From CySkin to ProxySKIN: Design, Implementation and Testing of a Multi-Modal Robotic Skin for Human-Robot Interaction.

The Industry 5.0 paradigm has a human-centered vision of the industrial scenario and foresees a close collaboration between humans and robots. Industrial manufacturing environments must be easily adaptable to different task requirements, possibly taking into account the ergonomics and production line flexibility. Therefore, external sensing infrastructures such as cameras and motion capture systems may not be sufficient or suitable as they limit the shop floor reconfigurability and increase setup costs. In this paper, we present the technological advancements leading to the realization of ProxySKIN, a skin-like sensory system based on networks of distributed proximity sensors and tactile sensors. This technology is designed to cover large areas of the robot body and to provide a comprehensive perception of the surrounding space. ProxySKIN architecture is built on top of CySkin, a flexible artificial skin conceived to provide robots with the sense of touch, and arrays of Time-of-Flight (ToF) sensors. We provide a characterization of the arrays of proximity sensors and we motivate the design choices that lead to ProxySKIN, analyzing the effects of light interference on a ToF, due to the activity of other sensing devices. The obtained results show that a large number of proximity sensors can be embedded in our distributed sensing architecture and incorporated onto the body of a robotic platform, opening new scenarios for complex applications.

Unraveling Biomarker Signatures in Triple-Negative Breast Cancer: A Systematic Review for Targeted Approaches.

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, marked by poor outcomes and dismal prognosis. Due to the absence of targetable receptors, chemotherapy still represents the main therapeutic option. Therefore, current research is now focusing on understanding the specific molecular pathways implicated in TNBC, in order to identify novel biomarker signatures and develop targeted therapies able to improve its clinical management. With the aim of identifying novel molecular features characterizing TNBC, elucidating the mechanisms by which these molecular biomarkers are implicated in the tumor development and progression, and assessing the impact on cancerous cells following their inhibition or modulation, we conducted a literature search from the earliest works to December 2023 on PubMed, Scopus, and Web Of Science. A total of 146 studies were selected. The results obtained demonstrated that TNBC is characterized by a heterogeneous molecular profile. Several biomarkers have proven not only to be characteristic of TNBC but also to serve as potential effective therapeutic targets, holding the promise of a new era of personalized treatments able to improve its prognosis. The pre-clinical findings that have emerged from our systematic review set the stage for further investigation in forthcoming clinical trials.

New Frontiers in Pancreatic Cancer Management: Current Treatment Options and the Emerging Role of Neoadjuvant Therapy.

Pancreatic ductal adenocarcinoma (PDAC) ranks among the 15 most prevalent cancers globally, characterized by aggressive growth and late-stage diagnosis. Advances in imaging and surgical techniques have redefined the classification of pancreatic PDAC into resectable, borderline resectable, and locally advanced pancreatic cancer. While surgery remains the most effective treatment, only 20% of patients are eligible at diagnosis, necessitating innovative strategies to improve outcomes. Therefore, traditional treatment paradigms, primarily surgical resection for eligible patients, are increasingly supplemented by neoadjuvant therapies (NAT), which include chemotherapy, radiotherapy, or a combination of both. By administering systemic therapy prior to surgery, NAT aims to reduce tumor size and increase the feasibility of complete surgical resection, thus enhancing overall survival rates and potentially allowing more patients to undergo curative surgeries. Recent advances in treatment protocols, such as FOLFIRINOX and gemcitabine-nab-paclitaxel, now integral to NAT strategies, have shown promising results in increasing the proportion of patients eligible for surgery by effectively reducing tumor size and addressing micrometastatic disease. Additionally, they offer improved response rates and survival benefits compared to traditional regimes. Despite these advancements, the role of NAT continues to evolve, necessitating ongoing research to optimize treatment regimens, minimize adverse effects, and identify patient populations that would benefit most from these approaches. Through a detailed analysis of current literature and recent clinical trials, this review highlights the transformative potential of NAT in managing PDAC, especially in patients with borderline resectable or locally advanced stages, promising a shift towards more personalized and effective management strategies for PDAC.

Perioperative interventions to reduce pancreatic fistula following pancreatoduodenectomy: meta-analysis.

