European Surgical Research最新文献

Cancer immunotherapy has transformed the therapeutic landscape of oncology by harnessing the body's immune system to recognise and eliminate malignant cells. In certain tumour types, such as melanoma and non-small cell lung cancer, immune-based therapies have led to durable clinical responses and significantly improved survival. These successes have fuelled the rapid integration of immunotherapeutic approaches into standard treatment regimens. However, their effectiveness in the majority of solid tumours remains limited. Several biological and physical barriers underlie this limited efficacy. A major challenge is the immunosuppressive nature of the tumour microenvironment (TME), which hampers effective immune cell infiltration and function. In many solid tumours, chronic inflammation, poor antigen presentation, a low mutational burden, and the presence of suppressive myeloid and stromal cells create an environment resistant to immune activation. In addition, high intra-tumoral pressure and abnormal vasculature further restrict drug delivery and immune cell trafficking, particularly in desmoplastic cancers such as pancreatic and prostate cancer. Recent advances in immuno-oncology have focused on strategies to overcome these barriers and convert 'cold' tumours, those lacking immune cell infiltration, into 'hot', immune-inflamed tumours. Despite this progress, clinical translation has proven to be complex, with mixed results across various tumour types. While some patients derive long-term benefit from immunotherapy, others exhibit primary or acquired resistance, underscoring the need for better patient stratification and predictive biomarkers. This review provides a comprehensive overview of the evolving field of immunotherapy for solid tumours, discussing key mechanisms of immune resistance, the role of the tumour microenvironment (TME), and the multifactorial nature of therapeutic failure. It highlights the importance of understanding tumour-immune interactions in their full biological context, and explores current thinking on how to reshape the immune landscape of solid tumours. By addressing both immunological and physical barriers, future approaches may broaden the benefit of immunotherapy beyond its current scope, ultimately improving outcomes for patients with traditionally treatment-resistant cancers.

Introduction: Robotic gastrectomy offers perioperative advantages such as reduced blood loss and faster recovery; however, infectious complications remain a significant concern. In this study, we aimed to identify the predictive factors for postoperative infectious complications following radical robotic gastrectomy in patients with gastric or esophagogastric junctional cancer.

Methods: This retrospective single-center study analysed data from 155 patients with gastric or esophagogastric junction cancer who underwent curative robotic gastrectomy between December 2017 and April 2025 to identify predictive factors for postoperative infectious complications. Twenty-two variables, including nutritional indices and surgical factors, were evaluated.

Results: A total of 18 patients developed Clavien-Dindo grade II-IIIa infectious complications. Infectious complications included pneumonia (n=5, 3.2%), intra-abdominal abscess (n=5, 3.2%), anastomotic leakage (n=3, 1.9%), cholecystitis (n=2, 1.2%), nonocclusive mesenteric ischemia (n=1, 0.6%), bile leakage (n=1, 0.6%), and sepsis (n=1, 0.6%). The number of patients with complications and American Society of Anesthesiologists Physical Status (ASA-PS) class ≥3 (p=0.006) and preoperative smoking (p=0.012) was higher than that among patients without complications. Although hemoglobin levels (p=0.041) and lymphocyte-to-monocyte ratios (LMR, p=0.017) were lower in patients with complications, the platelet-to-lymphocyte ratios (p=0.034) were higher. Multivariate analysis revealed that current smoking (odds ratio, 3.21; 95% confidence interval, 1.24-18.21) and ASA-PS class of ≥3 (odds ratio, 3.8; 95% confidence interval, 1.18-7.52) were identified as predictors of infectious complications.

Conclusion: Robotic gastrectomy offers technical advantages, but optimizing patient-specific risk is essential for the best outcomes. Preoperative smoking and a high ASA-PS class were independent predictors of infectious complications following robotic gastrectomy. Enhanced perioperative management targeting these risk factors may reduce postoperative morbidity.

Background: Sentinel lymph node biopsy (SLNB) is important in the management of malignant melanoma and is currently performed by pre-operatively injecting a colloid nanomaterial labeled with Technetium (99mTc). Intra-operatively, Patent Blue (PB) is injected to improve the visualization of the lymphatic tract. However, this technique is associated with disadvantages such as radiation exposure and logistic challenges due to short half-live time of 99mTc. Superparamagnetic iron-oxide (SPIO) is a non-radioactive alternative using a magnetic tracer (Magtrace® (Endomagnetics Ltd.)). Several studies showed that SPIO is non-inferior to 99mTc and PB in breast cancer patients. SPIO is expected to be non-inferior in melanoma patients as well. This study aims to evaluate the non-inferiority of pre-operative MRI scanning using SPIO compared to lymphoscintigraphy (LS) and SPECT/CT using 99mTc for identifying SLN status in melanoma patients. Additionally, the non-inferiority of SPIO/magnetometer (Sentimag®, Endomagnetics Ltd.) in comparison with gold standard (99mTc) will be evaluated for SLN procedures in melanoma patients.

