Showing papers in "Journal of Cancer Research and Clinical Oncology in 2022"

Role of PSMA-ligands imaging in Renal Cell Carcinoma management: current status and future perspectives

Abstract: Renal masses detection is continually increasing worldwide, with Renal Cell Carcinoma (RCC) accounting for approximately 90% of all renal cancers and remaining one of the most aggressive urological malignancies. Despite improvements in cancer management, accurate diagnosis and treatment strategy of RCC by computed tomography (CT) and magnetic resonance imaging (MRI) are still challenging. Prostate-Specific Membrane Antigen (PSMA) is known to be highly expressed on the endothelial cells of the neovasculature of several solid tumors other than prostate cancer, including RCC. In this context, recent preliminary studies reported a promising role for positron emission tomography (PET)/CT with radiolabeled molecules targeting PSMA, in alternative to fluorodeoxyglucose (FDG) in RCC patients.The aim of our review is to provide an updated overview of current evidences and major limitations regarding the use of PSMA PET/CT in RCC.A literature search, up to 31 December 2021, was performed using the following electronic databases: PubMed, SCOPUS, Web of Science, and Google Scholar.The findings of this review suggest that PSMA PET/CT could represent a valid imaging option for diagnosis, staging, and therapy response evaluation in RCC, particularly in clear cell RCC.Further studies are needed for this "relatively" new imaging modality to consolidate its indications, timing, and practical procedures.

The pan-immune-inflammation value and systemic immune-inflammation index in advanced melanoma patients under immunotherapy

Abstract: To evaluate the pan-immune-inflammation value (PIV) and systemic immune-inflammation index (SII) in patients with cutaneous melanoma (CM) under immune checkpoint inhibitor (ICI) therapy.PIV and SII were calculated before the start of ICI therapy and at time of progression/death in patients with metastatic CM (stage III/IV). Sex-age-matched CM patients in stage I/II and healthy subjects (HC) served as controls.The median PIV of stage III/IV patients was significantly (P = 0.0011) higher than in stage I/II patients and HC. SII was significantly (P = 0.00044) lower in HC than in CM patients. At baseline, PIV and SII did significantly correlate with lactate dehydrogenase (P = 0.045/0.017). However, ROC curve statistics revealed that SII and PIV were not significantly associated with clinical parameters, including best response to ICI treatment (P = 0.87/0.64), progression-free survival (P = 0.73/0.91), and melanoma-specific survival (P = 0.13/0.17). Moreover, there were no significant changes of PIV and SII from baseline to progression/death (P = 0.38/0.52).Even though both immune-inflammation biomarkers showed some power to differentiate between CM stages and HC, respectively, PIV and SII seem not to be significant predictors for clinical outcome measures of CM patients under ICI therapy.

Pan-immune-inflammation value independently predicts disease recurrence in patients with Merkel cell carcinoma

Abstract: We aimed to determine whether the pan-immune-inflammation value (PIV) of patients with Merkel cell carcinoma (MCC) at primary diagnosis differs from controls and whether it is associated with disease stage and outcome.In this retrospective study, we recruited MCC patients with stage I-III. PIV was calculated from absolute complete blood cell counts obtained within one week at MCC diagnosis as follows: [neutrophils (103/mm3) × platelets (103/mm3) × monocytes (103/mm3)]/lymphocytes (103/mm3). As controls, we studied age-gender-matched cutaneous melanoma (CM, stage I-III) patients and healthy controls (HC). Univariate and multivariate statistics were used.The median PIV in MCC patients was significantly increased compared to both CM patients as well as healthy controls. PIV of MCC patients in stage II and III was significantly higher compared to stage I patients. ROC analysis revealed that MCC recurrence was significantly associated with a PIV greater than 372 [p < 0.0001, Youden index 0.58; hazard ratio: 4 (95% confidence interval: 1.7 to 9.2)]. In multivariate analysis, only a PIV greater than 372 and higher MCC stage were determined as independent predictors for disease recurrence.We determined, for the first time, the prognostic ability of the promising blood-based biomarker PIV in MCC patients and observed that PIV is increased in MCC patients in dependence on disease stage and independently predicts MCC recurrence.

