Real-world data on efficacy/safety and economic impact of nivolumab administered every 2 and 4 weeks among Japanese patients.

AIM: A new treatment interval for nivolumab administration at 480 mg every 4 weeks, in addition to 240 mg every 2 weeks, was approved in Japan in 2020. Using model-based evaluation, it was speculated that the effects or safety of nivolumab do not differ between the two treatment intervals; however, real-world data on nivolumab efficacy, safety, and economic impact are lacking. Accordingly, we aimed to examine the effects of nivolumab treatment intervals (2 weeks vs. 4 weeks) in terms of efficacy, safety, and economic impact in Japanese patients with cancer. METHODS: We retrospectively analyzed 126 patients treated with nivolumab. The patients were divided into two groups depending on whether they received nivolumab at 240 mg every 2 weeks (2-week group) or 480 mg every 4 weeks (4-week group). RESULTS: Efficacy results found no significant difference between the 4- and 2-week groups considering median overall survival (p = 0.70) and median progression-free survival (p = 0.57). The incidence of any grade and ≥  grade 3 immune-related adverse events did not differ between the 4-week and 2-week groups (any grade, p = 0.13; ≥  grade 3, p = 0.36). Excluding drug costs, the 4-week group had significantly lower medical costs than the 2-week group (2-week vs. 4-week: mean, 94,659 JPY [679.0 USD] vs. 58,737 JPY [421.3 USD]; p < 0.05). CONCLUSION: Collectively, our findings suggest that nivolumab 480 mg every 4 weeks may be more effective than nivolumab 240 mg every 2 weeks in terms of economic impact.

Analyses of tertiary lymphoid structures observed in cases of Merkel cell carcinoma showing spontaneous regression.

Merkel cell carcinoma (MCC) is a high-grade skin cancer, but spontaneous regression is observed at a markedly higher frequency than in other carcinomas. Although spontaneous regression is a phenomenon that greatly impacts treatment planning, we still cannot predict it. We previously reported on the prognostic impact of the presence or absence of tertiary lymphoid structures (TLS) and of Merkel cell polyomavirus (MCPyV) infection. To learn more about the spontaneous regression of MCC, detailed analyses were performed focusing on spontaneous regression cases. We collected 71 Japanese patients with MCC including 6 cases of spontaneous regression. Samples were analysed by immunostaining, spatial single-cell analysis using PhenoCycler, and RNA sequencing using the next-generation sequencer (NGS). All 6 cases of spontaneous regression were positive for MCPyV. TLS was positive in all 5 cases analysed. Spatial single-cell analyses revealed that PD-L1-positive tumour cells were in close proximity to CD20-positive B cell and CD3-, 4-positive T cells. Gene set enrichment analysis between MCPyV-positive and TLS-positive samples and other samples showed significantly high enrichment of "B-cell-mediated immunity" gene sets in the MCPyV-positive and TLS-positive groups. In conclusion, TLS may play an important role in the spontaneous regression of MCC.

[Evaluation of Changes in Membranous Septum Length during the Cardiac Cycle and by Measurement Methods Using the Preoperative CT for Transcatheter Aortic Valve Replacement: A Single-center Cross-sectional Study].

PURPOSE: The purpose of this study was to evaluate the changes in membranous septum (MS) length during the cardiac cycle and by measurement methods using the preoperative computed tomography (CT) images for transcatheter aortic valve replacement (TAVR). METHOD: Among 34 consecutive patients who underwent preoperative contrast-enhanced CT for TAVR, we measured MS lengths by three measurement methods (coronal, stretched, and reformatted coronal view method) at 10% intervals in the cardiac cycle. RESULT: MS lengths differed between the three measurement methods in all cardiac phases. Moderate correlations were observed between the MS lengths measured by the coronal view method and the other two methods. In contrast, strong correlations were observed between the MS lengths measured by the stretched view method and the reformatted coronal view method. The frequencies of the minimum and maximum MS lengths during the cardiac cycle tended to be highest at R-R 90% and R-R 30%, respectively. The median MS lengths at R-R 90% were smaller than those at R-R 30% in all measurement methods. CONCLUSION: The MS length in patients undergoing contrast-enhanced CT for TAVR varies notably depending on the cardiac cycle and measurement methods. When evaluating MS length, it is crucial to consider the measurement method and to perform measurements during diastole in order to evaluate the minimum value during the cardiac cycle.

