects in reducing proliferation of PDAC cells in culture and the growth of xenograft tumours. The level of inhibition was greater than that of silencing oncomiR-21 alone. In PDACs from patients, high levels of the combination of miR-21, miR-23a, and miR-27a was a strong independent predictor of short overall survival after surgical resection (hazard ratio 3·21, 95% CI 1·78-5·78). High expression of this combination was also associated with a more aggressive tumour phenotype: more microscopic tumour infiltration at resection margin and increased perineural invasion. INTERPRETATION: In an integrated data analysis, we identified functional miRNA-mRNA interactions that contribute to PDAC growth. These findings indicate that miRNAs act together to promote tumour progression and that future therapeutic strategies might require inhibition of several miRNAs. Furthermore, high tumour expression of the miR-21, miR-23a, and miR-27a combination could have potential use in the future as a prognostic signature for patients with PDAC. FUNDING: Peel Medical Research Trust, Alliance Family Foundation, Action Against Cancer, National Institute for Health Research, Association for International Cancer Research, Jason Boas Fellowship, Imperial Biomedical Research Centre, Rosetrees Trust, Joseph Ettedgui Charitable Foundation.

MicroRNAs cooperatively inhibit a network of tumor suppressor genes to promote pancreatic tumor growth and progression.

BACKGROUND & AIMS: There has not been a broad analysis of the combined effects of altered activities of microRNAs (miRNAs) in pancreatic ductal adenocarcinoma (PDAC) cells, and it is unclear how these might affect tumor progression or patient outcomes. METHODS: We combined data from miRNA and messenger RNA (mRNA) expression profiles and bioinformatic analyses to identify an miRNA-mRNA regulatory network in PDAC cell lines (PANC-1 and MIA PaCa-2) and in PDAC samples from patients. We used this information to identify miRNAs that contribute most to tumorigenesis. RESULTS: We identified 3 miRNAs (MIR21, MIR23A, and MIR27A) that acted as cooperative repressors of a network of tumor suppressor genes that included PDCD4, BTG2, and NEDD4L. Inhibition of MIR21, MIR23A, and MIR27A had synergistic effects in reducing proliferation of PDAC cells in culture and growth of xenograft tumors in mice. The level of inhibition was greater than that of inhibition of MIR21 alone. In 91 PDAC samples from patients, high levels of a combination of MIR21, MIR23A, and MIR27A were associated with shorter survival times after surgical resection. CONCLUSIONS: In an integrated data analysis, we identified functional miRNA-mRNA interactions that contribute to growth of PDACs. These findings indicate that miRNAs act together to promote tumor progression; therapeutic strategies might require inhibition of several miRNAs.

Pancreatic cancer: current understanding of molecular and genetic aetiologies.

Pancreatic ductal adenocarcinoma (PDAC) is one of the few cancers where prognosis has not improved over the past few decades. However, there have been several advances in our understanding of the disease leading to earlier detection and targeted therapeutic treatment. It is now understood that specific somatic and germline mutations lead to the development of the disease, and the risk factors associated with this are clearer. Further, several precursor lesions have been identified which, with early detection and surveillance, allows treatment before the development of carcinoma. PDAC can now be diagnosed with a high sensitivity and specificity following advances in radiology, and treatment can be commenced at an earlier stage of the disease. With continued research we are hopeful that the next decade will see an improved survival rate for all patients with pancreatic cancer.

Pancreatic cancer: current management and treatment strategies.

