Pierre-Alain Clavien’s research while affiliated with University of Zurich and other places

Background: Iron deficiency anemia in the perioperative setting is treated predominantly with intravenous iron formulation, of which ferric carboxymaltose may induce hypophosphatemia by modulating fibroblast growth factor 23. Methods: In this single-center, prospective, randomized, double-blind trial, we consented 92 adult patients scheduled for elective major abdominal or thoracic surgery. These patients either had isolated iron deficiency (plasma ferritin <100 ng/mL or transferrin saturation < 20 %) or iron deficiency anemia (hemoglobin (Hb) 100–130 g/L with plasma ferritin <100 ng/mL or transferrin saturation < 20 %). Preoperatively, participants received a single preoperative intravenous dose of ferric carboxymaltose and were then randomly assigned to receive either phosphate or placebo, administered orally three times a day for 30 days corresponding to an 18 mmol dose of daily phosphate supplementation in the intervention group. The primary endpoint was the minimum serum phosphate concentration during follow-up visits. The key secondary efficacy endpoint was mean perioperative hemoglobin concentration of postoperative days 0, 2 and 4, assessing the non-inferiority of additional phosphate supplementation. Results: We randomly consented 46 patients in each group (mean ± SD age 56 ± 17 years, 57 % female). Minimal phosphate concentration was 0.49 ± 0.21 mmol/L in the treatment group and 0.42 ± 0.17 mmol/L in the placebo group (p = 0.12, two-sided p-value). Average mean hemoglobin was 110 ± 16 g/L in the treatment and 113 ± 13 g/L in the placebo group (p = 0.023, one-sided p-value for non-inferiority). Hypophosphatemia occurred in 32 patients (70 %) of the treatment group and in 39 patients (85 %) of the placebo group (odds ratio 0.15, 95 % CI from 0.02 to 0.77, p = 0.014). Secondary outcomes, such as rescue medication use, core muscle strength and MOCA test scores, did not differ between groups. Conclusion: Co-administration of oral phosphate supplementation to ferric carboxymaltose cannot prevent hypophosphatemia. However, hypophosphatemia occurs in fewer patients. Phosphate co-administration did not impede the treatment of iron deficiency anemia with ferric carboxymaltose.

Background Early allograft dysfunction (EAD) affects outcomes in liver transplantation (LT). Existing risk models developed for deceased-donor LT depend on posttransplant factors and fall short in living-donor LT (LDLT), where pretransplant evaluations are crucial for preventing EAD and justifying the donor’s risks. Methods This retrospective study analyzed data from 2944 adult patients who underwent LDLT at 17 centers between 2016 and 2020. We developed a logistic regression model to predict EAD based on this development cohort. We used data from 1020 patients at the King Faisal Transplant Center for external validation. Results In the development cohort, 321 patients (10.9%) experienced EAD. These patients had poorer health status, more liver decompensation, and higher requirements of hospitalization than those without EAD. Multivariable logistic regression identified independent pretransplant predictors of EAD: laboratory Model for End-Stage Liver Disease score (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.06-1.09), the necessity for hospitalization at the time of transplant (OR, 2.58; 95% CI, 2.00-3.30), and graft weight in kilogram (OR, 0.27; 95% CI, 0.17-0.45). Using these predictors, we developed the model for EAD after LDLT, which demonstrated strong discriminative ability in the development cohort with an area under the curve (AUC) of 0.71 (95% CI, 0.68-0.74). The model maintained high discrimination during internal validation (AUC, 0.70; 95% CI, 0.67-0.73) and showed a modest reduction in discriminative power in external validation (AUC, 0.65; 95% CI, 0.61-0.68). Conclusions EAD post-LDLT is influenced by the recipient’s pretransplant health condition and the graft weight. Integrating the model for EAD after LDLT into the pretransplant process of pairing donors and recipients can enhance the safety and efficacy of LDLT.

