Bariatric surgery improves cardiac function in morbidly obese patients with severe cardiomyopathy.

BACKGROUND: Longstanding morbid obesity can be associated with severe cardiomyopathy. However, the safety and efficacy of bariatric surgery in patients with severe cardiomyopathy has not been studied, and the effect of surgical weight loss on postoperative cardiac function is also unknown. In addition, morbidly obese patients have significantly increased mortality associated with cardiac transplantation, often precluding them from becoming recipients. METHODS: A retrospective study of patients with a left ventricular ejection fraction < or =35% who underwent bariatric surgery (1998-2005) was performed. Short-term morbidity/mortality, length of stay, excess weight loss, pre- and postoperative left ventricular ejection fraction, and New York Heart Association (NYHA) functional class were assessed. RESULTS: A total of 14 patients (10 men and 4 women) with a mean preoperative body mass index of 50.8 +/- 2.04 kg/m(2) underwent bariatric surgery (10 underwent laparoscopic Roux-en-Y gastric bypass, 1 open Roux-en-Y gastric bypass, 2 sleeve gastrectomy, and 1 laparoscopic gastric banding). The complications were pulmonary edema in 1, hypotension in 1, and transient renal insufficiency in 2. The median length of stay was 3.0 days (range 2-9). The mean excess weight loss at 6 months was 50.4%, with a decrease in the mean body mass index from 50.8 +/- 2.04 kg/m(2) to 36.8 +/- 1.72 kg/m(2). The mean left ventricular ejection fraction at 6 months had significantly improved from 23% +/- 2% to 32% +/- 4% (P = .04), correlating with improved functional capacity, as measured by the NYHA classification. Preoperatively, 2 patients (14%) had an NYHA classification of IV, 6 (43%) a classification of III, and 6 (43%) a classification of II. At 6 months postoperatively, no patient had an NYHA classification of IV, 2 (14%) had a classification of III, and 12 (86%) an NYHA classification of II. Two patients had undergone cardiac transplant evaluations preoperatively and underwent successful transplantation after weight loss. CONCLUSION: The results of our study have shown that bariatric surgery for patients with cardiomyopathy is feasible and effective. Surgically induced weight loss results in both subjective and objective improvement in cardiac function. In addition, surgical weight loss can provide a bridge to transplantation in patients who were prohibited secondary to their morbid obesity.

Treatment of refractory gastroesophageal reflux disease with radiofrequency energy (Stretta) in patients after Roux-en-Y gastric bypass.

BACKGROUND: Morbid obesity is associated with gastroesophageal reflux disease (GERD), which, in most cases, completely resolves after Roux-en-Y gastric bypass (RYGB). Patients with persistent or recurrent symptoms have limited surgical options. This study sought to evaluate the application of the Stretta procedure for patients with refractory GERD. METHODS: The medical records of all patients who underwent Stretta for refractory GERD after RYGB were reviewed. Demographic, preoperative, and postoperative reflux data were collected. Data are presented as mean +/- standard error of the mean. The t-test was used for comparison purposes. RESULTS: Of 369 patients, 7 received Stretta 27 +/- 6 months after RYGB. All were women with a mean age of 49 +/- 2 years. All the patients had experienced prebypass GERD symptoms for a duration of 45 +/- 8 months. The mean prebypass body mass index was 45 +/- 2 kg/m(2), and this was reduced to 29 +/- 2 kg/m(2) after laparoscopic RYGB (p < 0.001). Before Stretta, all patients underwent a 48-h Bravo pH study, which demonstrated reflux with a mean fraction time of 7% +/- 2% for pH lower than 4. After Stretta, five patients had complete resolution of their symptoms, with normalization of pH studies (mean fraction time of 3% +/- 0% for pH < 4). The follow-up period after Stretta was 20 +/- 2 months. One patient did not have adequate relief of symptoms after Stretta, and one patient was lost to follow-up evaluation. CONCLUSION: Stretta is a valid option in the treatment of persistent GERD for patients who have undergone gastric bypass. Further study is required to evaluate the long-term efficacy of this procedure.

