Search

Objectives To investigate the effect of nutritional therapy on body composition and resting energy expenditure(REE) post bariatric surgery in patients with obesity. Methods Six-step post-operative nutrition therapy during 3 months was performed for 47 patients undergoing bariatric surgery with laparoscopic sleeve gastrectomy. Body composition, REE and nutritonal biochemical indexes were determined in pre-surgery and post-surgery 1, 3 months. Predictive REE was calculated with Bernestin Formula. Repeated ANOVA analysis was done for the changes in the indicators of patients. Results Muscle mass reduced 8.33%±3.49% in post-surgery 1 month, and 2.86%±3.96% in post-surgery 3 months. Fat mass reduced 14.73%±5.44% in post-surgery 1 month and 16.61%±8.26% in post-surgery 3 months. There was no significant difference between REE and predicted REE with (9 339.16±2 620.59) kJ vs. (9 058.06±2 098.61) kJ in pre-surgery, P=0.593; and (7 228.20±2 066.61) kJ vs. (7 973.15±1 747.49) kJ in post-surgery 3 months, P=0.098. However, predicted REE (8 286.81±1 764.25) kJ was significant higher than REE (7 418.33±1 764.25) kJ in post-surgery 1 month, P=0.032. There was no significant difference in levels of vitamin-A, vitamin-B1, vitamin-B2, vitamin-B6, vitamin-C and serum ferritin between pre-surgery and post-surgery 1 month and post-surgery 3 months(P>0.05). A significant reduction of C-reactive protein was present with (9.03±9.42) mg/L in pre-surgery, (6.61±7.89) mg/L in post-surgery 1 month and (4.69±4.66) mg/L in post-surgery 3 months, P=0.020. Conclusions Nutritional therapy after bariatric surgery 3 months could delay the loss of skeletal muscle mass and adapt REE and reduce the inflammation level in patients with obesity.

Objective: To analyze the short-term efficacy of distal pancreatectomy with en bloc celiac axis resection (DP-CAR) in the treatment of locally advanced pancreatic body or tail cancer and the effect of vascular variation on morbidity after DP-CAR. Methods: A retrospective study was undertaken of 43 cases with pancreatic ductal adenocarcinoma diagnosed by pathological examination in the treatment of DP-CAR. R0 resection, morbidity and mortality were analyzed perioperatively with the effect of vascular variation. Results: R0 resection by DP-CAR was 81.4% in this study with mortality 7.0% and morbidity 45.6%. Eight cases were found with vascular variation. The postoperative morbidity in the group with vascular variation and in the group without vascular variation was 3/8 (37.5%) vs 17/35 (48.5%) and the mortality 1/8 (12.5%) vs 2/35 (5.7%), respectively. There was no significant difference statistically in morbidity and mortality between 2 groups. Conclusions: DP-CAR has the advantage of safety and feasibility. There would be no effect of vascular variation on morbidity after DP-CAR.

Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese individuals. We identified obesity-associated gut microbial species linked to changes in circulating metabolites. The abundance of Bacteroides thetaiotaomicron, a glutamate-fermenting commensal, was markedly decreased in obese individuals and was inversely correlated with serum glutamate concentration. Consistently, gavage with B. thetaiotaomicron reduced plasma glutamate concentration and alleviated diet-induced body-weight gain and adiposity in mice. Furthermore, weight-loss intervention by bariatric surgery partially reversed obesity-associated microbial and metabolic alterations in obese individuals, including the decreased abundance of B. thetaiotaomicron and the elevated serum glutamate concentration. Our findings identify previously unknown links between intestinal microbiota alterations, circulating amino acids and obesity, suggesting that it may be possible to intervene in obesity by targeting the gut microbiota., Author(s): Ruixin Liu [1]; Jie Hong [1]; Xiaoqiang Xu [2, 3]; Qiang Feng [2, 4]; Dongya Zhang [2]; Yanyun Gu [1]; Juan Shi [1]; Shaoqian Zhao [1]; Wen Liu [1]; [...]

