Postoperative lymphopaenia as a risk factor for postoperative infections in cancer surgery: A prospective multicentre cohort study (the EVALYMPH study).

BACKGROUND: Stress due to surgical trauma decreases postoperative lymphocyte counts (LCs), potentially favouring the occurrence of postoperative infections (PIs). OBJECTIVES: We aimed to determine whether postoperative lymphopaenia following thoracic or gastrointestinal cancer surgery is an independent risk factor for PIs and to identify modifiable factors related to anaesthesia and surgical procedures that might affect its occurrence. STUDY DESIGN: The EVALYMPH study was a prospective, multicentre cohort study with a 30-day patient follow-up. Multivariate analyses were performed to determine the risk factors for PIs and for postoperative lymphopaenia. SETTING: Patients were included from January 2016 to September 2017 in 25 French centres. PATIENTS: Adult patients admitted for thoracic or gastrointestinal cancer surgery were eligible for inclusion. MAIN OUTCOME MEASURE: PIs within 30 days after surgery were defined as urinary tract infections, pneumonia, surgical site infections and other infections (bloodstream infections or pleurisy). RESULTS: Of 1207 patients included, 273 (22.6%) developed at least one infection within 30 days after surgery, with a median [IQR] time to onset of 8 [5 to 11] days. An increased risk of PI was significantly associated with an ASA score of IV: hazard ratio (HR) 4.27 (95% confidence interval (CI), 1.87 to 9.72), surgery > 200 min (HR 1.58 (1.15 to 2.17) and lymphopaenia on postoperative day 1 (POD1) (HR 1.56 (1.08 to 2.25). This risk was associated with changes in postoperative LC over time (P = 0.001) but not with preoperative LC (P = 0.536).POD1 lymphopenia was related to patient characteristics and duration of surgery but not to potentially modifiable other surgical or anaesthetics factors. CONCLUSIONS: POD1 lymphopaenia was associated with PIs in patients undergoing thoracic or gastrointestinal cancer surgery. To individualise care, patient characteristics and surgery duration should be taken into account. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02799251.

Heavy metal in radiation therapy: A simple method to differentiate hip prosthesis materials.

BACKGROUND: In recent years, the number of hip replacement patients receiving radiation therapy has steadily increased. In parallel, strategies have been developed to reduce metal artifacts in computed tomography (CT) images and improve the accuracy of dose calculation algorithms. However, in certain situations, knowledge of the type of prosthesis material is required to accurately determine the dose distribution. PURPOSE: This study aims to identify physical materials in hip prostheses to correctly assign them in the treatment planning system and improve dose calculation accuracy. METHODS: We first verified the validity of the extended CT mass density calibration curve measured on titanium (Ti) and stainless steel (SS) metal inserts of two different diameters. Then using dedicated reference objects of various circular diameters, we developed a method based on interpolation functions to differentiate between Ti and SS material groups. Forty data sets from 18 patients were used to validate our method on two different reconstruction kernels: a standard Br44f and the electron DirectDensity (Sd40f) kernels from Siemens. RESULTS: Hounsfield units (HU) of Ti and SS inserts were found to vary widely depending on insert diameter, CT spectrum, and reconstruction kernels due to cupping artifacts. The largest HU difference (-79%) was obtained for SS at 70 kV with Br44f when the diameter increased from 8 to 30 mm. Therefore, under these conditions, the extended CT-density calibration curve is not recommended for heavy metal density determination. Using our interpolation-based method, we achieved excellent detection (100%) and material differentiation (100%) results for stems in both reconstruction kernels. At CT energies between 110 and 140 kV, the detection and material differentiation rates were 93.3% and 92.9% for the heads and 93.3% and 92.9% for the acetabular cups, respectively, with the Br44f. Similarly, the use of Sd40f resulted in detection and differentiation rates of 94.7% and 100% for the heads and 100% and 95.0% for the acetabular cups, respectively. CONCLUSION: This method makes it possible to differentiate between hip prosthesis materials and correctly assign them to the Ti or SS group without prior knowledge of the prosthesis type, regardless of the reconstruction kernels. In combination with the Acuros XB (Varian) or Monte Carlo dose algorithms, excellent dosimetric accuracy can be achieved even in the vicinity of hip prostheses. By performing basic measurements, the method can be adapted to other CT units and reconstruction kernels, replacing the use of an extended CT-density calibration curve.

