The alteration of fecal microbial and metabolic profile of gallstone patients in Taiwan: Single-center study.

BACKGROUND: Gallstone disease is a common health problem worldwide. The role of the gut microbiota in gallstone pathogenesis remains obscure. Our aim was to evaluate the association and crosstalk between gut microbiota, gut metabolomic, and metabolic parameters in cholesterol gallstone patients, pigmented gallstone patients, and controls. METHODS: We collected stool samples from healthy individuals and patients with gallstones in our hospital from March 2019 to February 2021. 16s rRNA sequencing was performed, followed by differential abundance analyses. Measurement of bile acids and short-chain fatty acids was conducted via targeted metabolomics. RESULT: Thirty healthy individuals and 20 gallstone patients were recruited. The intergroup difference of microbial composition was significant between control and gallstone patients. The control group had more abundant Faecalibacterium , Prevotella 9 , and Bacteroides plebeius DSM 17135 . The cholesterol stones group had higher Desulfovibrionaceae and Bacteroides uniformis than the other two groups, while the pigment stone group had more abundant Escherichia-Shigella . In the analysis of metabolites, only n-butyric acid had a significantly higher concentration in the controls than in the gallstone group ( p < 0.01). The level of 3α-hydroxy-12 ketolithocholic acid, deoxycholic acid, and cholic acid showed no intergroup differences but was correlated to the serum cholesterol level and bacterial richness and evenness. CONCLUSION: Our study revealed the key taxa that can discriminate between individuals with or without gallstones. We also identified metabolites that are possibly associated with metabolic parameter and bacterial diversity. However, the correlation of the metabolites to certain clusters of bacteria should be analyzed in a larger cohort.

Mitochondrial dysfunction decreases cisplatin sensitivity in gastric cancer cells through upregulation of integrated stress response and mitokine GDF15.

Gastric neoplasm is a high-mortality cancer worldwide. Chemoresistance is the obstacle against gastric cancer treatment. Mitochondrial dysfunction has been observed to promote malignant progression. However, the underlying mechanism is still unclear. The mitokine growth differentiation factor 15 (GDF15) is a significant biomarker for mitochondrial disorder and is activated by the integrated stress response (ISR) pathway. The serum level of GDF15 was found to be correlated with the poor prognosis of gastric cancer patients. In this study, we found that high GDF15 protein expression might increase disease recurrence in adjuvant chemotherapy-treated gastric cancer patients. Moreover, treatment with mitochondrial inhibitors, especially oligomycin (a complex V inhibitor) and salubrinal (an ISR activator), respectively, was found to upregulate GDF15 and enhance cisplatin insensitivity of human gastric cancer cells. Mechanistically, it was found that the activating transcription factor 4-C/EBP homologous protein pathway has a crucial function in the heightened manifestation of GDF15. In addition, reactive oxygen species-activated general control nonderepressible 2 mediates the oligomycin-induced ISR, and upregulates GDF15. The GDF15-glial cell-derived neurotrophic factor family receptor a-like-ISR-cystine/glutamate transporter-enhanced glutathione production was found to be involved in cisplatin resistance. These results suggest that mitochondrial dysfunction might enhance cisplatin insensitivity through GDF15 upregulation, and targeting mitokine GDF15-ISR regulation might be a strategy against cisplatin resistance of gastric cancer.

Growth differentiation factor 15 induces cisplatin resistance through upregulation of xCT expression and glutathione synthesis in gastric cancer.

