Surgical Cancer Care in Safety-Net Hospitals: a Systematic Review.

BACKGROUND: Tertiary medical centers in the USA provide specialized, high-volume surgical cancer care, contributing standards for quality and outcomes. For the most vulnerable populations, safety-net hospitals (SNHs) remain the predominant provider of both complex and routine healthcare needs. The objective of this study was to evaluate access to and quality of surgical oncology care within SNHs. METHODS: A comprehensive and systematic review of the literature was conducted using PubMed, EMBASE, and Cochrane Library databases to identify all studies (January 2000-October 2021) reporting the delivery of surgical cancer care at SNHs in the USA (PROSPERO #CRD42021290092). These studies describe the process and/or outcomes of surgical care for gastrointestinal, hepatopancreatobiliary, or breast cancer patients seeking treatment at SNHs. RESULTS: Of 3753 records, 37 studies met the inclusion criteria. Surgical care for breast cancer (43%) was the most represented, followed by colorectal (30%) and hepatopancreatobiliary (16%) cancers. Financial constraints, cultural and language barriers, and limitations to insurance coverage were cited as common reasons for disparities in care within SNHs. Advanced disease at presentation was common among cancer patients seeking care at SNHs (range, 24-61% of patients). Though reports comparing cancer survival between SNHs and non-SNHs were few, results were mixed, underscoring the variability in care seen across SNHs. CONCLUSIONS: These findings highlight barriers in care facing many cancer patients. Continued efforts should address improving both access and quality of care for SNH patients. Future models include a transition away from a two-tiered system of resourced and under-resourced hospitals toward an integrated cancer system.

Endothelial cell dysfunction during anoxia-reoxygenation is associated with a decrease in adenosine triphosphate levels, rearrangement in lipid bilayer phosphatidylserine asymmetry, and an increase in endothelial cell permeability.

BACKGROUND: Phosphatidylserine (PS) is normally confined in an energy-dependent manner to the inner leaflet of the lipid cell membrane. During cellular stress, PS is exteriorized to the outer layer, initiating a cascade of events. Because cellular stress is often accompanied by decreased energy levels and because maintaining PS asymmetry is an energy-dependent process, it would make sense that cellular stress associated with decreased energy levels is also associated with PS exteriorization that ultimately leads to endothelial cell dysfunction. Our hypothesis was that anoxia-reoxygenation (A-R) is associated with decreased adenosine triphosphate (ATP) levels, increased PS exteriorization on endothelial cell membranes, and increased endothelial cell membrane permeability. METHODS: The effect on ATP levels during A-R was measured via colorimetric assay in cultured cells. To measure the effect of A-R on PS levels, cultured cells underwent A-R and exteriorized PS levels and also total cell PS were measured via biofluorescence assay. Finally, we measured endothelial cell monolayer permeability to albumin after A-R. RESULTS: The ATP levels in cell culture decreased 27% from baseline after A-R (p < 0.02). There was over a twofold increase in exteriorized PS as compared with controls (p < 0.01). Interestingly, we found that during A-R, the total amount of cellular PS increased (p < 0.01). The finding that total PS changed twofold over normal cells suggested that not only is there a change in the distribution of PS across the cell membrane, but there may also be an increase in the amount of PS inside the cell. Finally, A-R increased endothelial cell monolayer permeability (p < 0.01). CONCLUSION: We found that endothelial cell dysfunction during A-R is associated with decreased ATP levels, increased PS exteriorization, and increased in monolayer permeability. This supports the idea that PS exteriorization may a key event during clinical scenarios involving oxygen lack and may 1 day lead to novel therapies in these situations.

The heart of the matter: utility of ultrasound of cardiac activity during traumatic arrest.

