Surgical versus endoscopic gastroenterostomy for gastric outlet obstruction: a retrospective multicentric comparative study of technical and clinical success.

PURPOSE: Gastric outlet obstruction (GOO) is mainly due to advanced malignant disease. GOO can be treated by surgical gastroenterostomy (SGE), endoscopic enteral stenting (EES), or endoscopic ultrasound-guided gastroenterostomy (EUS-GE) to improve the quality of life. METHODS: Between 2009 and 2022, patients undergoing SGE or EUS-GE for GOO were included at three centers. Technical and clinical success rates, post-procedure adverse events (AEs), length of hospital stay (LOS), 30-day all-cause mortality, and recurrence of GOO were retrospectively analyzed and compared between SGE and EUS-GE. Predictive factors for technical and clinical failure after SGE and EUS-GE were identified. RESULTS: Of the 97 patients included, 56 (57.7%) had an EUS-GE and 41 (42.3%) had an SGE for GOO, with 62 (63.9%) GOO due to malignancy and 35 (36.1%) to benign disease. The median follow-up time was 13,4 months (range 1 days-106 months), with no difference between the two groups (p = 0.962). Technical (p = 0.133) and clinical (p = 0.229) success rates, severe morbidity (p = 0.708), 30-day all-cause mortality (p = 0.277) and GOO recurrence (p = 1) were similar. EUS-GE had shorter median procedure duration (p < 0.001), lower post-procedure ileus rate (p < 0.001), and shorter median LOS (p < 0.001) than SGE. In univariate analysis, no risk factors for technical or clinical failure in SGE were identified and abdominal pain reported before the procedure was a risk factor for technical failure in the EUS-GE group. No risk factor for clinical failure was identified for EUS-GE. In the subgroup of GOO due to benign disease, SGE was associated with better technical success (p = 0.035) with no difference in clinical success rate compared to EUS-GE (p = 1). CONCLUSION: EUS-GE provides similar long-lasting symptom relief as SGE for GOO whether for benign or malignant disease. SGE may still be indicated in centers with limited experience with EUS-GE or may be reserved for patients in whom endoscopic technique fails.

The impact of cirrhosis on short and long postoperative outcomes after distal pancreatectomy.

BACKGROUND: The impact of cirrhosis on the postoperative outcomes of distal pancreatectomy is yet to be reported. We aimed to evaluate the outcomes of distal pancreatectomy in patients with cirrhosis. METHODS: We conducted a retrospective, multicentric study patients with cirrhosis who underwent planned distal pancreatectomy between 2008 and 2020 in French high volume centers. Patients with cirrhosis were matched 1:4 for demographic, surgical, and histologic criteria with patients without cirrhosis. The primary endpoint was severe morbidity (Clavien-Dindo grade ≥III). The secondary endpoints were postoperative complications, specifically related to cirrhosis and pancreatic surgery, and survival for patients with pancreatic adenocarcinoma. RESULTS: Overall, 32 patients with cirrhosis were matched with 128 patients without cirrhosis. Most patients (93.5%) had Child-Pugh A cirrhosis. The severe morbidity rate after distal pancreatectomy was higher in patients with cirrhosis than in those without cirrhosis (28.13% vs 25.75%, P = .11. The operative time was significantly longer in the cirrhotic group compared with controls (P = .01). However, patients with and without cirrhosis had comparable blood loss and conversion rates. Postoperatively, the two groups had similar rates of pancreatic fistula, hemorrhage, reoperation, postoperative mortality, and survival rates at 1, 3, and 5 years. CONCLUSION: The current study suggests that distal pancreatectomy in high-volume centers is feasible for patients with compensated cirrhosis.

Predictive value of C-reactive protein for postoperative liver-specific surgical site infections.

