The failing Fontan: what's NEXT...?

The Fontan procedure represents the final stage of the transition to single ventricle physiology. Conversion of very complex congenital heart anatomy, such as hypoplastic left heart syndrome, double-outlet right ventricle or double-inlet left ventricle, to a single ventricle has grown in popularity as morbidity and mortality have improved. As these patients grow, survivors are at risk for impaired ventricular dysfunction, plastic bronchitis, protein-losing enteropathy and late failure. Late failing Fontan patients represent a particularly vexing scenario for clinicians, as the only durable treatment option is cardiac transplantation. However, in the short-term, some of these patients require support beyond medical management, with mechanical circulatory support via extracorporeal life support or a ventricular assist device. We report the successful bridge of an adolescent female post-Fontan conversion with late severe cardiac failure. The patient was initially resuscitated with extracorporeal life support, transitioned to a single Berlin Heart EXCOR® ventricular assist device and, subsequently, underwent successful cardiac transplantation.

Total artificial heart in the pediatric patient with biventricular heart failure.

Mechanical circulatory support emerged for the pediatric population in the late 1980s as a bridge to cardiac transplantation. The Total Artificial Heart (TAH-t) (SynCardia Systems Inc., Tuscon, AZ) has been approved for compassionate use by the Food and Drug Administration for patients with end-stage biventricular heart failure as a bridge to heart transplantation since 1985 and has had FDA approval since 2004. However, of the 1,061 patients placed on the TAH-t, only 21 (2%) were under the age 18. SynCardia Systems, Inc. recommends a minimum patient body surface area (BSA) of 1.7 m(2), thus, limiting pediatric application of this device. This unique case report shares this pediatric institution's first experience with the TAH-t. A 14-year-old male was admitted with dilated cardiomyopathy and severe biventricular heart failure. The patient rapidly decompensated, requiring extracorporeal life support. An echocardiogram revealed severe biventricular dysfunction and diffuse clot formation in the left ventricle and outflow tract. The decision was made to transition to biventricular assist device. The biventricular failure and clot formation helped guide the team to the TAH-t, in spite of a BSA (1.5 m(2)) below the recommendation of 1.7 m(2). A computed tomography (CT) scan of the thorax, in conjunction with a novel three-dimensional (3D) modeling system and team, assisted in determining appropriate fit. Chest CT and 3D modeling following implantation were utilized to determine all major vascular structures were unobstructed and the bronchi were open. The virtual 3D model confirmed appropriate device fit with no evidence of compression to the left pulmonary veins. The postoperative course was complicated by a left lung opacification. The left lung anomalies proved to be atelectasis and improved with aggressive recruitment maneuvers. The patient was supported for 11 days prior to transplantation. Chest CT and 3D modeling were crucial in assessing whether the device would fit, as well as postoperative complications in this smaller pediatric patient.

Sickle cell disease and complex congenital cardiac surgery: a case report and review of the pathophysiology and perioperative management.

Sickle cell anemia and thalassemia are hemoglobinopathies rarely encountered in the United States. Compounded with congenital heart disease, patients with sickle cell disease (SCD) requiring cardiopulmonary bypass and open-heart surgery represent the proverbial "needle in the haystack". As such, there is some trepidation on the part of clinicians when these patients present for complex cardiac surgery. SCD is an autosomal, recessive condition that results from a single nucleotide polymorphism in the ß-globin gene. Hemoglobin SS molecules (HgbSS) with this point mutation can polymerize under the right conditions, stiffening the erythrocyte membrane and distorting the cellular structure to the characteristic sickle shape. This shape change alters cellular transit through the microvasculature. As a result, circumstances such as hypoxia, hypothermia, acidosis or diminished blood flow can lead to aggregation, vascular occlusion and thrombosis. Chronically, SCD can give rise to multiorgan damage secondary to hemolysis and vascular obstruction. This review and case study details an 11-year-old African-American male with known SCD who presented to the cardiothoracic surgical service with congenital heart disease consisting of an anomalous, intramural right coronary artery arising from the left coronary sinus for surgical consultation and subsequent surgical correction. This case report will include a review of the pathophysiology and current literature regarding preoperative, intraoperative and postoperative management of SCD patients.

Chronology of the Barrett's metaplasia-dysplasia-carcinoma sequence.

The objective of this study was to assess the course over time of the Barrett's metaplasia-dysplasia-carcinoma sequence. The method used was a retrospective analysis of the medical records of a patient series with a median follow-up of 25 months. The study was undertaken in a university hospital foregut laboratory. The progress of seven patients was followed through the sequence of Barrett's esophagus, low-grade dysplasia and high-grade dysplasia to cancer. They all underwent subsequent esophagectomy and were found to have intramucosal adenocarcinoma. The main outcome measure was the time from the first diagnosis of intestinal metaplasia to the development of low-grade dysplasia, high-grade dysplasia and adenocarcinoma. Low-grade dysplasia developed in a median of 24 months, high-grade dysplasia after a median of 33 months and cancer after 36 months. All patients underwent esophagectomy with reconstruction and no patient has had a recurrence at a median follow-up of 25 months (range 10-204 months). Patients on Barrett's surveillance who develop early esophageal adenocarcinoma did so within approximately 3 years after the diagnosis of non-dysplastic Barrett's esophagus.

