A Potentially Malignant Giant Esophageal Paraganglioma.

Paragangliomas are rare neuroendocrine tumors derived from extraadrenal autonomic paraganglia, which may secrete catecholamines. They are potentially metastatic and require very long-term follow-up. Esophageal paragangliomas are extremely rare and present a diagnostic challenge. Lack of clinical suspicion and unrecognized catecholamine hypersecretion may lead to hemodynamic instabilities during surgery. Two patients with esophageal paragangliomas were previously reported. We report a 39-year-old man with a giant high-risk esophageal paraganglioma who underwent a hybrid minimally invasive 3-hole esophagectomy.

Modified Endoscopic Vacuum Therapy for Nonhealing Esophageal Anastomotic Leak: Technique Description and Review of Literature.

BACKGROUND: Endoscopic vacuum-assisted closure (EVAC) therapy is increasingly being used as a new promising method for repairing upper gastrointestinal defects of different etiologies with high success rates. EVAC therapy consists of placing a sponge either within the lumen or within an abscess cavity connected with a nasogastric (NG) tube to a negative pressure system, thus decreasing bacterial contamination and edema and promoting granulation tissue proliferation, thereby gradually decreasing the cavity size until complete closure. Herein, we describe a modified technique for EVAC therapy in which the NG tube is passed into the esophagus through an existing intrapleural drain tract using a rendezvous technique. The small residual fistula was amendable to fibrin glue embolization. This allows easier sponge placement and exchange compared to traditional EVAC technique, and allows oral intake during treatment. We also review the literature regarding other endoscopic treatment options for esophageal anastomotic leaks and perforations. METHODS: The PubMed database was searched using the terms "esophagus," "esophageal," "leak," "fistula," "endoluminal vacuum-assisted closure (VAC)," "endoscopic VAC," "stent," "sealant," "glue," and "over-the-scope clip (OTSC)." Reference lists of identified articles were searched for further articles, and the "similar articles" function was used on all included articles. RESULTS: Complete closure of the nonhealing fistula was achieved after 8 days of EVAC treatment and fibrin glue embolization. CONCLUSIONS: Modified EVAC technique as described is feasible and safe. To the best of our knowledge, this is the first description of this technique. The technique allows easier sponge placement and exchange compared to traditional EVAC technique, and allows oral intake during treatment.

Valve Replacement in Patients with Carcinoid Heart Disease: Choosing the Right Valve at the Right Time.

BACKGROUND AND AIM OF THE STUDY: The prosthetic valve of choice in patients with carcinoid valve disease (CVD) remains controversial due to the limited life expectancy of patients with advanced-stage neuroendocrine tumors (NETs) on the one hand, and concerns regarding structural valve deterioration (SVD) on the other hand. METHODS: The records of 17 patients (11 females, seven males; mean age 65 ± 11 years; undergoing 18 operations) with primarily right heart failure due to CVD were reviewed. All patients received somatostatin analogs perioperatively. Hospital and follow up data (acquired via direct patient contact and echocardiography) collected included baseline characteristics, procedural details, and clinical outcomes. RESULTS: The primary NET site was the ileum (n = 11), lungs (n = 2) and stomach, colon and appendix (n = 1 each). In one patient the primary tumor location could not be identified. Preoperative urinary levels of 5-hydroxyindole acetic acid (5-HIAA; 61 ± 36 mg/24 h) and serum levels of chromogranin A (2926 ± 4057 ng/ml) were 10- and 50-fold greater than normal, respectively. A total of 23 valves was implanted: five tricuspid valve replacements (TVR; four tissue and one mechanical), TVR and pulmonary valve replacements (PVR; three tissue and one mechanical), and TVR and mitral valve replacements (MVR; one tissue and two mechanical). The 30-day mortality was 11% (n = 2). No patient experienced a carcinoid crisis. The mean follow up was 24 ± 21 months (range: 4-85 months). Four patients (receiving seven valves) developed SVD at 12, 14, 15, and 20 months after surgery, and all of these patients died. The actuarial four-year survival and freedom from SVD were 23 ± 14% and 43 ± 15%, respectively. CONCLUSIONS: The data acquired suggested that the main advantage of tissue valve prostheses, namely to avoid lifelong, intense anticoagulation, might be offset by accelerated SVD. The use of mechanical valves should be considered in CVD patients with a large primary tumor mass and persistent high urinary levels of 5-HIAA, and who are unresponsive to therapy.