BACKGROUND: C-reactive protein is a useful biological tool to predict infectious complications, but its predictive value in detecting organ-specific surgical site infection after liver resection has never been studied. We aimed to evaluate the predictive value of c-reactive protein and determine the cut-off values to detect postoperative liver resection-surgical site infection. METHODS: A multicentric analysis of consecutive patients with liver resection between 2018 and 2021 was performed. The predictive value of postoperative day 1, postoperative day 3, and postoperative day 5 C-reactive protein levels was evaluated using the area under the receiver operating characteristic curve. Cut-off values were determined using the Youden index in a 500-fold bootstrap resampling of 500 patients treated at 3 centers, who comprised the development cohort and were tested in an external independent validation cohort of 166 patients at a fourth center. RESULTS: Among the 500 patients who underwent liver resection of the development cohort, liver resection-surgical site infection occurred in 66 patients (13.2%), and the median time to diagnosis was 6.0 days (interquartile range, 4.0-9.0) days. Median C-reactive protein levels were significantly higher on postoperative day 1, postoperative day 3, and postoperative day 5 in the liver resection-surgical site infection group compared with the non-surgical site infection group (50.5 vs 34.5 ng/mL, 148.0 vs 72.5 ng/mL, and 128.4 vs 35.2 ng/mL, respectively; P < .001). Postoperative day 3 and postoperative day 5 C-reactive protein-level area under the curve values were 0.76 (95% confidence interval, 0.64-0.88, P < .001) and 0.82 (95% confidence interval, 0.72-0.92, P < .001), respectively. Postoperative day 3 and postoperative day 5 optimal cut-off values of 100 mg/L and 87.0 mg/L could be used to rule out liver resection-surgical site infection, with a negative predictive value of 87.0% (interquartile range, 70.2-93.8) and 76.0% (interquartile range, 65.0-88.0), respectively, in the validation cohort. CONCLUSION: Postoperative day 3 and postoperative day 5 C-reactive protein levels may be valuable predictive tools for liver resection-surgical site infection and aid in hospital discharge decision-making in the absence of other liver-related complications.

The falciform/round ligament "flooring," an effective method to reduce life-threatening post-pancreatectomy hemorrhage occurrence.

PURPOSE: Late post-pancreatectomy hemorrhage (PPH) represents the most severe complication after pancreatic surgery. We have measured the efficacy of major vessels "flooring" with falciform/round ligament to prevent life-threatening grade C late PPH after pancreaticoduodenectomy (PD) and distal pancreatectomy (DP). METHODS: All consecutive patients who underwent PD and DP between 2013 and 2021 were retrospectively reviewed on a prospectively maintained database. The cohort was divided in two groups: "flooring" vs. "no flooring" method group. The "no flooring" group had omental flap interposition. Patient characteristics and operative and postoperative data including clinically relevant postoperative pancreatic fistula (CR-POPF), late PPH (grade B and C), and 90-day mortality were compared between the two groups. RESULTS: Two hundred and forty patients underwent pancreatic resections, including 143 PD and 97 DP. The "flooring" method was performed in 61 patients (39 PD and 22 DP). No difference was found between the two groups concerning severe morbidity, CR-POPF, delayed PPH, and mortality rate. The rate of patients requiring postoperative intensive care unit was lower in the "flooring" than in the "no flooring" method group (11.5% vs. 25.1%, p = 0.030). Among patients with grade B/C late PPH (n = 30), the rate of life-threatening grade C late PPH was lower in the "flooring" than in the "no flooring" method group (28.6% (n = 2/7) vs. 82.6% (n = 19/24), p = 0.014). Risk factor analysis showed that the "flooring" method was the only protective factor against grade C late PPH occurrence (p = 0.013). CONCLUSION: The "flooring" method using the falciform/round ligament should be considered during pancreatectomies to reduce the occurrence of life-threatening grade C late PPH.

