Melissa E. Hogg

HIV and anal cancer outcomes: A single institution's experience

PURPOSE: The purpose of this study is to identify the effect of HIV status on outcome of treatment for squamous-cell carcinoma of the anal canal. METHODS: A retrospective review was performed on all patients with squamous-cell carcinoma of the anal canal treated at a single academic institution between January 1996 and December 2006. RESULTS: Our search identified 87 (21 HIV-positive) patients who had invasive squamous-cell cancer. The median follow-up was 38 months. Eighty-five percent of HIV-negative patients and 81 percent of HIV-positive were identified as complete responders at 6 weeks after completion of combined modality therapy. Eight percent of HIV-negative and 29 percent of HIV-positive patients developed recurrent disease after 6 months (P = 0.0009). Overall survival for HIV-negative and HIV-positive patients was 71 percent and 73 percent, respectively. CONCLUSIONS: HIV-positive patients respond equally to combined modality therapy but have recurrences more frequently than patients who are HIV negative. Overall survival in these two groups is equivalent.

Long-term sac behavior after endovascular abdominal aortic aneurysm repair with the Excluder low-permeability endoprosthesis

PURPOSE Sac regression is a surrogate marker for clinical success in endovascular aneurysm repair (EVAR) and has been shown to be device-specific. The low porosity Excluder endograft (Excluder low-permeability endoprosthesis [ELPE]; W. L. Gore & Associates Inc, Flagstaff, Ariz) introduced in 2004 was reported in early follow-up to be associated with sac regression rates similar to other endografts, unlike the original Excluder which suffered from sac growth secondary to fluid accumulation in the sac. The purpose of this study was to determine whether this behavior is durable in mid-term to long-term follow-up. METHODS Between July 2004 and December 2007, 301 patients underwent EVAR of an abdominal aortic aneurysm (AAA) with the ELPE at two institutions. Baseline sac size was measured by computed tomography (CT) scan at 1 month after repair. Follow-up beyond 1 year was either with a CT or ultrasound scan. Changes in sac size ≥5 mm from baseline were determined to be significant. Endoleak history was assessed with respect to sac behavior using χ(2) and logistic regression analysis. RESULTS Two hundred sixteen patients (mean age 73.6 years and 76% men) had at least 1-year follow-up imaging available for analysis. Mean follow-up was 2.6 years (range, 1-5 years). The average minor-axis diameter was 52 mm at baseline. The proportion of patients with sac regression was similar during the study period: 58%, 66%, 60%, 59%, and 63% at 1 to 5 years, respectively. The proportion of patients with sac growth increased over time to 14.8% at 4-year follow-up. The probability of freedom from sac growth at 4 years was 82.4%. Eighty patients (37.7%) had an endoleak detected at some time during follow-up with 29.6% (16 of 54) residual endoleak rate at 4 years; 13 of the residual 16 endoleaks were type II. All patients with sac growth had endoleaks at some time during the study compared with only 18% of patients with sac regression (P < .0001). CONCLUSION A sustained sac regression after AAA exclusion with ELPE is noted up to 5-year follow-up. Sac enlargement was observed only in the setting of a current or previous endoleak, with no cases of suspected hygroma formation noted.

Poly(diol‐co‐citrate)s as Novel Elastomeric Perivascular Wraps for the Reduction of Neointimal Hyperplasia

The synthesis of poly(diol-co-citrate) elastomers that are biocompatible with vascular cells and can modulate the kinetics of the NO release based on the diol of selection is reported. NO-mediated cytostatic or cytotoxic effects can be controlled depending on the NO dose and the exposure time. When implanted in vivo in a rat carotid artery injury model, these materials demonstrate a significant reduction of neointimal hyperplasia. This is the first report of a NO-releasing polymer fabricated in the form of an elastomeric perivascular wrap for the treatment of neointimal hyperplasia. These elastomers also show promise for other cardiovascular pathologies where NO-based therapies could be beneficial.

