Lap. Nissen fundoplication leads to better respiratory symptom control than Toupet in the long term of 20 years.

INTRODUCTION: Having performed anti-reflux surgery for thirty years, it was important to reexamine our patients in the long term to enlarge the body of evidence concerning classical and extraesophageal symptoms that are differently controlled by Nissen or Toupet fundoplication. OBJECTIVES: We report a cohort of 155 GERD patients who underwent fundoplication within a tailored approach between 1994 and 2000. Changes in the perioperative functional outcome, GERD symptoms, and quality of life are being analyzed 10 and 20 years after the operation. RESULTS: The operation resulted in a superior quality of life compared to a patient cohort treated with PPI therapy. We found that both surgical methods (laparoscopic Nissen fundoplication and laparoscopic Toupet fundoplication) cure classical symptoms equally (heartburn, regurgitation, and dysphagia). GERD patients receiving a Toupet fundoplication seem more likely to suffer from extraesophageal GERD symptoms 10 and 20 years after surgery than patients with a Nissen fundoplication. On the other hand, some patients with Nissen fundoplication report dysphagia even 10 and 20 years after surgery. CONCLUSION: Both the laparoscopic Nissen and Toupet fundoplications provide excellent symptom control in the long term. Moreover, the Nissen fundoplication seems to be superior in controlling extraesophageal reflux symptoms, but at the expense of dysphagia. In summary, tailoring the operation based on symptoms seems advantageous.

Linear or circular: Anastomotic ulcer after gastric bypass surgery.

BACKGROUND: After laparoscopic Gastric Bypass Procedure (GBP), anastomotic ulcers (AU) at the gastrojejunostomy (GJ) occur in up to 16% of the patients. Surgical techniques seem to influence the development of AU, but this is still a matter of discussion. This study aims to compare the incidence of AU in circular-stapled (CS) versus linear-stapled (LS) gastrojejunostomy. METHODS: Single-centre retrospective analysis of 241 (m 77 /f 164) consecutive patients (126 CS, 115 LS) with primary or revisional GBP including Roux-Y-Gastric Bypass (RYGB) and One-Anastomosis Gastric Bypass (OAGB) between 01/2014 and 01/2018. Follow-up with oesophagogastroduodenoscopy was only performed in symptomatic patients. Age, body mass index (BMI), comorbidities, smoking and medication were analyzed in both groups. The data are reported as total numbers (%) and mean ± standard deviation. RESULTS: AU occurred significantly more often in the CS group than in the LS group (p = 0.0034). Moreover, refractory AU and the need for revisional surgery were higher in the CS group. Smoking correlates significantly with the development of AU, whereas other risk factors had no impact on its incidence. CONCLUSION: Linear-stapled gastrojejunostomy with a long and narrow pouch should be the preferable procedure for reducing AU development risk. Smoking cessation minimizes the risk for AU and is a necessary part of the treatment.

Arterial Hypertension as a Risk Factor for Reduced Glomerular Filtration Rate after Living Kidney Donation.

Living kidney donation represents the optimal renal replacement therapy, but recent data suggest an increased long-term renal risk for the donor. Here, we evaluated the risk for reduced estimated glomerular filtration rate (eGFR), death, and major cardiovascular events such as nonfatal myocardial infarction or cerebrovascular event including TIA (transient ischemic attack) and stroke in 225 donors, who underwent pre-donation examinations and live donor nephrectomy between 1985 and 2014 at our center. The median follow-up time was 8.7 years (1.0-29.1). In multivariate analysis, age and arterial hypertension at baseline were significantly associated with a higher risk of adverse renal outcomes, such as (1) eGFR <60 mL/min/1.73 m2 (age per year: HR (hazard ratio) 1.05, 95% confidence interval (CI) 1.03-1.08, hypertension: HR 2.25, 95% CI 1.22-3.98), (2) eGFR <60 mL/min/1.73 m2 and a decrease of ≥40% from baseline (age: HR 1.08, 95% CI 1.03-1.13, hypertension: HR 4.22, 95% CI 1.72-10.36), and (3) eGFR <45 mL/min/1.73 m2 (age: HR 1.12, 95% CI 1.05-1.20, hypertension: HR 5.06, 95% CI 1.49-17.22). In addition, eGFR at time of donation (per mL/min/1.73 m2) was associated with a lower risk of (1) eGFR <60 mL/min/1.73 m2 (HR 0.98, 95% CI 0.97-1.00) and (2) eGFR <45 mL/min/1.73 m2 (HR 0.95, 95% CI 0.90-1.00). Age was the only significant predictor for death or major cardiovascular event (HR 1.08, 95% CI 1.01-1.16). In conclusion, arterial hypertension, lower eGFR, and age at the time of donation are strong predictors for adverse renal outcomes in living kidney donors.

