Ivan Kristo

Short‐term complications of wide‐lumen stapled anastomosis after ileocolic resection for Crohn’s disease: who is at risk?

Aim  There is growing evidence that stapled anastomoses are similarly effective compared to hand‐sewn anastomoses in Crohn’s patients. This study was designed to assess safety and limitations of wide‐lumen stapled ileocolic anastomoses.

Effect of intraportal infusion of tacrolimus on ischaemic reperfusion injury in orthotopic liver transplantation: a randomized controlled trial

The increased use of older and/or marginal donor organs in liver transplantation over the last decade calls for strategies to minimize ischaemic reperfusion (I/R) injury to prevent early graft failure. Tacrolimus, a very potent and effective calcineurin inhibitor, was selected because of its ability to ameliorate I/R injury. A randomized, blinded, controlled single‐centre trial of 26 liver transplant recipients was performed between February 2008 and December 2009. Donor organs were randomized to be perfused intraportally during liver transplantation with 1.5 l 5% albumin infusion containing either 20 ng/ml tacrolimus or placebo. The primary end point was liver function as assessed by aspartate transaminase (AST) or alanine transaminase (ALT) levels 6 days after transplantation. Treatment effectiveness was tested by transcriptome‐wide analysis of biopsies. There was no difference in the primary end point, i.e. AST (IU/l) and ALT (IU/l) at day 6 after transplantation between groups. Furthermore, choleastatic parameters as well as parameters of liver synthesis were not different between groups. However, tacrolimus treatment suppressed inflammation and immune response in the transplanted liver on a genome‐wide basis. Intrahepatic administration of tacrolimus did not result in a reduction of AST and ALT within the first week after transplantation. (ClinicalTrials.gov number: NCT00609388)

Impaired metabolism in donor kidney grafts after steroid pretreatment

We recently showed in a randomized control trial that steroid pretreatment of the deceased organ donor suppressed inflammation in the transplant organ but did not reduce the rate or duration of delayed graft function (DGF). This study sought to elucidate such of those factors that caused DGF in the steroid‐treated subjects. Genome‐wide gene expression profiles were used from 20 steroid‐pretreated donor‐organs and were analyzed on the level of regulatory protein–protein interaction networks. Significance analysis of microarrays (SAM) yielded 63 significantly down‐regulated sequences associated with DGF that could be functionally categorized according to Protein ANalysis THrough Evolutionary Relationships ontologies into two main biologic processes: transport (P < 0.001) and metabolism (P < 0.001). The identified genes suggest hypoxia as the cause of DGF, which cannot be counterbalanced by steroid treatment. Our data showed that molecular pathways affected by ischemia such as transport and metabolism are associated with DGF. Potential interventional targeted therapy based on these findings includes peroxisome proliferator‐activated receptor agonists or caspase inhibitors.

Surgical recurrence in Crohn’s disease: Are we getting better?

Crohns disease (CD) still remains a challenging chronic inflammatory disorder, both for colorectal surgeons and gastroenterologists. The need for recurrent surgery following primary intestinal resection is still considerable, though recent evidence suggested a declining rate of recurrence. Several conflicting surgical parameters have been identified that might impact on the postoperative outcome positively, such as access to the abdomen, anastomotic configuration or type of disease. Additionally, promising results have been achieved with the increased use of immunosuppressive medications in CD. Consequently, the question arises if we are getting better as a result of novel medical and surgical strategies.

Diagnosis and treatment of benign inflammatory esophageal diseases

SummaryBackgroundNowadays, benign inflammatory esophageal diseases represent a rising socioeconomic burden. Recently, novel therapeutic approaches have been introduced to enrich personalized surgical options.MethodsA PubMed research was conducted and merged with institutional guidelines and data.ResultsMagnetic sphincter augmentation strengthens the lower esophageal sphincter and therefore recreates the natural reflux barrier. Electrical sphincter stimulation offers the possibility to personalize minimal invasive treatment and considers even changing lifestyles. Endoscopic antireflux procedures try to mimic the outcome of laparoscopic fundoplication and aim to improve the angle of His. However, laparoscopic fundoplication remains the surgical treatment of choice in advanced reflux disease.Reflux can also cause eosinophilic infiltration and therefore hinders diagnosis of eosinophilic esophagitis. Once diagnosis is established, dietary modifications and topical steroids offer relevant relief. Reflux produces Barrett’s esophagus, a neoplastic progression, which is commonly treated with radiofrequency ablation.ConclusionNovel therapeutic options are facing the rising incidence of benign inflammatory diseases.

