Influence of pancreaticoduodenectomy for periampullary carcinoma on intestinal microbiome and metabolites
Ontology highlight
ABSTRACT:
SUBMITTER:
PROVIDER: S-EPMC10831615 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundThe aim of this meta-analysis was to compare the long-term survival, mortality, morbidity and the operation-related events in patients with periampullary and pancreatic carcinoma undergoing pylorus-preserving pancreaticoduodenectomy (PPPD) and pylorus-resecting pancreaticoduodenectomy (PRPD).MethodA systematic search of literature databases (Cochrane Library, PubMed, EMBASE and Web of Science) was performed to identify studies. Outcome measures comparing PPPD versus PRPD for periampullary and pancreatic carcinoma were long-term survival, mortality, morbidity (overall morbidity, delayed gastric emptying [DGE], pancreatic fistula, wound infection, postoperative bleeding, biliary leakage, ascites and gastroenterostomy leakage) and operation related events (hospital stays, operating time, intraoperative blood loss and red blood cell transfusions).ResultsEight randomized controlled trials (RCTs) including 622 patients were identified and included in the analysis. Among these patients, it revealed no difference in long-term survival between the PPPD and PRPD groups (HR = 0.23, p = 0.11). There was a lower rate of DGE (RR = 2.35, p = 0.04, 95% CI, 1.06-5.21) with PRPD. Mortality, overall morbidity, pancreatic fistula, wound infection, postoperative bleeding, biliary leakage, ascites and gastroenterostomy leakage were not significantly different between the groups. PPPDs were performed more quickly than PRPDs (WMD = 53.25 minutes, p = 0.01, 95% CI, 12.53-93.97); and there was less estimated intraoperative blood loss (WMD = 365.21 ml, p = 0.006, 95% CI, 102.71-627.71) and fewer red blood cell transfusions (WMD = 0.29 U, p = 0.003, 95% CI, 0.10-0.48) in patients undergoing PPPD. The hospital stays showed no significant difference.ConclusionsPPPD had advantages over PRPD in operating time, intraoperative blood loss and red blood cell transfusions, but had a significantly higher rate of DGE for periampullary and pancreatic carcinoma. PPPD and PRPD had comparable mortality and morbidity including pancreatic fistulas, wound infections, postoperative bleeding, biliary leakage, ascites and gastroenterostomy leakage. Our conclusions were limited by the available data. Further evaluations of high-quality RCTs are needed.
| S-EPMC3946060 | biostudies-literature
Project description:BackgroundPeriampullary adenocarcinoma (PAAC) had a poor prognosis, and pancreaticoduodenectomy (PD) remains the only potentially curative treatment. The study aimed to identify the impact of different clinicopathological factors on long-term survival following PD for PAAC.Patients and methodsThis study is a retrospective cohort study for the patients who underwent PD for pathologically proven PAAC from January 2010 to January 2019. Statistical analysis was done using Cox regression multivariate analyses for independent risk factors for survival.ResultThere were 137 patients with PAAC who underwent PD, 79 patients (57.7%) underwent pylorus-preserving PD. Pancreatico-jejunostomy was done in 108 patients (78.8%). The primary analysis showed that risk factors for poor long-term survival include patients with co-morbidities like hypertension or ischemic heart disease, Carbohydrate Antigen 19-9 > 400U/ml, tumor size > 3 cm, poor tumor differentiation, positive lymph nodes invasion, lymphovascular invasion, and Perineural invasion. Multivariate analysis demonstrated that large tumor size > 3 cm (HR: 0.177, 95%CI: 0.084-0.374, P = 0.002), poorly differentiated tumor (HR: 0.059, 95%CI: 0.020-0.0174, P = 0.016), and perineural invasion in the pathological study (HR: 0.101, 95%CI: 0.046-0.224, P = 0.006) were independent risk factors for poor 5-years survival. The prognosis was better in ampullary adenocarcinoma (5-year survival was 42.1%) than pancreatic adenocarcinoma (5-year survival was 24.3%). The 1, 3, 5 and 7-year overall survival rates were 84.5%, 57.4%, 35.9% and 20.1% respectively.ConclusionIt seems from the current study that Tumor size > 3 cm, poor tumor differentiation, and Perineural invasion were independent predictors of poor survival in patients with PAAC.
