Newly diagnosed Crohn's disease, and hepatocellular and renal cell carcinoma in a bariatric surgery patient-dealing with the complexity of obesity-associated diseases: a case report and review of the literature.

BACKGROUND: Bariatric surgery candidates commonly suffer from conditions that constitute the metabolic syndrome. But they also have a higher risk for autoimmune and malignant diseases. Obesity-associated comorbidities aside from the metabolic syndrome are often given insufficient attention in the clinical routine, including preoperative work-ups for bariatric surgery. CASE PRESENTATION: We retrospectively report the case of a 65 years old Caucasian patient who was diagnosed with Crohn's disease prior to, a hepatocellular carcinoma during, and a renal cell carcinoma post bariatric surgery. The relevance of these diseases for decision making in bariatric procedures and current recommendations for preoperative bariatric work-ups are discussed. In our case, the diagnosis of Crohn's disease led to the performance of a sleeve gastrectomy instead of a Roux-en-Y gastric bypass and a previously unknown hepatocellular carcinoma was simultaneously removed by hepatic wedge resection. CONCLUSIONS: Preoperative endoscopy and imaging techniques can be valuable since surprising pre- and intraoperative findings can force the bariatric surgeon to change the initially planned operative strategy. But the diagnostic accuracy of abdominal ultrasound may be limited in bariatric surgery patients. With the expansion of bariatric surgery, the complexity of bariatric surgery patients is also likely to increase. However, with the appropriate awareness and strategies, bariatric surgery can be safely executed and even contribute to the treatment of severe comorbidities that exceed the metabolic spectrum.

Barrett`s Esophagus in Bariatric Surgery: Regression or Progression?

INTRODUCTION: Morbid obesity is well known as a risk factor for gastroesophageal reflux disease (GERD) and its related disorders such as Barrett's esophagus (BE). This study aimed to evaluate the development of BE in patients who underwent bariatric surgery. MATERIALS AND METHODS: Using a single-center prospectively established database of obese patients who underwent bariatric surgery from 01/2012 to 12/2019, we retrospectively compared the preoperative endoscopic findings of BE to those after 1-2 years and 3-5 years following bariatric surgery. The change of BE was detected endoscopically according to Prague classification and histologically according to the British guidelines of detecting columnar epithelium on the distal esophagus. RESULTS: Among 914 obese patients who underwent bariatric surgery and received a preoperative esophagogastroduodenoscopy (EGD), we found 119 patients (13%) with BE. A follow-up EGD was performed in 74 of the BE patients (62.2%). A total of 37 (50%) patients underwent a follow-up EGD after 1-2 years and 45 (60.8%) patients underwent it after 3-5 years. Among many clinical parameters, the surgical procedure was the only significant factor for the change of BE after bariatric surgery (p < 0.05). A regression of BE was found in 19 patients (n = 54, 35%) after laparoscopic Roux-en-Y- gastric bypass (LRYGB). Furthermore, a progression of BE was detected in six patients (n = 20, 30%) after laparoscopic sleeve gastrectomy (LSG). CONCLUSION: RYGB should be considered in obese patients with BE. Detecting BE prior to bariatric surgery may have an impact on decision-making regarding the suitable surgical bariatric procedure.

[Current evidence on loop length in intestinal bypass procedures]. / Aktuelle Evidenz zur Schlingenlänge bei intestinalen Bypassverfahren.

BACKGROUND: Intestinal bypass procedures are well recognized for their long-term weight reduction and control of metabolic comorbidities. The selection of the length of the small bowel loop has a significant influence on the positive and also negative effects of the chosen procedure but national and international standardization are missing. OBJECTIVE: The aim of this article is to give an overview of the current evidence on the various intestinal bypass procedures and the influence of the chosen small bowel loop length on the desired and adverse postoperative outcomes. The IFSO 2019 consensus recommendations on the standardization of bariatric surgery and metabolic procedures form the basis of these considerations. MATERIAL AND METHODS: The current literature was searched for comparative studies addressing the question of different small bowel loop lengths in a Roux-en­Y gastric bypass, one anastomosis gastric bypass, single anastomosis duodenoileal bypass with sleeve gastrectomy and biliopancreatic diversion (with duodenal switch). RESULTS: Due to the heterogeneity of currently available studies and interindividual differences in total small bowel lengths in humans, it is difficult to give definitive recommendations for the choice of small bowel loop lengths. The longer the biliopancreatic loop (BPL) or the shorter the common channel (CC), the higher is the risk of (severe) malnutrition. To prevent malnutrition, the BPL should not be longer than 200 cm and the CC should have a length of at least 200 cm. CONCLUSION: The intestinal bypass procedures recommended in the German S3 guidelines are safe and show good long-term outcomes. As part of the postbariatric follow-up, the nutritional status of patients following an intestinal bypass has to be followed-up on the long term in order to avoid malnutrition preferably prior to a clinical manifestation.

Optimization of extracellular matrix for primary human hepatocyte cultures using mixed collagen-Matrigel matrices.

Loss of differentiation of primary human hepatocytes (PHHs) ex vivo is a known problem of in vitro liver models. Culture optimizations using collagen type I and Matrigel reduce the dedifferentiation process but are not able to prevent it. While neither of these extracellular matrices (ECMs) on their own correspond to the authentic hepatic ECM, a combination of them could more closely resemble the in vivo situation. Our study aimed to systematically analyze the influence of mixed matrices composed of collagen type I and Matrigel on the maintenance and reestablishment of hepatic functions. Therefore, PHHs were cultured on mixed collagen-Matrigel matrices in monolayer and sandwich cultures and viability, metabolic capacity, differentiation markers, cellular arrangement and the cells' ability to repolarize and form functional bile canaliculi were assessed by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), functional assays and immunofluorescence microscopy. Our results show that mixed matrices were superior to pure matrices in maintaining metabolic capacity and hepatic differentiation. In contrast, Matrigel supplementation can impair the development of a proper hepatocytic polarization. Our systematic study helps to compose an optimized ECM to maintain and reestablish hepatic differentiation on cellular and multicellular levels in human liver models.