Laparoscopic sleeve gastrectomy as an initial weight-loss procedure for high-risk patients with morbid obesity.

BACKGROUND: The surgical treatment of obesity in the high-risk, high-body-mass-index (BMI) (>60) patient remains a challenge. Major morbidity and mortality in these patients can approach 38% and 6%, respectively. In an effort to achieve more favorable outcomes, we have employed a two-stage approach to such high-risk patients. This study evaluates our initial outcomes with this technique. METHODS: In this study, patients underwent laparoscopic sleeve gastrectomy (LSG) as a first stage during the period January 2002-February 2004. After achieving significant weight loss and reduction in co-morbidities, these patients then proceeded with the second stage, laparoscopic Roux-en-Y gastric bypass (LRYGBP). RESULTS: During this time, 126 patients underwent LSG (53% female). The mean age was 49.5 +/- 0.9 years, and the mean BMI was 65.3 +/- 0.8 (range 45-91). Operative risk assessment determined that 42% were American Society of Anesthesiologists physical status score (ASA) III and 52% were ASA IV. The mean number of co-morbid conditions per patient was 9.3 +/- 0.3 with a median of 10 (range 3-17). There was one distant mortality and the incidence of major complications was 13%. Mean excess weight after LSG at 1 year was 46%. Thirty-six patients with a mean BMI of 49.1 +/- 1.3 (excess weight loss, EWL, 38%) had the second-stage LRYGBP. The mean number of co-morbidities in this group was 6.4 +/- 0.1 (reduced from 9). The ASA class of the majority of patients had been downstaged at the time of LRYGB. The mean time interval between the first and second stages was 12.6 +/- 0.8 months. The mean and median hospital stays were 3 +/- 1.7 and 2.5 (range 2-7) days, respectively. There were no deaths, and the incidence of major complications was 8%. CONCLUSION: The staging concept of LSG followed by LRYGBP is a safe and effective surgical approach for high-risk patients seeking bariatric surgery.

The impact of laparoscopic bariatric workshops on the practice patterns of surgeons.

BACKGROUND: This study was designed to evaluate the impact of a 2-day laparoscopic bariatric workshop on the practice patterns of participating surgeons. METHODS: From October 1998 to June 2002, 18 laparoscopic bariatric workshops were attended by 300 surgeons. Questionnaires were mailed to all participants. RESULTS: Responses were received from 124 surgeons (41%), among whom were 56 bariatric surgeons (open) (45%), 30 advanced laparoscopic surgeons (24%), and 38 surgeons who performed neither bariatric nor advanced laparoscopic surgery (31%). The questionnaire responses showed that 46 surgeons (37%) currently are performing laparoscopic gastric bypass (LGB), 38 (31%) are performing open gastric bypass, and 39 (32%) are not performing bariatric surgery. Since completion of the course, 46 surgeons have performed 8,893 LGBs (mean, 193 cases/surgeon). Overall, 87 of the surgeons (70%) thought that a limited preceptorship was necessary before performance of LGB, yet only 25% underwent this additional training. According to a poll, the respondents thought that, on the average, 50 cases (range, 10-150 cases) are needed for a claim of proficiency. CONCLUSION: Laparoscopic bariatric workshops are effective educational tools for surgeons wishing to adopt bariatric surgery. Open bariatric surgeons have the highest rates of adopting laparoscopic techniques and tend to participate in more adjunctive training before performing LGB. There was consensus that the learning curve is steep, and that additional training often is necessary. The authors propose a mechanism for post-residency skill acquisition for advanced laparoscopic surgery.

What happens to the rectus abdominus fascia after laparoscopic ventral hernia repair?

