Trends and hotspots in gastrointestinal neoplasms risk assessment: A bibliometric analysis from 1984 to 2022

BACKGROUND Gastrointestinal neoplasm(GN)significantly impact the global cancer burden and mortality,necessitating early detection and treatment.Understanding the evolution and current state of research in this field is vital.AIM To conducts a comprehensive bibliometric analysis of publications from 1984 to 2022 to elucidate the trends and hotspots in the GN risk assessment research,focusing on key contributors,institutions,and thematic evolution.METHODS This study conducted a bibliometric analysis of data from the Web of Science Core Collection database using the"bibliometrix"R package,VOSviewer,and CiteSpace.The analysis focused on the distribution of publications,contributions by institutions and countries,and trends in keywords.The methods included data synthesis,network analysis,and visualization of international collaboration networks.RESULTS This analysis of 1371 articles on GN risk assessment revealed a notable evolution in terms of research focus and collaboration.It highlights the United States'critical role in advancing this field,with significant contributions from institutions such as Brigham and Women's Hospital and the National Cancer Institute.The last five years,substantial advancements have been made,representing nearly 45%of the examined literature.Publication rates have dramatically increased,from 20 articles in 2002 to 112 in 2022,reflecting intensified research efforts.This study underscores a growing trend toward interdisciplinary and international collaboration,with the Journal of Clinical Oncology standing out as a key publication outlet.This shift toward more comprehensive and collaborative research methods marks a significant step in addressing GN risks.CONCLUSION This study underscores advancements in GN risk assessment through genetic analyses and machine learning and reveals significant geographical disparities in research emphasis.This calls for enhanced global collaboration and integration of artificial intelligence to improve cancer prevention and treatment accuracy,ultimately enhancing worldwide patient care.

Advanced glycation end-product expression is upregulated in the gastrointestinal tract of type 2 diabetic rats

AIM:To investigate changes in advanced glycation end products(AGEs) and their receptor(RAGE) expression in the gastrointestinal(GI) tract in type 2 diabetic rats.METHODS:Eight inherited type 2 diabetic rats GotoKakizak(GK) and ten age-matched normal rats were used in the study.From 18 wk of age,the body weight and blood glucose were measured every week and 2 wk respectively.When the rats reached 32 wk,twocentimeter segments of esophagus,duodenum,jejunum,ileum,and colon were excised and the wet weight was measured.The segments were fixed in 10% formalin,embedded in paraffin and five micron sections were cut.The layer thickness was measured in Hematoxylin and Eosin-stained slides.AGE [N epsilon-(carboxymethyl) lysine and N epsilon-(carboxyethyl)lysine] and RAGE were detected by immunohistochemistry staining and image analysis was done using Sigmascan Pro 4.0 image analysis software.RESULTS:The blood glucose concentration(mmol/L) at 18 wk age was highest in the GK group(8.88 ± 1.87 vs 6.90 ± 0.43,P < 0.001),a difference that continued to exist until the end of the experiment.The wet weight per unit length(mg/cm) increased in esophagus,jejunum and colon from the normal to the GK group(60.64 ± 9.96 vs 68.56 ± 11.69,P < 0.05 for esophagus; 87.01 ± 9.35 vs 105.29 ± 15.45,P < 0.01 for jejunum; 91.37 ± 7.25 vs 97.28 ± 10.90,P < 0.05 for colon).Histologically,the layer thickness of the GItract was higher for esophagus,jejunum and colon in the GK group [full thickness(μm):575.37 ± 69.22 vs 753.20 ± 150.41,P < 0.01 for esophagus; 813.51 ± 44.44 vs 884.81 ± 45.31,P < 0.05 for jejunum; 467.12 ± 65.92 vs 572.26 ± 93.60,P < 0.05 for colon].In esophagus,the AGE and RAGE mainly distributed in striated muscle cells and squamous epithelial cells.The AGE distribution was much stronger in the GK group compared to the normal group both in the striated muscle layer and mucosa layer(immuno-positive area/ total measuring area %:4.52 ± 0.89 vs 10.96 ± 1.34,P < 0.01 for muscle; 8.90 ± 2.62 vs 22.45 ± 1.26,P < 0.01 for mucosa).No visible difference was found for RAGE distribution between the two groups.In the intestine AGE and RAGE distributed in epithelial cells of villi and crypt.RAGE was also found in neurons in the myenteric and submucosal plexus.The intensity of AGE staining in mucosa of all segments and RAGE staining in neurons in all segments were strongest in the diabetes group.Significant difference for AGE was found in the epithelial cells of villi and crypt in duodenum(immunopositive area/total measuring area %:13.37 ± 3.51 vs 37.48 ± 8.43,P < 0.05 for villi; 0.38 ± 0.12 vs 1.87 ± 0.53,P < 0.05 for crypt) and for RAGE in neurons of all segments(e.g.,for jejunum:no staining neurons% 0 vs 0,mild 36.0 ± 5.2 vs 28.7 ± 3.5,moderate 53.2 ± 4.8 vs 55.8 ± 5.4,strong 10.7 ± 1.1 vs 15.4 ± 2.0,P < 0.05).In the colon,RAGE was primarily found in neurons in the myenteric and submucosal plexus.It was stronger in the diabetes group than in the normal group(no staining neurons% 6.2 ± 0.2 vs 0.3 ± 0.04,mild 14.9 ± 2.1 vs 17.6 ± 1.5,moderate 53.1 ± 4.6 vs 44.7 ± 4.4,strong 25.6 ± 18 vs 43.6 ± 4.0,P < 0.05).In the rectum,RAGE was primarily found in the mucosa epithelial cells.CONCLUSION:The AGE and RAGE expression was upregulated in the GI tract of GK diabetic rats and may contribute to GI dysfunction in type 2 diabetic patients.