Critical Investigation of the Usability of Hepatoma Cell Lines HepG2 and Huh7 as Models for the Metabolic Representation of Resectable Hepatocellular Carcinoma.

Metabolic alterations in hepatocellular carcinoma (HCC) are fundamental for the development of diagnostic screening and therapeutic intervention since energy metabolism plays a central role in differentiated hepatocytes. In HCC research, hepatoma cell lines (HCLs) like HepG2 and Huh7 cells are still the gold standard. In this study, we characterized the metabolic profiles of primary human hepatoma cells (PHCs), HCLs and primary human hepatocytes (PHHs) to determine their differentiation states. PHCs and PHHs (HCC-PHHs) were isolated from surgical specimens of HCC patients and their energy metabolism was compared to PHHs from non-HCC patients and the HepG2 and Huh7 cells at different levels (transcript, protein, function). Our analyses showed successful isolation of PHCs with a purity of 50-73% (CK18+). The transcript data revealed that changes in mRNA expression levels had already occurred in HCC-PHHs. While many genes were overexpressed in PHCs and HCC-PHHs, the changes were mostly not translated to the protein level. Downregulated metabolic key players of PHCs revealed a correlation with malign transformation and were predominantly pronounced in multilocular HCC. Therefore, HCLs failed to reflect these expression patterns of PHCs at the transcript and protein levels. The metabolic characteristics of PHCs are closer to those of HCC-PHHs than to HCLs. This should be taken into account for future optimized tumor metabolism research.

Influence of Genistein on Hepatic Lipid Metabolism in an In Vitro Model of Hepatic Steatosis.

Nonalcoholic fatty liver disease (NAFLD) is among the leading causes of end-stage liver disease. The impaired hepatic lipid metabolism in NAFLD is exhibited by dysregulated PPARα and SREBP-1c signaling pathways, which are central transcription factors associated with lipid degradation and de novo lipogenesis. Despite the growing prevalence of this disease, current pharmacological treatment options are unsatisfactory. Genistein, a soy isoflavone, has beneficial effects on lipid metabolism and may be a candidate for NAFLD treatment. In an in vitro model of hepatic steatosis, primary human hepatocytes (PHHs) were incubated with free fatty acids (FFAs) and different doses of genistein. Lipid accumulation and the cytotoxic effects of FFAs and genistein treatment were evaluated by colorimetric and enzymatic assays. Changes in lipid homeostasis were examined by RT-qPCR and Western blot analyses. PPARα protein expression was induced in steatotic PHHs, accompanied by an increase in CPT1L and ACSL1 mRNA. Genistein treatment increased PPARα protein expression only in control PHHs, while CPTL1 and ACSL1 were unchanged and PPARα mRNA was reduced. In steatotic PHHs, genistein reversed the increase in activated SREBP-1c protein. The model realistically reflected the molecular changes in hepatic steatosis. Genistein suppressed the activation of SREBP-1c in steatotic hepatocytes, but the genistein-mediated effects on PPARα were abolished by high hepatic lipid levels.

Prolonged Lipid Accumulation in Cultured Primary Human Hepatocytes Rather Leads to ER Stress than Oxidative Stress.

Overweight has become a major health care problem in Western societies and is accompanied by an increasing incidence and prevalence of non-alcoholic fatty liver disease (NAFLD). The progression from NAFLD to non-alcoholic steatohepatitis (NASH) marks a crucial tipping point in the progression of severe and irreversible liver diseases. This study aims to gain further insight into the molecular processes leading to the evolution from steatosis to steatohepatitis. Steatosis was induced in cultures of primary human hepatocytes by continuous five-day exposure to free fatty acids (FFAs). The kinetics of lipid accumulation, lipotoxicity, and oxidative stress were measured. Additionally, ER stress was evaluated by analyzing the protein expression profiles of its key players: PERK, IRE1a, and ATF6a. Our data revealed that hepatocytes are capable of storing enormous amounts of lipids without showing signs of lipotoxicity. Prolonged lipid accumulation did not create an imbalance in hepatocyte redox homeostasis or a reduction in antioxidative capacity. However, we observed an FFA-dependent increase in ER stress, revealing thresholds for triggering the activation of pathways associated with lipid stress, inhibition of protein translation, and apoptosis. Our study clearly showed that even severe lipid accumulation can be attenuated by cellular defenses, but regenerative capacities may be reduced.

Classification of hyperspectral endocrine tissue images using support vector machines.

BACKGROUND: Thyroidectomy is one of the most commonly performed surgical procedures. The region of the neck has a very complex structural organization. It would be beneficial to introduce a tool that can assist the surgeon in tissue discrimination during the procedure. One such solution is the noninvasive and contactless technique, called hyperspectral imaging (HSI). METHODS: To interpret the HSI data, we implemented a supervised classification method to automatically discriminate the parathyroid, the thyroid, and the recurrent laryngeal nerve from surrounding tissue(muscle, skin) and materials (instruments, gauze). A leave-one-patient-out cross-validation was performed. RESULTS: The best performance was obtained using support vector machine (SVM) with a classification and visualization in less than 1.4 seconds. A mean patient accuracy of 68% ± 23% was obtained for all tissues and material types. CONCLUSIONS: The proposed method showed promising results and have to be confirmed on a larger cohort of patient data.