Disease Recurrence-The Sword of Damocles in Kidney Transplantation for Primary Focal Segmental Glomerulosclerosis.

A major obstacle in kidney transplantation for primary focal segmental glomerulosclerosis (FSGS) is the risk of disease recurrence. Recurrent FSGS affects up to 60% of first kidney grafts and exceeds 80% in patients who have lost their first graft due to recurrent FSGS. Clinical and experimental evidence support the hypothesis that a circulating permeability factor is the mediator in the pathogenesis of primary and recurrent disease. Despite all efforts, the causing agent has not yet been identified. Several treatment options for the management of recurrent FSGS have been proposed. In addition to plasma exchange, B-cell depleting antibodies are effective in recurrent FSGS. This indicates, that the secretion and/or activity of the postulated circulating permeability factor(s) may be B-cell related. This review summarizes the current knowledge on permeability factor(s) possibly related to the disease and discusses strategies for the management of recurrent FSGS. These include profound B-cell depletion prior to transplantation, as well as the salvage of an allograft affected by recurrent FSGS by transfer into a second recipient.

Laparoscopic Adjustable Gastric Banding: an Underestimated Risk Factor for the Development of Esophageal Cancer?-a Nationwide Survey.

BACKGROUND: Approximately 14% of Austria's 8.5 million inhabitants have a body mass index (BMI) > 30 kg/m2. The laparoscopic adjustable gastric banding (LAGB) was introduced in Austria in 1994, where about 10.300 patients have received it so far. One of our LAGB patients developed an adenocarcinoma of the distal esophagus 13 years after implantation. OBJECTIVES: In order to calculate whether after LAGB patients are at higher risk for carcinoma of the esophagus, we performed a nationwide survey. METHODS: A questionnaire was sent to all surgical departments in Austria, primarily in order to detect cases with esophageal carcinoma after LAGB, but also to evaluate the policy in Austria concerning preoperative work-up, operation, and follow-up in LAGB patients. RESULTS: Since 1994, 37 of the 119 surgical departments in Austria have performed a total of about 10.300 LAGB implantations. Six patients have been identified with esophageal cancer following LAGB. The WHO statistical report on esophageal cancer shows an incidence of 2.8/100.000 per year in Austria, about 1/3 of which cases are adenocarcinoma of the distal esophagus. CONCLUSION: Following LAGB, the incidence of esophageal cancer might be up to fivefold higher than the aged standardized overall population of Austria.

Successful management of recurrent focal segmental glomerulosclerosis.

Primary focal segmental glomerulosclerosis (FSGS) recurs in up to 55% of patients after kidney transplantation. Herein we report the successful management of recurrent FSGS. A 5-year-old boy with primary FSGS received a deceased donor renal transplant. Immediate and fulminant recurrence of FSGS caused anuric graft failure that was resistant to plasmapheresis and rituximab. After exclusion of structural or immunologic damage to the kidney by repeated biopsies, the allograft was retrieved from the first recipient on day 27 and transplanted into a 52-year-old second recipient who had vascular nephropathy. Immediately after retransplantation, the allograft regained function with excellent graft function persistent now at 3 years after transplant. After 2 years on hemodialysis, the boy was listed for kidney retransplantation. To prevent FSGS recurrence, pretreatment with ofatumumab was performed. Nephrotic range proteinuria still occurred after the second transplantation, which responded, however, to daily plasma exchange in combination with ofatumumab. At 8 months after kidney retransplantation graft function is good. The clinical course supports the hypothesis of a circulating permeability factor in the pathogenesis of FSGS. Successful ofatumumab pretreatment implicates a key role of B cells. Herein we provide a description of successful management of kidney failure by FSGS, carefully avoiding waste of organs.