Oral Xeloda plus bi-platinu two-way combined chemotherapy in treatment of advanced gastrointestinal malignancies

AIM： To compare the effect, adverse events, cost-effectiveness and dose intensity （DI） of oral Xeloda vs calcium folinate （CF）/5-FU combination chemotherapy in patients with advanced gastrointestinal malignancies, both combined with bi-platinu two-way chemotherapy.METHODS： A total of 131 patients were enrolled and randomly selected to receive either oral Xeloda （X group） or CF/5-FU （control group）. Oral Xeloda 1 000 mg/m^2 was administered twice daily from d 1 to 14 in X group, while CF 200 mg/m^2 was taken as a 2-h intravenous infusion followed by 5-FU 600 mg/m^2 intravenously for 4-6 h on d 1-5 in control group. Cisplatin and oxaliplatin were administered in the same way to both the groups： cisplatin 60-80 mg/m^2 by hyperthermic intraperitoneal administration, and oxaliplatin 130 mg/m^2 intravenouslyfor 2 h on d 1. All the drugs were recycled every 21 d, with at least two cycles. Pyridoxine 50 mg was given t.i.d. orally for prophylaxis of the hand-foot syndrome （HFS）. Then the effect, adverse events, cost-effectiveness and DI of the two groups were evaluated.RESULTS： Hundred and fourteen cases （87.0%） finished more than two chemotherapy cycles. The overall response rate of them was 52.5% （X group） and 42.4% （control group） respectively. Tumor progression time （TTP） was 7.35 mo vs5.95 too, and 1-year survival rate was 53.1% vs 44.5%. There was a remarkable statistical significance of TTP and 1-year survival between the two groups. The main Xelocla-related adverse events were myelosuppression, gastrointestinal toxicity, neurotoxicity and HFS, which were mild and well tolerable. Therefore, no patients withdrew from the study due to side effects before two chemotherapy cycles were finished. Both groups finished pre-arranged DI and the relative DI was nearly 1.0. The average cost for 1 patient in one cycle was ￥9 137.35 （X group） and ￥8 961.72 （control group）, or US ＄1 100.89 in X group and ＄1 079.73 in control group. To add 1% to the response rate costs ￥ 161.44 vs ￥210.37 respectively （US ＄19.45 vs ＄25.35）. One-month prolongation of TTP costs ￥1 243.18 vs ￥1 506.17 （US ＄149.78 vs ＄181.47）. Escalation of 1% of 1-year survival costs ￥172.74 vs ￥201.64 （US ＄20.75 vs ＄24.29）. CONCLUSION： Oral Xeloda combined with bi-platinu two-way combination chemotherapy is efficient and tolerable for patients with advanced gastrointestinal malignancies; meanwhile the expenditure is similar to that of CF/5-FU combined with bi-platinu chemotherapy, and will be cheaper if we are concerned about the increase of the response rate, TTP or 1-year-survival rate pharmacoeconomically.

