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.

Hepatocellular loss of mTOR aggravates tumor burden in nonalcoholic steatohepatitis-related HCC.

Obesity and associated nonalcoholic steatohepatitis (NASH) are on the rise globally. NASH became an important driver of hepatocellular carcinoma (HCC) in recent years. Activation of the central metabolic regulator mTOR (mechanistic target of rapamycin) is frequently observed in HCCs. However, mTOR inhibition failed to improve the outcome of HCC therapies, demonstrating the need for a better understanding of the molecular and functional consequences of mTOR blockade. We established a murine NASH-driven HCC model based on long-term western diet feeding combined with hepatocellular mTOR-inactivation. We evaluated tumor load and whole-body fat percentage via µCT-scans, analyzed metabolic blood parameters and tissue proteome profiles. Additionally, we used a bioinformatic model to access liver and HCC mitochondrial metabolic functions. The tumor burden was massively increased via mTOR-knockout. Several signs argue for extensive metabolic reprogramming of glucose, fatty acid, bile acid and cholesterol metabolism. Kinetic modeling revealed reduced oxygen consumption in KO-tumors. NASH-derived HCC pathogenesis is driven by metabolic disturbances and should be considered separately from those caused by other etiologies. We conclude that mTOR functions as tumor suppressor in hepatocytes especially under long-term western diet feeding. However, some of the detrimental consequences of this diet are attenuated by mTOR blockade.

Choice of Polymer, but Not Mesh Structure Variation, Reduces the Risk of Bacterial Infection with Staphylococcus aureus In Vivo.

BACKGROUND: Synthetic mesh material is of great importance for surgical incisional hernia repair. The physical and biochemical characteristics of the mesh influence mechanical stability and the foreign body tissue reaction. The influence on bacterial infections, however, remains ill-defined. The aim of the present study was to evaluate the influence of a modified mesh structure with variation in filament linking on the occurrence of bacterial infection that is indicated by the occurrence of CD68+, CD4+, and CD8+ cells in two different materials. METHODS: A total of 56 male Sprague Dawley rats received a surgical mesh implant in a subcutaneous abdominal position. The mesh of two different polymers (polypropylene (PP) and polyvinylidenfluoride (PVDF)) and two different structures (standard structure and bold structure with higher filament linking) were compared. During the implantation, the meshes were infected with Staphylococcus (S.) aureus. After 7 and 21 days, meshes were explanted, and the early and late tissue responses to infection were histologically evaluated. RESULTS: Overall, the inflammatory tissue response was higher at 7 days when compared to 21 days. At 7 days, PP meshes of the standard structure (PP-S) showed the strongest inflammatory tissue response in comparison to all the other groups. At 21 days, no statistically significant difference between different meshes was detected. CD8+ cytotoxic T cells showed a significant difference at 21 days but not at 7 days. PP meshes of both structures showed a higher infiltration of CD8+ T cells than PVDF meshes. CD4+ T helper cells differed at 7 days but not at 21 days, and PVDF meshes in a bold structure showed the highest CD4+ T cell count. The number of CD68+ macrophages was also significantly higher in PP meshes in a standard structure when compared to PVDF meshes at 21 days. CONCLUSION: The inflammatory tissue response to S. aureus infection appears to be highest during the early period after mesh implantation. PP meshes showed a higher inflammatory response than PVDF meshes. The mesh material appears to be more important for the risk of infection than the variation in filament linking.

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.

No difference in outcomes between large- and small-pore meshes in a prospective, randomized, multicenter trial investigating open retromuscular meshplasty for incisional hernia repair.