Methods: A prospective single-arm non-inferiority study is being performed at the department of surgical oncology at the Zuyderland Medical Center Sittard, the Netherlands. One-hundred-and-forty adult patients with primary melanoma stage I-II with an indication for wide local excision (1 cm) and SLNB will be included. All patients will undergo lymphatic mapping with Magtrace® and 99mTc. The MRI protocol proved to be feasible in the previously conducted pilot study. The MRI protocol will be implemented if it proves to be non-inferior with a margin of 5%.

Clinicaltrials: gov number: NCT05145829.

Discussion: Elimination of radiation exposure is beneficial for both patients and healthcare personnel. Moreover, logistic challenges will be eliminated as SPIO can be injected several days before surgery, immediately followed by MRI scanning. Scheduled surgeries will not be jeopardized by pre-operative logistics and procedures. It will increase both hospital-oriented productivity, patient-friendliness and comfort as surgical delays are avoided.

Background: Allosensitization, defined as the presence of anti-HLA antibodies before transplantation, prolongs the waiting list time and increases the waiting list mortality in patients awaiting for heart transplantation. Treatment protocols have been developed to reduce the load of preformed anti-HLA antibodies (pfDSA), defined as desensitization, and allow safe transplantation across the anti-HLA antibody barrier. Aim of this review is to give an overview on the actual desensitisation strategies in heart transplantation.

Summary: Desensitization can be performed before transplantation or at the time of transplantation when a donor offer becomes available. Treatment protocols should include drugs and interventions that clear pfDSA, target antibody production, and mitigate antibody-mediated graft damage. By now, several transplant centers have developed their own protocols, with optimal graft survival, freedom from antibody-mediated rejection (AMR) and from coronary allograft vasculopathy, without any significant adverse events. The evolution of the immunoassays for pfDSA detection has allowed a better precision in pfDSA characterization, such as measurement of titer and complement-binding capacity. These refinements have permitted crossing acceptable pfDSA without any need of desensitization.

Key messages: Crossing the HLA barrier is feasible and safe in heart transplantation. The complexity and redundancy of the immune pathways requires the identification of the appropriate therapy for each patient. Desensitization protocols should include more than one drug and intervention.

Background: Sentinel lymph node biopsy (SLNB) is a pivotal technique for evaluating regional lymphatic spread in breast, melanoma, and gynecologic malignancies. It minimizes surgical morbidity by avoiding complete lymphadenectomy in early-stage disease. The standard dual-tracer approach-combining a radiocolloid such as technetium-99m with a blue dye like patent blue or isosulfan blue-has high sensitivity but is not universally accessible. Radiocolloids require nuclear medicine facilities' licensing and pose logistical burdens, while patent blue may provoke allergic reactions, including anaphylaxis. These limitations are particularly pronounced in low- and middle-income countries (LMICs), where access and affordability are ongoing challenges. Methylene blue (MB), a low-cost, widely available dye, has gained traction as an alternative tracer, offering a safer and more feasible option for SLNB in resource-limited settings.

Objective: This systematic review evaluates the diagnostic accuracy, detection reliability, and safety profile of methylene blue dye in SLNB across diverse oncologic sites, emphasizing comparing outcomes with traditional dual-tracer approaches.

Methods: A systematic review of PubMed, Embase, Scopus, and Cochrane Library was conducted for studies published from 2000 to 2025. Inclusion criteria comprised clinical studies utilizing MB for SLNB in breast, melanoma, gynaecological, or other solid tumours, reporting outcomes such as detection rate, false-negative rate, or tracer-related complications. Data were extracted and synthesized descriptively. Where possible, pooled performance metrics were calculated.

Results: Twenty-five studies encompassing 5,240 patients were included. The pooled sentinel node detection rate using MB alone was 84.5% (72.0-96.2%), with a false-negative rate of 8.6%. When MB was combined with radiocolloid, detection rates improved to 96.1%, and false-negative rates dropped below 5%. Adverse effects were rare, with skin necrosis in fewer than 2% of cases and no serious allergic events reported. Most studies focused on breast cancer (18/25), while data on melanoma and gynecologic cancers were comparatively limited.