The 5-year survival of patients with pancreatic cancer is poor and, despite oncological advances over the past two decades, has not significantly improved. However, there have been several surgical and oncological advances which have improved morbidity and mortality in surgery and more efficacious chemotherapy regimens, resulting in a better patient experience and an increase in survival by a number of months. Most patients have a tumour at the head of the pancreas and those with resectable disease undergo a pancreaticoduodenectomy, which can be performed laparoscopically. Those who have a pancreatic resection have an increased survival in comparison with those receiving oncological treatment only; however, only a quarter of patients have resectable disease at diagnosis. Some centres are now performing venous resections and/or arterial resections in order to increase the number of patients eligible for curative surgery. Innovative techniques using ablation technologies to downstage tumours for resection are also being investigated. After surgery, all patients should be offered adjuvant gemcitabine-based chemotherapy. Those with locally advanced tumours not suitable for surgery should be offered FOLFIRINOX chemotherapy, after which the tumour may be suitable for surgical resection. The use of radiotherapy in this group of patients is controversial but offered by a few centres. Patients with metastatic disease at diagnosis should also be offered FOLFIRINOX chemotherapy, which can improve survival by a few months. As our knowledge of the tumour biology of pancreatic cancer progresses, a number of new agents targeting specific genes and proteins are under investigation and there is hope that median survival will continue to improve over the next decade.

Is there a 'margin' for error in pancreatic cancer surgery?

Evaluation of: Gnerlich JL, Luka SR, Deshpande AD et al. Microscopic margins and patterns of treatment failure in resected pancreatic adenocarcinoma. Arch. Surg. 147(8), 753-760 (2012). Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with one of the worst 5-year survival rates of any malignancy. Even after potentially curative surgical resection, disease may progress rapidly. It is therefore important to identify clinicopathologic factors that influence survival and may be modified to improve outcomes. The evaluated article presents data from a retrospective review of patients who underwent surgical resection for PDAC. Local recurrence (LR), distant recurrence and survival were compared between patients with a negative resection margin (R0) and those with a positive resection margin (R1). Patients with R1 posterior margins, in particular, were more likely to have LR and worse LR-free survival. In addition, this was more pronounced if patients had lymph-node involvement. Similar results have been reported in other studies and this study illustrates that standardized pathological reporting of PDAC specimens may allow further investigation of factors affecting R1 patients.

Cell-free DNA for the detection of pancreatic, liver and upper gastrointestinal cancers: has progress been made?

Detecting alterations in blood cell-free DNA (cfDNA) is hoped to be a novel, noninvasive method for diagnosing, prognosing and monitoring cancer patients. Several studies have assessed the usefulness of measuring tumor-specific genetic and epigenetic changes of cfDNA, such as loss of heterozygosity, frequency of mutations, alterations of microsatellites and the methylation of genes in patient blood samples. However, few well-designed trials have been carried out to translate these findings effectively. In this review, we have assessed the clinical utility of cfDNA in pancreatic, liver and upper gastrointestinal malignancies.

Reactive lymphoid hyperplasia of the pancreas: a clinical conundrum.

CONTEXT: Localized reactive lymphoid hyperplasia is a rare condition characterized by the presence of lymphoid follicles. CASE REPORT: We describe a case of a 60-year-old woman who presented with right upper quadrant pain and was found to have a reactive nodular hyperplasia of the pancreas involving the uncinate process, body and tail of the gland. Due to the multifocal distribution of these hypoechoic vascular lesions, a total pancreatectomy was performed since malignancy could not be safely excluded. CONCLUSION: There have been a handful of cases reporting reactive lymphoid hyperplasia affecting the pancreas; however, it is uncommon to perform such a radical pancreatic resection for this benign condition.

The Atlantic divide: contrasting surgical robotics training in the USA, UK and Ireland.

The uptake of robotic surgery is rapidly increasing worldwide across surgical specialties. However, there is currently a much higher use of robotic surgery in the United States of America (USA) compared to the United Kingdom (UK) and Ireland. Reduced exposure to robotic surgery in training may lead to longer learning curves and worse patient outcomes. We aimed to identify whether any difference exists in exposure to robotic surgery during general surgical training between trainees in the USA, UK and Ireland. Over a 15-week period from September 2021, a survey was distributed through the professional networks of the research team. Participants were USA, UK or Irish trainees who were part of a formal general surgical training curriculum. 116 survey responses were received. US trainees (n = 34) had all had robotic simulator experience, compared to only 37.93% of UK (n = 58) and 75.00% of Irish (n = 24) trainees (p < 0.00001). 91.18% of US trainees had performed 15 or more cases as the console surgeon, compared to only 3.44% of UK and 16.67% of Irish trainees (p < 0.00001). Fifty UK trainees (86.21%) and 22 Irish trainees (91.67%) compared to 12 US trainees (35.29%) do not think they have had adequate robotics training (p < 0.00001). Surgical trainees in the USA have had significantly more exposure to training in robotic surgery than their UK and Irish counterparts.