A controlled intervention to increase participation in cardiac rehabilitation.

BACKGROUND: Cardiac rehabilitation programs are greatly underutilized. DESIGN: This study was a multicenter interventional controlled cohort study. METHODS: From cardiothoracic departments of five medical centers, 520 coronary artery bypass graft (CABG) patients (386 men) were enrolled in the control arm and 504 CABG patients (394 men) in the intervention arm of our study. A 1-hour seminar to medical staff on the benefits of cardiac rehabilitation followed the control phase and preceded the intervention phase. Patients in the intervention arm received written and oral explanations on cardiac rehabilitation benefits and eligibility, and a follow-up telephone call 2 weeks after hospital discharge. Patients in both study arms were interviewed in the hospital prior to CABG surgery and in their homes a year later. RESULTS: Rates of participation in cardiac rehabilitation were 16.5% (86/520) for the control arm and 31.0% (156/504) for the intervention arm (p < 0.001). Factors strongly associated with participation in cardiac rehabilitation were: belonging to the intervention arm (OR: 2.06 95% CI: 1.46-2.90, p < 0.0001), male sex, average or above average income, sports related physical activity before surgery, younger age and BMI > 30 kg/m(2). Particularly high increases in participation rates following the implementation were observed among subpopulations of 10 years or less education and those reporting below average income. "Lack of knowledge" regarding cardiac rehabilitation was the reason most commonly stated for not participating in a cardiac rehabilitation program. CONCLUSION: Participation in cardiac rehabilitation almost doubled following a low cost intervention with significant effects on subpopulations that have been underrepresented in cardiac rehabilitation programs.

The role of combined carotid endarterectomy and coronary artery bypass grafting in the era of carotid stenting in view of long-term results.

OBJECTIVES: The management of concomitant coronary and carotid artery disease is still in evolution. The surgical options are staged approach--carotid endarterectomy (CEA), followed by coronary artery bypass grafting (CABG) or a reversed-staged approach, or combined approach--CEA and CABG under the same anaesthesia. In view of the percutaneous carotid artery stenting option, we have reviewed our short- and long-term experience with combined CEA and CABG to define the role of this procedure. METHODS: From January 1992 to December 2006, we operated on 80 patients performing combined carotid endarterctomy and myocardial revascularization. Short- and long-term results were reviewed. RESULTS: Operative mortality was 3.7%. Perioperative cerebrovascular accident (CVA) occurred in 2 patients (2.5%). Perioperative myocardial infarction (MI) occurred in 3 patients (3.7%). Combined complications of death + MI + CVA = 10%. During the mean follow-up of 10 ± 3.2 years (1-14 years), 6 patients (7.6%) had neurological events. Freedom from neurological events for 10 years was 92 ± 4%. Nearly 17 (21.5%) had cardiac events. The 5-year and 10-year survival rates were 74 ± 5 and 62 ± 6%, respectively. CONCLUSIONS: Although the short-term results of the non-surgical carotid therapeutic alternative is similar to our surgical results, there are limitations to carotid artery stenting: the need for aggressive antiplatelets therapy, and the haemodynamic changes during the procedure that may be unacceptable for patients with unstable coronary artery disease. Therefore, there is still a role for concomitant surgical CEA and CABG to the results of which the other options should be compared.

Energy transfer from systole to diastole: a novel device-based approach for the treatment of diastolic heart failure.