The Clinical Study of Multigene Combination Test to Guide Chemotherapy Combined with Targeted Therapy in Patients with Advanced Gastrointestinal Tumors

Objective:To study the clinical effects of multigene combination test to guide chemotherapy combined with targeted therapy in patients with advanced gastrointestinal tumors.Methods:The samples were selected from 60 patients with advanced gastrointestinal tumors admitted to our hospital from March 2019 to July 2020,and were divided into a study group and a control group using a random number table model;patients in the control group did not undergo genetic testing and FOLLOX4+PD-1 chemotherapy,while patients in the study group underwent TYMS,ERCC1,EGFR,and KRAS and VEGF gene expression levels test,and the sensitive treatment plan was determined based on the test results,and the clinical indexes were compared between the two groups.Results:By comparing the total effective rate,survival time,and time to disease progression of chemotherapy in the two groups,the study group has a significant advantage(P<0.05).Conclusion:The combination of chemotherapy and targeted therapy for advanced gastrointestinal tumor patients can improve the efficiency of chemotherapy and prolong the time of disease progression and survival,which is worthy of comprehensive promotion.

Predictive Value of Body Composition Analysis for the Prognosis of Patients with Advanced Gastrointestinal Tumors

Objective There is strong evidence that the body composition can affect the progression-free survival(PFS)and overall survival(OS)in patients with a variety of cancers.The main objective of this study was to investigate the effect of body composition on the prognosis of patients with advanced gastrointestinal and colorectal cancers who received first-line palliative chemotherapy.Methods Patients who were newly-diagnosed with advanced gastrointestinal or colorectal cancer and received standard first-line palliative chemotherapy from January 2017 to December 2018 were included in this retrospective study.An analysis of computed tomography images was performed to determine the skeletal muscle index(SMI),which reflects the skeletal muscle mass and skeletal muscle density(SMD)related to muscle strength.A Kaplan-Meier survival analysis and log-rank test were used to compare the survival relationships among groups stratified by the SMI,and a Cox proportional hazard model was used for a multivariate analysis.Results A total of 108 patients met the inclusion criteria,including 41 cases of gastric cancer,46 cases of left colorectal cancer,and 21 cases of right colon cancer.In patients with gastric cancer,the OS of women was significantly shorter than that of men.The OS of patients with a low SMI,low SMD,and low phase angle(PA)was significantly shorter than that of patients with high values(P≤0.05).In the multivariate analysis,the SMD was significantly associated with the patients'long-term survival[Hazard Ratio(HR)=0.904,95%CI:0.840~0.974,P=0.008].For patients with a low SMI and PA,the PFS was significantly shorter than that of patients with high values(P≤0.05).In patients with left colon cancer,the PA and SMD were both independent risk factors for a poorer long-term prognosis(HR=0.375,95%CI:=0.167~0.840,P=0.017;HR=0.887,95%CI:0.824~0.954,P=0.001).Among right colon cancer patients,the PFS and OS of those with a low SMD were significantly lower than those for patients with high values(P≤0.05).Conclusion The PA is an independent risk factor for the OS of left colon cancer patients;the SMD is an independent risk factor for the survival of patients with gastric cancer,left colon cancer,and right colon cancer.

Survival prognostic analysis of laparoscopic D2 radical resection for locally advanced gastric cancer: A multicenter cohort study

