ABSTRACT
Objective:To construct a preoperative rehabilitation program for gastric cancer patients, aiming to provide scientific and reasonable preoperative guidance for gastric cancer patients.Methods:On the basis of literature research and expert group meeting, the first draft of the preoperative rehabilitation program for gastric cancer patients was constructed. From October 2021 to January 2022, the Delphi method was used to conduct 2 rounds of expert letter inquiries to 16 experts in related fields from 11 hospitals in Jiangsu Province, and the entries were revised according to the experts′ inquiries.Results:In the two rounds of expert correspondence, the positive coefficients of experts were 88.89% and 100.00%, and the authority coefficients of experts were both 0.88. The coordination coefficients of the items in the two rounds of inquiry were 0.279 and 0.290, respectively. The final program consisted of 3 first-level entries, 11 second-level entries and 32 third-level entries.Conclusions:The scheme constructed in this study is scientific, reliable and applicable, and is worth being promoted further in clinical practice.
ABSTRACT
Objective:To analyze the influencing factors of the medical insurance balance of hospitalization expenses for gastric cancer surgery patients under DRG payment, for reference for promoting the reform of DRG payment in public hospitals and controlling hospitalization expenses reasonably.Methods:The gastric cancer patients enrolled in the gastroenterology department of a tertiary comprehensive hospital from January to July 2022 were selected as the research subjects. The indicators such as patient age, medical insurance balance, hospitalization expenses and their composition were extracted from the hospital information management system and the medical insurance settlement system a certain city. Descriptive analysis was conducted for all data, and stepwise multiple linear regression was used to analyze the influencing factors of patients′ medical insurance balance. Monte Carlo simulation method was used to simulate different combination scenarios of various influencing factors to analyze the probability of medical insurance balance.Results:A total of 205 patients were contained, including 117 in the medical insurance balance group and 88 in the loss group. The difference in hospitalization expenses and medical insurance balance between the two groups of patients were statistically significant ( P<0.05). The intervention of medical insurance specialists, correct DRG enrollment, parenteral nutrition preparation costs, anti infective drug costs, examination costs, and consumables costs were the influencing factors of patient medical insurance balance ( P<0.05). Through Monte Carlo simulation verification, patients with different cost parenteral nutrition preparations, or different anti infective drug schemes had the higher probability of medical insurance balance in the scenario where the medical insurance commissioner intervenes and the DRG enrollment was correct. Conclusions:The hospital adopted interventions from medical insurance specialists to ensure the correct DRG enrollment of patients, accurate use of parenteral nutrition and anti infective drugs, and reasonable control the cost of examinations and consumables, which could increase the probability of medical insurance balance for gastric cancer surgery patients. In the future, hospitals should further promote the procurement of drug consumables in bulk, reduce unnecessary examinations, develop standardized perioperative nutritional interventions and anti infection treatment pathways, ensure the accuracy of DRG enrollment, optimize clinical diagnosis and treatment pathways to improve the efficiency of medical insurance fund utilization and provide high-quality medical services for patients.
ABSTRACT
Objective:To summarize the clinical characteristics of primary retroperitoneal tumors (PRT).Methods:All PRT cases undergoing surgical resection during recent 10 years at our center were retrospectively analyzed.Results:Tumors in all 92 cases were of malignant in 64 cases, borderline in 10 and benign PRT in 18, among which liposarcoma and leiomyosarcoma were the most common types. The tumor size and Ki-67 was significantly higher in malignant compared to borderline or benign PRT. The multifocal rate was 50%, en-bloc resection rate was 72%, R 0 rate was 61%, and combined organ resection rate was 41% in malignant PRTs. Small intestine and the colon were the most frequently resected organs. During 9.3 years of follow-up period, the 1-, 3- and 5-year cumulative reoperation rate of malignant PRT was 10.6%, 44.7% and 62.9%, respectively, and the median re-operation period was 4.0 years. The 1-, 3- and 5-year cumulative survival rate was 90.1%, 73.0% and 64.2%, respectively, and the median survival period was 6.1 years. None of postoperative borderline or benign PRT recurred or needed re-operation or deceased. Conclusion:Most of PRTs were malignant, presenting themsehies as a challenge to surgery with unfaror prognosis.