Despite similar clinical features metabolomics reveals distinct signatures in insulin resistant and progressively obese minipigs

Obesity is a major contributor to the silent and progressive development of type 2 diabetes (T2D) whose prevention could be improved if individuals at risk were identified earlier. Our aim is to identify early phenotypes that precede T2D in diet-induced obese minipigs. We fed four groups of minipigs (n = 5–10) either normal-fat or high-fat high-sugar diet during 2, 4, or 6 months. Morphometric features were recorded, and metabolomics and clinical parameters were assessed on fasting plasma samples. Multivariate statistical analysis on 46 morphometrical and clinical parameters allowed to differentiate 4 distinct phenotypes: NFC (control group) and three others (HF2M, HF4M, HF6M) corresponding to the different stages of the obesity progression. Compared to NFC, we observed a rapid progression of body weight and fat mass (4-, 7-, and tenfold) in obese phenotypes. Insulin resistance (IR; 2.5-fold increase of HOMA-IR) and mild dyslipidemia (1.2- and twofold increase in total cholesterol and HDL) were already present in the HF2M and remained stable in HF4M and HF6M. Plasma metabolome revealed subtle changes of 23 metabolites among the obese groups, including a progressive switch in energy metabolism from amino acids to lipids, and a transient increase in de novo lipogenesis and TCA-related metabolites in HF2M. Low anti-oxidative capacities and anti-inflammatory response metabolites were found in the HF4M, and a perturbed hexose metabolism was observed in HF6M. Overall, we show that IR and progressively obese minipigs reveal phenotype-specific metabolomic signatures for which some of the identified metabolites could be considered as potential biomarkers of early progression to TD2. (AU)

Compared with Milk Protein, a Wheat and Pea Protein Blend Reduces High-Fat, High-Sucrose Induced Metabolic Dysregulations while Similarly Supporting Tissue Protein Anabolism in Rats.

BACKGROUND: Plant proteins (PPs) have been associated with better cardiovascular health than animal proteins (APs) in epidemiological studies. However, the underlying metabolic mechanisms remain mostly unknown. OBJECTIVES: Using a combination of cutting-edge isotopic methods, we aimed to better characterize the differences in protein and energy metabolisms induced by dietary protein sources (PP compared with AP) in a prudent or western dietary context. METHODS: Male Wistar rats (n = 44, 8 wk old) were fed for 4.5 mo with isoproteic diets differing in their protein isolate sources, either AP (100% milk) or PP (50%:50% pea: wheat) and being normal (NFS) or high (HFS) in sucrose (6% or 15% kcal) and saturated fat (7% or 20% kcal), respectively. We measured body weight and composition, hepatic enzyme activities and lipid content, and plasma metabolites. In the intestine, liver, adipose tissues, and skeletal muscles, we concomitantly assessed the extent of amino acid (AA) trafficking using a 15N natural abundance method, the rates of macronutrient routing to dispensable AA using a 13C natural abundance method, and the metabolic fluxes of protein synthesis (PS) and de novo lipogenesis using a 2H labeling method. Data were analyzed using ANOVA and Mixed models. RESULTS: At the whole-body level, PP limited HFS-induced insulin resistance (-27% in HOMA-IR between HFS groups, P < 0.05). In the liver, PP induced lower lipid content (-17%, P < 0.01) and de novo lipogenesis (-24%, P < 0.05). In the different tissues studied, PP induced higher AA transamination accompanied by higher routings of dietary carbohydrates and lipids toward dispensable AA synthesis by glycolysis and ß-oxidation, resulting in similar tissue PS and protein mass. CONCLUSIONS: In growing rats, compared with AP, a balanced blend of PP similarly supports protein anabolism while better limiting whole-body and tissue metabolic dysregulations through mechanisms related to their less optimal AA profile for direct channeling to PS.

An Ex Situ Cadaver Liver Training Model Continuously Pressurized to Simulate Specific Skills Involved in Laparoscopic Liver Resection: the Lap-Liver Trainer.