Accurate diagnosis and grading are critical for pancreatic neuroendocrine neoplasm (pNEN) management. This study compares the diagnostic and grading value of 68Ga-DOTATATE PET/MR and 18F-FDG PET/MR for pNENs separately as well as in combination. A total of 36 patients with histologically confirmed pNENs, who underwent both 68Ga-DOTATATE PET/MR and 18F-FDG PET/MR within 2 weeks from 2020 to 2021, were retrospectively collected and analyzed. The maximum standardized uptake values of 68Ga-DOTATATE (G-SUVmax) and 18F-FDG (F-SUVmax) on PET and the minimum values of apparent diffusion coefficient (ADCmin) on MR were measured on the lesions with known histological grading (25 by surgery, 11 by biopsy). Receiver-operating characteristic analysis was applied to determine the cutoffs of these parameters or their combinations for differentiation between G1 and G2, as well as between low-grade and high-grade pNENs. The Spearman rank correlation coefficient was used to assess the correlation between the imaging parameters and the maximum tumor diameters. The detection rate of 68Ga-DOTATATE PET imaging alone was 95%, 87.5%, and 37.5% for G1, G2, and G3, respectively. Adding 18F-FDG PET or MR sequences of PET/MR increased the detection rate to 100% in all grades. Among the three parameters, G-SUVmax had the highest diagnostic rate in predicting tumor grade. It presented a sensitivity of 87.5% and a specificity of 80.0% with a cutoff value of 42.75 for differentiating G2 from G1 pNETs and a sensitivity and specificity of 100% and 71.4% with a cutoff value of 32.75 in predicting high-grade pNENs. The ratio of G-SUVmax to F-SUVmax (G-SUVmax/F-SUVmax) showed slight improvement in the diagnostic rate, while the product of G-SUVmax and ADCmin (G-SUVmax*ADCmin) did not improve the diagnostic rate. 68Ga-DOTATATE PET/MR alone is sufficient for the diagnosis of pNENs and the prediction of various grades. [ABSTRACT FROM AUTHOR]

Objective: Pancreatic neuroendocrine tumors (pNETs) causing ectopic adrenal corticotropic hormone (ACTH) syndrome (EAS) are rare and aggressive with little known information. We aimed to elucidate the clinical features and molecular mechanisms of pNETs with EAS by methylation analysis.Methods: Seven patients with ectopic ACTH-secreting pNETs who were diagnosed at Shanghai Clinical Endocrine and Metabolic Diseases Center and Pancreatic Disease Center in Ruijin Hospital between 2001 and 2019 were enrolled. Twenty patients with ectopic ACTH-secreting thymic neuroendocrine tumors (TNETs) and 7 with nonfunctional pNETs (nf-pNETs) were also enrolled as controls. We collected clinical data and measured POMC promoter CpG methylation.Results: All 7 patients had elevated ACTH and urinary free cortisol (UFC) levels with positive ACTH staining in the pancreas and were diagnosed with ectopic ACTH-secreting pNET. Of the 7 patients, 6 underwent surgery and 1 underwent transarterial embolization (TAE). Two patients were free of disease after surgery; 2 died within 90 days after surgery; and 3 had metastases and died within 1 year. Compared with ACTH-secreting TNETs, ACTH-secreting pNETs had similar clinical and biochemical features but a significantly poorer prognosis. POMC promoter CpG methylation was significantly lower in ACTH-secreting pNETs than in nf-pNETs and normal pancreas.Conclusions: ACTH-secreting pNETs are aggressive and fatal. Surgery is definitively curative for patients with resectable primary tumors without metastasis. Pro-opiomelanocortin (POMC) promoter hypomethylation caused pNETs to produce ACTH. This study further supplements the genetic features of ACTH-secreting NETs. [ABSTRACT FROM AUTHOR]

Abstract: The peptide segment of prostatic acid phosphatase (PAP248–286) aggregates to form SEVI (semen‐derived enhancer of virus infection) amyloid fibrils. These are characteristic seminal amyloids that have the ability to promote the effect of HIV infection. In this paper, we explore the binding of sulfonated compounds with PAP248–286 through an in silico study. Three derivatives of suramin, NF110, NF279, and NF340, are selected. All of these sulfonated molecules bind to PAP248–286 and alter the conformation of the peptide, even though they have various structures, sizes, and configurations. The compounds bind with PAP248–286 through multiple interactions, such as hydrogen‐bonding interactions, hydrophobic interactions, π–π stacking interactions, and electrostatic interactions. However, NF110, which has an X‐shaped configuration, has the highest binding affinity of the three derivatives investigated. We also perform surface plasmon resonance and a Congo red assay to validate the results. The interactions between PAP248–286 and the sulfonated compounds are proposed to depend on the orientations of the sulfonate groups and the specific configurations of the compounds instead of the number of sulfonate groups. NF110 molecules occupy the exposed binding sites of PAP248–286, blocking interactions between the peptides. Therefore, these compounds are important in inhibiting the aggregation of PAP248–286. Herein, we provide useful information to develop new efficient microbicides to antagonize seminal amyloid fibrils and to block HIV transmission. [ABSTRACT FROM AUTHOR]

