Evaluation of a pain management program for patients with median arcuate ligament syndrome.

Objectives: Median arcuate ligament syndrome is a complex disorder potentially caused by variation in the position of the median arcuate ligament. Symptomology involves chronic abdominal pain, nausea, and malnourishment. Pain management modalities and short-term outcomes for patients undergoing operative surgery for median arcuate ligament syndrome have yet to be fully evaluated. Our hospital implemented a pain management consultation program in 2017 focused on perioperative pain management. The objective of this study is to assess if the introduction of a pain management consultation program concurrent with median arcuate ligament syndrome surgery impacts patient outcomes and post-operative pain management strategies in these patients. Methods: De-identified data was collected retrospectively from our hospital's electronic medical records system, identifying median arcuate ligament syndrome patients and using International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes from September 2017 to August 2021. Patients were grouped into the "consultation" cohort if they had scheduled and attended a pre-operative pain consultation. Pre-operative and discharge medications, pain scores, and demographics were collected to evaluate if the initiative impacted outcomes. Results: Median arcuate ligament syndrome patients who had a pre-operative pain management consultation had higher rates of pre-operative opioid (35.5%; p = 0.01) and non-opioid use (60.7%; p < 0.001). Patients without a pre-operative consultation that did not use opioids pre-operatively were more likely to be discharged on one or more opioids. Differences were also found for psychiatric medication at discharge (p < 0.001) with patients receiving pain consultation indicating higher percentages of use. Conclusion: Special consideration on prescribing pain medication should be part of discharge planning for median arcuate ligament syndrome patients. Addition of a pain management consultation can aid in these decisions.

Angiogenesis: an adaptive dynamic biological patterning problem.

Formation of functionally adequate vascular networks by angiogenesis presents a problem in biological patterning. Generated without predetermined spatial patterns, networks must develop hierarchical tree-like structures for efficient convective transport over large distances, combined with dense space-filling meshes for short diffusion distances to every point in the tissue. Moreover, networks must be capable of restructuring in response to changing functional demands without interruption of blood flow. Here, theoretical simulations based on experimental data are used to demonstrate that this patterning problem can be solved through over-abundant stochastic generation of vessels in response to a growth factor generated in hypoxic tissue regions, in parallel with refinement by structural adaptation and pruning. Essential biological mechanisms for generation of adequate and efficient vascular patterns are identified and impairments in vascular properties resulting from defects in these mechanisms are predicted. The results provide a framework for understanding vascular network formation in normal or pathological conditions and for predicting effects of therapies targeting angiogenesis.

Clinical and anatomic outcomes of endovenous radiofrequency ablation performed on symptomatic small-diameter great saphenous veins.

OBJECTIVE: The efficacy of radiofrequency ablation (RFA) for symptomatic varicose veins is well established. Alternatively, there is less consensus and little data on outcomes when treating great saphenous veins (GSV) of small diameter (≤5 mm). The purpose of this study is to assess clinical and anatomical outcomes of RFA on symptomatic patients with small GSV. METHODS: A retrospective analysis was performed on our symptomatic patients who received RFA of incompetent GSV without any concomitant adjunctive procedures between January 2008 and December 2011. Limbs with GSV thigh diameter ≤5 mm and >5 mm on duplex while standing were subject to review. Clinical success was defined as an improvement in Venous Clinical Severity Score (VCSS) at 3 months. Anatomic success was defined as absence of venous flow ≤3 cm distal to the saphenofemoral junction on duplex ultrasound examination. Changes in CEAP class were noted. RESULTS: In 307 patients, 55 limbs in 44 patients met inclusion criteria. Baseline median VCSS was 4 (interquartile range [IQR], 4, 5) for those patients with diameter ≤5 mm. Clinical success was seen in 83% of limbs at 3 months with a median VCSS change of -2 (IQR, -3, -1). None of the treated limbs had phlebectomy for symptomatic refluxing GSV varicosities prior to 3-month follow up. One phlebectomy was performed for cosmesis at 78 days postprocedure. Anatomic success was achieved in 96% of limbs at 3 months. Baseline median CEAP was 2 (IQR, 2, 2). The median CEAP change at 3 months was 0 (IQR, -1, 0). One patient experienced thrombus extension into the saphenofemoral junction at 4 days. CONCLUSIONS: In our experience, RFA of symptomatic small-diameter GSV provides comparable clinical and anatomic outcomes to that of current published data. Our findings suggest that these patients benefit clinically from RFA.