BACKGROUND: Laparoscopic liver resection (LLR) requires delicate skills. The aim of the study was to develop a training model mimicking as much as possible intraoperative bleeding and bile leakage during LLR. We also assessed the educational value of the training model. METHODS: The Lap-liver trainer (LLT) combined a continuously pressurized ex situ cadaver liver and a customized mannequin. The customized mannequin was designed by computer-aided design and manufactured by 3D printing. The left lateral sectionectomy (LLS) was chosen to assess the feasibility of a LLR with the LLT. Eighteen volunteers were recruited to perform LLS and to assess the educational value of the LLT using a Likert scale. RESULTS: The customized mannequin consisted of a close laparoscopic training device based on a simplified reconstruction of the abdominal cavity in laparoscopic conditions. Ex situ cadaver livers were pressurized to simulate blood and bile supplies. Each expert surgeon (n = 3) performed two LLS. They were highly satisfied of simulation conditions (4.80 ± 0.45) and strongly recommended that the LLT should be incorporated into a teaching program (5.00 ± 0.0). Eight novice and 4 intermediate surgeons completed a teaching program and performed a LLS. Overall, the level of satisfaction was high (4.92 ± 0.29), and performing such a procedure under simulation conditions benefited their learning and clinical practice (4.92 ± 0.29). CONCLUSIONS: The LLT could provide better opportunities for trainees to acquire and practice LLR skills in a more realistic environment and to improve their ability to deal with specific events related to LLR.

PVRIG Expression Is an Independent Prognostic Factor and a New Potential Target for Immunotherapy in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a frequent and deadly cancer in need of new treatments. Immunotherapy has shown promising results in several solid tumors. The TIGIT/DNAM-1 axis gathers targets for new immune checkpoint inhibitors (ICIs). Here, we aimed at highlighting the potential of this axis as a new therapeutic option for HCC. For this, we built a large transcriptomic database of 683 HCC samples, clinically annotated, and 319 normal liver tissues. We interrogated this database for the transcriptomic expression of each member of the TIGIT/DNAM-1 axis and tested their prognostic value for survival. We then focused on the most discriminant one for these criteria, i.e., PVRIG, and analyzed the clinical characteristics, the disease-free and overall survivals, and biological pathways associated with PVRIG High tumors. Among all members of the TIGIT/DNAM-1 axis, PVRIG expression was higher in tumors than in normal liver, was heterogeneous across tumors, and was the only member with independent prognostic value for better survival. PVRIG High tumors were characterized by a higher lymphocytic infiltrate and enriched for signatures associated with tertiary lymphoid structures and better anti-tumor immune response. These results suggest that patients with PVRIG High tumors might be good candidates for immune therapy involving ICIs, notably ICIs targeting the TIGIT/DNAM-1 axis. Further functional and clinical validation is urgently required.

Despite similar clinical features metabolomics reveals distinct signatures in insulin resistant and progressively obese minipigs.

Obesity is a major contributor to the silent and progressive development of type 2 diabetes (T2D) whose prevention could be improved if individuals at risk were identified earlier. Our aim is to identify early phenotypes that precede T2D in diet-induced obese minipigs. We fed four groups of minipigs (n = 5-10) either normal-fat or high-fat high-sugar diet during 2, 4, or 6 months. Morphometric features were recorded, and metabolomics and clinical parameters were assessed on fasting plasma samples. Multivariate statistical analysis on 46 morphometrical and clinical parameters allowed to differentiate 4 distinct phenotypes: NFC (control group) and three others (HF2M, HF4M, HF6M) corresponding to the different stages of the obesity progression. Compared to NFC, we observed a rapid progression of body weight and fat mass (4-, 7-, and tenfold) in obese phenotypes. Insulin resistance (IR; 2.5-fold increase of HOMA-IR) and mild dyslipidemia (1.2- and twofold increase in total cholesterol and HDL) were already present in the HF2M and remained stable in HF4M and HF6M. Plasma metabolome revealed subtle changes of 23 metabolites among the obese groups, including a progressive switch in energy metabolism from amino acids to lipids, and a transient increase in de novo lipogenesis and TCA-related metabolites in HF2M. Low anti-oxidative capacities and anti-inflammatory response metabolites were found in the HF4M, and a perturbed hexose metabolism was observed in HF6M. Overall, we show that IR and progressively obese minipigs reveal phenotype-specific metabolomic signatures for which some of the identified metabolites could be considered as potential biomarkers of early progression to TD2.