Effect of Nitric Oxide on Neointimal Hyperplasia based on Sex and Hormone Status

Nitric oxide (NO)-based therapies decrease neointimal hyperplasia; however, studies have been performed only in male animal models. Thus, we sought to evaluate the effect of NO on vascular smooth muscle cells (VSMC) in vitro and neointimal hyperplasia in vivo based on sex and hormone status. In hormone-replete medium, male VSMC proliferated at greater rates than female VSMC. In hormone-depleted medium, female VSMC proliferated at greater rates than male VSMC. However, in both hormone environments, NO inhibited proliferation and migration to a greater extent in male compared to female VSMC. These findings correlated with greater G₀/G₁ cell cycle arrest and changes in cell cycle protein expression in male compared to female VSMC after exposure to NO. Next, the rat carotid artery injury model was used to assess the effect of NO on neointimal hyperplasia in vivo. Consistent with the in vitro data, NO was significantly more effective at inhibiting neointimal hyperplasia in hormonally intact males compared to females using weight-based dosing. An increased weight-based dose of NO in females was able to achieve efficacy equal to that in males. Surprisingly, NO was less effective at inhibiting neointimal hyperplasia in castrated animals of both sexes. In conclusion, these data suggest that NO inhibits neointimal hyperplasia more effectively in males compared to females and in hormonally intact compared to castrated rats, indicating that the effects of NO in the vasculature may be sex- and hormone-dependent.

Insulin enhances the effect of nitric oxide at inhibiting neointimal hyperplasia in a rat model of type 1 diabetes

Diabetes confers greater restenosis from neointimal hyperplasia following vascular interventions. While localized administration of nitric oxide (NO) is known to inhibit neointimal hyperplasia, the effect of NO in type 1 diabetes is unknown. Thus the aim of this study was to determine the efficacy of NO following arterial injury, with and without exogenous insulin administration. Vascular smooth muscle cells (VSMC) from lean Zucker (LZ) rats were exposed to the NO donor, DETA/NO, following treatment with different glucose and/or insulin concentrations. DETA/NO inhibited VSMC proliferation in a concentration-dependent manner to a greater extent in VSMC exposed to normal-glucose vs. high-glucose environments, and even more effectively in normal-glucose/high-insulin and high-glucose/high-insulin environments. G(0)/G(1) cell cycle arrest and cell death were not responsible for the enhanced efficacy of NO in these environments. Next, type 1 diabetes was induced in LZ rats with streptozotocin. The rat carotid artery injury model was performed. Type 1 diabetic rats experienced no significant reduction in neointimal hyperplasia following arterial injury and treatment with the NO donor PROLI/NO. However, daily administration of insulin to type 1 diabetic rats restored the efficacy of NO at inhibiting neointimal hyperplasia (60% reduction, P < 0.05). In conclusion, these data demonstrate that NO is ineffective at inhibiting neointimal hyperplasia in an uncontrolled rat model of type 1 diabetes; however, insulin administration restores the efficacy of NO at inhibiting neointimal hyperplasia. Thus insulin may play a role in regulating the downstream beneficial effects of NO in the vasculature.

Percutaneous thoracic and abdominal aortic aneurysm repair: techniques and outcomes.

Endovascular repair of infrarenal abdominal aortic aneurysms (EVAR) has become a widely accepted treatment modality. The conventional approach of an EVAR involves bilateral groin incisions to expose the femoral arteries followed by introducer sheath placement, which is typically performed with the use of general or epidural anesthesia. As technology trends toward less invasive methods and sheath sizes become smaller, the use of a total percutaneous approach to endovascular repair of aortic pathology is becoming more common. In this review, we present a brief history of percutaneous closure devices for common femoral artery access, factors important in patient selection, the technique of performing a percutaneous EVAR procedure, early and late complications, and overall outcomes of percutaneous approaches for the endovascular treatment of aortic pathology.

The Role of Estrogen Receptor α and β in Regulating Vascular Smooth Muscle Cell Proliferation is Based on Sex