| S-EPMC7452109 | biostudies-literature
Project description:The metabolite-rich environment that is the intestinal lumen contains metabolic by-products deriving from microbial fermentation and host cell metabolism, with resident macrophages being constantly exposed to this metabolic flux. Succinate, lactate and itaconate are three metabolites secreted by primed macrophages due to a fragmented tri-carboxylic acid (TCA) cycle. Additionally, succinate and lactate are known by-products of microbial fermentation. How these metabolites impact biological functioning of resident macrophages particularly in response to bacterial infection remains poorly understood. We have investigated the potential influence of these metabolites on macrophage phagocytosis and clearance of Escherichia coli (E. coli) infection. Treatment of murine bone-marrow-derived macrophages (BMDMs) with succinate reduced numbers of intracellular E. coli early during infection, while lactate-treated BMDMs displayed no difference throughout the course of infection. Treatment of BMDMs with itaconate lead to higher levels of intracellular E. coli early in the infection with bacterial burden subsequently reduced at later time-points compared to untreated macrophages, indicative of enhanced engulfment and killing capabilities of macrophages in response to itaconate. Expression of engulfment mediators MARCKS, RhoB, and CDC42 were reduced or unchanged following succinate or lactate treatment and increased in itaconate-treated macrophages following E. coli infection. Nitric oxide (NO) levels varied while pro- and anti-inflammatory cytokines differed in secretory levels in all metabolite-treated macrophages post-infection with E. coli or in response to lipopolysaccharide (LPS) stimulation. Finally, the basal phenotypic profile of metabolite-treated macrophages was altered according to marker gene expression, describing how fluid macrophage phenotype can be in response to the microenvironment. Collectively, our data suggests that microbe- and host-derived metabolites can drive distinct macrophage functional phenotypes in response to infection, whereby succinate and itaconate regulate phagocytosis and bactericidal mechanisms, limiting the intracellular bacterial niche and impeding the pathogenesis of infection.
| S-EPMC8327167 | biostudies-literature
Project description:Globally, liver cancer poses a serious threat to human health and quality of life. Despite numerous studies on the microbial composition of the gut in hepatocellular carcinoma (HCC), little is known about the interactions of the gut microbiota and metabolites and their role in HCC. This study examined the composition of the gut microbiota and serum metabolic profiles in 68 patients with HCC, 33 patients with liver cirrhosis (LC), and 34 healthy individuals (NC) using a combination of metagenome sequencing and liquid chromatography-mass spectrometry (LC-MS). The composition of the serum metabolites and the structure of the intestinal microbiota were found to be significantly altered in HCC patients compared to non-HCC patients. LEfSe and metabolic pathway enrichment analysis were used to identify two key species (Odoribacter splanchnicus and Ruminococcus bicirculans) and five key metabolites (ouabain, taurochenodeoxycholic acid, glycochenodeoxycholate, theophylline, and xanthine) associated with HCC, which then were combined to create panels for HCC diagnosis. The study discovered that the diagnostic performance of the metabolome was superior to that of the microbiome, and a panel comprised of key species and key metabolites outperformed alpha-fetoprotein (AFP) in terms of diagnostic value. Spearman's rank correlation test was used to determine the relationship between the intestinal flora and serum metabolites and their impact on hepatocarcinogenesis and progression. A random forest model was used to assess the diagnostic performance of the different histologies alone and in combination. In summary, this study describes the characteristics of HCC patients' intestinal flora and serum metabolism, demonstrates that HCC is caused by the interaction of intestinal flora and serum metabolites, and suggests that two key species and five key metabolites may be potential markers for the diagnosis of HCC.
| S-EPMC10227431 | biostudies-literature
Project description:IntroductionMinimally invasive pancreaticoduodenectomy is a technically complex technique, that is being used to treat periampullary malignancy. We provide our experience with laparoscopic-assisted pancreaticoduodenectomy (LAPD) with statistics on the outcomes of periampullary cancer patients.Material and methodThirty patients underwent surgery between June 1, 2016 and May 30, 2020, with 21 undergoing classical PD and 9 undergoing pylorus-preserving pancreaticoduodenectomy (PPPD). Prospectively gathered data on surgical outcomes and long-term oncological results are given.ResultsThe median operative time was 277.5 min (range, 258.7-330 min), and the median intraoperative estimated blood loss was 319.5 mL (range, 241.2-425 mL). The rate of conversion to OPD, surgical reintervention, and mortality was 20%, 13.3%, and 10% respectively. Cumulative surgery-related morbidity was 33.4%, including bleeding (n = 4), severe POPF (n = 4), biliary fistula (n = 1), DGE (n = 2), and intestinal obstruction (n = 1). Pathologic diagnoses were AoV cancer (n = 23), distal CBD cancer (n = 4), PDAC (n = 2), and AoV NET (n = 1). The mean survival time of the LAPD group was 29.9 months. The long-term survival time of the N0 group was 36.8 months, which was significantly longer than that of the N1 group. The long-term survival times of stages I-B, II-A, and II-B were 36.9, 26.5, and 15.7 months, respectively (p = 0.016).ConclusionLAPD has a high rate of conversion to OPD, morbidity, and mortality. However, LPD is feasible technique for highly selected patients. Lymph node metastasis and stage of disease are the risk factors for long-term survival.