The type of loose seton for complex anal fistula is essential to improve perianal comfort and quality of life

The use of a loose seton for complex anal fistulae can cause perianal discomfort and reduced quality of life. The aim of this study was to assess the impact of the novel knot‐free Comfort Drain on quality of life, perianal comfort and faecal continence compared to conventional loose setons.

Non‐persistent effect of short‐term bisphosphonate treatment in preventing fractures after liver transplantation

Bone disease is one of the most common complications after transplantation, affecting many transplant patients; some of them have recurrent fractures. We recently showed that high-dose zoledronic acid (ZOL) prevents bone fractures after orthotopic liver transplantation (OLT) [1]. The anti-re-absorptive action of ZOL became evident after 6 months, resulting in a beneficial outcome on bone matrix mineralization [2]. Renal function was not affected by bisphosphonate therapy. This study was carried out to determine whether a high-dose bisphosphonate treatment within the first 12 months exerted long-term beneficial effects on bone mineralization and turnover, preventing fractures. For this purpose, all subjects received conventional X-ray, bone mineral density (BMD) measurements and determination of serologic markers of bone turnover 3 years after transplantation. The long-term consequence of this treatment is yet to be investigated. Baseline characteristics, cumulative steroid dose, creatinine values and liver function parameters did not differ significantly. A total of 96 patients underwent randomization (49 patients in the control (CON) group and 47 in the ZOL group) at the beginning of the trial and 29 patients were analysed in the CON and 28 in the ZOL group after 36 months of engraftment. The ZOL and CON groups did not differ significantly in major baseline characteristics (Table 1). Three new fractures at 12 months after OLT occurred in the ZOL group (total numbers over 36 months: n = 7), these ‘late’ fractures were asymptomatic and detected by X-ray: no further fractures could be seen after 12 months in the CON group (total numbers over 36 months: n = 11). Two patients with ‘late’ fractures had a normal BMD after 12 months. The third patient had osteopenia at the lumbar spine after 1 year of transplantation. All fractures were vertebral fractures. No clinical sign or biochemical parameter could be detected to predict these late fractures. The preventive effect of bisphosphonate treatment after engraftment for fractures was not sustained from 12 months to 3 years (P = 0.076) (Fig. 1). BMD of the femoral neck and lumbar spine increased significantly in both groups (P < 0.001) from the time of transplantation until the third year after OLT. The increase in BMD t-scores of the lumbar spine in the same time interval also reached statistical significance in both groups (P = 0.006). No statistically significant differences could be detected in BMD t-scores of the femoral neck in both groups 36 months after OLT (P = 0.125). Osteoprotegerin, C-telopeptide, calcitonin, iPTH, osteocalcin and bone specific alkaline phosphatase were not significantly different at 12 and 36 months after OLT between both groups. Accordingly, adequate conversion of 25OHVitD to bioactive 1,25 (OH)-VitD occurred within 12 months in both groups and continued to be sufficient in the following years. Serum calcium and phosphate levels were similar in both groups at every time point (Table 2). One patient suffered from osteonecrosis of the jaw 25 months after OLT and 13 months after the last ZOL infusion. CON-, but not ZOL, -treated patients lost bone mineral density at femoral neck in the first 6 months. From the sixth month onwards, femoral neck BMD increased in both groups, being statistically higher at 3 years than at 12 months. The BMD of the lumbar spine increased in the ZOL the CON group in the first 12 months without a statistically significant difference between the groups. After 1 year, the BMD of lumbar spine increased and was statistically higher at 3 years than that at 12 months. This effect is most likely driven by the fact that the corticosteroid doses are significantly higher early after transplantation than doses used for the maintenance of immunosuppression after the first year. Millonig et al. [3] used a study protocol involving alendronate in combination with calcium/VitD to prevent bone loss after OLT. The study was not powered to assess fractures. In this trial, patients were stratified by BMD before transplantation and patients with osteopenia or osteoporosis received alendronate after OLT. Similar to like their results, we found that patients who received bisphosphonate did not experience significant bone loss in the lumbar spine in the early phase after OLT. We could even demonstrate a significant increase of BMD in femo-

