Warren J. Gasper

Has recognition of the relationship between mortality rates and hospital volume for major cancer surgery in California made a difference?: A follow-up analysis of another decade.

Background:Previous reports showed that in California during the early 1990s, operative mortality rates for esophageal, pancreatic, and hepatic cancers were inversely related to hospital volume. It is unknown whether this information has affected referral patterns or operative mortality rates. Objectives:Data were analyzed for the 10 years that followed the period covered in the initial studies to determine if: (a) the operative mortality rates had decreased; and (b) a greater proportion of patients with esophageal, pancreatic, and hepatic cancers were treated at high-volume centers. Methods:Hospital discharge data were obtained for 8901 patients who had resections for cancer of the esophagus, 2404 patients; pancreas, 5294 patients; and liver, 1203 patients in California between 1995 and 2004. Logistic regression models were used to calculate adjusted mortality rates at high- and low-volume centers by year. The data were compared with the published results for California during the years 1990–1994. Results:Operative mortality rates decreased for esophageal, pancreatic, and hepatic resections during the more recent 10 years. Concomitantly, the proportion of patients treated at high-volume centers increased, as did the number of high-volume centers. There was a substantial increase in the proportion of esophagectomies performed in high-volume hospitals, while the overall number of esophagectomies dropped by 22%. For the other 2 operations, total volume and the volume in high-volume hospitals increased greatly, and the volume in low-volume hospitals was about the same during the 3 periods. The mortality rates decreased at all levels of the volume range. Finally, the performance from one period to the next in individual hospitals was mostly similar, but an occasional outlier was also noted. Conclusions:More resections for esophageal, pancreatic, and hepatic cancer were performed at high volume centers, but mortality rates decreased for all hospital categories. The data suggest that modern hospitals act as complex adaptive systems, whose outputs are determined from the interactions between internal agents and are resistant to analysis by isolating and studying the individual contributions. It is tempting to attribute the desirable changes in these data (eg, more operations being done in high volume centers and better mortality rates at all levels) as consequences of pressures over the past few decades on hospitals to assume greater responsibility for their quality of care and to become more integrated internally. Thus, many factors appear to influence the volume-outcome relationships, and the identity and individual contributions of these influences may be immune to reductionist analysis. There is substantial evidence that high volume should be part of high quality for these complex operations. Nevertheless, measuring outcomes directly, rather than concentrating on their correlates, may be a more reliable index of hospital performance.

Predicting Strangulated Small Bowel Obstruction: An Old Problem Revisited

BackgroundDiagnosing intestinal strangulation complicating a small bowel obstruction (SBO) remains a considerable challenge. Despite decades of experience and numerous studies, no clinical indicators have been identified that reliably predict this life-threatening condition. Our goal was to determine which clinical indicators in patients with SBO can be used to independently predict the presence of strangulated intestine.MethodsMedical records were reviewed for 192 adult patients operated on for acute SBO over an 11-year period (1996–2006). Seventy-two preoperative clinical, laboratory, and radiologic findings at admission were examined. Data from patients with strangulated intestine were compared to data from patients without bowel compromise. Likelihood ratios were generated for each significant parameter in a multivariate logistic regression analysis.ResultsForty-four patients had bowel strangulation requiring bowel resection, and 148 had no strangulation. The most significant independent predictor of bowel strangulation was the computed tomography (CT) finding of reduced wall enhancement, with a sensitivity and specificity of 56% and 94% [likelihood ratio (LR) 9.3]. Elevated white blood cell (WBC) count and guarding were moderately predictive (LR 1.7 and 2.8).ConclusionRegression analysis of multiple preoperative criteria demonstrates that reduced wall enhancement on CT, peritoneal signs, and elevated WBC are the only variables independently predictive of bowel strangulation in patients with SBO.