Gastric cancer is a common cancer worldwide, particularly in East Asia. Chemotherapy is used in adjuvant or palliative therapies for gastric cancer. However, subsequent chemoresistance often develops. Growth differentiation factor 15 (GDF15) links to several cancers, but its effect on chemoresistance in gastric cancer remains unclear. Here, we analyzed clinical samples from genetic databases and included patients with gastric cancer. We dissected the regulatory mechanism underlying GDF15-mediated resistance of cisplatin in human gastric cancer cells. We showed that GDF15 serum levels might be a valuable biomarker for predicting prognosis in gastric cancer. The expressions of GDF15 and its receptor glial cell-derived neurotrophic factor family receptor a-like (GFRAL) in gastric tumors are important for malignant progression. Moreover, GDF15 expression is increased in gastric cancer cells with cisplatin resistance, resulting from elevated intracellular glutathione (GSH) and antioxidant activities. Upregulated GDF15 could increase intracellular GSH content by activating the GFRAL-GCN2-eIF2α-ATF4 signaling, enhancing cystine-uptake transporter xCT expression, and contributing biosynthesis of GSH in human gastric cancer cells. In conclusion, our results indicate that GDF15 could induce chemoresistance by upregulating xCT expression and GSH biosynthesis in human gastric cancer cells. Targeting GDF15 could be a promising treatment method for gastric cancer progression.

Immunoprofile of adenosquamous carcinoma in gastric cancer.

BACKGROUND: Gastric adenosquamous carcinoma (GASC) is a rare subtype of gastric cancer. Research on GASC treatment is limited, and its outcome is usually poor. We investigated the clinical features, immunoprofile of GASC, and determined the optimal treatment modality for these patients. METHODS: Patients with GASC from Taipei Veterans General Hospital were retrospectively reviewed. Clinical features and treatment outcomes were evaluated. Adequate samples were examined for surrogate biomarkers for immunotherapy by IHC staining. RESULTS: Total 14 (0.35%) GASC patients were found among 4034 gastric cancer patients. The median tumor size was 6.8 cm in 10 patients with stage III GASC, and all these patients underwent radical gastrectomy followed by adjuvant therapy. The median progression-free survival (PFS) and overall survival (OS) were 6.0 and 11.5 months, respectively. Two patients with stage IV GASC received frontline immunotherapy. Their median PFS and OS were 9.0 and 12.5 months. In immunoprofiling, 25.0% (n = 3), 75.0% (n = 9), and 33.3% (n = 4) of the samples had deficient mismatch repair (dMMR) protein, combined positive score (CPS) of ≥1, and CPS of ≥10, respectively. The univariate analysis revealed that programmed death-ligand 1 ≥5% (HR: 0.12; 95% CI: 0.01-0.97; p = 0.047) was significant associated with superior OS. One stage IV patient with CPS ≥10 and dMMR proteins received nivolumab monotherapy as frontline treatment that resulted 14-month PFS. CONCLUSION: Patients with GASC are more likely to yield positive results for CPS and dMMR. Biomarkers should be examined, and immunotherapy can be considered as frontline systemic treatment.

Elevated PD-L1 Expression and Microsatellite Instability in Elderly Patients With Gastric Cancer.

Immunotherapy in combination with chemotherapy is the current treatment of choice for frontline programmed cell death ligand 1 (PD-L1)-positive gastric cancer. However, the best treatment strategy remains an unmet medical need for elderly or fragile patients with gastric cancer. Previous studies have revealed that PD-L1 expression, Epstein-Barr virus association, and microsatellite instability-high (MSI-H) are the potential predictive biomarkers for immunotherapy use in gastric cancer. In this study, we showed that PD-L1 expression, tumor mutation burden, and the proportion of MSI-H were significantly elevated in elderly patients with gastric cancer who were older than 70 years compared with patients younger than 70 years from analysis of The Cancer Genome Atlas gastric adenocarcinoma cohort [≥70/<70: MSI-H: 26.8%/15.0%, P =0.003; tumor mutation burden: 6.7/5.1 Mut/Mb, P =0.0004; PD-L1 mRNA: 5.6/3.9 counts per million mapped reads, P =0.005]. In our real-world study, 416 gastric cancer patients were analyzed and showed similar results (≥70/<70: MSI-H: 12.5%/6.6%, P =0.041; combined positive score ≥1: 38.1%/21.5%, P <0.001). We also evaluated 16 elderly patients with gastric cancer treated with immunotherapy and revealed an objective response of 43.8%, a median overall survival of 14.8 months, and a median progression-free survival of 7.0 months. Our research showed that a durable clinical response could be expected when treating elderly patients with gastric cancer with immunotherapy, and this approach is worth further study.