Waist to hip ratio is a better predictor of esophageal acid exposure than body mass index

Obesity and gastroesophageal reflux disease (GERD) are major health problems showing an inconstant relationship in the literature. Therefore, anthropometric parameters which are predictive and can simply be assessed at first patient presentation may lead to a better patient selection for ambulatory reflux monitoring. We aimed to examine the association of body mass index (BMI) and waist to hip ratio (WHR) with gastroesophageal reflux activity during 24 hour‐pH‐impedance monitoring.

Austrian expert panel recommendation for radiofrequency ablation of Barrett's esophagus

SummaryBackgroundBarrett’s esophagus (BE) represents the premalignant manifestation of gastroesophageal reflux disease and includes columnar lined esophagus with intestinal metaplasia, low-grade dysplasia, high-grade dysplasia and cancer.MethodsAn Austrian panel of expert meeting was held at the Medical University Vienna, June 2015, to establish and define recommendations for the endoscopic treatment of BE with and without dysplasia and cancer. Recommendations are based on critical analysis of published evidence. Statistics were not applied.ResultsDiagnosis of cancer and dysplasia is to be reconfirmed by a second expert pathologist. Advanced cancer (> T1a) requires surgical resection ± adjuvant therapies. Treatment of T1a early cancer, high- and low-grade dysplasia should include endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA). In the presence of increased cancer risk, BE without dysplasia should be treated by RFA within clinical studies only. Elimination of any early cancer, dysplasia and IM defines complete response, that is, post RFA histopathology shows squamous, cardiac or oxyntocardiac mucosa lined esophagus (Chandrasoma classification). Follow-up endoscopies are timed according to the base line histopathology. Down grade from cancer to dysplasia or from dysplasia to non-dysplastic BE defines partial response, respectively. Based on esophageal function testing, reflux is treated by medical or surgical therapy.ConclusionIn Austria, RFA ± EMR is recommended for BE containing early cancer or dysplasia. Non-dysplastic BE with an increased cancer risk should be offered RFA within clinical trials to assess the efficacy for cancer prevention in this group of patients.

The modified glasgow prognostic score is an independent prognostic indicator in neoadjuvantly treated adenocarcinoma of the esophagogastric junction

The modified Glasgow Prognostic Score (mGPS) combines the indicators of decreased plasma albumin and elevated CRP. In a number of malignancies, elevated mGPS is associated with poor survival. Aim of this study was to investigate the prognostic role of mGPS in patients with neoadjuvantly treated adenocarcinomas of the esophagogastric junction 256 patients from a prospective database undergoing surgical resection after neoadjuvant treatment between 2003 and 2014 were evaluated. mGPS was scored as 0, 1, or 2 based on CRP (>1.0 mg/dl) and albumin (<35 g/L) from blood samples taken prior (preNT-mGPS) and after (postNT-mGPS) neoadjuvant therapy. Scores were correlated with clinicopathological patients’ characteristics. From 155 Patients, sufficient data was available. Median follow-up was 63.8 months (33.3–89.5 months). In univariate analysis, Cox proportional hazard model shows significant shorter patients OS (p = 0.04) and DFS (p = 0.02) for increased postNT-mGPS, preNT-hypoalbuminemia (OS: p = 0.003; DFS: p = 0.002) and post-NT-CRP (OS: p = 0.03; DFS: p = 0.04). Elevated postNT-mGPS and preNT-hypoalbuminemia remained significant prognostic factors in multivariate analysis for OS (p = 0.02; p = 0.005,) and DFS (p = 0.02, p = 0.004) with tumor differentiation and tumor staging as significant covariates. PostNT-mGPS and preNT-hypoalbuminemia are independent prognostic indicators in patients with neoadjuvantly treated adenocarcinomas of the esophagogastric junction and significantly associated with diminished OS and DFS.