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World Journal of Gastrointestinal... Oct 2023Our previous study found that the telomerase-associated protein 1 (, rs938886 and rs1713449) and homo sapiens RecQ like helicase 5 (, rs820196) single nucleotide...
BACKGROUND
Our previous study found that the telomerase-associated protein 1 (, rs938886 and rs1713449) and homo sapiens RecQ like helicase 5 (, rs820196) single nucleotide polymorphisms (SNPs) were associated with changes in heart rate (HR) ≥ 30% during peritoneal lavage with distilled water after gastrectomy. This study established a single tube method for detecting these three SNPs using two-dimensional (2D) polymerase chain reaction (PCR), and investigated whether SNP-SNP and SNP-environment interactions increase the risk of high HR variability (HRV).
AIM
To investigate whether genotypes, genetic patterns, SNP-SNP and SNP-environment interactions were associated with HRV.
METHODS
2D PCR was used to establish a single-tube method to detect rs938886 and rs1713449 and rs820196, and the results were compared with those of sanger sequencing. After adjusting for confounders such as age, sex, smoking, hypertension, and thyroid dysfunction, a nonconditional logistic regression model was used to assess the associations between the genotypes and the genetic patterns (codominant, dominant, overdominant, recessive, and additive) of the three SNPs and a risk ≥ 15% or ≥ 30% of a sudden drop in HR during postoperative peritoneal lavage in patients with gastric cancer. Gene-gene and gene-environment interactions were analyzed using generalized multifactor dimensionality reduction.
RESULTS
The coincidence rate between the 2D PCR and sequencing was 100%. When the HRV cutoff value was 15%, the patients with the (rs820196) TC genotype had a higher risk of high HRV than those who had the TT genotype (odds ratio = 1.97; 95%CI: 1.05-3.70; = 0.045). Under the codominant and overdominant models, the TC genotype of (rs820196) was associated with a higher risk of HR decrease relative to the TT and TT + CC genotypes ( = 0.031 and 0.016, respectively). When the HRV cutoff value was 30%, patients carrying the GC-TC genotypes of rs938886 and rs820196 showed a higher HRV risk when compared with the GG-TT genotype carriers ( = 0.01). In the three-factor model of rs938886, rs820196, and rs1713449, patients carrying the GC-TC-CT genotype had a higher risk of HRV compared with the wild-type GG-TT-CC carriers ( = 0.01). For rs820196, nonsmokers with the TC genotype had a higher HRV risk compared with nonsmokers carrying the TT genotype ( = 0.04). When the HRV cutoff value was 15%, patients carrying the TT-TT and the TC-CT genotypes of rs820196 and rs1713449 showed a higher HRV risk when compared with TT-CC genotype carriers ( = 0.04 and 0.01, respectively). Patients carrying the GC-CT-TC genotypes of rs938886, rs1713449, and rs820196 showed a higher HRV risk compared with GG-CC-TT genotype carriers ( = 0.02). When the HRV cutoff value was 15%, the best-fitting models for the interactions between the SNPs and the environment were the rs820196-smoking ( = 0.022) and rs820196-hypertension ( = 0.043) models. Consistent with the results of the previous grouping, for rs820196, the TC genotype nonsmokers had a higher HRV risk compared with nonsmokers carrying the TT genotype ( = 0.01).
CONCLUSION
The polymorphism of the and genes were associated with HRV during peritoneal lavage with distilled water after gastrectomy.
PubMed: 37969699
DOI: 10.4240/wjgs.v15.i10.2154 -
Journal of Gastrointestinal Cancer Mar 2024Gastric cancer is the fifth most common malignant tumor worldwide. Many attempts have been made over the years to investigate the relationship between tumor markers and...
PURPOSE
Gastric cancer is the fifth most common malignant tumor worldwide. Many attempts have been made over the years to investigate the relationship between tumor markers and the risk of recurrence. This study aims to explore the predictive value of tumor markers measured in peritoneal washing during staging laparoscopy, regarding peritoneal carcinomatosis and mortality within 1 year.
METHODS
Patients with locally advanced gastric cancer, staged as at least usT2anyNM0 were submitted to staging laparoscopy in a Portuguese single center. CA 19.9, CEA, CA 125, and CA 72.4 were measured in the peritoneal washing after being harvested during staging laparoscopy.
