Correlation between radiologic features on contrastenhanced CT and pathological tumor grades in pancreatic neuroendocrine neoplasms

Contrast-enhanced computed tomography(CT)contributes to the increasing detection of pancreatic neuroendocrine neoplasms(PNENs).Nevertheless,its value for differentiating pathological tumor grades is not well recognized.In this report,we have conducted a retrospective study on the relationship between the 2017 World Health Organization(WHO)classification and CT imaging features in 94 patients.Most of the investigated features eventually provided statistically significant indicators for discerning PNENs G3 from PNENs G1/G2,including tumor size,shape,margin,heterogeneity,intratumoral blood vessels,vascular invasion,enhancement pattern in both contrast phases,enhancement degree in both phases,tumor-to-pancreas contrast ratio in both phases,common bile duct dilatation,lymph node metastases,and liver metastases.Ill-defined tumor margin was an independent predictor for PNENs G3 with the highest area under the curve(AUC)of 0.906 in the multivariable logistic regression and receiver operating characteristic curve analysis.The portal enhancement ratio(PER)was shown the highest AUC of 0.855 in terms of quantitative features.Our data suggest that the traditional contrastenhanced CT still plays a vital role in differentiation of tumor grades and heterogeneity analysis prior to treatment.

Leveraging machine learning techniques for predicting pancreatic neuroendocrine tumor grades using biochemical and tumor markers

BACKGROUND The incidence of pancreatic neuroendocrine tumors (PNETs) is now increasing rapidly. The tumor grade of PNETs significantly affects the treatment strategy and prognosis. However, there is still no effective way to non-invasively classify PNET grades. Machine learning (ML) algorithms have shown potential in improving the prediction accuracy using comprehensive data. AIM To provide a ML approach to predict PNET tumor grade using clinical data. METHODS The clinical data of histologically confirmed PNET cases between 2012 and 2018 were collected. A method of minimum P for the Chi-square test was used to divide the continuous variables into binary variables. The continuous variables were transformed into binary variables according to the cutoff value, while the P value was minimum. Four classical supervised ML models, including logistic regression, support vector machine (SVM), linear discriminant analysis (LDA) and multi-layer perceptron (MLP) were trained by clinical data, and the models were labeled with the pathological tumor grade of each PNET patient. The performance of each model, including the weight of the different parameters, were evaluated. RESULTS In total, 91 PNET cases were included in this study, in which 32 were G1, 48 were G2 and 11 were G3. The results showed that there were significant differences among the clinical parameters of patients with different grades. Patients with higher grades tended to have higher values of total bilirubin, alpha fetoprotein, carcinoembryonic antigen, carbohydrate antigen 19-9 and carbohydrate antigen 72-4. Among the models we used, LDA performed best in predicting the PNET tumor grade. Meanwhile, MLP had the highest recall rate for G3 cases. All of the models stabilized when the sample size was over 70 percent of the total, except for SVM. Different parameters varied in affecting the outcomes of the models. Overall, alanine transaminase, total bilirubin, carcinoembryonic antigen, carbohydrate antigen 19-9 and carbohydrate antigen 72-4 affected the outcome greater than other parameters. CONCLUSION ML could be a simple and effective method in non-invasively predicting PNET grades by using the routine data obtained from the results of biochemical and tumor markers.

Pancreatic neuroendocrine tumor Grade 1 patients followed up without surgery:Case series

Among the three grades of neuroendocrine tumors(NETs),the prognosis for Grade 1(G1) with surgery is very good.Therefore,we evaluated the prognoses of pancreatic NET(PNET) G1 patients without surgery.A total of 8 patients who were diagnosed with NET G1,with an observation period of more than 6 mo until surgery or without surgery,were recruited.The patients who underwent surgery were ultimately diagnosed using specimens obtained during the surgery,whereas the patients who did not undergo surgery were diagnosed using specimens obtained by endoscopic ultrasonography-guided fine needle aspiration.Overall,we mainly evaluated the observation period and tumor growth.The observation period for the five cases with surgery ranged from 6-80 mo,and tumor growth was observed in one case.In contrast,the observation period for the three cases without surgery ranged from 17-54 mo,and tumor growth was not observed.Therefore,although the first-choice treatment for NETs is surgery,our experience includes certain NET G1 patients who were followed up without surgery.

Mixed pancreatic ductal adenocarcinoma and well-differentiated neuroendocrine tumor:A case report

BACKGROUND Pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms(MiNENs)are rare malignancies affecting the pancreas.The World Health Organization defines MiNENs as neoplasms composed of morphologically recognizable neuroendocrine and non-neuroendocrine components,each constituting 30%or more of the tumor volume.Adenocarcinoma-neuroendocrine carcinoma is the most frequent MiNEN combination.A well-differentiated neuroendocrine tumor(NET)component is rarely reported in MiNENs.CASE SUMMARY Here we report a rare case with intermingled components of ductal adenocarcinoma and grade 1 well-differentiated NET in the pancreas.The two tumors show distinct histology and significant differentiation discrepancy(poorly differentiated high grade adenocarcinoma and well-differentiated low grade NET),and also present as metastases in separate lymph nodes.Next generation sequencing of the two components demonstrates KRAS and TP53 mutations in the ductal adenocarcinoma,but no genetic alterations in the NET,suggesting divergent origins for these two components.Although tumors like this meet the diagnostic criteria for MiNEN,clinicians often find the diagnosis and staging confusing and impractical for clinical management.CONCLUSION Mixed NET/non-NET tumors with distinct histology and molecular profiles might be better classified as collision tumors rather than MiNENs.

