Although mutated HLA ligands are considered ideal cancer-specific immunotherapy targets, evidence for their presentation is lacking in hepatocellular carcinomas (HCCs). Employing a unique multi-omics approach comprising a neoepitope identification pipeline, we assessed exome-derived mutations naturally presented as HLA class I ligands in HCCs. In-depth multi-omics analyses included whole exome and transcriptome sequencing to define individual patient-specific search spaces of neoepitope candidates. Evidence for the natural presentation of mutated HLA ligands was investigated through an in silico pipeline integrating proteome and HLA ligandome profiling data. The approach was successfully validated in a state-of-the-art dataset from malignant melanoma, and despite multi-omics evidence for somatic mutations, mutated naturally presented HLA ligands remained elusive in HCCs. An analysis of extensive cancer datasets confirmed fundamental differences of tumor mutational burden in HCC and malignant melanoma, challenging the notion that exome-derived mutations contribute relevantly to the expectable neoepitope pool in malignancies with only few mutations. This study suggests that exome-derived mutated HLA ligands appear to be rarely presented in HCCs, inter alia resulting from a low mutational burden as compared to other malignancies such as malignant melanoma. Our results therefore demand widening the target scope for personalized immunotherapy beyond this limited range of mutated neoepitopes, particularly for malignancies with similar or lower mutational burden.

Background: There is a rapidly growing literature available on right hemicolectomy comparing the short- and long-term outcomes of robotic right colectomy (RRC) to that of laparoscopic right colectomy (LRC). The aim of this meta-analysis is to revise current comparative literature systematically. Methods: A systematic review of comparative studies published between 2000 to 2021 in PubMed, Scopus and Embase was performed. The primary endpoint was postoperative morbidity, mortality and long-term oncological results. Secondary endpoints consist of blood loss, conversion rates, complications, time to first flatus, hospital stay and incisional hernia rate. Results: 25 of 322 studies were considered for data extraction. A total of 16,099 individual patients who underwent RRC (n = 1842) or LRC (n = 14,257) between 2002 and 2020 were identified. Operative time was significantly shorter in the LRC group (LRC 165.31 min ± 43.08 vs. RRC 207.38 min ± 189.13, MD: −42.01 (95% CI: −51.06−32.96), p < 0.001). Blood loss was significantly lower in the RRC group (LRC 63.57 ± 35.21 vs. RRC 53.62 ± 34.02, MD: 10.03 (95% CI: 1.61–18.45), p = 0.02) as well as conversion rate (LRC 1155/11,629 vs. RRC 94/1534, OR: 1.65 (1.28–2.13), p < 0.001) and hospital stay (LRC 6.15 ± 31.77 vs. RRC 5.31 ± 1.65, MD: 0.84 (95% CI: 0.29–1.38), p = 0.003). Oncological long-term results did not differ between both groups. Conclusion: The advantages of robotic colorectal procedures were clearly demonstrated. RRC can be regarded as safe and feasible. Most of the included studies were retrospective with a limited level of evidence. Further randomized trials would be suitable.

Background: Malnutrition and skeletal muscle waste (sarcopenia) are known as predictive factors for a poor postoperative outcome. Paradoxically, obesity seems to be associated with a survival advantage in wasting diseases such as cancer. Thus, the interpretation of body composition indices and their impact on rectal cancer therapy has become more and more complex. The aim of this study was to evaluate body composition indices in locally advanced rectal cancer patients prior to therapy and their impact on short- and long-term outcomes. Methods: Between 2008 and 2018, 96 patients were included in this study. Pre-therapeutic CT scans were used to evaluate visceral and subcutaneous fat mass, as well as muscle mass. Body composition indices were compared to body mass index, morbidity, anastomotic leakage rate, local recurrency rate, and oncological long-term outcomes. Results: Increased visceral fat (p < 0.01), subcutaneous fat (p < 0.01), and total fat mass (p = 0.001) were associated with overweight. Skeletal muscle waste (sarcopenia) (p = 0.045), age (p = 0.004), comorbidities (p < 0.01), and sarcopenic obesity (p = 0.02) were significantly associated with increased overall morbidity. The anastomotic leakage rate was significantly influenced when comorbidities were present (p = 0.006). Patients with sarcopenic obesity showed significantly worse disease-free (p = 0.04) and overall survival (p = 0.0019). The local recurrency rate was not influenced by body composition indices. Conclusion: Muscle waste, older age, and comorbidities were demonstrated as strong risk factors for increased overall morbidity. Sarcopenic obesity was associated with worse DFS and OS. This study underlines the role of nutrition and appropriate physical activity prior to therapy.