| S-EPMC8417344 | biostudies-literature
Project description:The protozoan parasite Cryptosporidium sp. is a leading cause of diarrheal disease in those with compromised or underdeveloped immune systems, particularly infants and toddlers in resource-poor localities. As an enteric pathogen, Cryptosporidium sp. invades the apical surface of intestinal epithelial cells, where it resides in close proximity to metabolites in the intestinal lumen. However, the effect of gut metabolites on susceptibility to Cryptosporidium infection remains largely unstudied. Here, we first identified which gut metabolites are prevalent in neonatal mice when they are most susceptible to Cryptosporidium parvum infection and then tested the isolated effects of these metabolites on C. parvum invasion and growth in intestinal epithelial cells. Our findings demonstrate that medium or long-chain saturated fatty acids inhibit C. parvum growth, perhaps by negatively affecting the streamlined metabolism in C. parvum, which is unable to synthesize fatty acids. Conversely, long-chain unsaturated fatty acids enhanced C. parvum invasion, possibly by modulating membrane fluidity. Hence, gut metabolites, either from diet or produced by the microbiota, influence C. parvum growth in vitro and may also contribute to the early susceptibility to cryptosporidiosis seen in young animals.IMPORTANCECryptosporidium sp. occupies a unique intracellular niche that exposes the parasite to both host cell contents and the intestinal lumen, including metabolites from the diet and produced by the microbiota. Both dietary and microbial products change over the course of early development and could contribute to the changes seen in susceptibility to cryptosporidiosis in humans and mice. Consistent with this model, we show that the immature gut metabolome influenced the growth of Cryptosporidium parvumin vitro Interestingly, metabolites that significantly altered parasite growth were fatty acids, a class of molecules that Cryptosporidium sp. is unable to synthesize de novo The enhancing effects of polyunsaturated fatty acids and the inhibitory effects of saturated fatty acids presented in this study may provide a framework for future studies into this enteric parasite's interactions with exogenous fatty acids during the initial stages of infection.
| S-EPMC7773987 | biostudies-literature
Project description:BackgroundMinimally invasive pancreatoduodenectomy (MIPD) has been gradually attempted. However, whether MIPD is superior, equal or inferior to its conventional open pancreatoduodenectomy (OPD) is not clear.MethodsStudies published up to May 2017 were searched in PubMed, Embase, Cochrane Library, and Web of Science. Main outcomes were comprehensively reviewed and measured including conversion to open approach, operation time (OP), estimated blood loss (EBL), transfusion, length of hospital stay (LOS), overall complications, postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), post-pancreatectomy hemorrhage (PPH), readmission, reoperation and reasons of preoperative death, number of retrieved lymph nodes (RLN), surgical margins, recurrence, and survival. The software of Review Manage version 5.1 was used for meta-analysis.ResultsOne hundred studies were included for systematic review and 26 out of them (totally 3402 cases, 1064 for MIPD, 2338 for OPD) were included for meta-analysis. In the early years, most articles were case reports or non-control case series studies, while in the last 6 years high-volume and comparative researches were increasing gradually. Systematic review revealed conversion rates of MIPD to OPD ranged from 0% to 40%. The mean or median OP of MIPD ranged from 276 to 657 min. The total POPF rates vary between 3.8% and 50% observed in all systematic reviewed studies. Meta-analysis demonstrated MIPD had longer OP (WMD = 99.4 min; 95%CI: 46.0 ~ 152.8, P < 0.01), lower blood loss (WMD = -0.54 ml; 95% CI, -0.88 ~ -0.20 ml; P < 0.01), lower transfusion rate (RR = 0.73, 95%CI: 0.57 ~ 0.94, P = 0.02), shorter LOS (WMD = -3.49 days; 95%CI: -4.83 ~ -2.15, P < 0.01). There was no significant difference in time to oral intake, postoperative complications, POPF, reoperation, readmission, perioperative mortality and number of retrieved lymph nodes.ConclusionOur study demonstrates MIPD is technically feasible and safety on the basis of historical studies. MIPD is associated with less blood loss, faster postoperative recovery, shorter length of hospitalization and longer operation time. These findings are waiting for being confirmed with robust prospective comparative studies and randomized clinical trials.