Predictive factors of non-operative management failure in 494 blunt liver injuries: a multicenter retrospective study.

Non-operative management (NOM) has become the major treatment of blunt liver trauma (BLT) with a NOM failure rate of 3-15% due to liver-related complications. The aim of the study was to determine the predictive factors and a risk-stratified score of NOM failure. From 2013 to 2021, all patients with BLT in three trauma centers were included; clinical, biological, radiological and outcome data were retrospectively analyzed. Predictive factors and a risk-stratified score associated with NOM failure were identified. Four hundred and ninety-four patients with BLT were included. Among them, 80 (16.2%) had isolated BLT. Fifty-nine patients (11.9%) underwent emergent operative management (OM) on the day of admission and 435 (88.1%) had a NOM. NOM failure rate was 11.5%. Patients with a NOM failure more frequently had a hemoperitoneum (p < 0.001), liver bleeding (p < 0.001), blood transfusion (p < 0.001) and angioembolization (p < 0.001) compared to patient with a successful NOM. In multivariate analysis, the presence of hemoperitoneum (OR = 5.71; 95 CI [1.29-25.45]), angioembolization (OR = 8.73; 95 CI [2.04-38.44] and severe liver injury (AAST IV or V) (OR = 8.97; 95 CI [3.36-23.99]) were independent predictive factors of NOM failure. When these three factors were associated, NOM failure rate was 83.3%. The AAST grade, the presence of hemoperitoneum and the realization of liver angioembolization on the day of admission are three independent predictive factors of NOM failure. Our risk-score based on these three factors stratify the risk of NOM failure in BLT and could be used for a more appropriate level of medical survey adapted to each patient. Level of evidence: prospective observational cohort study, Level III.

Postprandial Responses on Serum Metabolome to Milk and Yogurt Intake in Young and Older Men.

The identification and validation of biomarkers of food intake (BFIs) is a promising approach to develop more objective and complementary tools to the traditional dietary assessment methods. Concerning dairy, their evaluation in terms of intake is not simple, given the variety of existing foods, making it difficult to establish the association between specific dairy products consumption and the effects on human health, which is also dependent on the study population. Here, we aimed at identifying BFI of both milk (M) and yogurt (Y) in 14 healthy young (20-35 years) and 14 older (65-80 years). After a 3-week run-in period of dairy exclusion from the diet, the subjects acutely consumed 600 ml of M or Y. Metabolomics analyses were conducted on serum samples during the following 6 h (LC-MS and GC-MS). Several metabolites showing increased iAUC after milk or yogurt intake were considered as potential BFI, including lactose (M > Y, 2-fold), galactitol (M > Y, 1.5-fold), galactonate (M > Y, 1.2-fold), sphingosine-1-phosphate (M > Y from 2.1-fold), as well as an annotated disaccharide (Y > M, 3.6-fold). Delayed serum kinetics were also observed after Y compared to M intake lysine (+22 min), phenylalanine (+45 min), tyrosine (+30min), threonine (+38 min) 3-phenyllactic acid (+30 min), lactose (+30 min), galactitol (+45min) and galactonate (+30 min). The statistical significance of certain discriminant metabolites, such as sphingosine-1-phosphate and several free fatty acids, was not maintained in the older group. This could be related to the physiological modifications induced by aging, like dysregulated lipid metabolism, including delayed appearance of dodecanoic acid (+60 min) or altered postprandial appearance of myristic acid (+70% Cmax), 3-dehydroxycarnitine (-26% Cmin), decanoylcarnitine (-51% Cmin) and dodecanoylcarnitine (-40% Cmin). In conclusion, candidate BFI of milk or yogurt could be identified based on the modified postprandial response resulting from the fermentation of milk to yogurt. Moreover, population specificities (e.g., aging) should also be considered in future studies to obtain more accurate and specific BFI.

