Students and physicians differ in perception of quality of life in patients with tumors of the upper gastrointestinal tract.

Health-related quality of life (HRQoL) has recently gained importance as treatment options for tumors of the upper GI tract lead to improved long-term survival. HRQoL is often estimated by physicians even though their reliability and the impact of outside factors such as contact time and level of medical education is unclear. Therefore, in this study we investigated the correlation between physicians', students', and patients' assessment of HRQoL. 54 patients presenting with tumors of the upper GI tract were included and asked to fill out the standardized HRQoL questionnaires EORTC QLQ-C30 and QLQ-OG25. Attending physicians and medical students filled out the same questionnaires through estimation of patients' HRQoL. Correlation was assessed through Pearson's and Kendall's τb coefficients. Physicians' and patients' assessments correlated for one out of six of the functional and a third of the symptom scores. Students' and patients' assessments correlated for one third of the functional and two thirds of the symptom scores. Students tended to underestimate patients' symptom burden while physicians tended to overestimate it. Physicians failed to correctly assess several pathognomonic symptoms in this study. Students showed higher correlation with patients' symptoms than physicians. Even so, this adds to mounting evidence that shows the benefit of using patient-reported outcomes as a gold standard regarding HRQoL.

Quality of Life, Sarcopenia and Nutritional Status in Patients with Esophagogastric Tumors before and after Neoadjuvant Therapy.

(1) Background: Health-related quality of life (HRQoL) gains importance as novel treatment options for individuals with esophagogastric tumors to improve long-term survival. Impaired HRQoL has been shown to be a predictor of overall survival. Sarcopenia is a known prognostic factor for postoperative complications. As the regular control of sarcopenia through CT scans might not always be possible and HRQoL and nutritional scores are easier to obtain, this study aimed to assess the relationship between nutritional scores, HRQoL and skeletal muscle mass in patients undergoing chemotherapy for cancers of the upper gastrointestinal tract. (2) Methods: Eighty patients presenting with tumors of the upper GI tract were included and asked to fill out the standardized HRQoL questionnaire, EORTC's QLQ-C30. Nutritional status was assessed using the MNA, MUST and NRS 2002 scores. Sarcopenia was determined semi-automatically based on the skeletal muscle index at the L3 vertebrae level in staging CT scans. (3) Results: In chemo-naïve patients, HRQoL summary scores correlated significantly with nutritional scores and SMI. SMI and HRQoL prior to neoadjuvant therapy correlated significantly with SMI after treatment. (4) Conclusions: HRQoL is a helpful tool for assessing patients' overall constitution. The correlation of HRQoL summary scores and SMI might allow for a rough assessment of skeletal muscle status through HRQoL assessment in chemo-naïve patients.

Impairment of Nutritional Status and Quality of Life Following Minimal-Invasive Esophagectomy-A Prospective Cohort Analysis.

Minimal-invasive resection of the esophagus for esophageal cancer has led to a relevant decrease in postoperative morbidity. Postoperatively, patients still suffer from surgical and adjuvant therapy-related symptoms impairing nutrition and quality of life. The aim of this study was to evaluate the nutritional status and associated symptoms six months after esophagectomy. Patients who attended follow-up examination six months after minimal-invasive esophagectomy were included. Blood and fecal tests, quality of life surveys (QLQ-C30 and QLQ-OG25) and nutritional risk screening (NRS) were performed. Twenty-four patients participated. The mean weight loss was 11 kg. A significant decrease in vitamin B12 (737 to 467 pg/mL; p = 0.033), ferritin (302 to 126 ng/mL; p = 0.012) and haptoglobin (227 to 152 mg/dL; p = 0.025) was found. In total, 47% of the patients had an impaired pancreatic function (fecal elastase < 500 µg/g). Physical (72 to 58; p = 0.034) and social functioning (67 to 40; p = 0.022) was significantly diminished, while self-reported global health status remained stable (52 to 54). The number of patients screened and found to be in need of nutritional support according to NRS score decreased slightly (59% to 52%). After MIE, patients should be meticulously monitored for nutritional status after surgery.