Exercise medicine for cancer cachexia: targeted exercise to counteract mechanisms and treatment side effects

Abstract: Abstract Purpose Cancer-induced muscle wasting (i.e., cancer cachexia, CC) is a common and devastating syndrome that results in the death of more than 1 in 5 patients. Although primarily a result of elevated inflammation, there are multiple mechanisms that complement and amplify one another. Research on the use of exercise to manage CC is still limited, while exercise for CC management has been recently discouraged. Moreover, there is a lack of understanding that exercise is not a single medicine, but mode, type, dosage, and timing (exercise prescription) have distinct health outcomes. The purpose of this review was to examine the effects of these modes and subtypes to identify the most optimal form and dosage of exercise therapy specific to each underlying mechanism of CC. Methods The relevant literatures from MEDLINE and Scopus databases were examined. Results Exercise can counteract the most prominent mechanisms and signs of CC including muscle wasting, increased protein turnover, systemic inflammation, reduced appetite and anorexia, increased energy expenditure and fat wasting, insulin resistance, metabolic dysregulation, gut dysbiosis, hypogonadism, impaired oxidative capacity, mitochondrial dysfunction, and cancer treatments side-effects. There are different modes of exercise, and each mode has different sub-types that induce vastly diverse changes when performed over multiple sessions. Choosing suboptimal exercise modes, types, or dosages can be counterproductive and could further contribute to the mechanisms of CC without impacting muscle growth. Conclusion Available evidence shows that patients with CC can safely undertake higher-intensity resistance exercise programs, and benefit from increases in body mass and muscle mass.

High expression of cuproptosis-related gene FDX1 in relation to good prognosis and immune cells infiltration in colon adenocarcinoma (COAD)

Abstract: Abstract Background Cuproptosis induced by FDX1 is a newly discovered mechanism regulating cell death. However, the role of FDX1 in the pathogenesis of colon adenocarcinoma (COAD) remains to be studied. Methods FDX1 expression was analyzed with The Cancer Genome Atlas (TCGA) database and Human Protein Atlas (HPA) database. Association between FDX1 expression and COAD prognosis was investigated via the Kaplan–Meier (KM) survival curve. The differentially expressed genes (DEGs) of FDX1 were screened with R packages and the PPI were constructed via STRING database. Cytoscape software was used to detect the most profound modules in the PPIs network. CancerSEA database was used to analyze the effect of FDX1 expression levels on different functional status of COAD cells. The relationship between FDX1 expression and immune infiltration of COAD was analyzed by TIMER2.0 database. The COAD patients with high expression of FDX1 by Western blot, and the levels of immune infiltration were measured by flow cytometry. Results FDX1 was low expressed in most cancers, such as BRCA, KICH, and COAD. The overall survival (OS) and disease-specific survival (DSS) of COAD with high FDX1 expression were better than that of the low expression group. GO-KEGG enrichment analysis revealed that FDX1 and its co-expressed genes played an important role in the pathogenesis of COAD. Moreover, FDX1 expression in COAD were positively associated with “quiescence” and “inflammation” but negatively correlated with “invasion”. FDX1 expression was positively correlated with infiltration levels of CD8 + T cells, NK cells, and neutrophils. Oppositely, FDX1 expression was negatively correlated with that of CD4 + T cells and cancer-associated fibroblasts (CAFs). Finally, 6 COAD patients with high expression of FDX1 were screened, and the proportion of CD8 + T cells in cancer tissues of these patients was significantly higher than that in paracancerous, while the CD4 + T cells presented the opposite pattern. Conclusion FDX1 plays a role in inducing cuproptosis and modulating tumor immunity, which could be considered as potential therapeutic targets in COAD.