Anesthetic Challenges in Robotic-assisted Urologic Surgery.

Robotic-assisted surgery has evolved over the past two decades with constantly improving technology, assisting surgeons in multiple subspecialty disciplines. The surgical requirements of lithotomy and steep Trendelenburg positions, along with the creation of a pneumoperitoneum and limited access to the patient, all present anesthetic management challenges in urologic surgery. Patient positioning requirements can cause significant physiologic effects and may result in many complications. Good communication among team members and knowledge of the nuances of robotic surgery have the potential to improve patient outcomes, increase efficiency, and reduce surgical and anesthetic complications.

Endovascular vs open repair for ruptured abdominal aortic aneurysm.

OBJECTIVE: Endovascular repair (EVAR) of ruptured abdominal aortic aneurysm (rAAA) has become first-line therapy at our institution and is performed under a standardized protocol. We compare perioperative mortality, midterm survival, and morbidity after EVAR and open surgical repair (OSR). METHODS: Records were retrospectively reviewed from May 2000 to September 2010 for repair of infrarenal rAAAs. Primary end points included perioperative mortality and midterm survival. Secondary end points included acute limb ischemia, length of stay, ventilator-dependent respiratory failure, myocardial infarction, renal failure, abdominal compartment syndrome, and secondary intervention. Statistical analysis was performed using the t-test, χ(2) test, the Fisher exact test, and logistic regression calculations. Midterm survival was assessed with Kaplan-Meier analysis and Cox proportional hazard models. RESULTS: Seventy-four infrarenal rAAAs were repaired, 19 by EVAR and 55 by OSR. Despite increased age and comorbidity in the EVAR patients, perioperative mortality was 15.7% for EVAR, which was significantly lower than the 49% for OSR (odds ratio, 0.19; 95% CI, 0.05-0.74; P = .008). Midterm survival also favored EVAR (hazard ratio, 0.40; 95% CI, 0.21-0.77; P = .028, adjusted for age and sex). Mean follow-up was 20 months, and 1-year survival was 60% for EVAR vs 45% for OSR. Mean length of stay for patients surviving >1 day was 10 days for EVAR and 21 days for OSR (P = .004). Ventilator-dependent respiratory failure was 5% in the EVAR group vs 42% for OSR (odds ratio, 0.08; 95% CI, 0.01-0.62; P = .001). CONCLUSIONS: EVAR of rAAA has a superior perioperative survival advantage and decreased morbidity vs OSR. Although not statistically significant, overall survival favors EVAR. We recommend that EVAR be considered as the first-line treatment of rAAAs and practiced as the standard of care.

CT colonography versus colonoscopy for the detection of advanced neoplasia.

BACKGROUND: Advanced neoplasia represents the primary target for colorectal-cancer screening and prevention. We compared the diagnostic yield from parallel computed tomographic colonography (CTC) and optical colonoscopy (OC) screening programs. METHODS: We compared primary CTC screening in 3120 consecutive adults (mean [+/-SD] age, 57.0+/-7.2 years) with primary OC screening in 3163 consecutive adults (mean age, 58.1+/-7.8 years). The main outcome measures included the detection of advanced neoplasia (advanced adenomas and carcinomas) and the total number of harvested polyps. Referral for polypectomy during OC was offered for all CTC-detected polyps of at least 6 mm in size. Patients with one or two small polyps (6 to 9 mm) also were offered the option of CTC surveillance. During primary OC, nearly all detected polyps were removed, regardless of size, according to established practice guidelines. RESULTS: During CTC and OC screening, 123 and 121 advanced neoplasms were found, including 14 and 4 invasive cancers, respectively. The referral rate for OC in the primary CTC screening group was 7.9% (246 of 3120 patients). Advanced neoplasia was confirmed in 100 of the 3120 patients in the CTC group (3.2%) and in 107 of the 3163 patients in the OC group (3.4%), not including 158 patients with 193 unresected CTC-detected polyps of 6 to 9 mm who were undergoing surveillance. The total numbers of polyps removed in the CTC and OC groups were 561 and 2434, respectively. There were seven colonic perforations in the OC group and none in the CTC group. CONCLUSIONS: Primary CTC and OC screening strategies resulted in similar detection rates for advanced neoplasia, although the numbers of polypectomies and complications were considerably smaller in the CTC group. These findings support the use of CTC as a primary screening test before therapeutic OC.