Robotic Distal Pancreatectomy Yields Superior Outcomes Compared to Laparoscopic Technique: A Single Surgeon Experience of 123 Consecutive Cases.

Technical limitations of laparoscopic distal pancreatectomy (LDP), in comparison to robotic distal pancreatectomy (RDP), may translate to high conversion rates and morbidity. LDP and RDP procedures performed between December 2008 and January 2023 in our tertiary referral hepatobiliary and pancreatic centres were analysed and compared with regard to short-term outcomes. A total of 62 consecutive LDP cases and 61 RDP cases were performed. There was more conversion to open surgeries in the laparoscopic group compared with the robotic group (21.0% vs. 1.6%, p = 0.001). The LDP group also had a higher rate of postoperative complications (43.5% vs. 23.0%, p = 0.005). However, there was no significant difference between the two groups in terms of major complication or pancreatic fistular after operations (p = 0.20 and p = 0.71, respectively). For planned spleen-preserving operations, the RDP group had a shorter mean operative time (147 min vs. 194 min, p = 0.015) and a reduced total length of hospital stay compared with the LDP group (4 days vs. 7 days, p = 0.0002). The failure rate for spleen preservation was 0% in RDP and 20% (n = 5/25) in the LDP group (p = 0.009). RDP offered a better method for splenic preservation with Kimura's technique compared with LDP to avoid the risk of splenic infarction and gastric varices related to ligation and division of splenic pedicles. RDP should be the standard operation for the resection of pancreatic tumours at the body and tail of the pancreas without involving the celiac axis or common hepatic artery.

Artificial intelligence in the detection, characterisation and prediction of hepatocellular carcinoma: a narrative review.

Hepatocellular carcinoma (HCC) is a significant cause of morbidity and mortality worldwide. Despite significant advancements in detection and treatment of HCC, its management remains a challenge. Artificial intelligence (AI) has played a role in medicine for several decades, however, clinically applicable AI-driven solutions have only started to emerge, due to gradual improvement in sensitivity and specificity of AI, and implementation of convoluted neural networks. A review of the existing literature has been conducted to determine the role of AI in HCC, and three main domains were identified in the search: detection, characterisation and prediction. Implementation of AI models into detection of HCC has immense potential, as AI excels at analysis and integration of large datasets. The use of biomarkers, with the rise of '-omics', can revolutionise the detection of HCC. Tumour characterisation (differentiation between benign masses, HCC, and other malignant tumours, as well as staging and grading) using AI was shown to be superior to classical statistical methods, based on radiological and pathological images. Finally, AI solutions for predicting treatment outcomes and survival emerged in recent years with the potential to shape future HCC guidelines. These AI algorithms based on a combination of clinical data and imaging-extracted features can also support clinical decision making, especially treatment choice. However, AI research on HCC has several limitations, hindering its clinical adoption; small sample size, single-centre data collection, lack of collaboration and transparency, lack of external validation, and model overfitting all results in low generalisability of the results that currently exist. AI has potential to revolutionise detection, characterisation and prediction of HCC, however, for AI solutions to reach widespread clinical adoption, interdisciplinary collaboration is needed, to foster an environment in which AI solutions can be further improved, validated and included in treatment algorithms. In conclusion, AI has a multifaceted role in HCC across all aspects of the disease and its importance can increase in the near future, as more sophisticated technologies emerge.

Hepatic epithelioid hemangioendothelioma (HEHE)-rare vascular malignancy mimicking cholangiocarcinoma: a case report.

