Laparoscopic Adjustable Banded Sleeve Gastrectomy as a Primary Procedure for the Super-Super Obese (Body Mass Index > 60 kg/m<Superscript>2</Superscript>)

Isolated laparoscopic sleeve gastrectomy is increasingly being used for the treatment of morbid obesity. However, doubts still persist regarding long-term weight loss, and the 5-year results are awaited. Whether the aetiology of failed excess weight loss is the result of an inadequate sleeve or attributable to dilatation of the sleeve is not clear. In an effort to prevent gastric dilatation and increase gastric restriction to promote further weight loss in the long term, we performed a combined procedure of laparoscopic adjustable gastric banding with sleeve gastrectomy. The patient was a 39-year-old woman with a life-long history of obesity and a body mass index of 79.8 kg/m². The surgical technique of the laparoscopic adjustable gastric banded sleeve gastrectomy is described. There were no immediate complications, and the patient was discharged home on the third postoperative day. She is doing extremely well on clinic follow-up at 6 weeks. To the best of our knowledge, laparoscopic adjustable gastric banded sleeve gastrectomy, as a primary operation, has not been described in the literature. It is hoped that this combined procedure will be most useful in the super-super obese (body mass index > 60) patients. More patients with a long-term follow-up are necessary to provide definitive conclusions regarding long-term benefits and complications of this combined bariatric procedure.     

Combined Risk Allele Score of Eight Type 2 Diabetes Genes Is Associated With Reduced First-Phase Glucose-Stimulated Insulin Secretion During Hyperglycemic Clamps

OBJECTIVE

At least 20 type 2 diabetes loci have now been identified, and several of these are associated with altered β-cell function. In this study, we have investigated the combined effects of eight known β-cell loci on insulin secretion stimulated by three different secretagogues during hyperglycemic clamps.

RESEARCH DESIGN AND METHODS

A total of 447 subjects originating from four independent studies in the Netherlands and Germany (256 with normal glucose tolerance [NGT]/191 with impaired glucose tolerance [IGT]) underwent a hyperglycemic clamp. A subset had an extended clamp with additional glucagon-like peptide (GLP)-1 and arginine (n = 224). We next genotyped single nucleotide polymorphisms in TCF7L2, KCNJ11, CDKAL1, IGF2BP2, HHEX/IDE, CDKN2A/B, SLC30A8, and MTNR1B and calculated a risk allele score by risk allele counting.

RESULTS

The risk allele score was associated with lower first-phase glucose-stimulated insulin secretion (GSIS) (P = 7.1 × 10⁻⁶). The effect size was equal in subjects with NGT and IGT. We also noted an inverse correlation with the disposition index (P = 1.6 × 10⁻³). When we stratified the study population according to the number of risk alleles into three groups, those with a medium- or high-risk allele score had 9 and 23% lower first-phase GSIS. Second-phase GSIS, insulin sensitivity index and GLP-1, or arginine-stimulated insulin release were not significantly different.

CONCLUSIONS

A combined risk allele score for eight known β-cell genes is associated with the rapid first-phase GSIS and the disposition index. The slower second-phase GSIS, GLP-1, and arginine-stimulated insulin secretion are not associated, suggesting that especially processes involved in rapid granule recruitment and exocytosis are affected in the majority of risk loci.Type 2 diabetes is a polygenic disease in which the contribution of a number of detrimental gene variants in combination with environmental factors is thought to be necessary for the development of disease. In the past 2 years, results of several genome-wide association studies (GWASs) have been published (1–5), leading to a rapidly increasing number of detrimental type 2 diabetes susceptibility loci. More recently, it has indeed been shown that combining information from these diabetes loci into a risk allele score for all loci enhances diabetes risk (6–9). However, the predictive power of this combined risk allele score is yet insufficient to substitute or largely improve predictive power of known clinical risk factors (8,9). At present, little is known about how these gene variants in combination affect insulin secretion or insulin resistance. Based on recent data, mainly obtained from oral glucose tolerance tests (OGTTs), it was shown that a combined risk allele score from gene variants associated with type 2 diabetes is associated with insulin secretion and not with insulin sensitivity (10–13). However, the OGTT is unable to distinguish between first- and second-phase insulin secretion. Furthermore, other secretagogues, like glucagon-like peptide (GLP)-1 and arginine, were not included in these studies.It is thought that the rapid recruitment and release of insulin granules from the readily releasable pool (RRP) is responsible for the first phase of insulin secretion, whereas the slower prolonged second phase involves recruitment to the membrane of more distant granules and de novo insulin synthesis. Although the exact pathways regulating both phases of glucose-stimulated insulin secretion (GSIS) are not completely resolved, it seems logical that they are at least in part different. This is further corroborated by our recent observation that the heritability for both phases of GSIS in twins is derived from partly nonoverlapping sets of genes (13a).Also, other nonglucose, stimuli-like incretins and amino acids can evoke an insulin response. Detailed phenotypic investigations of the response to these different stimuli may help to elucidate which processes are primarily affected by these loci. Previously, we have already shown that type 2 diabetes genes/loci can have different effects on first- and second-phase GSIS, as measured using hyperglycemic clamps. Also, based on the method of stimulation (i.e., oral versus intravenous), the outcome may differ substantially (14–17), which provides further clues about the mechanism by which they affect insulin secretion.In this study, we genotyped gene variants in TCF7L2, KCNJ11, HHEX/IDE, CDKAL1, IGF2BP2, SLC30A8, CDKN2A/CDKN2B, and MTNR1B in 447 hyperglycemic clamped subjects (256 with normal glucose tolerance [NGT] and 191 with impaired glucose tolerance [IGT]) from four independent studies in the Netherlands and Germany. These eight loci were chosen based on the fact that they were reproducibly associated with β-cell function in various studies (rev. in 18,19). A combined risk allele score of all eight gene variants was calculated for each individual and tested against the various detailed measurements of β-cell function using the hyperglycemic clamp, generally considered to be the gold standard for quantification of first- and second-phase GSIS (20). Furthermore, we also assessed the combined effect of these eight genes on two other stimuli, GLP-1 and arginine-stimulated insulin secretion during hyperglycemia, in a subset of the study sample (n = 224). The latter test provides an estimation of the maximal insulin secretion capacity of a subject and may, according to animal studies, serve as a proxy for β-cell mass (21).     

