Bariatric surgery and prevention of cardiovascular events and mortality in morbid obesity: mechanisms of action and choice of surgery.

AIMS: Obesity is associated with increased cardiovascular (CV) morbidity and mortality. Weight loss improves several risk factors for CV diseases, but anti-obesity medications and lifestyle interventions have failed to modify primary CV endpoints. This paper reviews bariatric surgery in prevention of CV diseases and CV mortality, and analyzes the possible mechanisms involved. DATA SYNTHESIS: In morbidly obese patients bariatric surgery results in stable weight loss and in long-term reduction in the prevalence and incidence of obesity-related comorbidities; controlled trials have shown superiority of bariatric surgery over medical therapy in inducing significant weight loss and improvement of CV risk factors. Bariatric surgery induces several metabolic improvements (resolution of type 2 diabetes mellitus, improvement of lipid metabolism and of insulin resistance, reduction of visceral fat, of subclinical endothelial dysfunction and inflammation), and functional improvements (reduction of hypertension, of sympathetic overactivity, of left and right ventricular hypertrophy), which can explain the protective effect towards CV disease. CONCLUSIONS: Reduction of CV diseases is mediated by the pleiotropic effects of weight loss through surgery. Available data do not allow conclusions on the comparative efficacy of different surgical techniques; the choice of the surgical technique for a single patient remains an open question, and it is likely that the degree of prevention of CV diseases depends, among other factors, on the baseline conditions of patients. Large prospective studies are needed to address this issue in morbidly obese patients.

Accuracy of transrectal ultrasound after preoperative radiochemotherapy compared to computed tomography and magnetic resonance in locally advanced rectal cancer.

INTRODUCTION: The aim of the present study was to compare the restaging results obtained by transrectal ultrasound (TRUS), computed tomography (CT), and magnetic resonance imaging (MRI) performed after preoperative chemoradiation with pathologic staging of the operative specimen. METHODS: From January 2008 to December 2009, all the consecutive patients with locally advanced rectal cancer that underwent neoadjuvant therapy at our department were evaluated. The results of diagnostic examinations and the definitive pathological examination were considered and compared. RESULTS: Thirty-seven patients were included in the study (27 males, 73%), mean age was 65.5 years (range 45­82 years). In all the patients TRUS and CT and in 20 patients MRI were performed before and after the treatment. Concerning the depth of invasion after treatment TRUS agreed with histopathology in 25/37 patients (67.5%), CT agreed in 22/ 37 cases (59.5%), and MRI in 12/20 cases (60%). Considering only neoplasia with stage T3, TRUS agreed in 23/24 cases (96%), CT in 19 cases (79%), and MRI in 10/12 cases (83.5%). Considering the tumors that did not exceed the rectal wall (T0, T1, and T2), TRUS agreed with histology in 2/13 cases (15.5%),CTin 3/13 cases (23%), andMRI 2/8 cases (25%). Concerning the presence of positive lymph nodes TRUS agreed with histology in 28/37 cases (75.5%), while CT agreed in 21/37 cases (56.5%) and MRI in 11/20 cases (55%). The concordance between the techniques was found to be low. CONCLUSIONS: Transrectal ultrasonography resulted as the most accurate method to determine neoplastic wall infiltration and lymph node involvement even after radiochemotherapy. In most cases, considering the poor correlation between the diagnostic procedures and the disagreement of the results, a restaging performed only with TRUS could be proposed, limiting the use of the other imaging methods to selected cases.

Inherited multitumoral syndromes including colorectal carcinoma.

Inherited multitumoral syndromes including colorectal carcinoma are the followings: familial adenomatous polyposis (FAP), hereditary non-polyposis colon cancer (HNPCC) and Peutz-Jeghers syndrome (PJS). The studies of genotype-phenotype correlation have shown that various types of colonic polyposis are related with germline mutation of adenomatous polyposis coli (APC) gene, that is also responsible for a wide number of extracolonic manifestations. Concerning severity of polyposis, it has been suggested to perform ileorectal anastomosis in patients with intermediate FAP, whereas it has been suggested to remove the rectum from the beginning and to perform ileopouch anastomosis in patients with severe FAP (germline APC mutations between codons 1250 and 1464, i.e. mutation cluster region-MCR). Concerning extracolonic manifestations, original studies from our laboratory have shown that three peculiar, even if unusual extracolonic manifestations of FAP, were in the 5' portion of the gene, but almost always outside of MCR. In particular, in some patients or in some kindreds all these manifestations may be present together. It is suggested, from one hand, because of the wide variety of genotype-phenotype correlation word of caution before selecting surgical treatment simply on the basis of the germline mutations, on the other hand co-segregation of some extracolonic manifestations could facilitate intensive screening, early diagnosis and optimal time for treatment.