The effect of pleural adhesions on pediatric cystic fibrosis patients undergoing lung transplantation.

The degree of pleural scarring complicating cystic fibrosis (CF) lung disease is thought to impact on the outcome of adult lung transplantation. This has not been previously studied in the pediatric population. We studied all patients undergoing lung transplantation at Children's Hospital Los Angeles from 1993 through 2000. Operative times, grade of pleural scarring, blood product transfusion requirements, and perioperative mortality were compared for patients with cystic fibrosis (35) versus those without this diagnosis (11). Patients with CF were slightly older (14.7+/-3.8 vs 10.6+/-5.6 years; P = 0.01) but had similar weights (34.8+/-8.7 vs 34.4+/-12.3 kg). The degree of pleural scarring was greater in the CF group but was only severe in four patients. Scarring did not impact on operative times (237+/-46 vs 219+/-39 minutes; P = 0.22) or cardiopulmonary bypass times (127+/-40 vs 133+/-49 minutes). Total perioperative blood requirements for the two groups were similar (35.6+/-14.9 vs 42.8+/-76.7 cm3/kg; P = 0.82). Pleural scarring in the pediatric CF patients undergoing lung transplantation is only severe in a minority of patients. It does not increase duration of operation nor blood transfusion requirements. CT scanning is consequently unnecessary in the preoperative workup of CF patients being evaluated for transplantation. CF patients undergoing transplantation have perioperative outcomes similar to those of noncystic patients.

Laparoscopic ultrasonic epithelial ablation of the lower esophagus after nissen fundoplication in a porcine model: assessment of tissue damage and healing process.

A substantial population of patients with Barrett's esophagus has undergone antireflux surgery but still requires annual surveillance endoscopy. These patients would benefit from a definitive ablation of the Barrett's mucosa, which would remove the malignant potential of this disease. This study evaluates the efficacy of applying ultrasonic energy to remove the epithelium of the lower esophagus in a porcine model with prior Nissen fundoplication. Four Yakutan minipigs underwent laparoscopic Nissen fundoplication. After 2 weeks they underwent transgastric Cavitron ultrasonic surgical aspirator (CUSA; Valleylab, Boulder, CO) ablation of the lower esophageal epithelium. Healing of the mucosa was assessed by endoscopy at 2 weeks and pathological examination at 4 weeks after ablation. All pigs underwent successful laparoscopic Nissen fundoplication. Complete lower esophageal epithelial ablation was accomplished through the fundoplication in three animals. One pig developed a bezoar that prohibited ablation. At 2 weeks endoscopy showed patchy squamous epithelial regeneration, which was confirmed histologically. Esophageal specimens at 4 weeks showed complete regeneration of squamous epithelium with a partially healed small ulcer in one animal. No stricture formation was seen. We conclude that the CUSA technique can completely ablate Barrett's mucosa in the setting of a prior antireflux procedure. Healing with squamous mucosal regeneration is rapid and complete.

Occult esophageal adenocarcinoma: extent of disease and implications for effective therapy.

OBJECTIVE: The need for esophagectomy in patients with Barrett's esophagus, with no endoscopically visible lesion, and a biopsy showing high-grade dysplasia or adenocarcinoma has been questioned. Recently, endoscopic techniques to ablate the neoplastic mucosa have been encouraged. The aim of this study was to determine the extent of disease present in patients with clinically occult esophageal adenocarcinoma to define the magnitude of therapy required to achieve cure. METHODS: Thirty-three patients with high-grade dysplasia (23 patients) or adenocarcinoma (10 patients) and no endoscopically visible lesion underwent repeat endoscopy and systematic biopsy followed by esophagectomy. The surgical specimens were analyzed to determine the biopsy error rate in detecting occult adenocarcinoma. In those with cancer, the depth of wall penetration and the presence of lymph node metastases on conventional histology and immunohistochemistry staining was determined. The findings were compared with those in 12 patients (1 with high-grade dysplasia, 11 with adenocarcinoma) who had visible lesions on endoscopy. RESULTS: The biopsy error rate for detecting occult adenocarcinoma was 43%. Of 25 patients with cancer and no visible lesion, the cancer was limited to the mucosa in 22 (88%) and to the submucosa in 3 (12%). After en bloc esophagectomy, one patient without a visible lesion had a single node metastasis on conventional histology. No additional node metastases were identified on immunohistochemistry. The 5-year survival rate after esophagectomy was 90%. Patients with endoscopically visible lesions were significantly more likely to have invasion beyond the mucosa (9/12 vs. 3/25, p = 0.01) and involvement of lymph nodes (5/9 vs. 1/10, p = 0.057). CONCLUSIONS: Endoscopy with systematic biopsy cannot reliably exclude the presence of occult adenocarcinoma in Barrett's esophagus. The lack of an endoscopically visible lesion does not preclude cancer invasion beyond the muscularis mucosae, cautioning against the use of mucosal ablative procedures. The rarity of lymph node metastases in these patients encourages a more limited resection with greater emphasis on improved alimentary function (esophageal stripping with vagal nerve preservation) to provide a quality of life compatible with the excellent 5-year survival rate of 90%.