Accuracy of tumor grade by preoperative curettage and associated clinicopathologic factors in clinical stage Ⅰ endometriod adenocarcinoma

Background Preoperative tumor grading becomes one of the most important predictors for lymphadenectomy at primary surgery for clinical stage Ⅰ endometriod adenocarcinoma. However, there is an inconsistency of tumor grade between preoperative curettage and final hysterectomy specimens, and its associated factors are poorly understood. This study aimed to evaluate the accuracy of tumor grade by preoperative curettage so as to achieve a better stratified management for clinical stage Ⅰ endometriod adenocarcinoma. Methods Clinical data of totally 687 patients with clinical stage Ⅰ endometriod adenocarcinoma who underwent preoperative curettage and primary surgery were retrospectively collected. Compared with final hysterectomy specimens, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of tumor grade by preoperative curettage were calculated and their associations with clinicopathologic parameters, including age, status of menopause, position of uterus, location and size of lesion, histological grade, depth of myometrial invasion, cervical invasion, extrauterine spread, peritoneal cytology, metastasis to retroperitoneal lymph node, serum CA125 level, and hormone receptor status, were analyzed. Results In final hysterectomy specimens, 139 of 259 grade 1 patients by curettage were upgraded to grade 1 or 2; 31 of 296 grade 2 were upgraded to grade 3, with a significantly discrepant rate of 40.9% （281/687） and an upgraded rate of 24.7% （170/687）. The specificity and negative predictive value for grade 3 were 90.7% and 89.9%, while the sensitivity and positive predictive value for grade 1 were 67.1% and 40.9%, respectively. Conclusions Preoperative tumor grade by curettage does not accurately predict final histological results, especially in those classified as grade 1. Complete surgical staging seems to be necessary for clinical stage Ⅰ endometriod adenocarcinoma.

The association of inherited variation in the CLOCK gene with breast cancer tumor grade

Background:Sufficient sleep and maintenance of circadian rhythm are important to health.We have shown that short duration of sleep before diagnosis is associated with higher-grade tumors among breast cancer patients.Earlier studies suggest that genetic variation in the CLOCK gene is associated with risk of cancers,including breast cancer.Studies of the association of genetic variation,including in CLOCK,and tumor grade,a standard marker of tumor aggressiveness,are lacking.Methods:We investigated the relationship between single nucleotide polymorphisms(SNPs)in the CLOCK gene and tumor grade and estrogen receptor,progesterone receptor,and human epi-dermal growth factor receptor 2 status in 293 breast cancer patients.Nine SNPs were determined by standard TaqMan assays.Tumor grade,receptor status,and other clinical variables were abstracted from medical records.Results:Two SNPs were excluded because of poor genotyping performance.None of the remaining seven variants had a statistically significant association with breast cancer tumor grade or with receptor status.Conclusion:As with all novel studies,further work is needed to examine the association of CLOCK and other genes in the circadian rhythm pathway with breast cancer tumor grade in other populations.

Tumor regression grades:Potential outcome predictor of locally advanced rectal adenocarcinoma after preoperative radiotherapy

AIM:To analyze tumor regression grade(TRG)for prognosis of locally advanced rectal adenocarcinoma(LARA)treated with preoperative radiotherapy.METHODS:One hundred and ninety patients with clinical stageⅡ/ⅢLARA were studied.All patients underwent radical surgery(between 2004 and 2010)after 30-Gy/10-fraction preoperative radiotherapy(preRT).All 190 patients received a short course of preRT and were reassessed for disease recurrence and survival;the slides of surgical specimens were reviewed and classified according to Mandard TRG.We compared patients with good response(Mandard TRG1 or TRG2)vs patients with bad/poor response(Mandard TRG3-5).Outcomes evaluated were 5-year overall survival(OS),5-year disease-free survival(DFS),and local,distant and mixed recurrence.Fisher’s exact test orχ2 test,logrank test and proportional hazards regression analysis were used to calculate the probability that Mandard TRG was associated with patient outcomes.RESULTS:One hundred and sixty-six of 190 patients(87.4%)were identified as Mandard bad responders(TRG3-5).High Mandard grade was correlated with tumor height(41.7%<6 cm vs 58.3%≥6 cm,P=0.050),yp T stage(75%yp T0-2 vs 25%yp T3-4,P=0.000),and yp N stage(75%yp N0 vs 25%yp N1,P=0.031).In univariate survival analysis,Mandard grade bad responders had significantly worse OS and DFSthan good responders(TRG1/2)(OS,83.1%vs 96.4%,P=0.000;DFS,72.3%vs 92.0%,P=0.002).In multivariate survival analysis,Mandard bad responders had significantly worse DFS than Mandard good responders(DFS 3.8 years(95%CI:1.2-12.2 years,P=0.026).CONCLUSION:Mandard grade good responders had a favorable prognosis.TRG may be a potential predictor for DFS in LARA after pre-RT.