Vein graft failure

After the creation of an autogenous lower extremity bypass graft, the vein must undergo a series of dynamic structural changes to stabilize the arterial hemodynamic forces. These changes, which are commonly referred to as remodeling, include an inflammatory response, the development of a neointima, matrix turnover, and cellular proliferation and apoptosis. The sum total of these processes results in dramatic alterations in the physical and biomechanical attributes of the arterialized vein. The most clinically obvious and easily measured of these is lumen remodeling of the graft. However, although somewhat less precise, wall thickness, matrix composition, and endothelial changes can be measured in vivo within the healing vein graft. Recent translational work has demonstrated the clinical relevance of remodeling as it relates to vein graft patency and the systemic factors influencing it. By correlating histologic and molecular changes in the vein, insights into potential therapeutic strategies to prevent bypass failure and areas for future investigation are explored.

Antireflux surgery for patients with end-stage lung disease before and after lung transplantation

BackgroundGastroesophageal reflux disease (GERD) is prevalent among patients with end-stage lung disease (ESLD). This disease can lead to microaspiration and may be a risk factor for lung damage before and after transplantation. A fundoplication is the best way to stop reflux, but little is known about the safety of elective antireflux surgery for patients with ESLD. This study aimed to report the safety of laparoscopic fundoplication for patients with ESLD and GERD before or after lung transplantation.MethodsBetween January 1997 and January 2007, 305 patients were listed for lung transplantation, and 189 patients underwent the procedure. In 2003, routine esophageal studies were added to the pretransplantation evaluation. After the authors’ initial experience, gastric emptying studies were added as well.ResultsA total of 35 patients with GERD or delayed gastric emptying were referred for surgical intervention. A laparoscopic fundoplication was performed for 32 patients (27 total and 5 partial). For three patients, a pyloroplasty also was performed. Two patients had a pyloroplasty without fundoplication. Of the 35 operations, 15 were performed before and 20 after transplantation. Gastric emptying of solids or liquids was delayed in 12 (92%) of 13 posttransplantation studies and 3 (60%) of 5 pretransplantation studies. All operations were completed laparoscopically, and 33 patients recovered uneventfully (94%). The median hospital length of stay was 2 days (range, 1–34 days) for the patients admitted to undergo elective operations. Hospitalization was not prolonged for the three patients who had fundoplications immediately after transplantation.ConclusionsThe results of this study show that laparoscopic antireflux surgery can be performed safely by an experienced multidisciplinary team for selected patients with ESLD before or after lung transplantation, and that gastric emptying is frequently abnormal and should be objectively measured in ESLD patients.

USPIO-enhanced MR Angiography of Arteriovenous Fistulas in Patients with Renal Failure

PURPOSE To determine the feasibility of using ferumoxytol-enhanced magnetic resonance (MR) angiography to depict the vasculature of hemodialysis fistulas and improve image quality compared with nonenhanced time-of-flight (TOF) MR angiography. MATERIALS AND METHODS The study was institutional review board approved and was in compliance with HIPAA regulations. All participants provided written informed consent. TOF and first-pass ferumoxytol-enhanced MR angiography were performed in 10 patients with upper extremity autogenous fistulas. Ferumoxytol was administered as a bolus solution containing 430 μmol of elemental iron. A qualitative comparison was performed on maximum intensity projection images. Lumen depiction was evaluated by using a five-point scale. The uniformity of intraluminal signal intensity was measured as the ratio between the mean signal intensity of the entirety of the imaged fistula and its standard deviation. The contrast-to-noise ratio (CNR) between intraluminal signal and adjacent tissue was evaluated as a function of image acquisition time. Lumen depiction scores, luminal signal heterogeneity, and CNR efficiency were compared between TOF and ferumoxytol-enhanced MR angiography by using a Wilcoxon-Mann-Whitney test. RESULTS Flow artifacts were greatly reduced by the use of ferumoxytol-enhanced MR angiography. Ferumoxytol-enhanced MR angiography had significantly better performance than TOF MR angiography as measured with the following: lumen depiction scores in all segments (mean, 4.7±0.1 [standard error of the mean]; vs 3.0±0.3 for arterial inflow, 4.1±0.3 vs 1.9±0.3 for arterial outflow, 3.7±0.3 vs 1.8±0.2 for anastomosis, and 4.5±0.2 vs 2.1±0.2 for venous outflow; P<.001), intraluminal signal homogeneity (0.3±0.02 vs 0.4±0.06, P=.005), and CNR efficiency in the venous outflow (5.1±0.6 vs 2.5±0.4, P=.01). CONCLUSION This study demonstrates the feasibility of using ferumoxytol-enhanced MR angiography in imaging hemodialysis fistulas with consistently superior image quality compared with nonenhanced TOF MR angiography.