UNLABELLED: We hypothesized that attachment of elastic coil to the left ventricular (LV) wall, capable of exerting outward forces may allow the transfer of energy from systole to diastole and improve diastolic function. METHODS AND RESULTS: An extra-ventricular-device, composed of a series of elastic elements interposed between spiral screws attached to the epimyocardium of the LV free-wall was developed. The hemodynamic and mechanical effects of the device were tested using a computerized model, an in vitro model utilizing a computerized-controlled fluid pump, eight healthy sheep and 10 mini-pigs induced with diastolic dysfunction by renal wrapping. The computerized and in vitro models predicted a reduction of the LV diastolic pressure curve and partial normalization of the pressure-volume loop. The sheep study demonstrated preservation of animal's wellbeing including maintaining cardiac mechanical function with stable energy transfer from systole to diastole throughout the 6 months follow-up. The mini-pigs study showed an increase in the early diastolic to systolic strain-rate ratio in the mid-endocardial level (23 ± 10%, P = 0.008) and an increase in early apical reverse rotation rate of 50% (P = 0.016 compared to control). CONCLUSIONS: This study presents a novel concept of using a mechanical device to transfer energy from systole to diastole, potentially enhancing diastolic function.

The effect of the cryosurgical cox-maze procedure on pulmonary veins diameter and left atrial size: computed tomography angiographic assessment.

OBJECTIVE: : The Cox-Maze procedure using cryoablation results in transmural lesions, which follow the lesion pattern of the cut-and-sew Cox-Maze procedure. The purpose of our study was to evaluate the effect of the Cox-Maze procedure on left atrial and pulmonary vein size using computed tomography angiogram (CTA). An additional aim was to evaluate pulmonary vein anatomic variability. METHODS: : Six patients (four women and two men; ages 39-63 years, mean age 54.3) underwent chest CTA 1 day before and 38 to 104 days (mean 62.6 days) after the cryosurgical Cox-Maze procedure. Measurements of pulmonary vein ostia and left atrial cranio-caudal, left-to-right and anterior-posterior diameters were derived by consensus. The change in diameters after therapy was compared using the Wilcoxon nonparametric test for paired measurements. Four patients (1 woman and 3 men; age 57-73 years; mean age 59) were evaluated with postoperative CTA alone 296-530 days (mean 447) after surgery, for the development of postoperative pulmonary vein stenosis. A single patient underwent preoperative CTA, but surgery was not performed. Pulmonary venous anatomy was recorded in all 11 patients. RESULTS: : Sinus rhythm was restored in all operated patients. No focal ostial stenosis of the pulmonary veins was observed. The quantitative assessment in the six patients with preoperative and postoperative studies disclosed only slight changes in pulmonary vein diameter with either reduction or dilatation of no more than 20% from baseline (P > 0.05). There was a consistent trend toward decrease in left atrial dimensions, which did not reach statistical significance. Six patients (55%) had standard pulmonary venous anatomy and five patients (45%) had at least one variation in their pulmonary vein anatomy. CONCLUSIONS: : In this study, we found that a very intensive cryoablation protocol around the pulmonary veins did not result in pulmonary vein stenosis. In addition, a relatively high incidence of anatomic variations of the pulmonary veins was documented.

Myocardial metabolism altered by ischemic preconditioning and enflurane in off-pump coronary artery surgery.

OBJECTIVE: During off-pump coronary artery bypass (OPCAB) surgery, the heart is subjected to ischemia and reperfusion. The authors hypothesized that the volatile anesthetics are as effective as ischemic preconditioning (IPC) in preserving myocardial function during off-pump cardiac surgery, and this effect is because of multiple mechanisms of action. Therefore, the effects of enflurane with its calcium inhibition and antioxidative properties were compared with mechanical IPC in preserving myocardial cellular markers. DESIGN: A prospective, randomized, controlled, and partly blinded study. SETTING: A tertiary care university hospital. PARTICIPANTS: Twenty-five patients undergoing elective single-graft OPCAB surgery. INTERVENTIONS: Patients were randomized into 3 groups: (1) control (n = 8), (2) a single 5-minute ischemia/reperfusion interval of IPC before coronary occlusion (n = 9), and (3) 1.6% enflurane anesthesia 15 minutes before and during graft attachment (n = 8). Arterial and coronary sinus venous blood were analyzed for biochemical indices of ischemia and hydroxyl radical generation. MEASUREMENTS AND MAIN RESULTS: Although the hemodynamic changes were small, myocardial lactate production in the control group increased by 120%, whereas in the enflurane group it decreased significantly (p < 0.01) compared with the control and IPC groups. Oxygen utilization in the control group was 44% higher (p < 0.03), and there was also a larger release of the hydroxyl radical-dependent adduct 2,3-dihydroxybenzoic acid (225% increase, p < 0.05) compared with both study groups. During reperfusion, initial anterior wall hypokinesis by TEE was observed, with slow recovery during reperfusion compared with early recovery in both study groups. CONCLUSIONS: Coronary occlusion during OPCAB surgery results in increased production of ischemia-related metabolic products. The application of methods such as IPC or volatile anesthesia appears to reduce the metabolic deficit, free-radical production, and physiologic changes.

