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Gastric Cancer : Official Journal of... May 2023The prognosis of advanced gastric cancer (GC) invading the gastric serosa remains poor, mainly owing to high incidence of peritoneal recurrence. Patients with peritoneal...
Exosomal hsa-let-7g-3p and hsa-miR-10395-3p derived from peritoneal lavage predict peritoneal metastasis and the efficacy of neoadjuvant intraperitoneal and systemic chemotherapy in patients with gastric cancer.
BACKGROUND
The prognosis of advanced gastric cancer (GC) invading the gastric serosa remains poor, mainly owing to high incidence of peritoneal recurrence. Patients with peritoneal metastases are often treated with neoadjuvant intraperitoneal and systemic chemotherapies (NIPS). Good responders to NIPS often undergo conversion gastrectomy. This study aims to explore biomarkers predicting the occurrence of peritoneal metastasis (PM) and evaluating the efficacy of NIPS in GC patients.
METHODS
We collected six peritoneal lavage (PL) samples from two patients with PM, two without PM, and two with diminished PM after NIPS via intraperitoneal access ports. We equally isolated microRNAs from exosomes derived from PL samples for deep sequencing. Two microRNAs (hsa-let-7g-3p and hsa-miR-10395-3p) were identified, and their expression levels were examined in PL samples of 99 GC patients using qRT-PCR. Moreover, we performed in vivo and in vitro functional assays to investigate effects of these microRNAs on metastasis and chemoresistance of GC cells.
RESULTS
Exosomal microRNA expression profiling of six PL samples indicated that the microRNA signature in exosomes of PLs from patients with diminished PM was similar to that from patients without PM. Expression levels of hsa-let-7g-3p and hsa-miR-10395-3p were associated with PM. In vivo and in vitro functional assays confirmed that hsa-let-7g-3p and hsa-miR-10395-3p are involved in GC metastasis and chemoresistance.
CONCLUSION
PL-derived exosomes in GC contain large amounts of microRNAs related to PM. Moreover, hsa-let-7g-3p and hsa-miR-10395-3p could be used as biomarkers predicting PM and NIPS efficacy and are involved in GC metastasis and chemoresistance.
Topics: Humans; Peritoneal Neoplasms; Stomach Neoplasms; Peritoneal Lavage; Neoadjuvant Therapy; MicroRNAs; Biomarkers; Exosomes; Gene Expression Regulation, Neoplastic
PubMed: 36738390
DOI: 10.1007/s10120-023-01368-3 -
Langenbeck's Archives of Surgery Feb 2022In the last two decades, there has been a Copernican revolution in the decision-making for the treatment of Diverticular Disease.
BACKGROUND
In the last two decades, there has been a Copernican revolution in the decision-making for the treatment of Diverticular Disease.
PURPOSE
This article provides a report on the state-of-the-art of surgery for sigmoid diverticulitis.
CONCLUSION
Acute diverticulitis is the most common reason for colonic resection after cancer; in the last decade, the indication for surgical resection has become more and more infrequent also in emergency. Currently, emergency surgery is seldom indicated, mostly for severe abdominal infective complications. Nowadays, uncomplicated diverticulitis is the most frequent presentation of diverticular disease and it is usually approached with a conservative medical treatment. Non-Operative Management may be considered also for complicated diverticulitis with abdominal abscess. At present, there is consensus among experts that the hemodynamic response to the initial fluid resuscitation should guide the emergency surgical approach to patients with severe sepsis or septic shock. In hemodynamically stable patients, a laparoscopic approach is the first choice, and surgeons with advanced laparoscopic skills report advantages in terms of lower postoperative complication rates. At the moment, the so-called Hartmann's procedure is only indicated in severe generalized peritonitis with metabolic derangement or in severely ill patients. Some authors suggested laparoscopic peritoneal lavage as a bridge to surgery or also as a definitive treatment without colonic resection in selected patients. In case of hemodynamic instability not responding to fluid resuscitation, an initial damage control surgery seems to be more attractive than a Hartmann's procedure, and it is associated with a high rate of primary anastomosis.
Topics: Anastomosis, Surgical; Colostomy; Diverticulitis; Diverticulitis, Colonic; Humans; Intestinal Perforation; Laparoscopy; Peritoneal Lavage; Peritonitis
PubMed: 34557938
DOI: 10.1007/s00423-021-02288-5 -
International Journal of Surgery... Nov 2023Staging laparoscopy for gastric cancer is recommended to assess the tumor's locoregional extension and exclude peritoneal disease. As there is no consensus on optimizing...
BACKGROUND
Staging laparoscopy for gastric cancer is recommended to assess the tumor's locoregional extension and exclude peritoneal disease. As there is no consensus on optimizing the procedure's diagnostic accuracy, we aimed to systematically review the literature on operative techniques, followed by peritoneal lavage fluid assessment in gastric cancer patients. Specifically, we sought to indicate the most common characteristics of the procedure and cytological evaluation.
