February 2025

Synopsis: This study performed clinical monitoring and assessment of an ongoing phase 1/2a clinical trial investigating the utility of regulatory dendritic cells (DCregs) as a novel immunosuppressive therapy in patients undergoing living donor liver transplant. The authors found that one pretransplant infusion of DCregs had lasting immunomodulatory effects specifically within peripheral and allograft T cells and NK cells compared to patients treated with conventional immunosuppression.

Summary: Immunosuppression in transplantation is non-specific, leading to complications such as opportunistic infections, increased rates of cancer, and potentially serious off target side effects such as nephrotoxicity. Immune cell-based therapies are a potentially promising way to provide organ specific immunosuppression and reduce the need for conventional immunosuppressive drugs. Trials have studied the utility of regulatory T cells and myeloid cells; however, results remain equivocal. Little focus has been provided to DCregs, which constitutively express donor MHC antigens and promote tolerance to organ allografts in rodents. This study assessed samples from an ongoing first-in-human phase 1/2a trial, investigated the feasibility, safety, and early efficacy of ex vivo-generated, donor-derived DCreg infusion one week prior to patients undergoing living donor liver transplant. 

This study compared 13 patients who received DCreg infusion 1 week prior to transplant (STUDY) compared to 40 propensity matched patients who received standard of care immunosuppression (SOC). Baseline characteristics of the two groups were similar. The majority were Caucasian females who had non-alcoholic steatohepatitis (NASH) as the primary diagnosis for transplant. At one year of follow up, there was no re-transplantation events or differences in technical complications, infectious complications, allograft function or biopsy-confirmed acute cellular rejection. In the STUDY group, 23.1% of patients were weaned off mycophenolate mofetil and on tacrolimus monotherapy compared to 11.3% in the SOC group (P=0.35). Further clinical results are expected to be presented in 5 years once the study ends.

The investigators collected peripheral blood mononuclear cells (PBMCs) from patients prior to transplant and 12 months after transplantation. They then ran flow cytometry on these samples specifically looking at T cell and NK cell populations. They did not observe differences in total CD4 or CD8 T cell populations. However, DCreg treated patients at 1 year post transplant had a reduction in CD8+T-bet+Eomes+ cells, which are a subclass of effector CD8 T cells with enhanced memory and cytotoxicity. In two different NK cell populations, there was also a reduction in T-bet+Eomes+ cells both between SOC and STUDY pts at 12 months and between pretreatment and 12 months post-transplant in the STUDY group. It was also noted that there was an increase in a tolerogenic subset of DCs in the 12-month STUDY samples compared to SOC samples and pre-infusion STUDY samples. Finally, cytokine and chemokine analysis of peripheral blood showed that there were higher concentrations of type 1 T helper cells and pro-inflammatory cytokines in the SOC group at 12 months. This correlated with the changes observed in the CD8 T cell and NK cell population in their flow data.

Next, the investigators performed single cell RNA sequencing (scRNA-seq) on allograft biopsies of STUDY and SOC patients at 12 months. Using there scRNA-seq results and a curated database of ligand-receptor complex interactions, they analyzed intercellular communication between STUDY and SOC biopsies. They found that there was a global reduction in total number and mean strength of cell-cell interactions in the STUDY pts. They also found a reduction in CD8 T cell interactions. Differential gene expression analysis of all CD8 T cell subsets suggested a down-regulation of Th1 effector function and pro-inflammatory signaling. There was also a reduction in key effector genes such as CCL3, CCL4, GZMB and GZMM in NK cell subsets within pts given DCregs. Finally, the investigators performed immunofluorescense on biopsies and found that there was a reduction in graft-infiltrating CD4, CD8 T cells and subpopulations of NK cells in the STUDY group compared to the SOC group.  

The limitations of this study include the open-label design, which may introduce bias in data interpretation. The sample size was limited due to the cost of generating donor-derived regulatory dendritic cells (DCreg), which might limit statistical power. Additionally, while changes in donor-reactive T cell clones and cytokine expression were observed, the study did not conclusively establish whether these changes directly translate to long-term tolerance or reduced immunosuppression requirements. 

Bottom Line: The authors found that a single pretransplant infusion of a novel cellular-based immunosuppressive therapy (DCregs) led to immunomodulatory effects on both peripheral and allograft immune cells one year after liver transplant, which could potentially reduce the need for conventional immunosuppressive drugs. 

Synopsis: This randomized clinical trial evaluated the effectiveness of an automatic quality control system (AQCS) in increasing adenoma detection rates (ADR) during routine colonoscopies by moderate- and low-level detectors. The study found that the use of AQCS significantly improved ADR compared to standard colonoscopy (SC).