Comparison of the mutation patterns between tumor tissue and cell-free DNA in stage IV gastric cancer.

Compared to stage I-III gastric cancer (GC), the level of cell-free DNA (cfDNA) was significantly higher in stage IV GC. The mutation patterns of different metastatic patterns between cfDNA and tumor DNA in stage IV GC have not yet been reported. We used next-generation sequencing (NGS) to analyze cfDNA and tumor DNA in 56 stage IV GC patients. Tumor DNA and cfDNA were analyzed using a 29-gene NGS panel. In tumor samples, the most commonly mutated gene was TP53 (64%), followed by ARID1A (62%), KMT2C (60%) and KMT2D (58%). In cfDNA samples, the most commonly mutated genes were FAT4 (19%) and MACF1 (19%), followed by KMT2D (18%), ARID1A (14%) and LRP1B (14%). The concordance of mutation patterns in these 29 genes was 42.0% between cfDNA and tumor DNA. A specificity of 100% was found when using the mutation status of cfDNA to predict mutations in tumor samples. The sensitivity of the mutation status of cfDNA to predict mutation in tumor samples was highest in FAT4 (88.9%), followed by MACF1 (80%), CDH1 (75%) and PLB1 (75%). For cfDNA with PLB1 mutations, patients were more likely to develop distant lymphatic metastasis than peritoneal metastasis. Patients with multiple-site metastases had significantly more mutated spots than patients with single-site metastasis. Due to the high sensitivity and specificity of some genes in the prediction of mutation in tumor samples, monitoring the mutation pattern of cfDNA may be useful in the stage IV GC treatment.

Early cholecystectomy following percutaneous transhepatic gallbladder drainage is effective for moderate to severe acute cholecystitis in the octogenarians.

BACKGROUND: Acute cholecystitis (AC) is a life-threatening infectious/inflammatory disease in older patients. This study aimed to investigate the safety and optimal timing of surgery in patients aged ≥ 80 years with moderate to severe AC who received percutaneous transhepatic gallbladder drainage (PTGBD). METHODS: From January 2008 to February 2021, 152 patients were retrospectively enrolled. Clinical outcomes were compared among patients who received laparoscopic cholecystectomy (LC), open cholecystectomy (OC), and conversion surgery, and between those who received early (< 6 weeks after PTGBD) and delayed cholecystectomy (≥ 6 weeks after PTGBD). Logistic regression analysis was used to identify risk factors for recurrent AC, further biliary events, conversion, and perioperative complications. RESULTS: Sixty-seven patients underwent LC, 62 underwent OC, and 23 underwent conversion surgery. Operation-related complications and mortality rates did not differ among the types of surgery; however, LC group had shorter operative time than the other groups. Eighty-two patients underwent early cholecystectomy, while 70 underwent delayed cholecystectomy. There were no differences in operative time, operation-related complications, and mortality rates between the groups. However, higher rates of recurrent AC and biliary events were observed in the delayed cholecystectomy group (52.9% vs. 4.9% and 57.1% vs. 8.5%, p < 0.001). On multivariate analysis, delayed cholecystectomy was a significant risk factor for recurrent AC (odds ratio [OR] = 19.42, p < 0.001) and further biliary events (OR = 15.95, p < 0.001). CONCLUSIONS: Early cholecystectomy is recommended for patients aged ≥ 80 years with moderate to severe AC following PTGBD.

The clinicopathological and genetic differences among gastric cancer patients with no recurrence, early recurrence, and late recurrence after curative surgery.