Milestones in Surgical Complication Reporting: Clavien-Dindo Classification 20 Years and Comprehensive Complication Index 10 Years.

OBJECTIVE: To provide improved guidance for the consistent application of the Clavien-Dindo classification (CDC) and Comprehensive Complication Index (CCI ® ) in challenging clinical scenarios. BACKGROUND: Standardized outcome reporting is key for the proper assessment of surgical procedures. A recent consensus conference recommended the CDC and the CCI ® for assessing postoperative morbidity. Several challenging scenarios for grading complications still require evidence-based guidance, and the use of the 2 metrics in randomized controlled trials (RCTs) remains unexplored. METHODS: We assessed the use of the CDC and CCI ® as an outcome measure in a systematic literature search. In addition, we asked 163 international surgeons to critically evaluate and independently grade complications in 20 complex clinical scenarios. Finally, a Core Group of 5 experts used this information to develop consistent recommendations. RESULTS: Until July 2023, 1327 RCTs selected the CDC and/or CCI ® to assess morbidity. Annual use was steadily increasing with now over 200 new RCTs per year. However, only a third (n = 335) of published RCTs provided the complete range of CDC grades, including all subgrades. Eighty-nine out of 163 surgeons (response rate: 55%) completed the questionnaire that served as a basis for the recommendations: repetitive interventions that are required to treat one complication, complications followed by further complications, complications occurring before referral, and expected and unrelated complications to the original procedure should all be counted separately and included in the CCI ® . Invasive blank diagnostic interventions should not be considered a complication. CONCLUSIONS: The increasing use of the CDC and CCI ® in RCTs highlights the importance of their standardized application. The current consensus on various difficult scenarios may offer novel guidance for the consistent use of the CDC and CCI ® , aiming to improve complication reporting and better quality control, ultimately benefiting all health care stakeholders and, first and foremost, all patients.

Surgeon-Scientists Going Extinct: Last Call for Action or Too Late?

OBJECTIVE: To define the concept of surgeon-scientists and identify the root causes of their decline in number and impact. The secondary aim was to provide actionable remedies. BACKGROUND: Surgeons who conduct research in addition to patient care are referred to as "surgeon-scientists." While their value to society remains undisputed, their numbers and associated impact have been plunging. While reasons have been well identified along with proposals for countermeasures, their application has largely failed. METHODS: We conducted a systematic review covering all aspects of surgeon-scientists together with a global online survey among 141 young academic surgeons. Using gap analysis, we determined implementation gaps for proposed measures. Then, we developed a comprehensive rescue package. RESULTS: A surgeon-scientist must actively and continuously engage in both patient care and research. Competence in either field must be established through protected training and criteria of excellence, particularly reflecting contribution to innovation. The decline of surgeon-scientists has reached an unprecedented magnitude. Leadership turning hospitals into "profit factories" is one reason, a flawed selection process not exclusively based on excellence is another. Most importantly, the appreciation for the academic mission has vanished. Along with fundamentally addressing these root causes, surgeon-scientists' path to excellence must be streamlined, and their continuous devotion to innovation cherished. CONCLUSIONS: The journey of the surgeon-scientist is at a crossroads. As a society, we either adapt and shift our priorities again towards innovation or capitulate to greed for profit, permanently losing these invaluable professionals. Successful rescue packages must not only involve hospitals and universities but also the political sphere.

Revolutionizing Organ Transplantation With Robotic Surgery.

