Protective Role of the Portocaval Shunt in Liver Transplantation.

BACKGROUND: Advances in medical management and surgical technique have resulted in stepwise improvements in early post-transplant survival rates. Modifications in the surgical technique, such as the realization of the portocaval shunt (PCS), could influence survival rates. The aim of this study was to evaluate the mortality rate for 12 months after liver transplantation, analyzing the causes and risk factors related to its development and assessing the impact that PCS could have on them. METHODS: A total of 231 recipients were included in the retrospective, longitudinal, and nonrandomized study. RESULTS: The overall survival of the transplant was 85.2% (197 patients). The most frequent cause of death was infection (38.2%), followed by the multiorgan failure of multiple etiology (23.5%). Most of the risk factors related to mortality correspond to variables of the postoperative period. The results of the multivariate analysis identified the main risk factors for death: the presence of surgical complications and the need for renal replacement therapy. In contrast, the performance of PCS exerted a protective effect, reducing the probability of death by 70%. CONCLUSIONS: Despite the good results obtained in several studies, there is still debate regarding the benefit of its realization. In our study, PCS was a factor associated with a reduction in mortality, with a markedly lower probability of adverse events. However, we agree with other authors on the need for larger and randomized studies to adequately determine the validity of such results.

Luschka Duct Leak: An Unexpected Cause of Choleperitoneum After Liver Transplant.

The anatomic variabilities in ducts of Luschka put patients at risk during hepatobiliary surgery. Clinically relevant bile leakage is the cause of 0.4% to 1.2% of complications of cholecystectomies, with almost one-third of complications caused by an inadvertent injury to the duct of Luschka. However, bile leakage from a duct of Luschka after liver transplant is rare, and only one previously published report has been found. Here, we report a case of a 67-year-old male patient who underwent liver transplant for cirrhosis due to hepatitis C virus infection. After transplant, the patient had a choleperitoneum caused by bile leakage from a duct of Luschka. The donor surgery had been performed by surgeons from another institution, and they had also performed the previous cholecystectomy. Fifteen days after surgery, a cholangiography showed bile leakage near the anastomosis. A new intervention was decided. After confirmation of the integrity of the anastomosis, methylene blue was injected through the Kehr's tube, which escaped from a duct of Luschka. The duct was closed, and an intraoperative cholangiography confirmed that the biliary tree was intact. After this intervention, a new bile leakage was observed, resulting in an endoscopic retrograde cholangiopancreatography scan and sphincterotomy. The Kehr's tube was kept open until leak resolution. Although unusual after liver transplant, this complication should be considered in cases of bile leakage. The ducts of Luschka are difficult to see during cholecystectomy in the graft due to perivesicular edema.

Sinosanal undifferentiated carcinoma with liver metastasis: surgical management.

BACKGROUND: Sinonasal undifferentiated carcinoma (SNUC) is a rare tumor with poor prognosis and high incidence of distant metastasis, even when a good loco-regional control is achieved. CASE: We report the case of a 43-year-old female with SNUC diagnosis. Craniofacial resection with orbital exenteration and radiotherapy in tumor bed and lymph node chain was performed. After 10 months, SNUC hepatic relapse (sIII and sVIII) is diagnosed. We administered chemotherapy and then, surgical resection was carried out. After surgery, two new relapses were diagnosed, at 9 and 21 months where surgical management was performed in both cases. 56 months after SNUC diagnosis, the patient has no evidence of recurrence. DISCUSSION: Recommended oncological clinical guidelines for distant metastases in SNUC are chemotherapy. Surgical management in oligometastatic disease in SNUC should be considered.

Serum Bioavailable Vitamin D Concentrations and Bone Mineral Density in Women After Obesity Surgery.