Efficacy and safety of TM5614 in combination with paclitaxel in the treatment of paclitaxel-resistant cutaneous angiosarcoma: Phase II study protocol.

Cutaneous angiosarcoma (CAS) is an endothelial cell-derived, highly aggressive type of vascular tumour. Although chemoradiotherapy with paclitaxel (PTX) is recognized as a first-line therapy for CAS, second-line therapy for CAS remains controversial, and there is no standard therapy for taxane-resistant CAS. Plasminogen activator inhibitor-1 (PAI-1) is associated with poor clinical outcomes, and elevated levels of PAI-1 in both tissue and serum are correlated with poor response to therapy in various cancers, including skin cancers. Since PAI-1 protects endothelial cells from Fas ligand-mediated apoptosis, PAI-1 inhibition might induce apoptosis of endothelial cell-derived tumours such as CAS. This is a single-arm, open-label, multi-institutional, Phase 2 clinical trial to assess the efficacy and safety of PTX in combination with TM5614 (PAI-1 inhibitor) in patients with PTX-resistant CAS. PTX will be administered for 28 weeks, with oral administration of TM5614. The primary endpoint of this study will be the overall response rate (ORR) at 28 weeks after starting treatment (central image evaluation). The secondary endpoint will include the ORR at 28 weeks after starting treatment (investigator evaluation), ORR at 8 weeks and 16 weeks after initiation of treatment (central and investigator evaluation), progression-free survival, overall survival, disease control rate and safety profiles. Assuming the null hypothesis of a response rate of 13.6% and an alternative hypothesis of 45%, a minimum of 15 patients are required to achieve a two-sided, Type I error of 5% and power of 70% based on the exact binomial distribution. Data quality control will be conducted by a combination of centralized (remote) and on-site monitoring. This study will contribute to the development of novel combination therapy for PTX-resistant CAS patients, which remains an unmet clinical need.

Eosinophil may be a predictor of immune-related adverse events induced by different immune checkpoint inhibitor types: A retrospective multidisciplinary study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause severe immune-related adverse events (irAEs). However, biomarkers for irAEs common to different types of ICIs and cancers have not been reported. This study examined whether eosinophils can be used as a predictor of irAEs. METHODS: Six hundred fourteen patients with cancer (esophageal, gastric, head and neck, lung, melanoma, renal cell, urothelial, and other cancer) received anti-PD-1, anti-PD-L1, or anti-CTLA-4 plus anti-PD-1 therapy. The patients were divided into two groups depending on whether they experienced irAEs (irAE group) or not (non-irAE group). Eosinophils were examined before the two-course treatment. RESULTS: Patients in the irAE group who received anti-PD-1 or anti-CTLA-4 plus anti-PD-1 therapy had higher eosinophils before the two-course treatment than those in the non-irAE group (p < 0.05). The eosinophils in the anti-PD-L1 therapy group tended to increase in the irAE group. Furthermore, eosinophils in gastric, head and neck, lung, melanoma, renal, and urothelial cancers were significantly higher in the irAE group than in the non-irAE group (p < 0.05). The optimal cutoff value for eosinophils against irAEs was 3.0% (area under the curve = 0.668). In multivariate analyses, eosinophils of ≥3.0% were an independent factor for irAEs (odds ratio: 2.57, 95% CI: 1.79-3.67). CONCLUSION: An increased eosinophil before the two-course treatment may be a predictor of irAEs in various cancers treated with different ICIs.

Effectiveness Treatment of a BRAF-ZKSCAN5 Fusion Gene Melanoma Case with Dabrafenib/Trametinib.