Successful restoration of function of frozen and thawed isolated rat hearts.

OBJECTIVE: Long-term organ preservation for transplantation may allow optimal donor-recipient matching with potential reduction in the incidence and severity of rejection. Complete cessation of metabolism may be obtained by freezing. Previous attempts to freeze intact mammalian hearts were limited to -3.6 degrees C, restricting tissue ice content to 34%. We hypothesized that our method will allow recovery of function of the intact rat heart after freezing to -8 degrees C, a temperature at which most of the tissue water is frozen. METHODS: Isolated rat hearts were attached to a Langendorff apparatus. After normothermic perfusion, cold cardioplegia was induced followed by perfusion with a cryoprotecting agent. Hearts were than frozen to -8 degrees C (45 +/- 8 minutes), thawed, and reperfused (60 minutes). RESULTS: All frozen and thawed hearts regained normal electric activity. At -8 degrees C, ice content was 64.36% +/- 13%. The use of 10% ethylene glycol for cryoprotection (n = 13) resulted in recovery (mean +/- standard deviation) of 49.7% +/- 21.8% of +dP/dt, 48.0% +/- 23.5% of -dP/dt, 65.2% +/- 30.8% of coronary flow, and 50.4% +/- 23.9% of left ventricular developed pressure. Hearts in this group (n = 4) maintained 81.3% +/- 10% viability compared with 69.3% +/- 14% (not significant) in control hearts kept at 0 degrees C for the same duration. Energy stores, represented by adenosine triphosphate and phosphocreatine, were depleted to 12.2 +/- 6.1 micromol/g dry weight and 22.5 +/- 6.4 micromol/g dry weight, respectively, compared with 19.0 +/- 2.5 micromol/g dry weight and 36.6 +/- 3.0 micromol/g dry weight, respectively (P < .05) in the control hearts. The integrity of muscle fibers and intracellular organelles after thawing and reperfusion was demonstrated by electron microscopy. CONCLUSION: We demonstrate for the first time the feasibility of functional recovery after freezing and thawing of the isolated rat heart while maintaining structural integrity and viability.

[Evolution of the surgical repair of thoracoabdominal aortic aneurysm].

BACKGROUND: Thoracoabdominal aortic aneurysm repair requires complex surgery. Clamping of the descending aorta during the operation results in organ malperfusion, ischemia, and in some cases, irreversible end-organ damage and death. Several methods for organ preservation during the operation evolved, resulting in decreased post-operative organ malfunction. Re-attachment of intercostal arteries, cerebrospinal fluid drainage, and temporary bypass of the clamped aorta and selective perfusion of the spinal cord, intestine, liver and kidneys are widely used during the operation. OBJECTIVES: To determine the impact of implementation of protective measures on the outcome of thoracoabdominal surgery over a decade. METHODS: Between March 1993 and March 2003, 11 patients (age 41-80 years, average 60 years) underwent thoracoabdominal aortic aneurysm repair in our hospital. Different methods for organ preservation were used during the operation. RESULTS: The early survival is 91%. One patient suffered from paraplegia and one from mild temporary paraparesis. Two patients died during the follow-up period (at 5 months from pneumonia and at 2 years from aortic arch rupture). CONCLUSIONS: Implementation of all adjuncts to protect the organs dependent on aortic perfusion may eliminate the ischemic consequences of aortic clamping.