OBJECTIVE: The aim of this study was to evaluate the impact of robotic techniques on organ transplantation outcomes. BACKGROUND: The evolution of organ transplantation is becoming influenced by the adoption of minimally invasive techniques, transitioning from laparoscopic to robotic methods. Robotic surgery has emerged as a significant advancement, providing superior precision and outcomes compared with traditional approaches. METHODS: This perspective includes a systematic review of the literature, original data from a high-volume center, as well as an international survey focusing on perceptions related to robotic versus laparoscopic and open approaches. RESULTS: The systematic review and meta-analysis revealed lower morbidity with robotic donor nephrectomy, recipient kidney transplant and donor hepatectomy. Our center's experience, with over 3000 minimally invasive transplant procedures (kidney, liver, donor, and recipient), supports the superiority of robotic transplant surgery (RTS). The global survey confirms this shift, revealing a preference for robotic approaches due to their reduced morbidity, despite challenges such as access to the robotic system and cost. CONCLUSIONS: This comprehensive overview including a systematic review, original data, and perceptions derived from the international survey demonstrate the superiority of robotic transplant surgery (RTS) across a range of organ transplantations, for both donors and recipients. The future of RTS depends on the efforts of the surgical community in addressing challenges such as economic implications, the need for specialized surgical training for numerous surgeons, as well as wide access to robotic systems worldwide.

Revolutionizing Liver Transplantation: Transitioning to an Elective Procedure Through Ex Situ Normothermic Machine Perfusion - A Benefit Analysis.

OBJECTIVE: To assess the impact of normothermic machine perfusion (NMP) on patients, medical teams, and costs by gathering global insights and exploring current limitations. BACKGROUND: NMP for ex situ liver graft perfusion is gaining increasing attention for its capability to extend graft preservation. It has the potential to transform liver transplantation (LT) from an urgent to a purely elective procedure, which could revolutionize LT logistics, reduce burden on patients and health care providers, and decrease costs. METHODS: A 31-item survey was sent to international transplant directors to gather their NMP experiences and vision. In addition, we performed a systematic review on cost-analysis in LT and assessed studies on cost-benefit in converting urgent-to-elective procedures. We compared the costs of available NMPs and conducted a sensitivity analysis of NMP's cost benefits. RESULTS: Of 120 transplant programs contacted, 64 (53%) responded, spanning North America (31%), Europe (42%), Asia (22%), and South America (5%). Of the total, 60% had adopted NMP, with larger centers (>100 transplants/year) in North America and Europe more likely to use it. The main NMP systems were OrganOx-metra (39%), XVIVO (36%), and TransMedics-OCS (15%). Despite NMP adoption, 41% of centers still perform >50% of LTs at nights/weekends. Centers recognized NMP's benefits, including improved work satisfaction and patient outcomes, but faced challenges like high costs and machine complexity. 16% would invest $100,000 to 500'000, 33% would invest $50,000 to 100'000, 38% would invest $10,000 to 50'000, and 14% would invest <$10,000 in NMP. These results were strengthened by a cost analysis for NMP in emergency-to-elective LT transition. Accordingly, while liver perfusions with disposables up to $10,000 resulted in overall positive net balances, this effect was lost when disposables' cost amounted to >$40,000/organ. CONCLUSIONS: The adoption of NMP is hindered by high costs and operational complexity. Making LT elective through NMP could reduce costs and improve outcomes, but overcoming barriers requires national reimbursements and simplified, automated NMP systems for multiday preservation.

Incidence of postoperative complications is underestimated if outcome data are recorded by interns and first year residents in a low volume hospital setting.

The aim of this study is to evaluate the accuracy of outcome reporting after elective visceral surgery in a low volume district hospital. Outcome measurement as well as transparent reporting of surgical complications becomes more and more important. In the future, financial and personal resources may be distributed due to reported quality and thus, it is in the main interest of healthcare providers that outcome data are accurately collected. Between 10/2020 and 09/2021 postoperative complications during the hospitalisation were recorded using the Clavien-Dindo classification (CDC) and comprehensive complication index by residents of a surgical department in a district hospital. After one year of prospective data collection, data were retrospectively analyzed and re-evaluated for accuracy by senior consultant surgeons. In 575 patients undergoing elective general or visceral surgery interns and residents reported an overall rate of patients with complications of 7.3% (n = 42) during the hospitalization phase, whereas a rate of 18.3% (n = 105) was revealed after retrospective analysis by senior consultant surgeons. Thus, residents failed to report patients with postoperative complications in 60% of cases (63/105). In the 42 cases, in which complications were initially reported, the grading of complications was correct only in 33.3% of cases (n = 14). Complication grades that were most missed were CDC grade I and II. Quality of outcome measurement in a district hospital is poor if done by unexperienced residents and significantly underestimates the true complication rate. Outcome measurement must be done or supervised by experienced surgeons to ensure correct and reliable outcome data.