INTRODUCTION: Low bone mass after obesity surgery may arise as a consequence of chronic malabsorption of calcium and vitamin D. However, we have not found any role of serum 25-hydroxyvitamin D or of polymorphisms in the vitamin D receptor gene in previous studies. PURPOSE: To investigate the circulating bioavailable 25-hydroxyvitamin D in women after bariatric procedures and its association with bone mass. PATIENTS AND METHODS: The study consisted of 91 women on follow-up for 7 ± 2 years after bariatric surgery. We measured bone mineral density (BMD), serum parathormone (PTH), 25-hydroxyvitamin D, and vitamin D binding protein (VDBP). All patients were genotyped for two variants in the coding region of VDBP (rs4588 and rs7041). Bioavailable 25-hydroxyvitamin D was calculated in double homozygotes. RESULTS: We found a negative correlation between bioavailable 25-hydroxyvitamin D and PTH (r = -0.373, P = 0.018), but not with BMD at lumbar spine (r = -0.065, P = 0.682) or hip (r = -0.029, P = 0.857). When adjusting by age, similar results were found for PTH (r = -0.441, P = 0.005), BMD at lumbar spine (r = -0.026, P = 0.874) and hip (r = -0.096, P = 0.561). After multivariate linear regression, forcing bioavailable 25-hydroxyvitamin D into the model resulted in a weak significant association with BMD at the lumbar spine (ß = - 0.247, P = 0.025). CONCLUSIONS: Serum bioavailable 25-hydroxyvitamin D concentrations are not associated with bone mass loss after bariatric surgery in women. The negative association with serum PTH levels suggests that vitamin D supplementation partly improves secondary hyperparathyroidism, yet other mechanisms may contribute to low bone mass after bariatric surgery.

The role of serum osteoprotegerin and receptor-activator of nuclear factor-κB ligand in metabolic bone disease of women after obesity surgery.

Metabolic bone disease may appear as a complication of obesity surgery. Because an imbalance in the osteoprotegerin and receptor-activator of nuclear factor-κB ligand system may underlie osteoporosis, we aimed to study this system in humans in the metabolic bone disease occurring after obesity surgery. In this study we included sixty women with a mean age of 47 ± 10 years studied 7 ± 2 years after bariatric surgery. The variables studied were bone mineral density, ß-isomer of C-terminal telopeptide of type I collagen cross-links (a bone resorption marker), the bone formation markers osteocalcin and N-terminal propeptide of procollagen 1, serum osteoprotegerin and receptor-activator of nuclear factor-κB ligand. Serum osteoprotegerin inversely correlated with the bone remodeling markers osteocalcin, ß-isomer of C-terminal telopeptide of type I collagen cross-links and N-terminal propeptide of procollagen 1. The osteoprotegerin and receptor-activator of nuclear factor-κB ligand ratio also correlated inversely with serum parathormone and osteocalcin. Bone mineral density at the lumbar spine was associated with age (ß = -0.235, P = 0.046), percentage of weight loss (ß = 0.421, P = 0.001) and osteoprotegerin and receptor-activator of nuclear factor-κB ligand ratio (ß = 0.259, P = 0.029) in stepwise multivariate analysis (R 2 = 0.29, F = 7.49, P < 0.001). Bone mineral density at the hip site was associated only with percentage of weight loss (ß = 0.464, P < 0.001) in stepwise multivariate regression (R 2 = 0.21, F = 15.1, P < 0.001). These data show that the osteoprotegerin and receptor-activator of nuclear factor-κB ligand system is associated with bone markers and bone mineral density at the lumbar spine after obesity surgery.

Effects of bariatric surgery on male obesity-associated secondary hypogonadism: comparison of laparoscopic gastric bypass with restrictive procedures.