RESULTS
Thirty-eight patients were enrolled. After 1 year, 20 patients did not recur (52.5%), 11 (28.9%) developed carcinomatosis, and 7 (18.4%) had distant metastasis. Mortality reached 23.7% (n = 9). A statistically significant prediction of carcinomatosis was obtained for CA 125 (cutoff: 107.6 U/mL (p = 0.019)) and CEA (cutoff: 2.0 ng/mL (p = 0.020)) with 87.5% and 75% sensitivity, respectively. Prediction of mortality was significant for CA 125 (cutoff: 103.8 U/mL (p = 0.044)) and CA 125 + CEA (p = 0.030). CEA and CA 125 had NPVs of 87.9% and 93.1% regarding PC, respectively. NPVs of 88.9% and 89.2% were met concerning mortality, for the same tumor markers.
CONCLUSION
Performing the peritoneal liquid harvest during staging laparoscopy makes this analysis cost effective, reproducible, and does not add further morbidity. CA 125 and CEA, individually and in association, are good predictors of progression of disease and mortality within a year of staging laparoscopy in GC patients.
Topics: Humans; Stomach Neoplasms; Peritoneal Neoplasms; Male; Female; Middle Aged; Biomarkers, Tumor; Aged; Neoplasm Staging; Peritoneal Lavage; CA-125 Antigen; Laparoscopy; Carcinoembryonic Antigen; Adult; CA-19-9 Antigen; Predictive Value of Tests; Neoplasm Recurrence, Local; Prognosis; Aged, 80 and over
PubMed: 37966631
DOI: 10.1007/s12029-023-00984-7 -
Cell & Bioscience Nov 2023Ovarian cancer (OC) typically develops an immunosuppressive microenvironment by funtional changes of host immune cells. Dysregulated m6A level is associated with cancer...
BACKGROUND
Ovarian cancer (OC) typically develops an immunosuppressive microenvironment by funtional changes of host immune cells. Dysregulated m6A level is associated with cancer progression via the intrinsic oncogenic pathways. However, the role of m6A in regulating host immune cell function during anti-tumor immunity needs comprehensive analysis. This study aimed to investigate the role of METTL3, a catalytic subunit of the methyltransferase complex, in regulating host immune cell response against OC.
METHODS
In this study, myeloid-specific Mettl3 gene knockout (Mettl3-cKO) mice were bred using the Cre-LoxP system. Intraperitoneally injection of ID8 cells was used as a syngeneic OC model. Furthermore, the compositions of immune cell populations were analyzed by flow cytometry and single-cell sequencing. Moreover, chemokines and cytokines secretion were assessed using ELISA. Lastly, the role of METTL3 in regulating IL-1β secretion and inflammasome activation in bone marrow-derived macrophages cocultured with ID8 cells was specified by ELISA and immunoblotting.
RESULTS
It was revealed that OC cell growth was enhanced in Mettl3-cKO mice. Furthermore, a shift of decreased M1 to increased M2 macrophage polarization was observed during OC progression. Moreover, Mettl3 depletion in myeloid lineage cells increased secretion of CCL2 and CXCL2 in peritoneal lavage fluild. Interestingly, Mettl3 deficiency enhanced IL-1β secretion induced by viable ID8 cells independent of inflammasome activation and cell death. Therefore, OC cells in tumor-bearing mice trigger a slight inflammatory response with a low-to-moderate secretion of pro-inflammatory cytokines and chemokines.
CONCLUSION
This study provides new insights into METTL3-mediated m6A methylation, which regulates host immune response against OC.
PubMed: 37932814
DOI: 10.1186/s13578-023-01149-6 -
International Journal of Surgery Case... Nov 2023Gastric lymphomas are non-Hodgkin's lymphomas originating from mucosa-associated lymphoid tissue (MALT). Surgical intervention is recommended in cases of complications...
INTRODUCTION AND IMPORTANCE
Gastric lymphomas are non-Hodgkin's lymphomas originating from mucosa-associated lymphoid tissue (MALT). Surgical intervention is recommended in cases of complications such as obstruction, bleeding, or perforation, although the choice of treatment can be a subject of debate and may entail life-threatening risks. This case report aims to describe a complex case of gastric MALT lymphoma with perforation requiring surgical intervention.
CASE PRESENTATION
A 47-year-old patient with a history of extranodal marginal zone B cell lymphoma presented to the Emergency Department with epigastric pain. Physical examination revealed a patient with hemodynamic instability and generalized abdominal tenderness. An abdominal CT scan revealed intraperitoneal air and effusion, along with a gastric wall defect. An emergent laparotomy was performed, revealing widespread purulent peritonitis resulting from a centimetric perforation in the anterior wall of the stomach near the lesser curvature. Following peritoneal lavage, we repaired the perforation and performed external drainage. The postoperative course was complicated by renal failure, and the patient succumbed to the illness two days after surgery.