BACKGROUND: Data on interventions to reduce postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD) are conflicting. The aim of this study was to assimilate data from RCTs. METHODS: MEDLINE and Embase databases were searched systematically for RCTs evaluating interventions to reduce all grades of POPF or clinically relevant (CR) POPF after PD. Meta-analysis was undertaken for interventions investigated in multiple studies. A post hoc analysis of negative RCTs assessed whether these had appropriate statistical power. RESULTS: Among 22 interventions (7512 patients, 55 studies), 12 were assessed by multiple studies, and subjected to meta-analysis. Of these, external pancreatic duct drainage was the only intervention associated with reduced rates of both CR-POPF (odds ratio (OR) 0.40, 95 per cent c.i. 0.20 to 0.80) and all-POPF (OR 0.42, 0.25 to 0.70). Ulinastatin was associated with reduced rates of CR-POPF (OR 0.24, 0.06 to 0.93). Invagination (versus duct-to-mucosa) pancreatojejunostomy was associated with reduced rates of all-POPF (OR 0.60, 0.40 to 0.90). Most negative RCTs were found to be underpowered, with post hoc power calculations indicating that interventions would need to reduce the POPF rate to 1 per cent or less in order to achieve 80 per cent power in 16 of 34 (all-POPF) and 19 of 25 (CR-POPF) studies respectively. CONCLUSION: This meta-analysis supports a role for several interventions to reduce POPF after PD. RCTs in this field were often relatively small and underpowered, especially those evaluating CR-POPF.

High Values of Drain Fluid Epidermal Growth Factor and Transforming Growth Factor-Beta Are Associated with the Development of Pancreatic Fistula after Pancreatoduodenectomy.

INTRODUCTION: Postoperative inflammatory response may act as a major determinant of anastomotic failure after pancreaticoduodenectomy. In this pilot study, we investigated the potential role of drain fluid cytokines in predicting postoperative pancreatic fistula (POPF). METHODS: Drain fluid TGF-ß, IGF-1, EGF, and IL-6, together with serum amylase and drain fluid amylase, were measured on POD1 and correlated with the development of POPF. RESULTS: The study population consisted of 66 patients. POPF and Clavien-Dindo ≥3 morbidity rates were 12.1% and 9.1%, respectively. Patients developing POPF presented significantly higher values of POD1 serum amylase level (477 vs. 54 UI/L, p < 0.001), drain fluid amylase (7,500 vs. 127 UI/L, p < 0.001), TGFß (94 vs. 40 pg/g, p = 0.045), and EGF (17 vs. 13, p = 0.015). There were no differences in terms of IGF-1 and IL-6 values. CONCLUSION: Assessing the local inflammatory response after pancreatoduodenectomy could represent a promising field of research since both TGFß and EGF seem to be associated with the occurrence of POPF.

External validation of postoperative pancreatic fistula prediction scores in pancreatoduodenectomy: a systematic review and meta-analysis.

BACKGROUND: Multiple risk scores claim to predict the probability of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy. It is unclear which scores have undergone external validation and are the most accurate. The aim of this study was to identify risk scores for POPF, and assess the clinical validity of these scores. METHODS: Areas under receiving operator characteristic curve (AUROCs) were extracted from studies that performed external validation of POPF risk scores. These were pooled for each risk score, using intercept-only random-effects meta-regression models. RESULTS: Systematic review identified 34 risk scores, of which six had been subjected to external validation, and so included in the meta-analysis, (Tokyo (N=2 validation studies), Birmingham (N=5), FRS (N=19), a-FRS (N=12), m-FRS (N=3) and ua-FRS (N=3) scores). Overall predictive accuracies were similar for all six scores, with pooled AUROCs of 0.61, 0.70, 0.71, 0.70, 0.70 and 0.72, respectively. Considerably heterogeneity was observed, with I2 statistics ranging from 52.1-88.6%. CONCLUSION: Most risk scores lack external validation; where this was performed, risk scores were found to have limited predictive accuracy. . Consensus is needed for which score to use in clinical practice. Due to the limited predictive accuracy, future studies to derive a more accurate risk score are warranted.

Risk factors to differentiate between benign proximal biliary strictures and perihilar cholangiocarcinoma.