Helicobacter pylori is not associated with the manifestations of gastroesophageal reflux disease.

HYPOTHESIS: Helicobacter pylori is not associated with gastroesophageal reflux disease and its complications, including adenocarcinoma of the esophagus and the gastroesophageal junction (GEJ). DESIGN: Retrospective analysis. SETTING: University tertiary referral center. PATIENTS: Two hundred twenty-nine patients with symptoms suggestive of foregut disease underwent esophageal manometry, 24-hour pH monitoring, and upper gastrointestinal tract endoscopy, with biopsy specimens obtained from the gastric antrum, the GEJ, and the distal esophagus. In these and in an additional 114 patients with adenocarcinoma of the esophagus and the GEJ, the presence of H. pylori was determined by Giemsa stain. The presence of gastroesophageal reflux disease, defined by abnormal esophageal acid exposure, and its manifestations (carditis, erosive esophagitis, intestinal metaplasia limited to the GEJ, Barrett esophagus, and adenocarcinoma of the esophagus and GEJ) were correlated with the presence of H. pylori. RESULTS: Helicobacter pylori was found on the biopsy specimens of the gastric antrum in 14.0% (32/229) of the patients with benign disease. It was not related to the features of gastroesophageal reflux disease, including abnormal esophageal acid exposure, erosive esophagitis, or Barrett esophagus. The presence of inflamed cardiac mucosa at the GEJ or carditis was inversely related to H. pylori infection and strongly associated with increased esophageal acid exposure. There was no association between the presence of intestinal metaplasia and H. pylori infection. Helicobacter pylori was found in 22 (19.3%) of the 114 patients with esophageal adenocarcinoma, which was not different from the prevalence of H. pylori in patients with benign disease. CONCLUSION: Helicobacter pylori plays no role in the pathogenesis of gastroesophageal reflux disease or its complications.

Genetic engineering of stent grafts with a highly efficient pseudotyped retroviral vector.

PURPOSE: The purpose of this study was first to compare the gene transfer efficiency of amphotrophic murine leukemia viral vector (ampho-MuLV) with the efficiency of MuLV pseudotyped with the vesicular stomatitis virus G glycoprotein (VSVG-MuLV) in tissue of vascular origin. The second purpose of this study was to determine cell retention after the implantation of genetically engineered stent grafts. METHODS: Gene transfer efficiency was ascertained with the b-galactosidase assay. The target tissues included endothelial cells (ECs), smooth muscle cells (SMCs), and human saphenous veins (HSVs). Polyurethane stent grafts were suffused with lac Z-transduced ECs and SMCs that were harvested from porcine jugular vein. The grafts were implanted into the iliac artery of each pig whose jugular vein had been harvested. Cell retention was analyzed at 1 and 4 weeks with X-Gal staining. RESULTS: VSVG-MuLV transduction efficiency exceeded that of ampho-MuLV in human ECs (VSVG-MuLV, n = 24, 89% +/- 6%; ampho-MuLV, n = 18, 14% +/- 6%; P <. 001), human SMCs (VSVG-MuLV, n = 5, 92% +/- 3%; ampho-MuLV, n = 4, 17% +/- 2%; P <.001), pig ECs (VSVG-MuLV, n = 4, 81% +/- 2%; ampho-MuLV, n = 4, 13% +/- 3%; P <.001), and pig SMCs (VSVG-MuLV, n = 5, 89% +/- 3%; ampho-MuLV, n = 4, 16% +/- 1%; P <.001). As much as a 10-fold higher transduction efficiency was observed with VSVG-MuLV in HSVs. After the stent graft implantation, the engineered cells were retained and proliferated on the stent membrane, with ingrowth into the underlying intima. CONCLUSION: VSVG-MuLV significantly increased the gene transfer efficiency in vascular SMCs and ECs and in organ-cultured HSVs. The cells were retained and proliferated on stent grafts for the short term in the pig.

Node status in transmural esophageal adenocarcinoma and outcome after en bloc esophagectomy.