CASE DISCUSSION
Gastric lymphomas, primarily linked to H. pylori infection. Diagnosis relies on endoscopy and histopathology. Endoscopic manifestations vary, making biopsy crucial. H. pylori eradication is the initial treatment, but resistance may require chemotherapy. Gastric lymphoma complications include perforation, with life-threatening consequences. Perforations can occur due to lymphoma or chemotherapy. Timely intervention with suturing is crucial for patient management. The postoperative course is difficult to manage due to the immune system deficiency.
CONCLUSION
Bowel perforation in gastric lymphomas significantly contributes to morbidity and mortality. Early diagnosis and emergent surgery are imperative to mitigate complications and reduce septicemia even in young patients.
PubMed: 37931503
DOI: 10.1016/j.ijscr.2023.109010 -
Revista Da Associacao Medica Brasileira... 2023In this study, we aimed to determine the impact of the antiangiogenic medications, namely, aflibercept and cabergoline in the prevention and treatment of ovarian...
OBJECTIVE
In this study, we aimed to determine the impact of the antiangiogenic medications, namely, aflibercept and cabergoline in the prevention and treatment of ovarian hyperstimulation syndrome in a rat model.
METHODS
A total of 36 female Wistar rats were randomly allocated to one of the five groups, including disease-free and ovarian hyperstimulation syndrome controls: Group no OHSS (control, n=6) received saline only intraperitoneally (i.p.); group just OHSS (ovarian hyperstimulation syndrome only, n=6) received 10 IU pregnant mare serum gonadotropin and 30 IU human chorionic gonadotropin subcutaneously to produce ovarian hyperstimulation syndrome; group cabergoline+OHSS (cabergoline+ovarian hyperstimulation syndrome, n=8) received 100 μg/kg oral cabergoline; group aflibercept (12.5 mg/kg)+OHSS (aflibercept+ovarian hyperstimulation syndrome, n=8) received 12.5 mg/kg i.p. aflibercept; and group aflibercept (25 mg/kg)+OHSS (aflibercept+ovarian hyperstimulation syndrome, n=8) received 25 mg/kg i.p. aflibercept. The groups were compared for ovarian weight, immunohistochemical vascular endothelial growth factor expression, spectrophotometric vascular permeability evaluated with methylene blue solution in peritoneal lavage, and body weight growth.
RESULTS
Vascular endothelial growth factor immunoexpression was substantially greater in the just OHSS group (22.00±10.20%) than in the aflibercept (12.5 mg/kg)+OHSS (7.87±6.13%) and aflibercept (25 mg/kg)+OHSS (5.63±4.53%) groups (p=0.008 and p=0.005, respectively). Post-hoc tests indicated that cabergoline, 12.5 mg/kg aflibercept, and 25 mg/kg aflibercept decreased vascular permeability compared to the untreated ovarian hyperstimulation syndrome group (p=0.003, p=0.003, and p=0.001, respectively). JOH group had the heaviest ovaries, whereas aflibercept (25 mg/kg)+OHSS group had the lightest. In terms of body weight gain, cabergoline+OHSS group was substantially greater than the aflibercept (12.5 mg/kg)+OHSS and aflibercept (25 mg/kg)+OHSS groups (p=0.006 and p=0.007, respectively).
CONCLUSION
Aflibercept, an antiangiogenic medication, decreased ovarian hyperstimulation syndrome by lowering the vascular permeability and vascular endothelial growth factor expression.
Topics: Humans; Pregnancy; Horses; Rats; Female; Animals; Ovarian Hyperstimulation Syndrome; Cabergoline; Rats, Wistar; Vascular Endothelial Growth Factor A; Body Weight
PubMed: 37909622
DOI: 10.1590/1806-9282.20230789 -
Acta Medica Okayama Oct 2023Gastric cancer with peritoneal metastases is typically a devastating diagnosis. Ligamentum teres hepatis (LTH) metastasis is an extremely rare presentation with only...