Neoadjuvant Chemoradiation Versus Hyperfractionated Accelerated Radiotherapy in Locally Advanced Rectal Cancer

Background Neoadjuvant therapy is increasingly used in resectable locally advanced rectal cancer. The exact role of the addition of chemotherapy is not established. We compared neoadjuvant therapy using chemoradiation (CRT) or hyperfractionated accelerated radiotherapy (HART). Methods Clinical, pathological, and survival data were obtained from patients with resectable stage II or III rectal cancer within 7 cm from the anal verge. A group of 50 patients was treated with a preoperative dose of 41.6 Gy of radiotherapy (RT) in two daily fractions of 1.6 Gy over 13 days immediately followed by surgery (HART). A second group of 96 patients received 45 Gy of conventionally fractionated RT in 25 daily fractions of 1.8 Gy combined with 5-fluorouracil–based chemotherapy followed by surgery within 4 to 6 weeks (CRT). Both groups were compared in terms of morbidity, pathological downstaging, local recurrence, and survival. Results Both groups were comparable in terms of preoperative clinicopathological variables. The mean distance from the anal verge was 5.8 cm (HART) versus 4.9 cm (CRT). Sphincter preservation was possible in 74% (HART) versus 83.5% (CRT) of patients (P = .013). The clinical anastomotic leak rate was 2% (HART) versus 2.2% (CRT). Pathological complete response was observed in 4% (HART) versus 18% (CRT) of the resected specimens (P = .002). A pelvic recurrence developed in 6% (HART) versus 4.4% (CRT) of patients (P = .98). Overall 5-year survival was 58% (HART) versus 66% (CRT) (P = .19); disease-free 5-year survival was 51% (HART) versus 62% (CRT) (P = .037). Conclusions Compared with preoperative HART followed by immediate surgery, preoperative CRT followed by a 6-week waiting period enhances pathological response and increases sphincter preservation rate. This could be explained by the addition of chemotherapy or the longer interval between neoadjuvant therapy and surgery. No statistically significant difference was observed in local control or overall survival.     

Bicuspid pulmonary valve with atrial septal defect leading to pulmonary aneurysm

Pulmonary artery aneurysms are rare. We describe 2 adult patients with pulmonary artery aneurysm with normal pulmonary pressure associated with bicuspid pulmonary valve and atrial septal defect. One patient presented with moderate pulmonary valve stenosis and was treated with open surgery; the other patient had a small atrial septal defect and mild pulmonary valve insufficiency and is periodically still being evaluated. Hemodynamic alterations associated with a pulmonary artery aneurysm are described; the influence of additional volume overload and intrinsic wall abnormalities in pulmonary valvular lesions as potential triggers for the development of these aneurysms are analyzed and therapeutic strategies are discussed.     

alpha-Galactosidase A deficiency in Dutch patients on dialysis: a critical appraisal of screening for Fabry disease.

