Characterizing the Immune Environment in Peritoneal Carcinomatosis: Insights for Novel Immunotherapy Strategies.

BACKGROUND OR PURPOSE: Carcinomatosis, a distinct pattern of metastatic cancer in the peritoneal cavity, poses challenges for treatment and has limited therapeutic options. Understanding the immune environment of peritoneal surface malignancies is crucial for developing effective immunotherapeutic approaches. This study characterizes soluble immune mediators in the peritoneal fluid of patients with and without carcinomatosis to identify targets for novel treatment strategies. PATIENTS AND METHODS: Serum and peritoneal fluid samples were collected from surgical patients, and a multianalyte analysis was performed using the Luminex platform. Patient characteristics, tumor sites, and sample collection details were recorded. Soluble immune mediator levels were measured and compared between peritoneal fluid and serum samples and among clinical subgroups. Statistical analysis was conducted to assess differences in analyte concentrations and correlations between samples. RESULTS: There were 39 patients included in the study, with varying surgical indications. Significant differences were observed in soluble immune mediator levels between peritoneal fluid and serum, with peritoneal fluid exhibiting lower concentrations. Carcinomatosis was associated with elevated levels of proinflammatory mediators, including IL-6 and IL-8, while adaptive immune response markers were low in peritoneal fluid. CONCLUSIONS: The peritoneal immune microenvironment in carcinomatosis favors innate immunity, presenting a challenging environment for effective antitumor response. High levels of proinflammatory mediators suggest potential targets for intervention, such as the IL-6 axis, FGF2, IL-8, and CCL2; these could be explored as potential mitigators of malignant ascites and enhance anti-tumor immune responses. These findings provide valuable insights for developing immunotherapy strategies and improving outcomes in patients with peritoneal carcinomatosis.

Defining the Values and Quality of Life of Cancer Survivors Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: An International Survey Study.

BACKGROUND: Advances in treatment of peritoneal surface malignancies including cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS±HIPEC) have led to long-term survivorship, yet the subsequent quality of life (QOL) and values of these patients are unknown. PATIENTS AND METHODS: Survivors were offered surveys via online support groups. Novel items assessed how patients prioritized experience, costs, longevity, and wellbeing. RESULTS: Of the 453 gastrointestinal/hepatobiliary (GI/HPB) surgical patients that responded, 74 underwent CRS±HIPEC and were 54±12 years old, 87% female, and 93% white. Respondents averaged 29 months from diagnosis, with a maximum survival of 20 years. With a moderate level of agreement (W = 39%), rankings of value metrics among respondents were predictable (p < 0.001). Longevity and functional independence were ranked highest; treatment experience and cost of treatment were ranked lowest (p < 0.001). Those who underwent CRS±HIPEC or other GI/HPB surgeries reported the same rank order. QOL in CRS±HIPEC survivors, both mental (M-QOL) (44±13) and physical (P-QOL) (41±11) were lower than in the general population (50±10); p < 0.001. Impairments persisted throughout survivorship, but M-QOL improved over time (p < 0.05). When comparing CRS±HIPEC with other GI/HPB cancer surgery survivors, M-QOL (43±13 versus 43±14, p = 0.85) and P-QOL (40±11 versus 42±12, p = 0.41) were similar. CONCLUSIONS: Although CRS±HIPEC survivors experience long-term mental and physical health impairments, they were similar to those experienced by survivors of other GI/HPB cancer surgeries, and their QOL improved significantly throughout survivorship. As CRS±HIPEC survivors prioritize longevity above all other metrics, survival benefit may outweigh a temporary reduction in QOL.

The Impact of Under-triage on Trauma Outcomes in Older Populations ≥65 Years.