BACKGROUND: One criticism of laparoscopic ventral hernia repair (LVH) is that the rectus muscles are not re-approximated to the midline, and the effect of LVH repair on the fascial edges is unclear. Progressive migration of the fascial edges toward the midline has been observed anecdotally, but objective evidence remains limited. The purpose of this study is to observe the effect of LVH repair on the rectus abdominus fascia. METHODS: Patients undergoing LVH repair with defects > 10 cm in horizontal diameter were identified prospectively and enrolled. All were repaired laparoscopically with intraperitoneal placement of mesh (DualMesh, W.L. Gore and Associates) using a standard approach. Radio-opaque clips were placed at the fascial edges intraoperatively to mark the defect, and plain abdominal films were taken postoperatively (Time 1) to establish the initial distance between clips (measured in cm). A subsequent follow-up film was taken (Time 2), and the difference in clip distance per patient was recorded. Results were analyzed using a chi-squared test. RESULTS: Twelve patients qualified for analysis and their results were compared. Mean fascial defect size was 15.1 cm (range 8.3-22.0). With respect to change in clip distance from Times 1 to 2, three events were observed: (1) Diminished (i.e. medialized), (2) Enlarged, or (3) No Change. Ten patients (83%) medialized, one patient enlarged, and one patient showed no change (chi2 (d.f. = 2) 9.17, p < 0.0023). CONCLUSIONS: Medialization of the rectus abdominus fascia occurs in the majority of patients undergoing LVH repair. Causes for this phenomenon are unclear: however eliminating intrabdominal pressure with intraperitoneal mesh placement likely plays a role.

Repair of ventral hernias in morbidly obese patients undergoing laparoscopic gastric bypass should not be deferred.

BACKGROUND: There is no consensus regarding the optimal treatment of ventral hernias in patients who present for weight loss surgery. METHODS: Medical records of consecutive morbidly obese patients who underwent laparoscopic Roux-en-Y (LRYGB) gastric bypass with a secondary diagnosis of ventral hernia were reviewed. Only patients who were beyond 6 months of follow-up were included. RESULTS: The study population was 85 patients. There were three groups of patients according to the method of repair: primary repair (59), small intestine submucosa (SIS) (12), and deferred treatment (14). Average follow-up was 26 months. There was a 22% recurrence in the primary repair group. There were no recurrences in the SIS group. Five of the patients in the deferred treatment group (37.5%) presented with small bowel obstruction due to incarceration. CONCLUSION: Biomaterial mesh (SIS) repair of ventral hernias concomitant with LRYGB resulted in the most favorable outcome albeit having short follow-up. Concomitant primary repair is associated with a high rate of recurrence. All incarcerated ventral hernias should be repaired concomitant with LRYGB, as deferment may result in small bowel obstruction.

Laparoscopic vs open resection for the treatment of diverticular disease.

INTRODUCTION: The aim of this study was to evaluate whether laparoscopic colon resection (LCR) offers any advantages over open colon resection (OCR) in the treatment of diverticular disease. METHODS: Between 1992 and 2002, 95 patients underwent LCR and 80 patients underwent OCR for the treatment of diverticular disease. Demographics, details of operative procedure, outcome, and pathology were compared. RESULTS: Patients in both groups were matched for age, sex, body mass index, history of previous abdominal operations, comorbidities, location of the disease, and presence of complications. LCR resulted in significantly less estimated blood loss and postoperative complications, shorter time to first bowel movement, and shorter length of stay than the OCR. There was no difference in operative time, intraoperative complications, mortality rates between groups. CONCLUSIONS: LCR is a safe and effective approach for the treatment of patients with diverticular disease. It results in less estimated blood loss, shorter time to first bowel movement, less postoperative complications, and shorter length of hospital stay.

Can current technology be integrated to facilitate laparoscopic living donor hepatectomy?