ABSTRACT
@#Starvation therapy is an emerging oncological treatment that targets the abnormally elevated nutrient uptake and metabolic pathways to inhibit and kill tumors. In addition to glucose, the targets of starvation therapy also include other nutrients in tumor cells.However, concerns like ineffective targeting and drug tolerance probably have an impact on their clinical translation.Nanomaterial-assisted starvation treatment has been developing quickly in recent years to address these concerns.In this review, several exemplary nanomedicines for starvation therapy and combined starvation therapy with other therapies were offered.They target nutrients other than glucose metabolism, including lactic acid, amino acids, and lipids, using nanomaterials to improve the efficacy of starvation therapy.This review provides reference for further development of nanomedicines with starvation treatment effect.
ABSTRACT
Objective:To analyze the clinical characteristics and the risk factors of acute mechanical small bowel obstruction in adults.Methods:The clinical data of 487 adult patients with acute mechanical small bowel obstruction treated in Drum Tower Hospital Clinical College of Nanjing Medical University from June 2010 to December 2020 were retrospectively analyzed. There were 259 cases of strangulated obstruction (strangulation group) and 228 cases of non-strangulated obstruction (simple group). The cases in the strangulation group were confirmed by operation or pathology, the cases in the simple group were confirmed by non-operative therapy ( n=167) or operation ( n=61). The clinical data, including age, abdominal pain, vomiting, tenderness, rebound pain and muscle defense; the CT signs, including transitional zone, dilatation of intestinal loop, high density of intestinal wall; laboratory test results, including white blood cell count, lactate dehydrogenase (LDH) and C-reactive protein (CRP) were analyzed in both groups. Univariate and multivariate regression were used to identify risk factors of strangulated small bowel obstruction. Results:There were significant significances in gender (male vs.female: χ2=4.35, OR=0.67), rebound pain (χ2=170.98, OR=45.12), muscle tension(χ2=113.79, OR=29.32), American Society of Anesthesiologists score (ASA score)≥3 (χ2=12.94, OR=51.58), white blood cell count ( t=6.19, OR=1.14), LDH ( t=2.37, OR=1.00), CRP ( t=2.23, OR=1.01), albumin ( t=2.04, OR=0.97), mesenteric fluid sign (χ2=49.44, OR=5.40), increased bowel wall density (χ2=222.78, OR=62.66), bowel wall thickening sign (χ2=43.81, OR=3.49), ascites (χ2=237.29, OR=43.01), beak sign (χ2=231.50, OR=56.62), mesenteric fat stranding (χ2=242.65, OR=34.90), and stranding sign(χ2=224.79, OR=53.48) between strangulation group and simple group ( P<0.01). The multivariate regression analysis showed that mesenteric fluid sign ( OR=12.94), muscle tension ( OR=7.28), ascites ( OR=6.42), increased bowel wall density ( OR=4.30), bowel wall thickening sign ( OR=1.85), white blood cell count ( OR=1.14) and gender (male vs. female: OR=0.50) were risk factors of strangulated small bowel obstruction. Conclusion:In acute mechanical small bowel obstruction,for female patients presenting mesenteric fluid sign, muscle tension, ascites, increased bowel wall density, bowel wall thickening sign and increased white blood cell count, the strangulated obstruction is likely to occur.
ABSTRACT
Clinical data of 289 patients aged 60 years old and above with acute intestinal obstruction operated in Drum Tower Hospital during June 2010 to December 2020 were analyzed retrospectively. Among 289 cases, 97 cases(33.6%)had tumor, 66(22.8%)had external hernias, 44(15.2%)had adhesions, 36(12.5%)had volvulus, 20(6.9%)had internal hernias, 8(2.8%)had intussusception and 18(6.2%)had other causes. Of 156 strangulated intestinal obstruction cases, 51 cases(32.7%)had external hernias,36(23.1%)had volvulus, 26(16.7%)had adhesions, 18(11.5%)had internal hernias, 14(9.0%)had tumor, 8(5.1%)had intussusception, and 3(1.9%)had other causes. There was a history of abdominal surgery in 88.6%(39/44)cases of adhesion, 85.0% (17/20) cases of internal hernia and 61.1%(22/36)cases of volvulus. For patients with acute intestinal obstruction caused by intestinal tumor, the cases of small bowel obstruction, strangulated intestinal obstruction and the strangulated large bowel were significantly less than those of large bowel obstruction, the non-strangulated intestinal obstruction and the non-strangulated large bowel obstruction (5 vs. 92, 14 vs. 80, 12 vs. 83, respectively; all P<0.05). For patients with strangulated intestinal obstruction caused by external hernias, volvulus, internal hernias and intussusception were significantly more than those with non-strangulated intestinal obstruction groups(51 vs.15, 36 vs. 0, 18 vs. 2, 8 vs. 0, respectively; P<0.05). The patients with strangulated large bowel obstruction caused by external hernias( n=4) and volvulus( n=9)were significantly more than those with non-strangulated large bowel obstruction( n=1 and 0, respectively; P<0.05). The patients with strangulated small bowel obstruction caused by adhesions( n=26)and volvulus( n=27)were significantly more than those with non-strangulated small bowel obstruction( n=18 and 0,respectively; P<0.05).The study showed that the principal causes of emergency operation for acute intestinal obstruction and strangulated intestinal obstruction are intestinal tumor and external hernias in elderly patients.