Use of three-dimensional tissue cultures to model extravascular transport and predict in vivo activity of hypoxia-targeted anticancer drugs.

BACKGROUND: Because of the inefficient vasculature of solid tumors, anticancer drugs must penetrate relatively long distances through the extravascular compartment. The requirement for such diffusion may limit their activity, especially that of hypoxia-targeted drugs. We tested whether a three-dimensional pharmacokinetic/pharmacodynamic (PK/PD) model based on a representative mapped tumor microvascular network could predict the therapeutic activity of anticancer drugs in mouse xenograft tumors. METHODS: Diffusion coefficients of the hypoxia-activated anticancer drug tirapazamine (TPZ) and of 15 TPZ analogs were estimated by measuring their transport through HT29 colon cancer multicellular layers (MCLs). Anoxic cytotoxic potency (by clonogenic assay) and metabolism of the TPZ analogs were measured in HT29 cell suspensions, and their plasma pharmacokinetics was measured in CD-1 nude mice. This information was used to create a spatially resolved PK/PD model for the tumor microvascular network. Model predictions were compared with actual hypoxic cell kill as measured by clonogenic assays on HT29 xenograft tumors 18 hours after treatment with each TPZ analog. RESULTS: Modeling TPZ transport in the tumor microvascular network showed substantial drug depletion in the most hypoxic regions, with predicted maximum cell kill of only 3 logs, compared with more than 10 logs if there were no transport impediment. A large range of tissue diffusion coefficients (0.027 x 10(-6)-1.87 x 10(-6) cm2/s) was observed for the TPZ analogs. There was a strong correlation between model-predicted and measured hypoxic cell kill (R2 = 0.89) but a poor correlation when the model did not include extravascular transport (R2 = 0.32). CONCLUSIONS: Extravascular transport in tumors, and its consequences for tumor cell killing, can be predicted by measuring drug penetration through MCLs in vitro and modeling pharmacokinetics at each position in three-dimensional microvascular networks.

An inflammatory checkpoint regulates recruitment of graft-versus-host reactive T cells to peripheral tissues.

Transfer of T cells to freshly irradiated allogeneic recipients leads to their rapid recruitment to nonlymphoid tissues, where they induce graft-versus-host disease (GVHD). In contrast, when donor T cells are transferred to established mixed chimeras (MCs), GVHD is not induced despite a robust graft-versus-host (GVH) reaction that eliminates normal and malignant host hematopoietic cells. We demonstrate here that donor GVH-reactive T cells transferred to MCs or freshly irradiated mice undergo similar expansion and activation, with similar up-regulation of homing molecules required for entry to nonlymphoid tissues. Using dynamic two-photon in vivo microscopy, we show that these activated T cells do not enter GVHD target tissues in established MCs, contrary to the dogma that activated T cells inevitably traffic to nonlymphoid tissues. Instead, we show that the presence of inflammation within a nonlymphoid tissue is a prerequisite for the trafficking of activated T cells to that site. Our studies help to explain the paradox whereby GVH-reactive T cells can mediate graft-versus-leukemia responses without inducing GVHD in established MCs.

Host MHC class II+ antigen-presenting cells and CD4 cells are required for CD8-mediated graft-versus-leukemia responses following delayed donor leukocyte infusions.