Lessons learned: the first consecutive 1000 patients of the CCCMunichLMU Molecular Tumor Board

Abstract: In 2016, the University of Munich Molecular Tumor Board (MTB) was implemented to initiate a precision oncology program. This review of cases was conducted to assess clinical implications and functionality of the program, to identify current limitations and to inform future directions of these efforts.Charts, molecular profiles, and tumor board decisions of the first 1000 consecutive cases (01/2016-03/2020) were reviewed. Descriptive statistics were applied to describe relevant findings.Of the first 1000 patients presented to the MTB; 914 patients received comprehensive genomic profiling. Median age of patients was 56 years and 58% were female. The most prevalent diagnoses were breast (16%) and colorectal cancer (10%). Different types of targeted or genome-wide sequencing assays were used; most of them offered by the local department of pathology. Testing was technically successful in 88%. In 41% of cases, a genomic alteration triggered a therapeutic recommendation. The fraction of patients receiving a tumor board recommendation differed significantly between malignancies ranging from over 50% in breast or biliary tract to less than 30% in pancreatic cancers. Based on a retrospective chart review, 17% of patients with an MTB recommendation received appropriate treatment.Based on these retrospective analyses, patients with certain malignancies (breast and biliary tract cancer) tend to be more likely to have actionable variants. The low rate of therapeutic implementation (17% of patients receiving a tumor board recommendation) underscores the importance of meticulous follow-up for these patients and ensuring broad access to innovative therapies for patients receiving molecular tumor profiling.

Effects and duration of exercise-based prehabilitation in surgical therapy of colon and rectal cancer: a systematic review and meta-analysis

Abstract: Abstract Purpose Functional capacity is an independent indicator of morbidity in colon and rectal cancer surgery. This systematic review describes the evaluated and synthesized effects of exercise prehabilitation depending on the duration of interventions on functional and postoperative outcomes in colon and rectal cancer surgery. Methods Three electronic databases (MEDLINE Pubmed, Web of Sciences, and Cochrane Registry) were systematically searched (January 2022) for controlled trials that investigated the effects of prehabilitation prior to colo-rectal cancer resection. Results Twenty-three studies were included in this systematic review and 14 in our meta-analyses assessing these outcomes: the 6 min walk distance (6MWD), postoperative overall complications, and length of stay (LOS). We observed a significant improvement in preoperative functional capacity as measured with 6MWD (mean difference: 30.8 m; 95% CI 13.3, 48.3; p = 0.0005) due to prehabilitation. No reductions in LOS (mean difference: – 0.27 days; 95% CI – 0.93, 0.40; p = 0.5) or postoperative overall complications (Odds ratio: 0.84; 95% CI 0.53, 1.31; p = 0.44) were observed. Prehabilitation lasting more than 3 weeks tended to lower overall complications (Odds ratio: 0.66; 95% CI 0.4, 1.1; p = 0.11). However, the prehabilitation time periods differed between colon and rectal carcinoma resections. Conclusion Prehabilitation while the patient is preparing to undergo surgery for colorectal carcinoma improves functional capacity; and might reduce postoperative overall complications, but does not shorten the LOS. The studies we reviewed differ in target variables, design, and the intervention’s time period. Multicenter studies with sufficient statistical power and differentiating between colon and rectal carcinoma are needed to develop implementation strategies in the health care system. Registration PROSPERO CRD42022310532

Decrease in the number of patients diagnosed with cancer during the COVID-19 pandemic in Germany

Abstract: Little is known on how coronavirus disease 2019 (COVID-19) has impacted cancer diagnosis in Germany since the first lockdown in March 2020. Therefore, this retrospective study aimed to compare the number of patients newly diagnosed with cancer in general and specialized practices in Germany between April 2020–March 2021 and April 2019–March 2020. Patients aged ≥ 18 years with at least 1 visit to 1 of 1403 general and specialized practices in Germany in April 2020–March 2021 (n = 3,804,596) and April 2019–March 2020 (n = 3,913,386) were included in this retrospective study. Specialized practices were composed of gynecology, dermatology and urology practices. Cancer diagnoses included all types of cancer documented using the International Classification of Diseases, 10th revision (ICD-10 codes: C00-C97). The number of patients newly diagnosed with cancer per practice was compared between April 2020–March 2021 and April 2019–March 2020 using Wilcoxon tests. There were 126,379 and 138,996 patients diagnosed with cancer in April 2020–March 2021 and April 2019–March 2020, respectively. The number of patients diagnosed with cancer decreased in all types of practice, and this decrease was significant in general practices (− 7.1%, p value = 0.038). In terms of cancer type, this decrease was particularly pronounced for skin cancers (− 12.8%, p value = 0.025). The COVID-19 pandemic has been associated with a decrease in the number of patients newly diagnosed with cancer in general and specialized practices in Germany. Public health interventions are urgently warranted to mitigate the deleterious effects of this health crisis on cancer diagnosis.