BACKGROUND With the development of minimally invasive surgical techniques,the use of laparoscopic D2 radical surgery for the treatment of locally advanced gastric cancer(GC)has gradually increased.However,the effect of this procedure on survival and prognosis remains controversial.This study evaluated the survival and prognosis of patients receiving laparoscopic D2 radical resection for the treatment of locally advanced GC to provide more reliable clinical evidence,guide clinical decision-making,optimize treatment strategies,and improve the survival rate and quality of life of patients.METHODS A retrospective cohort study was performed.Clinicopathological data from 652 patients with locally advanced GC in our hospitals from December 2013 to December 2023 were collected.There were 442 males and 210 females.The mean age was 57±12 years.All patients underwent a laparoscopic D2 radical operation for distal GC.The patients were followed up in the outpatient department and by telephone to determine their tumor recurrence,metastasis,and survival.The follow-up period ended in December 2023.Normally distributed data are expressed as the mean±SD,and normally distributed data are expressed as M(Q1,Q3)or M(range).Statistical data are expressed as absolute numbers or percentages;theχ^(2) test was used for comparisons between groups,and the Mann-Whitney U nonparametric test was used for comparisons of rank data.The life table method was used to calculate the survival rate,the Kaplan-Meier method was used to construct survival curves,the log rank test was used for survival analysis,and the Cox risk regression model was used for univariate and multifactor analysis.RESULTS The median overall survival(OS)time for the 652 patients was 81 months,with a 10-year OS rate of 46.1%.Patients with TNM stages II and III had 10-year OS rates of 59.6%and 37.5%,respectively,which were significantly different(P<0.05).Univariate analysis indicated that factors such as age,maximum tumor diameter,tumor diffe-rentiation grade(low to undifferentiated),pathological TNM stage,pathological T stage,pathological N stage(N2,N3),and postoperative chemotherapy significantly influenced the 10-year OS rate for patients with locally advanced GC following laparoscopic D2 radical resection for distal stomach cancer[hazard ratio(HR):1.45,1.64,1.45,1.64,1.37,2.05,1.30,1.68,3.08,and 0.56 with confidence intervals(CIs)of 1.15-1.84,1.32-2.03,1.05-1.77,1.62-2.59,1.05-1.61,1.17-2.42,2.15-4.41,and 0.44-0.70,respectively;P<0.05].Multifactor analysis revealed that a tumor diameter greater than 4 cm,low tumor differentiation,and pathological TNM stage III were independent risk factors for the 10-year OS rate in these patients(HR:1.48,1.44,1.81 with a 95%CI:1.19-1.84).Additionally,postoperative chemotherapy emerged as an independent protective factor for the 10-year OS rate(HR:0.57,95%CI:0.45-0.73;P<0.05).CONCLUSION A maximum tumor diameter exceeding 4 cm,low tumor differentiation,and pathological TNM stage III were identified as independent risk factors for the 10-year OS rate in patients with locally advanced GC following laparoscopic D2 radical resection for distal GC.Conversely,postoperative chemotherapy was found to be an independent protective factor for the 10-year OS rate in these patients.

Perspective on the practical indications of endoscopic submucosal dissection of gastrointestinal neoplasms

Endoscopic submucosal dissection (ESD) is a new endoluminal therapeutic technique involving the use of cutting devices to permit a larger resection of the tissue over the muscularis propria. The major advantages of the technique in comparison with polypectomy and endoscopic mucosal resection are controllable resection size and shape and en bloc resection of a large lesion or a lesion with ulcerative findings. This technique is applied for the endoscopic treatment of epithelial neoplasms in the gastrointestinal tract from the pharynx to the rectum. Furthermore, some carcinoids and submucosal tumors in the gastrointestinal tract are treated by ESD. To determine the indication, two aspects should be considered. The first is a little likelihood of lymph node metastasis and the second is the technical resectability. In this review, practical guidelines of ESD for the gastrointestinal neoplasms are discussed based on the evidence found in the literature.

Photodynamic therapy for middle-advanced stage upper gastrointestinal carcinomas: A systematic review and meta-analysis

AIM To determine the therapeutic effect of photodynamic therapy(PDT) for middle-advanced stage upper gastrointestinal carcinomas. METHODS We searched PubM ed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Database from inception to April 2018 for randomized controlled studies. These studies compared PDT with other palliative therapies(radiotherapy, chemotherapy, or Nd:YAG laser) and compared PDT, radiotherapy, or chemotherapy alone with PDT combined with chemotherapy/radiotherapy. In our meta-analysis, both fixed and random effects models were used to estimate the risk ratio(RR) for dichotomous outcomes(the response rate and one-year survival rate).RESULTS Ten random controlled clinical studies with 953 patients were included in the analysis. The effective rate for PDT was better than that of radiotherapy or Nd:YAG laser for the treatment of middle-advanced upper gastrointestinal carcinomas [RR = 1.36; 95% confidence interval(CI): 1.13-1.65; P = 0.001]. In addition, PDT combined with chemotherapy had significantly better efficacy and a higher one-year survival rate than PDT or chemotherapy alone(significant remission rate, RR = 1.62; 95%CI: 1.34-1.97; P < 0.00001; one-year survival rate, RR = 1.81; 95%CI: 1.13-2.89; P = 0.01).CONCLUSION PDT is a useful method for the treatment of middleadvanced stage upper gastrointestinal carcinomas. PDT combined with chemotherapy or radiotherapy can enhance its efficacy and prolong survival time.