BACKGROUND: Living donor hepatectomy (LDH) is a technically demanding procedure that is an alternative for providing livers for transplantation. Unlike liver resections for other pathology, LDH requires preservation of the major vessels and biliary tree. This study was performed to determine if current technology can be integrated to perform laparoscopic LDH. METHODS: Six adult sheep underwent laparoscopic LDH of the left lateral segment under general anesthesia. Instruments utilized included standard dissecting instruments, ultrasound, ultrasonic dissectors, CUSA, the TissueLink Floating Ball, and endoscopic staplers. RESULTS: LDH-harvested liver grafts were 44% of whole liver weight. Estimated blood loss was 300 cc. Warm ischemia time was 5-7 min. Grafts were delivered through 18-cm abdominal wounds. Major vessels and biliary anatomy were positively identified in the grafts. CONCLUSIONS: Laparoscopic LDH can be performed with available technology. Theoretical advantages include reduced liver manipulation and smaller wound size.

KTP laser ablation of Barrett's esophagus after anti-reflux surgery results in long-term loss of intestinal metaplasia. Potassium-titanyl-phosphate.

BACKGROUND: Efforts to ablate Barrett's epithelium have met with mixed results. We report the long-term follow-up evaluation of the preliminary cohort of patients who underwent thermal ablation of Barrett's epithelium with the potassium-titanyl-phosphate (KTP) laser after anti-reflux surgery. METHODS: Nine patients with intestinal metaplasia (IM) of the esophagus underwent fundoplication (7 laparoscopic Nissen, 1 laparoscopic Toupet, 1 open Nissen) between May 1993 and October 1994. Three patients had an IM less than 3 cm long (33%). One year after the operation, all the patients were symptom free, had discontinued medications, and had a normal 24-h pH study. From June 1995 to February 1996, these patients underwent a median of two (range, 1-5) endoscopic procedures with directed mucosal ablation using the KTP laser. A comparative cohort of 21 patients (IM length, <3cm; 38%) treated during the same period with fundoplication alone served as a control. The patients were followed prospectively with annual or biennial endoscopy and biopsy. All the patients were contacted by mail, telephone, or clinic visit annually to determine symptomatic and quality-of-life outcome of antireflux surgery. RESULTS: The mean follow-up period was 6.8 years (range, 6-7.5 years). At this writing, the study patients are alive and well. Eight of the patients have experienced histologic loss of IM (89%) according to their last biopsy result. One patient has had regression of low-grade dysplasia to IM. The patients treated with fundoplication alone had a mean follow-up period of 5.6 years (range, 4.7-7.2 years). On the basis of the last biopsy result, 7 of 21 patients (33%) had no evidence of IM. CONCLUSIONS: A program of tailored antireflux surgery followed by thermal mucosal ablation causes a loss of IM in a majority of patients with Barrett's esophagus. This may represent a significant improvement in histologic outcome over that of treatment with fundoplication alone (p = 0.007 Fisher's exact test).

Long-term outcome of laparoscopic repair of paraesophageal hernia.

BACKGROUND: It has been reported that the laparoscopic repair of paraesophageal hernias is associated with higher complication and recurrence rates than the open methods of repair. METHODS: We identified 136 consecutive patients who underwent laparoscopic repair of a paraesophageal hernia between 1993 and 1999. Patient demographics and symptom scores for regurgitation, heartburn, chest pain, and dysphagia at presentation and at last follow-up were recorded (0 = none, 1 = mild, 2 = moderate, 3 = severe). The operative records were reviewed, and early and late complications were noted. Only patients with a follow-up of >1 were included in the analysis. RESULTS: The median age was 64 years, and there was a female preponderance (1.8:1). Most patients had some medical comorbidity; the American Society of Anesthesiologists (ASA) scores were <2 in eight patients and ?2 in 117 patients. Three laparoscopic operations were converted to open procedures. There were nine intraoperative complications, five early complications, and three related deaths (morbidity and mortality rates of 10.2% and 2.2%, respectively). Follow-up data were available for 83 patients (66%), and the mean follow-up time was 40 months (range, 12-82). The percentage of patients experiencing chest pain, dysphagia, heartburn, and regurgitation in the moderate to severe range dropped from a range of 34-47% to 5-7% (p <0.05). Three patients underwent repeat laparoscopic repair for symptomatic recurrence. CONCLUSION: The laparoscopic repair of paraesophageal hernias provides excellent long-term symptomatic relief in the majority of patients and has a low rate of symptomatic recurrence. The complication and death rates may be related in part to the higher incidence of comorbidities in this somewhat elderly patient population.