Effects of SARS-CoV-2 infections in patients with cancer on mortality, ICU admission and incidence: a systematic review with meta-analysis involving 709,908 participants and 31,732 cancer patients

Abstract: Cancer patients constitute one of the highest-risk patient groups during the COVID-19 pandemic. In this study, it was aimed to perform a systematic review and meta-analysis to determine both the incidence and ICU (Intensive Care Unit) admission rates and mortality in SARS-CoV-2 infected cancer patients. The PRISMA guidelines were closely followed during the design, analysis, and reporting of this systematic review and meta-analysis. A comprehensive literature search was performed for the published papers in PubMed/Medline, Scopus, medRxiv, Embase, and Web of Science (WoS) databases. SARS-CoV-2 infection pooled incidence in the cancer populations and the risk ratio (RR) of ICU admission rates/mortality in cancer and non-cancer groups, with 95% confidence intervals (CIs), were calculated using the random-effects model. A total of 58 studies, involving 709,908 participants and 31,732 cancer patients, were included in this study. The incidence in cancer patients was calculated as 8% (95% CI: 8–9%). Analysis results showed that mortality and ICU admission rate was significantly higher in patients with cancer (RR = 2.26, 95% CI: 1.94–2.62, P < 0.001; RR = 1.45, 95% CI: 1.28–1.64, p < 0.001, respectively). As a result, cancer was an important comorbidity and risk factor for all SARS-CoV-2 infected patients. This infection could result in severe and even fatal events in cancer patients. Cancer is associated with a poor prognosis in the COVID-19 pandemic. Cancer patients should be assessed more sensitively in the COVID-19 outbreak.

Statins and the risk of gastric, colorectal, and esophageal cancer incidence and mortality: a cohort study based on data from the Korean national health insurance claims database

Abstract: This study investigated the association between the use of statins, the incidence of gastric, colorectal, and esophageal cancers, and mortality between January 2005 and June 2013 in South Korea.We compared patients aged 45-70 years statin users for at least 6 months to non-statin users matched by age and sex, from 2004 to June 2013 using the National Health Insurance database. Main outcomes were gastric, colorectal, and esophageal cancer incidence and mortality. Cox proportional hazard regression was used to calculate the adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) among overall cohort and matched cohort after propensity score matching with a 1:1 ratio.Out of 1,008,101 people, 20,473 incident cancers, 3938 cancer deaths occurred and 7669 incident cancer, 1438 cancer death in matched cohort. The aHRs for the association between the risk of cancers and statin use were 0.7 (95% CI 0.65-0.74) for gastric cancer, 0.73 (95% CI 0.69-0.78) for colorectal cancer, and 0.55 (95% CI 0.43-0.71) for esophageal cancer. There were associations between statin use and decreased gastric cancer mortality (HR 0.46, 95% CI 0.52-0.57), colorectal cancer mortality (HR 0.43, 95% CI 0.36-0.51), and esophageal cancer mortality (HR 0.41, 95% CI 0.27-0.50) in the overall cohort and this pattern was similar in the matched cohort.Statin use for at least 6 months was significantly associated with a lower risk of stomach, colorectal, and esophageal cancer incidence as well as cancer mortality after a diagnosis.