Ultraslim endoscopy with flexible spectral imaging color enhancement for upper gastrointestinal neoplasms

AIM:To conduct a preliminary study on the effect of flexible spectral imaging color enhancement (FICE) used in combination with ultraslim endoscopy by focusing on the enhanced contrast between tumor and non-tumor lesions. METHODS: We examined 50 lesions of 40 patients with epithelial tumors of the upper gastrointestinal tract before endoscopic submucosal dissection using ultraslim endoscopy with conventional natural color imag ing and with FICE imaging. We retrospectively invest igated the effect of the use of FICE on endoscopic diagn osis in comparison with normal light. RESULTS: Visibility of the epithelial tumors of the upper gastrointestinal tract with FICE was superior to normal light in 54% of the observations and comparable to normal light in 46% of the observations. There was no lesion for which visibility with FICE was inferior to that with normal light. FICE visualized 69.6% of hyperemic lesions and 58.8% of discolored lesions better than conventional endoscopy with natural color imaging. FICE sign if icantly improved the visibility of lesions with hyp ere mia or discoloration compared with normocolored lesions. CONCLUSION: This study suggests that the use of FICE would improve the ability of ultraslim endoscopy to detect epithelial tumors of the upper gastrointestinal tract.

Conventional radiological strategy of common gastrointestinal neoplasms

This article summarizes the clinical characteristics and imaging features of common gastrointestinal(GI) neoplasms in terms of conventional radiological imaging methods. Barium studies are readily available for displaying primary malignancies and are minimallyor not at all invasive. A neoplasm may be manifested as various imaging findings, including mucosal disruption, soft mass, ulcer, submucosal invasion and lumen stenosis on barium studies. Benign tumors typically appear as smoothly marginated intramural masses. Malignant neoplasms most often appear as irregular infiltrative lesions on barium examination. Tumor extension to adjacent GI segments may be indistinct on barium images. Cross-sectional images such as computed tomography and magnetic resonance imaging may provide more accurate details of the adjacent organ invasion, omental or peritoneal spread.

Clinical management of advanced gastric cancer: The role of new molecular drugs

Gastric cancer is the fourth most common malignant neoplasm and the second leading cause of death for cancer in Western countries with more than 20000 new cases yearly diagnosed in the United States. Surgery represents the main approach for this disease but, notwithstanding the advances in surgical techniques, we observed a minimal improvement in terms of overall survival with a significant increasing of relapsing disease rates. Despite the development of new drugs has significantly improved the effectiveness of chemotherapy, the prognosis of patients with unresectable or metastatic gastric adenocarcinoma remains poor. Recently, several molecular target agents have been investigated; in particular, trastuzumab represents the first target molecule showing improvements in overall survival in human epithelial growth factor 2-positive gastric cancer patients. New molecules targeting vascular epithelial growth factor, mammalian target of rapamycin, and anti hepatocyte growth factor-c-Met pathway are also under investigation, with interesting results. Anyway, it seems necessary to select more accurately the population to treat with new agents by the identification of new biomarkers in order to optimize the results. In this paper we review the actual &#x0201c;scenario&#x0201d; of targeted treatments, also focusing on the new agents in development for gastric cancer and gastro-esophageal carcinoma, discussing their efficacy and potential applications in clinical practice.

