Peritoneal Cancer Index Correlates with Radiographic Assessment of Colorectal Carcinomatosis.

Background: The Peritoneal Cancer Index (PCI), calculated intraoperatively, has previously yielded mixed results when correlated with computed tomography. This study aimed to quantify variation in this scoring method comparing radiologists' and surgeons' radiologic PCI (rPCI) assessment.

Methods: The rPCI of 104 patients treated at a single institution for peritoneal carcinomatosis was calculated by an abdominal radiologist and a surgeon.

The Landscape of ctDNA in Appendiceal Adenocarcinoma.

Purpose: Appendiceal adenocarcinoma is a rare malignancy with distinct histopathologic subtypes and a natural history with metastasis primarily limited to the peritoneum. Little is known about the molecular pathogenesis of appendiceal adenocarcinoma relative to common tumors.

Experimental Design: We analyzed molecular data for patients within the Guardant Health database with appendix cancer (n = 718).

The Neonatal Innate Immune Response to Sepsis: Checkpoint Proteins as Novel Mediators of This Response and as Possible Therapeutic/Diagnostic Levers.

Sepsis, a dysfunctional immune response to infection leading to life-threatening organ injury, represents a significant global health issue. Neonatal sepsis is disproportionately prevalent and has a cost burden of 2-3 times that of adult patients. Despite this, no widely accepted definition for neonatal sepsis or recommendations for management exist and those created for pediatric patients are significantly limited in their applicability to this unique population.

Survival and Pulmonary Injury After Neonatal Sepsis: PD1/PDL1's Contributions to Mouse and Human Immunopathology.

Morbidity and mortality associated with neonatal sepsis remains a healthcare crisis. PD1 neonatal mice endured experimental sepsis, in the form of cecal slurry (CS), and showed improved rates of survival compared to wildtype (WT) counterparts. End-organ injury, particularly of the lung, contributes to the devastation set forth by neonatal sepsis.

Malignant Bowel Obstruction in the Time of the COVID-19 Pandemic.

Regardless of the anatomic site of malignant bowel obstruction leading to the need for palliative intervention, decisions must consider the natural history of the disease, the availability and success of nonsurgical treatments, the individual patient's symptom severity, goals, preferences, quality, and expectancy of life. Therapy for symptoms must remain flexible and individualized because the specific needs of the patient will change as disease progresses. Because strangulation is uncommon, malignant bowel obstruction is usually not a surgical emergency.

Improving the value of palliative surgery by optimizing patient selection: The role of long-term survival on high impact palliative intent operations.

Background: In order to better characterize outcomes of palliative surgery (PS), we evaluated patients that experienced top quartile survival to elucidate predictors of high impact PS.

Methods: All PS performed on advanced cancer patients from 2003 to 2017 were identified from a PS database.

Results: 167 patients were identified.

Blockade of endothelial, but not epithelial, cell expression of PD-L1 following severe shock attenuates the development of indirect acute lung injury in mice.

This study sets out to establish the comparative contribution of PD-L1 expression by pulmonary endothelial cells (ECs) and/or epithelial cells (EpiCs) to the development of indirect acute lung injury (iALI) by taking advantage of the observation that treatment with naked siRNA by intratracheal delivery in mice primarily affects lung EpiCs, but not lung ECs, while intravenous delivery of liposomal-encapsulated siRNA largely targets vascular ECs including the lung, but not pulmonary EpiCs. We showed that using a mouse model of iALI [induced by hemorrhagic shock followed by septic challenge (Hem-CLP)], PD-L1 expression on pulmonary ECs or EpiCs was significantly upregulated in the iALI mice at 24 h post-septic insult. After documenting the selective ability of intratracheal versus intravenous delivery of PD-L1 siRNA to inhibit PD-L1 expression on EpiCs versus ECs, respectively, we observed that the iALI-induced elevation of cytokine/chemokine levels (in the bronchoalveolar lavage fluid, lung lysates, or plasma), lung myeloperoxidase and caspase-3 activities could largely only be inhibited by intravenous, but not intratracheal, delivery of PD-L1 siRNA.

Novel Role for PD-1:PD-L1 as Mediator of Pulmonary Vascular Endothelial Cell Functions in Pathogenesis of Indirect ARDS in Mice.

Deficiency of the co-inhibitory receptor, Programmed cell death receptor (PD)-1, provides a survival benefit in our murine shock/sepsis model for the development of indirect acute respiratory distress syndrome (iARDS). Further, of clinical significance, patients that develop ARDS express increased PD-1 on their blood leukocytes. While PD-1 expression and its regulatory role have been associated with mainly T-cell responses, the contribution of its primary ligand, PD-L1, broadly expressed on non-immune cells such as lung endothelial cells (ECs) as well as immune cells, is less well-understood.