STUDY DESIGN: A randomized, controlled, prospective multicenter clinical trial with a parallel group design was initiated in eight surgical centers to compare a large-pore polypropylene mesh (Ultrapro®) to a small-pore polypropylene mesh (Premilene®) within a standardized retromuscular meshplasty for incisional hernia repair. METHODS: Between 2004 and 2006, patients with a fascial defect with a minimum diameter of 4 cm after vertical midline laparotomy were recruited for the trial. Patients underwent retromuscular meshplasty with either a large-pore or a small-pore mesh to identify the superiority of the large-pore mesh. Follow-up visits were scheduled at 5 and 21 days and 4, 12, and 24 months after surgery. A clinical examination, a modified short form 36 (SF-36®), a daily activity questionnaire, and an ultrasound investigation of the abdominal wall were completed at every follow-up visit. The primary outcome criterion was foreign body sensation at the 12-month visit, and the secondary endpoint criteria were the occurrence of hematoma, seroma, and chronic pain within 24 months postoperatively. RESULTS: In 8 centers, 181 patients were included in the study. Neither foreign body sensation within the first year after surgery (27.5% Ultrapro®, 32.2% Premilene®) nor the time until the first occurrence of foreign body sensation within the first year was significantly different between the groups. Regarding the secondary endpoints, no significant differences could be observed. At the 2-year follow-up, recurrences occurred in 5 Ultrapro® patients (5.5%) and 4 Premilene® patients (4.4%). CONCLUSION: Despite considerable differences in theoretical and experimental works, we have not been able to identify differences in surgical or patient-reported outcomes between the use of large- and small-pore meshes for retromuscular incisional hernia repair. TRIAL REGISTRATION: Clinical Trials NCT04961346 (16.06.2021) retrospectively registered.

Machine learning prediction model for postoperative outcome after perforated appendicitis.

PURPOSE: Appendectomy for acute appendicitis is one of the most common operative procedures worldwide in both children and adults. In particular, complicated (perforated) cases show high variability in individual outcomes. Here, we developed and validated a machine learning prediction model for postoperative outcome of perforated appendicitis. METHODS: Retrospective analyses of patients with clinically and histologically verified perforated appendicitis over 10 years were performed. Demographic and surgical baseline characteristics were used as competing predictors of single-patient outcomes along multiple dimensions via a random forest classifier with stratified subsampling. To assess whether complications could be predicted in new, individual cases, the ensuing models were evaluated using a replicated 10-fold cross-validation. RESULTS: A total of 163 patients were included in the study. Sixty-four patients underwent laparoscopic surgery, whereas ninety-nine patients got a primary open procedure. Interval from admission to appendectomy was 9 ± 12 h and duration of the surgery was 74 ± 38 min. Forty-three patients needed intensive care treatment. Overall mortality was 0.6 % and morbidity rate was 15%. Severe complications as assessed by Clavien-Dindo > 3 were predictable in new cases with an accuracy of 68%. Need for ICU stay (> 24 h) could be predicted with an accuracy of 88%, whereas prolonged hospitalization (greater than 7-15 days) was predicted by the model with an accuracy of 76%. CONCLUSION: We demonstrate that complications following surgery, and in particular, health care system-related outcomes like intensive care treatment and extended hospitalization, may be well predicted at the individual level from demographic and surgical baseline characteristics through machine learning approaches.

Roux-en-Y Versus One Anastomosis Gastric Bypass as Redo-Operations Following Sleeve Gastrectomy: A Retrospective Study.

BACKGROUND: Aim of this study was to improve knowledge about the best conversional bariatric procedure following sleeve gastrectomy (SG). METHODS: Data of conversional Roux-en-Y gastric bypass (RYGB) and of one anastomosis gastric bypass (OAGB) after SG were collected prospectively and analyzed retrospectively. Weight loss parameters, gastroesophageal reflux disease (GERD) and comorbidities outcomes were recorded. RESULTS: Total of 123 patients (90 female, mean age 44 ± 0.9 years, mean body mass index (BMI) 42 ± 0.8 kg/m2) had either RYGB (n = 68) or OAGB (n = 55). Perioperative mortality was zero. Mean surgery time was significantly shorter for OAGB (168 ± 7.2 vs. 201 ± 6.8 min). Perioperative complication rates were not significantly (ns) different between RYGB and OAGB. Total body weight loss (TBWL) in RYGB and OAGB was 18 ± 2.2% and 18 ± 1.9% (12 months) and 18 ± 3.0% and 23 ± 2.6% (24 months; ns), respectively. Length of (individualized) biliopancreatic limb (BPL) correlated significantly with weight loss. Remission rates after 12 months of RYGB and OAGB for arterial hypertension (aHt) were 89% and 92%, for obstructive sleep apnea (OSAS) 56% and 82%, for Type 2 diabetes mellitus (T2DM) 100% and 92%, for osteoarthritis 64% and 85% and for GERD 89% versus 87% (ns), respectively. Nutritional deficiencies were comparable in RYGB (n = 11) and OAGB (n = 14) group (ns). CONCLUSION: Both RYGB and OAGB are effective conversional procedures after SG, leading to comparable TBWL, BMI-loss and high remission rates of comorbidities including GERD. Significantly shorter operation times were in favor of OAGB. BPL, which was longer in OAGB was significantly related to higher %TBWL and %BMI-loss compared to RYGB.