Background: Patients with resected pancreatic adenocarcinoma (PAAD) often experience short-term relapse and dismal survival, suggesting an urgent need to develop predictive and/or prognostic biomarkers for these populations. Given the potential associations of the human leukocyte antigen class I ( HLA -I) genotype with oncogenic mutational profile and immunotherapy efficacy, we aimed to assess whether differential HLA -I genotype could predict the postoperative outcomes in resected PAAD patients., Materials and Methods: HLA -I ( A , B , and C ) genotyping and somatic variants of 608 Chinese PAAD patients were determined by targeted next-generation sequencing of matched blood cells and tumor tissues. HLA - A / B alleles were classified with the available definition of 12 supertypes. The Kaplan-Meier curves of disease-free survival (DFS) and multivariable Cox proportional-hazards regression analyses were performed to determine the survival difference in 226 selected patients with radical resection. Early-stage (I-II) patients constituted the majority (82%, 185/226) and some stage I-II individuals with high-quality tumor samples were analyzed by RNA-sequencing to examine immunophenotypes., Results: Patients with HLA-A02 + B62 + B44 - had significantly shorter DFS (median, 239 vs. 410 days; hazard ratio=1.65, P =0.0189) than patients without this genotype. Notably, stage I-II patients carrying HLA-A02 + B62 + B44 - had sharply shorter DFS than those without HLA-A02 + B62 + B44 - (median, 237 vs. 427 days; hazard ratio=1.85, P =0.007). Multivariate analysis revealed that HLA-A02 + B62 + B44 - was associated with significantly inferior DFS ( P =0.014) in stage I-II patients but not in stage III patients. Mechanistically, HLA-A02 + B62 + B44 - patients were associated with a high rate of KRAS G12D and TP53 mutations, lower HLA-A expression, and less inflamed T-cell infiltration., Conclusion: The current results suggest that a specific combination of germline HLA-A02/B62/B44 supertype, HLA-A02 + B62 + B44 - , was a potential predictor for DFS in early-stage PAAD patients after surgery., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Accurate diagnosis and grading are critical for pancreatic neuroendocrine neoplasm (pNEN) management. This study compares the diagnostic and grading value of 68 Ga-DOTATATE PET/MR and 18 F-FDG PET/MR for pNENs separately as well as in combination. A total of 36 patients with histologically confirmed pNENs, who underwent both 68 Ga-DOTATATE PET/MR and 18 F-FDG PET/MR within 2 weeks from 2020 to 2021, were retrospectively collected and analyzed. The maximum standardized uptake values of 68 Ga-DOTATATE (G-SUVmax) and 18 F-FDG (F-SUVmax) on PET and the minimum values of apparent diffusion coefficient (ADCmin) on MR were measured on the lesions with known histological grading (25 by surgery, 11 by biopsy). Receiver-operating characteristic analysis was applied to determine the cutoffs of these parameters or their combinations for differentiation between G1 and G2, as well as between low-grade and high-grade pNENs. The Spearman rank correlation coefficient was used to assess the correlation between the imaging parameters and the maximum tumor diameters. The detection rate of 68 Ga-DOTATATE PET imaging alone was 95%, 87.5%, and 37.5% for G1, G2, and G3, respectively. Adding 18 F-FDG PET or MR sequences of PET/MR increased the detection rate to 100% in all grades. Among the three parameters, G-SUVmax had the highest diagnostic rate in predicting tumor grade. It presented a sensitivity of 87.5% and a specificity of 80.0% with a cutoff value of 42.75 for differentiating G2 from G1 pNETs and a sensitivity and specificity of 100% and 71.4% with a cutoff value of 32.75 in predicting high-grade pNENs. The ratio of G-SUVmax to F-SUVmax (G-SUVmax/F-SUVmax) showed slight improvement in the diagnostic rate, while the product of G-SUVmax and ADCmin (G-SUVmax*ADCmin) did not improve the diagnostic rate. 68 Ga-DOTATATE PET/MR alone is sufficient for the diagnosis of pNENs and the prediction of various grades., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Zhao, Pan, Ju, Huang, Jiang, Jin and Zhang.)