| S-EPMC5701376 | biostudies-literature
Project description:ObjectivesThe intestinal microbiome can modulate immune function through production of microbial-derived short-chain fatty acids. We explored whether intestinal dysbiosis in children with sepsis leads to changes in microbial-derived short-chain fatty acids in plasma and stool that are associated with immunometabolic dysfunction in peripheral blood mononuclear cells.DesignProspective observational pilot study.SettingSingle academic PICU.PatientsForty-three children with sepsis/septic shock and 44 healthy controls.Measurements and main resultsStool and plasma samples were serially collected for sepsis patients; stool was collected once for controls. The intestinal microbiome was assessed using 16S ribosomal RNA sequencing and alpha- and beta-diversity were determined. We measured short-chain fatty acids using liquid chromatography, peripheral blood mononuclear cell mitochondrial respiration using high-resolution respirometry, and immune function using ex vivo lipopolysaccharide-stimulated whole blood tumor necrosis factor-α. Sepsis patients exhibited reduced microbial diversity compared with healthy controls, with lower alpha- and beta-diversity. Reduced microbial diversity among sepsis patients (mainly from lower abundance of commensal obligate anaerobes) was associated with increased acetic and propionic acid and decreased butyric, isobutyric, and caproic acid. Decreased levels of plasma butyric acid were further associated with lower peripheral blood mononuclear cell mitochondrial respiration, which in turn, was associated with lower lipopolysaccharide-stimulated tumor necrosis factor-α. However, neither intestinal dysbiosis nor specific patterns of short-chain fatty acids were associated with lipopolysaccharide-stimulated tumor necrosis factor-α.ConclusionsIntestinal dysbiosis was associated with altered short-chain fatty acid metabolites in children with sepsis, but these findings were not linked directly to mitochondrial or immunologic changes. More detailed mechanistic studies are needed to test the role of microbial-derived short-chain fatty acids in the progression of sepsis.
| S-EPMC7994045 | biostudies-literature
Project description:Disruptions in the human gut microbiome have been associated with a cycle of hepatocyte injury and regeneration characteristic of chronic liver disease. Evidence suggests that the gut microbiota can promote the development of hepatocellular carcinoma through the persistence of this inflammation by inducing genetic and epigenetic changes leading to cancer. As the gut microbiome is known for its effect on host metabolism and immune response, it comes as no surprise that the gut microbiome may have a role in the response to therapeutic strategies such as immunotherapy and chemotherapy for liver cancer. Gut microbiota may influence the efficacy of immunotherapy by regulating the responses to immune checkpoint inhibitors in patients with hepatocellular carcinoma. Here, we review the mechanisms by which gut microbiota influences hepatic carcinogenesis, the immune checkpoint inhibitors currently being used to treat hepatocellular carcinoma, as well as summarize the current findings to support the potential critical role of gut microbiome in hepatocellular carcinoma (HCC) immunotherapy.
| S-EPMC8346024 | biostudies-literature
Project description:BACKGROUND: The most frequent complication following gastroenterostomy (GE) for gastric outlet obstruction is delayed gastric emptying (DGE), which occurs in roughly 20% of patients. There is evidence that DGE may be linked to the longitudinal incision of the jejunum and that a transverse incision (cross-section GE) may decrease the incidence of DGE following GE. PATIENTS AND METHODS: In contrast to the orthodox GE, the jejunum is severed transversely up to a margin of 1.5 cm at the mesenteric border and the anastomosis is created with a single running suture. A Braun anastomosis is added 20-30 cm distally to the GE. Patients were followed prospectively with special regard to the occurrence of DGE. RESULTS: Between 1 August 1994 and 1 August 1998, 25 patients underwent cross-section GE, mostly because of an irresectable periampullary carcinoma. Eight patients exhibited clinical signs of gastric outlet obstruction preoperatively, while in 17 the GE was performed on a prophylactic basis. A biliary bypass was added in 15 patients. There was no disruption of the GE, but one patient died in hospital (4%). The nasogastric tube was withdrawn on the first postoperative day (range 0-6 days), a liquid diet was started on the fifth day (range 2-7 days) and a full regular diet was tolerated at a median of 9 days (6-14 days).The incidence of DGE was 4%: only the single patient who died fulfilled the formal criteria for DGE. DISCUSSION: In contrast to orthodox GE, DGE seems to be of minor clinical importance following cross-section GE. As the technique is easy to perform, is free of specific complications and leads to a low incidence of DGE, it should be considered as an alternative to conventional GE.
| S-EPMC2020797 | biostudies-other