BACKGROUND: The clinical utility of determining cardiac motion on ultrasound has been reported for patients presenting in pulseless medical cardiac arrest. However, the relationship between ultrasound-documented cardiac activity and the probability of surviving pulseless electrical activity has not been examined in populations with trauma. We hypothesized that cardiac activity on ultrasound predicts survival for patients presenting in pulseless traumatic arrest. METHODS: We conducted a retrospective analysis at our university-based urban trauma center of adult patients with trauma, who were pulseless on hospital arrival. Results of cardiac ultrasound performed during trauma resuscitations were compared with the electrocardiogram (EKG) rhythm and survival. RESULTS: Among 318 pulseless patients with trauma, 162 had both EKG tracings and a cardiac ultrasound, and 4.3% of these 162 patients survived to hospital admission. Survival was higher for those with cardiac motion than for those without it (23.5% vs. 1.9% for patients with EKG electrical activity, p = 0.002, and 66.7% vs. 0% for patients without EKG electrical activity, p < 0.001). The sensitivity of ultrasound cardiac motion to predict survival to hospital admission was 86% (specificity, 91%; positive predictive value, 30%; negative predictive value, 99%). When examined by mechanism, sensitivity was 100% for the 111 patients with penetrating trauma and 75% for the 50 patients with blunt trauma. CONCLUSION: Survival in pulseless traumatic arrest is very low, but survival for patients with no cardiac motion on ultrasound is also exceedingly rare. Cardiac ultrasound had a negative predictive value approaching 100% for survival to hospital admission. For patients with prolonged prehospital cardiopulmonary resuscitation, ultrasound evaluation of cardiac motion in pulseless patients with trauma may be a rapid way to help determine which patients have no chance of survival in the setting of lethal injuries, so that futile resuscitations can be stopped.

Single-contrast computed tomography for the triage of patients with penetrating torso trauma.

BACKGROUND: We have used single-contrast (intravenous contrast only) computed tomography (SCCT) for triaging hemodynamically stable patients with penetrating torso trauma. We hypothesized that SCCT safely determines the need for operative exploration. Furthermore, trauma surgeons without specialized training in body imaging can accurately apply this modality. METHODS: We retrospectively reviewed the records of patients with penetrating torso injuries at a university-based urban trauma center to establish the accuracy of SCCT in determining the need for exploratory laparotomy. The scan was considered positive or negative with respect to the need for exploratory laparotomy as documented by the attending surgeon, who may have considered the read of the on call radiologist if available. In a separate study, four trauma surgeons independently reviewed 42 SCCT scans to establish whether the scans alone could be used to determine whether operative exploration was necessary. RESULTS: Between 1997 and 2008, 306 hemodynamically stable patients with penetrating torso trauma were triaged by SCCT. Overall, SCCT predicted the need for laparotomy with 98% sensitivity and 90% specificity. The positive predictive value was 84% and the negative predictive value (NPV) was 99%. In the 222 patients with gunshot wounds, SCCT had 100% sensitivity and 100% NPV. In the 84 patients with stab wounds, SCCT had 92% sensitivity and 97% NPV. Trauma surgeon agreement in the retrospective review of 42 computed tomography scans was "nearly perfect": positive predictive value was 93% and NPV was 92% for determining the need for exploratory laparotomy surgery. CONCLUSIONS: SCCT is safe and effective for triaging hemodynamically stable patients with penetrating torso trauma. It successfully determined the need for operative intervention with appropriate clinical accuracy without the additional costs, morbidity, and delay of oral and rectal contrast. Trauma surgeons can reproducibly interpret SCCT with high-predictive accuracy as to whether patients with penetrating torso trauma require operative exploration.

Glucagon-like peptide-1 protects mesenteric endothelium from injury during inflammation.