Insulin Resistance Is the Main Characteristic of Metabolically Unhealthy Obesity (MUO) Associated with NASH in Patients Undergoing Bariatric Surgery.

(1) Background: Metabolically healthy obesity (MHO) is a concept that applies to obese patients without any elements of metabolic syndrome (metS). In turn, metabolically unhealthy obesity (MUO) defines the presence of elements of metS in obese patients. The components of MUO can be divided into subgroups regarding the elements of inflammation, lipid and glucose metabolism and cardiovascular disease. MUO patients appear to be at greater risk of developing non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) compared to MHO patients. The aim of this study was to evaluate the influence of different MUO components on NAFLD and NASH in patients with morbid obesity undergoing bariatric surgery. (2) Methods: 141 patients undergoing bariatric surgery from September 2015 and October 2021 at RWTH Aachen university hospital (Germany) were included. Patients were evaluated pre-operatively for characteristics of metS and MUO (HbA1c, HOMA, CRP, BMI, fasting glucose, LDL, TG, HDL and the presence of arterial hypertension). Intraoperatively, a liver biopsy was taken from the left liver lobe and evaluated for the presence of NAFLD or NASH. In ordinal regression analyses, different factors were evaluated for their influence on NAFLD and NASH. (3) Results: Mean BMI of the patients was 52.3 kg/m2 (36-74.8, SD 8.4). Together, the parameters HbA1c, HOMA, CRP, BMI, fasting glucose, LDL, TG, HDL and the presence of arterial hypertension accounted for a significant amount of variance in the outcome, with a likelihood ratio of χ2 (9) = 41.547, p < 0.001, for predicting the presence of NASH. Only HOMA was an independent predictor of NASH (B = 0.102, SE = 0.0373, p = 0.007). Evaluation of steatosis showed a similar trend (likelihood ratio χ2 (9) = 40.272, p < 0.001). Independent predictors of steatosis were HbA1c (B = 0.833, SE = 0.343, p = 0.015) and HOMA (B = 0.136, SE = 0.039, p < 0.001). (4) Conclusions: The above-mentioned model, including components of MUO, was significant for diagnosing NASH in patients with morbid obesity undergoing bariatric surgery. Out of the different subitems, HOMA independently predicted the presence of NASH and steatosis, while HbA1c independently predicted steatosis and fibrosis. Taken together, the parameter of glucose metabolism appears to be more accurate for the prediction of NASH than the parameters of lipid metabolism, inflammation or the presence of cardiovascular disease.

Telomere length dynamics measured by flow-FISH in patients with obesity undergoing bariatric surgery.

Obesity has negative effects on comorbidities, health-related quality of life and survival. Telomere length (TL) changes after bariatric surgery have been reported, but the studies are contradictory, and analyses using state-of-the art techniques for TL measurement, such as flow-FISH, are sparse. We measured TL dynamics via flow-FISH in patients undergoing bariatric surgery and compared their TL with 105 healthy individuals. Patients with obesity who underwent bariatric surgery were included. Lymphocyte and granulocyte absolute and age-adjusted (aa) TL were analyzed by flow-FISH before (preoperative cohort, n = 45) and after surgery (follow-up cohort, n = 35) at month 5.5 ± 3.9 (mean ± standard deviation [SD]). The initial lymphocyte aaTL was significantly shorter (-0.37 kb ± 0.18 kb, P = 0.045) in patients with obesity, while the granulocyte aaTL was not different from that in the healthy comparison population (0.28 kb ± 0.17 kb, P = 0.11). The telomere dynamics after surgery showed an increase in mean TL in both lymphocytes and granulocytes of patients with a pronounced BMI loss of ≥ 10 kg/m2. We did not find any association between TL increase after surgery and age, sex or the type of procedure selected for bariatric surgery. We confirmed that patients suffering from obesity have significantly shorter lymphocyte TL using flow-FISH. Along with and dependent on the degree of weight reduction after bariatric surgery, TL significantly increased in both lymphocytes and granulocytes after a mean of 5.5 months. Our results show that bariatric surgery affects not only body weight but also biomarkers of aging, such as TL.