Laparoscopic sleeve gastrectomy: gateway to kidney transplantation.

BACKGROUND: The prevalence of obesity and obesity-related morbidity in end-stage renal disease patients is rising. Although it is established that obesity does not abrogate the transplant benefit with respect to lower long-term mortality and cardiovascular risk, it is associated with increased graft failure, delayed graft function, surgical complications, prolonged hospital stay, and costs. OBJECTIVES: To examine the safety and efficacy of LSG (laparoscopic sleeve gastrectomy) in renal transplant candidates and evaluate transplant outcomes. SETTING: Single-center prospective nonrandomized trial METHODS: We here report on a prospective single-center trial establishing a 2-step approach for obese renal transplant candidates. Patients with end-stage renal disease and a BMI (body mass index) of 35 kg/m2 or higher underwent laparoscopic sleeve gastrectomy. After reaching a BMI of<35 kg/m2, patients were waitlisted for kidney transplantation. Age, gender, body mass index (BMI), associated co-morbidities, cause of end-stage renal disease, surgical complications, and outcome after kidney transplantation (graft survival, incidence of delayed graft function, incidence of rejection, serum creatinine) were collected. RESULTS: LSG was performed in 8 renal transplant candidates with a mean BMI of 38.8 kg/m2 each. BMI dropped to below 35 kg/m2 within a median of 3 months. Percent excess body mass index loss (%EBMIL) was 62.7% at 1 year after LSG. Within 17 months (mean) after metabolic surgery, 7 patients underwent kidney transplantation. All transplants were successful with a serum creatinine of 1.9±.8 mg/dL at discharge and stable allograft function thereafter. Mean follow-up was 3.2±1.4 years; no patient was lost to follow-up. CONCLUSION: LSG is safe and efficacious for treatment of obesity in renal transplant candidates. Rapid and sustained weight loss and subsequent waitlisting for kidney transplantation may reduce overall and in particular posttransplant patient morbidity.

The role of lipocalin-2 in liver regeneration.

BACKGROUND & AIMS: Various immune mediators such as interleukin-6 (IL-6) have been implicated in the process of liver regeneration. Lipocalin-2 (LCN2) has been recently characterized as a prototypic immune mediator produced by various cell types being involved mainly in host defence. In addition, numerous studies have demonstrated its clinical value as a biomarker. This study aimed at defining the role of LCN2 in liver regeneration. METHODS: We studied LCN2 expression in wild-type mice in a model of partial hepatectomy (PH). Furthermore, we evaluated liver regeneration after PH in LCN-deficient mice compared to littermate controls. Serum levels of LCN2 were assessed in a small group of patients undergoing hepatic resection. RESULTS: LCN2 is dramatically induced in livers and sera of wild-type mice after PH, whereas liver LCN2-receptor expression was decreased. Sham operations did not affect hepatic and serum LCN2 expression. Although LCN2-deficient mice exhibited increased baseline liver expression indices, LCN2-deficient mice did not differ from wild-type mice with respect to hepatic proliferation suggesting that this molecule is not involved in hepatic repair. Only serum IL-1ß levels were slightly lower in LCN(-/-) mice, whereas IL-6 serum levels did not differ between various tested animal groups. In humans undergoing hepatic resection, LCN2 levels increased significantly within 24 h following surgery. CONCLUSIONS: LCN2, although massively induced in mice after PH, is not relevant in murine hepatic regeneration. Further, human studies have to define whether LCN2 could evolve as biomarker after liver surgery.

Proteomics in transplantation.