Glucagon-like peptide-1 (GLP-1) is a proglucagon-derived hormone with cellular protective actions. We hypothesized that GLP-1 would protect the endothelium from injury during inflammation. Our aims were to determine the: (1) effect of GLP-1 on basal microvascular permeability, (2) effect of GLP-1 on increased microvascular permeability induced by lipopolysaccaride (LPS), (3) involvement of the GLP-1 receptor in GLP-1 activity, and (4) involvement of the cAMP/PKA pathway in GLP-1 activity. Microvascular permeability (L(p)) of rat mesenteric post-capillary venules was measured in vivo. First, the effect of GLP-1 on basal L(p) was measured. Second, after systemic LPS injection, L(p) was measured after subsequent perfusion with GLP-1. Thirdly, L(p) was measured after LPS injection and perfusion with GLP-1+GLP-1 receptor antagonist. Lastly, L(p) was measured after LPS injection and perfusion with GLP-1+inhibitors of the cAMP/PKA pathway. Results are presented as mean area under the curve (AUC)+/-SEM. GLP-1 had no effect on L(p) (AUC: baseline=27+/-1.4, GLP-1=1+/-0.4, p=0.08). LPS increased L(p) two-fold (AUC: LPS=54+/-1.7, p<0.0001). GLP-1 reduced the LPS increase in L(p) by 75% (AUC: LPS+GLP-1=34+/-1.5, p<0.0001). GLP-1 antagonism reduced the effects of GLP-1 by 60% (AUC: LPS+GLP-1+antagonist=46+/-2.0, p<0.001). The cAMP synthesis inhibitor reduced the effects of GLP-1 by 60% (AUC: LPS+GLP-1+cAMP inhibitor=46+/-1.5, p<0.0001). The PKA inhibitor reduced the effects of GLP-1 by 100% (AUC: LPS+GLP-1+PKA inhibitor=56+/-1.5, p<0.0001). GLP-1 attenuates the increase in microvascular permeability induced by LPS. GLP-1 may protect the endothelium during inflammation, thus decreasing third-space fluid loss.

Trauma training in simulation: translating skills from SIM time to real time.

BACKGROUND: : Training surgical residents to manage critically injured patients in a timely fashion presents a significant challenge. Simulation may have a role in this educational process, but only if it can be demonstrated that skills learned in a simulated environment translate into enhanced performance in real-life trauma situations. METHODS: : A five-part, scenario-based trauma curriculum was developed specifically for this study. Midlevel surgical residents were randomized to receiving this curriculum in didactic lecture (LEC) fashion or with the use of a human performance simulator (HPS). A written learning objectives test was administered at the completion of the training. The first four major trauma resuscitations performed by each participating resident were captured on videotape in the emergency department and graded by two experienced judges blinded to the method of training. The assessment tool used by the judges included an evaluation of both initial trauma evaluation or treatment skills (part I) and crisis management skills (part II) as well as an overall score (poor/fail, adequate, or excellent). RESULTS: : The two groups of residents received almost identical scores on the posttraining written test. Average SIM and LEC scores for part I were also similar between the two groups. However, SIM-trained residents received higher overall scores and higher scores for part II crisis management skills compared with the LEC group, which was most evident in the scores received for the teamwork category (p = 0.04). CONCLUSIONS: : A trauma curriculum incorporating simulation shows promise in developing crisis management skills that are essential for evaluation of critically injured patients.

Endothelin-1 reduces mesenteric microvascular hydraulic permeability via cyclic AMP and protein kinase A signal transduction.