ABSTRACT
Background:Malnutrition is common in patients with cancer, whichadversely affectsthesurvival and quality of life ofcancer patients.However, there is no national data on the prevalence of malnutrition inChinese cancer patients. Thisstudy aims to evaluate the prevalenceof malnutrition and quality of life(QOL)ofChinese patients with localregional, recurrentor metastatic cancer,to address the prognostic value of nutritional status and QOLon the survival of cancer patients in China and to validate the patient-generated subjective global assessment (PG-SGA) questionnaire in Chinese cancer patients.Methods:Thisisanobservational,multi-centered,and hospital-based prospective cohort study.We aimed to recruit 50,000 cancer patients (age 18and above)overan 8-year period.Data collection will occur within 48hrafter patientsare admitted to hospital, 30-days after hospital admission, and the follow-up will be conducted1-8years after enrolment. The primary outcomeisoverall survival, and secondaryoutcomes arelength of hospital stay and hospital costs. Factors measured are demographic characteristics, tumor characteristics, anthropometry measurements,hematological measurement, body composition, PG-SGAscores,Karnofsky performance status scores,and QLQ C30 scores. This protocol wasapproved by local ethical committees of all the participant hospitals.Conclusions: This multi-centered, large-scale, long-time follow-up prospective study will help diagnose malnutrition in cancer patients in China, and identify the related risk factors associated with the negative outcomes. The anticipated results will highlight the need for a truly scientific appraisal of nutrition therapy, and help to improve outcomes among cancer patients in China.Trial Registration: The trial has been registered with the Chinese Clinical Trial Registry, ChiCTR1800020329. Registered on 19 December 2018
ABSTRACT
Gastric stem cells are adult stem cells found in the gastric tissues,which possess high self-renewal capability,proliferation rate and multiple differentiation capability.They can regenerate all the gastric mucosa epithelial cells.Gastric stem cells play an important role in the self-renewal and injury repair,making epithelium of gastric mucosa in the dynamic balance and maintaining the integrity of gastric mucosa.With the constant deepening of stem cell research,the application of gastric stem cells provides a new means for the study of gastric physiology and diseases.Since the first report by Barker in 2010,gastric organoids have soon become a model of interest and are highly desirable as tools for studying gastric diseases.As an optimal experimental model,gastric organoids are superior to animal model and conventional cell culture.Gastric organoids are comprised of all major types of gastric epithelial cells,represent the architecture and function remarkably similar to those of the gastric epithelium,faithfully recapitulating the functional gastric epithelium ex vivo.Especially gastric organoids derived from the human body,which allow the investigation of the function of human stomach in the ex vivo setting.In this review,research progresses of gastric stem cells and their application in establishment of gastric organoids are summarized.
ABSTRACT
Colonic organoids are three-dimensional organotypic cultures of the colonic stem cells or pluripotent stem cells. Its essence is the culture of colonic stem cells or pluripotent stem cells, and their derived intestinal epithelial cells, intestinal endocrine cells and goblet cells in basement membrane extract with specific growth factors. Colonic organoids are comprised of all major types of colonic epithelial cells and represent the architecture and function remarkably similar to those of the colonic epithelium, faithfully recapitulating the functional colonic epithelium ex vivo. As a superior basic experimental model, colonic organoids are representing advantages over conventional cell models and animal models in many aspects, such as high successful rate, short productive cycle, and high consistency with source tissue. Since first reported in 2011, colonic organoids have soon become an important topic in the field of colonic diseases. It has now been applied in the field of physiology of colonic epithelium, infectious diarrhea, ulcerative colitis, regeneration of intestinal injury, and colon tumors. In this review, we summarize the research advances of establishment and application of colonic organoids.