Different risk factors for advanced colorectal neoplasm in young adults

AIM: To compare the risk of developing advanced colorectal neoplasm(ACRN) according to age in Koreans.METHODS: A total of 70428 Koreans from an occupational cohort who underwent a colonoscopy between 2003 and 2012 at Kangbuk Samsung Hospital were retrospectively selected. We evaluated and compared odds ratios(OR) for ACRN between the young-adults(YA < 50 years) and in the older-adults(OA ≥ 50 years). ACRN was defined as an adenoma ≥ 10 mm in diameter, adenoma with any component of villous histology, high-grade dysplasia, or invasive cancer.RESULTS: In the YA group, age(OR = 1.08, 95%CI: 1.06-1.09), male sex(OR = 1.26, 95%CI: 1.02-1.55), current smoking(OR = 1.37, 95%CI: 1.15-1.63), family history of colorectal cancer(OR = 1.46, 95%CI: 1.01-2.10), diabetes mellitus related factors(OR = 1.27, 95%CI: 1.06-1.54), obesity(OR = 1.23, 95%CI: 1.03-1.47), CEA(OR = 1.04, 95%CI: 1.01-1.09) and low-density lipoprotein-cholesterol(OR = 1.01, 95%CI: 1.01-1.02) were related with an increased risk of ACRN. However, age(OR = 1.08, 95%CI: 1.06-1.09), male sex(OR = 2.12, 95%CI: 1.68-2.68), current smoking(OR = 1.38, 95%CI: 1.12-1.71), obesity(OR = 1.34, 95%CI: 1.09-1.65) and CEA(OR = 1.05, 95%CI: 1.01-1.09) also increased the risk of ACRN in the OA group.CONCLUSION: The risks of ACRN differed based on age group. Different colonoscopic screening strategies are appropriate for particular subjects with risk factors for ACRN, even in subjects younger than 50 years.

Neoadjuvant vs adjuvant pelvic radiotherapy for locally advanced rectal cancer: Which is superior?

The treatment of locally advanced rectal cancer including timing and dosage of radiotherapy, degree of sphincter preservation with neoadjuvant radiotherapy, and short and long term effects of radiotherapy are controversial topics. The MEDLINE, Cochrane Library databases, and meeting proceedings from the American Society of Clinical Oncology, were searched for reports of randomized controlled trials and meta-analyses comparing neoadjuvant and adjuvant radiotherapy with surgery to surgery alone for rectal cancer. Neoadjuvant radiotherapy shows superior results in terms of local control compared to adjuvant radiotherapy. Neither adjuvant or neoadjuvant radiotherapy impacts overall survival. Short course versus long course neoadjuvant radiotherapy remains controversial. There is insufficient data to conclude that neoadjuvant therapy improves rates of sphincter preserving surgery. Radiation significantly impacts anorectal and sexual function and includes both acute and long term toxicity. Data demonstrate that neoadjuvant radiation causes less toxicity compared to adjuvant radiotherapy, and specifically short course neoadjuvant radiation results in less toxicity than long course neoadjuvant radiation. Neoadjuvant radiotherapy is the preferred modality for administering radiation in locally advanced rectal cancer. There are significant side effects from radiation, including anorectal and sexual dysfunction, which may be less with short course neoadjuvant radiation.

Effectiveness of integrated nursing interventions for fatigue in patients with advanced cancer:a systematic review of randomized controlled trials

Objective:To evaluate the effectiveness of integrated nursing interventions for fatigue in patients with advanced cancer.Methods:Medline,Pubmed,Embase,CINAHL,Web of Science,and the Cochrane Library were searched systematically till June 2017.A systematic review was conducted to collect randomized controlled trials(RCTs)reporting on the effect of nurse-driven interventions to improve fatigue in patients with advanced cancer.Quality assessment was conducted using the Cochrane Collaboration’s risk of bias tool.Results:Six RCTs involving 736 adult participants were included.The fatigue intensity was improved significantly by nursing interventions.The analyzed results revealed significant improvements in the intervention group:less than 3 months(standard mean difference[SMD]=?0.33,95%confidence interval[CI][?0.48,?0.19],P<0.01)and more than or equal to 3 months(SMD=?0.40,95%CI[?0.57,?0.24],P<0.01).Four studies with a moderate risk of bias were judged,and the remaining studies were at high risk of bias.Conclusions:The results indicate that integrated nursing interventions may relieve fatigue in patients with advanced cancer.However,due to the high risk of bias in most of the included studies and the diversity of interventions,the results and implementation process should be carefully monitored.

Validation of serum tumor biomarkers in predicting advanced cystic mucinous neoplasm of the pancreas