Gastric cancer with peritoneal metastases is typically a devastating diagnosis. Ligamentum teres hepatis (LTH) metastasis is an extremely rare presentation with only four known cases. Herein, we report salvage surgery of successive metastases to the abdominal wall and LTH in a patient originally presenting with advanced gastric cancer with peritoneal metastasis, leading to long-term survival. A 72-year-old man with advanced gastric cancer underwent curative-intent distal gastrectomy with D2 lymph node dissection for gastric outlet obstruction. During this procedure, three small peritoneal metastases were detected in the lesser omentum, the small mesentery, and the mesocolon; however, intraoperative abdominal lavage cytology was negative. We added cytoreductive surgery for peritoneal metastasis. The pathological diagnosis of the gastric cancer was tubular adenocarcinoma with pT4aN1pM1(PER/P1b)CY0 stage IV (Japanese classification of gastric carcinoma/JCGC 15th), or T4N1M1b stage IV (UICC 7th). Post-operative adjuvant chemotherapy with S-1 (TS-1)+cisplatin (CDDP) was administered for 8 months followed by S-1 monotherapy for 4 months. At 28 months after the initial surgery, a follow-up computed tomography (CT) detected a small mass beneath the upper abdominal wall. The ass showed mild avidity on 18F-fluorodeoxyglucose positron-emission (FDG-PET) CT. Salvage resection was performed for diagnosis and treatment, and pathological findings were consistent with primary gastric cancer metastasis. At 49 months after the initial gastrectomy, a new lesion was detected in the LTH with a similar level of avidity on FDG-PET CT as the abdominal wall metastatic lesion. We performed a second salvage surgery for the LTH tumor, which also showed pathology of gastric cancer metastasis. There has been no recurrence up to 1 year after the LTH surgery. With multidisciplinary treatment the patient has survived almost 5 years after the initial gastrectomy. Curative-intent gastrectomy with cytoreductive surgery followed by adjuvant chemotherapy for advanced gastric cancer with localized peritoneal metastasis might have had a survival benefit in our patient. Successive salvage surgeries for oligometastatic lesions in the abdominal wall and the LTH also yielded favorable outcomes.
Topics: Male; Humans; Aged; Stomach Neoplasms; Peritoneal Neoplasms; Fluorodeoxyglucose F18; Abdominal Wall; Round Ligament of Liver; Cisplatin; Gastrectomy; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37899267
DOI: 10.18926/AMO/65979 -
Journal of Clinical Medicine Oct 2023: In the treatment of post-cholecystectomy bile leaks, endoscopic naso-biliary drainage (ENBD) or biliary stenting using plastic stents is the standard of care. Fully...
: In the treatment of post-cholecystectomy bile leaks, endoscopic naso-biliary drainage (ENBD) or biliary stenting using plastic stents is the standard of care. Fully covered self-expandable metal stent (FCSEMS) placement across the sphincter of Oddi is considered a salvage therapy for refractory cases, but pancreatitis and migration are the major concerns. Intraductal placement of a dumbbell-shaped FCSEMS (D-SEMS) could avoid these drawbacks of FCMSESs. In this retrospective study, we investigated the usefulness of intraductal placement of the D-SEMS for post-cholecystectomy bile leaks. : Six patients who underwent intraductal placement of the D-SEMS for post-cholecystectomy bile leaks were enrolled. This method was performed as initial treatment in three patients and as salvage treatment in three ENBD refractory cases. : Technical and clinical successes were obtained in 6 (100%) patients and 5 (83%) patients, respectively. One clinically unsuccessful patient required laparoscopic peritoneal lavage. The early adverse event was one case of mild pancreatitis (17%). The median duration of the D-SEMS indwelling was 61 days (42-606 days) with no migration cases, all of which were successfully removed. The median follow-up after index ERCP was 761 (range: 161-1392) days with no cases of recurrent bile leaks. : Intraductal placement of the D-SEMS for post-cholecystectomy bile leaks might be safe and effective even in refractory cases.
PubMed: 37892668
DOI: 10.3390/jcm12206530 -
Frontiers in Oncology 2023Currently, gastric cancer with positive lavage cytology without gross peritoneal dissemination (GC-CY1) is a special type of metastatic form with poor prognosis....
Study protocol of a phase II clinical trial evaluating the efficacy of neoadjuvant intraperitoneal and systemic albumin-bound paclitaxel combined with camrelizumab and S-1 in the treatment of patients with exfoliative cell-positive gastric cancer.
BACKGROUND
Currently, gastric cancer with positive lavage cytology without gross peritoneal dissemination (GC-CY1) is a special type of metastatic form with poor prognosis. Consensus guidelines on treatment strategies for patients with GC-CY1 have not been established. This study involves a single-arm, prospective, phase II clinical trial to examine the efficacy and safety of neoadjuvant intraperitoneal and systemic (NIPS) albumin-bound paclitaxel combined with Camrelizumab and S-1 in the treatment of GC-CY1 patients.
METHODS/DESIGN
This is a prospective single-center exploratory study, and the primary endpoints of the trial are R0 resection rate and conversion rate of abdominal free cancer cells (FCCs), with secondary endpoints of 3-year progression-free survival (PFS); 3-year overall survival (OS); objective remission rate (ORR); disease control rate (DCR); safety and TRG classification.