BACKGROUND: To date, few reports have investigated the genetic alterations and clinicopathological features among gastric cancer (GC) patients with no tumor recurrence, early recurrence, and late recurrence following curative surgery. METHODS: A total of 473 GC patients undergoing curative surgery were included. The clinicopathological characteristics, patient prognosis, recurrence patterns, and genetic alterations were compared between GC patients with early recurrence and late recurrence. RESULTS: Among the 473 GC patients, 119 had early recurrence (<2 years) and 45 had late recurrence (≥2 years). Patients with early recurrence had tumor size larger than 5 cm, fewer superficial-type tumors, more lymphovascular invasion, more advanced pathological T and N categories and Tumor, Node, Metastasis (TNM) stages, and worse 5-year overall survival than patients with late recurrence and no recurrence. For intestinal-type GC, patients with no tumor recurrence had more Helicobacter pylori infection than patients with early recurrence and late recurrence; for diffuse-type GC patients, the frequency of PIK3CA amplification was the highest in early recurrence, followed by late recurrence and no recurrence. GC patients with single-site recurrence had more ARID1A mutations than those with multiple-site recurrence. Multivariate analysis demonstrated that age, tumor recurrence, and pathological N categories were independent prognostic factors. CONCLUSION: PIK3CA amplifications were more common in diffuse-type GC with early recurrence, whereas ARID1A mutations were more common in patients with single-site recurrence. Targeted therapy and immunotherapy might be helpful for these patients.

Comparative analyses of complete chloroplast genomes reveal interspecific difference and intraspecific variation of Tripterygium genus.

The genus Tripterygium was of great medicinal value and attracted much attention on the taxonomic study using morphological and molecular methods. In this study, we assembled 12 chloroplast genomes of Tripterygium to reveal interspecific difference and intraspecific variation. The sequence length (156,692-157,061 bp) and structure of Tripterygium were conserved. Comparative analyses presented abundant variable regions for further study. Meanwhile, we determined the ndhB gene under positive selection through adaptive evolution analysis. And the phylogenetic analyses based on 15 chloroplast genomes supported the monophyly of Tripterygium hypoglaucum and the potential sister relationship between Tripterygium wilfordii and Tripterygium regelii. Molecular dating analysis indicated that the divergence time within Tripterygium was approximately 5.99 Ma (95% HPD = 3.11-8.68 Ma). The results in our study provided new insights into the taxonomy, evolution process, and phylogenetic construction of Tripterygium using complete plastid genomes.

Effect of epidural analgesia on cancer outcomes after gastric cancer resection: a single-centre cohort study in Taiwan.

OBJECTIVE: To investigate the influence of epidural anaesthesia and analgesia (EA) on cancer recurrence and overall survival after surgery for gastric cancer. STUDY DESIGN AND SETTING: A retrospective study which involved patients with stage I-III gastric cancer undergoing curative resection in a medical centre from January 2012 to December 2017 and followed up until December 2019 through electronic medical chart review. Patient demographics, anaesthetic and surgical characteristics and pathologic features were also gathered. PRIMARY AND SECONDARY OUTCOME MEASURES: The effects of EA on postoperative cancer recurrence and overall survival were evaluated using proportional hazards regression models with inverse probability of treatment weighting (IPTW). Multivariable Cox regression analyses were conducted for sensitivity analysis as well. RESULTS: Among the 413 patients with median follow-up of 38.5 months (IQR: 22.1-59.7), 66 (16.0%) received EA after gastric cancer surgery. EA was not associated with greater cancer recurrence (IPTW-adjusted HR: 0.55, 95% CI: 0.27 to 1.13, p=0.102) or cancer specific (IPTW- adjusted HR: 0.53, 95% CI: 0.27 to 1.04, p=0.07) and all-cause mortality (IPTW-adjusted HR: 0.65, 95% CI: 0.37 to 1.16, p=0.143) after gastric cancer resections. For sensitivity analysis, multivariable Cox regression analysis also generated non-significant EA effects on cancer recurrence and survival after surgery. CONCLUSIONS: There was no significant association between EA and cancer recurrence or overall survival in patients with stage I-III gastric cancer receiving surgical resection of primary tumour. Prospective study should be considered to elucidate the relationship between EA and cancer outcomes after gastric cancer surgery.