Oral administration of L-arginine reduces intimal hyperplasia in balloon-injured rat carotid arteries.

Endogenous nitric oxide (NO) is produced from L-arginine by NO synthase. We evaluated the effect of oral administration of L-arginine on intimal hyperplasia in balloon-injured rat carotid arteries. Thirty Sprague-Dawley rats underwent balloon denudation on the left common carotid artery. Fifteen rats were treated with L-arginine in drinking water (2.5 mg/mL) two days before injury and were continued for 2 weeks. Another 15 rats served as controls. All animals survived without complications or body weight loss. In the treated group, daily intake of L-arginine was 170 +/- 43 mg/day. Plasma arginine levels were 130 +/- 32 micromol/L prior to L-arginine intake, 165 +/- 42 micromol/L at the day of injury, and 162 +/- 26 micromol/L at sacrifice. Intimal hyperplasia developed in all balloon-injured arteries in both control and L-arginine-treated animals. However, L-arginine-treated animals showed a 65% reduction of the intima/media area ratio and a 26% reduction of the intimal cell proliferation compared with control animals. These data indicate that adequate amounts of L-arginine were ingested by the rats and that oral administration of L-arginine significantly reduced intimal hyperplasia of balloon-injured arteries without any detectable toxicity.

Boundary layer infusion of basic fibroblast growth factor accelerates intimal hyperplasia in endarterectomized canine artery.

We examined the effects of human recombinant basic fibroblast growth factor (bFGF) on the proliferation and migration of cultured dog smooth muscle cells (SMCs) and endothelial cells (ECs) and the effect of continuous local boundary layer infusion of bFGF on intimal hyperplasia in endarterectomized dog artery. In vitro proliferation and migration of dog SMCs or ECs were performed using direct counting and Boyden's chamber, respectively. At a dose of 10 ng/mL, bFGF significantly promoted both SMC and EC proliferation (7- and 4-fold, respectively) and migration (2.3- and 1.9-fold, respectively). Six dogs underwent bilateral carotid endarterectomies. A newly designed local infusion device with an osmotic pump continuously delivered bFGF to one artery or vehicle solution to the contralateral artery for 14 days. The intimal thickness and area in the bFGF-treated vessels were increased by 72 and 81%, respectively, compared with control arteries (P < 0.05). As assessed by the bromodeoxyuridine index, the proliferative activity was increased by 73% in bFGF-treated arteries (P = 0.03). Furthermore, cell proliferation at the distal anastomoses of local infusion device was significantly increased in the bFGF-infused grafts compared with distal anastomoses in the control grafts (13.24 +/- 1.24% versus 5.24 +/- 1.01%, P < 0.01). These data demonstrate that human recombinant bFGF has a potent effect on dog SMC and EC proliferation and migration, and that local infusion of exogenous bFGF significantly enhances the intimal hyperplasia formation and cell proliferation to vascular injury. We conclude that the bFGF pathway may contribute to the development of intimal hyperplastic lesions.

Time-course study of intimal hyperplasia in the endarterectomized canine artery.