Two Polyurethane Adhesives for PVDF Fixation Show Superior Biocompatibility in a Rat Model.

BACKGROUND: The current standard for open and laparoscopic repair of incisional hernia consist of an abdominal wall augmentation by mesh implantation. However, the ideal fixation method of the prothesis material remains under discussion, due to potential complications of conventional fixation methods such as chronic abdominal pain or intestinal obstruction. As the use of adhesive based mesh fixation is an option of growing interest, the aim of this experimental study was to investigate the strength and biocompatibility of two newly developed polyurethane-based adhesives in comparison to a cyanoacrylatic adhesive, which is currently in clinical use. METHODS: Two experimental polyurethane/urea-based adhesives (Adhesive-A and Adhesive-B) were compared to a conventional cyanoacrylatic adhesive and an untreated control group. Biomechanical testing was carried out using a pull-out test in uniaxial tensile mode, while biocompatibility assessment was performed in a rat model with 40 Sprague-Dawley rats receiving a subcutaneous implanted PVDF mesh fixed by the corresponding adhesive. Histological and immunohistochemical analysis by a Tissue FAXS system examined the tissue integration of the mesh/adhesive combination and characterized the foreign body reaction. RESULTS: Biomechanical testing of the mesh/adhesive combinations showed a minimal strength of 15.08 N without a significant difference between the groups. Cellular penetration into the mesh/adhesive interface was significantly improved after application of polyurethane adhesives and Adhesive-A showed a significantly lower migration of CD68 positive cells to the adhesive sites compared to cyanoacrylate after 7 days. CONCLUSION: The developed polyurethane-based adhesives are a promising alternative with sufficient adhesive strength and superior short-term biocompatibility to cyanoacrylate.

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.

Safety of laparoscopic hepatectomy in patients with severe comorbidities - A propensity score matched analysis.

BACKGROUND: Laparoscopic hepatectomy (LH) is nowadays considered as the standard of care for various liver malignancies. However, studies focusing on perioperative outcome after LH in patients with severe comorbidities are still sparse. METHODS: 247 patients, who underwent LH between January 2016 and March 2020 at European surgical center Aachen Maastricht (ESCAM) were retrospectively analyzed regarding surgical outcome. All patients were categorized according to the ASA guidelines and a propensity score matched (PSM) analysis was performed to compare patients with severe comorbidities with patients with minor or no comorbidities. RESULTS: After PSM, no statistically significant differences regarding clinical characteristics were observed. We performed major resections in 26.4% of h-ASA (ASA > 2) patients and 19.4% of l-ASA (ASA≤2) patients, respectively (P = .322). Overall morbidity (Clavien-Dindo≥1) was observed more frequently in the h-ASA group (h-ASA: 25.0% vs. l-ASA: 8.3%; P = .007) while analysis of major morbidity (Clavien-Dindo≥3b) showed a non-significant tendency for more complications in h-ASA patients (h-ASA: 8.3% vs. l-ASA: 1.4%; P = .053). A subgroup analysis identified major resection (HR = 5.05; P = .006) as an independent risk factor for the occurrence of any postoperative complication and chronic kidney disease (HR = 22.59; P = .030) and liver fibrosis (HR = 30.16; P = .031) as risk factors for the occurrence of major complications in h-ASA patients. CONCLUSION: LH in patients with severe systemic comorbidities shows a strong tendency towards an increased rate of major complications. Careful patient selection with respect to the planned extent of resection and the presence of chronic kidney disease and liver fibrosis should be performed to improve perioperative results.

Cyclin E1 in Murine and Human Liver Cancer: A Promising Target for Therapeutic Intervention during Tumour Progression.