We have previously shown that endothelin-1 (ET-1) decreases microvascular hydraulic permeability. In this study, we tested the hypothesis that ET-1 exerts its permeability-decreasing effect through cAMP, cGMP, and protein kinase A (PKA) by determining the effect of ET-1 on venular fluid leak during inhibition of cAMP synthesis, inhibition of cGMP degredation, and inhibition of PKA. Rat mesenteric venules were cannulated to measure hydraulic permeability, L(p) (units x 10(-7)cm/(s cmH(2)O)). L(p) was measured during continuous perfusion of 80 pM ET-1 and either (1) an inhibitor of cAMP synthesis (10 microM 2',5'ddA), (2) an inhibitor of cGMP degradation (100 microM Zaprinast), or (3) an inhibitor of PKA (10 microM H-89). Inhibition of cAMP synthesis blocked the permeability decreasing effects of ET-1. The peak L(p) of the cAMP inhibitor alone and with ET-1 was 4.11+/-0.53 and 3.86+/-0.19, respectively (p=0.36, n=6). Inhibition of cGMP degradation did not block the permeability decreasing effects of ET-1. The peak L(p) during inhibition of cGMP degradation alone and with ET-1 was 2.26+/-0.15 and 1.44+/-0.09, respectively (p<0.001, n=6). Inhibition of PKA activation blocked the permeability decreasing effects of ET-1. The peak L(p) of the PKA inhibitor alone and with ET-1 was 2.70+/-0.15 and 2.59+/-0.15, respectively (p=0.38, n=6). The data support the notion that the signal transduction mechanism of ET-1 with regard to decreasing microvascular fluid leak involves cAMP production and PKA activation, but not cGMP degradation. Further understanding of intracellular mechanisms that control microvascular fluid leak could lead to the development of a pharmacologic therapy to control third space fluid loss in severely injured or septic patients.

Angiotensin II type 2 receptor decreases ischemia reperfusion induced fluid leak.

BACKGROUND: Intravascular volume loss from ischemia-reperfusion (IR) injury is a major clinical concern. We hypothesize that angiotensin II decreases IR-mediated microvascular fluid leak via the angiotensin II type 2 receptor in a cAMP dependent manner. We therefore sought to determine hydraulic permeability after IR of venules treated with 1) angiotensin II, 2) angiotensin II and cAMP synthesis inhibitor, and 3) angiotensin II and an angiotensin II type 2 receptor antagonist. METHODS: Rat mesenteric post-capillary venules were micro-cannulated to measure hydraulic permeability (L(p)). IR was achieved by placing animals in a 5% oxygen environment and preventing venular flow, after which blood flow was allowed to resume. L(p) was measured after IR and treatment with 1) angiotensin II (20 nm), 2) angiotensin II (20 nm) + cAMP synthesis inhibitor (DDA,10uM), and 3) angiotensin II (20 nm) + type 2 receptor antagonist (PD-123319, 300 mum) (n=6 in each group). RESULTS: Compared with the seven-fold increase in L(p) because of IR alone: 1) angiotensin II attenuated the seven-fold increase by 50% (P<0.005), 2) cAMP inhibition did not change the effect of angiotensin II on leak, and the type 2 receptor antagonist completely blocked the effects of angiotensin II on IR mediated leak. CONCLUSION: Treatment with angiotensin II attenuated increases in hydraulic permeability because of IR by 50%. Inhibition of cAMP synthesis did not change the effect of angiotensin II on IR mediated leak, and angiotensin II type 2 receptor inhibition completely blocked the effects of angiotensin II. These results indicate that angiotensin II decreases IR induced leak via the angiotensin II type 2 receptor in a cAMP independent manner. A better understanding of mediators that reduce intravascular fluid loss from IR-induced microvascular dysfunction may help clinicians treat uncontrolled fluid extravasation that occurs during shock and sepsis.

Deep vein harvest: predicting need for fasciotomy.