Bariatric surgery results in the complete resolution of male obesity-associated secondary hypogonadism (MOSH) in many patients. However, the effects of different bariatric surgical procedures on male sexual hormone profiles and sexual dysfunction have not been compared to date. We compared the pre- and post-operative (at least 6 months after initial surgery) sex hormone profiles of 20 severely obese men submitted to laparoscopic gastric bypass (LGB) with 15 similar patients submitted to restrictive techniques (sleeve gastrectomy in 10 and adjustable gastric banding in 5). We calculated free testosterone (FT) levels from total testosterone (TT) and sex hormone binding globulin (SHBG) concentrations. Fasting glucose and insulin levels served for homeostatic model assessment of insulin resistance (HOMAIR). MOSH was present in 25 and 16 of the 35 patients when considering TT and FT concentrations respectively, resolving after surgery in all but one of them. When considering all obese men as a whole, patients submitted to LGB or restrictive procedures did not differ in terms of excess weight loss, in the decrease of fasting glucose and insulin, HOMAIR and waist circumference, or in the increase of serum 25-hydroxyvitamin D, TT and FT levels. The improvement in TT correlated with the decrease in fasting glucose (r = -0.390, P = 0.021), insulin (r = -0.425, P = 0.015) and HOMAIR (r = -0.380, P = 0.029), and with the increase in SHBG (r = 0.692, P < 0.001). The increase in FT correlated with the decrease in fasting glucose (r = -0.360, P = 0.034). LGB and restrictive techniques are equally effective in producing a remission of MOSH.

Copper and zinc serum levels after derivative bariatric surgery: differences between Roux-en-Y Gastric bypass and biliopancreatic diversion.

BACKGROUND: There are limited data on the prevalence of copper and zinc deficiency in the long term after bariatric surgery. METHODS: We analysed copper and zinc serum levels in a cohort of 141 patients, 52 who underwent Roux-en-Y gastric bypass (RYGB) and 89 biliopancreatic diversion (BPD), with a follow-up of 5 years. RESULTS: Mean copper level was significantly lower in the BPD group (P < 0.0001 vs. RYGB). Forty-five (50.6%) BPD patients had, at least once, a low copper level, and half of them, 27 (30.3%) patients, had repeatedly low levels. In this group, serum copper level correlated positively with total leukocyte and granulocyte count (r = 0.14, P = 0.002, and r = 0.17, P < 0.001, respectively). However, no patient had clinical evidence of haematological or neurological disorders. Only two RYGB patients (3.8%) had copper deficiency. Mean zinc level was also significantly lower in the BPD group (P < 0.0001). All but one BPD patient had hypozincaemia at least once, and the percentage of patients with hypozincaemia ranged from 44.9% to 74.2%. In RYGB patients, zinc deficiency peaked at 48 and 60 months (15.4% and 21.2%, respectively). The zinc level was determined by the alimentary limb length in this group, but the common channel length had no influence on copper and zinc levels in the BPD group. CONCLUSIONS: Hypocupremia, and especially hypozincaemia, are frequent findings in BPD patients, but rarely found in patients who underwent RYGB, particularly short RYGB. Our data also suggest that a long-standing and severe hypocupremia is required to develop neurological and haematological disorders after bariatric surgery.

Gene expression profiling of subcutaneous adipose tissue in morbid obesity using a focused microarray: distinct expression of cell-cycle- and differentiation-related genes.