ABSTRACT
OBJECTIVE@#To investigate the risk factors of methicillin-resistant Staphylococcus aureus(MRSA) enterocolitis after gastrointestinal surgery.@*METHODS@#Clinical and pathological data of 17 cases with MRSA enteritis after gastrointestinal surgery from March 2015 to March 2017 at Department of General Surgery of Affiliated Drum Tower Hospital were retrospectively analyzed.@*INCLUSION CRITERIA@#(1) age of 18 to 80 years;(2) with history of gastrointestinal surgery; (3) diarrhea symptoms within 7 days after gastrointestinal surgery; (4) use of antibiotics before diarrhea; (5) fecal smear showing a large number of gram positive cocci; (6) fecal culture suggested the presence of MRSA; (7) application of antibiotic therapy against MRSA was effective.@*EXCLUSION CRITERIA@#(1)clostridium difficile toxin positive; (2) toxic shock syndrome caused by food poisoning. According to gender, age, and inpatient ward, 1:2 pairing was performed, and 34 patients with non-MRSA enteritis from the hospitalized cases in the same ward were selected as the control group for retrospective case-control study. There were no significant differences in the gender, age, and constitution index between two groups (all P>0.05), indicating that the two groups were comparable. The χ² test was used to perform univariate analysis on 11 factors, including the nature of the primary disease, colorectal surgery, emergency surgery, use of multiple antibiotics, preoperative bowel preparation, perioperative hormone, intraoperative intraperitoneal chemotherapy, perioperative nasogastric tube, diabetes history, intensive care unit stay, and previous infectious disease hospitalization, and then multivariate logistic regression analysis was performed.@*RESULTS@#MRSA enteritis occurred 3 to 5 days after surgery in all the 17 cases, and 4 cases developed septic shock rapidly. Univariate analysis showed that the operation site (colorectal surgery) (χ²=4.747, P=0.029) and use of two antibiotics before MRSA enteritis (χ²=3.959, P=0.047) were associated with MRSA enteritis after gastrointestinal surgery. Multivariate logistic regression analysis revealed that colorectal surgery was the only independent risk factor for MRSA enteritis after gastrointestinal surgery(OR=5.526, 95%CI: 1.350-22.602,P=0.017), while the use of two antibiotics was not (OR=0.204, 95%CI:0.051-0.819, P=0.025).@*CONCLUSIONS@#MRSA enteritis has a rapid onset, and a high incidence of septic shock, which requires immediate attention. Colorectal surgery is an independent risk factor for MRSA enteritis.
Subject(s)
Humans , Anti-Bacterial Agents , Case-Control Studies , Colorectal Surgery , Digestive System Surgical Procedures , Enterocolitis , Microbiology , Methicillin-Resistant Staphylococcus aureus , Retrospective Studies , Risk Factors , Staphylococcal InfectionsABSTRACT
Gastric organoid is the organotypic cultures of gastric stem cells or pluripotent stem cells. Gastric organoid is comprised of all major types of gastric epithelial cells and represent the architecture and function remarkably similar to those of the gastric epithelium, faithfully recapitulating the functional gastric epithelium ex vivo. As ideal basic experimental model, gastric organoid has advantages over animal models and conventional cell model in many aspects. Gastric organoid derived from human gastric tissue, in particular, allows the investigation of the function of human stomach in the ex vivo setting. It has now been applied in the field of formation and physiology of the stomach, Helicobacter pylori infection-associated diseases, research of the pathogenic gene, screening and development of drugs, and regenerative medicine. What is more, as an innovative pre-clinical cancer model, gastric cancer organoid has provided important insights in the development of gastric cancer and screening of antitumor drugs, such as simulating the occurrence and development of gastric cancer, screening and development of antitumor drugs, personalized medication and targeted therapy for gastric cancer, and combined application with patient-derived xenograft. In this review, we summarize the establishment and application of gastric and gastric cancer organoids, especially in modeling gastric cancer, basic research and drug development.