A Long-Term Comparative Study Between One Anastomosis Gastric Bypass and Sleeve Gastrectomy.

BACKGROUND: One anastomosis gastric bypass (OAGB) has become increasingly accepted in bariatric surgery and meanwhile represents the third most common procedure worldwide. While it shows promising weight loss results and comorbidity resolution, questions about issues such as reflux or nutritional deficiencies (ND) persist in the long term. On the other hand, the most frequently performed sleeve gastrectomy (SG) has to accept growing criticism regarding long-term results and reflux issues. There is a particular lack of long-term comparative data for both procedures. This study presents our long-term experience. METHODS: We evaluated OAGB and SG patients retrospectively comparing for weight loss and resolution of comorbidities as well as perioperative and long-term complications in a follow-up period of 5 years. RESULTS: Nine hundred eleven OAGB and 241 SG were included in the study. OAGB had a shorter operation time and hospital stay. Overall complication rate did not differ in both groups. Ulcers were more frequent in OAGB (7.7% vs. 1.7%, p = 0.001), whereas insufficient weight loss (IWL)/weight regain (WR) proved to be more prevalent in SG (25.7% vs. 6.4%, p < 0.001). The same held true for reflux (17.8% vs. 8.3%, p < .001). On the other hand, ND were more common in OAGB (20.0% vs. 12.0%, p = 0.005). Revisional surgery was more often indicated after SG. Analysis by linear mixed model showed that OAGB achieved a lower BMI/higher loss of BMI. Improvement of T2DM (94.6% vs. 85.2%, p = 0.008) and sleep apnea (88.8% vs. 78.8%, p = 0.01) was superior in OAGB. CONCLUSIONS: OAGB had a superior effect on weight loss as well as improvement of T2DM and sleep apnea. Furthermore, long-term problems such as IWL/WR and reflux were more related to SG. On the other hand, a malabsorptive procedure such as OAGB showed a higher risk for ND. Our findings support the available data in the literature.

Serum Levels of CXCL13 Are an Independent Predictor of Survival Following Resection of Biliary Tract Cancer.

BACKGROUND: The prognosis of biliary tract cancer (BTC) has remained very poor. Although tumor resection represents a potentially curative therapy for selected patients, tumor recurrence is common, and 5-year survival rates have remained below 50%. As stratification algorithms comprising the parameters of individual tumor biology are missing, the identification of ideal patients for extensive tumor surgery is often challenging. The CXC chemokine family exerts decisive functions in cell-cell interactions and has only recently been associated with cancer, but little is known about their function in BTC. Here, we aim to evaluate a potential role of circulating CXCL1, CXCL10 and CXCL13 in patients with resectable BTC. METHODS: Serum levels of CXCL1, CXCL10 and CXCL13 were measured by multiplex immunoassay in a cohort of 119 BTC patients undergoing tumor resection and 50 control samples. RESULTS: Circulating levels of CXCL1, CXCL10 and CXCL13 were all significantly elevated in BTC patients compared to healthy controls and increased the diagnostic power of established tumor markers such as CA19-9 when used in combination. Importantly, elevated levels of CXCL13 both before and after tumor resection identified a subgroup of patients with significantly impaired outcomes following tumor resection. As such, BTC patients with initial CXCL13 levels above the ideal prognostic cut-off value (25.01 pg/mL) had a median overall survival (OS) of 290 days compared to 969 days for patients with low initial CXCL13 levels. The prognostic value of circulating CXCL13 was further confirmed by uni- and multivariate Cox regression analyses. Finally, the individual kinetics of CXCL13 before and after tumor resection were also indicative of patient outcomes. CONCLUSION: Our data support a fundamental role of the CXC chemokine family in BTC and identified circulating levels of CXCL13 as a previously unrecognized marker for predicting outcomes following the resection of BTC.

Golgi Protein 73 (GP73) Serum Levels Predict Outcome after Resection of Biliary Tract Cancer.

