Roberta Vella

Background: Robotic liver resections (RLRs) are rapidly expanding, yet the association between the learning curve, procedural complexity, and outcomes at intermediate-volume centers remains poorly defined. We evaluated the learning-curve trajectory and perioperative outcomes of a single surgeon’s initial RLR experience according to procedural complexity (IWATE difficulty score). Methods: We retrospectively analyzed 58 consecutive RLRs at an intermediate-volume center. We stratified outcomes by IWATE difficulty category and chronological tertile (early/middle/late). Textbook outcomes (TOs) and a composite failure endpoint (conversion, major complications [Clavien–Dindo ≥ IIIa] and 90-day mortality) were also assessed. Learning-curve behavior was examined with CUSUM and risk-adjusted CUSUM (RA-CUSUM) analyses. Results: Fifty-four procedures (93.1%) were minor resections and four were major hepatectomies; two were classified as IWATE Expert difficulty. Median estimated blood loss was 100 mL; conversion occurred in 10.3%, overall morbidity in 10.3% and severe complications (Clavien–Dindo ≥ IIIa) in 3.4%, with no mortalities within 90 days. TOs were achieved in 69.0% using the Delphi (TOLS) definition and in 46.6% using a length-of-stay-extended definition. Operative time and length of stay increased significantly with IWATE difficulty (p < 0.001 and p = 0.030), as did the composite failure endpoint (p = 0.039), whereas blood loss and complications did not. TOs decreased with difficulty under the extended definition (p = 0.016). No outcome except estimated blood loss differed across chronological tertiles (p = 0.032). Operative time was associated with the IWATE score (26.3 min per point; R² = 0.32) but not with case order (p = 0.93). CUSUM and RA-CUSUM curves showed a non-linear, multiphase pattern without an identifiable inflection point, with extremes attributable to individual high-complexity procedures. Conclusions: In this exploratory single-surgeon series, consisting predominantly of minor resections, no case-number threshold could be identified, and perioperative outcomes were more closely associated with procedural complexity than with chronological experience, supporting a complexity-adjusted interpretation of RLR outcomes rather than a fixed case-number learning threshold.

Objective: To evaluate short-term outcomes and identify predictors of morbidity and mortality following multivisceral oncologic resections involving the pancreas. Summary background data: Multivisceral resections including the pancreas are required for locally advanced abdominal malignancies but are associated with considerable perioperative risk. While smaller series suggest acceptable outcomes in selected patients, large-scale international data are lacking to guide surgical decision-making and risk stratification. Methods: This was a retrospective cohort study of 1283 patients from 31 international centers who underwent multivisceral oncologic resections involving the pancreas. Patient demographics, tumor characteristics, operative details, and 90-day postoperative outcomes were analyzed. Results: The cohort had a mean age of 64.7 years, and 54.7% were male. Distal pancreatectomy was the most frequent procedure (60.5%), and R0 resection was achieved in 60.9% of cases. The 90-day mortality was 6.9%, highest in patients with gastric adenocarcinoma (16.7%). Major complications (Clavien–Dindo grade III–V) occurred in 34.4% of patients. Higher ASA classification and open surgical approach were independently associated with increased morbidity and mortality. Prolonged operative time was associated with morbidity only. Female gender and treatment at high-volume centers were protective. In patients with pancreatic tumors, resection involving the colon (OR: 1.78, P < 0.001), stomach (OR: 1.33, P = 0.042), or three or more organs (OR: 1.75, P = 0.006) significantly increased complication rates. Conclusions: Multivisceral resections involving the pancreas are associated with relevant perioperative risk. Optimizing patient selection, favoring minimally invasive techniques when feasible in selected patients, and centralizing care to high-volume centers may help improve outcomes for these complex surgical procedures.

Background: Recent advances in multimodal therapies have increased the potential for resectability of borderline resectable and locally advanced pancreatic ductal adenocarcinoma (PDAC). We herein describe the conservative resection strategy adopted at our institution and the oncological outcomes of patients with PDAC and arterial involvement. Methods: This retrospective single-centre study included patients diagnosed with PDAC and radiologic evidence of arterial involvement who underwent surgical exploration between January 2014 and June 2024. All patients received induction chemotherapy (±radiotherapy). Survival outcomes were analyzed using the Kaplan–Meier and Cox proportional hazards models. Logistic regression analyses were used to identify predictors of resectability and recurrence. Results: A total of 76 patients were included: 59 underwent pancreatic resection with arterial divestment (AD) in case of persistent arterial involvement and 17 were deemed unresectable at laparotomy. Neoadjuvant folfirinox was significantly associated with increased odds of resection (HR = 3.23, 95% CI: 1.59–9.90, p = 0.040). Median overall survival from diagnosis was 33 months (29–39) in resected patients and 26 months (16–29) in non-resected patients (p = 0.0176). Surgical resection and Ca 19,9 normalization after induction therapy were associated with reduced mortality risk (HR = 0.38, 95% CI: 0.19–0.75, p = 0.005 and HR = 0.56, 95% CI: 0.35–0.88, p = 0.014, respectively). Conclusions: Despite a limited sample size and retrospective nature, these findings highlight the value of multimodal strategies in managing PDAC with arterial involvement. AD represents a valuable technique associated with acceptable outcomes in selected patients. Future interventional prospective studies are needed to optimize patient selection and validate the prognostic role of extended surgical procedures.