Conclusion: Methylene blue is a viable alternative for SLNB, particularly in environments where dual-tracer methods are impractical. Though slightly less sensitive than dual-tracer techniques, MB offers substantial advantages in cost, safety, and accessibility. Further multicenter studies and long-term outcomes are needed to support its broader adoption in global oncology practice.

Introduction: Lymph node metastasis is crucial in determining prognosis and treatment for gastric cancer. Vascular Endothelial Growth Factor-C (VEGF-C), known for its role in lymphangiogenesis, has been linked to metastasis in various cancers. This study investigates the correlation between VEGF-C expression, lymph node metastasis, and overall survival in gastric cancer patients.

Methods: This retrospective cohort study included 109 patients who underwent gastrectomy and D2 lymphadenectomy for gastric adenocarcinoma between 2011 and 2019. VEGF-C expression was evaluated via immunohistochemistry. Clinical data, including demographics, tumor characteristics, lymph node involvement, and survival outcomes, were analyzed. Cox regression identified factors affecting mortality.

Results: VEGF-C expression was categorized as absent, low, or high. Although no significant association was found between VEGF-C expression and lymphatic metastasis, lymphatic invasion was more frequent (87.9%) in patients with high VEGF-C expression. VEGF-C was significantly associated with perineural invasion and the development of distant metastasis during follow-up, highlighting its potential role in tumor progression beyond lymphatic dissemination. Cox regression identified T3/T4 tumors, metastasis during follow-up, and lack of adjuvant radiotherapy as independent prognostic factors for overall survival.

Conclusion: While VEGF-C was not directly linked to lymph node metastasis, its strong association with perineural invasion and subsequent metastasis highlights its potential prognostic value in identifying aggressive tumor behavior. Further studies are needed to clarify its prognostic significance in gastric cancer.

Introduction The shortage of donor grafts for kidney transplantation remains a critical challenge. En bloc kidney transplantation (EBKT) from small deceased pediatric donors can potentially expand the donor pool. This study aimed to investigate the safety of pediatric-donor EBKT in adults compared with the standard deceased kidney transplantation (SDKT). Methods This retrospective study was performed to compare outcomes after pediatric-donor EBKT (n = 17; donor weight, 9.8  4.0 kg) and SDKT (n = 72; donor weight, 79.6  18.4 kg) in adult recipients at our center. Outcomes of EBKT from donors weighing 10 kg were compared with those from donors weighing ≥10 kg. The primary outcome was death-censored graft survival. Secondary outcomes included patient survival, serum creatinine, and the incidence of postoperative complications. Results The death-censored graft survival rates at 1, 5, and 10 years were 0.86 ± 0.09, 0.86 ± 0.09, and 0.86 ± 0.09, respectively, for pediatric-donor EBKTs, and 0.84 ± 0.05, 0.76 ± 0.07, and 0.64 ± 0.13, respectively, for SDKTs (P > 0.05). The patient survival rates at 1, 5, and 10 years were 0.93 ± 0.06, 0.67 ± 0.16, and 0.24 ± 0.20, respectively, for pediatric-donor EBKTs, and 0.86 ± 0.04, 0.60 ± 0.08, and 0.42 ± 0.10, respectively, for SDKTs (P > 0.05). No significant differences were observed between pediatric-donor EBKT and SDKT groups in postoperative complications (P > 0.05). Subgroup analysis of pediatric-donor EBKT by donor body weight revealed no significant differences (P > 0.05) in long-term graft and patient survival. Conclusion Pediatric-donor EBKT in adults is a safe approach, with outcomes comparable to those of SDKT in our study. Moreover, EBKT from donors weighing <10 kg demonstrated comparable long-term graft and patient survival to that from donors weighing ≥10 kg. Considering the small sample size and the increased mortality observed over time, further research involving larger cohorts is necessary to validate these findings and to refine criteria for optimal recipient selection.

Purpose: To identify independent risk factors for bile leakage and incisional infection after choledocholithotomy and to explore the potential association between bile leakage and incisional infection.

Methods: A retrospective study was conducted on 621 patients who underwent laparoscopic or open choledocholithotomy combined with cholecystectomy between January 2017 and October 2024. Clinical data were collected, and univariate analysis followed by binary logistic regression was used to identify independent risk factors for postoperative bile leakage and incisional infection.