INTRODUCTION: Fabry disease or alpha-galactosidase A (alpha-Gal A) deficiency is an X-linked lysosomal storage disorder that often leads to renal insufficiency in males and occasionally in females. The disease is rare, but its prevalence may be underestimated due to its variable clinical picture. Enzyme supplementation therapy with rHu-alphaGal A is currently available. Limited experience has so far shown that therapy may at best stabilize renal function. Despite these preliminary findings, much effort is being put into screening high-risk groups for undiagnosed alpha-Gal A deficiency. We studied the prevalence of alpha-Gal A deficiency in a Dutch dialysis cohort to establish possible underdiagnosis. We discuss the benefits of screening for Fabry disease. METHODS: Activity of alpha-Gal A in whole blood was measured in a group of 508 male Dutch dialysis patients. RESULTS: Of the 508 patients studied only one patient, already known with Fabry disease, had a alpha-Gal A deficiency, a prevalence of 0.22% (95 CI 0-1.1%). CONCLUSIONS: No undiagnosed Fabry patients were found, indicating that in our studied cohort there is no large-scale underestimation of its prevalence. Even though screening of dialysis patients for Fabry disease might identify patients who remain otherwise unrecognized, screening of high-risk populations for alpha-Gal A deficiency should be carried out with caution since long-term efficacy of treatment is currently unknown.     

Impact of several histopathological prognosticators and local tumour extension on oncological outcome in pT3b/c N0M0 renal cell carcinoma

OBJECTIVE

To investigate the prognostic relevance of different histopathological features and local tumour extension in patients with pT3b/c N0M0 renal cell carcinoma (RCC), as recently new proposals of reclassifying tumour fat invasion in pT3b/c RCC have been made but the effect of other histopathological tumour characteristics and combinations thereof with tumour invasion has yet to be determined in these patients.

PATIENTS AND METHODS

Between 1990 and 2006, 1943 patients underwent surgical treatment for renal tumours in our institution, of which 175 patients (8.7%) had pT3b/c RCC. After exclusion of 57 patients (32.6%) with lymph node and/or distant metastases at the time of diagnosis, 118 (67.4%) remained for retrospective analysis. Different histopathological features and local tumour extension were studied for their association with cancer‐specific‐survival (CSS) and progression‐free‐survival (PFS) by univariate and multivariate analyses. Histopathology was reviewed and revised according to the 2002 Tumour‐Nodes‐Metastasis (TNM) classification system by one pathologist (S.B.). CSS and PFS were estimated by the Kaplan–Meier method.

RESULTS

Follow‐up data were obtained from 110 patients at a median (range) of 3.2 (0.3–16.1) years. In univariate analysis, microvascular invasion (MVI) and capsular invasion increased the risk of tumour progression by 2.05‐ and 2.72‐times (P = 0.037 and P < 0.001). Overall, tumour fat invasion (TFI) and the presence of areas composed by cells with eosinophilic cytoplasm were associated with a higher risk of progression (P = 0.001 and P = 0.011) and reduced CSS (P = 0.037 and P = 0.017). In multivariate analysis, MVI and capsular invasion were associated with a two‐fold increased risk of dying from cancer (hazard risk ratio, HR 2.22, P = 0.045 and HR 2.31, P = 0.011). TFI in general (P = 0.004) and specifically coexistent perirenal fat invasion (PFI) and renal sinus fat invasion (RSFI) were associated with a three‐fold increased risk of developing tumour progression (HR 3.36, P = 0.001). The 10‐year CSS and PFS rates were 39% and 36% for all patients, 47% and 45% for pT3b/c RCC with no PFI or RSFI, and 25% and 10% for PFI + RSFI.

CONCLUSION

Patients with pT3b/c RCC with MVI, capsular invasion, TFI and especially PFI + RSFI, have a markedly reduced prognosis compared with patients with pT3b/c RCC without these features. When these results are corroborated by additional studies and external validation, modification of the TNM classification system would be a sensible consequence.     

Preservation of Muscular and Elastic Artery Distensibility After an Intercontinental Cryoconserved Exchange: Theoretical Advances in Arterial Homograft Generation and Utilization

While the situation of tissue donation and transplantation differs between Latin American and European countries, a common problem is tissue deficiency. Hence, at present, there is a pressing need to generate alternatives so as to increase the possibilities of obtaining the requested materials. Consequently, it would be of significant interest to establish an intercontinental network for tissue exchange, to improve international cooperation, and to help patients that need tissue transplantation, and to evaluate the feasibility of using an intercontinental network for the exchange of cryopreserved arteries (cryografts), preserving the arterial distensibility and ensuring a reduced native artery–cryograft biomechanical mismatch. Distensibility was studied in ovine arteries divided into three groups: intact (in vivo tests, conscious animals), fresh control (in vitro tests immediately after the artery excision, Uruguay), and cryografts (in vitro tests of cryopreserved-transported-defrosted arteries, Spain). Histological studies were performed so as to analyze changes in the endothelial layer and elastic components. The comparison between fresh control and cryografts showed that neither the cryopreservation nor the exchange network impaired the distensibility, despite the expected histological changes found in the cryografts. The comparison between intact and cryografts showed that the cryografts would be capable of ensuring a reduced biomechanical mismatch. The cryopreservation and the intercontinental network designed for artery exchange preserved the arterial distensibility. It could be possible to transfer cryografts between Latin America and Europe to be used in cardiovascular surgeries and/or for tissue banking reprocessing, with basic biomechanical properties similar to those of the fresh and/or native arteries.