Background Deep learning (DL) models can potentially improve prognostication of rectal cancer but have not been systematically assessed. Purpose To develop and validate an MRI DL model for predicting survival in patients with rectal cancer based on segmented tumor volumes from pretreatment T2-weighted MRI scans. Materials and Methods DL models were trained and validated on retrospectively collected MRI scans of patients with rectal cancer diagnosed between August 2003 and April 2021 at two centers. Patients were excluded from the study if there were concurrent malignant neoplasms, prior anticancer treatment, incomplete course of neoadjuvant therapy, or no radical surgery performed. The Harrell C-index was used to determine the best model, which was applied to internal and external test sets. Patients were stratified into high- and low-risk groups based on a fixed cutoff calculated in the training set. A multimodal model was also assessed, which used DL model-computed risk score and pretreatment carcinoembryonic antigen level as input. Results The training set included 507 patients (median age, 56 years [IQR, 46-64 years]; 355 men). In the validation set (n = 218; median age, 55 years [IQR, 47-63 years]; 144 men), the best algorithm reached a C-index of 0.82 for overall survival. The best model reached hazard ratios of 3.0 (95% CI: 1.0, 9.0) in the high-risk group in the internal test set (n = 112; median age, 60 years [IQR, 52-70 years]; 76 men) and 2.3 (95% CI: 1.0, 5.4) in the external test set (n = 58; median age, 57 years [IQR, 50-67 years]; 38 men). The multimodal model further improved the performance, with a C-index of 0.86 and 0.67 for the validation and external test set, respectively. Conclusion A DL model based on preoperative MRI was able to predict survival of patients with rectal cancer. The model could be used as a preoperative risk stratification tool. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Langs in this issue.

Alterations of body composition, especially decreased muscle mass (sarcopenia) and impaired muscle quality (myosteatosis), are associated with inferior outcomes in various clinical conditions. The data of 100 consecutive patients who underwent partial hepatectomy for hepatocellular carcinoma (HCC) at a German university medical centre were retrospectively analysed (May 2008–December 2019). Myosteatosis and sarcopenia were evaluated using preoperative computed-tomography-based segmentation. We investigated the predictive role of alterations in body composition on perioperative morbidity, mortality and long-term oncological outcome. Myosteatotic patients were significantly inferior in terms of major postoperative complications (Clavien–Dindo ≥ 3b; 25% vs. 5%, p = 0.007), and myosteatosis could be confirmed as an independent risk factor for perioperative morbidity in multivariate analysis (odds ratio: 6.184, confidence interval: 1.184–32.305, p = 0.031). Both sarcopenic and myosteatotic patients received more intraoperative blood transfusions (1.6 ± 22 vs. 0.3 ± 1 units, p = 0.000; 1.4 ± 2.1 vs. 0.3 ± 0.8 units, respectively, p = 0.002). In terms of long-term overall and recurrence-free survival, no statistically significant differences could be found between the groups, although survival was tendentially worse in patients with reduced muscle density (median survival: 41 vs. 60 months, p = 0.223). This study confirms the prognostic role of myosteatosis in patients suffering from HCC with a particularly strong value in the perioperative phase and supports the role of muscle quality over quantity in this setting. Further studies are warranted to validate these findings.

The platelet-to-lymphocyte ratio (PLR), an inflammatory parameter, has shown prognostic value in several malignancies. The aim of this meta-analysis was to determine the impact of pretreatment PLR on the oncological outcome in patients with cholangiocarcinoma (CCA). A systematic literature search has been carried out in the PubMed and Google Scholar databases for pertinent papers published between January 2000 and August 2021. Within a random-effects model, the pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated to investigate the relationships among the PLR, overall survival (OS), and disease-free survival (DFS). Subgroup analysis, sensitivity analysis, and publication bias were also conducted to further evaluate the relationship. A total of 20 articles comprising 5429 patients were included in this meta-analysis. Overall, the pooled outcomes revealed that a high PLR before treatment is associated with impaired OS (HR = 1.14; 95% CI = 1.06–1.24; p < 0.01) and DFS (HR = 1.57; 95% CI = 1.19–2.07; p < 0.01). Subgroup analysis revealed that this association is not influenced by the treatment modality (surgical vs. non-surgical), PLR cut-off values, or sample size of the included studies. An elevated pretreatment PLR is prognostic for the OS and DFS of CCA patients. More high-quality studies are required to investigate the pathophysiological basis of the observation and the prognostic value of the PLR in clinical management as well as for patient selection.