Results: Bile leakage occurred in 60 patients (9.7%). Multivariate analysis showed that open surgery (OR = 1.672), acute biliary inflammation (OR = 2.469), advanced age (OR = 1.061), continuous suturing (OR = 4.991), prolonged operative time (OR = 1.005), and bile pathogen infection (OR = 2.37) were independent risk factors (all P < 0.05). Among 181 patients who underwent open or converted surgery, 40 (22.1%) developed incisional infections. Independent risk factors for incisional infection included advanced age (OR = 1.055), prolonged operation time (OR = 1.006), elevated postoperative WBC count within 24 hours (OR = 1.149), emergency surgery (OR = 3.745), longer incision length (OR = 1.141), and postoperative bile leakage (OR = 14.027) (all P < 0.05), indicating a strong association between bile leakage and subsequent wound infection.

Conclusion: Open surgery, acute inflammation, older age, continuous suturing, and intra-biliary infection significantly increase the risk of postoperative bile leakage. Moreover, bile leakage was identified as a strong independent predictor of incisional infection. In addition, prolonged operative time, elevated early postoperative leukocyte count, emergency surgery, and longer incisions were also associated with increased infection risk.

Introduction: Pressure injuries (PIs) in patients with diabetes mellitus (DM) still impacts patients' health and places a heavy burden on healthcare systems. Stage I and stage II PIs are particularly prevalent among individuals with diabetes. Without timely and appropriate interventions, these injuries can progress to more severe stages, requiring prolonged recovery periods. Thus, the development of preclinical animal models that can mimic stage I or II pressure injuries in diabetic patients is urgently needed to understand the mechanisms of injury formation and healing.

Methods: In this study, magnets were used to compress the dorsal sides of mice for 2 hours (h), 4 h, 8 h, or 16 h according to the ischaemia-reperfusion principle, and the changes in compressed skin in diabetic (db/db) and nondiabetic (WT) mice were compared at different ischaemia exposure times and cycle times.

Results: After 2 h of ischemia, there was no significant injury in WT and db/db mice. On the third day following 4 h of ischemia, both db/db and WT mice exhibited characteristics resembling human stage II pressure injuries, with damage primarily confined to the epidermis and upper dermis. Ischemia durations of 8 and 16 h resulted in more severe full-thickness skin defects, including exposed subcutaneous adipose tissue and inward contraction of wound margins. After ischaemia (I) for 4 h and reperfusion (R) for 24 h, the morphology of fibroblasts in the compressed skin area of db/db mice changed, and the expression of TGF-β1 decreased significantly compared with those in WT mice. On day 5, epidermal-dermal separation and pronounced infiltration of inflammatory cells were evident in both groups. On day 10, db/db mice exhibited delayed wound closure, as well as impaired regeneration of the panniculus carnosus and dermis, with significantly decreased mRNA levels of VEGF and HSP90.

Conclusion: Ischaemia lasting 4 h is the appropriate duration for generating stage II pressure injuries in diabetic mice, which may be applicable to generate a reproducible model of stage II pressure injury caused by ischaemia-reperfusion injury. This model offers a valuable experimental tool for in-depth investigation of the pathogenesis of diabetic pressure injuries and for the development of novel therapeutic strategies.

Banna miniature inbred pigs (BNs) are highly inbred strains derived from Diannan miniature pigs (DNs) through full-sibling or parent‒offspring mating protocols developed in 1980. BNs could be potentially used as organ donors for xenotransplantation, but the biological characteristics of BNs have not yet been systematically reported. In this study, the body growth, organ development, reproductive performance, and blood chemistry of BNs were evaluated and compared with those of Göttingen minipigs (GMs) and other Chinese native mini-pig breeds to provide a fundamental basis for their application. The results revealed that the birth weight of BNs was 0.49±0.12 kg and that the body weight at 6 months of age was less than 30 kg. From 4 months of age, the body weight of BN sows was significantly greater than that of boars (P<0.05), which remained consistent until 10 months of age. The ages of the sexual and body maturity of BNs was 4~5 and 10 months, respectively. The number of live piglets per litter, birth weight, weaning weight, litter weight at birth, and weaning weight were significantly lower than those of DNs (P<0.01). The physiological parameters of BNs, including hematocrit, mean cell volume, hemoglobin concentrations, reticulocyte count, basophils, platelet count, and fibrinogens, and the biochemical parameters, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, albumin, total bilirubin, carbamide, creatinine, triglyceride, total cholesterol, lactate dehydrogenase, glucose, and ion levels, were significantly different from those of GMs. Organ weights and coefficients for different ranges of body weights were obtained. The reference values of the blood physiological and biochemical parameters of BNs were established, and some indices were different from those of GMs and other breeds. This information could be helpful in selecting BNs for preclinical and clinical trials of xenotransplantation, thereby promoting their application in biomedical research.