Strategic Decoy Peptides Interfere with MSI1/AGO2 Interaction to Elicit Tumor Suppression Effects.

Peptide drugs that target protein-protein interactions have attracted mounting research efforts towards clinical developments over the past decades. Increasing reports have indicated that expression of Musashi 1 (MSI1) is tightly correlated to high grade of cancers as well as enrichment of cancer stem cells. Treatment failure in malignant tumors glioblastoma multiform (GBM) had also been correlated to CSC-regulating properties of MSI1. It is thus imperative to develop new therapeutics that could effectively improve current regimens used in clinics. MSI1 and AGO2 are two emerging oncogenic molecules that both contribute to GBM tumorigenesis through mRNA regulation of targets involved in apoptosis and cell cycle. In this study, we designed peptide arrays covering the C-terminus of MSI1 and identified two peptides (Pep#11 and Pep#26) that could specifically interfere with the binding with AGO2. Our Biacore analyses ascertained binding between the identified peptides and AGO2. Recombinant reporter system Gaussian luciferase and fluorescent bioconjugate techniques were employed to determine biological functions and pharmacokinetic characteristics of these two peptides. Our data suggested that Pep#11 and Pep#26 could function as decoy peptides by mimicking the interaction function of MSI1 with its binding partner AGO2 in vitro and in vivo. Further experiments using GMB animal models corroborated the ability of Pep#11 and Pep#26 in disrupting MSI1/AGO2 interaction and consequently anti-tumorigenicity and prolonged survival rates. These striking therapeutic efficacies orchestrated by the synthetic peptides were attributed to the decoy function to C-terminal MSI1, especially in malignant brain tumors and glioblastoma.

Microsatellite Instability, Epstein-Barr Virus, and Programmed Cell Death Ligand 1 as Predictive Markers for Immunotherapy in Gastric Cancer.

Immunotherapy benefits selected cases of gastric cancer (GC), but the correlation between biomarkers and prognosis is still unclear. Fifty-two patients with GC who underwent immunotherapy were enrolled from June 2016 to December 2020. Their clinical features and biomarkers-microsatellite instability-high (MSI-H), programmed cell death ligand 1 (PD-L1) combined positive score (CPS), and Epstein-Barr encoding region (EBER)-were analyzed. Eight patients had MSI-H, five patients had EBER, 29 patients had CPS ≥ 1, and 20 patients had no biomarker. The overall response rates (ORRs) of the MSI-H, EBER, PD-L1 CPS ≥ 1, and all-negative group were 75%, 60%, 44.8%, and 15%, respectively. Compared with that of the all-negative group, progression-free survival (PFS) was better in the MSI-H (p = 0.018), CPS ≥ 5 (p = 0.012), and CPS ≥ 10 (p = 0.006) groups, but not in the EBER (p = 0.2) and CPS ≥ 1 groups (p = 0.35). Ten patients had combined biomarkers, CPS ≥ 1 with either MSI-H or EBER. The ORRs were 66.7% for CPS ≥ 1 and MSI-H and 75% for CPS ≥ 1 and EBER. PFS was better in patients with combined biomarkers (p = 0.01). MSI-H, EBER, and CPS are useful biomarkers for predicting the efficacy of immunotherapy.

Confirming the TMEM232 gene associated with atopic dermatitis through targeted capture sequencing.

Atopic dermatitis (AD) is a common and complex skin disorder, and the 5q22.1 region had been reported to be associated with AD. To confirm the susceptibility gene for AD in the 5q22.1 region by haplotype and targeted capture sequencing. The haplotypes were reconstructed with the genotyping data of four SNPs and six deletions from 3624 Chinese Hans AD patients and 5076 controls. The targeted capture sequencing spanning 5q22.1 region was performed in the selected samples. The gene level enrichment analysis was done using loss of function variants. A total of 62 haplotypes were found, and the H15 haplotype had the strongest association with AD (P = 3.92 × 10-10, OR 0.17, 95% CI 0.09-0.32). However, no co-segregation mutation sites were found in the sequencing analysis within the 16 selected samples, while the enrichment analysis indicated that TMEM232 was significantly associated with AD (P = 7.33 × 10-5, OR 0.33, 95% CI 0.19-0.58). This study confirms previous findings that the TMEM232 gene is associated with AD by haplotype analysis and targeted capture sequencing.