METHODS
This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The protocol for this systematic review was registered on PROSPERO database (CRD: 42022306746). On September 2022, a search was carried out using Embase, Medline ALL, Cochrane Central Register of Controlled Trials, and Web of Science Core Collection.
RESULTS
The search identified 1632 studies on staging laparoscopy and 2190 studies on peritoneal fluid assessment. Some 212 studies were included. Open Hasson was the method of choice in accessing the peritoneal cavity in 65% of the studies, followed by establishing a pneumoperitoneum at 10-12 mmHg in 52% of reports. Most frequently, the patient was positioned supine (70%), while a 30° scope and three ports were used to assess the peritoneal cavity clockwise (72%, 77%, and 85%, respectively). Right and left upper abdomen quadrants were the predominant area of laparoscopic exploration (both 65%), followed by the primary tumor region (54%), liver and pelvis (both 30%), and small bowel and spleen (19% and 17%, respectively). Regions of peritoneal lavage and aspiration were limited to the pelvis (50%), followed by right and left upper abdomen quadrants (37.5% and 50%, respectively). No studies compared different methods of operative techniques or analysis of ascites/fluid.
CONCLUSIONS
This study indicates a high heterogeneity in the technique of staging laparoscopy and peritoneal fluid assessment in gastric cancer patients. Further research and initiatives to reach a consensus on the standardization of the procedure are warranted.
Topics: Humans; Stomach Neoplasms; Ascitic Fluid; Neoplasm Staging; Laparoscopy; Peritoneal Lavage
PubMed: 37581636
DOI: 10.1097/JS9.0000000000000632 -
The Journal of Clinical Investigation Dec 2021Excessive inflammation drives the progression from sepsis to septic shock. Macrophage migration inhibitory factor (MIF) is of interest because MIF promoter polymorphisms...
Excessive inflammation drives the progression from sepsis to septic shock. Macrophage migration inhibitory factor (MIF) is of interest because MIF promoter polymorphisms predict mortality in different infections, and anti-MIF antibody improves survival in experimental models when administered 8 hours after infectious insult. The recent description of a second MIF superfamily member, D-dopachrome tautomerase (D-DT/MIF-2), prompted closer investigation of MIF-dependent responses. We subjected Mif-/- and Mif-2-/- mice to polymicrobial sepsis and observed a survival benefit with Mif but not Mif-2 deficiency. Survival was associated with reduced numbers of small peritoneal macrophages (SPMs) that, in contrast to large peritoneal macrophages (LPMs), were recruited into the peritoneal cavity. LPMs produced higher quantities of MIF than SPMs, but SPMs expressed higher levels of inflammatory cytokines and the MIF receptors CD74 and CXCR2. Adoptive transfer of WT SPMs into Mif-/- hosts reduced the protective effect of Mif deficiency in polymicrobial sepsis. Notably, MIF-2 lacks the pseudo-(E)LR motif present in MIF that mediates CXCR2 engagement and SPM migration, supporting a specific role for MIF in the recruitment and accumulation of inflammatory SPMs.
Topics: Animals; Cytokines; Disease Models, Animal; Female; Flow Cytometry; Gene Expression Profiling; Inflammation; Intramolecular Oxidoreductases; Leukocyte Count; Macrophage Migration-Inhibitory Factors; Macrophages; Macrophages, Peritoneal; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Peritoneal Lavage; Phenotype; Protein Binding; RNA-Seq; Sepsis; Signal Transduction
PubMed: 34850744
DOI: 10.1172/JCI127171 -
World Journal of Gastrointestinal... Mar 2023Gastric cancer (GC) is one of the most common malignant tumors. After resection, one of the major problems is its peritoneal dissemination and recurrence. Some free... (Clinical Trial)
Clinical Trial
BACKGROUND
Gastric cancer (GC) is one of the most common malignant tumors. After resection, one of the major problems is its peritoneal dissemination and recurrence. Some free cancer cells may still exist after resection. In addition, the surgery itself may lead to the dissemination of tumor cells. Therefore, it is necessary to remove residual tumor cells. Recently, some researchers found that extensive intraoperative peritoneal lavage (EIPL) plus intraperitoneal chemotherapy can improve the prognosis of patients and eradicate peritoneal free cancer for GC patients. However, few studies explored the safety and long-term outcome of EIPL after curative gastrectomy.
AIM
To evaluate the efficacy and long-term outcome of advanced GC patients treated with EIPL.