New 5-mm laparoscopic pneumodissector device to improve laparoscopic dissection: an experimental study of its safety in a swine model.

BACKGROUND: To improve the laparoscopic surgical dissection, the aim of the study was to assess the safety of burst of high-pressure CO2 using a 5-mm laparoscopic pneumodissector (PD) operating at different flow rates and for different operating times regarding the risk of gas embolism (GE) in a swine model. METHODS: The first step was to define the settings use of the PD device ensuring no GE. Successive procedures were conducted by laparotomy: cholecystectomy, the PD was placed 10 mm deep in the liver and the PD was directly introduced into the lumen of the inferior vena cava. Different PD flow rates of 5, 10, and 15 mL/s were used. The second step was to assess the safety of the device (PD group) during a laparoscopic dissection task (cystic and hepatic pedicles dissection, cholecystectomy and right nephrectomy) in comparison with the use of a standard laparoscopic hook device (control group). PD flow rate was 10 mL/s and consecutive burst of high-pressure CO2 was delivered for 3-5 s. RESULTS: In the first step (n = 17 swine), no GE occurred during cholecystectomy regardless of the PD flow rate used. When the PD was placed in the liver or into the inferior vena cava, no severe or fatal GE occurred when a burst of high-pressure CO2 was applied for 3 or 5 s with PD flow rates of 5 and 10 mL/s. In the second step (PD group, n = 10; control group, n = 10), no GE occurred in the PD group. The use of the PD did not increase operative time or blood loss. The quality of the dissection was significantly improved compared to the control group. CONCLUSIONS: The 5-mm laparoscopic PD appears to be free from CO2 GE risk when consecutive bursts of high-pressure CO2 are delivered for 3-5 s with a flow rate of 10 mL/s.

Prognostic impact of splenic vessel involvement and tumor size in distal pancreatectomy for adenocarcinoma: a retrospective multicentric cohort study.

PURPOSE: Splenic vessel involvement occurs frequently in pancreatic ductal adenocarcinoma (PDAC) of the body and the tail (B/T) but the impact on survival is unknown. We assessed the influence of radiological and pathologic involvement of splenic artery (p-SA +) and vein (p-SV +) on patient outcomes after distal pancreatectomy (DP) for PDAC. METHODS: From 2013 to 2019, all DP for PDAC in five centers were included. Factors associated with overall (OS) and disease-free (DFS) survival were identified. RESULTS: Among the 76 patients included, 5 (6.6%) had p-SA + only, 11 (14.5%) had p-SV + only, and 24 (31.6%) had both p-SA + and p-SV + . The preoperative CT-scan accuracy to predict p-SV + and p-SA + was high (sensitivity: 91.4% and 82.8%, respectively; negative predictive value: 89.7% and 88.3%, respectively). The 5-year OS and DFS rates were 3.9% and 8.3%, respectively. Multivariate analysis identified splenic vessel involvement (i.e., p-SA + or p-SV + , or both p-SA + and p-SV +) as the only independent factor influencing DFS (HR 4.04; 95% CI [1.22-13.44], p = 0.023). Tumor size ≥ 30 mm was the only independent factor influencing OS (HR 4.04; 95% CI [1.26-12.95], p = 0.019) and was associated with a high risk of p-SA + (p = 0.001) and p-SV + (p < 0.001). CONCLUSION: Tumor size ≥ 30 mm and splenic vessel involvement occurred in more than half of the patients who underwent DP for PDAC and had negative impact on long-term survival. Preoperative CT-scan was reliable to identify splenic vessel involvement in B/T PDAC. Large tumor size and radiological splenic vessel involvement could be taken into account to propose a neoadjuvant treatment.

Development of a novel educational tool to assess skills in laparoscopic liver surgery using the Delphi methodology: the laparoscopic liver skills scale (LLSS).