The Associations between Perioperative Blood Transfusion and Long-Term Outcomes after Stomach Cancer Surgery.

BACKGROUND: Whether perioperative packed red blood cell (pRBC) transfusion is associated with inferior long-term outcomes after stomach cancer surgery remains controversial. METHODS: This research used a retrospective cohort study. Patients with stage I~III stomach cancer undergoing tumor resection were collected at a tertiary medical center. Patient characteristics, surgical features and pathologic findings were gathered from an electronic medical chart review. The associations of perioperative pRBC transfusion with postoperative disease-free and overall survivals were evaluated using Cox regression analysis with an inverse probability of treatment weighting (IPTW). Restricted cubic spline functions were employed to characterize dose-response relationships between the amount of transfusion and cancer outcomes after surgery. RESULTS: Among the 569 patients, 160 (28.1%) received perioperative pRBC transfusion. Perioperative transfusion was associated with worse disease-free survival (IPTW adjusted HR: 1.42, 95% CI: 1.18-1.71, p < 0.001) and overall survival (IPTW adjusted HR: 1.27, 95% CI: 1.05-1.55, p = 0.014). A non-linear dose-response relationship was noted between the amount of transfusions and worse disease-free or overall survival. CONCLUSIONS: Perioperative pRBC transfusion was associated with worse disease-free and overall survival after stomach cancer surgery, and strategies aiming to minimize perioperative transfusion exposure should be further considered to reduce the potential risk.

Cardia Gastric Cancer Is Associated With Increased PIK3CA Amplifications and HER2 Expression Than Noncardia Gastric Cancer According to Lauren Classification.

BACKGROUND: To date, few reports have investigated genetic alterations and clinicopathological features in cardia and noncardia gastric cancer (GC). METHODS: In total, 435 GC patients receiving curative surgery were included. The clinicopathological features, recurrence patterns, prognoses and genetic alterations were compared between cardia and noncardia GC patients. RESULTS: Among the 435 enrolled patients, 47 (10.8%) had cardia GC. Compared with noncardia GC, cardia GC was associated with more intestinal-type tumors and similar initial recurrence patterns and 5-year overall survival (OS; 50.8% vs. 50.5%, P = 0.480) and disease-free survival (DFS; 48.6% vs. 48.9%, P = 0.392) rates. For both intestinal-type GC and diffuse-type GC, the clinicopathological features and 5-year OS and DFS rates were not significantly different between the cardia and noncardia GC patients. Multivariable analysis showed that cardia GC was not an independent prognostic factor. Compared with noncardia GC, cardia GC was associated with increased PIK3CA amplification than in patients with intestinal-type GC and was associated with increased HER2 expression in patients with diffuse-type GC. CONCLUSIONS: Cardia GC is not an independent prognostic factor. In cardia GC patients with intestinal-type GC, PIK3CA amplification was more common, and in those with diffuse-type GC, HER2 expression was more common. Targeted therapy may be beneficial for these patient subgroups.

Molecular Diagnosis of Neurofibromatosis by Multigene Panel Testing.