Attitudes toward a COVID-19 vaccine and vaccination status in cancer patients: a cross-sectional survey

Abstract: We aim to assess attitudes toward a COVID-19 vaccine and vaccination status in cancer patients and to explore additional factors such as the level of information and comprehensibility and accessibility of this information, anxiety symptoms in general and toward COVID-19, and general health literacy.We included 425 outpatients (mean age 61.4, age range 30-88 years, 60.5% women) of the Psychosocial Counseling Center for Cancer patients of the Department of Medical Psychology and Medical Sociology, Leipzig. We recorded attitudes toward a COVID-19 vaccine and vaccination status via self-report. The impact of psychosocial factors, including anxiety (GAD-7), COVID-19-specific anxiety (OCS; FCV-19S) and health literacy (HLS-EU-Q16) were analyzed with point-biserial correlations using Pearson's r.We found that the vast majority (95.5%) reported being vaccinated against COVID-19 and that overall trust in safety and protective effects of a COVID-19 vaccine was high (90.9%). The vaccination readiness among nonvaccinated cancer survivors was low to very low with "fear of side effects" the most mentioned (72.2%) reason against a COVID-19 vaccine. There was no significant correlation between vaccination status and fear or anxiety symptomatology, and health literacy. Obsessive thoughts about COVID-19 was significantly higher in nonvaccinated cancer patients.Majority of respondents are positive about COVID-19 vaccine, accompanied by a very high rate of COVID-19 immunization in our sample. Further studies with a larger sample of nonvaccinated cancer patients should further investigate the relationship on fear and vaccination hesitancy and align communication strategies accordingly.

Brain infiltration of breast cancer stem cells is facilitated by paracrine signaling by inhibitor of differentiation 3 to nuclear respiratory factor 1

Abstract: Treatment options for brain metastatic breast cancer are limited because the molecular mechanism for how breast cancer cells infiltrate the brain is not fully understood. For breast tumors to metastasize to the brain first, cells need to detach from the primary tumor, enter in the blood circulation, survive within the microvascular niche, and then cross the blood-brain barrier (BBB) to colonize into the brain. It is critical to understand how breast cancer cells transmigrate through the BBB to prevent brain metastasis. Nuclear respiratory factor 1 (NRF1) transcription factor has been reported to be highly active in several human cancers and its aberrant expression facilitates in the acquisition of breast cancer stem cells (BCSCs). Inhibitor of differentiation protein 3 (ID3), a transcription regulating protein, induces pluripotent endothelial stem cells (ESCs). Herein, we investigated if NRF1-induced BCSCs could cross a BBB model and guiding of BCSCs by ID3-induced ESCs across the BBB. BCSCs and ESCs were subjected to functional gain/loss experiments to determine if NRF1/ID3 contributed to lineage-specific BCSCs organ entry. First, we tested whether NRF1 promoted migration of breast cancer using a BBB model consisting of BCSCs or MDA-MB231 cells, brain endothelial cell layer, and astrocytes. NRF1 overexpression increased the propensity for BCSCs and NRF1-induced MDA-MB231 cells to adhere to brain endothelial cells and migrate across a human BBB model. Increased adhesion of NRF1-induced BCSCs to ESCsID3 was detected. NRF1-induced BCSCs crossed through the BBB model and this was promoted by ESCsID3. We also showed that environmental relevant exposure to PCBs (PCB153 and PCB77) produced differential effects. Treatment with PCB153 showed increased growth of NRF1-induced BCSCs tumor spheroids and increased in vivo migration of ESCsID3. Exosomal ID3 released from endothelial cells also supported the growth of NRF1-induced BCSCs and provide the basis for paracrine effects by ESCsID3 associated with breast tumors. Xenograft experiments showed that ID3 overexpressing brain ESCs not only supported the growth of BCSC tumor spheroids but guided them to the neural crest in zebrafish. These findings show for the first time a novel role for ID3 and NRF1 by which ESCsID3 help guide BCSCsNRF1 to distant metastatic sites where they most likely facilitate the colonization, survival, and proliferation of BCSCs. This knowledge is important for pre-clinical testing of NRF1/ID3 modifying agents to prevent the spread of breast cancer to the brain.

