Gene polymorphisms associated with sudden decreases in heart rate during extensive peritoneal lavage with distilled water after gastrectomy

BACKGROUND Our previous study found that the telomerase-associated protein 1(TEP1,rs938886 and rs1713449)and homo sapiens RecQ like helicase 5(RECQL5,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 TEP1 rs938886 and rs1713449 and RECQL5 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 geneenvironment 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 RECQL5(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;P=0.045).Under the codominant and overdominant models,the TC genotype of RECQL5(rs820196)was associated with a higher risk of HR decrease relative to the TT and TT+CC genotypes(P=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(P=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(P=0.01).For rs820196,nonsmokers with the TC genotype had a higher HRV risk compared with nonsmokers carrying the TT genotype(P=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(P=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(P=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(P=0.022)and rs820196-hypertension(P=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(P=0.01).CONCLUSION The polymorphism of the RECQL5 and TEP1 genes were associated with HRV during peritoneal lavage with distilled water after gastrectomy.

Efficacy and outcome of extensive intraoperative peritoneal lavage plus surgery vs surgery alone with advanced gastric cancer patients

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(P<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(P<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(P=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(P<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.

Clinical significance of telomerase activity in peritoneal lavage fluid from patients with gastric cancer and its relationship with cellular proliferation

AIM： To evaluate the efficacy of telomerase activity assay and peritoneal lavage cytology （PLC） examination in peritoneal lavage fluid for the prediction of peritoneal metastasis in gastric cancer patients, and to explore the relationship between telomerase activity and proliferating cell nuclear antigen expression.METHODS： Telomeric repeated amplification protocol （TRAP）-enzyme-linked immunosorbent assay （ELISA） was performed to measure the telomerase activity in 60 patients with gastric cancer and 50 with peptic ulcer. PLC analysis of the 60 patients with gastric cancer was used for comparison. The proliferating cell nuclear antigen （PCNA） in gastric carcinoma was immunohistochemically examined.RESULTS： The telomerase activity and PLC positive rate in peritoneal lavage fluid from patients with gastric cancer was 41.7% （25/60）, and 25.0% （15/60）, respectively. The positive rate of telomerase activity was significantly higher than that Qf PLC in the group of pT, （15/16 vs 9/16, P 〈 0.05）, P1-3 （13/13 vs 9/13, P 〈 0.05） and diffuse type （22/42 vs 13/42, P 〈 0.05）. The patients with positive telomerase activity, peritoneal metastasis, and serosal invasion had significantly higher levels of average PCNA proliferation index （PI）, （55.00 ± 6.59 vs 27.43 ± 7.72, 57.26 ±10.18 vs 29.15 ±8.31, and 49.82 ± 6.74 vs 24.65 ±7.33, respectively, P 〈 0.05）.CONCLUSION： The TRAP assay for telomerase activity is a useful adjunct for cytologic method in the diagnosis of peritoneal micrometastasis and well related to higher proliferating activity of gastric cancer. The results of this study also suggest a promising future therapeutic strategy for treating peritoneal dissemination based on telomerase inhibition.

Impact of metabolism-related mutations on the heart rate of gastric cancer patients after peritoneal lavage

BACKGROUND During surgery for gastric cancer,peritoneal lavage using warm distilled water can cause temporary hemodynamic changes.AIM To examine the associations between changes in heart rate and single nucleotide polymorphisms(SNPs).METHODS This was a prospective observational study of patients with gastric cancer who underwent gastrectomy and peritoneal hypotonic lavage at the Third Af
liated Hospital of Soochow University from March 2018 to March 2019.Related SNPs were selected,and the verified exons were analyzed.Heart rate and blood pressure(BP)were measured before and after lavage.The patients were grouped as heart rate change≥30%vs<30%.Comparison and regression analyses of the selected SNPs were performed between the two groups.RESULTS According to the inclusion/exclusion criteria,194 patients were included in the analysis.Of these patients,138 were male,with a mean age of 65.9±0.8 years,and 56 were female,with a mean age of 65.0±1.3 years.Heart rate dropped by 0%-10%in 65 participants,by 10%-15%in 29,by 15%-20%in 23,by 20%-50%in 39,by 50%-100%in four,six had a cardiac arrest,and 28 had an increase in heart rate.Considering the possible impact of exonic SNPs on the phenotypes,TEP1(rs938886),TEP1(rs1713449),and RECQL5(rs820196)were analyzed.The haplotype analysis suggested that the haplotypes CTT[odds ratio(OR)=2.018,95%confidence interval(CI):1.012-4.025,P=0.0430]and GCC(OR=2.293,95%CI:1.174-4.477,P=0.0131)of TEP1(rs938886),TEP1(rs1713449),and RECQL5(rs820196)increased the risk of a drop in heart rate>30%.CONCLUSION The TEP1(rs938886),TEP1(rs1713449),and RECQL5(rs820196)SNPs were associated with changes in heart rate≥30%during intraperitoneal lavage using distilled water after gastrectomy for gastric cancer.