BACKGROUND Early detection of advanced cystic mucinous neoplasms[(A-cMNs),defined as high-grade dysplasia or malignancy]of the pancreas is of great significance.As a simple and feasible detection method,serum tumor markers(STMs)may be used to predict advanced intraductal papillary mucinous neoplasms(IPMNs)and mucinous cystic neoplasms(MCNs).However,there are few studies on the usefulness of STMs other than carbohydrate antigen(CA)19-9 for early detection of A-cMNs.AIM To study the ability of five STMs-CA19-9,carcinoembryonic antigen(CEA),CA125,CA724,and CA242 to predict A-cMNs and distinguish IPMNs and MCNs.METHODS We mainly measured the levels of each STM in patients pathologically diagnosed with cMNs.The mean levels of STMs and the number of A-cMN subjects with a higher STM level than the cutoff were compared respectively to identify the ability of STMs to predict A-cMNs and distinguish MCNs from IPMNs.A receiver operating characteristic curve with the area under curve(AUC)was also created to identify the performance of the five STMs.RESULTS A total of 187 patients with cMNs were identified and 72 of them showed AcMNs.We found that CA19-9 exhibited the highest sensitivity(SE)(54.2%)and accuracy(76.5%)and a moderate ability(AUC=0.766)to predict A-cMNs.In predicting high-grade dysplasia IPMNs,the SE of CA19-9 decreased to 38.5%.The ability of CEA,CA125,and CA724 to predict A-cMNs was low(AUC=0.651,0.583,and 0.618,respectively).The predictive ability of CA242 was not identified.The combination of STMs improved the SE to 62.5%.CA125 may be specific to the diagnosis of advanced MCNs.CONCLUSION CA19-9 has a moderate ability,and CEA,CA125,and CA724 have a low ability to predict A-cMNs.The combination of STM testing could improve SE in predicting A-cMNs.

Pemertrexed combined with cisplatin in the treatment of advanced non-small cell lung cancer:a case report and literature review

The aim of our study was to explore the value of second-line treatment for advanced non-small cell lung cancer (NSCLC). One patient with metastatic adenocarcinoma of NSCLC was given second-line treatment of pemertrexed/cisplatin. Follow-up was made to observe progression free survival (PFS) and survival time. She was given 4 cycles first-line treatment of recombinant human endostatin plus gemcitabine/cisplatin previously; the efficacy was CR and PFS was 10.2 months. After the 5th cycle treatment of pemetrexed/cisplatin, the efficacy of the primary tumor was CR, and bone metastases was stable. PFS was 6.6 months, and the patient has been survival for 22 months. Quality of life (QOL) of the patient was improved. When advanced NSCLC is recurrence or metastasis, starting second-line treatment of pemetrexed/cisplatin timely can prolong survival time and improve QOL.

Critical considerations for the management of gastrointestinal mixed neuroendocrine non-neuroendocrine neoplasms and pure neuroendocrine carcinomas

Mixed neuroendocrine non-neuroendocrine neoplasms constitute rare tumors that are located mainly in the gastrointestinal(GI)tract and have high degrees of malignancy,and the frequency of these tumors has been increasing.They consist of a neuroendocrine neoplastic component with another component of adenocarcinoma usually and have a dismal prognosis.The rare GI pure neuroendocrine carcinoma is highly aggressive and requires complex and extensive management since a genetic distinction exists between it and GI non-neuroendocrine neoplasms,which are generally slow-growing lesions.The most common GI-mixed neuroendocrine non-neuroendocrine neoplasms are colorectal,followed by gastric,mainly in the gastroesophageal junction.Current imaging modalities of nuclear medicine and radiology play important roles in the accuracy of diagnosis.Liquid biopsy may contribute to early detection and timely diagnosis.Ultrasonography,either endoscopic or abdominal,is a technique that contributes to a diagnosis;additionally,contrast-enhanced ultrasonography is very helpful in followup appointments.Histopathology establishes a definite diagnosis and stage by evaluating the cell differentiation grade and the cell proliferation index Ki67.The genetic profile can be valuable in diagnosis and gene therapy.Surgical resection with wide lymphadenectomy,whenever possible,and adjuvant chemotherapy constitute the main therapeutic management strategies.Targeted therapy and immunotherapy achieve encouraging results.

Expression and Clinical Significance of Cytokeratin-19 and Thymidine Kinase-1 in Advanced Gastrointestinal Cancer