In an effort to characterize intimal hyperplastic lesions, we have undertaken a time-course study in a canine endarterectomy model of intimal hyperplasia. Twenty dogs underwent surgical endarterectomies of the carotid arteries. A total of 23 of 27 (85%) injured arteries were patent, which consisted of 6, 8, 5, and 4 arteries found to be patent at 1, 2, 5, and 11 weeks, respectively. Measurable intimal thickening developed at 1 week (0.08 +/- 0.01 mm) and at 2 weeks (0.13 +/- 0.02 mm), maximized at 5 weeks (0.29 +/- 0.03 mm), and subsided at 11 weeks (0.21 +/- 0.01 mm) after injury. Endothelial cells covering intimal hyperplastic tissues were seen only at 11 weeks. The intimal cell proliferation rate reached a maximum of 24% at 1 week, decreased dramatically at 2 weeks, and remained at low levels but higher than baseline levels at 5 and 11 weeks. Extracellular matrix (ECM) content accounted for 29% of total intimal volume at 1 week after endarterectomy and increased to 37, 40, and 47% at 2, 5, and 11 weeks, respectively. These data demonstrate that maximum intimal cell proliferation occurs at 1 week and maximum intimal hyperplasia at 5 weeks after arterial injury. Intimal ECM content increased with time after injury throughout the duration of this study. The uniform and consistent intimal lesion that was established in this large animal model is clinically relevant and can be used to study cellular and molecular mechanisms of restenosis and to evaluate therapeutic interventions.

Recombinant mitotoxin basic fibroblast growth factor-saporin reduces venous anastomotic intimal hyperplasia in the arteriovenous graft.

BACKGROUND: The plant cytotoxin saporin (SAP) is a potent ribosome-inactivating protein. When conjugated to basic fibroblast growth factor (FGF2), it selectively kills proliferating cells that have upregulated FGF receptors. In this study, we evaluated the effect of the recombinant chimeric mitotoxin rFGF2-SAP on venous anastomotic intimal hyperplasia, a major cause of failure of arteriovenous (AV) grafts. METHODS AND RESULTS: Recently designed expanded polytet-rafluoroethylene-based local infusion devices were implanted bilaterally as femoral AV conduits in six dogs. The venous anastomoses were the sites of continuous delivery of rFGF2-SAP (2.7 micrograms.kg-1.d-1) to one side and vehicle (4.6 microL.kg-1.d-1) as control to the contralateral side for 14 days. All animals survived, and all grafts were patent. Liver enzyme levels and histological analyses of liver, kidneys, and brain were normal, indicating the absence of systemic toxicity. Morphometric measurements and measurements of cell proliferation by bromodeoxyuridine index analysis were performed at both arterial and venous anastomoses. There were no significant differences between the treated grafts and the control grafts in intimal hyperplasia and intimal cell proliferation at the arterial anastomoses. In contrast, rFGF2-SAP reduced intimal thickness by 32%, intimal area by 40%, and cell proliferation index by 33% at the treated venous anastomoses compared with the control venous anastomoses (P < .05). CONCLUSIONS: These data demonstrate that local infusion of rFGF2-SAP significantly reduces venous anastomotic intimal hyperplasia and cell proliferation without systemic toxicity. This study suggests a new strategy for reducing intimal hyperplasia by the selective killing of proliferating smooth muscle cells with a potent chimeric mitotoxin through a novel local infusion device.

Normothermic renal artery perfusion: a comparison of perfusates.

Hypothermia and preservative perfusates have been used to decrease ischemic renal injury. This study was performed to identify the preservative function of perfusates independent of the effects of hypothermia. Rats underwent 45 minutes of renal ischemia. Rectal and renal parenchyma temperatures were monitored and maintained within 1 degree C of normal. Perfusates were University of Wisconsin solution (UW), Euro-Collins solution, normal saline solution, and Ringer's lactate solution. A nonperfused ischemic control and a nonischemic control group were also evaluated. Parameters evaluated included serum creatinine and blood urea nitrogen levels, renal ischemic injury grade, renal weight, and gross appearance of the injured kidney. Rats treated with UW solution were found to have a significantly lower creatinine, blood urea nitrogen, and injury grade than the other three perfused groups. The external gross appearance of the UW-treated kidneys was normal, whereas that of the other groups demonstrated moderate to severe injury. Although the mean right/left renal weight difference of the UW-treated group was lower than that of the other three groups, this was not statistically significant. Under normothermic conditions in rats, UW solution affords significant renal protection from ischemia. Euro-Collins, normal saline, and Ringer's lactate solutions display no significant protective effect.