Hepatic epithelioid hemangioendothelioma (HEHE) is a rare, often misdiagnosed malignancy of vascular origin. We describe a case of a 36-year-old, who presented with a burning sensation in his chest on exercise and was believed to have bilobar intrahepatic cholangiocarcinoma. After receiving chemotherapy with partial response, the patient underwent staged resection with modified associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) procedure-laparoscopic radiofrequency-assisted ALPPS (RALPPS). Histological examination of the stage 1 specimen revealed HEHE deposits in the left lobe of the liver. The patient proceeded to have stage 2 open right hepatectomy with concurring histology. Ninety-day follow-up computed tomography scan showed almost complete resolution of HEHE lesions. Low incidence, non-specific clinical and radiological characteristics all contribute to high HEHE misdiagnosis rate. Histological analysis can be used for confirmation of the diagnosis; however, specialist staining is required, which is not routinely performed. Multiple treatments are available against HEHE, but only liver resection and liver transplantation are potentially curative. ALPPS and its modifications (such as RALPPS) offer an alternative from conventional two-stage hepatectomy for patients with extensive bilobar HEHE, who are at risk of developing post-hepatectomy liver failure or patients with anomalous hepatic vasculature anatomy which makes portal vein embolisation (PVE) challenging.

Can we predict long-term survival in resectable pancreatic ductal adenocarcinoma?

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumour associated with poor 5-year survival. We aimed to determine factors which differentiate short and long-term survivors and identify a prognostic biomarker. METHODS: Over a ten-year period, patients with resected PDAC who developed disease recurrence within 12 months (Group I) and those who had no disease recurrence for 24 months (Group II) were identified. Clinicopathological data was analysed. Ion Torrent high-throughput sequencing on DNA extracted from FFPE tumour samples was used to identify mutations. Additionally, peripheral blood samples were analysed for variants in cell-free DNA, circulating tumour cells (CTCs), and microRNAs. RESULTS: Multivariable analysis of clinicopathological factors showed that a positive medial resection margin was significantly associated with short disease-free survival (p = 0.007). Group I patients (n = 21) had a higher frequency of the KRAS mutant mean variant allele (16.93% ± 11.04) compared to those in Group II (n = 13; 7.55% ± 5.76, p = 0.0078). Group I patients also trended towards having a KRAS c.35G>A p.Gly12Asp mutation in addition to variants in other genes, such as TP53, CDKN2A, and SMAD4. Mutational status of cell-free DNA, and number of CTCs, was not found to be useful in this study. A circulating miRNA (hsa-miR-548ah-5p) was found to be significantly differentially expressed. CONCLUSIONS: Medial resection margin status and the frequency of KRAS mutation in the tumour tissue are independent prognostic indicators for resectable PDAC. Circulating miRNA hsa-miR-548ah-5p has the potential to be used as a prognostic biomarker.

Rapid Induction of Liver Regeneration for Major Hepatectomy (REBIRTH): A Randomized Controlled Trial of Portal Vein Embolisation versus ALPPS Assisted with Radiofrequency.

To avoid liver insufficiency following major hepatic resection, portal vein embolisation (PVE) is used to induce liver hypertrophy pre-operatively. Associating liver partition with portal vein ligation for staged hepatectomy assisted with radiofrequency (RALPPS) was introduced as an alternative method. A randomized controlled trial comparing PVE with RALPPS for the pre-operative manipulation of liver volume in patients with a future liver remnant volume (FLRV) ≤25% (or ≤35% if receiving preoperative chemotherapy) was conducted. The primary endpoint was increase in size of the FLRV. The secondary endpoints were length of time taken for the volume gain, morbidity, operation length and post-operative liver function. Between July 2015 and October 2017, 57 patients were randomised to RALPPS (n = 29) and PVE (n = 28). The mean percentage of increase in the FLRV was 80.7 ± 13.7% after a median 20 days following RALPPS compared to 18.4 ± 9.8% after 35 days (p < 0.001) following PVE. Twenty-four patients after RALPPS and 21 after PVE underwent stage-2 operation. Final resection was achieved in 92.3% and 66.6% patients in RALPPS and PVE, respectively (p = 0.007). There was no difference in morbidity, and one 30-day mortality after RALPPS (p = 0.991) was reported. RALPPS is more effective than PVE in increasing FLRV and the number of patients for surgical resection.