The most important driver gene in malignant melanoma is the BRAF mutation, and molecularly targeted therapies targeting mutations, mainly V600E and V600k, are used in clinical practice. In this report, we treated a patient with malignant melanoma expressing a rare BRAF-ZKSCAN5 fusion gene with dabrafenib/trametinib. The patient was a 71-year-old female. She was diagnosed with malignant melanoma (pT4aN3M0, STAGE IIIC) of the abdomen with axillary lymph node metastasis. She underwent extended resection and axillary lymph node dissection and was treated with adjuvant therapy, but lung and mediastinal lymph node metastases developed. The patient was treated with immune checkpoint inhibitors for metastatic lesions and achieved complete remission, but relapsed and metastatic lesions appeared in the cervical lymph nodes. Next-generation sequencing revealed the BRAF-ZKSCAN5 fusion gene, and treatment with dabrafenib/trametinib was initiated. After 1 month of treatment, tumor growth stopped and the length of the tumor shrank by 22.2%, but she developed grade 3 adverse events of nausea, fatigue, and diarrhea and had difficulty exercising, forcing her to discontinue treatment after 6 weeks. The tumor continued to shrink during drug administration. This case report may provide insight into treatment options for cases in which the BRAF fusion gene was observed, which is expected to be detected in large numbers by next-generation sequencing in the future.

Corrigendum: Dendritic cell proliferation by primary cilium in atopic dermatitis.

[This corrects the article DOI: 10.3389/fmolb.2023.1149828.].

Normal growth curve of choroid plexus in children: implications for assessing hydrocephalus due to choroid plexus hyperplasia.

OBJECTIVE: Pediatric hydrocephalus requires evaluation while accounting for growth of the intracranial structures, but information on choroid plexus growth in children is lacking. This study aimed to create normal growth curves for intracranial volume, choroid plexus volume, and lateral ventricles volume. Additionally, the authors aimed to objectively assess the degree of hydrocephalus caused by choroid plexus hyperplasia (CPH) and to examine the impact of surgical procedures. METHODS: This retrospective study analyzed the head CT scans of pediatric patients with minor head trauma treated at Osaka Women's and Children's Hospital between March 2006 and May 2023. The study segmented and calculated intracranial, choroid plexus, and lateral ventricles volumes. The study also calculated the correlation coefficients among these 3 parameters. Patients aged 0 to 10 years were divided into 15 age-related clusters, and mean ± SD values were calculated for each cluster. Growth curves were created by plotting mean values sequentially. Volume obtained from patients with CPH were z-normalized using mean and SD values and compared. RESULTS: A total of 229 CT scans (94 from females) were analyzed, and positive correlations were observed among intracranial volume, choroid plexus volume, and lateral ventricles volume, with the strongest correlation between the choroid plexus and lateral ventricles volumes. The growth rate of intracranial volume was rapid until approximately 20 months of age, while those of choroid plexus volume and lateral ventricles volume increased rapidly until approximately 1 year of age. Subsequently, choroid plexus volume and lateral ventricles volume plateaued at 1.5 ml and 10 ml, respectively. Three patients with CPH were enrolled and quantitatively evaluated on the basis of the z-normalized volume. Notable abnormal volumes of the choroid plexus (range z-normalized values 24.11-51.17) and lateral ventricles (46.78-122.36) were observed. In 2 patients, improvements in the z-normalized values of intracranial volume and lateral ventricles volume were observed after surgical interventions. Additionally, in 1 patient, choroid plexus volume was reduced by approximately 24% (range z-normalized values 51.17-38.93) after bilateral endoscopic plexus coagulation. CONCLUSIONS: This study provides normal growth curves for intracranial volume, choroid plexus volume, and lateral ventricles volume. Knowledge of these normal values holds the potential for objective assessment of abnormal values associated with hydrocephalus and choroid plexus diseases such as CPH.

Clinical Outcomes of Radiation Therapy for Angiosarcoma of the Scalp and Face: A Multi-Institutional Observational Study.