Gastroesophageal Reflux Disease and Connective Tissue Disorders: Pathophysiology and Implications for Treatment

IntroductionIt has been postulated that in patients with connective tissue disorders (CTD) and gastroesophageal reflux disease (GERD), esophageal function is generally deteriorated, often with complete absence of peristalsis. This belief has led to the common recommendation of avoiding antireflux surgery for fear of creating or worsening dysphagia.MethodsWe hypothesized that in most patients with CTD and GERD: (a) esophageal function is often preserved; (b) peristalsis is more frequently absent when end-stage lung disease (ESLD) is also present; (c) a tailored surgical approach (partial or total fundoplication) based on the findings of esophageal manometry allows control of reflux symptoms without a high incidence of postoperative dysphagia. Forty-eight patients with CTD were evaluated by esophageal manometry and 24-hour pH monitoring (EFT). Twenty patients (group A) had EFT because of foregut symptoms, and 28 patients with ESLD (group B) had EFT as part of the lung transplant evaluation. Two hundred and eighty-six consecutive patients with GERD by pH monitoring served as a control group (group C). A laparoscopic fundoplication was performed in two group A patients (total), eight group B patients (three patients total, five patients partial) and in all group C patients (total).ResultsEsophageal peristalsis was preserved in all patients with CTD and GERD. In contrast, peristalsis was absent in about half of patients when ESLD was also present. A tailored surgical approach resulted in control of reflux symptoms in all patients. One patient only developed postoperative dysphagia, which resolved with two Savary dilatations.ConclusionThese data show that esophageal motor function is preserved in most patients with CTD, so that they should be offered antireflux surgery early in the course of their disease to prevent esophageal and respiratory complications. In patients with ESLD in whom peristalsis is absent, a partial rather than a total fundoplication should be performed, as it allows control of reflux symptoms while avoiding postoperative dysphagia.

Lung transplantation in patients with connective tissue disorders and esophageal dysmotility.

Lung and esophageal dysfunction are common in patients with connective tissue disease (CTD). Recent reports have suggested a link between pathologic gastroesophageal reflux and bronchiolitis obliterans syndrome (BOS) after lung transplant. Because patients with CTD have a high incidence of esophageal dysmotility and reflux, this group may be at increased risk of allograft dysfunction after lung transplantation. Little is known about antireflux surgery in these patients. Our aims were to describe: (i) the esophageal motility and reflux profile of patients with CTD referred for lung transplantation; and (ii) the safety and outcomes of laparoscopic fundoplication in this group. A retrospective review of 26 patients with CTD referred for lung transplantation between July 2003 and June 2007 at a single center. Esophageal studies included manometry and ambulatory 24-h pH monitoring. Twenty-three patients had esophageal manometry and ambulatory 24-h pH monitoring. Nineteen patients (83%) had pathologic distal reflux and 7 (30%) also had pathologic proximal reflux. Eighteen patients (78%) had impaired or absent peristalsis. Eleven of 26 patients underwent lung transplantation. Ten patients are alive at a median follow-up of 26 months (range 3-45) and one has bronchiolitis obliterans syndrome-1. Six patients had a laparoscopic fundoplication, 1 before transplantation and 5 after. All fundoplication patients are alive at median follow-up of 25 months (range 19-45). In conclusion, esophageal dysmotility and reflux are common in CTD patients referred for lung transplant. For this group, laparoscopic fundoplication is safe in experienced hands.