OBJECTIVE: Deep thigh veins, including the superficial femoral, superficial femoropopliteal, and profunda femoris veins, are versatile autogenous conduits for arterial reconstruction. Although late venous complications are unusual, deep vein harvest may induce severe venous hypertension and predispose the limb to acute compartment syndrome. The purpose of this study was to define the frequency of fasciotomy in patients undergoing deep vein harvest and to identify clinical predictors of the need for fasciotomy after deep vein harvest. METHODS: Over 9 years, 162 patients underwent arterial reconstruction with deep vein harvested from 264 limbs. Indications for deep vein harvest included aortofemoral reconstruction in 127 patients, brachiocephalic arterial reconstruction in 22 patients, and visceral arterial reconstruction in 13 patients. RESULTS: Fasciotomy was performed in 47 of 264 limbs (17.8%) after deep vein harvest. The prevalence of fasciotomy after deep vein harvest was 20.6% for patients requiring aortofemoral reconstruction, whereas no patients underwent fasciotomy after deep vein harvest for mesenteric or brachiocephalic arterial reconstruction (P =.0068). Fasciotomy was performed in 20.7% of limbs after complete deep vein harvest to a level below the adductor hiatus, but no fasciotomies were performed in patients undergoing subtotal deep vein harvest, ending above the adductor hiatus (P =.0023). The mean preoperative ankle-brachial index (ABI) was significantly lower in limbs requiring fasciotomy (ABI, 0.39 +/- 0.05), compared with patients who did not require fasciotomy (ABI, 0.79 +/- 0.02; P <.0001). Fasciotomy was performed in 76.0% of limbs undergoing concurrent ipsilateral greater saphenous vein (GSV) and deep vein harvest, compared with 11.7% of patients undergoing deep vein harvest alone (P <.0001). The mean volume of intraoperative fluid administered to patients requiring fasciotomy was almost 50% higher than the fluid resuscitation received by patients who did not require fasciotomy (9.6 +/- 1.2 L vs 6.5 +/- 0.6 L; P <.0001). Logistic regression analysis determined that lower preoperative ABI (odds ratio [OR], 60.1; 95% confidence interval [CI], 12.5-289.3; P <.0001) and concurrent harvest of the ipsilateral GSV (OR, 9.9; 95% CI, 3.1-31.3; P <.0001) were predictors of the need for fasciotomy. CONCLUSIONS: One in four patients undergoing deep vein harvest for aortofemoral reconstruction may be expected to develop acute compartment syndrome and require fasciotomy. The risk appears to be greatest in patients with severe lower extremity ischemia and in patients undergoing simultaneous GSV and deep vein harvest. Prophylactic fasciotomy may be appropriate in patients with both risk factors, but vigilance for the development of compartment syndrome after deep vein harvest is required in all patients undergoing deep vein harvest for aortofemoral reconstruction.

Early and late presentations of radiation arteritis.

Radiotherapy (XRT) plays a prominent role in the therapy of a variety of malignancies. Improved survival for malignancies treated with XRT has produced a growing subset of patients who present several years later with arterial occlusive disease in the irradiated field. Establishing a presumptive diagnosis of radiation arteritis (RA) is based on clinical history and the arteriographic appearance of lesions. The lesions of RA often occur in atypical locations with adjacent arterial beds largely spared of atherosclerosis. The indications for intervention for RA do not differ significantly from atherosclerotic arterial lesions. In most cases, RA lesions do not merit treatment unless they become symptomatic. However, asymptomatic carotid artery lesions should be considered for intervention because they are particularly prone to progression and development of neurologic symptoms. Percutaneous and endovascular techniques are viable treatment options for lesions with favorable anatomy. Operative interventions often require extraanatomic approaches and autogenous conduits to optimize outcomes in irradiated fields.

Comparison of superficial femoral vein and saphenous vein as conduits for mesenteric arterial bypass.