BACKGROUND: The aim of this study was to evaluate potential risk factors associated with benign lesions and perihilar cholangiocarcinoma (PHC) in patients presenting with proximal biliary strictures (PBS). METHODS: Patients with PBS who were referred to a specialist HPB centre between 2008 and 2016 were identified. Patients with primary sclerosing cholangitis, metastatic PHC or hilar obstruction by a peripheral tumour were excluded. The final diagnosis was determined either by (1) resection histology or (2) combination of biopsy and clinical course. Multivariable analysis of clinical, laboratory and radiological data was undertaken to identify independent predictors of benign and malignant lesions. RESULTS: 155 consecutive patients were identified, including 25 patients (16%) with benign PBS. Abdominal pain (odds ratio [OR] 3.36; p = 0.027), serum CA19.9 < 100 U/ml (OR 10.35; p = 0.001), and absence of mass on imaging (OR 4.66; p = 0.004) were all associated with the presence of benign lesions on multivariable analysis. CONCLUSIONS: This study has identified several independent variables that may differentiate between benign and malignant proximal biliary strictures. A larger multi-institutional study would be warranted to validate these findings, and to develop a risk score to stratify patients with suspected PHC.

Laparoscopic right posterior sectionectomy (LRPS): surgical techniques and clinical outcomes.

BACKGROUND: Right posterior sectionectomy is one of the most technically challenging laparoscopic liver resections. Currently, there is limited published data regarding the technique and results required to better understand its safety and feasibility. AIM: To report our experience, results and techniques, highlighting a variety of tips and tricks to facilitate this resection. A video is attached for technical demonstration. METHODS: Retrospective review of prospectively maintained databases from June 2006 to June 2016. Three different techniques were used: resection following hilar inflow control, inflow control at Rouviere's sulcus and resection with intra parenchymal control. RESULTS: 29 LRPS were performed over a 10-year period. Median operative time was 240 min (150-480). Pringle's manoeuvre was performed in 19 (65.5%) with a median total duration of 35 (20-75) min. Median perioperative blood loss was 600 (100-2500) ml. Additional liver resections were performed in 16 (55.1%). There were two(6.9%) laparoscopic to open conversions. Median postoperative hospital stay was 5 (2-30) days. The median size of the tumour resected was 25 (10-54) mm with median number of resected lesions were 2 (1-4), median free resection margin was 9.5 (1-45) mm, margins were infiltrated (R1) in two (6.7%) cases. There was one death within 30-days (3.4%). CONCLUSION: LRPS is feasible, efficient and safe. However, it is a technically challenging procedure and requires advance skills in liver and laparoscopic surgery. Surgeons should be familiar with a variety of approaches as each offers different advantages depending on the location and nature of the lesion, surgical preference and intraoperative findings.

Clinical impact of the updated international postoperative pancreatic fistula definition in distal pancreatectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) remains the most common complication after distal pancreatectomy. The International Study Group on Pancreatic Surgery definition of POPF is used worldwide. Recently, an update of the definition was published. The aim of this study was to determine the clinical impact of the update. METHODS: An international retrospective validation study, including patients who underwent DP (2005 -2016) in 5 centers was performed. Distribution of complications amongst POPF grades were compared for the old and updated definition. RESULTS: In total, 1089 patients were included. The incidence of POPF decreased with the updated definition from 47% to 24% (P < 0.01), largely because a downgrade of grade A and grade B into biochemical leak. Comparable morbidity was seen in the old and updated 'no POPF group' (Clavien -Dindo 3 5% vs. 6% P = 0.320 and hospital stay (7 vs. 7 days P = 0.301). The change in definition of POPF grade B resulted in more Clavien -Dindo 3 (38% vs. 51%) P < 0.01) and longer hospital stay (9 [9 -13] vs. 9 days [7 -15] P < 0.01) in the updated `grade B group'. CONCLUSION: Applying the updated POPF definition showed improved discrimination between grades and should therefore be used to report POPF after DP.

Effects of dietary components on cancer of the digestive system.