Improved early morbidity and mortality after Fontan operation: the Mayo Clinic experience, 1987 to 1992.

OBJECTIVES: This study sought to evaluate changes in early morbidity and mortality as well as predictors of outcome in our most recent 339 patients undergoing modified Fontan operations. BACKGROUND: The Fontan operation is the preferred definitive palliation for patients with functional single ventricles. Previously reported early mortality rates after Fontan operation have been substantial. METHODS: Records of 339 consecutive patients who had a Fontan operation at the Mayo Clinic between 1987 and 1992 (recent cohort) were reviewed. This cohort was compared with the previous 500 patients who had Fontan operations performed between 1973 and 1986 (early cohort). RESULTS: Recently, overall early mortality after Fontan has decreased significantly compared with that for the early cohort (from 16% to 9%, p = 0.002). This decline occurred despite increased anatomic complexity of patients. Short-term posthospital survival has also improved significantly in recent patients. One-year survival improved to 88% from 79%, and 5-year survival to 81% from 73% (p = 0.006). Patients with common atrioventricular valves and those who took daily preoperative diuretic medication or had either postoperative renal failure or elevated postbypass right atrial pressure were at increased risk for early mortality. Young age was not found to be a risk factor for early mortality. Early mortality for patients with heterotaxia decreased dramatically: recent 30-day mortality was 15% compared with 41% in the early heterotaxy cohort. CONCLUSIONS: Many factors may have contributed to decreased early mortality after Fontan. Improved patient selection, younger age at time of operation, refinements in surgical techniques and postoperative management may all have had important roles. Proposed technical modifications of the Fontan operation must be evaluated in light of these improved results.

Long-term outcome in congenitally corrected transposition of the great arteries: a multi-institutional study.

OBJECTIVES: The purpose of this study was to determine long-term outcome in adults with congenitally corrected transposition of the great arteries (CCTGA), with particular emphasis on systemic ventricular dysfunction and congestive heart failure (CHF). BACKGROUND: Patients with CCTGA have the anatomical right ventricle as their systemic pumping chamber, with ventricular dysfunction and CHF being relatively common in older adults. METHODS: Retrospective analysis of records of 182 patients from 19 institutions were reviewed to determine current status and possible risk factors for systemic ventricular dysfunction and CHF. Factors considered included age, gender, associated cardiac defects, operative history, heart block, arrhythmias and tricuspid (i.e., systemic atrioventricular) regurgitation (TR). RESULTS: Both CHF and systemic ventricular dysfunction were common in groups with or without associated cardiac lesions. By age 45, 67% of patients with associated lesions had CHF, and 25% of patients without associated lesions had this complication. The rates of systemic ventricular dysfunction and CHF were higher with increasing age, the presence of significant associated cardiac lesions, history of arrhythmia, pacemaker implantation, prior surgery of any type, and particularly with tricuspid valvuloplasty or replacement. Aortic regurgitation (a previously unreported problem) was also relatively common in this patient population. CONCLUSIONS: Patients with CCTGA are increasingly subject to CHF with advancing age; this complication is extremely common by the fourth and fifth decades. Tricuspid (systemic atrioventricular) valvular regurgitation is strongly associated with RV (anatomical right ventricle connected to aorta in CCTGA patients; systemic ventricle in CCTGA) dysfunction and CHF; whether it is causative or a secondary complication remains speculative.

Thyroid carcinoma usually occurs in patients with familial adenomatous polyposis in the absence of biallelic inactivation of the adenomatous polyposis coli gene.

Papillary thyroid carcinoma (PTC) is a rare extracolonic manifestation of familial adenomatous polyposis, determined by germline mutations of the adenomatous polyposis coli (APC) gene. The aim of this study was to assess the presence of loss of heterozygosity of APC in the thyroid tumoral tissue. Specimens from six female patients, aged 20-36, were analyzed for germline and somatic mutations of the APC gene by restriction enzyme analysis and sequence analysis. Five of the six also had analysis for ret/PTC, a chimeric gene, the activation of which is restricted to papillary TC. Because a previous study showed that germline mutations in familial adenomatous polyposis-associated thyroid carcinoma were located between codons 140 and 1513, the search for somatic mutations of the APC gene was restricted to this genomic area. Three of the six patients, belonging to the same kindred, had a germline mutation at codon 1061. The remaining three, one per kindred, had germline mutations at codons 1061, 1061, and 1309, respectively. None of the six patients had loss of heterozygosity for APC or somatic mutation in the explored genomic area (codon 545 and codons 1061-1678). Four of five had activation of ret/PTC in the thyroid tumoral tissue, as ret/PTC1 isoform. Either APC has a tissue-specific dominant effect in the thyroid gland or the germline mutation confers a generic susceptibility to cancer development, but other factors (sex-related factors, environmental radiation, modifier genes) are also required for TC development. This usually involves ret/PTC activation, suggesting a possible cooperation between altered function of APC and gain of function of ret.