Angiosarcoma of the scalp and face (ASF) is a rare, aggressive tumor often treated with multimodal therapy, including radiation therapy (RT). This study assessed RT outcomes for ASF and identified prognostic factors. Data from 68 non-metastatic ASF patients undergoing RT with or without other therapies were analyzed. Median radiation dose was 66 Gy in 33 fractions (interquartile range (IQR) 60-70 Gy in 28-35 fractions). Local control (LC), progression-free survival (PFS), and overall survival (OS) rates were calculated using Kaplan-Meier analysis. Multivariate analyses and adverse event evaluation were conducted. Median patient age was 75 years (IQR 71-80 years), with a median follow-up of 17 months (IQR 11-42 months). One-/three-year LC rates were 57/37%, PFS rates were 44/22%, and OS rates were 81/44%. Multivariate analyses showed that an equivalent dose in a 2 Gy fraction (EQD2) >66 Gy correlated with improved LC (HR 2.35, 95% CI 1.03-5.32, p = 0.041). Combining chemotherapy (HR 2.43, 95% CI 1.08-5.46, p = 0.032) or surgery (HR 2.41, 95% CI 1.03-5.59, p = 0.041) improved PFS. No factors influenced OS. Late grade 3+ toxicities occurred in 1%, with one patient developing a grade 4 skin ulcer. These findings suggest that EQD2 > 66 Gy and combining chemotherapy or surgery can enhance LC or PFS in ASF. Further prospective studies are needed to determine the optimal treatment strategy for this rare malignancy, particularly in elderly patients.

Evaluation of prognostic prediction ability of the novel Japanese risk factor scoring system in a Japanese cohort of resectable cutaneous squamous cell carcinoma: A retrospective cross-sectional study.

Japanese patients with very high-risk cutaneous squamous cell carcinomas (cSCCs), based on the National Comprehensive Cancer Network guidelines, have been reported to display a higher cumulative incidence of relapse and disease-specific death (DSD) than those with high-risk cSCC. Therefore, prognosis prediction is crucial for Japanese patients with very high-risk cSCCs. Herein, we aimed to evaluate the prognostic prediction ability of our novel Japanese Risk Factor Scoring Systems (JARF scoring) in a Japanese cohort of cSSC patients. Data of 424 Japanese patients with resectable very high-risk cSCCs were analysed. We compared the prognostic ability of the following three staging systems: Brigham and Women's Hospital (BWH) tumour staging, number of NCCN very high-risk factors, and JARF scoring, including recurrent tumour, high-risk histological features, deep tumour invasion and lymphatic or vascular involvement as risk factors. The prognostic ability of these staging systems was evaluated according to the cumulative incidence of local recurrence (LR), regional lymph node metastasis (RLNM), DSD, and overall survival (OS). When BWH staging was used, high T stage led to significantly poor outcomes only in the cumulative incidence of RLNM (p = 0.01). The presence of very high-risk NCCN factors led to significantly poor outcomes in terms of RLNM (p = 0.03) and OS (p = 0.02). Meanwhile, a high number of risk factors in the JARF scoring system clearly led to poor outcomes in terms of LR (p = 0.01), RLNM (p < 0.01), DSD (p = 0.03), and OS (p < 0.01). The JARF scoring system may accurately predict the risk of recurrence and death in very high-risk cSCC patients in Japan.

Dendritic cell proliferation by primary cilium in atopic dermatitis.

Introduction: Atopic dermatitis (AD) is a common allergic eczema that affects up to 10% of adults in developed countries. Immune cells in the epidermis, namely, Langerhans cells (LCs), contribute to the pathogenesis of AD, although their exact role(s) in disease remain unclear. Methods: We performed immunostaining on human skin and peripheral blood mononuclear cells (PBMCs) and visualized primary cilium. Result and discussion: We show that human dendritic cells (DCs) and LCs have a previously unknown primary cilium-like structure. The primary cilium was assembled during DC proliferation in response to the Th2 cytokine GM-CSF, and its formation was halted by DC maturation agents. This suggests that the role of primary cilium is to transduce proliferation signaling. The platelet-derived growth factor receptor alpha (PDGFRα) pathway, which is known for transducing proliferation signals in the primary cilium, promoted DC proliferation in a manner dependent on the intraflagellar transport (IFT) system. We also examined the epidermal samples from AD patients, and observed aberrantly ciliated LCs and keratinocytes in immature and proliferating states. Our results identify a potential relationship between the primary cilium and allergic skin barrier disorders, and suggest that targeting the primary cilium may contribute to treating AD.