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) was considered a promising treatment for patients with peritoneal metastasis from colorectal cancer. However, the recently published randomized controlled PRODIGE 7 trial failed to demonstrate survival benefits through the addition of short-term oxaliplatin-based HIPEC. Constituting a complex multifactorial treatment, we investigated HIPEC in a preclinical model concerning the elimination of minimal tumor residues, thereby aiming to better understand the size of effects and respective clinical trial results. Patient samples of peritoneal perfusates obtained during HIPEC treatments and oxaliplatin-containing solutions at clinically relevant dosages, conforming with established HIPEC protocols, were assessed regarding their ability to eliminate modelled ~100 µm thickness cancer cell layers. Impedance-based real-time cell analysis and classical end-point assays were used. Flow cytometry was employed to determine the effect of different HIPEC drug solvents on tumor cell properties. Effectiveness of peritoneal perfusate patient samples and defined oxaliplatin-containing solutions proved limited but reproducible. HIPEC simulations for 30 min reduced the normalized cell index below 50% with peritoneal perfusates from merely 3 out of 9 patients within 72 h, indicating full-thickness cytotoxic effects. Instead, prolonging HIPEC to 1 h enhanced these effects and comprised 7 patients’ samples, while continuous drug exposure invariably resulted in complete cell death. Further, frequently used drug diluents caused approximately 25% cell size reduction within 30 min. Prolonging oxaliplatin exposure improved effectiveness of HIPEC to eliminate micrometastases in our preclinical model. Accordingly, insufficient penetration depth, short exposure time, and the physicochemical impact of drug solvents may constitute critical factors.

Background: The treatment of locally advanced rectal cancer (LARC) has steadily progressed over the past four decades, with recent focus shifting towards total neoadjuvant therapy (TNT). This survey aims to elucidate the perceived surgical challenges faced by Austrian colorectal surgeons performing total mesorectal excision (TME), focusing on the increased complexity and surgical difficulty introduced by intensified treatment regimens. Methods: A comprehensive survey was conducted among Austrian colorectal surgeons to explore various aspects of managing and performing TME following TNT. The survey included questions on the general management of LARC within their institutions and utilized a five-point Likert scale to assess the respondents’ perceptions and experiences regarding surgical precision and post-operative morbidity associated with TNT. Results: A total of 31 surgeons (54% response rate) completed the survey. Regarding multidisciplinary therapy preferences, 56% of respondents preferred conventional neoadjuvant therapy regimens, with 32% favoring chemoradiotherapy and 24% opting for short-course radiotherapy, while 31% chose TNT. The majority of respondents (65%) reported quality differences in tissue dissection during TME following TNT, with 57% experiencing difficulties in identifying tissue planes and 47% noting increased tissue fragility. Increased bleeding was reported by 32% of respondents. In cases of regrowth after a watch-and-wait approach, 64% observed quality changes in tissue dissection, and 47% noted tissue fragility. Conclusions: The survey results indicate that TNT impairs surgical precision due to changes in tissue quality and challenges in identifying surgical planes. Given the critical importance of surgical precision in achieving low local recurrence rates in mid-to-low LARC, these challenges could significantly impact patient outcomes. Further prospective studies are required to elucidate the extent of these effects.

Objective: Tailored approaches in gastrointestinal oncology have been more frequently introduced in past years and for patients with peritoneal metastases. This article attempts to overview the current strategies in surgical gastrointestinal oncology, with a focus on gastrointestinal peritoneal metastases. Methods: In 2019, all patients undergoing PIPAC therapy in Germany were retrospectively analyzed regarding morbidity and in-hospital mortality rates. Furthermore, patients with chemotherapy-refractory peritoneal metastases from gastric cancer undergoing PIPAC-therapy at our institution were analyzed. Results: In 2019, 534 patients received PIPAC treatment in german hospitals. The in-hospital mortality rate was 0%. In total, 36 patients suffered from postoperative complications (8%). From April 2016 to September 2021, a total of 44 patients underwent 93 PIPAC applications at our institution. The non-access-rate was 0%. The median PRGS was two (range, 1–4). Eleven patients (44%) showed histologically stable disease, whereas six patients (24%) showed histological regression. Median survival, calculated from the date of the first PIPAC application, was 181 days (range, 43–636 days). Conclusions: PIPAC is a safe and feasible procedure with a low in-hospital morbidity and mortality. Furthermore, PIPAC in the palliative and chemorefractory setting and is an appealing approach for patient management in the future.