Germline mutations of the APC gene in patients with familial adenomatous polyposis-associated thyroid carcinoma: results from a European cooperative study.

Papillary thyroid carcinoma (PTC) is one extracolonic manifestation affecting about 1-2% of patients with familial adenomatous polyposis (FAP). Ninety-seven patients with FAP-associated PTC have previously been reported, including 6 pairs of siblings. During a European collaborative study, 15 patients with FAP-associated PTC were collected. All 15 patients were females. The mean age at thyroidectomy was 24.9 yr (range, 19-39 yr). In 13 subjects, APC germline mutations had been detected; they were at codons 140, 593, 778, 976, 993, 1061 (n = 5), 1105 (n = 1), and 1309 (n = 2), respectively. A review of the literature added 11 other patients with FAP-associated PTC and detection of germline APC mutations; they were at codons 313 (n = 2), 698 (n = 3), 848 (n = 2), 1209 (n = 2), 1061 (n = 1), and 1105 (n = 1), respectively. The latter led to formation of the same stop codon (TAA) at 1125-1126 as the mutation at codon 1061. Therefore, 21 of 24 mutations were in exon 15 in the genomic area usually associated with congenital hypertrophy of the retinal pigment epithelium (CHRPE), i.e. codons 463-1387. Typical CHRPE was found in 17 of 18 affected patients who had specific screening. Interestingly, 22 of the 24 patients had their mutation out of the mutation cluster region (codons 1286-1513), which is currently considered the hot spot mutation area, in particular for extracolonic manifestations of FAP. The difference in the incidence of germline mutations before and after codon 1220 between PTC and non-PTC FAP patients was statistically significant (P<0.05) for both patients and kindreds (P = 0.005 and P = 0.049, respectively). Even if most mutations were scattered throughout the entire 5'-portion of exon 15, 8 of 23 patients (6 with mutation at 1061 and 2 with mutation at 1105; i.e. more than one third) had the same truncated protein product. The awareness that patients with PTC usually have APC mutations that cluster in a well defined genomic area, in addition to giving a deeper insight into gene function, could facilitate both earlier diagnosis and better treatment. In particular, intensive screening for thyroid nodules after age 15 yr is recommended when a single patient or an entire kindred have CHRPE and/or mutations in the 5'-portion of exon 15.

The ret/ptc1 oncogene is activated in familial adenomatous polyposis-associated thyroid papillary carcinomas.

Familial adenomatous polyposis (FAP) is caused by germ-line mutations of the apc gene, and it is associated with an increased risk of developing papillary thyroid carcinomas. We have previously reported that a significant fraction of sporadic human papillary thyroid carcinomas is characterized by gene rearrangements affecting the ret protooncogene. These rearrangements generate chimeric transforming oncogenes designated ret/ptc. By a combined immunohistochemical and RT-PCR approach, we analyzed, for ret/ptc oncogene activation, papillary thyroid carcinomas occurred in two FAP kindreds, both showing typical apc gene mutations. Kindred 1 had seven members affected by FAP, and among these, three patients showed papillary thyroid carcinomas. Kindred 2 had two patients, mother and daughter, affected by colonic polyposis; the 20-yr-old daughter showed also a papillary carcinoma. Here we report that ret/ptc1 oncogene was activated in two of the three papillary carcinomas of FAP kindred 1 and in the papillary carcinoma of FAP kindred 2. These findings document that loss of function of apc coexists with gain of function of ret in some papillary thyroid carcinomas, suggesting that ret/ptc1 oncogene activation could be a progression step in the development of FAP-associated thyroid tumors.

Cost-effectiveness of transaxillary muscle-sparing same-day operative closure of patent ductus arteriosus.

Transaxillary muscle-sparing patent ductus arteriosus closure performed as same-day surgery is described in 10 patients. This approach provides a superb cosmetic result while obviating the need for thoracostomy tube placement.