Background： As the clinical value of cytokeratin-19 （CK 19） and thymidine kinase-1 （TK1 ） in advanced gastrointestinal cancer remains controversial, we investigated their expression and clinical significance in this disease. Methods： A total of 171 advanced gastrointestinal cancer patients were prospectively enrolled in this study. The mRNA level of CK 19 was detected using quantitative real-time reverse transcription-polymerase chain reaction （PCR） in all patients, along with a control group of fifty healthy individuals. Furthermore, detection of TK1 protein was carried out in 96 patients using a chemiluminescence dot blot assay. The primary endpoint was overall survival （OS） time. Results： Positive CKl 9 mRNA expression was detected in 74 （43.3%） of the 171 patients and positive TK1 expression was detected in 66 （68.8%） of the 96 patients. Furthermore, of the 96 patients, 36 （37.5%） were positive for both TK1 protein and CK19 mRNA, 30 （31.3%） were negative for TK1 protein, and 15 （15.6%） were negative for TKl protein and positive for CK19 mRNA. The results indicated that patients who were positive for CK 19 mRNA expression had significantly shorter OS times than those who were negative for it （median OS 7.7 vs. 9.7 months, respectively; P = 0.02）. Moreover, patients who were positive tbr CK 19 mRNA and TK 1 protein expression had shorter OS times （median OS 6.1 months） than those who were positive for CKl9 mRNA and negative for TKl protein expression （median OS 9.1 months; P： 0.028）. Positive CK 19 mRNA expression was significantly associated with shorter OS in the univariate analysis （P = 0.027）. Based on a multivariate Cox regression analysis, CK19 mRNA together with TK1 protein expression （P = 0.024） was an independent predictor for OS in gastrointestinal cancer patients. Conclusions： Our results suggest that positive expression ofCKl9 mRNA and TK1 protein is closely correlated with poor prognosis in advanced gastrointestinal cancer. Furthermore, both CKl9 and TKl are possible gastrointestinal cancer biomarkers.

Organoid models of gastrointestinal Neoplasms:Origin,current status and future applications in personalized medicine

The in vitro organoid model is a major technological breakthrough that has been established as an important tool in many basic biological and clinical applications.This near-physiological 3D culture system accurately models various biological processes,including tissue renewal,stem cell/niche functions and tissue responses to drugs,mutations or damage.Organoids have the potential value of being an accurate model for disease predictions or drug screening applications and to identify the ideal treatment for that patient.Carcinogenesis can be modeled by mutating specific cancer genes in wild-type organoids;and patient-derived organoids provide an important resource in the development of personalized cancer treatment.Organoids from cancer patients could be used to identify the ideal treatment for a specific patient by growing matched healthy and diseased organoids from human cancer patients which additionally enables clinical screens for drug combinations.Organoids could also provide autologous cells ordin the futuredtissue for transplantation.In this review,we discuss the current advances,challenges and potential applications of this technique in gastrointestinal neoplasms.

Mixed neuroendocrine–nonneuroendocrine neoplasms of the gastrointestinal system:An update

Mixed neuroendocrine-nonneuroendocrine neoplasms(Mi NENs)of the digestive tract are a rare heterogeneous group of tumors that present many challenges in terms of diagnosis and treatment.Over the years,the diagnostic criteria,classification,and clinical behavior of these tumors have been the subjects of ongoing debate,and the various changes in their nomenclature have strengthened the challenges associated with Mi NENs.This review is performed to provide an understanding of the key factors involved in the evolution of the designation of these tumors as Mi NEN,highlight the current diagnostic criteria,summarize the latest data on pathogenesis and provide information on available treatments.Moreover,this work seeks to increase the awareness about these rare neoplasms by presenting the clinicopathological features and prognostic factors that play important roles in their behavior and discussing their different regions of origin in the gastrointestinal system(GIS).Currently,the Mi NEN category also includes tumors in the GIS with a nonneuroendocrine component and epithelial tumors other than adenocarcinoma,depending on the organ of origin.Diagnosis is based on the presence of both morphological components in more than 30%of the tumor.However,this value needs to be reconfirmed with further studies and may be a limiting factor in the diagnosis of Mi NEN by biopsy.Furthermore,available clinicopathological data suggest that the inclusion of amphicrine tumors in the definition of Mi NEN is not supportive and warrants further investigation.The diagnosis of these tumors is not solely based on immunohistochemical findings.They are not hybrid tumors and both components can act independently;thus,careful grading of each component separately is required.In addition to parameters such as the metastatic state of the tumor at the time of diagnosis and the feasibility of surgical resection,the aggressive potential of both components has paramount importance in the choice of treatment.Regardless of the organ of origin within the GIS,almost Mi NENs are tumors with poor prognosis and are frequently encountered in the elderly and men.They are most frequently reported in the colorectum,where data from molecular studies indicate a monoclonal origin;however,further studies are required to provide additional support for this origin.