Friedrich Dessauer (1881-1963): the forgotten medical physicist, politician, and philosopher.

Today, the name Friedrich Dessauer is almost forgotten; however, his scientific, social, and political works should not be. Dessauer's professional career began at a young age as a professor of physics in Frankfurt am Main. It is said that he published 400 papers and 65 book chapters and pamphlets. He was a technical inventor who established laws that dealt with theories to explain the limited understanding of the effects of radiation on cells. He advocated for methods to improve the therapeutic ratio. As a devout Catholic politician, Dessauer was an early opponent of National Socialism. This led to him being thrown into prison for political reasons in 1933. He did not leave until 1934, and then for Istanbul, largely thanks to Turkish efforts and his appointment as director of a large new institution. While he was already a well-known physicist in Germany, he had to start from scratch in order to build a modern institute. A recent article in the journal Radiotherapy and Oncology celebrated his important contributions to radiology from Turkey. After his contract in Istanbul expired in 1937, he left for the small University of Fribourg in Switzerland, where he was unfortunately unable to continue his scientific productivity. Dessauer wrote textbooks as well as political and philosophical books, and attempted to bridge the gap between Catholicism and science. Additionally, after the war, he began to teach again in Frankfurt. In photos of Dessauer, radiation-induced skin changes on his face and hands were clearly visible. Towards the end of his life, he received many medals and honors for his achievements in Germany, some of them posthumously.

Towards a Standardization of Learning Curve Assessment in Minimally Invasive Liver Surgery.

OBJECTIVE: The aim was to analyze the learning curves of minimal invasive liver surgery(MILS) and propose a standardized reporting. SUMMARY BACKGROUND DATA: MILS offers benefits compared to open resections. For a safe introduction along the learning curve, formal training is recommended. However, definitions of learning curves and methods to assess it lack standardization. METHODS: A systematic review of PubMed, Web of Science, and CENTRAL databases identified studies on learning curves in MILS. The primary outcome was the number needed to overcome the learning curve. Secondary outcomes included endpoints defining learning curves, and characterization of different learning phases(competency, proficiency and mastery). RESULTS: 60 articles with 12'241 patients and 102 learning curve analyses were included. The laparoscopic and robotic approach was evaluated in 71 and 18 analyses and both approaches combined in 13 analyses. Sixty-one analyses (60%) based the learning curve on statistical calculations. The most often used parameters to define learning curves were operative time (n=64), blood loss (n=54), conversion (n=42) and postoperative complications (n=38). Overall competency, proficiency and mastery were reached after 34 (IQR 19-56), 50 (IQR 24-74), 58 (IQR 24-100) procedures respectively. Intraoperative parameters improved earlier (operative time: competency to proficiency to mastery: -13%, 2%; blood loss: competency to proficiency to mastery: -33%, 0%; conversion rate (competency to proficiency to mastery; -21%, -29%), whereas postoperative complications improved later (competency to proficiency to mastery: -25%, -41%). CONCLUSIONS: This review summarizes the highest evidence on learning curves in MILS taking into account different definitions and confounding factors. A standardized three-phase reporting of learning phases (competency, proficiency, mastery) is proposed and should be followed.

Improvements of the shape and strength of the diaphragm after endoscopic lung volume reduction.