Cyclin E1 (CCNE1) is a regulatory subunit of Cyclin-dependent kinase 2 (CDK2) and is thought to control the transition of quiescent cells into cell cycle progression. Recently, we identified CCNE1 and CDK2 as key factors for the initiation of hepatocellular carcinoma (HCC). In the present study, we dissected the contributions of CCNE1 and CDK2 for HCC progression in mice and patients. Therefore, we generated genetically modified mice allowing inducible deletion of Ccne1 or Cdk2. After initiation of HCC, using the hepatocarcinogen diethylnitrosamine (DEN), we deleted Ccne1 or Cdk2 and subsequently analysed HCC progression. The relevance of CCNE1 or CDK2 for human HCC progression was investigated by in silico database analysis. Interventional deletion of Ccne1, but not of Cdk2, substantially reduced the HCC burden in mice. Ccne1-deficient HCCs were characterised by attenuated proliferation, impaired DNA damage response and downregulation of markers for stemness and microinvasion. Additionally, the tumour microenvironment of Ccne1-deficient mice showed a reduction in immune mediators, myeloid cells and cancer-associated fibroblasts. In sharp contrast, Cdk2 was dispensable for HCC progression in mice. In agreement with our mouse data, CCNE1 was overexpressed in HCC patients independent of risk factors, and associated with reduced disease-free survival, a common signature for enhanced chromosomal instability, proliferation, dedifferentiation and invasion. However, CDK2 lacked diagnostic or prognostic value in HCC patients. In summary, CCNE1 drives HCC progression in a CDK2-independent manner in mice and man. Therefore, interventional inactivation of CCNE1 represents a promising strategy the treatment of liver cancer.

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.

Incisional hernia repair by synthetic mesh prosthesis in patients with inflammatory bowel disease: a comparative analysis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have a high-life time risk undergoing abdominal surgery and are prone to develop incisional hernias (IH) in the postoperative course. Therefore, we investigated the role of IBD as perioperative risk factor in open ventral hernia repair (OVHR) as well as the impact of IBD on hernia recurrence during postoperative follow-up. METHODS: The postoperative course of 223 patients (Non-IBD (n = 199) and IBD (n = 34)) who underwent OVHR were compared by means of extensive group comparisons and binary logistic regressions. Hernia recurrence was investigated in the IBD group according to the Kaplan-Meier method and risk factors for recurrence determined by Cox regressions. RESULTS: General complications (≥ Clavien-Dindo I) occurred in 30.9% (72/233) and major complications (≥ Clavien-Dindo IIIb) in 7.7% (18/233) of the overall cohort with IBD being the single independent risk-factor for major complications (OR = 4.2, p = 0.007). Further, IBD patients displayed a recurrence rate of 26.5% (9/34) after a median follow-up of 36 months. Multivariable analysis revealed higher rates of recurrence in patients with ulcerative colitis (UC, 8/15, HR = 11.7) compared to patients with Crohn's disease (CD, 1/19, HR = 1.0, p = 0.021). CONCLUSION: IBD is a significant risk factor for major postoperative morbidity after OVHR. In addition, individuals with IBD show high rates of hernia recurrence over time with UC patients being more prone to recurrence than patients with CD.

Liver transplantation in malignant disease.

Liver transplantation for malignant disease has gained increasing attention as part of transplant oncology. Following the implementation of the Milan criteria, hepatocellular carcinoma (HCC) was the first generally accepted indication for transplantation in patients with cancer. Subsequently, more liberal criteria for HCC have been developed, and research on this topic is still ongoing. The evident success of liver transplantation for HCC has led to the attempt to extend its indication to other malignancies. Regarding perihilar cholangiocarcinoma, more and more evidence supports the use of liver transplantation, especially after neoadjuvant therapy. In addition, some data also show a benefit for selected patients with very early stage intrahepatic cholangiocarcinoma. Hepatic epithelioid hemangioendothelioma is a very rare but nonetheless established indication for liver transplantation in primary liver cancer. In contrast, patients with hepatic angiosarcoma are currently not considered to be optimal candidates. In secondary liver tumors, neuroendocrine cancer liver metastases are an accepted but comparability rare indication for liver transplantation. Recently, some evidence has been published supporting the use of liver transplantation even for colorectal liver metastases. This review summarizes the current evidence for liver transplantation for primary and secondary liver cancer.

Association of Body Composition and Sarcopenia with NASH in Obese Patients.