Proteomics and biochemical profiling have emerged as exciting and powerful tools in clinical biomarker research. In the field of transplantation, proteomics aims not only at developing noninvasive means for immune monitoring but also to gain mechanistic insights into the pathophysiology of the alloimmune response and hence defining new therapeutic targets. This chapter provides an overview of proteomic biomarker-driven approaches and its underlying concepts and discusses the advantages, clinical implications, challenges, and limitations of this novel modality as it relates to solid organ transplantation.

Nighttime procedures are not associated with adverse outcomes in kidney transplantation.

Surgeries performed during the night are associated with higher complication rates. The aim of this study was to determine the impact of nighttime surgery on the outcome after kidney transplantation. In all, 873 deceased donor kidney transplants were retrospectively analyzed and grouped according to the time of surgery: daytime (8 AM to 8 PM, n = 610) versus nighttime (8 PM to 8 AM, n = 263). Statistical analysis compared patient/graft survival, rate of delayed graft function (DGF), acute rejection rate, and surgical complications. One and 5-year patient and graft survival did not differ between daytime and nighttime transplants. DGF occurred in 31.1% of daytime compared to 37.6% of nighttime procedures (P = 0.06). Acute allograft rejection was observed in 22.6% of daytime compared to 18.3% in nighttime graft recipients (P = 0.15). Nighttime procedures were associated with 22.4% complications compared to 22.1% in daytime procedures (P = 0.92). Most importantly, if transplantations were postponed until the next morning, cold ischemia time (CIT) would have increased from 16.6 h to 24.6 h (P < 0.0001) which would have resulted in decreased long-term survival (P < 0.02). Nighttime kidney transplants are neither associated with a higher surgical complication rate nor worse 5-year outcomes than daytime procedures, thus are justified to keep CIT short.

Biomarker discovery in transplantation--proteomic adventure or mission impossible?

Optimal management of transplanted organs requires specific and sensitive biomarkers for immunologic graft monitoring and subsequently patient tailored treatment. Proteomic science has emerged as an attractive tool in clinical biomarker research generating massive amounts of proteomic-driven data. However, critical interpretation of these data requires basic knowledge of proteomic principles and technology. This review provides an overview of proteomic approaches along with their advantages and limitations. Furthermore, this article summarizes the current status of biomarker achievements in the different areas of solid organ transplantation and discusses the hurdles that have precluded routine clinical application of these promising markers so far.

Proteomics--a blessing or a curse? Application of proteomics technology to transplant medicine.

Proteomics has emerged as a powerful tool in clinical biomarker research. In the field of transplantation, proteomics aims not only at developing noninvasive tools for immune monitoring and identifying biomarkers of allograft rejection but also to gain mechanistic insights into the pathophysiology of an alloimmune response and hence defining new therapeutic targets. A basic knowledge of proteomic technology is a prerequisite to appreciate the complex data generated and required for critical evaluation/interpretation of proteomic-driven studies. This review provides an overview of proteomic approaches and its underlying concepts and discusses the advantages, clinical implications, challenges, and limitations of this exciting modality in transplantation.

Single-center experience with third and fourth kidney transplants.

Kidney retransplantation is often associated with a higher immunological risk than is primary renal transplantation. Faced with increasing organ shortage and growing waiting lists, results of kidney retransplantation are of particular interest. Fifty-six third and fourth kidney transplants were analyzed retrospectively. Parameters included patient and donor demographics, operative details, incidence of surgical, immunological and infectious complications and patient and graft survival. Patients receiving third kidney grafts had 1- and 5-year patient/graft survival rates of 97.4%/72.9% and 88.9%/53.6%, respectively. Episodes of acute rejection and delayed graft function were observed in 44% and 49% of these patients. Fourth kidney transplantation was associated with 1- and 2-year patient/graft survival rates of 84.8%/68.5% and 63.6%/47%, respectively. Acute rejection and delayed graft function occurred in 33% and in 60% of cases. Acceptable patient and graft survival may be achieved after third and fourth kidney transplantation. Graft losses in this sensitized population are mainly because of rejection. Profound immunosuppression may lead to major infectious problems.