DISCUSSION
This study is the first to apply NIPS albumin-bound paclitaxel combined with Camrelizumab and S-1 to the conversion therapy of GC-CY1 patients. It is speculated that this combination of regimens will increase the negative conversion rate of FCCs by 20%, which will provide innovative insights into conversion treatment ideas for GC-CY1 patients to be managed in a more comprehensive and optimized manner.
CLINICAL TRIAL REGISTRATION
http://clinicaltrials.gov/, identifier NCT05410847.
PubMed: 37841441
DOI: 10.3389/fonc.2023.1201928 -
World Journal of Surgical Oncology Oct 2023To investigate the risk factors associated with the development of occult peritoneal metastasis in advanced gastric cancer, and establish and externally validate a...
BACKGROUND
To investigate the risk factors associated with the development of occult peritoneal metastasis in advanced gastric cancer, and establish and externally validate a nomogram for predicting the occurrence of occult peritoneal metastasis in patients with advanced gastric cancer.
METHODS
A total of 111 patients with advanced gastric cancer who underwent laparoscopic exploration or peritoneal lavage cytology examination at the Affiliated Drum Tower Hospital of Nanjing University Medical School from August 2014 to December 2021 were retrospectively analyzed. The patients diagnosed between 2019 and 2021 were assigned to the training set (n = 64), while those diagnosed between 2014 and 2016 constituted the external validation set (n = 47). In the training set, patients were classified into two groups based on preoperative imaging and postoperative pathological data: the occult peritoneal metastasis group (OPMG) and the peritoneal metastasis negative group (PMNG). In the validation set, patients were classified into the occult peritoneal metastasis group (CY1P0, OPMG) and the peritoneal metastasis negative group (CY0P0, PMNG) based on peritoneal lavage cytology results. A nomogram was constructed using univariate and multivariate analyses. The performance of the nomogram was evaluated using Harrell's C-index, the area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), and calibration plots.
RESULTS
This study analyzed 22 potential variables of OPM in 111 gastric cancer patients who underwent laparoscopic exploration or peritoneal lavage cytology examination. Logistic regression analysis results showed that Lauren classification, CLDN18.2 score and CA125 were independent risk factors for OPM in patients with gastric cancer. We developed a simple and easy-to-use prediction nomogram of occult peritoneal metastasis in advanced gastric cancer. This nomogram had an excellent diagnostic performance. The AUC of the bootstrap model in the training set was 0.771 and in the validation set was 0.711. This model showed a good fitting and calibration and positive net benefits in decision curve analysis.
CONCLUSION
We have developed a prediction nomogram of OPM for gastric cancer. This novel nomogram has the potential to enhance diagnostic accuracy for occult peritoneal metastasis in gastric cancer patients.
Topics: Humans; Retrospective Studies; Peritoneal Neoplasms; Stomach Neoplasms; Nomograms; Peritoneum; Claudins
PubMed: 37833730
DOI: 10.1186/s12957-023-03188-2 -
Journal of Inflammation Research 2023Intra-abdominal infection is a complex pathophysiological process involving multiple systems and organs of the body. Abdominal infections complicated by severe sepsis or...
PURPOSE
Intra-abdominal infection is a complex pathophysiological process involving multiple systems and organs of the body. Abdominal infections complicated by severe sepsis or septic shock have a high mortality rate of 30-50%. Therefore, novel strategies to treat sepsis are urgently needed.
METHODS
Andrographolide (AD), the main active ingredient of , reportedly exerts beneficial effects on mice with sepsis. However, its exact mechanism of action in attenuating inflammation due to intra-abdominal sepsis remains unclear to date. Hence, this study aimed to examine the therapeutic effects of AD on cecal ligation and puncture (CLP)-induced sepsis and elucidate the underlying mechanisms.
RESULTS
Results showed that AD therapy could significantly improve the 7-day survival rate and alleviate pathological organ injury in mice with CLP. In addition, AD treatment decreased the levels of proinflammatory factors, such as tumor necrosis factor-α and interleukin (IL)-6 in the peritoneal cavity fluid and blood and increased the level of anti-inflammatory factor IL-10 in the peritoneal cavity fluid of mice with CLP. Moreover, bacterial counts in the blood and peritoneal lavage fluid were lower in the mice treated with AD than in those untreated. Mechanistically, AD treatment increased the percentage and phagocytic activity of macrophages in the peritoneal cavity.
CONCLUSION
These data showed that AD can improve the survival of mice with intra-abdominal sepsis by enhancing bacterial clearance, as evidenced by the increased percentages and phagocytic activity of macrophages in the peritoneal cavity. This study is the first to demonstrate the protective effects of AD against intra-abdominal sepsis.
PubMed: 37822531
DOI: 10.2147/JIR.S422342