Clinical experience with venetoclax in patients with newly diagnosed, relapsed, or refractory acute myeloid leukemia

Abstract: Diagnosis of acute myeloid leukemia (AML) is associated with poor outcome in elderly and unfit patients. Recently, approval of the BCL-2 inhibitor venetoclax (VEN) in combination with hypo-methylating agents (HMA) led to a significant improvement of response rates and survival. Further, application in the relapsed or refractory (r/r) AML setting or in context of allogeneic stem cell transplantation (alloHSCT) seems feasible.Fifty-six consecutive adult AML patients on VEN from January 2019 to June 2021 were analyzed retrospectively. Patients received VEN either as first-line treatment, as subsequent therapy (r/r AML excluding prior alloHSCT), or at relapse after alloHSCT. VEN was administered orally in 28-day cycles either combined with HMA or low-dose cytarabine (LDAC).After a median follow-up of 11.5 (range 6.1-22.3) months, median overall survival (OS) from start of VEN treatment was 13.3 (2.2-20.5) months, 5.0 (0.8-24.3) months and 4.0 (1.5-22.1) months for first-line, subsequent line treatment and at relapse post-alloHSCT, respectively. Median OS was 11.5 (10-22.3) months from start of VEN when subsequent alloHSCT was carried out. Relapse-free survival (RFS) for the total cohort was 10.2 (2.2 - 24.3) months. Overall response rate (composite complete remission + partial remission) was 51.8% for the total cohort (61.1% for VEN first-line treatment, 52.2% for subsequent line and 42.8% at relapse post-alloHSCT). Subgroup analysis revealed a significantly reduced median OS in FLT3-ITD mutated AML with 3.4 (1.9-4.9) months versus 10.4 (0.8-24.3) months for non-mutated cases, (HR 4.45, 95% CI 0.89-22.13, p = 0.0002). Patients harboring NPM1 or IDH1/2 mutations lacking co-occurrence of FLT3-ITD showed a survival advantage over patients without those mutations (11.2 (5-24.3) months versus 5.0 (0.8-22.1) months, respectively, (HR 0.53, 95% CI 0.23 - 1.21, p = 0.131). Multivariate analysis revealed mutated NPM1 as a significant prognostic variable for achieving complete remission (CR) (HR 19.14, 95% CI 2.30 - 436.2, p < 0.05). The most common adverse events were hematological, with grade 3 and 4 neutropenia and thrombocytopenia reported in 44.6% and 14.5% of patients, respectively.Detailed analyses on efficacy for common clinical scenarios, such as first-line treatment, subsequent therapy (r/r AML), and application prior to and post-alloHSCT, are presented. The findings suggest VEN treatment combinations efficacious not only in first-line setting but also in r/r AML. Furthermore, VEN might play a role in a subgroup of patients with failure to conventional chemotherapy as a salvage regimen aiming for potential curative alloHSCT.

Clinical benefit and cost-effectiveness analysis of liquid biopsy application in patients with advanced non-small cell lung cancer (NSCLC): a modelling approach

Abstract: Targeted therapies are effective therapeutic approaches in advanced stages of NSCLC and require precise molecular profiling to identify oncogenic drivers. Differential diagnosis on a molecular level contributes to clinical decision making. Liquid biopsy (LB) use has demonstrated its potential to serve as an alternative to tissue biopsy (TB) particularly in cases where tissue sampling is not feasible or insufficient. We aimed at evaluating the cost-effectiveness of ctDNA-based LB use (molecular multigene testing) according to German care guidelines for metastatic NSCLC.A Markov model was developed to compare the costs and clinical benefits associated with the use of LB as an add-on to TB according to the guidelines for NSCLC patients. Usual care TB served as comparator. A microsimulation model was used to simulate a cohort of non-squamous NSCLC patients stage IV. The parameters used for modelling were obtained from the literature and from the prospective German CRISP registry ("Clinical Research platform Into molecular testing, treatment, and outcome of non-Small cell lung carcinoma Patients"). For each pathway, average direct medical costs, and QALYs gained per patient were used for calculating incremental cost-effectiveness ratios (ICER).The use of LB as an add-on was costlier (€144,981 vs. €144,587) but more effective measured in QALYs (1.20 vs. 1.19) for the care pathway of NSCLC patients (ICER €53,909/QALY). Cost-effectiveness was shown for EGFR-mutated patients (ICER €-13,247/QALY).Including LB as an add-on into the care pathway of advanced NSCLC has positive clinical effects in terms of QALYs accompanied by a moderate cost-effectiveness.