The peptide segment of prostatic acid phosphatase (PAP 248-286 ) aggregates to form SEVI (semen-derived enhancer of virus infection) amyloid fibrils. These are characteristic seminal amyloids that have the ability to promote the effect of HIV infection. In this paper, we explore the binding of sulfonated compounds with PAP 248-286 through an in silico study. Three derivatives of suramin, NF110, NF279, and NF340, are selected. All of these sulfonated molecules bind to PAP 248-286 and alter the conformation of the peptide, even though they have various structures, sizes, and configurations. The compounds bind with PAP 248-286 through multiple interactions, such as hydrogen-bonding interactions, hydrophobic interactions, π-π stacking interactions, and electrostatic interactions. However, NF110, which has an X-shaped configuration, has the highest binding affinity of the three derivatives investigated. We also perform surface plasmon resonance and a Congo red assay to validate the results. The interactions between PAP 248-286 and the sulfonated compounds are proposed to depend on the orientations of the sulfonate groups and the specific configurations of the compounds instead of the number of sulfonate groups. NF110 molecules occupy the exposed binding sites of PAP 248-286 , blocking interactions between the peptides. Therefore, these compounds are important in inhibiting the aggregation of PAP 248-286 . Herein, we provide useful information to develop new efficient microbicides to antagonize seminal amyloid fibrils and to block HIV transmission.

Background: To explore the effectiveness, safety, and efficacy of the robot-assisted surgery in the radical resection of pancreatic ductal adenocarcinoma (PDAC)., Methods: The clinical data of 72 patients with PDAC who underwent radical resection using the da Vinci Surgical System from April 2010 to December 2014 were retrospectively analyzed., Results: Among these 72 patients, three were converted to conventional laparotomy due to the vascular invasion or due to the difficulties in tissue isolation from the surrounding organs. Among 39 patients who underwent the pancreatoduodenectomy, the average operative time was 395.3±118.8 min, and the mean intra-operative blood loss was 447.3±269.9 mL. Among 31 patients who underwent the distal pancreatectomy (DP), the average operative time was 185.5±74.1 min, and the mean intra-operative blood loss was 267.1±305.3 mL. In two patients who received the middle pancreatectomy (MP), the average operative time was 225 min and mean intra-operative blood loss was 100 mL. Among all the 72 patients, an average of 4.2±2.6 lymph nodes were dissected, with an average hospital stay of 22.6±10.7 days. Complications were observed in 18 patients, which included pancreatic fistula (n=11), bile leak (n=5), anastomotic bleeding (n=2), pancreatic fistula complicated with portal vein thrombosis (n=1), and anastomotic bleeding complicated with acute renal failure (n=1). Except that one patient died due to post-operative bleeding and acute renal failure, all the other patients were cured after conservative treatment. These 72 patients were followed for 1-45 (15.6±5.8) months, during which 10 patients died. Eleven patients suffered from recurrence or metastasis, among which 6 had local recurrence, 4 had liver metastasis, and 1 had ascites accompnaied with incision site tumor metastasis., Conclusions: Radical resection of PDAC by robotic surgical system is safe and feasible. It has less surgical trauma and enables faster post-operative recovery, and therefore can achieve the lymph node dissection scope and tumor resection margin required by the standards of radical resection for pancreatic cancer. Nevertheless, its long-term efficacy requires further validation.

Traditional post-surgical chemotherapy for pancreatic cancer is notorious for its devastating side effects due to the high dosage required. On the other hand, legitimate concerns have been raised about nanoparticle-mediated drug delivery because of its potential cytotoxicity. Therefore, we explored the local delivery of a reduced dosage of FOLFIRINOX, a four-drug regimen comprising oxaliplatin, leucovorin, irinotecan, and fluorouracil, for pancreatic cancer using a biocompatible drug-eluting scaffold as a novel chemotherapy strategy after palliative surgery. In vitro assays showed that FOLFIRINOX in the scaffold caused massive apoptosis and thereby a decrease in the viability of pancreatic cancer cells, confirming the chemotherapeutic capability of the drug-eluting scaffold. In vivo studies in an orthotopic murine xenograft model demonstrated that the FOLFIRINOX in the scaffold had antitumorigenic and antimetastatic effects comparable with those achieved by intraperitoneal injection, despite the dose released by the scaffold being roughly two thirds lower. A mechanistic study attributed our results to the excellent ability of the FOLFIRINOX in the scaffold to destroy the CD133(+)CXCR4(+) cell population responsible for pancreatic tumorigenesis and metastasis. This clinically oriented study gives rise to a promising alternative strategy for postsurgical management of pancreatic cancer, featuring a local chemotherapeutic effect with considerable attenuation of side effects.