OBJECTIVE: Adenocarcinoma has replaced squamous cell as the most common esophageal cancer in the United States. The purpose of this study was to determine the prevalence and location of lymph node metastases, the feasibility of performing an R0 resection, and disease recurrence and survival in patients with transmural adenocarcinoma of the lower esophagus and gastroesophageal junction. METHODS: Forty-four patients with transmural adenocarcinoma underwent en bloc esophagectomy with systematic thoracic and abdominal lymphadenectomy. They were followed up for a median of 23 months. RESULTS: Actuarial survival for the entire group was 26% at 5 years. The most important predictors of the likelihood of recurrent disease and 5-year survival were the presence and number of lymph node metastases and the ratio of involved to total removed nodes. Seven patients (16%) were found to have no lymph node metastases and had an 85% 5-year survival. In contrast, patients with more than 4 involved nodes or a node ratio greater than 0.1 had a high likelihood of recurrence and death. Location of involved lymph nodes did not predict the likelihood of recurrence or death. Despite all patients having transmural tumors, recurrence within the field of the en bloc resection occurred in only 1 patient (2%). CONCLUSIONS: En bloc esophagectomy in patients with transmural esophageal adenocarcinoma is required to obtain the survival benefit of an R0 resection, to adequately assess lymphatic tumor burden, and to be able to predict the likelihood of recurrence and death and thereby guide the use of postoperative adjuvant therapy.

The extent of Barrett's esophagus depends on the status of the lower esophageal sphincter and the degree of esophageal acid exposure.

OBJECTIVE: The purpose of this study was to assess whether the extent of intestinal metaplasia is related to the severity of the gastroesophageal reflux disease. METHODS: A total of 556 consecutive patients with symptoms suggestive of foregut disease had upper gastrointestinal endoscopy with extensive biopsies from the gastroesophageal junction and the esophagus. All patients had esophageal motility and 24-hour pH monitoring. In 411 patients, cardiac-type mucosa was identified; in 147 patients, the cardiac-type mucosa showed intestinal metaplasia. They were divided into 3 groups based on the extent of intestinal metaplasia commonly seen clinically: long segments (>3 cm), short segments (<3 cm), and limited to the gastroesophageal junction. The duration of symptoms, the status of the lower esophageal sphincter, the degree of esophageal acid exposure, and the time to clear a reflux episode were assessed in each group. RESULTS: The presence of intestinal metaplasia in cardiac-type mucosa was associated with the hallmarks of gastroesophageal reflux disease. The extent of intestinal metaplasia correlated strongly with the degree of esophageal acid exposure (r = 0.711; P <.001) and inversely with the lower esophageal sphincter pressure (r = 0.351; P <.001) and length (r = 0. 259; P =.002). Patients with a long segment of intestinal metaplasia (>3 cm) had longer duration of symptoms (16 years) than those patients with a segment of intestinal metaplasia less than 3 cm (10 years; P =.048) or those patients with intestinal metaplasia limited to the gastroesophageal junction (10 years; P =.01). CONCLUSION: The extent of intestinal metaplasia, that is, Barrett's esophagus, is related to the status of the lower esophageal sphincter and the degree of esophageal acid exposure.

Prevalence and location of nodal metastases in distal esophageal adenocarcinoma confined to the wall: implications for therapy.

OBJECTIVE: The purpose of this study was to characterize the prevalence and location of regional lymph node metastases in adenocarcinoma confined to the esophagal wall, to determine the extent of dissection required, and to investigate the applicability of nonoperative therapy. METHODS: Histologic evaluation of the resected specimens after en bloc esophagogastrectomy with mediastinal and abdominal lymphadenectomy was performed on 37 patients with adenocarcinoma confined to the esophageal wall. Follow-up was complete in all patients (median 24 months). RESULTS: Fifteen patients (41%) had intramucosal tumors. Twelve (32%) had submucosal tumors and 10 (27%) had muscular invasion. The prevalence of regional lymph node metastases (15/37 patients, 41%) increased progressively with depth of tumor invasion, with involved nodes identified in 80% of patients with muscular invasion. Lymph node metastases were also more common at distant node stations in intramuscular tumors (5/10, 50%). Actuarial survival for the entire group was 63% at 5 years. Recurrence was identified in 6 of the 37 patients (16%), with the risk of recurrence correlating with tumor depth. CONCLUSIONS: Tumor depth is a strong predictor of the probabilities of regional lymph node metastases, the likelihood of involvement of distant node groups, and the risk of recurrence. Patients with invasion of the muscular wall are at particularly high risk. En bloc esophagectomy with mediastinal and abdominal lymphadenectomy has the highest likelihood of achieving an R0 resection. The long-term survival and low recurrence rate achieved with an en bloc esophagectomy emphasizes the importance of an aggressive lymph node dissection to remove all potentially involved nodes.