METHODS
According to the inclusion and exclusion criteria, a total of 150 patients with advanced GC were enrolled in this study. The patients were randomly allocated to two groups. All patients received laparotomy. For the non-EIPL group, peritoneal lavage was washed using no more than 3 L of warm saline. In the EIPL group, patients received 10 L or more of saline (1 L at a time) before the closure of the abdomen. The surviving rate analysis was compared by the Kaplan-Meier method. The prognostic factors were carried out using the Cox appropriate hazard pattern.
RESULTS
The basic information in the EIPL group and the non-EIPL group had no significant difference. The median follow-up time was 30 mo (range: 0-45 mo). The 1- and 3-year overall survival (OS) rates were 71.0% and 26.5%, respectively. The symptoms of ileus and abdominal abscess appeared more frequently in the non-EIPL group ( < 0.05). For the OS of patients, the EIPL, Borrmann classification, tumor size, N stage, T stage and vascular invasion were significant indicators. Then multivariate analysis revealed that EIPL, tumor size, vascular invasion, N stage and T stage were independent prognostic factors. The prognosis of the EIPL group was better than the non-EIPL group ( < 0.001). The 3-year survival rate of the EIPL group (38.4%) was higher than the non-EIPL group (21.7%). For the recurrence-free survival (RFS) of patients, the risk factor of RFS included EIPL, N stage, vascular invasion, type of surgery, tumor location, Borrmann classification, and tumor size. EIPL and tumor size were independent risk factors. The RFS curve of the EIPL group was better than the non-EIPL group ( = 0.004), and the recurrence rate of the EIPL group (24.7%) was lower than the non-EIPL group (46.4%). The overall recurrence rate and peritoneum recurrence rate in the EIPL group was lower than the non-EIPL group ( < 0.05).
CONCLUSION
EIPL can reduce the possibility of perioperative complications including ileus and abdominal abscess. In addition, the overall survival curve and RFS curve were better in the EIPL group.
PubMed: 37032799
DOI: 10.4240/wjgs.v15.i3.430 -
Journal of Visualized Experiments : JoVE Jul 2022Sepsis is a dysregulated host immune response to microbial invasion or tissue damage, leading to organ injury at a site distant from that of the infection or damage....
Sepsis is a dysregulated host immune response to microbial invasion or tissue damage, leading to organ injury at a site distant from that of the infection or damage. Currently, the widely used mice models of sepsis include lipopolysaccharide (LPS)-induced endotoxemia, cecal ligation and puncture (CLP), and monobacterial infection model systems. This protocol describes a method to study the host responses during Salmonella Typhimurium infection-induced septic peritonitis in mice. S. Typhimurium, a Gram-negative intracellular pathogen, causes typhoid-like disease in mice. This protocol elaborates the culture preparation, induction of septic peritonitis in mice through intraperitoneal injection, and methods to study systemic host responses. Furthermore, the assessment of bacterial burden in different organs and the flow cytometric analysis of increased neutrophil numbers in the peritoneal lavage is presented. Salmonella Typhimurium-induced sepsis in mice leads to an increase in proinflammatory cytokines and rapid infiltration of neutrophils in the peritoneal cavity, leading to lower survival. Every step in this protocol has been optimized, resulting in high reproducibility of the pathogenesis of septic peritonitis. This model is useful for studying immunological responses during bacterial sepsis, the roles of different genes in disease progression, and the effects of drugs to attenuate sepsis.
Topics: Animals; Cecum; Cytokines; Disease Models, Animal; Mice; Mice, Inbred C57BL; Neutrophils; Peritonitis; Reproducibility of Results; Salmonella typhimurium; Sepsis
PubMed: 35969050
DOI: 10.3791/63695 -
The American Surgeon Jun 2022Peritoneal lavage cytology (PLC) can detect advanced disease in gastric adenocarcinoma (GC); however, routine practice remains controversial. Furthermore, the effect of...
BACKGROUND
Peritoneal lavage cytology (PLC) can detect advanced disease in gastric adenocarcinoma (GC); however, routine practice remains controversial. Furthermore, the effect of neoadjuvant chemotherapy (NAC) on cytological detection of carcinomatosis is unknown.
METHODS
Using a 2012-2020 prospective database, we retrospectively reviewed patients with GC who underwent NAC followed by a staging laparoscopic peritoneal lavage with or without biopsy of suspicious peritoneal nodules. PLC results were considered discordant if they did not align with the peritoneal biopsy results. Patients with benign peritoneal cytology (Cyt-) or biopsy results who had postoperative time to carcinomatosis of <6 months were considered to have diagnostic failure of peritoneal lavage.
RESULTS
Fifty-five patients with GC who underwent NAC followed by staging diagnostic laparoscopy with peritoneal lavage were identified. The majority of the patients in the cohort had Cyt- lavage (89.1%). Of the patients who underwent resection, 76.1% had T3 or greater disease on final pathology and 66% had nodal metastases. In 23 patients (41.8%) who had both peritoneal lavage and biopsy, four cases (17.4%) had discordant results. Diagnostic failure rate was 20% at 6 months and 42.2% at 12 months. The median time to carcinomatosis in patients who were Cyt- or biopsy negative was 7.9 months.