BACKGROUND: Tumor resection represents the only potentially curative therapy for patients with biliary tract cancer. Nevertheless, disease recurrence is observed in about 50% of patients, leading to a 5-years survival rate of less than 50%. The Golgi protein 73 (GP73), a type II Golgi transmembrane protein, exerts important functions of intracellular protein processing and transportation. Circulating GP73 has recently been suggested as a prognostic marker following resection of hepatocellular carcinoma (HCC) but its role in the context of BTC has remained unknown. In this study, we evaluate a potential role of circulating GP73 as a novel biomarker in patients with resectable BTC. METHODS: GP73 serum levels were measured by immunoassay in n = 97 BTC and n = 40 HCC patients as well as n = 31 healthy controls. Results were correlated with clinical data. RESULTS: Serum GP73 levels were significantly elevated in BTC patients compared to healthy controls but lower compared to HCC patients. The combination of GP73/CA19-9 showed a sensitivity and specificity of 83.5% and 90.3% regarding the differentiation of BTC patients and healthy controls. BTC patients with baseline GP73 levels above the ideal cut-off value (42.47 ng/mL) showed a significantly reduced median overall survival (193 days) compared to patients with preoperative GP73 levels below this cut-off (882 days). These results were confirmed in uni- and multivariate Cox-regression analysis including several clinicopathological parameters such as age, ECOG performance status, tumor stage as well as established tumor markers and parameters of liver and kidney function. CONCLUSIONS: GP73 represents a previously unrecognized biomarker in the patients with resectable BTC that identifies patients with an impaired postoperative outcome. If larger clinical trials confirmed these findings, measurement of GP73 serum levels might become a novel tool in the challenging preoperative stratification process of patients with resectable BTC.

Clinical outcomes after one anastomosis gastric bypass versus sleeve gastrectomy in super-super-obese patients.

BACKGROUND: Bariatric surgery in super-super-obese (SSO) patients remains a continuous challenge due to intraabdominal fat masses, higher liver volume and existing comorbidities. A convenient procedure in SSO patients is one anastomosis gastric bypass (OAGB). The aim of this study was to compare the outcome of SSO patients undergoing OAGB in comparison to laparoscopic sleeve gastrectomy (LSG). METHODS: We retrospectively reviewed data from SSO patients who underwent OAGB and LSG in our institution between 2008 and 2020. Primary endpoints included percentage total body weight loss and percentage BMI loss at 12, 24, and 36 months after the operation. Secondary endpoints were perioperative complications, procedure length, length of hospital stay and outcome of comorbidities. RESULTS: 243 patients were included in this study. 93 patients underwent LSG and 150 underwent OAGB. At any of the time points evaluated, weight loss in patients after OAGB was greater than in LSG patients, while procedure length was significantly shorter for OAGB than LSG (81.4 vs. 92.1 min, p-value < 0.001). Additionally, mean length of hospital stay was shorter in the OAGB group (3.4 vs. 4.5 days, p-value < 0.001). There were more severe complications (Clavien-Dindo ≥ 3a) in the LSG group (11.8% vs 2.7%, p-value = 0.005). CONCLUSION: In this retrospective analysis, OAGB was superior to LSG in terms of weight loss in SSO patients. Procedure length and hospital stay were shorter after OAGB in comparison to LSG and there were fewer severe complications. OAGB can therefore be regarded a safe and effective treatment modality for SSO patients.

Comparative Analysis of Circulating Biomarkers for Patients Undergoing Resection of Colorectal Liver Metastases.