[Criteria for the acceptable heart donor: maximizing the use of hearts recovered from potential donors in Israel].

The shortage of available donor hearts limits the number of cardiac transplantations worldwide and in Israel as well. This organ shortage results in 15%-20% annual mortality of heart transplant candidates. For the sub-group of hospitalized decompensated heart failure patients depending on continuous inotropic support (Status I), the annual mortality is over 50%. Suboptimal utilization of donor hearts has been one of the reasons for the organ shortage. In 2004, only 42% of the potential donor hearts in Israel were eventually transplanted. The objective of this report is to define guidelines regarding the suitability of potential cardiac donors allowing more liberal criteria for accepting borderline donor hearts. Implementing the new guidelines will permit the utilization of organs that otherwise would have been discarded.

Interaction between beta2 adrenergic receptor polymorphisms determines the extent of isoproterenol-induced vasodilatation ex vivo.

OBJECTIVES: Single nucleotide polymorphisms at nucleotides 46, 79 and 491 of the beta2 adrenergic receptor (beta2AR) gene modify its pharmacological properties and may alter the response to agonists. The purpose of this study was to evaluate the role played by beta2AR polymorphisms on isoproterenol-induced relaxation of internal mammary arteries ex vivo. METHODS: Internal mammary leftover segments were collected from 96 patients undergoing coronary artery bypass operation. Vascular rings were allowed to reach equilibrium with physiological Krebs solution before precontraction with U46619. Using the organ bath technique, cumulative dose-response curve of isoproterenol was constructed and average EC50 calculated. beta2AR genotyping was performed using a PCR-RFLP analysis. RESULTS: Arterial segments obtained from Gly16 homozygotes displayed reduced sensitivity to isoproterenol compared with carriers of Arg16 allele(s) [Mean (-log) EC50+/-SD, 6.42+/-0.24, 95% confidence interval (CI) 6.32-6.53 vs. 6.67+/-0.25, 95% CI 6.62-6.73, P<0.001]. Among Gly16 homozygotes, the presence of two Glu27 alleles restored vascular response to the level noted among Arg16 carriers (6.58+/-0.17, 95% CI 6.41-6.76). The least response to isoproterenol was noted in a single patient carrying the Gly16Gly-Gln27Glu-Thr164Ile combined genotype requiring almost six-fold higher isoproterenol concentration than carriers of the wild-type genotype to achieve half the maximal arterial dilatation (17.78 x 10(-7) vs. 3.01 x 10(-7) +/- 2.62 x 10(-7) mol/l). CONCLUSIONS: Vascular dilatation by isoproterenol is determined by a complex interaction between polymorphisms at nucleotides 46, 79 and 491 of the beta2AR gene. Further studies are warranted to evaluate the effect of additional polymorphisms in the coding and noncoding regions on vascular reactivity.

Warfarin metabolism and anticoagulant effect: a prospective, observational study of the impact of CYP2C9 genetic polymorphism in the presence of drug-disease and drug-drug interactions.