Transgraft infusion of heparin to prevent early thrombosis of expanded PTFE grafts in canine femoral veins.

Recently we designed an expanded polytetrafluoroethylene (ePTFE)-based local infusion device that delivers therapeutic agents directly through the graft wall in the region adjacent to the upstream anastomosis, thereby achieving a high drug concentration downstream along the graft-blood interface. In this study we evaluated the effects of infusing heparin by this method on graft patency and neointimal hyperplasia in a canine model of femoral vein replacement. Five dogs underwent bilateral femoral vein replacement with the device. In each case one graft was infused with continuous heparin (48 U/kg/day) while the contralateral control graft received phosphate-buffered saline solution for 14 days. All heparin-treated grafts were patent and all control grafts were thrombosed at 14 days. There was no significant difference in systemic activated partial thromboplastin time among samples taken preoperatively, at 48 hours, and at 14 days of implantation (p > 0.5). There was no significant difference in neointimal hyperplasia between the upstream and downstream anastomoses in heparin-treated grafts. These data demonstrate that the transgraft infusion of heparin preserved venous ePTFE graft patency without measurable systemic anticoagulation. Thus this approach may represent an attractive strategy for maintaining patency of synthetic venous grafts.

Renal artery perfusion modifies ischemia/reperfusion injury.

Renal ischemic and reperfusion injury is a significant complication of major aortic and renovascular surgery. The delivery of a preservative agent just prior to reperfusion of an ischemic kidney may decrease the reperfusion injury. The purpose of this study was to evaluate the effects of renal artery perfusates delivered at the termination of an ischemic period. Five groups of rats were evaluated. All rats underwent left nephrectomy. The right kidney was made ischemic for 45 min by occlusion of the renal artery and vein. Ischemic control animals had no renal artery perfusion. Nonischemic control animals had no renal vessel occlusion or perfusion. The other three groups were perfused during the final 4 min of ischemia with one of the following: normal saline (NS), phosphate-buffered saline (PBS), or anti-ICAM-1-antibody (mAb). The blood urea nitrogen (BUN), serum creatinine (Cr), and renal histopathologic injury of each group were compared. The ischemic control group had significantly better renal function than the group perfused with NS or mAb at 72 hr. There was no significant difference between the ischemic control and PBS groups in renal function or morphologic injury. It is concluded that none of the perfusates in the study had protected the kidney from ischemic and reperfusion injury. NS delivered in this manner was injurious to the kidney.

Local infusion of FGF-saporin reduces intimal hyperplasia.

The recent conjugation of the potent ribosome-inactivating protein saporin (SAP) with basic fibroblast growth factor (FGF2) to form recombinant (r)FGF2-SAP permits increased selectivity of this mitoxin for cells exhibiting upregulated FGF receptors. Systemic administration of rFGF-SAP in therapeutic doses, however, may be associated with significant liver toxicity. In this blinded study, we used a local boundary layer infusion approach to increase local drug concentration while minimizing the risk of side effects. Six dogs underwent bilateral carotid endarterectomies. Expanded polytetrafluoroethylene infusion devices, blindly primed with rFGF2-SAP to one artery or vehicle to the contralateral vessel, were anastomosed proximal to the injured segments so that each animal served as its own control. rFGF2-SAP (2 microgram/kg/day) or vehicle (5 microl/hr) was continuously delivered for 14 days from an osmotic reservoir, through the wall of the graft infusion device. Euthanasia was carried out at 14 days and the processed arteries were blindly analyzed for intimal thickening and cellular proliferation. All dogs survived until sacrifice with no clinical side effects. Liver function tests at euthanasia were not significantly altered when compared to baseline values. Intimal area in rFGF2-SAP-treated vessels averaged 0.31 +/- 0.10 mm2 versus 0.57 +/- 0.24 mm2 in the control segments (P = 0.02), a relative reduction of 46%. Cell proliferation, however, was not significantly different at 14 days postendarterectomy (2.40 +/- 1.31% vs 2.39 +/- 0.45%). From this study it can be concluded that locally delivered rFGF2-SAP reduces intimal hyperplasia and that the boundary layer infusion strategy is an effective means for delivering high local drug concentration while minimizing systemic drug effects.