Association of tetraspanin CD9 with transmembrane TGFα confers alterations in cell-surface presentation of TGFα and cytoskeletal organization

Ligand presentation is a major determinant of receptor activation. The epidermal growth factor receptor (EGFR), a tyrosine kinase receptor, is activated by growth factors of the transforming growth factor α (TGFα) family. The tetraspanin CD9 interacts with transmembrane TGFα and decreases its ectodomain shedding to release soluble TGFα. Here we report that CD9 has a role in the maturation of transmembrane TGFα and its stabilization at the cell surface, and in the cell-surface distribution in polarized epithelial cells. Furthermore, coexpression of CD9 and TGFα confers changes in cytoskeletal organization with a decrease in actin stress fibers and focal adhesions, and changes in RhoA and Rac1 GTPase activity. These alterations are reversed by blocking EGFR signaling. Finally, we demonstrate changes in cell adhesion and migration resulting from coexpression of TGFα with CD9. These results provide insight into the role of CD9 in the presentation of TGFα in epithelial and carcinoma cells, whose physiology is driven by ligand-induced EGFR activation.

Associations of endothelial dysfunction and arterial stiffness with intradialytic hypotension and hypertension

Intradialytic hypotension and hypertension are both independently associated with mortality among persons with end‐stage renal disease on hemodialysis. Endothelial dysfunction and arterial stiffness are two possible mechanisms underlying these phenomena, but their association with hemodynamic instability during dialysis has not been evaluated. Thirty patients were recruited from chronic dialysis units at San Francisco General Hospital and San Francisco Veterans Affairs Medical Center. Endothelial dysfunction was assessed with flow‐mediated dilation of the brachial artery after upper arm occlusion. Arterial stiffness was assessed using carotid‐femoral pulse wave velocity measured by tonometry. Intradialytic hypotension and hypertension were defined as the average decrease in systolic blood pressure (SBP) over 1 week, as well as the frequency over 1 month of hypotension or hypertension. Every 5% decrease in flow‐mediated dilation was associated with a 7.5 mmHg decrease in SBP after adjustment for phosphorus, body mass index, atherosclerosis, and ultrafiltration (P=0.02). Every 5 m/s increase in pulse wave velocity was associated with an 8 mmHg increase in SBP after adjustment for predialysis SBP and ultrafiltration (P=0.03). Over 1 month, every 5% lower flow‐mediated dilation was associated with a 10% higher frequency of hypotension (P=0.09), and every 5 m/s increase in pulse wave velocity was associated with an 15% higher frequency of hypertension (P=0.02). In a cross‐sectional analysis of 30 dialysis patients, endothelial dysfunction and arterial stiffness were independently associated with intradialytic hypotension and intradialytic hypertension, respectively. Elucidating these potential mechanisms of hemodynamic instability during dialysis may facilitate development of treatment strategies specific to this pathophysiology.

Walking Disability in Patients with Peripheral Artery Disease is Associated with Arterial Endothelial Function

OBJECTIVE Patients with peripheral artery disease (PAD) have varying degrees of walking disability that do not completely correlate with ankle-brachial index (ABI) or angiographic anatomy. We hypothesized that endothelial function (EF) is an independent predictor of symptom severity in PAD patients. METHODS This was a cross-sectional study of 100 PAD patients presenting to a vascular surgery clinic. All patients received ABI testing and brachial artery flow-mediated, endothelium-dependent vasodilation (FMD) to assess arterial EF. Symptom severity and walking disability reported by Rutherford category was based on the patients self-report during the clinic visit and recorded by the investigator-vascular surgeons. Demographic, biochemical, and physiologic parameters were entered into regression equations to determine association with symptom severity. RESULTS Patients were a mean age of 66 ± 8 years, and 43% had diabetes. Mean FMD was 7.4%, indicating impaired EF. EF progressively declined as Rutherford category increased (P = .01). Brachial artery FMD, ABI, systolic blood pressure, C-reactive protein, low-density lipoprotein, high-density lipoprotein, β-blocker use, and a history of diabetes or coronary artery disease were all associated with Rutherford category (all P < .05). Multivariable regression showed EF (P < .02) and ABI (P < .0001) were independently associated with walking disability. When the cohort was restricted to claudicant patients (n = 73), EF remained associated with walking disability after adjustment for other covariates (P = .0001). CONCLUSIONS Symptom severity in PAD is multifactorial, reflecting impaired hemodynamics and vascular dysfunction. This is the first report demonstrating that walking disability in PAD is associated with arterial EF. The mechanistic link underlying these observations remains to be defined.