Cancer is the second leading cause of death in developed countries and poor diet and physical inactivity are major risk factors in cancer-related deaths. Therefore, interventions to reduce levels of smoking, improve diet, and increase physical activity must become much higher priorities in the general population's health and health care systems. The consumption of fruit and vegetables exerts a preventive effect towards cancer and in recent years natural dietary agents have attracted great attention in the scientific community and among the general public. Foods, such as tomatoes, olive oil, broccoli, garlic, onions, berries, soy bean, honey, tea, aloe vera, grapes, rosemary, basil, chili peppers, carrots, pomegranate, and curcuma contain active components that can influence the initiation and the progression of carcinogenesis, acting on pathways implied in cell proliferation, apoptosis and metastasis. The present review illustrates the main foods and their active components, including their antioxidant, cytotoxic, and pro-apoptotic properties, with a particular focus on the evidence related to cancers of the digestive system.

Exploring the Multifaceted Landscape of MASLD: A Comprehensive Synthesis of Recent Studies, from Pathophysiology to Organoids and Beyond.

Non-alcoholic fatty liver disease (NAFLD) is a widespread contributor to chronic liver disease globally. A recent consensus on renaming liver disease was established, and metabolic dysfunction-associated steatotic liver disease, MASLD, was chosen as the replacement for NAFLD. The disease's range extends from the less severe MASLD, previously known as non-alcoholic fatty liver (NAFL), to the more intense metabolic dysfunction-associated steatohepatitis (MASH), previously known as non-alcoholic steatohepatitis (NASH), characterized by inflammation and apoptosis. This research project endeavors to comprehensively synthesize the most recent studies on MASLD, encompassing a wide spectrum of topics such as pathophysiology, risk factors, dietary influences, lifestyle management, genetics, epigenetics, therapeutic approaches, and the prospective trajectory of MASLD, particularly exploring its connection with organoids.

Use of Fluorescence Imaging in Liver Transplant Surgery.

Liver transplant surgery is a complex procedure that demands high knowledge of surgical anatomy and the precise recognition and preservation of structures. To address this, the use of fluorescence imaging has facilitated the identification of anatomical structures such as biliary ducts, arteries, and liver segmentation. Indocyanine green is among the most commonly utilized fluorescent agents, not just during surgery but also in the pre- and postoperative phases, where it is used to assess graft failure by measuring the plasma disappearance rate. New advancements such as artificial intelligence paired with fluorescence imaging have the potential to enhance patient outcomes. Additionally, technologies such as augmented reality and mixed reality could be integrated into surgical procedures, broadening the scope of possibilities for improving patient safety.

Robotic Vascular Resection in Pancreatic Ductal Adenocarcinoma: A Systematic Review.

(1) Background: This study comprehensively compared robotic pancreatic surgery with vascular resection (RPS-VR) to other surgical procedures in the treatment of pancreatic ductal adenocarcinoma (PDAC). (2) Methods: A systematic review of relevant literature was conducted to assess a range of crucial surgical and oncological outcomes. (3) Results: Findings indicate that robotic surgery with vascular resections (VRs) significantly prolongs the duration of surgery compared to other surgical procedures, and they notably demonstrate an equal hospital stay. While some studies reported a lower conversion rate and a higher rate of blood loss and blood transfusion in the RPS-VR group, others found no significant disparity. Furthermore, RPS-VR consistently correlated with comparable recurrence rates, free margins R0, postoperative mortality, and complication rates. Concerning the last one, certain reviews reported a higher rate of major complications. Overall survival and disease-free survival remained comparable between the RPS-VR and other surgical techniques in treating PDAC. (4) Conclusions: The analysis emphasizes how RPS-VR is a resembling approach in terms of surgical outcomes and aligns with existing literature findings in this field.

Liver transplantation vs liver resection in HCC: promoting extensive collaborative research through a survival meta-analysis of meta-analyses.