Tumor immune microenvironment of cutaneous angiosarcoma with cancer testis antigens and the formation of tertiary lymphoid structures.

Cutaneous angiosarcoma (CAS) is a highly malignant tumor with few effective treatments. Although the indication for immune checkpoint inhibitors such as anti-PD-1 antibodies is expected to expand, there are many unknowns regarding the tumor immune microenvironment in CAS, which is generally considered an immunologically "cold" tumor. Our previous study demonstrated that tertiary lymphoid structures (TLSs) were associated with a favorable prognosis in CAS. However, we still don't know what the difference is between cases of TLS-rich and TLS-poor. Furthermore, the number of TLSs can vary significantly between lesions in the same case, for example, between primary and recurrence. To analyze the changes in the tumor immune microenvironment in CAS in more detail, we performed comprehensive RNA sequencing using a Next-generation sequencer (NGS). Sixty-two samples from 31 cases of CAS treated at Nagoya City University were collected. NGS and gene set enrichment analysis (GSEA) were performed on 15 samples among them. Immunohistochemistry and prognostic analysis by Kaplan-Meier method were performed on all 62 samples. NGS results showed that NY-ESO-1 (CTAG1B) was significantly upregulated in the TLS-positive cases. Immune checkpoint molecules including programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) were upregulated in TLS-negative or TLS-low cases and seemed to associate with the suppression of TLS formation. In a comparison of primary and recurrent lesions, other cancer-testis antigens (CTAs) including XAGE-1B were significantly upregulated in recurrent lesions. The number of infiltrating CD8-positive cells and TLSs showed no significant trend between primary and recurrent lesions. However, the PD-L1 expression of tumor cells was significantly lower in recurrent than in primary lesions. Chemokines correlated with NY-ESO-1 expression were CCL21 and CXCL8, and only CCL21 correlated with the number of TLS. There was no chemokine associated with XAGE-1. NY-ESO-1 and XAGE-1 are detectable by immunohistochemistry. Although each cannot be a prognostic marker by itself, they can be a helpful marker in combination with the number of TLSs. CTAs play an essential role in forming the tumor immune microenvironment in CAS. These findings are evidence that CAS is an immunologically "hot" tumor and provides us with potential therapeutic targets and encourages the expansion of immunotherapy indications.

Differences in the immune microenvironment between improved and non-improved cases of vitiligo after halo nevus excision.

BACKGROUND: Halo nevus, also called Sutton's nevus, is a nevus cell nevus surrounded by vitiligo thought to be caused by a T-cell mediated immune response to the nevus antigen. The immune microenvironment is mysterious, however, as vitiligo often does not improve even when the nevus cells are removed. OBJECTIVES: To analyze the clinical course and immune microenvironment of patients with halo nevus who had undergone nevus excision. METHODS: We collected 54 halo nevus patients and performed multivariate analysis and immunohistochemical analysis, including multiplexed immune cell phenotyping and spatial single-cell analyses using the PhenoCycler® assay. RESULTS: Multivariate analysis revealed that only the presence or absence of vitiligo vulgaris at the time of consultation was associated with improvement in the surrounding vitiligo following excision. Expression of programmed death-ligand 1 in nevus cells was significantly higher in non-improved cases compared with improved cases. The PhenoCycler® assay revealed that CD107a-positive and CD21-positive cells were more prevalent in improved cases than in non-improved cases. In the improved cases, active cell-cell interactions, centered on CD21-positive cells, were observed, whereas in the non-improved cases, cell-cell interactions were sparse. Instead, a dense infiltration of CD8-positive cells and CD3 and CD4-positive cells was observed in non-improved cases. CONCLUSION: Elucidation of the immune microenvironment of halo nevus is also relevant to melanoma-associated vitiligo and will contribute to our understanding of tumor immunity.