Subject(s)
Humans , Helicobacter Infections , Organ Culture Techniques , Reference Standards , Organoids , Research , Stomach NeoplasmsABSTRACT
Increasing attention is focused on the down-regulation of miRNAs in cancer process. Nuclear receptor subfamily 2 (NR2F2, also known as COUP-TFII) is involved in the development of many types of cancers, but its role in gastric cancer remains elusive. In this experiment, oncomine and Kaplan-meier database revealed that NR2F2 was up-regulated in gastric cancer and that the high NR2F2 expression contributed to poor survival. MicroRNA-27b was targeted and down-regulated by NR2F2 in human gastric cancer tissues and cells. The ectopic expression of miR-27b inhibited gastric cancer cell proliferation and tumor growth in vitro and in vivo. Assays suggested that the overexpression of miR-27b could promote MGC-803 cells' migration and invasion and retard their metastasis to the liver. In addition, down-regulation of miR-27b enhanced GES-1 cells' proliferation and metastasis in vitro. These findings reveal that miR-27b is a tumor suppressor in gastric cancer and a biomarker for improving patients' survival.
Subject(s)
Animals , Female , Humans , Male , Biomarkers, Tumor , Genetics , Metabolism , COUP Transcription Factor II , Genetics , Metabolism , Cell Line, Tumor , Genes, Tumor Suppressor , Heterografts , Mice, Nude , MicroRNAs , Genetics , Metabolism , Neoplasm Metastasis , Neoplasm Proteins , Genetics , Metabolism , Neoplasm Transplantation , RNA, Neoplasm , Genetics , Metabolism , Stomach Neoplasms , Genetics , Metabolism , PathologyABSTRACT
Abdominal incisional hernia is a common postoperative complication. With the development of a new type of surgical anti-adhesion mesh, mesh repair has become a widely-adopted procedure, particularly in the laparoscopic era. However, there were few reports about use of these new meshes to repair incisional hernia in the abdominal cavity. In this report, we present two cases: one a 72-year-old male and the other a 62-year-old female. Both of those patients suffered incisional hernias during abdominal operations, and therefore underwent open incisional hernia anti-adhesion mesh repair operations. Both of them had recurrent incisional hernias after the first repair operation. During the second hernia repair operation via laparoscopy, tissue from the intestine and omentum were found to have adhered seriously to the old meshes, which could cause many serious problems. We need to pay more attention to the issue of adhesion, try to determine possible reasons and improve in our future work
Subject(s)
Humans , Female , Male , Middle Aged , Aged , Surgical Mesh/adverse effects , Postoperative Complications , Laparoscopy , Herniorrhaphy/adverse effects , Tissue AdhesionsABSTRACT
Objective To evaluate the risk factors of early gastric cancer with lymph node metastasis.Methods Clinicopathological data of 461 early gastric cancer cases admitted at Drum Tower Hospital from June 2010 to December 2015 were retrospectively analyzed.Results Of these 461 cases of early gastric cancer there were 338 male cases and 123 female cases,with male to female ratio of 2.74∶ 1.There were 48(10.4%) patients with lymph node metastasis.Female patients had a higher rate of metastasis (P =0.000).Lymph node metastasis rate in males,menopause females,premenopause females is 7.3%,16.3%,29.0% respectively.Females had metastasis 5 years earlier than males (x2 =31.877,P =0.000).Metastasis rate in M invasion was 6.0% and in SM invasion was 17.4% (x2 =12.055,P =0.001).Conclusions There were much more males than females in early gastric cancer patients though females having a higher rate of lymph node metastasis.Gender,age and depth of invasion is independent risk factors for lymph node metastasis in early gastric cancer.
ABSTRACT
Objective To explore the clinical efficacy of navigation of sentinel lymph node (SLN) combined with endoscopic submucosal dissection (ESD) for non curative treatment of early gastric cancer.Methods Clinical data of 9 cases with early gastric cancer treated with ESD from August 2015 to December 2015 were enrolled.The SLNs were explored by laparoscopy after nano carbon or indocyanine green(ICG) was injected under endoscopy.Then all stained nodes were resected by laparoscopy.Results The mean number of SLN were 2.75±1.50 in ICG group,which was significantly smaller than the number in nano carbon group(8.40±4.93) according to the laparoscopic pathology,so the accuracy of ICG was higher than that of nano carbon.But ICG performed better in development.The postoperative complications such as postoperative intestinal obstruction,enteritis and gastric paralysis were found in 5 patients of nano carbon group.But no serious complications after operation were found in patients of ICG group.Conclusion Application of ICG can help avoid the excessive removal of tissue,and reduce the incidence of complications.ICG,as a new type of tracer for early gastric cancer,shows good application prospects.