BACKGROUND: Undertriage of older trauma patients is implicated as a cause for outcome disparities. Undertriage is defined by an Injury Severity Score (ISS) ≥16 without full trauma activation. We hypothesized that in patients ≥65 years, undertriage is associated with unfavorable discharge. METHODS: This is a retrospective study of patients ≥65 years admitted at a Level 1 Trauma Center between July 2016 and June 2018 with blunt trauma. The Matrix method was used to determine the undertriage rate, and outcomes were compared between undertriaged and fully activated patients with ISS ≥16. Favorable outcomes in undertriaged patients instigated further analyses to determine factors that predicted unfavorable discharge condition, defined by discharge from the hospital with severe disability, persistent vegetative state, and in-hospital death. RESULTS: The undertriage rate was 7.9%. When compared to fully activated patients with ISS ≥16, a lower percentage of undertriaged patients were discharged in an unfavorable condition (16.6% vs 64.7%, P < .001). On the multivariate analysis, male sex (OR = 1.52), preexisting coronary artery disease (OR = 1.86), age >90 years (OR = 2.31), ISS 16-25 (OR = 3.50), Glasgow Coma Score (GCS) ≤14 (OR = 6.34), and ISS >25 (OR = 9.64) were significant independent risk factors for unfavorable discharge. DISCUSSION: The undertriage rate in patients ≥65 years was higher than the accepted standard (5%). However, undertriaged patients had better outcomes than those fully activated with ISS ≥16. Factors more predictive of unfavorable discharge condition were GCS ≤14 and ISS >25. These data suggest that ISS alone is a poor marker for assessing undertriage in older patients. Additional parameters established in this study should be considered as potential markers for better predicting outcomes in older trauma patients.

The Provision of Acute Pediatric Surgical Care by Adult Acute Care General Surgeons : Is There a Learning Curve?

BACKGROUND: At our hospital, acute surgical care of children aged 6 and older is managed by adult acute care surgeons. Previously published data from a 10-year experience with this model demonstrated no differences in outcomes when compared with pediatric surgical benchmark data. This study assesses for the effects of a learning curve in the care of pediatric patients by comparing outcomes of patients treated in the first three years with those treated in the last 3 years during a 10-year experience with this model. DESIGN: This was a retrospective study of pediatric patients aged 6 and older who underwent an emergent or urgent, nontrauma surgical procedure by a general surgeon. Data was obtained via chart review and descriptive statistics were compared between patients operated on between January 1, 2009-January 1, 2012 and January 1, 2016-January 1, 2019. RESULTS: In all, 208 cases were performed in the early cohort and 192 cases in the late cohort. Appendectomy was the most common procedure in both intervals (88% early, 94.8% late). Although there was a significant decrease in open procedures in the later cohort (22.6% vs 4.7%, P < .001), there was no significant change in disease-specific complications or negative appendectomies. No consults to a fellowship-trained pediatric surgeon were required during either time period, although one was available if needed. CONCLUSIONS: Our data demonstrated a decrease in the number of open procedures in the later cohort. This may be due to an increased comfort level with pediatric laparoscopy over time. However, no significant changes in outcomes were observed. This study supports that acute care general surgeons can provide comparable care to pediatric patients within this age demographic and that although a learning curve, appears to exist with respect to pediatric laparoscopy, it is insignificant in terms of its effect on overall outcomes.

Bryostatin-1 Restores Blood Brain Barrier Integrity following Blast-Induced Traumatic Brain Injury.

Recent wars in Iraq and Afghanistan have accounted for an estimated 270,000 blast exposures among military personnel. Blast traumatic brain injury (TBI) is the 'signature injury' of modern warfare. Blood brain barrier (BBB) disruption following blast TBI can lead to long-term and diffuse neuroinflammation. In this study, we investigate for the first time the role of bryostatin-1, a specific protein kinase C (PKC) modulator, in ameliorating BBB breakdown. Thirty seven Sprague-Dawley rats were used for this study. We utilized a clinically relevant and validated blast model to expose animals to moderate blast exposure. Groups included: control, single blast exposure, and single blast exposure + bryostatin-1. Bryostatin-1 was administered i.p. 2.5 mg/kg after blast exposure. Evan's blue, immunohistochemistry, and western blot analysis were performed to assess injury. Evan's blue binds to albumin and is a marker for BBB disruption. The single blast exposure caused an increase in permeability compared to control (t = 4.808, p < 0.05), and a reduction back toward control levels when bryostatin-1 was administered (t = 5.113, p < 0.01). Three important PKC isozymes, PKCα, PKCδ, and PKCε, were co-localized primarily with endothelial cells but not astrocytes. Bryostatin-1 administration reduced toxic PKCα levels back toward control levels (t = 4.559, p < 0.01) and increased the neuroprotective isozyme PKCε (t = 6.102, p < 0.01). Bryostatin-1 caused a significant increase in the tight junction proteins VE-cadherin, ZO-1, and occludin through modulation of PKC activity. Bryostatin-1 ultimately decreased BBB breakdown potentially due to modulation of PKC isozymes. Future work will examine the role of bryostatin-1 in preventing chronic neurodegeneration following repetitive neurotrauma.