Background: HCC is a major global health concern, necessitating effective treatment strategies. This study conducts a meta-analysis of meta-analyses comparing liver resection (LR) and liver transplantation (LT) for HCC. Methods: The systematic review included meta-analyses comparing liver resection vs. liver transplantation in HCC, following PRISMA guidelines. Primary outcomes included 5-year overall survival (OS) and disease-free survival (DFS). AMSTAR-2 assessed study quality. Citation matrix and hierarchical clustering validated the consistency of the included studies. Results: A search identified 10 meta-analyses for inclusion. The median Pearson correlation coefficient for citations was 0.59 (IQR 0.41-0.65). LT showed better 5-year survival and disease-free survival in all HCC (OR): 0.79; 95% CI: 0.67-0.93, I^2:57% and OR: 0.44; 95% CI: 0.25-0.75, I^2:96%). Five-year survival in early HCC and ITT was 0.63 (95% CI: 0.50-0.78, I^2:0%) and 0.60 (95% CI: 0.39-0.92, I^2:0%). Salvage LT vs. Primary LT did not differ between 5-year survival and disease-free survival (OR: 0.62; 95% CI: 0.33-1.15, I^2:0% and 0.93; 95% CI: 0.82-1.04, I^2:0%). Conclusion: Overall, the study underscores the superior survival outcomes associated with LT over LR in HCC treatment, supported by comprehensive meta-analysis and clustering analysis. There was no difference in survival or recurrence rate between salvage LT and primary LT. Therefore, considering the organ shortage, HCC can be resected and transplanted in case of recurrence.

Surgical Resection in Colorectal Liver Metastasis: An Umbrella Review.

Surgical resection is the gold standard for treating synchronous colorectal liver metastases (CRLM). The resection of the primary tumor and metastatic lesions can follow different sequences: "simultaneous", "bowel-first", and "liver-first". Conservative approaches, such as parenchymal-sparing surgery and segmentectomy, may serve as alternatives to major hepatectomy. A comprehensive search of Medline, Epistemonikos, Scopus, and the Cochrane Library was conducted. Studies evaluating patients who underwent surgery for CRLM and reported survival results were included. Other secondary outcomes were analyzed, including disease-free survival, perioperative complications and mortality, and recurrence rates. Quality assessment was performed using the AMSTAR-2 method. No significant differences in overall survival, disease-free survival, and secondary outcomes were observed when comparing simultaneous to "bowel-first" resections, despite a higher rate of perioperative mortality in the former group. The 5-year OS was significantly higher for simultaneous resection compared to "liver-first" resection. No significant differences in OS and DFS were noted when comparing "liver-first" to "bowel-first" resection, or anatomic to non-anatomic resection. Our umbrella review validates simultaneous surgery as an effective oncological approach for treating SCRLM, though the increased risk of perioperative morbidity highlights the importance of selecting suitable patients. Non-anatomic resections might be favored to preserve liver function and enable future surgical interventions.

Laparoscopic versus open liver resection for colorectal liver metastasis: an umbrella review.

Introduction: This study comprehensively compared laparoscopic liver resection (LLR) to open liver resection (OLR) in treating colorectal cancer liver metastasis (CRLM). Methods: A systematic review of relevant literature was conducted to assess a range of crucial surgical and oncological outcomes. Results: Findings indicate that minimally invasive surgery (MIS) did not significantly prolong the duration of surgery compared to open liver resection and notably demonstrated lower blood transfusion rates and reduced intraoperative blood loss. While some studies favored MIS for its lower complication rates, others did not establish a statistically significant difference. One study identified a lower post-operative mortality rate in the MIS group. Furthermore, MIS consistently correlated with shorter hospital stays, indicative of expedited post-operative recovery. Concerning oncological outcomes, while certain meta-analyses reported a lower rate of cancer recurrence in the MIS group, others found no significant disparity. Overall survival and disease-free survival remained comparable between the MIS and open liver resection groups. Conclusion: The analysis emphasizes the potential advantages of LLR in terms of surgical outcomes and aligns with existing literature findings in this field. Systematic review registration: [website], identifier [registration number].

MicroRNA from pancreatic duct aspirate differentiates cystic lesions of the pancreas.