BACKGROUND: Obesity results from an imbalance between food intake and energy expenditure, which leads to an excess of adipose tissue. The excess of adipose tissue and adipocyte dysfunction associated with obesity are linked to the abnormal regulation of adipogenesis. The objective of this study was to analyze the expression profile of cell-cycle- and lipid-metabolism-related genes of adipose tissue in morbid obesity. METHODS: We used a custom-made focused cDNA microarray to determine the adipose tissue mRNA expression profile. Gene expression of subcutaneous abdominal fat samples from 15 morbidly obese women was compared with subcutaneous fat samples from 10 nonobese control patients. The findings were validated in an independent population of 31 obese women and 9 obese men and in an animal model of obesity (Lepob/ob mice) by real-time RT-PCR. RESULTS: Microarray analysis revealed that transcription factors that regulate the first stages of adipocyte differentiation, such as CCAAT/enhancer binding protein beta (C/EBPß) and JUN, were upregulated in the adipose tissues of morbidly obese patients. The expression of peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor which controls lipid metabolism and the final steps of preadipocyte conversion into mature adipocytes, was downregulated. The expression of three cyclin-dependent kinase inhibitors that regulate clonal expansion and postmitotic growth arrest during adipocyte differentiation was also altered in obese subjects: p18 and p27 were downregulated, and p21 was upregulated. Angiopoietin-like 4 (ANGPTL4), which regulates angiogenesis, lipid and glucose metabolism and it is know to increase dramatically in the early stages of adipocyte differentiation, was upregulated. The expression of C/EBPß, p18, p21, JUN, and ANGPTL4 presented similar alterations in subcutaneous adipose tissue of Lepob/ob mice. CONCLUSIONS: Our microarray gene profiling study revealed that the expression of genes involved in adipogenesis is profoundly altered in the subcutaneous adipose tissue of morbidly obese subjects. This expression pattern is consistent with an immature adipocyte phenotype that could reflect the expansion of the adipose tissue during obesity.

Vitamin D receptor polymorphisms in secondary hyperparathyroidism after Scopinaro's biliopancreatic diversion.

BACKGROUND: Secondary hyperparathyroidism is a frequent metabolic complication of bariatric surgery. Individual differences in calcium absorption determine chronic secondary hyperparathyroidism after biliopancreatic diversion in half of the patients who have normal levels of 25-hydroxyvitamin D. We aimed to evaluate if certain vitamin D receptor polymorphisms may be responsible for the latter. Cases and controls study including 57 patients after biliopancreatic diversion with a mean serum 25-hydroxyvitamin D above 20 ng/mL, separated into those with secondary hyperparathyroidism (n = 26, cases) and those without it (n = 31, controls). METHODS: Genotyping for restriction-length-fragment polymorphisms of the vitamin D receptor gene was carried out for FOK1, BSM1, APA1, and TAQ1, and haplotype structure was also constructed. RESULTS: There were no differences in the allelic or genotypes distribution of the four studied polymorphisms between patients and controls (P = 0.352 and P = 0.301 for FOK1, P = 0.733 and P = 0.924 for BSM1, P = 0.974 and P = 0.992 for APA1, and P = 0.995 and P = 0.928 for TAQ1, respectively). Haplotype analysis showed no differences between patients and controls (P = 0.495 for BAT, P = 1.000 for BAt, P = 0.508 for Bat and P = 0.924 for bAT haplotypes, respectively). Furthermore, haplotypes were not associated with serum PTH levels or with the ratio between serum PTH and 25-hydroxyvitamin D levels. CONCLUSION: Chronic secondary hyperparathyroidism after biliopancreatic diversion in patients with normal levels of 25-hydroxyvitamin D is not dependent on vitamin D receptor gene polymorphisms.

Chronic increase of bone turnover markers after biliopancreatic diversion is related to secondary hyperparathyroidism and weight loss. Relation with bone mineral density.

BACKGROUND: Biliopancreatic diversion (BPD) is the most effective bariatric procedure. Around 70% of these patients have secondary hyperparathyroidism (SH) in the long term as a consequence of calcium and vitamin D malabsorption. This work was aimed to study the influence of SH on bone turnover and its relationship with bone mineral density (BMD). METHODS: Bone turnover markers were determined in 63 BPD patients and 34 morbidly obese controls. In the BPD group, we also studied the influence of age, loss of weight, common channel length, PTH, vitamin D, and serum calcium on bone turnover as well as its relation with BMD. RESULTS: BPD patients showed significantly higher PTH, osteocalcin, and beta-CTx levels than controls. In the multivariate regression analysis, only PTH (beta=0.42; P=0.0002), menopausal status (beta=0.31; P=0.007) and the percentage of lost BMI (beta=-0.24; P=0.03) significantly predicted the osteocalcin level (R2=0.33; F=9.56; P<0.0001). Similarly, only PTH (beta=0.39; P=0.0005), menopausal status (beta=0.37; P=0.001) and the percentage of lost BMI (beta=-0.23; P=0.04) significantly predicted the beta-CTx level (R2=0.33; F=9.82; P<0.0001). Osteocalcin and beta-CTx levels correlated negatively with BMD at lumbar spine (r=-0.38, P=0.002 and r=-0.30, P=0.02, respectively). CONCLUSIONS: Chronic SH and the loss of weight determine a high rate of bone turnover that is associated with decreasing BMD in BPD patients.