Obese patients often suffer from sarcopenia or sarcopenic obesity (SO) that can trigger inflammatory diseases including non-alcoholic steatohepatitis (NASH). Sarcopenia and SO can be diagnosed through measuring parameters of body composition such as skeletal muscle mass (SMM), skeletal muscle index (SMI) and fat mass (FM) obtained by bioelectrical impedance analysis (BIA). The aim of this study was to assess the relationship of body composition and NASH in patients with obesity. A total of 138 patients with obesity that underwent bariatric surgery were included in this study. BIA was used to estimate body composition. A liver biopsy was taken intraoperatively and histological assessment of NASH was performed. A total of 23 patients (17%) were classified as NASH and 65 patients (47%) met the criteria for borderline NASH. Body mass index (BMI) was significantly higher in patients with NASH compared to borderline NASH and no NASH (56.3 kg/m2 vs. 51.6 kg/m2 vs. 48.6 kg/m2, p = 0.004). Concerning body composition, FM, but also SMM and SMI were significantly higher in patients with NASH (p-values 0.011, 0.005 and 0.006, resp.). Fat mass index (FMI) and weight-adjusted skeletal muscle index (SMI_weight) failed to reach statistical significance (p-values 0.067 and 0.661). In patients with obesity, higher FM were associated with NASH. Contrary to expectations, SMM and SMI were also higher in patients with NASH. Therefore, higher body fat, rather than sarcopenia and SO, might be decisive for development of NASH in patients with obesity.

Deletion of mTOR in liver epithelial cells enhances hepatic metastasis of colon cancer.

Activation of the mechanistic target of rapamycin (mTOR) pathway is frequently found in cancer, but mTOR inhibitors have thus far failed to demonstrate significant antiproliferative efficacy in the majority of cancer types. Besides cancer cell-intrinsic resistance mechanisms, it is conceivable that mTOR inhibitors impact on non-malignant host cells in a manner that ultimately supports resistance of cancer cells. Against this background, we sought to analyze the functional consequences of mTOR inhibition in hepatocytes for the growth of metastatic colon cancer. To this end, we established liver epithelial cell (LEC)-specific knockout (KO) of mTOR (mTORLEC ) mice. We used these mice to characterize the growth of colorectal liver metastases with or without partial hepatectomy to model different clinical settings. Although the LEC-specific loss of mTOR remained without effect on metastasis growth in intact liver, partial liver resection resulted in the formation of larger metastases in mTORLEC mice compared with wildtype controls. This was accompanied by significantly enhanced inflammatory activity in LEC-specific mTOR KO livers after partial liver resection. Analysis of NF-ĸB target gene expression and immunohistochemistry of p65 displayed a significant activation of NF-ĸB in mTORLEC mice, suggesting a functional importance of this pathway for the observed inflammatory phenotype. Taken together, we show an unexpected acceleration of liver metastases upon deletion of mTOR in LECs. Our results support the notion that non-malignant host cells can contribute to resistance against mTOR inhibitors and encourage testing whether anti-inflammatory drugs are able to improve the efficacy of mTOR inhibitors for cancer therapy. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

CT-Based Prediction of Liver Function and Post-PVE Hypertrophy Using an Artificial Neural Network.

BACKGROUND: This study aimed to evaluate whether hypertrophy after portal vein embolization (PVE) and maximum liver function capacity (LiMAx) are predictable by an artificial neural network (ANN) model based on computed tomography (CT) texture features. METHODS: We report a retrospective analysis on 118 patients undergoing preoperative assessment by CT before and after PVE for subsequent extended liver resection due to a malignant tumor at RWTH Aachen University Hospital. The LiMAx test was carried out in a subgroup of 55 patients prior to PVE. Associations between CT texture features and hypertrophy as well as liver function were assessed by a multilayer perceptron ANN model. RESULTS: Liver volumetry showed a median hypertrophy degree of 33.9% (16.5-60.4%) after PVE. Non-response, defined as a hypertrophy grade lower than 25%, was found in 36.5% (43/118) of the cases. The ANN prediction of the hypertrophy response showed a sensitivity of 95.8%, specificity of 44.4% and overall prediction accuracy of 74.6% (p < 0.001). The observed median LiMAx was 327 (248-433) µg/kg/h and was strongly correlated with the predicted LiMAx (R2 = 0.89). CONCLUSION: Our study shows that an ANN model based on CT texture features is able to predict the maximum liver function capacity and may be useful to assess potential hypertrophy after performing PVE.

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.