RATIONALE: Endoscopic lung volume reduction improves lung function, quality of life and exercise capacity in severe emphysema patients. However, its effect on the diaphragm function is not well understood. We hypothesised that endoscopic lung volume reduction increases its strength by modifying its shape. OBJECTIVES: To investigate changes in both diaphragm shape and strength induced by the insertion of endobronchial valves. METHODS: In 19 patients, both the diaphragm shape and strength were investigated respectively by 3D Slicer software applied on CT scans acquired at functional residual capacity and by transdiaphragmatic pressure measurements by bilateral magnetic stimulation of the phrenic nerves before and 3 months after unilateral valves insertion. MEASUREMENTS AND MAIN RESULTS: After lung volume reduction (median (IQR), 434 mL (-597 to -156], p<0.0001), diaphragm strength increased (transdiaphragmatic pressure: 3 cmH2O (2.3 to 4.2), p<0.0001). On the treated side, this increase was associated with an increase in the coronal (16 mm (13 to 24), p<0.0001) and sagittal (26 mm (21 to 30), p<0.0001) lengths as well as in the area of the zone of apposition (62 cm2 (3 to 100), p<0.0001) with a decrease in the coronal (8 mm (-12 to -4), p<0.0001) and sagittal (9 mm (-18 to -2), p=0.0029) radii of curvature. CONCLUSIONS: Endoscopic lung volume reduction modifies the diaphragm shape by increasing its length and its zone of apposition and by decreasing its radius of curvature on the treated side, resulting in an increase in its strength. TRIAL REGISTRATION NUMBER: NCT05799352.

Harmonizing Definitions and Perspectives in Extreme Liver Surgery: A Delphi Experts Consensus.

OBJECTIVE: To propose to our community a common language about extreme liver surgery. BACKGROUND: The lack of a clear definition of extreme liver surgery prevents convincing comparisons of results among centers. METHODS: We used a two-round Delphi methodology to quantify consensus among liver surgery experts. For inclusion in the final recommendations, we established a consensus when the positive responses (agree and totally agree) exceeded 70%. The study steering group summarized and reported the recommendations. In general, a five-point Likert scale with a neutral central value was used, and in a few cases multiple choices. Results are displayed as numbers and percentages. RESULTS: A two-round Delphi study was completed by 38 expert surgeons in complex hepatobiliary surgery. The surgeon´s median age was 58 years old (52-63) and the median years of experience was 25 years (20-31). For the proposed definitions of total vascular occlusion, hepatic flow occlusion and inferior vein occlusion, the degree of agreement was 97%, 81% and 84%, respectively. In situ approach (64%) was the preferred, followed by ante situ (22%) and ex situ (14%). Autologous or cadaveric graft for hepatic artery or hepatic vein repair were the most recommended (89%). The use of veno-venous bypass or portocaval shunt revealed the divergence depending on the case. Overall, 75% of the experts agreed with the proposed definition for extreme liver surgery. CONCLUSION: Obtaining a consensus on the definition of extreme liver surgery is essential to guarantee the correct management of patients with highly complex hepatobiliary oncological disease. The management of candidates for extreme liver surgery involves comprehensive care ranging from adequate patient selection to the appropriate surgical strategy.

The Differentiation between Progressive Disease and Treatment-Induced Effects with Perfusion-Weighted Arterial Spin-Labeling in High-Grade Gliomas.

BACKGROUND AND PURPOSE: Treatment-induced effects are difficult to differentiate from progressive disease in radiologically progressing diffuse gliomas after treatment. This retrospective, single-center cohort study investigated the diagnostic value of arterial spin-labeling perfusion in differentiating progressive disease from treatment-induced effects in irradiated patients with a high-grade glioma. MATERIALS AND METHODS: Adults with a high-grade glioma diagnosed between January 1, 2012, and December 31, 2018, with a new or increasing contrast-enhancing lesion after radiotherapy with or without chemotherapy and arterial spin-labeling were consecutively included. Arterial spin-labeling is part of the routine follow-up examinations of patients with a high-grade glioma. The outcomes of progressive disease or treatment-induced effects were defined after histologic or >6 weeks radiologic follow-up. Two neuroradiologists graded the arterial spin-labeling visually as negative (hypointense to gray matter) or positive (iso-/hyperintense). Additionally, the arterial spin-labeling signal intensity in the enhancing lesion was compared quantitatively with that in the contralateral normal brain. Diagnostic test properties and the Cohen κ inter- and intrarater reliability were determined. We present data according to the time after radiation therapy. RESULTS: We included 141 patients with 173 lesions (median age, 63 years). Ninety-four (54%) lesions showed treatment-induced effects, and 79 (46%), progressive disease. For visual analysis, the ORs of an arterial spin-labeling positive for progressive disease in the group with progression within 3, between 3 and 6, and after 6 months after radiation therapy were 0.65 (95% CI, 0.28-1.51; P = .319), 3.5 (95% CI, 0.69-17.89; P = .132), and 6.8 (95% CI, 1.48-32; P = .014). The areas under the curve were 0.456, 0.652, and 0.719. In quantitative analysis, the areas under the curve were 0.520, 0.588, and 0.587 in these groups. Inter- and intrarater reliability coefficients were 0.67 and 0.62. CONCLUSIONS: Arterial spin-labeling performed poorly in differentiating progressive disease from treatment-induced effects in high-grade gliomas within 6 months after radiation therapy, with fair performance after this period. Arterial spin-labeling may need to be combined with other imaging features and clinical information for better performance.