Summary: Despite the introduction of quality indicators aimed at improving adenoma detection rates during colonoscopies, adherence to these guidelines remains inconsistent. To address this issue, a computer-aided detection (CADe) device, known as the automatic quality control system (AQCS), was developed to provide real-time monitoring of key procedural metrics. The AQCS is designed to assess the timing of the colonoscopy intubation and withdrawal phases, monitor withdrawal stability, evaluate bowel preparation quality, and detect polyps during high-definition white-light colonoscopy.

This multicenter trial included 1,254 adult patients undergoing routine colonoscopies across multiple centers. Participants were randomly assigned to either the AQCS-assisted group (n = 627) or the SC group (n = 627). The AQCS was designed to measure withdrawal time, withdrawal stability, adequacy of bowel preparation, and detection of polyps during high-definition white-light colonoscopy. The primary outcome was ADR, defined as the proportion of patients with at least one adenoma detected, as confirmed by histopathologic examination. Secondary outcomes included ADR in academic and non-academic settings, ADR based on colonoscopist experience levels, the number of adenomas per colonoscopy (APC), withdrawal time without intervention, and adverse events.

Overall, ADR was significantly higher in the AQCS-assisted group compared to the SC group (32.7% vs. 22.6%). Subgroup analyses indicated that the improvement in ADR was consistent across different centers (academic: 29.3% vs. 20.8%, non-academic: 36.1% vs. 24.5%) and among colonoscopists with varying levels of experience (lower-level detectors: 30.0% vs. 20.0%, medium-level detectors: 38.1% vs. 27.7%). The number of adenomas per colonoscopy was significantly higher in the AQCS-assisted group (0.86 vs. 0.48 in SC). The mean withdrawal time without intervention was slightly increased with AQCS assistance (6.78 vs. 6.46 minutes). No serious adverse events were reported.

There are several limitations to this study. The potential for Hawthorne bias exists, as endoscopists were aware of patient assignments during procedures, which may have influenced detection rates. The study did not assess long-term outcomes, such as polyp recurrence or the impact on colorectal cancer incidence. Additionally, it did not evaluate the synergistic effects of other interventions, including mucosal exposure devices, image-enhanced technologies, or re-training courses.

Bottom line: The implementation of AQCS during routine colonoscopy procedures significantly increases adenoma detection rates, with consistent improvements across varying levels of colonoscopist experience and institutional settings. Further research is needed to explore the association between adenoma detection by AQCS and long-term outcomes, including colorectal cancer incidence and cost-effectiveness. 

Synopsis: This retrospective cohort study compares postoperative outcomes following esophagectomy between private equity-acquired and nonacquired health centers. The authors found that patients undergoing esophagectomy at private equity-acquired hospitals had worse postoperative outcomes than those treated at nonacquired hospitals.

Summary: In recent years, private equity firms have increasingly acquired outpatient practices and long-term care facilities, aiming to maximize profit and reduce inefficiencies. As these acquisitions expand into acute care hospitals, concerns have arisen about their impact on surgical care delivery, particularly for high-complexity procedures like esophagectomy. This study examines how private equity acquisition influences postoperative outcomes for esophagectomy patients.

The authors used the Medicare Provider Analysis and Review file to identify Medicare beneficiaries aged 65 to 99 who underwent elective esophagectomy between January 2016 and December 2020. The primary outcomes included 30-day mortality, occurrence of any complication, occurrence of serious complications (defined as at least one postoperative complication with a hospital stay exceeding the 75th percentile for esophagectomy), failure to rescue, and 30-day readmission rates. A multivariable logistic regression model was used to adjust for age, sex, Elixhauser comorbidities, procedure type, procedure approach, and year of surgery.

A total of 9,462 patients underwent esophagectomy across 132 private equity-acquired and 822 nonacquired hospitals. Compared to nonacquired hospitals, private equity-acquired hospitals had lower surgical volumes, lower nurse-to-patient ratios, and were less likely to be teaching institutions. Patients at private equity-acquired hospitals tended to have fewer comorbidities. However, after risk adjustment, patients at private equity-acquired hospitals had significantly worse postoperative outcomes, including higher 30-day mortality (8.1% vs. 4.9%, p = 0.002), higher rates of any complication (36.6% vs. 30.1%, p = 0.001), higher rates of serious complications (17.5% vs. 14.3%, p = 0.03), and higher failure-to-rescue rates (5.9% vs. 3.4%, p = 0.004). A sensitivity analysis controlling for hospital volume, using only hospitals in the lowest quartile of annual esophagectomy cases, confirmed that 30-day mortality and overall complication rates remained significantly higher at private equity-acquired hospitals. There was no statistically significant difference in serious complications, failure to rescue, or readmission rates between the two hospital types, though all outcomes favored undergoing esophagectomy at nonacquired hospitals.