Despite recent advances in therapy, liver metastasis from melanoma is still associated with poor prognosis. Although targeting the mTOR signaling pathway exerts potent anti-tumor activity, little is known about specific mTORC2 inhibition regarding liver metastasis. Using the novel mTORC2 specific inhibitor JR-AB2-011, we show significantly reduced migration and invasion capacity by impaired activation of MMP2 in melanoma cells. In addition, blockade of mTORC2 induces cell death by non-apoptotic pathways and reduces tumor cell proliferation rate dose-dependently. Furthermore, a significant reduction of liver metastasis was detected in a syngeneic murine metastasis model upon therapy with JR-AB2-011 as determined by in vivo imaging and necropsy. Hence, our study for the first time highlights the impact of the pharmacological blockade of mTORC2 as a potent novel anti-cancer approach for liver metastasis from melanoma.

Postoperative mortality in patients undergoing surgical and/or interventional treatment for acute mesenteric ischemia (AMI) has remained an unsolved problem in recent decades. Here, we investigated clinical predictors of postoperative mortality in a large European cohort of patients undergoing treatment for AMI. In total, 179 patients who underwent surgical and/or interventional treatment for AMI between 2009 and 2021 at our institution were included in this analysis. Associations between postoperative mortality and various clinical variables were assessed using univariate and multivariable binary logistic regression analysis. Most of the patients were diagnosed with arterial ischemia (AI; n = 104), while venous ischemia (VI; n = 21) and non-occlusive mesenteric ischemia (NOMI; n = 54) were present in a subset of patients. Overall inhouse mortality was 55.9% (100/179). Multivariable analyses identified leukocytes (HR = 1.08; p = 0.008), lactate (HR = 1.25; p = 0.01), bilirubin (HR = 2.05; p = 0.045), creatinine (HR = 1.48; p = 0.039), etiology (AI, VI or NOMI; p = 0.038) and portomesenteric vein gas (PMVG; HR = 23.02; p = 0.012) as independent predictors of postoperative mortality. In a subanalysis excluding patients with fatal prognosis at the first surgical exploration (n = 24), leukocytes (HR = 1.09; p = 0.004), lactate (HR = 1.27; p = 0.003), etiology (AI, VI or NOMI; p = 0.006), PMVG (HR = 17.02; p = 0.018) and intraoperative FFP transfusion (HR = 4.4; p = 0.025) were determined as independent predictors of postoperative mortality. Further, the risk of fatal outcome changed disproportionally with increased preoperative lactate values. The clinical outcome of patients with AMI was determined using a combination of pre- and intraoperative clinical and radiological characteristics. Serum lactate appears to be of major clinical importance as the risk of fatal outcome increases significantly with higher lactate values.

Melanoma is one of the most aggressive and lethal cancers worldwide. Despite recent progress in melanoma therapy, the prognosis for metastasized melanoma continues to be poor. Xanthohumol (XN), a prenylated chalcone derived from hop cones, is known to possess a broad spectrum of chemopreventive and anticancer activities. However, few studies have analyzed functional XN effects on melanoma cells and there have been no previous in vivo studies of its effects on metastasis. The aim of this study was to investigate the impact of XN on the tumorigenic and liver metastatic activity of melanoma cells. XN exhibited dose-dependent cytotoxic effects on human melanoma cell lines (Mel Ju; Mel Im) in vitro. Functional analysis in the subtoxic dose-range revealed that XN dose-dependently inhibited proliferation, colony formation, and migratory activity of melanoma cells. Subtoxic XN doses also induced markers of endoplasmic reticulum stress but inhibited the phosphorylation of the protumorigenic c-Jun N-terminal kinases (JNK). Furthermore, XN effects on hepatic metastasis were analyzed in a syngeneic murine model (splenic injection of murine B16 melanoma cells in C57/BL6 mice). Here, XN significantly reduced the formation of hepatic metastasis. Metastases formed in the liver of XN-treated mice revealed significantly larger areas of central necrosis and lower Ki67 expression scores compared to that of control mice. In conclusion, XN inhibits tumorigenicity of melanoma cells in vitro and significantly reduced hepatic metastasis of melanoma cells in mice. These data, in conjunction with an excellent safety profile that has been confirmed in previous studies, indicate XN as a promising novel agent for the treatment of hepatic (melanoma) metastasis.