ICU management of patients with suspected positive findings of diagnostic peritoneal lavage following blunt abdominal trauma

Objective: To explore the management for blunt abdominal trauma victims with probable positive diagnostic peritoneal lavage (DPL) findings. Methods: Data of 76 patients with probable positive DPL findings accepted to ICU in previous 10 years were reviewed. After admission, the patients were evaluated in a settled time according to the protocols of Advanced Trauma Life Support (ATLS). Vital signs were continuously monitored and DPL, ultrasound and/or CT scan were repeated when necessary. Results: Eighteen (24%) of 76 patients presented positive DPL findings after repeated DPL. Surgical findings confirmed 7 cases of spleen rupture, 3 hepatorrhexis (infra-Glisson capsule), 4 intestinal perforation, 2 gastric perforation, 1 colon perforation and 1 injured mesentery. Conclusions: Patients with probable positive DPL findings were admitted to ICU with vital signs continuously monitored. Repeated DPL with supplemental ultrasound and/or CT scan can work together to increase the sensitivity and accuracy of the diagnosis, reduce the rate of exploratory laparotomy, ensure patients’ safety and provide a reliable basis for therapeutic operations.

Significance of peritoneal lavage cytology based on genetic signatures in gastric cancer

Perit on eal metastasis is the most comm on patter n of recurre nee and the most freque nt cause of death after surgery in patie nts with gastric can cer.Perit on eal free can cer cells dissem in ated from the primary lesi on site have bee n con sidered the main cause of perit on eal metastasis.Perit on eal lavage cytological exam in ati on(PLC)has bee n show n to be an in depe ndent predictor of gastric cancer relapse after curative resection and poor overall survival.However,the conventional cytological examinations have high rates of false-positive and false-negative findings.To improve the sensitivity,molecular-based methods using reverse transcriptase polymerase chain reaction have been developed for detecting cancer cells in peritoneal wash fluids of patients with gastric cancer.We performed a PubMed search for articles describing PLC in gastric can cer.Releva nt articles were reviewed and data on available outcomes elaborated.The cli nical roles and attributes of PLC in gastric can cer were reviewed,and its future applicati on to this disease is discussed.

Stercoral perforation of the cecum:A case report

BACKGROUND With less than 90 reported cases to date,stercoral perforation of the colon is a rare occurrence.Stercoral ulceration is thought to occur due to ischemic pressure necrosis of the bowel wall,which is caused by the presence of a stercoraceous mass.To underscore this urgent surgical situation concerning clinical presentation,surgical treatment,and results,we present the case of a 66-year-old man with a stercoral perforation.CASE SUMMARY A 66-year-old man with a history of hypertension,hyperlipidemia,and gout presented at the emergency department with lower abdominal pain and a low-grade fever lasting for a few hours.Abdominal computed tomography indicated a suspected bezoar(approximately 7.6 cm)in the dilated cecum,accompanied by pericolic fat stranding,mild proximal dilatation of the ileum,pneumoperitoneum,and minimal ascites.Intraoperatively,feculent peritonitis with isolated cecal perforation were observed.Consequently,a right hemicolectomy with peritoneal lavage was performed.A histopathological examination supported the intraoperative findings.CONCLUSION In stercoral perforations,a diagnosis should be diligently pursued,especially in older adults,and prompt surgical intervention should be implemented.

Molecular diagnosis and therapy for occult peritoneal metastasis in gastric cancer patients

To apply an individualized oncological approach to gastric cancer patients,the accurate diagnosis of disease entities is required.Peritoneal metastasis is the most frequent mode of metastasis in gastric cancer,and the tumor-node-metastasis classification includes cytological detection of intraperitoneal cancer cells as part of the staging process,denoting metastatic disease.The accuracy of cytological diagnosis leaves room for improvement;therefore,highly sensitive molecular diagnostics,such as an enzyme immunoassay,reverse transcription polymerase chain reaction,and virusguided imaging,have been developed to detect minute cancer cells in the peritoneal cavity.Molecular targeting therapy has also been spun off from basic research in the past decade.Although conventional cytologyis still the mainstay,novel approaches could serve as practical complementary diagnostics to cytology in near future.

