An analysis of sexual dimorphism in the tumor microenvironment of colorectal cancer.

Women with colorectal cancer (CRC) have survival advantages over men, yet the underlying mechanisms are unclear. T cell infiltration within the CRC tumor microenvironment (TME) correlates strongly with survival. We hypothesized that women with CRC have increased T cell infiltration and differential gene expression in the TME compared to men. Tissue microarrays comprising primary tumor, tumor infiltrated lymph nodes, and uninvolved colon were created from CRC patients. Proportions of CD4 positive (CD4+) and CD8 positive (CD8+) T cells were identified using immunohistochemistry. TME immune- and cancer-related genetic expression from primary and metastatic CRC tumor were also evaluated via the NanoStringIO360 panel and The Cancer Genome Atlas Project database. CD4+ was higher in tumor samples from women compared to men (22.04% vs. 10.26%, p=0.002) and also in lymph node samples (39.54% vs. 8.56%, p=0.001). CD8+ was increased in uninvolved colon from women compared to men (59.40% vs. 43.61%, p=0.015), and in stage I/II tumors compared to III/IV in all patients (37.01% vs. 23.91%, p=0.009). Top CD8+ tertile patients survived longer compared to the bottom (43.9 months vs. 25.3 months, p=0.007). Differential gene expression was observed in pathways related to Treg function, T cell activity, and T cell exhaustion, amongst several others, in women compared to men. Thus, significant sexual dimorphism exists in the TME that could contribute to survival advantages observed in female patients with CRC.

The focused abdominal sonography for trauma examination can reliably identify patients with significant intra-abdominal hemorrhage in life-threatening pelvic fractures.

BACKGROUND: The focused abdominal sonography for trauma (FAST) examination has been reported to be unreliable in pelvic fracture patients. Additionally, given the advent of new therapeutic interventions, such as resuscitative endovascular balloon occlusion of the aorta (REBOA), rapid identification of intra-abdominal hemorrhage compared with Zone III hemorrhage may guide different therapeutic strategies. We hypothesized that FAST is reliable for detecting clinically significant intra-abdominal hemorrhage in the face of complex pelvic fractures. METHODS: Our pelvic fracture database of all hemodynamically unstable patients requiring intervention from January 1, 2005, to July 1, 2015, was reviewed. The FAST examination was compared with operative and computed tomography (CT) scan findings. Confirmatory evaluation for FAST(-) patients was considered positive if therapeutic intervention was required. RESULTS: During the study period, 81 patients in refractory shock with FAST imaging in our emergency department (ED) underwent pelvic packing. Mean age was 45 ± 2 years and Injury Severity Score was 50 ± 1.5. The FAST examination was negative in 53 patients; 52 patients did not require operative intervention for abdominal bleeding while one patient required splenectomy. The FAST examination was positive in 28 patients; 26 had findings confirmed by CT or laparotomy while two patients did not have intra-abdominal hemorrhage on further evaluation. The sensitivity and specificity for FAST in this population was 96% and 96%, respectively, positive predictive value was 93%, and negative predictive value was 98%. The false-negative and -positive rates for FAST were 2% and 7%. CONCLUSION: Focused abdominal sonography for trauma examination reliably identifies clinically significant hemoperitoneum in life-threatening, pelvic fracture related hemorrhage. The incidence of a false-negative FAST in this unstable pelvic fracture population was 2%. FAST results may be used when determining the role of REBOA in these multisystem trauma patients and requires further study. REBOA placement should be considered in hemodynamically unstable pelvic fracture patients who are FAST(-), while laparotomy should be used in FAST(+) patients. LEVEL OF EVIDENCE: Therapeutic, level IV.

Preperitoneal pelvic packing reduces mortality in patients with life-threatening hemorrhage due to unstable pelvic fractures.

BACKGROUND: A 2015 American Association for the Surgery of Trauma trial reported a 32% mortality for pelvic fracture patients in shock. Angioembolization (AE) is the most common intervention; the Maryland group revealed time to AE averaged 5 hours. The goal of this study was to evaluate the time to intervention and outcomes of an alternative approach for pelvic hemorrhage. We hypothesized that preperitoneal pelvic packing (PPP) results in a shorter time to intervention and lower mortality. METHODS: In 2004, we initiated a PPP protocol for pelvic fracture hemorrhage. RESULTS: During the 11-year study, 2,293 patients were admitted with pelvic fractures; 128 (6%) patients underwent PPP (mean age, 44 ± 2 years; Injury Severity Score (ISS), 48 ± 1.2). The lowest emergency department systolic blood pressure was 74 mm Hg and highest heart rate was 120. Median time to operation was 44 minutes and 3 additional operations were performed in 109 (85%) patients. Median RBC transfusions before SICU admission compared with the 24 postoperative hours were 8 versus 3 units (p < 0.05). After PPP, 16 (13%) patients underwent AE with a documented arterial blush.Mortality in this high-risk group was 21%. Death was due to brain injury (9), multiple organ failure (4), pulmonary or cardiac failure (6), withdrawal of support (4), adverse physiology (3), and Mucor infection (1). Of those patients with physiologic exhaustion, 2 died in the operating room at 89 and 100 minutes after arrival, whereas 1 died 9 hours after arrival. CONCLUSIONS: PPP results in a shorter time to intervention and lower mortality compared with modern series using AE. Examining mortality, only 3 (2%) deaths were attributed to the immediate sequelae of bleeding with physiologic failure. With time to death under 100 minutes in 2 patients, AE is unlikely to have been feasible. PPP should be used for pelvic fracture-related bleeding in the patient who remains unstable despite initial transfusion. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Expanded screening criteria for blunt cerebrovascular injury: a bigger impact than anticipated.

BACKGROUND: We implemented expanded screening criteria for blunt cerebrovascular injuries (BCVIs) in an attempt to capture the remaining 20% of patients not historically identified with earlier protocols. We hypothesized that these expanded criteria would capture the additional 20% of BCVI patients not previously identified. METHODS: Screening criteria for BCVI were expanded in 2011 after identifying new injury patterns. The study population included 4 years prior (2007 to 2010; classic) and following (2011 to 2014; expanded) implementation of expanded criteria. RESULTS: BCVIs were identified in 386 patients: 150 during the classic period (2.36% incidence) and 236 in the expanded period (2.99% incidence). In the expanded period, 155 patients were imaged based on classic screening criteria, 62 on expanded criteria (21 complex skull fractures, 20 upper rib fractures, 6 mandible fractures, 2 scalp degloving, 1 great vessel injury, and 12 combination), and 19 for other injuries and symptoms. CONCLUSIONS: There was a significant increase in the identification of BCVI following the adoption of expanded screening criteria, resulting in a substantial reduction of missed injuries. Expanded criteria should be adopted when screening for BCVI.