Herpes Virus Entry Mediator (HVEM) Expression Promotes Inflammation/ Organ Injury in Response to Experimental Indirect-Acute Lung Injury.

Therapeutic interventions to treat acute lung injury (ALI) remain largely limited to lung-protective strategies, as a real molecular pathophysiologically driven therapeutic intervention has yet to become available. While we have previously documented the expression of herpes virus entry mediator (HVEM) on leukocytes of septic mice and critically ill patients, its functional role in shock/sepsis-induced ALI has not yet been studied. Inasmuch, a murine model of indirect ALI (iALI) was induced by hemorrhagic shock (HEM) followed by cecal ligation and puncture (CLP), septic challenge and HVEM-siRNA or phosphate buffered saline was administrated by intratracheal instillation 2 h after hemorrhage to determine the role of HVEM in the development of experimental iALI.

A novel role for programmed cell death receptor ligand 2 in sepsis-induced hepatic dysfunction.

The liver is an organ that, when dysfunctional in a septic patient, is strongly associated with morbidity and mortality. Understanding the pathophysiology of liver failure during sepsis may lead to improved diagnostics and potential therapeutic targets. Historically, programmed cell death receptor (PD) ligand 1 (PD-L1) has been considered the primary ligand for its checkpoint molecule counterpart, PD-1, with PD-L2 rarely in the immunopathological spotlight.

Group 2 Innate Lymphoid Cells (ILC2s) Are Key Mediators of the Inflammatory Response in Polymicrobial Sepsis.

Sepsis remains a major public health concern, characterized by marked immune dysfunction. Innate lymphoid cells develop from a common lymphoid precursor but have a role in orchestrating inflammation during innate response to infection. Here, we investigate the pathologic contribution of the group 2 innate lymphoid cells (ILC2s) in a murine model of acute septic shock (cecal ligation and puncture).

A novel role for coinhibitory receptors/checkpoint proteins in the immunopathology of sepsis.

Coinhibitory molecules, such as PD-1, CTLA-4, 2B4, and BTLA, are an important new family of mediators in the pathophysiology of severe bacterial and/or fungal infection, as well as the combined insults of shock and sepsis. Further, the expression of these molecules may serve as indicators of the immune status of the septic individual. Using PD-1:PD-L as an example, we discuss in this review how such checkpoint molecules may affect the host response to infection by mediating the balance between effective immune defense and immune-mediated tissue injury.

PAD4 Deficiency Leads to Decreased Organ Dysfunction and Improved Survival in a Dual Insult Model of Hemorrhagic Shock and Sepsis.

Indirect acute respiratory distress syndrome (iARDS) is caused by a nonpulmonary inflammatory process resulting from insults such as nonpulmonary sepsis. Neutrophils are thought to play a significant role in mediating ARDS, with the development of iARDS being characterized by dysregulation and recruitment of activated neutrophils into the lung. Recently, a novel mechanism of microbial killing by neutrophils was identified through the formation of neutrophil extracellular traps (NETs).

Program Cell Death Receptor-1-Mediated Invariant Natural Killer T-Cell Control of Peritoneal Macrophage Modulates Survival in Neonatal Sepsis.

We have shown that invariant natural killer T (NKT) cells mediate sepsis-induced end-organ changes and immune responses, including macrophage bacterial phagocytosis, a finding regulated by the check point protein program cell death receptor-1 (PD-1). Furthermore, PD-1 mediates mortality in both adult and neonatal murine sepsis as well as in surgical patients. Given our previous findings, we hypothesize that NKT cells will also modulate neonatal sepsis survival, and that this effect is regulated in part through PD-1.

Improved survival after induction of sepsis by cecal slurry in PD-1 knockout murine neonates.

Background: Sepsis and the ensuing immune dysfunction continue to be major contributors to neonatal morbidity and mortality. Neonatal sepsis also is associated with profound immune dysfunction. We have recently identified a role for a family of coinhibitory molecules that are altered in murine sepsis and in critically ill adult patients, which may be a target for development of novel therapies.

Radiation-associated sarcoma after recurrent colorectal primary tumor: A complex surgical case.

Radiation associated sarcoma is a significant consequence of cancer therapy. Incidence of radiation associated sarcoma correlates with overall radiotherapy exposure. Prognosis is generally poor with 5 year survival rates lower than that for spontaneously occurring sarcomas.

Interactive Instrument-Driven Image Display in Laparoscopic Surgery.

Background: A significant limitation of minimally invasive surgery is dependence of the entire surgical team on a single endoscopic viewpoint. An individualized, instrument-driven image display system that allows all operators to simultaneously define their viewing frame of the surgical field may be the solution. We tested the efficacy of such a system using a modified Fundamentals of Laparoscopic Surgery™ (Society of American Gastrointestinal and Endoscopic Surgeons, Los Angeles, CA) bead transfer task.