PURPOSE: Gangrenous bowel, intraabdominal sepsis, and previous failed mesenteric bypass are indications for use of an autogenous conduit for mesenteric arterial reconstruction. Saphenous vein (SV) is often used as the autogenous conduit of choice, but it may be prone to graft stenosis or occlusion. Recent experience with superficial femoral vein (SFV) suggests that it is an excellent alternative conduit for major arterial reconstruction. The purpose of this study was to compare the outcomes of SV and SFV for mesenteric arterial bypass. METHODS: During a 7-year period, 26 patients underwent 43 mesenteric arterial bypass procedures with autogenous conduit. SV was used for 23 bypasses (53%), and SFV was used for 20 bypasses (47%). Indications for revascularization included chronic mesenteric ischemia (n = 15; 58%), acute mesenteric ischemia (n = 9; 35%), and mycotic aneurysm of the paravisceral aorta (n = 2; 7%). Three patients (11%) underwent revascularization with SV grafts and two patients (8%) with SFV grafts after previous failed mesenteric bypass. RESULTS: The 30-day mortality rate was 15%. Three deaths occurred after SV bypass for acute mesenteric ischemia, and one death occurred after a SFV bypass for a ruptured paravisceral mycotic aneurysm. Twenty-two surviving patients were followed for a mean of 31 +/- 6 months. Three of 11 patients (27%) who survived after SV bypass had recurrent mesenteric ischemia develop (acute, n = 1; chronic, n = 2) from graft thrombosis at a mean interval of 32 +/- 22 months after surgery. No patient had recurrent symptoms develop after SFV bypass. One of the three patients with SV graft failure died of acute mesenteric ischemia, and the other two patients underwent successful bypass with SFV. Symptomatic graft failure was significantly more likely to occur in patients receiving SV grafts compared with SFV grafts (P <.05). CONCLUSION: SFV yields acceptable clinical outcomes for mesenteric arterial bypass compared with SV. SFV is a viable alternative to SV when autogenous conduit is indicated for mesenteric arterial reconstruction.

Upregulation of autocrine-paracrine renin-angiotensin systems in chronic renovascular hypertension.

INTRODUCTION: The mechanism by which hypertension is maintained in renovascular hypertension remains poorly defined. Because plasma angiotensin II does not correlate with blood pressure in RVH, we postulated that activation of tissue-specific autocrine-paracrine renin-angiotensin systems may upregulate local production of angiotensin II and maintain hypertension in chronic RVH. METHODS: RVH was induced with a two-kidney one-clip (2K1C) rat model. Animals were killed at 1 or 12 weeks after surgery (acute or chronic RVH). Angiotensin II was quantitated with radioimmunoassay. Angiotensin II-type 1 (AT(1)) receptor density was determined with immunoblotting and immunohistochemistry. RESULTS: Blood pressure was significantly elevated in 2K1C animals compared with sham animals at 1 week (141 +/- 5 mm Hg versus 98 +/- 3 mm Hg; P <.0005) and at 12 weeks (164 +/- 14 mm Hg versus 110 +/- 7 mm Hg; P <.0005) after surgery. No significant difference was seen in plasma angiotensin II levels between 2K1C and control animals during acute (38.2 +/- 6.5 fmol/mL versus 27.6 +/- 6.8 fmol/mL; P = not significant) or chronic (40.1 +/- 17.4 fmol/mL versus 27.1 +/- 6.5 fmol/mL; P = not significant) RVH. During acute RVH, intrarenal angiotensin II was significantly increased in both the clipped (126.0 +/- 16.2 fmol/g versus 62.0 +/- 6.2 fmol/g; P <.005) and unclipped (78.9 +/- 6.3 fmol/g versus 39.9 +/- 2.5 fmol/g; P <.05) kidneys of 2K1C animals compared with control animals. Increased intrarenal angiotensin II levels persisted in chronic RVH in the clipped (147.4 +/- 37.7 fmol/g versus 59.2 +/- 8.7 fmol/g; P <.05) and unclipped (130.8 +/- 31.8 fmol/g versus 63.0 +/- 11.0 fmol/g; P <.05) kidneys of 2K1C animals compared with controls. Adrenal angiotensin II content of 2K1C animals was unchanged in acute RVH (493.7 +/- 51.4 fmol/g versus 522.6 +/- 80.5 fmol/g; P = not significant) but increased nearly three-fold over control animals during chronic RVH (1129.0 +/- 149.3 fmol/g versus 400.6 +/- 59.1 fmol/g; P <.0005). No significant difference in AT(1) receptor density was noted in renal tubules of clipped and unclipped kidneys or in the adrenal glands of 2K1C animals during acute or chronic RVH compared with control animals. CONCLUSION: Tissue angiotensin II production is upregulated in the kidneys and adrenal glands in chronic RVH, and AT(1) receptor density is maintained in these tissues, providing a potential mechanism for maintenance of hypertension in RVH.