Influence of aldo-keto reductase 1C3 polymorphisms in early-onset female psoriasis patients.

The principal pathology of psoriasis is impaired skin barrier function, epidermal thickening, and granular layer loss. Exposure to extrinsic factors such as tobacco smoke and air pollutants is associated with the development of psoriasis. Aryl hydrocarbon receptors (AHRs) are activated by extrinsic factors associated with the development of psoriasis and act as transcriptional regulators. Expression of aldo-keto reductase (AKR) 1C3 in the epidermal spinous layer regulates epidermal keratinocyte differentiation via the AHR signaling pathway. We investigated whether single nucleotide polymorphisms (SNPs) in AKR1C3 are associated with the pathogenesis of psoriasis. The proportions of rs12529 G/C, C/C variants, and rs12387 A/A, A/G variants were twofold higher in Japanese psoriasis patients (n = 231) compared with a Japanese healthy cohort. The SNPs were significantly more common than the majority variants in female patients with disease onset ≤ 22 years of age. Patients with rs12529 G > C and rs12387 A > G SNPs exhibited significantly lower AKR1C3 expression and higher expression of late differentiation markers. In conclusion, AKR1C3 downregulation caused by rs12529 G > C and rs12387 A > G SNPs in the epidermis induces abnormal early differentiation of keratinocytes and skin barrier dysfunction, which may contribute to the genetic pathogenesis of psoriasis in young females.

Anti-Inflammatory Role of TRPV4 in Human Macrophages.

The pathology of skin immune diseases such as atopic dermatitis is closely related to the overproduction of cytokines by macrophages. Although the pathological functions of macrophages in skin are known, mechanisms of how they detect the tissue environment remain unknown. TRPV4, a nonselective cation channel with high Ca2+ permeability, is activated at physiological temperatures from 27 to 35°C and involved in the functional control of macrophages. However, the relationship between TRPV4 function in macrophages and skin immune disease is unclear. In this study, we demonstrate that TRPV4 activation inhibits NF-κB signaling, resulting in the suppression of IL-1ß production in both human primary monocytes and macrophages derived from human primary monocytes. A TRPV4 activator also inhibited the differentiation of human primary monocytes into GM-CSF M1 macrophages but not M-CSF M2 macrophages. We also observed a significant increase in the number of inducible NO synthase-positive/TRPV4-negative dermal macrophages in atopic dermatitis compared with healthy human skin specimens. Our findings provide insight into the physiological relevance of TRPV4 to the regulation of macrophages during homeostasis maintenance and raise the potential for TRPV4 to be an anti-inflammatory target.

Complications and risk factors of punch biopsy: A retrospective large-scale study.

The authors analyzed the risk factors of punch biopsy by investigating the complications of the technique and their proportions. Patients who underwent punch biopsy in a dermatology clinic between November 2018 and November 2020 (n = 1294; mean age, 62.3 years; 540 men and 754 women) were enrolled in the current study. The most common complication was postoperative bleeding (0.9%). Wound infection (0.2%), surrounding skin damage (0.2%), and vagal reflex (0.1%) were also observed. The main risk factors for bleeding following biopsy were location of biopsy site outside of the trunk (odds ratio [OR], 4.60 [95% CI, 2.65-8.00]; p < 0.001) and platelet count lower than 150 000/µL (OR, 2.82 [95% CI, 1.69-4.73]; p < 0.001). When performing a punch biopsy, an adequate explanation of the risks and complications should be provided before obtaining informed consent. Further, blood sampling tests should be performed in advance and the types of cases that may require wound suture should be appropriately determined.

Stent implantation in a patient with non-hemorrhagic vertebral artery dissection associated with severe, continuously progressive stenosis in the posterior inferior cerebellar artery bifurcation region: A case report.