Surgical tumor resection has evolved as a potentially curative therapy for patients with resectable colorectal liver metastases (CRLM). However, disease recurrence is common and the available preoperative stratification strategies are often imprecise to identify the ideal candidates for surgical treatment, resulting in a postoperative 5-year survival rate below 50%. Data on the prognostic value of CEA, CA19-9 and other common laboratory parameters after CRLM resection are scarce and partly inconclusive. Here, we analyzed the prognostic potential of circulating CEA and CA19-9 in comparison to other standard laboratory markers in resectable CRLM patients. Serum levels of tumor markers and other laboratory parameters were analyzed in 125 patients with CRLM undergoing tumor resection at a tertiary referral center. Results were correlated with clinical data and outcome. Both tumor markers were significantly elevated in CRLM patients compared to healthy controls. Interestingly, elevated levels of CEA, CA19-9 and C-reactive protein (CRP) were associated with an unfavorable prognosis after CRLM resection in Kaplan-Meier curve analysis. However, only CEA and not CA19-9 or CRP serum levels were an independent prognostic marker in multivariate Cox regression analysis. Our data demonstrate that circulating levels of CEA rather than CA19-9 might be a valuable addition to the existing preoperative stratification algorithms to identify patients with a poor prognosis after CRLM resection.

General Practitioner's Knowledge about Bariatric Surgery Is Associated with Referral Practice to Bariatric Surgery Centers.

(1) Background: Patients seeking treatment for obesity and related diseases often contact general practitioners (GPs) first. The aim of this study was to evaluate GPs' knowledge about weight loss surgery (WLS) and potential stereotypes towards obese patients. (2) Methods: For this prospective cohort study, 204 GPs in the region of the bariatric surgery center at the University Hospital Aachen were included. The participants filled out a questionnaire comprising general treatment of obese patients, stigmatization towards obese patients (1-5 points) as well as knowledge regarding WLS (1-5 points). (3) Results: The mean age of the GPs was 54 years; 41% were female. Mean score for self-reported knowledge was 3.6 points out of 5. For stigma-related items, the mean score was 3.3 points out of 5. A total of 60% of the participants recognized bariatric surgery as being useful. Knowledge about bariatric surgery significantly correlated with the number of referrals to bariatric surgery centers (p < 0.001). No significant correlation was found between stigma and referral to surgery (p = 0.057). (4) Conclusions: The more GPs subjectively know about bariatric surgery, the more often they refer patients to bariatric surgery specialists-regardless of potentially present stereotypes. Therefore, GPs should be well informed about indications and opportunities of WLS.

Levels of Circulating PD-L1 Are Decreased in Patients with Resectable Cholangiocarcinoma.

Tumor resection represents the only curative treatment option for patients with biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma (CCA), perihilar and extrahepatic CCA and gallbladder cancer. However, many patients develop early tumor recurrence and are unlikely to benefit from surgery. Therefore, markers to identify ideal surgical candidates are urgently needed. Circulating programmed cell death 1 ligand 1 (PD-L1) has recently been associated with different malignancies, including pancreatic cancer which closely resembles BTC in terms of patients' prognosis and tumor biology. Here, we aim at evaluating a potential role of circulating PD-L1 as a novel biomarker for resectable BTC. METHODS: Serum levels of PD-L1 were analyzed by ELISA in 73 BTC patients and 42 healthy controls. RESULTS: Circulating levels of preoperative PD-L1 were significantly lower in patients with BTC compared to controls. Patients with low PD-L1 levels displayed a strong trend towards an impaired prognosis, and circulating PD-L1 was negatively correlated with experimental markers of promalignant tumor characteristics such as CCL1, CCL21, CCL25 and CCL26. For 37 out of 73 patients, postoperative PD-L1 levels were available. Interestingly, after tumor resection, circulating PD-L1 raised to almost normal levels. Notably, patients with further decreasing PD-L1 concentrations after surgery showed a trend towards an impaired postoperative outcome. CONCLUSION: Circulating PD-L1 levels were decreased in patients with resectable BTC. Lack of normalization of PD-L1 levels after surgery might identify patients at high risk for tumor recurrence or adverse outcome.

Development of a tailor-made surgical online learning platform, ensuring surgical education in times of the COVID19 pandemic.