Objective The aim of this study was to evaluate the different phases of the learning curve for robotic distal pancreatectomy (RDP) in international expert centers. Summary Background Data RDP is an emerging minimally invasive approach; however, only limited, mostly single center data are available on its safe implementation, including the learning curve. Methods Consecutive patients undergoing elective RDP from 16 expert centers across three continents were included to assess the learning curve. Based on the first 100 RDPs at each center, three cutoffs were used to define the learning curve: operative time for competency , major complications (Clavien–Dindo grade ≥III) for proficiency , and textbook outcome for mastery . Clinical outcomes before and after the cutoffs were compared. Results The learning curve analysis was conducted on 1109 of 2403 RDPs. Competency, proficiency, and mastery, respectively, were reached after 46, 63, and 73 RDP procedures. After competency, operative time decreased from 245 to 235 minutes ( P =0.002). Attaining proficiency was reflected by a reduction in the rate of major complications from 20% to 15% ( P =0.012), and mastery was associated with a higher proportion of patients with textbook outcome (71% vs. 63%; P =0.028). The postoperative pancreatic fistula rate remained stable along the learning curve, ranging between 18.5% and 21.5%. Previous laparoscopic experience accelerated the learning process by virtue of reduced operative time and an earlier decrease in major complications. Conclusion Competency , proficiency , and mastery for RDP were reached after 46, 63, and 73 procedures, respectively, at international expert centers. The findings highlight that the learning curves for intraoperative parameters are completed earlier; however, extensive experience is needed to master RDP.

The comparison of outcomes in liver transplantation (LT) is hampered by using clinically non-relevant surrogate endpoints and considerable variability in reported relevant post-transplant outcomes. Such variability stems from non-standard outcome measures across studies, variable definitions of the same complication, and different timing of reporting. The Clavien-Dindo classification was established to improve the rigor of outcome reporting but is non-specific to an intervention and there are unsolved dilemmas specifically related to liver transplantation. Core Outcome Sets (COS) have been used in other specialties to standardize outcomes research, but have not been defined for LT. Thus, we use the five major benchmarking studies published to date to define a 10-measure COS for LT using previously validated metrics. We further provide standard definitions for each of the 10 measures that may be used in international research on the topic. These definitions also include standard time-points for recording to facilitate between-study comparisons and future meta-analysis. These 10 outcomes are paired with 3 validated, procedure-independent metrics, including the Clavien-Dindo Classification and the Comprehensive Complications Index (CCI ® ). The Clavien scale and CCI ® are specifically reviewed to enhance their utility in LT, and their use along with the COS is explored. We encourage future studies to employ this COS along with the Clavien-Dindo grading system & CCI ® to improve reproducibility and generalizability of research concerning liver transplantation.

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 have 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 unprecedented magnitude. Leadership turning hospitals into «profit-factories» is one reason, a flawed selection process not exclusively based on excellence 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 for innovation cherished. Conclusion The journey of the surgeon-scientist is at crossroads. As society, we either adapt and shift our priorities again towards innovation or capitulate to the greed for profit, permanently losing these invaluable professionals. Successful rescue packages must not only involve hospitals and universities but also the political sphere.

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 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 two metrics in RCTs remains unexplored. Methods We assessed the use of the CDC and CCI® as an outcome measure in a systematic literature search. Additionally, we asked 163 international surgeons to critically evaluate and independently grade complications in 20 complex clinical scenarios. Finally, a core group of five 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 basis for the recommendations: Repetitive interventions that are required to treat one complication, complications followed by further complications, complications occurring prior to 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. Conclusion 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 healthcare stakeholders, and first and foremost, all patients.

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 pure elective procedure, which could revolutionize LT logistics, reduce burden on patients and healthcare providers, and decrease costs. Methods A 31-item survey was sent to international transplant directors to gather their NMP experiences and vision. Additionally, 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 on 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%). Sixty percent had adopted NMP, with larger centers (>100 transplants/year) in North America and Europe more likely to use it. 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 $100’000-500’000, 33$50’000-100’000, 38% $10’000-50’000, and 14$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. Conclusion 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 multi-day preservation.

Objective To evaluate the impact of robotic techniques on organ transplantation outcomes. Summary Background Data 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 to 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 3,000 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. Conclusion 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.