BACKGROUND: No specific performance assessment scales have been reported in laparoscopic liver resection. This study aimed at developing an objective scale specific for the assessment of technical skills for wedge resection in anterior segments (WRAS) and left lateral sectionectomy (LLS). METHODS: A laparoscopic liver skills scale (LLSS) was developed using a hierarchical task analysis. A Delphi method obtained consensus among five international experts on relevant steps that should be included into the LLSS for assessment of operative performances. The consensus was predefined using Cronbach's alpha > 0.80. RESULTS: A semi-structured review extracted 15 essential subtasks for full laparoscopic WRAS and LLS for evaluation in the Delphi survey. Two rounds of the survey were conducted. Three over 15 subtasks did not reach the predefined level of consensus. Based on the expert's comments, 13 subtasks were reformulated, 4 subtasks were added, and a revised skills scale was developed. After the 2nd round survey (Cronbach's alpha 0.84), 19 subtasks were adopted. The LLSS was composed of three main parts: patient positioning and intraoperative preparation (task 1 to 8), the core part of the WRAS and LLS procedure (tasks 9 to 14), and completion of procedure (task 15 to 19). CONCLUSIONS: The LLSS was developed for measuring the skill set for the education of safe and secure laparoscopic WRAS and LLS procedures in a dedicated training program. After validation, this scale could be also used as an assessment tool in the operating room and extrapolated as an operative roadmap to other complex procedures.

A Mix of Dietary Fibres Changes Interorgan Nutrients Exchanges and Muscle-Adipose Energy Handling in Overfed Mini-Pigs.

This study evaluates the capacity of a bread enriched with fermentable dietary fibres to modulate the metabolism and nutrients handling between tissues, gut and peripheral, in a context of overfeeding. Net fluxes of glucose, lactate, urea, short chain fatty acids (SCFA), and amino acids were recorded in control and overfed female mini-pigs supplemented or not with fibre-enriched bread. SCFA in fecal water and gene expressions, but not protein levels or metabolic fluxes, were measured in muscle, adipose tissue, and intestine. Fibre supplementation increased the potential for fatty acid oxidation and mitochondrial activity in muscle (acox, ucp2, sdha and cpt1-m, p < 0.05) as well as main regulatory transcription factors of metabolic activity such as pparα, pgc-1α and nrf2. All these features were associated with a reduced muscle fibre cross sectional area, resembling to controls (i.e., lean phenotype). SCFA may be direct inducers of these cross-talk alterations, as their feces content (+52%, p = 0.05) was increased in fibre-supplemented mini-pigs. The SCFA effects could be mediated at the gut level by an increased production of incretins (increased gcg mRNA, p < 0.05) and an up-regulation of SCFA receptors (increased gpr41 mRNA, p < 0.01). Hence, consumption of supplemented bread with fermentable fibres can be an appropriate strategy to activate muscle energy catabolism and limit the establishment of an obese phenotype.

Microbiota and Metabolite Modifications after Dietary Exclusion of Dairy Products and Reduced Consumption of Fermented Food in Young and Older Men.

The gut microbiota adapts to age-related changes in host physiology but is also affected by environmental stimuli, like diet. As a source of both pre- and probiotics, dairy and fermented foods modulate the gut microbiota composition, which makes them interesting food groups to use for the investigation of interactions between diet and ageing. Here we present the effects of excluding dairy products and limiting fermented food consumption for 19 days on gut microbiota composition and circulating metabolites of 28 healthy, young (YA) and older (OA) adult men. The intervention affected gut microbial composition in both groups, with significant increases in Akkermansia muciniphila and decreases in bacteria of the Clostridiales order. Lower fasting levels of glucose and insulin, as well as dairy-associated metabolites like lactose and pentadecanoic acid, were observed after the intervention, with no effect of age. The intervention also decreased HDL and LDL cholesterol levels. Dairy fat intake was positively associated with the HDL cholesterol changes but not with the LDL/HDL ratio. In conclusion, restricting the intake of dairy and fermented foods in men modified their gut microbiota and blood metabolites, while the impact of the dietary restrictions on these outcomes was more marked than the effect of age.