BACKGROUND: During the worldwide COVID-19 pandemic, the quality of surgical education experiences sudden major restrictions. Students' presence in the operating theater and on wards is reduced to a bare minimum and face-to-face teaching is diminished. Aim of this study was therefore to evaluate alternative but feasible educational concepts, such as an online-only-platform for undergraduates. OBJECTIVE: A new online platform for undergraduate surgical education was implemented. A virtual curriculum for online-only education was designed. METHODS: A video-based online platform was designed. Following this, a cohort of medical students participating in a (voluntary) surgical course was randomized into a test and control group. Prior to conducting a written exam, students in the test group prepared using the video platform. Students in the control group prepared with standard surgical text books. Results of the exam were used to compare educational means. RESULTS: Students in the test group preparing through the video-based online platform reached significantly higher scores in the written exams (p = 0.0001) than students of the control group. A trend towards reduced preparation time that did not reach statistical significance was detectable in the test group (p = 0.090). Scores of "perceived workload" and "desire to become a surgeon" offered no differences between the groups. (p = 0.474 and 1.000). CONCLUSIONS: An online-only, virtual curriculum proved feasible for surgical education in undergraduates. While blended learning concepts were applied in both groups, only the test group had access to case-based videos of surgical procedures and scored significantly better in the written exams. Thus, video-based virtual education offers a realistic alternative to face-to-face teaching or conventional text books in times of restricted access to the operating theatre.

Comparison of Liver Recovery After Sleeve Gastrectomy and Roux-en-Y-Gastric Bypass.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a common condition in patients with obesity. Bariatric surgery has often been proposed as a viable treatment option, but the ideal surgical procedure remains unclear. Inconsistently, reports on postoperative deterioration of liver function put further doubt on which technique to apply. Aim of this study was to assess the impact of Roux-en-Y-gastric bypass (RYGB) and sleeve gastrectomy (SG) on the postoperative recovery of liver function. METHODS: A total of 175 patients with obesity that underwent bariatric surgery in our institution were included in this prospective cohort study. BMI, laboratory values, and liver function capacity (using LiMAx) were assessed preoperatively and at 6 and 12 months postoperatively. Generalized linear model (GLM) was performed to determine variables influencing liver function capacity after the operation. RESULTS: Prior to operations, 64% of patients presented with a diminished liver function capacity, as measured by LiMAx test. Liver function capacity significantly recovered after 12 months in the SG group (300 µg/kg/h preop vs. 367 µg/kg/h postop) but not in the RYGB group (306 µg/kg/h preop vs. 349 µg/kg/h). Preoperative factors impeding liver function recovery included type 2 diabetes mellitus (T2DM), weight, male sex, AST/thrombocyte ratio (APRI), and gamma-glutamyltransferase (GGT). CONCLUSION: Bariatric surgery, especially sleeve gastrectomy, leads to an improvement of liver function. However, in some patients with T2DM, higher preoperative weight and male sex postoperative deterioration of liver function capacity may occur.

Minimally Invasive Thoracoabdominal Esophagectomy Is Superior to Minimally Invasive Gastrectomy in Terms of Health-Related Quality of Life.

Background and Objectives: There are two operative approaches for adenocarcinomas of the esophagogastric junction: thoracoabdominal esophagectomy or transhiatal extended gastrectomy. Both procedures can be performed minimally invasively. Dependent on the exact localization of the tumor, both approaches are feasible. Aim of this study was to compare the health-related quality of life (HRQOL) of patients after minimally invasive esophagectomy (MIE) with patients who underwent minimally invasive gastrectomy (MIG). Methods: All patients who underwent MIE or gastrectomy for malignoma since 2014 were identified from our clinical database. The identified patients were contacted and asked to fill out a quality of life questionnaire (QLQ) for general and gastrointestinal QOL (European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-OG25). Results: Global HRQOL scores were higher in patients after MIE than after MIG. After MIE, global HRQOL scores were close to the control population. In cancer-specific syndromes, patients after MIE reported lower symptom scores for financial problems, eating, reflux, and eating with others than patients after MIG. Conclusion: In terms of HRQOL, MIE proved superior to MIG in long-term follow-up in this study. Patients after MIE reported a HRQOL close to that of a healthy reference population.

Circulating levels of microRNA193a-5p predict outcome in early stage hepatocellular carcinoma.