Neurofibromatosis (NF) is an autosomal genetic disorder for which early and definite clinical diagnoses are difficult. To identify the diagnosis, five affected probands with suspected NF from unrelated families were included in this study. Molecular analysis was performed using multigene panel testing and Sanger sequencing. Ultradeep sequencing was used to analyze the mutation rate in the tissues from the proband with mosaic mutations. Three different pathogenic variants of the NF1 gene were found in three probands who mainly complained of café-au-lait macules (CALMs), including one frameshift variant c.5072_5073insTATAACTGTAACTCCTGGGTCAGGGAGTACACCAA:p.Tyr1692Ilefs in exon 37, one missense variant c.3826C > T:p.Arg1276Ter in exon 28, and one splicing variant c.4110 + 1G > T at the first base downstream of the 3'-end of exon 30. One NF1 gene mosaic variant was found in a proband who complained of cutaneous neurofibroma with the frameshift variant c.495_498del:p.Thr165fs in exon 5, and ultradeep sequencing showed the highest mutation rate of 10.81% in cutaneous neurofibromas. A frameshift variant, c.36_39del:p.Ser12fs in exon 1 of the NF2 gene, was found in a proband who presented with skin plaques and intracranial neurogenic tumors. All of these pathogenic variants were heterozygous, one was not reported, and one not in Chinese before. This study expands the pathogenic variant spectrum of NF and demonstrates the clinical diagnosis.

Differences in intestinal microbiota profiling after upper and lower gastrointestinal surgery.

BACKGROUND: We aimed to investigate the long-term effects of metabolic profiles and microbiota status in patients after upper gastrointestinal (GI) surgery and lower GI surgery and compared them with a control group. METHODS: In this cross-sectional study, we analyzed the occurrence of metabolic syndrome (MS) in 10 patients who underwent curative total gastrectomy with Roux-en-Y esophagojejunostomy (RYEJ) anastomosis, 11 patients who underwent curative partial colectomy with right hemicolectomy (RH), and 33 age- and sex-matched controls. Fecal samples were also analyzed by a next-generation sequencing method. RESULTS: Compared with the control group, the occurrence of MS was significantly lower among patients who underwent total gastrectomy with RYEJ than the controls over the long-term follow-up (>8 years; p < 0.05). Patients who received RH only had a trend of higher serum fasting glucose (p = 0.10). The diversity of the gut microbiota significantly decreased after RH in comparison with the control group and RYEJ group, respectively (p < 0.05). Principal component analysis revealed significant differences between the control, RYEJ, and RH groups (p < 0.001). At the genus level, the ratio of Prevotella to Bacteroides (P/B) was significantly higher in the RYEJ group than in the control group, whereas the P/B ratio was significantly lower in the RH group than in the control group (p < 0.05). CONCLUSION: Early gastric cancer patients who received total gastrectomy with RYEJ had a lower occurrence of MS than the controls, while early colorectal cancer patients who received RH were associated with a higher serum fasting glucose than the controls during long-term follow-up. In parallel with the metabolic differences, the P/B ratio was also significantly altered in patients after upper and lower GI surgery.

Comparison of the Long-term Outcome Between Billroth-I and Roux-en-Y Reconstruction Following Distal Gastrectomy for Gastric Cancer.

BACKGROUND: Various reconstruction methods have been performed following distal gastrectomy; however, each reconstruction method has its own advantages and disadvantages. This study aims to compare the long-term outcomes between Billroth-I (B-I) and Roux-en-Y (RY) reconstruction after distal gastrectomy for gastric cancer. METHODS: A total of 459 patients who underwent distal gastrectomy (B-I: 166, RY: 293) were included. Postoperative endoscopic findings and biliary tract stone formation were compared between the two groups. RESULTS: At 1 year and 2 years postoperatively, gastric residue was more common in the RY group, gastritis was similar between groups, and bile reflux was more common in the B-I group. At 5 years postoperatively, gastric residue was similar between the groups, while gastritis and bile reflux were more common in the B-I group. Gastroesophageal reflux was more common in the B-I group at 1 year postoperatively, but gastroesophageal reflux became not significantly different between the groups at 2 and 5 years postoperatively. Gallstone formation was more common in the RY group and in patients aged ≥ 65 years. CONCLUSION: During long-term follow-up, RY reconstruction was associated with lower incidence of bile reflux and gastritis, and higher incidence of gallstone formation than B-I reconstruction. The incidence of gastric residue was more common in the RY reconstruction group in the early postoperative period and became not significantly different between the two groups over time. For aged patients with RY reconstruction, cholecystectomy is recommended concurrently as gastrectomy.