Comparison of peritoneal free gastric cancer cells' detecting rates between laparoscopically assisted and open radical gastrectomy

Objective： To compare laparoscopic gastrectomy and conventional surgery on the dissemination and seeding of tumor cells. Methods：Intraoperative peritoneal lavage cytologic examination was performed in 65 patients with gastric cancer, during laparoscopic gastrectomy （n = 34） and conventional surgery （n = 31）. Cytology was examined twice, immediately after opening the peritoneal cavity and just before closing the abdomen. Saline was poured into the peritoneal cavity, and 100 ml fluid was retrieved after irrigation. Laparoscopic instruments were lavaged after surgery with 100 ml saline. Carbon dioxide （COz） was derived through the trocar side orifice after pneumoperitoneum during laparoscopic gastrectomy and filtered through 100 ml saline. Cytologic examination of the filtrate was performed after the filtration process. Results： The incidence of positive cytology during laparoscopic surgery was 32.26% in the preoperative lavage and 22.58% in the postoperative lavage. The incidence of positive cytology during conventional surgery was 41.18% before lavage and 26.47% after lavage. Only one positive cytology was detected in the CO2 filtrate gas. The incidence of positive cytology in the lavage of the instruments during laparoscopic surgery was 6.45 %. Conclusion： During gastric laparoscopic surgery, CO2 pneumoperitoneum does not affect tumor cell dissemination and seeding. In this study, laparoscopic techniques used in gastric cancer surgery were not associated with a higher risk for intraperitoneal dissemination of cancer cells than the conventional surgery.

Role of RECK methylation in gastric cancer and its clinical significance

AIM:To investigate the relation between RECK methylation and clinicopathological characteristics of gastric cancer patients and evaluate the role of RECK methylation in peritoneal metastasis of gastric cancer.METHODS:Methylation of RECK gene in 40 paired samples of gastric cancer and its corresponding adjacent normal mucosa,lymph nodes and peritoneal irrigation fluid was detected by methylation-specific polymerase chain reaction.RESULTS:Aberrant methylation of RECK gene was detected in 27.5%(11/40)of the adjacent normal mucosa samples,in 47.5%(19/40)of gastric cancer samples,in 57.1%(12/21)of the lymph node samples,and in 35%(14/40)of peritoneal irrigation fluid samples,respectively,with a significant difference between the adjacent normal mucosa and lymph node samples(P=0.023).Presence of RECK methylation in the primary tumor samples was significantly correlated with tumor invasion(P=0.023).The accuracy of RECK methylation in peritoneal lavage fluid samples for the diagnosis of peritoneal metastasis of gastric cancer was 72.5%(26/40),with a sensitivity of 66.7%(6/9) and a specificity of 74.2%(23/31).CONCLUSION:Aberrant methylation of RECK gene may provide useful information for the early diagnosis and treatment of peritoneal metastasis of gastric cancer.

Embryonic natural orifice transluminal endoscopic surgery in the treatment of severe acute pancreatitis complicated by abdominal compartment syndrome

BACKGROUND: The study aimed to estimate the value of embryonal natural orifice transluminal endoscopic surgery(ENOTES) in treating severe acute pancreatitis(SAP) complicated with abdominal compartment syndrome(ACS).METHODS: The patients, who were randomized into an ENOTES group and an operative group, underwent ENOTES and laparotomy, respectively. The results and complications of the two groups were compared.RESULTS: Enterocinesia was observed earlier in the ENOTES group than in the operative group. Acute Physiology and Chronic Health Evaluation II(APACHE II) score of patients in the ENOTES group was lower than that of the operative group on the 1st, 3rd and 5th post-operative day(P<0.05). The cure rate was 96.87% in the ENOTES group, which was statistically different from 78.12% in the operative group(P<0.05). There were significant differences in complications and mortality between the two groups(P<0.01).CONCLUSION: Compared with surgical decompression, ENOTES associated with flexible endoscope therapy is an effective and minimal invasive procedure with less complications.