Generally, the prognosis of non-hemorrhagic vertebral artery dissection is good. Treatment should be considered when stenosis progresses or when an aneurysm is formed. However, no clear treatment policy has been established. The purpose of this case report was to describe the treatment policy for non-hemorrhagic onset vertebral artery dissection with severe stenosis around the posterior inferior cerebellar artery (PICA) bifurcation and aneurysm, where stent placement in the vertebral artery was difficult. This report describes healing without complications with stent implantation in the PICA performed to treat non-hemorrhagic vertebral artery dissection with associated severe, continuously progressive stenosis in the PICA bifurcation region. A 36-year-old woman was examined at the authors' hospital for persistent pain in the left posterior neck. Left vertebral arteriography revealed stenosis due to dissection around the PICA bifurcation and aneurysm formation at the distal position. Due to the progression of stenosis, there were concerns about PICA occlusion, and stent implantation in the vertebral artery was performed via the PICA. Neck pain ceased immediately after surgery, and 3 months later, cerebral angiography showed favorable patency of the PICA and decreased aneurysm size. This case suggests that stent implantation in the PICA might be a useful treatment option for non-hemorrhagic vertebral artery dissection with associated severe stenosis in the PICA bifurcation region.

Knapperer Resektionsrand bei Plattenepithelkarzinomen mit hohem oder sehr hohem Risiko: eine retrospektive multizentrische Studie mit 1000 Patienten.

HINTERGRUND UND ZIELE: Bei kutanen Plattenepithelkarzinomen (PEK) ist die Einhaltung der in Leitlinien empfohlenen festen Resektionsränder oft schwierig und knappere Ränder sind wünschenswert. Ziel dieser Studie war die Bewertung des Auftretens von Rezidiven und krankheitsspezifischen Todesfällen bei knapperen Resektionsrändern für PEK mit hohem oder sehr hohem Risiko. PATIENTEN/METHODEN: PEK-Patienten mit hohem oder sehr hohem Risiko, bei denen eine Tumorexzision durchgeführt wurde, wurden retrospektiv untersucht. Die Patienten wurden in eine Gruppe mit Standardrand gemäß Leitlinienempfehlung (standard margin group, SMG) und eine Gruppe mit knapperen Rändern (narrower-margin group, NMG) eingeteilt. Gemeinsame primäre Endpunkte waren lokales Rezidiv, PEK-Rezidiv und PEK-bedingter Tod. Die Wahrscheinlichkeit eines PEK-bedingten Tods und konkurrierender Mortalitätsrisiken wurde mittels kumulativer Inzidenzfunktion (CIF) beschrieben. Unterschiede bei der CIF zwischen den Gruppen wurden mit dem Test nach Gray verglichen. ERGEBNISSE: Insgesamt wurden 1.000 Patienten mit PEK (hohes Risiko, 570; sehr hohes Risiko, 430) eingeschlossen. In der Kohorte mit hohem Risiko gab es keine signifikanten Unterschiede bei der unvollständigen Exzisionsrate (IER) zwischen SMG und NMG (2,6 % vs. 3,0 %, P > 0,99). In der Kohorte mit sehr hohem Risiko war die IER in der SMG jedoch signifikant geringer als in der NMG (8.9 % vs. 16.2 %, P = 0,03). Keine signifikanten Unterschiede zwischen SMG und NMG wurden für Lokalrezidiv (hohes Risiko, P = 0.56; sehr hohes Risiko, P = 0,70), PEK-Rezidiv (hohes Risiko, P = 0,30; sehr hohes Risiko, P = 0,47) und PEK-bedingtem Tod (hohes Risiko, P = 0,23; sehr hohes Risiko, P = 0,83) beobachtet. SCHLUSSFOLGERUNGEN: Die Größe des Resektionsrands hat einen begrenzten Einfluss auf Randkontrolle, Rezidive und krankheitsspezifischen Tod bei PEK mit hohem Risiko.