BACKGROUND We previously demonstrated that vascular smooth muscle cells (VSMC) proliferation and development of neointimal hyperplasia as well as the ability of nitric oxide (NO) to inhibit these processes is dependent on sex and hormone status. The aim of this study was to evaluate the role of estrogen receptor (ER) in mediating proliferation in male and female VSMC. MATERIALS AND METHODS Proliferation was assessed in primary rat aortic male and female VSMC using (3)H-thymidine incorporation in the presence or absence of ER alpha (α) inhibitor methyl-piperidino-pyrazole, the ER beta (β) inhibitor (R,R)-5,11-Diethyl-5,6,11,12-tetrahydro-2,8-chrysenediol, the combined ERαβ inhibitor ICI 182,780, and/or the NO donor DETA/NO. Proliferation was also assessed in primary aortic mouse VSMC harvested from wildtype (WT), ERα knockout (ERα KO), and ERβ knockout (ERβ KO) mice in the presence or absence of DETA/NO and the ERα, ERβ, and ERαβ inhibitors. Protein levels were assessed using Western blot analysis. RESULTS Protein expression of ERα and ERβ was present and equal in male and female VSMC, and did not change after exposure to NO. Inhibition of either ERα or ERβ had no effect on VSMC proliferation in the presence or absence of NO in either sex. However, inhibition of ERαβ in rat VSMC mitigated NO-mediated inhibition in female but not male VSMC (P < 0.05). Evaluation of proliferation in the knockout mice revealed distinct patterns. Male ERαKO and ERβKO VSMC proliferated faster than male WT VSMC (P < 0.05). Female ERβKO proliferated faster than female WT VSMC (P < 0.05), but female ERαKO VSMC proliferated slower than female WT VSMC (P < 0.05). Last, we evaluated the effect of combined inhibition of ERα and ERβ in these knockout strains. Combined ERαβ inhibition abrogated NO-mediated inhibition of VSMC proliferation in female WT and knockout VSMC (P < 0.05), but not in male VSMC. CONCLUSIONS These data clearly demonstrate a role for the ER in mediating VSMC proliferation in both sexes. However, these data suggest that the antiproliferative effects of NO may be regulated by the ER in females but not males.

Adventitial contributions of the extracellular signal–regulated kinase and Akt pathways to neointimal hyperplasia

BACKGROUND We recently reported that the efficacy of nitric oxide (NO) appears to be based on both sex and hormone status. The mechanism responsible for this differential efficacy is unknown. The aim of this study was to characterize the effect of sex, hormones, and NO on the extracellular signal-regulated kinase (ERK) and Akt signaling pathways after arterial injury. METHODS Male and female Sprague-Dawley rats underwent castration or sham surgery. Two weeks later, they underwent carotid artery balloon injury. Treatment groups included the following: control, injury, and injury + 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO) (n = 5 per group). Arteries were harvested 2 weeks after injury and assessed for phospho-ERK (pERK) and phospho-Akt (pAkt) expression. RESULTS After injury, more pERK and pAkt activity was seen in the adventitia than media in both sexes, regardless of hormone status (P < .05). In hormonally intact males, NO further increased pERK (44%) and pAkt (120%) after injury (P < .001). Castration attenuated the effects of NO. In hormonally intact females, NO caused the opposite pattern with pERK activity but did not affect pAkt activity. CONCLUSIONS After arterial injury, ERK and Akt activity is significantly greater in the adventitia than the media, and depends on sex, hormone status, and NO. Understanding adventitial regulation of proliferative signaling pathways will allow the development of targeted therapies for neointimal hyperplasia.

Minimally Invasive Pancreas Surgery

Abstract The introduction of laparoscopy in the 1980s has revolutionized the field of complex abdominal surgery. Traditional operations for almost all pancreatic resections and reconstructions have been described and replicated through a laparoscopic approach. Minimally invasive pancreatic surgeries are now well integrated into routine pancreatic resections and reconstructions at high-volume centers, with equivalent rates of mortality compared with open procedures. With the advent of robotic assistance, patients benefit from less intraoperative blood loss, expedited functional recovery, and shorter hospital stays. Meanwhile, surgeons benefit from binocular three-dimensional vision, scaling, stabilization of tremor, reduced operator fatigue, and improved ergonomics from the console-surgeon interface. This chapter will focus on the robotic approach, summarizing the data on the safety, efficacy, and technique of robotic approaches to minimally invasive pancreas surgery for both benign and malignant indications, showcasing the diversity of the platform for complex pancreatic operations.

Robotic vascular resections during Whipple procedure

Indications for resection of pancreatic cancers have evolved to include selected patients with involvement of peri-pancreatic vascular structures. Open Whipple procedures have been the standard approach for patients requiring reconstruction of the portal vein (PV) or superior mesenteric vein (SMV). Recently, high-volume centers are performing minimally invasive Whipple procedures with portovenous resections. Our institution has performed seventy robotic Whipple procedures with concomitant vascular resections. This report outlines our technique.