Background/Objectives: The increasing adoption of laparoscopic liver resection (LLR) and changes in clinical management may influence access to curative treatments for patients on the liver transplant waiting list. We aimed to analyze temporal trends in LLR use and to explore the association between the proportion of LLR and the dropout rate from the intention-to-treat (ITT) population. A secondary objective was to assess the risk of dropout or death versus curative treatment (transplantation or resection) in patients with hepatocellular carcinoma (HCC) compared with non-HCC candidates using a competing-risk model. Methods: We performed a retrospective cohort study of all patients listed for liver transplantation between 2015 and 2023. Annual rates of LLR and dropout were calculated, and their correlation was evaluated using Spearman’s rho. The risk of dropout/death and competing curative events (OLT, resection, or thermal ablation) was assessed using Fine–Gray competing-risk regression, adjusted for HCC status. Results: From 2015 to 2023, LLR accounted for a progressively increasing proportion of liver resections. A significant negative correlation was observed between annual LLR rates and dropout rates (ρ = −0.78, p = 0.008), indicating fewer ITT failures with greater LLR adoption. In the competing-risk analysis, HCC patients had a significantly lower subdistribution hazard for dropout/death (SHR 0.27, 95% CI 0.18–0.42, p < 0.001) and a higher probability of receiving a curative treatment (SHR 1.65, 95% CI 1.40–1.94, p < 0.001). Conclusions: The increased use of LLR was associated with improved access to curative therapies and a reduced dropout risk on the liver transplant waiting list. HCC patients showed a more favorable competing-risk profile compared with non-HCC candidates.

Sepsis constitutes a profoundly heterogeneous and dynamic clinical syndrome, precipitated by a maladaptive host response to infection in which the immune system’s regulatory balance is fundamentally disrupted. The intricate interplay between proinflammatory and anti-inflammatory pathways, ordinarily responsible for maintaining immune homeostasis, becomes pathologically skewed. Within this altered immunological landscape, cytokines serve as pivotal mediators, orchestrating a cascade of cellular events that may culminate in a rapid transition from systemic hyperinflammation to a state of immune exhaustion or suppression. This review offers a critical synthesis of the current scientific literature on the immunopathogenesis of sepsis, with a particular emphasis on the molecular and cellular mechanisms governing cytokine regulation. Special attention is directed toward elucidating the contribution of these mediators to the onset and progression of multiorgan dysfunction syndrome (MODS), a central and often fatal complication of severe sepsis. Through an integrative examination of the principal immune signaling networks and pathophysiological processes involved in sepsis, this review provides a cohesive theoretical framework positioning immune dysregulation as the fundamental axis of clinical deterioration. Such an approach underscores the imperative for a deeper insight into the immunological architecture of sepsis, thereby laying the groundwork for the rational design of targeted, mechanism-based therapeutic strategies.

Objective: This study aims to review the existing literature on the efficacy and safety of unconventional treatments among pancreatic cancer patients, including the use of natural products, dietary supplements, probiotics, whole medical systems, and body-based therapies. Methods: An electronic, systematic, and comprehensive literature review was conducted searching for studies up to November 2024 following the PRISMA 2020 guidelines. Randomized controlled trials and prospective and retrospective studies assessing the efficacy and safety of unconventional treatments for pancreatic cancer were considered eligible. Data on overall survival, quality of life, and treatment tolerability were extracted. Results: A total of 21 studies, providing data from 3095 patients, met the inclusion criteria. Various types of unconventional treatments are used in pancreatic cancer patients, including Chinese herbal medicine (CHM), mistletoe extract (ME), curcumin, and electroacupuncture. Among these, the use of CHM and curcumin concomitant with standard therapy was associated with survival and quality-of-life benefits. Electroacupuncture reduced pancreatic cancer pain intensity in a cost-effective manner. The data on ME are mixed and of insufficient quality for drawing definitive conclusions. Conclusions: Some unconventional treatments showed potential benefits in improving overall survival and quality of life in pancreatic cancer patients within an integrative oncology setting. Further high-quality studies are needed to provide robust, rigorous, and ethical evidence to support their integration into future guidelines, ensuring a holistic approach to cancer treatment.

This study aims to review existing literature on the effect of oral nutritional supplements (ONSs) during chemotherapy in older cancer patients. Electronic databases were searched for relevant studies up to March 2024. The risk of bias in the included studies was evaluated using the Cochrane tool. Eligible studies included randomized, prospective, and retrospective studies evaluating the effect of ONSs in elderly (median age > 65 years) cancer patients during chemotherapy. Data regarding chemotherapy adherence, toxicity, overall survival, and nutritional status were extracted. A total of ten studies, involving 1123 patients, were included. A meta-analysis of the results was not conducted due to the scarcity and heterogeneity of results. Some ONSs were associated with reduced incidence of chemotherapy side-effects, particularly oral mucositis, and improved nutritional status. There was limited or no evidence regarding the impact of ONSs on chemotherapy adherence or overall survival. Various types of ONS were investigated, including multimodal intervention with tailored nutritional counseling, whey protein supplements, amino acids supplements (including immune nutrition supplements), and fish oil omega-3-enriched supplements. ONSs showed promise in reducing chemotherapy side-effects and improving nutritional status in older cancer patients, but further studies are needed to explore their efficacy on chemotherapy adherence and overall survival. Future research should consider both chronological age and frailty criteria, account for dietary habits, and use specific nutritional assessment like Bioelectrical Impedance Analysis.

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