Ex vivo propagation in a novel 3D high-throughput co-culture system for multiple myeloma

Abstract: Abstract Purpose Multiple myeloma (MM) remains an incurable hematologic malignancy which ultimately develops drug resistance and evades treatment. Despite substantial therapeutic advances over the past years, the clinical failure rate of preclinically promising anti-MM drugs remains substantial. More realistic in vitro models are thus required to better predict clinical efficacy of a preclinically active compound. Methods Here, we report on the establishment of a conical agarose 3D co-culture platform for the preclinical propagation of primary MM cells ex vivo. Cell growth was compared to yet established 2D and liquid overlay systems. MM cell lines (MMCL: RPMI-8226, U266, OPM-2) and primary patient specimens were tested. Drug sensitivity was examined by exploring the cytotoxic effect of bortezomib and the deubiquitinase inhibitor auranofin under various conditions. Results In contrast to 2D and liquid overlay, cell proliferation in the 3D array followed a sigmoidal curve characterized by an initial growth delay but more durable proliferation of MMCL over 12 days of culture. Primary MM specimens did not expand in ex vivo monoculture, but required co-culture support by a human stromal cell line (HS-5, MSP-1). HS-5 induced a > fivefold increase in cluster volume and maintained long-term viability of primary MM cells for up to 21 days. Bortezomib and auranofin induced less cytotoxicity under 3D vs. 2D condition and in co- vs. monoculture, respectively. Conclusions This study introduces a novel model that is capable of long-term propagation and drug testing of primary MM specimens ex vivo overcoming some of the pitfalls of currently available in vitro models.

Association between compliance with enhanced recovery after surgery (ERAS) protocols and postoperative outcome in patients with primary liver cancer undergoing hepatic resection

Abstract: Enhanced recovery after surgery (ERAS) is a multidisciplinary, stress-minimizing approach that is associated with improved postoperative outcomes. However, whether the level of compliance with ERAS protocols impacts the postoperative outcome of patients with primary liver cancer undergoing liver resection is unknown. The study aimed to analyze the association between compliance with ERAS protocols and liver resection outcomes.This prospective cohort study consecutively recruited patients with primary liver cancer who were scheduled for elective liver surgery between January 2019 and December 2020 at the Department of Biliary Surgery, West China Hospital of Sichuan University. Twenty individual ERAS items were assessed in all patients. The patients were divided into two groups according to their degree of compliance with the ERAS interventions: an ERAS-compliant (ERAS-C) group of individuals who complied with over 75% of the ERAS components and an ERAS-noncompliant (ERAS-N) group. The primary outcomes were ERAS compliance, occurrence of major complications within 30 days postoperatively, and length of postoperative hospital stay. The secondary outcomes were 30-day readmissions, reoperations and other rehabilitation indicators. The study was registered at www.chictr.org.cn (identity number ChiCTR2000040021).Overall, 436 patients were enrolled; their mean age was 54 years (interquartile range [IQR], 47-66). Of these patients, 206 were allocated to the ERAS-C group, and the other 230 patients comprised the ERAS-N group. The overall compliance rate was 70% (IQR, 65%-80%). The ERAS-C group had higher compliance rates [80.00% (IQR, 75.00-85.00%)] than the ERAS-N group [65.00% (IQR, 65.00-70.00%)], P < 0.001). The ERAS-C group had significantly fewer major complications (7.77% vs. 15.65%, OR, 0.449, 95% CI, 0.241-0.836, P = 0.012) and shorter postoperative hospital stays (5 days [IQR, 4-6] vs. 6 days [IQR, 5-7], P < 0.001) than the ERAS-N group. Subgroup analysis indicated that compliance rates greater than 80%, between 65 and 80%, and lower than 65% were associated with decreased major complication rates (6.25%, 8.48% and 22.83%, respectively) and shorter postoperative hospital stays. However, the rates of ICU stay, readmission, reoperation and mortality within 30 days after surgery were not different between groups (P > 0.05).The results of this study suggest that higher compliance with ERAS components is associated with a lower incidence of major postoperative complications and a shorter postoperative hospital stay.