Adults with congenital heart disease: patient knowledge of endocarditis prophylaxis.

OBJECTIVE: To determine whether adults with congenital heart disease have adequate knowledge of infective endocarditis and endocarditis prophylaxis and to ascertain whether an educational program effectively improves patient knowledge and compliance. MATERIAL AND METHODS: We asked 102 consecutive patients to complete a 12-question survey to assess their knowledge of heart disease, infective endocarditis, and endocarditis prophylaxis. RESULTS: Of 102 patients, 100 (98%) completed the questionnaire. Sixty-eight patients knew the name of their heart disease. Fifty patients correctly defined endocarditis, but only 43 knew hygiene measures that could prevent endocarditis. Ninety-six patients knew that they needed to take "a medicine" before dental procedures, and 76 of those patients (79%) knew that an antibiotic was necessary. Patient use of cardiac medications and a history of endocarditis correlated significantly with knowledge of endocarditis. Patients who had been to the Adult Congenital Heart Disease Clinic at least once knew endocarditis prevention measures and the importance of regular dental and cardiology follow-up significantly more frequently than did first-time attendees. Despite educational counseling, however, patient recall of endocarditis and its prevention is disappointing. CONCLUSION: Many adults with congenital heart disease have inadequate knowledge of their cardiac lesion, endocarditis, and endocarditis prophylaxis. Educational efforts for adults with congenital heart disease need to be updated and reinforced regularly.

Use of intravascular stents for superior vena caval obstruction after the Mustard operation.

Obstruction of the systemic venous pathway is a complication in patients who have undergone the Mustard operation for complete transposition of the great arteries. In this report, we discuss intravascular stent placement in three patients for relief of superior vena caval obstruction after the Mustard operation. The clinical history, cardiac catheterization data, and echocardiographic data before and after stent placement are presented for each patient. Overall, four stents were placed. The mean gradients from the superior vena cava to the right atrium before stent placement were 10, 8, and 6 mm Hg, and they decreased to 3, 0, and 1 mm Hg immediately after stent placement. No complications occurred. Doppler echocardiographic assessment of mean gradients before and after stent placement correlated with the mean gradients determined by cardiac catheterization. Intravascular stent placement is effective for relief of baffle obstruction after the Mustard operation. Serial Doppler assessments of the gradient across the stent offer a noninvasive method for follow-up of these patients.

Anatomic correction of dextrotransposition of the great arteries in a 36-year-old patient.

During the 1960s, the Mustard or Senning operation was the conventional palliative therapy for patients with transposition of the great arteries. Many of these patients are now adults, and the durability of the morphologic right ventricle to function as the systemic ventricle is being questioned. Surgical options for such adult patients have traditionally been limited to cardiac transplantation. More recently, an arterial switch operation with take-down of the Mustard or Senning baffles has been reported. Herein we describe the clinical course of a 36-year-old woman who underwent a successful single-stage Mustard take-down, atrial reconstruction, and arterial switch operation.

Idiopathic restrictive cardiomyopathy in childhood: diagnostic features and clinical course.

OBJECTIVE: To describe the clinical course and outcome of children with idiopathic restrictive cardiomyopathy (IRCM) and to present the Doppler echocardiographic features of this disease in childhood. DESIGN: We reviewed the Mayo Clinic patient database for the period from 1975 to 1993 to identify children who underwent assessment for IRCM. MATERIAL AND METHODS: Clinical records and diagnostic studies, including two-dimensional (2-D), M-mode, and Doppler echocardiograms, were reviewed for each patient. Characteristics were analyzed statistically to determine potential predictors of outcome. RESULTS: Eight children (five girls and three boys) were diagnosed with IRCM between 1975 and 1993 at our institution. The median age at diagnosis was 11 years, and the median duration of follow-up was 11.5 years. Of the eight patients, five died (the median time from initial examination to death was 1 year). All five of these patients had clinical and radiographic evidence of pulmonary venous congestion. In all patients, 2-D and M-mode echocardiography revealed atrial enlargement without ventricular dilatation or hypertrophy. The four patients who underwent detailed diastolic Doppler assessment had findings consistent with restrictive filling and increased left ventricular end-diastolic pressure: (1) short mitral deceleration time, (2) increased pulmonary vein atrial reversal velocity and duration, and (3) pulmonary vein atrial reversal duration greater than mitral A-wave duration. CONCLUSION: The prognosis for children with IRCM is poor. In this small group of patients, absence of pulmonary venous congestion most consistently predicted extended survival. A combined 2-D and Doppler echocardiographic examination provides a reliable noninvasive means of assessing the physiologic and morphologic features of IRCM in children.