There are several limitations to this study. The use of Medicare claims data limits the clinical detail available, making it difficult to accurately account for certain factors, such as oncologic staging and use of multimodal therapy. Institutional-level structural characteristics, such as intensive care unit organization, staffing models, and multidisciplinary care teams, were not fully captured, potentially introducing unmeasured confounding. Since the study population consists only of Medicare beneficiaries aged 65 and older, the findings may not be generalizable to younger patients. Additionally, the timing of private equity acquisitions is unclear, preventing an analysis of temporal associations between acquisition and changes in patient outcomes. Furthermore, additional factors such as surgeon experience, hospital accreditation, and board certification were not analyzed but could significantly impact patient outcomes.

Bottom Line: Patients undergoing esophagectomy at private equity-acquired hospitals may experience worse postoperative outcomes compared to those treated at nonacquired hospitals. Addressing structural and systemic factors may help mitigate these risks. Alternatively, centralizing esophagectomy care to high-volume, nonacquired hospitals with greater surgical expertise may be a more effective strategy.  

Synopsis: This randomized, non-inferiority clinical trial compared thermal ablation with surgical resection for small colorectal liver metastases (CLM). The study was stopped early for meeting pre-defined criteria for early benefit and demonstrated that thermal ablation is non-inferior to surgical resection in terms of overall survival, disease-free survival, and recurrence rates for patients with small CLM, with fewer complications.

Summary: Over the last two decades, thermal ablative methods for colorectal liver metastases have gained popularity as adjuncts to surgical resection or as a standalone treatment when complete surgical removal of all metastatic sites is not feasible. The COLLISION trial was a multicenter, international, phase 3 randomized controlled trial conducted across 14 centers in the Netherlands, Belgium, and Italy. The goal was to assess the oncologic safety of thermal ablation compared to surgical resection in patients with small, resectable colorectal liver metastases. Patients over the age of 18 with ten or fewer small (≤3 cm) colorectal liver metastases were included in this study. Those with unresectable CLM, extrahepatic disease, an Eastern Cooperative Oncology Group (ECOG) performance status greater than 2, or contraindications to thermal ablation or surgery were excluded. Between August 2017 and February 2024, eligible patients were stratified into three groups according to disease burden (low, intermediate, and high) and randomly assigned in a 1:1 ratio to either thermal ablation (experimental group) or surgical resection (control group). The primary endpoint was overall survival, while secondary endpoints included disease-free survival, recurrence rates, and adverse events.

A preplanned interim analysis, conducted 12 months after enrolling 50% of the planned sample size (n = 309), included predefined stopping criteria based on futility, safety superiority, and local control outcomes. A total of 300 patients were randomly assigned to the experimental group (n = 148, 68% male, median age 67.9 years [IQR 29.2–85.7]) or the control group (n = 148, 72% male, median age 65.1 [IQR 31.4–87.4]). The median follow-up was 28.9 months (IQR 0.3–77.8), during which 30% of patients had died—47 (32%) in the experimental group and 43 (29%) in the control group. No significant difference in overall survival was observed between the two groups (median overall survival not reached; HR 1.05; 95% CI 0.69–1.58; p = 0.83). Subgroup analyses showed no significant differences in overall survival between the experimental and control groups, and there was no difference in distant tumor progression-free survival. The trial was stopped early after meeting predefined stopping rules. Additionally, adverse events were significantly more common in the surgical resection group than in the thermal ablation group (46% vs. 19%; p < 0.0001). Hospital stays were significantly longer in the control group (median 4 days [IQR 1–36]) compared to the experimental group (median 1 day [IQR 1–44]; p < 0.0001).

There are several limitations to this study. Long-term outcomes beyond five years could not be assessed. The lack of blinding may have introduced bias in treatment administration. The inclusion of only patients with small metastases may limit the generalizability of the findings to those with larger tumors. Additionally, because the trial was stopped early, the statistical power and robustness of its conclusions may be affected.

Bottom Line: Thermal ablation appears to be a non-inferior alternative to surgical resection for small colorectal liver metastases, providing a less invasive option for patients with small tumors. These findings challenge the notion that thermal ablation should be reserved only for unresectable CLM, advocating for a more individualized approach to treatment.