INTRODUCTION: Prognostication for cystic neoplasms of the pancreas continues to evolve. Beyond simple size and cystic fluid CEA determination, microRNA (miRNA) detection holds great promise as molecular diagnostics for cancer risk. In this study, we sought to identify miRNAs that could predict malignant potential of pancreatic cystic lesions. METHODS: RNA was harvested from the pancreatic duct aspirate of 72 cystic neoplasms of the pancreas. Samples with adequate RNA concentration (≥ 3 ng/µL) were selected for qRTPCR profiling using assays to 379 of the most common miRNAs. miRNA profiles were correlated with histopathology from resected specimens and grouped by benign (serous cystadenomas), premalignant (intraductal papillary mucinous neoplasms and mucinous cystadenomas), or malignant lesions (adenocarcinoma). RESULTS: Adequate RNA for analysis was obtained from 42 (58.3 %) of the samples. Malignant lesions were more likely to have adequate RNA (n = 17, 81 %) than either benign (n = 6, 33 %) or premalignant lesions (n = 19, 59 %; p = 0.011). Nine miRNA were identified as differentially expressed between benign and premalignant/malignant lesions (p < 0.05). A significant correlation was found between the number of differentially expressed miRNA and the likelihood of a premalignant/malignant lesion. All premalignant or malignant lesions expressed at least one miRNA surpassing the threshold of mean miRNA expression, whereas no benign lesions had more than one miRNA surpassing the threshold. CONCLUSIONS: The presence of RNA in the duct aspirate from patients with pancreatic cystic neoplasms may be a predictor of premalignancy or malignancy. miRNA may be utilized to further differentiate between benign, premalignant, and malignant cystic lesions of the pancreas.

The Role of mTOR Inhibitors after Liver Transplantation for Hepatocellular Carcinoma.

Liver transplantation is a treatment option for nonresectable patients with early-stage HCC, with more significant advantages when Milan criteria are fulfilled. An immunosuppressive regimen is required to reduce the risk of graft rejection after transplantation, and CNIs represent the drugs of choice in this setting. However, their inhibitory effect on T-cell activity accounts for a higher risk of tumour regrowth. mTOR inhibitors (mTORi) have been introduced as an alternative immunosuppressive approach to conventional CNI-based regimens to address both immunosuppression and cancer control. The PI3K-AKT-mTOR signalling pathway regulates protein translation, cell growth, and metabolism, and the pathway is frequently deregulated in human tumours. Several studies have suggested the role of mTORi in reducing HCC progression after LT, accounting for a lower recurrence rate. Furthermore, mTOR immunosuppression controls the renal damage associated with CNI exposure. Conversion to mTOR inhibitors is associated with stabilizing and recovering renal dysfunction, suggesting an essential renoprotective effect. Limitations in this therapeutic approach are related to their negative impact on lipid and glucose metabolism as well as on proteinuria development and wound healing. This review aims to summarize the roles of mTORi in managing patients with HCC undergoing LT. Strategies to overcome common adverse effects are also proposed.

Age and liver graft: a systematic review with meta-regression.

Increasing organ shortage results in extended criteria donors (ECD) being used to face the growing demand for liver grafts. The demographic change leads to greater use of elderly donors for liver transplantation, historically considered marginal donors. Age is still considered amongst ECD in liver transplantation as it could affect transplant outcomes. However, what is the cutoff for donor age is still unclear and debated. A search of PubMed, Scopus and Cochrane Library was performed. The primary outcome was 1-year graft survival (GS). The secondary outcome was overall biliary complications and 3-5 years of graft and overall survival. A meta-regression model was used to analyse the temporal trend relation in the survival outcome. The meta-analysis included 11 studies. Hazard ratios for 1-year (age cutoff of 70 and 80,) and 5-year GS (I2:0%) were similar irrespectively of the age group. The meta-regression analysis showed a significant correlation between the 1-year graft survival and the year of publication. (coef. 0.00027, 95% CI - 0.0001 to - 0.0003 p = 0.0009). Advanced-age donors showed an increased risk of overall biliary complications with an odd ratio (OR) of 1.89 (95% CI 1-3.65). Liver grafts potentially discharged because of high-risk failure show encouraging results, and GS in ECD has progressively improved with a temporal trend. Currently, the criteria of marginality vary amongst centres. Age alone cannot be considered amongst the extended criteria. First of all, because of the positive results in terms of septuagenarian graft survival. Moreover, the potential elderly donor-related adjunctive risk can be balanced by reducing other risk factors. A prospective multicentre study should investigate a multi-factorial model based on donor criteria, recipient features and new functional biomarkers to predict graft outcome, as proper donor-recipient matching seems to be the critical point for good outcomes.