ABSTRACT
Surgery is so far the most widely used and effective treatment of neoplastic diseases.However,residual tumour cells during surgery remain a major trigger of cancer recurrence and matastasis.Although intraoperative rapid pathological R0 resection can be achieved based on preoperative imageological examination,but for small satellite lesions and the naked eye can not find the error quickly and so often cause pathological presence of residual tumour cells.Thus,quick and accurate identification of residual cancer cells is crucial for prognosis of cancer patients.Indocyanine green (ICG) is a new type of fluorochrome that can stain tumours under the near-infrared fluorescence during surgery,the paper will be reviewed latest developments in the reagent for fluorescence in tumours.
ABSTRACT
Objective To explore the value of gemstone spectral imaging (GSI)in quantitative evaluation of Lauren classification of gastric cancer.Methods Fifty-two patients with gastric cancer confirmed by gastroscopy underwent contrast-enhanced spectral CT imaging preoperatively.The monoergic and iodine-based images were obtained by GSI Viewer software,CT value and iodine concentration (IC)of the lesions were measured,and normalized iodine concentration (NIC)was calculated.With the reference of postoperative pathology,data were analyzed by LSD method of one-way analysis of variance.Results The IC,NIC,spectrum curve slope of 40-70 keV,40-140 keV and 70-140 keV energy range of intestinal type,mixed type and diffuse type carcinoma in the arterial phase were 12.86±6.80 (100 μg/mL),0.13±0.06 ,2.50±1.26 ,0.99±0.51 ,0.34±0.20 ,18.54±6.49 (100 μg/mL),0.19±0.07, 3.56±1.24,1.42±0.50,0.50±0.18 and 24.52±9.68 (100 μg/mL),0.24±0.09,4.73±1.76,1.90±0.73,0.68±0.29,respectively. The values of intestinal type were all significantly lower than those of diffuse type (P <0.05).Comparison between intestinal-mixed type and mixed-diffuse type,the other parameters were no significant differences except IC between intestinal-mixed type (P=0.037).Conclusion The slope of spectrum curve,iodine concentration,and normalized iodine concentration could be helpful for preoperative evaluation of Lauren classification of gastric cancer.
ABSTRACT
Objective To explore the reason for remedy radical operation after endoscopic submucosal dissection (ESD) for early gastric cancer.Methods The clinical data of 26 early gastric cancer cases who received remedy radical gastrectomy after ESD between January 2012 to March 2015 in Nanjing Drum Tower Hospital were analyzed retrospectively.Results All cases were followed up and mid follow-up was 25 months.There was no death nor tumor reccurence cases during the follow-up.Three cases suffered from complications in radical surgery for gastric cancer including afferent jejunal loop obstruction,adhesive intestinal obstruction,stomach paralysis respectively,all were cured by conservative therapy.Postoperative pathology found lymph node metastasis in 3 cases.Conclusions En bloc resection and negative resection margin,as well as free lymphatic metastasis are two important factors determing the survival of early gastric cancer patients undergoing ESD treatment.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the factors which may influence the imatinib plasma concentration in Chinese patients with gastrointestinal stromal tumor(GIST), and to illuminate the significance of monitoring imatinib plasma concentration in adjuvant therapy for patients with GIST.</p><p><b>METHODS</b>A cross-sectional study with 60 GIST patients who accepted the imatinib therapy after surgery was conducted. They were respectively administrated in 10 domestic hospitals from December 2014 to April 2016, including The First Affiliated Hospital of Nanjing Medical University(n=28), The Affiliated Hospital of Nantong University(n=9), The Affiliated Hospital of Xuzhou Medical College(n=6), Nanjing Drum Tower Hospital(n=5), The Second Affiliated Hospital of Nanjing Medical University (n=2), Jingling Hospital (n=2), The Second People's Hospital of Lianyungang(n=2), Shandong Provincial Hospital(n=2), Jiangsu Province Tumor Hospital(n=2), and The First Affiliated Hospital of Zhejiang University(n=2). Some specific time points for collecting blood sample before and after taking imatinib were determined, then liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used for monitoring imatinib plasma concentration in patients with GIST. Linear regression analysis was used for the correlation analysis of imatinib plasma concentration with dosage, clinicopathologic feature and side effect.