CONCLUSION
PLC after NAC has a high diagnostic failure rate and inaccurately predicts carcinomatosis in 20% of patients with GC. Novel methods for identifying cytology positive GC after NAC should also be developed and evaluated, since the risk of peritoneal dissemination is high.
Topics: Adenocarcinoma; Humans; Laparoscopy; Neoadjuvant Therapy; Neoplasm Staging; Peritoneal Lavage; Peritoneal Neoplasms; Prognosis; Retrospective Studies; Stomach Neoplasms
PubMed: 33382351
DOI: 10.1177/0003134820984867 -
Annals of Medicine and Surgery (2012) Dec 2023
PubMed: 38098572
DOI: 10.1097/MS9.0000000000001444 -
Revista Do Colegio Brasileiro de... 2020to assess whether laparoscopy with peritoneal lavage is superior to computed tomography for staging gastric adenocarcinoma and whether it can modify the surgical... (Comparative Study)
Comparative Study
OBJECTIVE
to assess whether laparoscopy with peritoneal lavage is superior to computed tomography for staging gastric adenocarcinoma and whether it can modify the surgical approach.
METHODS
we conducted a retrospective study of 46 patients with gastric adenocarcinoma treated by the digestive surgery team of the Passo Fundo Clinics Hospital (RS), from January 2015 to December 2018, and submitted to laparoscopy with preoperative peritoneal lavage. All patients underwent preoperative clinical staging with computed tomography.
RESULTS
of the 46 patients analyzed, the majority had tumors located in the cardia (34.8%), poorly differentiated (69.6%), and subtype signet ring cells (65.2%). In 91.3%, the computed tomography scan did not identify peritoneal carcinomatosis or distant metastasis. Among these patients with negative computed tomography for distant disease, 21.8% had positive peritoneal lavage for neoplastic cells and had their therapeutic approaches modified.
CONCLUSION
laparoscopy and peritoneal lavage altered the surgical decision in 21.8% of patients, providing a more reliable preoperative staging in gastric adenocarcinoma.
Topics: Adenocarcinoma; Aged; Digestive System Surgical Procedures; Female; Gastrectomy; Humans; Laparoscopy; Male; Middle Aged; Neoplasm Staging; Peritoneal Lavage; Preoperative Care; Retrospective Studies; Stomach Neoplasms; Tomography, X-Ray Computed
PubMed: 32022110
DOI: 10.1590/0100-6991e-20192314 -
Saudi Pharmaceutical Journal : SPJ :... Jun 2024Post-operative peritoneal adhesions (PA) are a common and important clinical problem. In this study, we focused on the ameliorative efficacy of ginger and gingerol...
Intra-peritoneal lavage of rhizome and its active constituent gingerol impede inflammation, angiogenesis, and fibrosis following post-operative peritoneal adhesion in male rats.
Post-operative peritoneal adhesions (PA) are a common and important clinical problem. In this study, we focused on the ameliorative efficacy of ginger and gingerol compounds on surgical-induced peritoneal adhesion, and their strategies that disrupted the PA formation pathways to suppress their incidence. First, liquid chromatography-mass spectrometry (LC-MS) was established to separate and identify several chemical groups of ginger rhizome extract. In the next steps, male Wistar albino rats were randomly selected and divided into various groups, namely sham, control, ginger extract (0.6, 1.8, 5 %w/v), and gingerol (0.05, 0.1, 0.3, and 1 %w/v). Finally, we investigated the macroscopic parameters such as wound healing, body weight as well as spleen height and weight. In addition, visual peritoneal adhesion assessment was performed via Nair et al and Adhesion Scoring Scheme. Moreover, the microscopic parameters and biological assessment was performed via and immunoassays. The present findings revealed significant improvement in wound healing and reduction of the adhesion range, as Nair et al. and Adhesion Scoring Scheme scoring, in both the ginger and gingerol groups compared to the PA group (). Whereas, gingerol (0.3 % w/v) was able to increase the body weight in rats () at end stage of experiment. Also, inflammation, angiogenesis, and fibrosis were significantly decreased due to the downregulation of interleukin (IL)-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, vascular endothelial growth factor (VEGF), respectively, in the ginger and gingerol groups compared to the PA group (). In contrast, the levels of IL-10 were increased in the ginger and gingerol groups compared to the control group (). Our results proved that ginger rhizome and gingerol, as novel therapeutic compounds, could be used to prevent PA for their beneficial anti-inflammatory as well as anti-fibrosis properties in clinical trials. However, further clinical studies are required to approve the effectiveness of ginger and gingerol.
PubMed: 38737808
DOI: 10.1016/j.jsps.2024.102092