BACKGROUND: Cytocbrome P450 (CYP) 2C9 polymorphism affects the warfarin dosage requirement in stable outpatients. However, it is not known whether the CYP2C9 genotype contributes to the variability in warfarin dosage in the presence of drug-disease and drug-drug interactions. OBJECTIVE: The aim of this study was to examine the effects of CYP2C9 genetic polymorphism on warfarin dosage requirements in patients with severe comorbid conditions and those treated with medications that potentially interact with warfarin. METHODS: This prospective, observational study was conducted at Hadassah University Hospital, Jerusalem, Israel. Data from consecutive patients treated with warfarin for at least 3 months and admitted to the internal medicine ward were eligible for inclusion. Clinical data, international normalized ratio (INR), and warfarin dosage were recorded from medical records. The CYP2C9 genotype was determined using polymerase chain reaction restriction fragment length polymorphism, and plasma concentrations of (S)- and (R)-warfarin were determined by high-performance liquid chromatography using chiral methods. RESULTS: One hundred nineteen subjects (52% women) were studied. Mean age was 65.8 years (95% CI, 63.1-68.4), and weight was 74.9 kg (95% CI, 72.1-77.7). The mean warfarin dosage was 33% lower in patients with the CYP2C9-*1/*3 genotype (mean [SEM], 0.045 [0.006] mg/kg x d(-1)) compared with the CYP2C9-*1/*1 genotype (0.067 [0.004] mg/kg x d(-1)) (P=0.008); an intermediate value was found for the CYP2C9-*1/*2 genotype (0.062 [0.008] mg/kg x d(-1)). However, despite the lower dosage, INR was significantly higher in patients with the *1/*3 genotype (mean [95% CI], 3.29 [2.44-4.14]) (n=18) compared with the *1/*1 genotype (2.52 [2.34-2.71]) (n=64) (P=0.029). In addition to genotype, older age, congestive heart failure (CHF), and treatment with antibiotics were associated with lower warfarin dosages, whereas treatment with drug-metabolism inducers was associated with higher warfarin dosages. In addition, the ratios of (S)- to (R)-warfarin concentrations were significantly higher in patients with *1/*3 compared with those in patients with the *1/*1 genotype. CONCLUSIONS: In this study population of patients with severe comorbid conditions and those treated with medications that potentially interact with warfarin, CYP2C9 *1/*3 genotype, older age, CHF, and the use of antibiotics were associated with lower warfarin dosage requirements. The CYP2C9*1/*3 genotype, compared with CYP2C9 *1/*1, was associated with 33% lower mean warfarin dosage requirements and higher INR values, which were higher than the upper therapeutic range of INR (ie, 3). Genetic CYP2C9 polymorphism contributed to the variability in warfarin dosage requirements in the presence of drug-disease and drug-drug interactions.

Dexrazoxane prevents myocardial ischemia/reperfusion-induced oxidative stress in the rat heart.

INTRODUCTION: Dexrazoxane (Dex), used clinically to protect against anthracycline-induced cardiotoxicity, possesses iron-chelating properties. The present study was designed to examine whether Dex could inhibit the ischemia/reperfusion (I/R) induced damage to the rat heart. MATERIALS AND METHODS: Isolated perfused rat hearts were exposed to global ischemia (37 degrees C) and 60 min reperfusion. Dex was perfused for 10 min prior to the ischemia, or administered intraperitoneally (150 mg) 30 min prior to anesthesia of the rats. I/R caused a significant hemodynamic function decline in control hearts during the reperfusion (e.g., the work index LVDP X HR declined to 42.7+/-10%). Dex (200 microM) applied during the preischemia significantly increased the hemodynamic recovery following reperfusion (LVDP X HR recovered to 55.7+/-8.8%, p<0.05 vs. control). Intraperitoneal Dex, too, significantly increased the hemodynamic recovery of the reperfused hearts. I/R caused an increase in oxidation of cytosolic proteins, while Dex decreased this oxidation. DISCUSSION: The decrease in proteins carbonylation and correlative hemodynamic improvement suggests that Dex decreases I/R free radical formation and reperfusion injury.

Suicide bombing injuries: the Jerusalem experience of exceptional tissue damage posing a new challenge for the reconstructive surgeon.

BACKGROUND: Suicide bomb injuries vary in form and magnitude. From the onset of the second Palestinian "intifada" in October of 2000 until January of 2004, 577 victims of suicide bombings were admitted to the Hadassah-Hebrew University Medical Center. A single bomber carrying a handbag or belt containing multiple metal objects and explosives carried out most of the attacks. As a result, many of the victims suffered massive tissue destruction in addition to conventional blast injuries. METHODS: This article describes the management of this trauma-related "syndrome" of combined primary and high-magnitude secondary blast injury. RESULTS: The management of the extensive soft-tissue damage is described and two representative cases presented. CONCLUSION: Suicide bombing-related injuries in their present form are a true challenge for the reconstructive surgeon.