Postoperative day 1 combination of serum C-reactive protein and drain amylase values predicts risks of clinically relevant pancreatic fistula. The "90-1000" score.

BACKGROUND: Several scoring systems predict risks of clinically relevant postoperative pancreatic fistula after pancreatectomy, but none have emerged as the gold standard. This study aimed to evaluate the accuracy of postoperative day 1 drain amylase and serum C-reactive protein levels in predicting clinically relevant postoperative pancreatic fistula compared with intraoperative pancreatic characteristics. METHODS: Patients who underwent pancreatectomy between 2017 and 2019 were included prospectively. Cutoff values were determined using receiver operating characteristic curves, and a score combining postoperative day 1 drain amylase and serum C-reactive protein was tested in a multivariate logistic regression model to evaluate clinically relevant postoperative pancreatic fistula risk. RESULTS: A total of 274 pancreatic resections (182 pancreaticoduodenectomies and 92 distal pancreatectomies) were included. The pancreatic gland texture was "soft" in 47.8% (n = 131), and 55.8% (n = 153) had a small size main pancreatic duct (≤3 mm). Clinically relevant postoperative pancreatic fistula occurred in 58 patients (21.2%). Drain amylase ≥1,000 UI/L and serum C-reactive protein ≥90 mg/L were identified as the optimal cutoffs to predict clinically relevant postoperative pancreatic fistula. On multivariate analysis these cutoffs were independent predictors of clinically relevant postoperative pancreatic fistula after both pancreaticoduodenectomies (drain amylase: P < .001, serum C-reactive protein: P = .006) and distal pancreatectomies (drain amylase: P = .009, serum C-reactive protein: P = .001). The postoperative day 1 "90-1000" model, a 2-value score relying on these cutoffs, significantly (P < .001) outperformed intraoperative pancreatic parenchymal characteristics in predicting clinically relevant postoperative pancreatic fistula after both pancreaticoduodenectomies and distal pancreatectomies. A postoperative day 1 "90-1000" score = 0 had a negative predictive value of 97% and 94%, respectively, after pancreaticoduodenectomy and distal pancreatectomies. CONCLUSION: A combined score relying on postoperative day 1 values of drain amylase and serum C-reactive protein levels was accurate in predicting risks of clinically relevant postoperative pancreatic fistula after pancreatectomy.

Surgery of small bowel melanoma metastases in the era of efficient medical therapies: a retrospective cohort study.

Surgery of small bowel melanoma metastases has to be reconsidered in the era of targeted treatments and immunotherapy. To retrospectively assess context and outcomes of small bowel melanoma metastases resections. All consecutive melanoma patients who underwent resection of small bowel metastases between 2011 and 2017, in a single referral center, were retrospectively analyzed through melanoma-specific survival (MSS). A total of 20 patients were included with a 47.8 months median follow-up. Before small bowel surgery, eight patients (40%) were asymptomatic while seven had anemia and five patients had abdominal pain. All resections were decided on tumor boards except for three surgeries performed in the emergency setting. In the whole cohort, MSS was 89.5 months with 50% of patients alive at the study endpoint. We classified surgical indications in three groups: (1) surgery as a pivotal treatment for mono- or oligo-metastases limited to the small bowel (n = 6); (2) salvage surgery for symptomatic patients in order to preserve their chances to switch to an active line of medical treatment (n = 8); and (3) surgery of small bowel dissociated metastatic progression for patients otherwise controlled (n = 6), aiming at keeping patients with the same treatment or active follow-up. In these three situations, the objective of surgery was usually met, and most patients had a long median MSS after surgery: 70.3 months, 89.5 months and 72.4 months, respectively. Although medical treatments have dramatically improved survival in metastatic melanoma, surgical control of life-threatening localization like small bowel metastases is often a condition for long survival.