Do surgical and endoscopic sphincterotomy prevent or facilitate recurrent common duct stone formation?

The possible formation of brown recurrent common duct stones (RCS) as a long-term side effect of sphincterotomy (SPHT) has been evaluated in 63 patients with stone formation after cholecystectomy, 253 who underwent SPHT or choledocholithotomy, 131 with postoperative monitoring of bile bacteriologic characteristics through the T tube, and 20 with stone and bile analysis at both operations. In addition, findings are also reported in 145 patients who underwent surgical SPHT and radiologic review of up to 28 years after surgery, five who underwent ampullectomy, and 55 who underwent endoscopic SPHT. The RCS were usually brown (72.5% of cases), and were always associated with bile infection caused by Escherichia coli. Sixty-two percent of brown RCS were found after SPHT. Eleven percent of patients who underwent surgical SPHT, 9% who underwent endoscopic SPHT, and 66.6% who underwent ampullectomies had brown RCS. Sphincterotomy determined a fivefold greater incidence of postoperative bactibilia, and a seven-fold greater incidence of brown RCS, than did choledocholithotomy. It is suggested that: (1) since brown RCS are secondary to bile contamination from the duodenum, SPHT (and subsequent stricture), facilitating both bile contamination and bacterial overgrowth, could be considered a basic factor in the formation of these stones; and (2) since true RCS are mostly of the brown subtype, SPHT could prevent the occurrence of retained stones by flushing the stones that were missed during the first operation, but undoubtedly increases the total incidence of RCS.

Anomalous right coronary artery from the pulmonary artery in Taussig-Bing anomaly.

The presence of associated anomalies in patients with double-outlet right ventricle can significantly alter surgical intervention. Preoperative delineation of these anomalies can facilitate surgical planning and improve outcome. We describe a case in which the right coronary artery and anterior descending coronary artery arose from the pulmonary artery in a patient with double-outlet right ventricle with subpulmonary ventricular septal defect (Taussig-Bing anomaly). Recognition of this important anomaly prevented significant intraoperative myocardial damage by altering techniques of cardioplegia administration for myocardial preservation.

Intraatrial mitral valve insertion with native valve preservation in children.

Two patients underwent intraatrial mitral valve insertion for an unsuccessful valvotomy for severe mitral stenosis and left-sided atrioventricular valve insufficiency associated with corrected transposition utilizing a porcine valve from a valved conduit with preservation of the native valve. The valves were inserted using continuous suture distally at the mitral annulus and proximally at the pulled atrial wall distal to the pulmonary veins. Both patients had uneventful hospital course and are doing well at up to 6 months postoperatively. This approach provides a viable option for congenital mitral stenosis or insufficiency in children.

Recognition and management of obstructed pulmonary veins draining to the coronary sinus.

BACKGROUND: Obstruction of the pulmonary veins in total anomalous pulmonary venous drainage to the coronary sinus is generally considered rare. However, if it is present, the usual treatment of unroofing the coronary sinus will lead to a poor result. METHODS: Four patients with total anomalous pulmonary venous drainage to the coronary sinus with obstruction were identified over a 14-month period. Three patients in whom the diagnosis of obstruction was not made underwent coronary sinus unroofing. Retrospective review of the preoperative echocardiograms and Doppler studies showed the presence of obstruction in the vertical vein in 2 patients and in the branches in the other. In the fourth patient, obstruction in the vertical vein was recognized preoperatively with echocardiography and Doppler study. This patient underwent direct common pulmonary vein-left atrial anastomosis. RESULTS: All 3 patients who had coronary unroofing were seen with obstructed pulmonary veins 2 to 7 months postoperatively. After reoperation, 1 died, and the other 2 have done relatively well 3 1/2 and 15 months postoperatively. The patient who had an anastomosis between the common pulmonary vein and the left atrium is doing well 18 months postoperatively. CONCLUSIONS: Obstruction in total anomalous pulmonary venous drainage to the coronary sinus is not as rare as previously reported. To improve outcome, its presence should be sought using complete echocardiography including Doppler studies. When obstruction is present, transection of the vertical vein and common pulmonary vein-left atrial anastomosis through the superior approach is an attractive technique that also eliminates the right-to-left shunting associated with coronary sinus unroofing and simplifies closure of the atrial septal defect.