Rescue of myocytes and locomotion through AAV2/9-2YF intracisternal gene therapy in a rat model of creatine transporter deficiency.

Creatine deficiency syndromes (CDS), caused by mutations in GATM (AGAT), GAMT, and SLC6A8, mainly affect the central nervous system (CNS). CDS show brain creatine (Cr) deficiency, intellectual disability with severe speech delay, behavioral troubles, epilepsy, and motor dysfunction. AGAT/GAMT-deficient patients lack brain Cr synthesis but express the Cr transporter SLC6A8 at the blood-brain barrier and are thus treatable by oral supplementation of Cr. In contrast, no satisfactory treatment has been identified for Cr transporter deficiency (CTD), the most frequent of CDS. We used our Slc6a8Y389C CTD rat model to develop a new AAV2/9-2YF-driven gene therapy re-establishing the functional Slc6a8 transporter in rat CNS. We show, after intra-cisterna magna AAV2/9-2YF-Slc6a8-FLAG vector injection of postnatal day 11 pups, the transduction of Slc6a8-FLAG in cerebellum, medulla oblongata, and spinal cord as well as a partial recovery of Cr in these brain regions, together with full prevention of locomotion defaults and impairment of myocyte development observed in Slc6a8Y389 C/y male rats. While more work is needed to correct those CTD phenotypes more associated with forebrain structures, this study is the first demonstrating positive effects of an AAV-driven gene therapy on CTD and thus represents a very encouraging approach to treat the so-far untreatable CTD.

Recommendations on Robotic Hepato-Pancreato-Biliary Surgery. The Paris Jury-Based Consensus Conference.

OBJECTIVE: To establish the first consensus guidelines on the safety and indications of robotics in Hepato-Pancreatic-Biliary (HPB) surgery. The secondary aim was to identify priorities for future research. SUMMARY BACKGROUND DATA: HPB robotic surgery is reaching the IDEAL 2b exploration phase for innovative technology. An objective assessment endorsed by the HPB community is timely and needed. METHODS: The ROBOT4HPB conference developed consensus guidelines using the Zurich-Danish model. An impartial and multidisciplinary jury produced unbiased guidelines based on the work of ten expert panels answering predefined key questions and considering the best-quality evidence retrieved after a systematic review. The recommendations conformed with the GRADE and SIGN50 methodologies. RESULTS: Fifty-four experts from 20 countries considered 285 studies, and the conference included an audience of 220 attendees. The jury (n=10) produced recommendations or statements covering five sections of robotic HPB surgery: technology, training and expertise, outcome assessment, and liver and pancreatic procedures. The recommendations supported the feasibility of robotics for most HPB procedures and its potential value in extending minimally invasive indications, emphasizing however the importance of expertise to ensure safety. The concept of expertise was defined broadly, encompassing requirements for credentialing HPB robotics at a given center. The jury prioritized relevant questions for future trials and emphasized the need for prospective registries, including validated outcome metrics for the forthcoming assessment of HPB robotics. CONCLUSION: The ROBOT4HPB consensus represents a collaborative and multidisciplinary initiative, defining state-of-the-art expertise in HPB robotics procedures. It produced the first guidelines to encourage their safe use and promotion.

Full robotic versus open ALPPS: a bi-institutional comparison of perioperative outcomes.