Promoter Hypermethylation of KiSS-1 Gene in Gastric Cancer

Objective： To investigate the association between KiSS-1 methylation and clinicopathological characteristics of gastric cancer and evaluate the role of peritoneal lavage fluid in detecting peritoneal metastases. Methods： The methylation status of KiSS-1 gene in 40 gastric cancer specimens, the corresponding adjacent normal mucosa, lymph nodes and peritoneal lavage fluid was investigated by methylation-spcific polymerase chain reaction（MS-PCR）. Results： Aberrant methylation of KiSS-1 gene was detected in 55%（22/40） of the adjacent normal mucosa, 82.5% （33/40）of gastric cancer specimens, 80.95%（17/21） of the lymph nodes, and 42.5%（17/40） of peritoneal lavage fluid. Methylation in gastric carcinoma and lymphonode was more frequent than in non-neoplastic gastiric mucosa. Presence of KiSS-1 methylation in peritoneal lavage fluid was significantly correlated with tumor invasion （P=0.043）. The accuracy of KiSS-1 methylation in peritoneal lavage fluid for diagnosing peritoneal metastasis was 70%, with a sensitivity of 77.8% and a specificity of 67.7%. Conclusion： Aberrant methylation of KiSS-1 gene is a common event in the occurrence and progression of gastric carcinoma, which may provide useful information for the early diagnosis of peritoneal metastases and a new therapy for gastric cancer.

Molecular biomarkers for the detection of metastatic colorectal cancer cells

Approximately half of all patients with colorectal cancer develop local recurrence or distant metastasis during the course of their illness. Recently, the molecular detection of metastatic cancer cells in various types of clinical samples, such as lymph nodes, bone marrow, peripheral blood, and peritoneal lavage fluid, has been investigated as a potential prognostic marker. The prognostic value of molecular tumor cell detection was independent of the type of detection method used. As assays become more sensitive and quantitative, a more thorough assessment of the cancer status of patients will be based on molecular markers alone. At present, it is difficult to conclude that one specific molecular marker is superior to others. Comparative analyses are recommended to assess the prognostic impact of molecular analyses in the same patient and determine the biomarkers that provide the most accurate prognostic information.

IMMUNE TOLERANCE INDUCED BY GAMMA-RAY IRRADIATION

Objective: To detect the existence of immune tolerance induced by gamma-ray irradiation. Methods: Peritoneal cells were harvested from mice subjected to 5 Gy 60Co gamma-ray total body irradiation at 3d, 7d, 15d and 30d, then their counts, morphological changes and IL-12 gene expression were investigated. Results: After irradiation, the peritoneal cells were sharply reduced, the cell morphology shifted from round-like to polymorphic and fusiform with some processes, expression of IL-12 p35 was seriously suppressed, while that of IL-12 p40 greatly enhanced. Conclusion: Our data highly suggest that the gamma-ray irradiation could potentially induce dendritic cell (DC) commitment and immune tolerance.

Mesentery solitary fibrous tumor with postoperative recurrence and sarcomatosis: A case report and review of literature

BACKGROUND Solitary fibrous tumors are rare neoplasms of mesenchymal origin. They are often of low malignant potential and rarely metastasize. They frequently arise from the pleura and can occur at any soft tissue site in the body. However, these tumors rarely develop in the mesentery, peritoneal cavity or peritoneum.CASE SUMMARY We report on a scarce case of solitary fibrous tumor of the rectal mesentery showing sarcomatosis about 4 years after previous tumor resection. This 69-yearold male had no clinical symptoms but was transferred to our hospital because of a suspected tumor recurrence from follow-up abdominal computed tomography.Tumor markers(CEA, CA 19-9 and CA 125) were within the normal range. Open laparotomy showed sarcomatosis, and pathology confirmed its mesenchymal origin and diagnosis as the solitary fibrous tumor. Our case may be the second recurrent mesentery solitary fibrous tumor reported to date, and the only one with progression to sarcomatosis. There has been no evidence of recurrence in follow-up at the 28 th mo after extensive intra-operative peritoneal lavage and cytoreductive surgery.CONCLUSION Although there are few risk factors of cancer recurrence in this patient, careful long-term followup after cytoreductive surgery is necessary.

Liquid biopsy in endometrial cancer

Liquid biopsy(LB)is an emerging tool for the evaluation of relapse in several cancers and nowadays is used in lung cancer for primary detection and molecular characterization when tumoral tissue is not available.It can represent an innovative biospecimen for the screening,diagnosis,and monitoring of all types of cancer and for monitoring of therapeutic efficacy.LB includes several biofluids such as blood,urine,peritoneal fluid/lavage,and analytes(circulating tumor cells,circulating tumor DNA,long noncoding RNA,microRNA,vesicles,mRNA,and protein)that can play different roles in diagnosis,prognosis,and patient management as well as in the improvement of the knowledge of cancer evolution.Endometrial cancer(EC)is a tumor usually detected at low stage with a good prognosis,but few low risk cases,unexpectedly,can evolve to bad prognosis.Up to now,no molecular target exists to treat advanced stage or to define the evolution of low stage EC.This review focuses on how the LB may help in the management and characterization of patients affected by EC.