Aim: Early‐onset colorectal cancer (EOCC), defined as colorectal cancer (CRC) diagnosed in patients under the age of 50, has increased alarmingly in Western countries in recent decades. Although risk factors, diagnostics and treatment approaches have been studied, the subjective experiences of EOCC patients remain underexplored. This study aimed to identify patient‐perceived challenges and their unmet needs in Switzerland, a country with a high‐resource healthcare system with minimal waiting times for investigations and comprehensive healthcare coverage. Method: Nineteen semi‐structured interviews were conducted between 09/2023 and 06/2024 with EOCC patients following a constructivist grounded theory approach. Results: Participants from all cancer stages and aged between 30 and 50 years were recruited. We developed three main themes from the collected data: diagnostic delay, coping mechanisms and stigmatisation. Despite access to a well‐resourced healthcare system, study participants experienced diagnostic delays, indicating the need for increased physician awareness and improved risk‐based screening for high‐risk individuals. Participants' key coping strategies included self‐advocacy and participating in medical decision‐making, like prioritising fertility preservation over rushed treatment. Participants reported fear of stigmatisation and isolation after being diagnosed. Such stigma manifested in concerns over alopecia or living with an ostomy. Finally, participants experienced an internal shift in personal priorities resulting in post‐traumatic growth despite cancer diagnosis Conclusions: EOCC challenges current clinical practices. Better physician awareness, risk‐factor‐based screening policies, integrated discussions about individual treatment such as potential fertility issues and targeting stigma are critical for improving the EOCC patients' journey.

Pancreatic ductal adenocarcinoma (PDAC) is the deadliest major cancer and has a profoundly immunosuppressive tumor microenvironment (TME). Previous studies have shown that inhibition of the E1 enzyme, which catalyzes the small ubiquitin-like modifiers (SUMO), with the small molecule TAK-981, can reprogram the TME to enhance immune activation and suppress tumor growth. We found that the CD-155/TIGIT pathway, a key regulator of immune evasion in PDAC, is influenced by SUMOylation. We hypothesized that the combination of SUMO E1 and TIGIT inhibition would synergistically induce antitumor immune effects. We used a clinically relevant orthotopic mouse model that consistently develops liver metastases to study this combination therapy alone and in the perioperative setting with surgical resection. The combination of SUMO E1 and TIGIT inhibition significantly prolonged survival. Complete responders exhibited protective immunity and enhanced T-cell reactivity to model-specific alloantigens. Complementary immune analyses of resected tumors demonstrated that combination therapy more significantly reduces the abundance of regulatory FoxP3+CD4+ T cells than either monotherapy alone. Mechanistic studies suggest that SUMO E1 inhibition enhances antibody-mediated elimination of regulatory T cells through innate immune cells, potentially by activation of type I IFN responses. Our results highlight a mechanism to enhance the efficacy of anti-TIGIT therapy.

Kaplan-Meier survival curves and body weight of FC 1199 and FC 1245 orthotopic pancreatic tumor-bearing C57BL/6 mice treated with SUMOylation and TIGIT inhibitor, alone or in combination

Gating strategy for analysis of Treg population and TIGIT expression in bone marrow isolated cells

To explore how surgical learners - medical students on clinical rotation and residents - perceive morbidity and mortality meetings (M&Ms) as educational experiences and how these meetings shape perceived learning about surgical complications and errors. Qualitative study using convenience sampling and a constructivist grounded theory approach. Three surgical teaching hospitals in Switzerland. Thirty-two learners (15 residents and 17 final-year medical students) who attended M&Ms between January and July 2023. We developed five themes that together resembled a dramatic play: (1) M&Ms as a suboptimal learning theater, (2) learners as a silent audience, (3) hidden learning processes behind the scenes of surgical education, (4) the surgical team as supporting cast, and (5) chief surgeon as director. Learners reported barriers including limited preparation, unclear expectations, hierarchical structures, and time constraints. Confrontational interactions such as peer hostility discouraged participation, whereas supportive discussions facilitated reflection and normalization of complications and errors. Senior leadership was perceived as central in shaping both the tone and educational value of M&Ms. In this qualitative study, surgical learners reflected on structure, preparation, team dynamics, and senior surgical leadership as important factors shaping the educational value of M&Ms. These findings suggest that clearer learning goals, better preparation, protected opportunities to participate, psychological safety, and constructive leadership may help learners engage with, reflect on, and learn from surgical complications and errors.

Supplementary Table 1. Characteristics of PDAC patients