BACKGROUND: In primarily unresectable liver tumors, ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy) may offer curative two-stage hepatectomy trough a fast and extensive hypertrophy. However, concerns have been raised about the invasiveness of the procedure. Full robotic ALPPS has the potential to reduce the postoperative morbidity trough a less invasive access. The aim of this study was to compare the perioperative outcomes of open and full robotic ALPPS. METHODS: The bicentric study included open ALPPS cases from the University Hospital Zurich, Switzerland and robotic ALPPS cases from the University of Modena and Reggio Emilia, Italy from 01/2015 to 07/2022. Main outcomes were intraoperative parameters and overall complications. RESULTS: Open and full robotic ALPPS were performed in 36 and 7 cases. Robotic ALPPS was associated with less blood loss after both stages (418 ± 237 ml vs. 319 ± 197 ml; P = 0.04 and 631 ± 354 ml vs. 258 ± 53 ml; P = 0.01) as well as a higher rate of interstage discharge (86% vs. 37%; P = 0.02). OT was longer with robotic ALPPS after both stages (371 ± 70 min vs. 449 ± 81 min; P = 0.01 and 282 ± 87 min vs. 373 ± 90 min; P = 0.02). After ALPPS stage 2, there was no difference for overall complications (86% vs. 86%; P = 1.00) and major complications (43% vs. 39%; P = 0.86). The total length of hospital stay was similar (23 ± 17 days vs. 26 ± 13; P = 0.56). CONCLUSION: Robotic ALPPS was safely implemented and showed potential for improved perioperative outcomes compared to open ALPPS in an experienced robotic center. The robotic approach might bring the perioperative risk profile of ALPPS closer to interventional techniques of portal vein embolization/liver venous deprivation.

From Early to Mid-Term Results of Endoscopic Sleeve Gastroplasty: A Retrospective Analysis of a Bariatric Center.

PURPOSE: Global obesity rates have surged, necessitating effective interventions beyond traditional bariatric and metabolic surgery (BMS). Endoscopic Sleeve Gastroplasty (ESG) has emerged as a minimally invasive alternative, addressing limitations of eligibility criteria and patient reluctance associated with BMS. This study aims to present a 3-year experience with ESG, focusing on its mid-term efficacy in weight loss. MATERIALS AND METHODS: A retrospective, single-center study included 143 consecutive ESG patients (BMI > 30 kg/m2 or > 25 kg/m2 with obesity associated-diseases) from February 2019 to March 2023. Data on demographics, comorbidities, operative details, and follow-up outcomes were collected. The primary outcome was %TWL ≥ 15% at 12 months. Secondary outcomes were an optimal clinical response (OCR) at 24 and 36 months defined by %TWL ≥ 10% or %EWL ≥ 25%. RESULTS: ESG demonstrated a mean %TWL of 14.37% at 12 months, aligning with previous studies. Early postoperative complications were minimal (2.1%), with no mortality. Follow-up revealed a peak in weight loss at 9 months, but mid-term OCR was achieved in 41.2% at 3 years. The learning curve showed efficiency improvements after 26 procedures. CONCLUSION: ESG proves effective at one year, with a %TWL of 14.37%. However, mid-term efficacy beyond 12 months remains challenging, raising questions about the durability of weight loss. Despite a low complication rate, strategies for maintaining a long-term OCR, including potential repeat ESG, warrant further investigation.

Glucose controls lipolysis through Golgi PtdIns4P-mediated regulation of ATGL.