</p><p><b>RESULTS</b>Patients who could not tolerate 400 mg imatinib per day(n=3) received 300 mg per day. There was no significant difference in imatinib plasma concentration between patients with 300 mg and those with 400 mg imatinib(n=53)(P=0.527). However, the imatinib plasma concentration in patients with 600 mg imatinib per day (n=4) was significantly higher as compared to those with 400 mg(P=0.000). Linear regression analysis indicated a negative correlation between the imatinib plasma concentration in patients with 400mg imatinib per day for 90 days continuously and body surface area(R=0.074, P=0.035), but no significant correlations of with age, creatinine clearance and serum albumin concentration were observed (all P>0.05). The differences in imatinib plasma concentration were not statistically significant between patients of different gender and those taking proton-pump inhibitor (PPI) or not (both P>0.05). Difference in imatinib plasma concentration between patients with different surgery was significant (P=0.026). Compared to patients who underwent wedge resection, enterectomy and other surgeries, the imatinib plasma concentration of patients with subtotal gastrectomy or total gastrectomy decreased significantly (all P<0.05). After 90 days of taking imatinib continuously, linear regression analysis revealed a negative correlation between imatinib plasma concentration in patients with 400 mg imatinib per day and white blood cell count (R=0.103, P=0.013), and a positive correlation with serum alanine aminotransferase (ALT) concentration (R=0.076, P=0.033).</p><p><b>CONCLUSIONS</b>The imatinib plasma concentration in patients with larger body surface area, subtotal gastrectomy or total gastrectomy may be lower. For these patients, dosage of imatinib should be considered to increase in order to achieve effective plasma concentration. Excessive imatinib plasma concentration can result in some side effects, such as decrease of white blood cells and liver damage. Therefore, it is significant for receiving optimal clinical therapeutic efficacy to monitor imatinib plasma concentration, adjust imatinib dosage timely and keep imatinib plasma concentration in effective and safe range.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Antineoplastic Agents , Pharmacokinetics , Benzamides , Combined Modality Therapy , Cross-Sectional Studies , Gastrectomy , Gastrointestinal Stromal Tumors , Drug Therapy , General Surgery , Imatinib Mesylate , Pharmacokinetics , Piperazines , Pyrimidines , Tandem Mass SpectrometryABSTRACT
Objective To study the expression of intestinal dipeptide transporter 1 (PEPT1) protein in gastric cancer patients at different nutritional status,and to explore the possible regulatory mechanism.Methods According to Nutritional Risk Screening 2002 (NRS 2002) score,a total of 60 gastric cancer patients were divided into nutritional risk group (NRS 2002 score ≥ 3,n =18) and non-nutritional risk group (NRS 2002 score < 3,n =42).With specimens of the small intestinal mucosa taken during operation,the expression of intestinal PEPT1 protein was detected using Western blot.The serum concentration of tumor necrosis factor (TNF-o) were measured using enzyme-linked immunosorbent assay.The expression of PEPT1 in Caco-2 cells treated with different concentrations of TNF-α (20,50,100 μg/L) were detected using Western blot at different time points (24,48,72 hours).Results The expression of intestinal PEPT1 (0.63 vs.0.23,P =0.000) and serum TNF-o concentration (0.23 μg/L vs.0.17 μg/L,P =0.001) in the nutritional risk group were significantly higher than those in the non-nutritional risk group.In Caco-2 cells,those treated with different concentrations of TNF-α (20,50,100 μg/L) for 24 hours had significantly higher PEPT1 expression than the blank group did (0.68 vs.0.54,P =0.005 ; 0.72 vs.0.54,P =0.001 ;0.78 vs.0.54,P =0.000).The Caeo-2 cells treated with 50 μg/L TNF-α for 24,48,and 72 hours had significantly higher PEPT1 expression compared with the cells in the blank group (0.57 vs.0.52,P =0.004 ; 0.75 vs.0.52,P =0.000 ; 0.77 vs.0.52,P =0.000).Conclusion The expression of intestinal PEPT1 protein was increased in gastric cancer patients with nutritional risk,which was probably attributed to the regulation of TNF-α.