While tumor resection and liver transplantation (LT) represent potentially curative therapeutic options for patients with early-stage hepatocellular carcinoma (HCC), the identification of the ideal surgical candidates has remained challenging. Just recently, miRNA-193a-5p was described as a tumor suppressor in murine and human HCC but only little is known about circulating miRNA-193a-5p in HCC patients. Here, we evaluated serum levels of miR-193a-5p by qPCR in 41 HCC patients undergoing tumor resection (n = 33) or LT (n = 8) and 20 controls. Circulating relative miR-193a-5p levels were significantly elevated in HCC patients compared to healthy controls. While relative miR-193a-5p levels were comparable between patients of different underlying disease etiology and tumor size, high relative miR-193a-5p levels were predictive for the patients' postoperative outcome, which was confirmed in uni- and multivariate Cox-regression analysis. As such, HCC patients with a preoperative relative miR-193a-5p level above the ideal cut-off value (3.57) had a median overall survival (OS) of only 451 days compared to 1158 days in patients with a relative miR-193a-5p level below this cut-off value. Our data support a novel function of miR-193a-5p as a biomarker in early-stage HCC patients that might help to identify the best surgical candidates in terms of postoperative outcome.

Inhaled Argon Impedes Hepatic Regeneration after Ischemia/Reperfusion Injury in Rats.

Organoprotective effects of noble gases are subject of current research. One important field of interest is the effect of noble gases on hepatic regenerative capacity. For the noble gas argon, promising studies demonstrated remarkable experimental effects in neuronal and renal cells. The aim of this study was to investigate the effects of argon on the regenerative capacity of the liver after ischemia/reperfusion injury (IRI). Male, Sprague-Dawley rats underwent hepatic IRI by clamping of the hepatic artery. Expression of hepatoproliferative genes (HGF, IL-1ß, IL-6, TNF), cell cycle markers (BrdU, TUNEL, Ki-67), and liver enzymes (ALT, AST, Bilirubin, LDH) were assessed 3, 36, and 96 h after IRI. Expression of IL-1ß and IL-6 was significantly higher after argon inhalation after 36 h (IL-1ß 5.0 vs. 8.7 fold, p = 0.001; IL-6 9.6 vs. 19.1 fold, p = 0.05). Ki-67 was higher in the control group compared to the argon group after 36 h (214.0 vs. 38.7 positive cells/1000 hepatocytes, p = 0.045). Serum levels of AST and ALT did not differ significantly between groups. Our data indicate that argon inhalation has detrimental effects on liver regeneration after IRI as measured by elevated levels of the proinflammatory cytokines IL-1ß and IL-6 after 36 h. In line with these results, Ki-67 is decreased in the argon group, indicating a negative effect on liver regeneration in argon inhalation.

Circulating levels of soluble urokinase plasminogen activator receptor predict outcome after resection of biliary tract cancer.

BACKGROUND & AIMS: Surgical resection is the only potentially curative therapy for patients with biliary tract cancer (BTC), but 5-year survival rates after tumor resection have remained below 30%, corroborating the need for better stratification tools to identify the ideal surgical candidates. The soluble urokinase plasminogen activator receptor (suPAR) represents a mediator of inflammation and has been associated with distinct types of cancer. In this study, we evaluated a potential role of suPAR as a novel biomarker in patients undergoing BTC resection. METHODS: Tumor expression of uPAR was analyzed by immunohistochemistry in 108 BTC samples. Serum levels of suPAR were analyzed by ELISA in a training and validation cohort comprising a total of 117 patients with BTC and 76 healthy controls. RESULTS: High tumoral uPAR expression was associated with an adverse outcome after BTC resection. Accordingly, circulating levels of suPAR were significantly elevated in patients with BTC compared to healthy controls, as well as in patients with primary sclerosing cholangitis. Using a small training set, we established an optimal prognostic suPAR cut-off value of 3.72 ng/ml for patients with BTC. Importantly, preoperative suPAR serum levels above this cut-off value were associated with significantly impaired overall survival in both the training and validation cohort. Multivariate Cox-regression analysis including various clinicopathological parameters such as tumor stage, markers of inflammation and organ dysfunction, as well as tumor markers, revealed circulating suPAR levels as an independent prognostic marker following BTC resection. Finally, high preoperative suPAR levels were indicative of acute kidney injury after tumor resection. CONCLUSION: Circulating suPAR represents a previously unrecognized biomarker in patients with resectable BTC, which might help to preoperatively identify the ideal candidates for liver surgery. LAY SUMMARY: Surgical resection represents the only curative treatment option for patients with biliary tract cancer, but not all patients benefit to the same extent in terms of overall survival. Here, we provide evidence that serum levels of an inflammatory mediator (suPAR) are indicative of a patient's postoperative outcome and might thus help to identify the ideal surgical candidates.