Metabolic crosstalk of the major nutrients glucose, amino acids and fatty acids (FAs) ensures systemic metabolic homeostasis. The coordination between the supply of glucose and FAs to meet various physiological demands is especially important as improper nutrient levels lead to metabolic disorders, such as diabetes and metabolic dysfunction-associated steatohepatitis (MASH). In response to the oscillations in blood glucose levels, lipolysis is thought to be mainly regulated hormonally to control FA liberation from lipid droplets by insulin, catecholamine and glucagon. However, whether general cell-intrinsic mechanisms exist to directly modulate lipolysis via glucose sensing remains largely unknown. Here we report the identification of such an intrinsic mechanism, which involves Golgi PtdIns4P-mediated regulation of adipose triglyceride lipase (ATGL)-driven lipolysis via intracellular glucose sensing. Mechanistically, depletion of intracellular glucose results in lower Golgi PtdIns4P levels, and thus reduced assembly of the E3 ligase complex CUL7FBXW8 in the Golgi apparatus. Decreased levels of the E3 ligase complex lead to reduced polyubiquitylation of ATGL in the Golgi and enhancement of ATGL-driven lipolysis. This cell-intrinsic mechanism regulates both the pool of intracellular FAs and their extracellular release to meet physiological demands during fasting and glucose deprivation. Moreover, genetic and pharmacological manipulation of the Golgi PtdIns4P-CUL7FBXW8-ATGL axis in mouse models of simple hepatic steatosis and MASH, as well as during ex vivo perfusion of a human steatotic liver graft leads to the amelioration of steatosis, suggesting that this pathway might be a promising target for metabolic dysfunction-associated steatotic liver disease and possibly MASH.

Global Outcomes Benchmarks in Laparoscopic Liver Surgery for Segments 7 and 8: International Multicenter Analysis.

BACKGROUND: In recent years, there has been growing interest in laparoscopic liver resection (LLR) and the audit of the results of surgical procedures. The aim of this study was to define reference values for LLR in segments 7 and 8. STUDY DESIGN: Data on LLR in segments 7 and 8 between January 2000 and December 2020 were collected from 19 expert centers. Reference cases were defined as no previous hepatectomy, American Society of Anesthesiologists score less than 3, BMI less than 35 kg/m 2 , no chronic kidney disease, no cirrhosis and portal hypertension, no COPD (forced expiratory volume 1 <80%), and no cardiac disease. Reference values were obtained from the 75th percentile of the medians of all reference centers. RESULTS: Of 585 patients, 461 (78.8%) met the reference criteria. The overall complication rate was 27.5% (6% were Clavien-Dindo 3a or more) with a mean Comprehensive Complication Index of 7.5 ± 16.5. At 90-day follow-up, the reference values for overall complication were 31%, Clavien-Dindo 3a or more was 7.4%, conversion was 4.4%, hospital stay was less than 6 days, and readmission rate was <8.33%. Patients from Eastern centers categorized as low risk had a lower rate of overall complication (20.9% vs 31.2%, p = 0.01) with similar Clavien-Dindo 3a or more (5.5% and 4.8%, p = 0.83) compared with patients from Western centers, respectively. CONCLUSIONS: This study shows the need to establish standards for the postoperative outcomes in LLR based on the complexity of the resection and the location of the lesions.

REDISCOVER guidelines for borderline-resectable and locally advanced pancreatic cancer: management algorithm, unanswered questions, and future perspectives.

The REDISCOVER guidelines present 34 recommendations for the selection and perioperative care of borderline-resectable (BR-PDAC) and locally advanced ductal adenocarcinoma of the pancreas (LA-PDAC). These guidelines represent a significant shift from previous approaches, prioritizing tumor biology over anatomical features as the primary indication for resection. Condensed herein, they provide a practical management algorithm for clinical practice. However, the guidelines also highlight the need to redefine LA-PDAC to align with modern treatment strategies and to solve some contradictions within the current definition, such as grouping "difficult" and "impossible" to resect tumors together. Furthermore, the REDISCOVER guidelines highlight several areas requiring urgent research. These include the resection of the superior mesenteric artery, the management strategies for patients with LA-PDAC who are fit for surgery but unable to receive multi-agent neoadjuvant chemotherapy, the approach to patients with LA-PDAC who are fit for surgery but demonstrate high serum Ca 19.9 levels even after neoadjuvant treatment, and the optimal timing and number of chemotherapy cycles prior to surgery. Additionally, the role of primary chemoradiotherapy versus chemotherapy alone in LA-PDAC, the timing of surgical resection post-neoadjuvant/primary chemoradiotherapy, the efficacy of ablation therapies, and the management of oligometastasis in patients with LA-PDAC warrant investigation. Given the limited evidence for many issues, refining existing management strategies is imperative. The establishment of the REDISCOVER registry ( https://rediscover.unipi.it/ ) offers promise of a unified research platform to advance understanding and improve the management of BR-PDAC and LA-PDAC.