Retinol and alpha-tocopherol in morbid obesity and nonalcoholic fatty liver disease.

BACKGROUND: We aimed to study serum retinol and alpha-tocopherol in a cohort of obese patients and their possible association with several obesity-related conditions, given that the former may be implicated in a diminished capacity of anti-inflammatory and antioxidant potential in obese patients. METHODS: Eighty patients with morbid obesity participated in the study. Many clinical and biochemical variables were measured including serum retinol, alpha-tocopherol, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations. Fatty liver was detected by ultrasonography. RESULTS: Both serum retinol and alpha-tocopherol inversely correlated with body mass index (r = -0.334, P = 0.002 and r = -0.299, P = 0.007, respectively). Serum retinol inversely correlated with AST (r = -0.236, P = 0.036) and ALT (r = -0.241, P = 0.032). Multivariate regression analyses confirmed these results after correcting for the effects of other variables. Eighty-five percent of patients had fatty liver. When restricting the analysis to them, multivariate regression identified male sex (beta = 0.451, P = 0.003), age (beta = -0.275, P = 0.039), and serum retinol concentrations (beta = -0.414, P = 0.005) as predictive variables on serum AST (R (2) = 0.230, F = 3.408, P = 0.009) and male sex (beta = 0.448, P = 0.003), age (beta = -0.236, P = 0.046), insulin resistance determined by homeostasis model assessment (beta = 0.243, P = 0.050), and serum retinol concentrations (beta = -0.305, P = 0.022) as predictive variables on serum ALT (R (2) = 0.296, F = 5.817, P = 0.001). CONCLUSION: Serum retinol and alpha-tocopherol concentrations are inversely associated with body mass index in morbid obesity, and serum retinol is also inversely associated with serum concentrations of transaminases in those patients with nonalcoholic fatty liver disease.

The increase in serum visfatin after bariatric surgery in morbidly obese women is modulated by weight loss, waist circumference, and presence or absence of diabetes before surgery.

BACKGROUND: Previous studies addressing the changes in serum visfatin levels after bariatric surgery yielded conflicting results. METHODS: We measured serum visfatin levels in 41 morbidly obese women before bariatric surgery and after losing at least 15% of the initial weight, and analyzed the results taking into account the type of surgery, reproductive and diabetic status, among others. Body mass index, waist circumference, lipid profile, and insulin resistance determined by homeostasis model assessment (HOMA-IR) were also measured. RESULTS: Patients lost 30.3 +/- 6.1% of the initial body weight, and serum visfatin levels increased from 22.2 +/- 20.9 to 32.2 +/- 27.6 ng/ml (P = 0.031). A multiple regression model (R (2) = 0.314, F = 3.555, P = 0.017) including the percentage of weight loss, changes in waist circumference, HOMA-IR, high-density lipoprotein-cholesterol, and triglycerides (also expressed as percentage from baseline), the surgical procedure, time elapsed since surgery, and previous diabetic status as independent variables showed that weight loss (beta = -0.670, P = 0.010), previous diabetic status (beta = -0.330, P = 0.036), and change in waist circumference (beta = 0.556, P = 0.031) were the main determinants of the percentual increase in serum visfatin levels observed after bariatric surgery. CONCLUSION: Serum visfatin increased after bariatric surgery in relation to the amount of weight lost and to the changes in waist circumference, and this increase was higher in diabetic patients.