3D Optical Imaging as a New Tool for the Objective Evaluation of Body Shape Changes After Bariatric Surgery.

INTRODUCTION: Bariatric surgery is the most effective treatment option for obesity. It results in massive weight loss and improvement of obesity-related diseases. At the same time, it leads to a drastic change in body shape. These body shape changes are mainly measured by two-dimensional measurement methods, such as hip and waist circumference. These measurement methods suffer from significant measurement errors and poor reproducibility. Here, we present a three-dimensional measurement tool of the torso that can provide an objective and reproducible source for the detection of body shape changes after bariatric surgery. MATERIAL AND METHODS: In this study, 25 bariatric patients were scanned with Artec EVA®, an optical three-dimensional mobile scanner up to 1 week before and 6 months after surgery. Data were analyzed, and the volume of the torso, the abdominal circumference and distances between specific anatomical landmarks were calculated. The results of the processed three-dimensional measurements were compared with clinical data concerning weight loss and waist circumference. RESULTS: The volume of the torso decreased after bariatric surgery. Loss of volume correlated strongly with weight loss 6 months after the operation (r = 0.6425, p = 0.0005). Weight loss and three-dimensional processed data correlated better (r = 0.6121, p = 0.0011) than weight loss and waist circumference measured with a measuring tape (r = 0.3148, p = 0.1254). CONCLUSION: Three-dimensional imaging provides an objective and reproducible source for the detection of body shape changes after bariatric surgery. We recommend its use for the evaluation of central obesity, particularly for research issues and body imaging before and after bariatric surgery.

Noninvasive Evaluation of Liver Function in Morbidly Obese Patients.

BACKGROUND: More than half of the obese patients develop nonalcoholic fatty liver disease (NAFLD), which may further progress to nonalcoholic steatohepatitis (NASH) and cirrhosis. The aim of this study was to assess alterations in liver function in obese patients with a noninvasive liver function test. METHODS: In a prospective cohort study 102 morbidly obese patients undergoing bariatric surgery were evaluated for their liver function. Liver function capacity was determined by the LiMAx® test (enzymatic capacity of cytochrome P450 1A2). Liver biopsy specimens were obtained intraoperatively and classified according to the NAFLD Activity Score (NAS). NASH clinical score was additionally calculated from laboratory and clinical parameters. RESULTS: Median liver function capacity was 286 (IQR = 141) µg/kg/h. 27% of patients were histologically categorized as definite NASH, 39% as borderline, and 34% as not NASH. A significant correlation was observed between liver function capacity and NAS (r = -0.492; p < 0.001). The sensitivity and specificity of the LiMAx® test to distinguish between definite NASH and not NASH were 85.2% and 82.9% (AUROC 0.859), respectively. According to the NASH clinical scoring system, 14% were classified as low risk, 31% as intermediate, 26% as high, and 29% as very high risk. Liver function capacity is also significantly correlated with the NASH clinical scoring system (r = -0.411; p < 0.001). CONCLUSIONS: Obese patients show a diminished liver function capacity, especially those suffering from type 2 diabetes. The liver function capacity correlates with histological and clinical scoring systems. The LiMAx® test may be a valuable tool for noninvasive screening for NASH in obese patients.