Hepatic artery aneurysms: the management of 22 patients.

Hepatic artery aneurysms (HAAs) are being encountered with increasing frequency. A retrospective study of the management of HAAs at a single institution over an 18-year period is presented. The medical records of all patients diagnosed with HAA were reviewed. There were 22 patients who collectively had 23 HAAs. They were of equal gender distribution with a mean age of 53 +/- 16 years. Sixteen patients were symptomatic. Angiography was definitive in all cases and was necessary for determining therapy. There were 16 true aneurysms and 7 pseudoaneurysms. The method of treatment depended on the anatomic location of the aneurysm and the status of the patient. Treatment was by surgery (n = 10 patients), embolization (n = 8 patients), or by observation (n = 3 patients). There were two acute deaths; one patient died on admission without therapy, and one patient died following surgery. Two patients had surgical complications. Three of seven patients required repeat embolization, and one had open surgery after failed embolization. Three patients died of unrelated causes. The follow-up period was 2 months to 8 years. Thus, early HAA mortality and morbidity rates were 9.1 and 22.7%, respectively. Unless precluded by significant comorbidities, active treatment is advocated in the management of patients with HAAs. Surgery is the preferred treatment for extrahepatic lesions, while embolization is appropriate for intrahepatic aneurysms, the majority of which are pseudoaneurysms. Increased clinical awareness and aggressive, definitive management are necessary in obtaining optimal outcomes.

The management of splenic artery aneurysms: experience with 23 cases.

BACKGROUND: Splenic artery aneurysms (SAA) are rare clinical entities that carry the risk of rupture and fatal hemorrhage. They are being detected with increased frequency and often cause a clinical dilemma, particularly when small lesions occur in compromised patients. This paper relates our experience in the management of SAA over a 14-year period. PATIENTS AND METHODS: We analyzed data from the medical charts and radiological images of all patients diagnosed with SAA at Emory University Hospital from December 1979 to January 1993. RESULTS: A search of medical records discovered 23 patients who experienced 44 SAAs during the time period under study. Twelve patients had multiple SAAs, most of them in the distal third of the artery. Seven had SAAs > 2 cm in diameter. Modalities used to diagnose SAA included Doppler ultrasound in 9 patients, computerized tomography in 10, and arteriography in 21. Sixteen patients had portal hypertension. Splenomegaly was present in 13 of those with portal hypertension. Aneurysm excision and splenectomy were carried out emergently on 2 patients and electively on 1. Aneurysm ligation was performed on 3 patients. One patient underwent embolization of the lesion. Sixteen asymptomatic patients whose aneurysms were < 2 cm in diameter were treated expectantly for a mean period of 3 years. One patient who received active treatment died. There were no documented deaths attributable to SAA among patients treated by observation. Six patients in this group died of unrelated causes. The longest follow-up was 7 years. CONCLUSIONS: We support current criteria that call for active treatment of symptomatic or enlarging SAAs, with particular emphasis on treating women anticipating pregnancy and patients undergoing orthotopic liver transplantations. For most other cases, expectant treatment is acceptable.