Following bone marrow transplantation, delayed donor leukocyte infusions (DLIs) can induce graft-versus-leukemia (GVL) effects without graft-versus-host disease (GVHD). These antitumor responses are maximized by the presence of host hematopoietic antigen-presenting cells (APCs) at the time of DLI. Using a tumor-protection model, we demonstrate here that GVL activity following administration of DLIs to established mixed chimeras is dependent primarily on reactivity to allogeneic MHC antigens rather than minor histocompatibility or tumor-associated antigens. CD8(+) T-cell-dependent GVL responses against an MHC class II-negative tumor following delayed DLI require CD4(+) T-cell help and are reduced significantly when host APCs lack MHC class II expression. CD4(+) T cells primed by host APCs were required for maximal expansion of graft-versus-host reactive CD8(+) T cells but not their synthesis of IFN-gamma. In contrast, the GVL requirement for CD4(+) T-cell help was bypassed almost completely when DLI was administered to freshly irradiated recipients, indicating that the host environment is a major factor influencing the cellular mechanisms of GVL.

Synergistic effects of hyperoxic gas breathing and reduced oxygen consumption on tumor oxygenation: a theoretical model.

PURPOSE: To simulate effects of reduced oxygen consumption combined with hyperoxic gas breathing on tumor oxygenation, and to test for synergistic effects. METHODS AND MATERIALS: Diffusive oxygen transport was simulated for a small region of tumor containing a three-dimensional network of microvessels whose geometry was derived from in vivo observations. Changes in tissue partial pressure of oxygen (PO(2)) and hypoxic fraction (PO(2) < 5 mm Hg) resulting from a 30% reduction in oxygen consumption rate or breathing 100% oxygen were estimated. The synergistic effect was defined as the change in PO(2) with the two treatments combined, minus the sum of the changes with the separate treatments. RESULTS: Predicted hypoxic fractions were 37% in the control state, 11% with reduced consumption, 23% with oxygen breathing alone, and 0% with the combined treatment. The synergistic effect was about 4 mm Hg at tissue points with very low initial PO(2) levels and decreased as initial PO(2) increased. CONCLUSIONS: Reduction of oxygen consumption via the Crabtree effect, by administration of glucose, has been proposed as a means to improve tumor oxygenation during radiation treatment. The results support previous experimental studies showing that this approach is more effective when combined with breathing of hyperoxic gases.

Green's function methods for analysis of oxygen delivery to tissue by microvascular networks.

Delivery of oxygen to tissue is an essential function of the circulatory system. The distance that oxygen can diffuse into oxygen-consuming tissue is small, and so tissue oxygenation is critically dependent on the spatial arrangement of microvessels in tissue. Theoretical methods have been developed to simulate the spatial distribution of oxygen levels in tissue surrounding a network of microvessels. Here, numerical methods based on a Green's function approach are presented, for realistic three-dimensional network geometries derived from observations of skeletal muscle, brain, and tumor tissues. Relative to finite-difference methods, the Green's function approach reduces the number of unknowns in the numerical formulation and allows rapid computations even for complex vascular geometries. Generally, the boundary conditions on the exterior of the computational domain are not known. Imposition of a no-flux boundary condition can lead to exaggerated estimates of the extent of hypoxia in the tissue region. A new version of the method is described that avoids this problem and can be applied to arbitrarily shaped tissue domains.

A theoretical model for the effects of reduced hemoglobin-oxygen affinity on tumor oxygenation.

PURPOSE: To develop a theoretical model for oxygen delivery to tumors, and to use the model to simulate the effects of changing the affinity of hemoglobin for oxygen on tumor oxygenation. METHODS AND MATERIALS: Hemoglobin affinity is expressed in terms of P(50), the partial pressure of oxygen (Po(2)) at half saturation. Effects of changing P(50) on arterial Po(2) are predicted using an effective vessel approach to describe diffusive oxygen transport in the lungs, assuming fixed systemic oxygen demand and fixed blood flow rate. The decline in oxygen content of blood as it flows through normal tissue before entering the tumor region is assumed fixed. The hypoxic fraction of the tumor region is predicted using a three-dimensional simulation of diffusion from a network of vessels whose geometry is derived from observations of tumor microvasculature in the rat. RESULTS: In air-breathing rats, predicted hypoxic fraction decreases with moderate increases in P(50), but increases with further increases of P(50), in agreement with previous experimental results. In rats breathing hyperoxic gases, and in humans breathing either normoxic or hyperoxic gases, increased P(50) is predicted to improve tumor oxygenation. CONCLUSIONS: The results support the administration of synthetic agents to increase P(50) during radiation treatment of tumors.