Alterations of tumor-related genes do not exactly match the histopathological grade in gastric adenocarcinomas

AIM:To investigate the diverse characteristics of different pathological gradings of gastric adenocarcinoma (GA) using tumor-related genes.METHODS:GA tissues in different pathological gradings and normal tissues were subjected to tissue arrays.Expressions of 15 major tumor-related genes were detected by RNA in situ hybridization along with 3' terminal digoxin-labeled anti-sense single strandedoligonucleotide and locked nucleic acid modifying probe within the tissue array.The data obtained were processed by support vector machines by four different feature selection methods to discover the respective critical gene/gene subsets contributing to the GA activities of different pathological gradings.RESULTS:In comparison of poorly differentiated GA with normal tissues,tumor-related gene TP53 plays a key role,although other six tumor-related genes could also achieve the Area Under Curve (AUC) of the receiver operating characteristic independently by more than 80%.Comparing the well differentiated GA with normal tissues,we found that 11 tumor-related genes could independently obtain the AUC by more than 80%,but only the gene subsets,TP53,RB and PTEN,play a key role.Only the gene subsets,Bcl10,UVRAG,APC,Beclin1,NM23,PTEN and RB could distinguish between the poorly differentiated and well differentiated GA.None of a single gene could obtain a valid distinction.CONCLUSION:Different from the traditional point of view,the well differentiated cancer tissues have more alterations of important tumor-related genes than the poorly differentiated cancer tissues.

RELATION BETWEEN MORPHOMETRIC GRADES OF BLADDER TUMOR AND PROGNOSIS

The relation between morphometric grades (M grading) of 84 cases of bladder tumor and prognoses was evaluated. The results shown that the higher the M grading, the lower the survival rate and the higher the recurrence rate. As the M grade increases, the tumor has partial of total absence of ABO(H) antigens of tumor cell surface and could be accompanied with muscular invasion. When recurring, the tumor has a poor prognosis if M grading increases from lower to higher grades. The morphometric grading system is able to make a quantitative pathologic diagnosis and can predict the biological behavior of bladder tumors.

Synchronous Mucinous Borderline Tumor of the Ovary and Low-Grade Appendiceal Mucinous Neoplasm

We present a rare case of synchronous mucinous borderline tumor of the ovary and low-grade appendiceal mucinous neoplasm (LAMN). We performed a left adnexectomy to diagnose the left ovarian borderline malignancy and an ileostomy because of the swollen appendix during the operation. It was diagnosed as left ovarian mucinous borderline malignancy and LAMN. LAMN causes peritoneal dissemination, ovarian metastasis, and peritoneal pseudomyxoma. The appendix and ovary are close to each other anatomically and can metastasize if there is a tumor in either. For ovarian mucinous tumors, it is necessary to search the gastrointestinal tract, especially the appendix, as the primary lesion. For appendix tumors, it is necessary to search for the ovary. Since LAMN may be associated with borderline ovarian malignancies, as in this case, there is a possibility of the duplication of tumors when searching for ovarian mucinous tumors as the primary tumor and if ovarian tumors are found. Since LAMN and mucinous ovarian tumors have similar histological features, immunohistochemical staining is useful for their differentiation because they show different immunostaining patterns.

A Case of Low-Grade Appendiceal Mucinous Neoplasm of Its Difficultly to Distinguish from a Right Ovarian Tumor Due to Postmenopause

We here present a rare case of appendiceal tumor mimicking ovarian tumor in menopause woman. The patient was a 56-year-old woman, G1P1, who presented to our hospital with a right adnexal cyst diagnosed at another hospital. Transvaginal echocardiography showed a cyst in the right adnexal region, and pelvic contrast-enhanced MRI revealed a small cyst in the same region. The left ovary was atrophic and identifiable. It was unclear whether the cyst was contiguous with the gastrointestinal tract. Blood tests showed no elevation of tumor markers. We considered its possibility of a gastrointestinal origin, but since right normal ovary was not found, we thought the tumor was of ovarian origin and decided on a laparoscopic resection of the right adnexa. Intraoperatively, we observed atrophied bilateral normal ovaries, and the pelvic tumor was contiguous to the appendix. Surgeons performed a laparoscopic appendectomy after consultation with us. After resection we searched the abdominal and pelvic cavities, but found no obvious disseminated lesions. The histological diagnosis was low-grade appendiceal mucinous neoplasm (LAMN), a rare benign tumor of the appendix. Appendiceal tumors can be difficult to differentiate from right ovarian tumors due to their close anatomic location in the pelvis. It is possible to determine whether the tumor is of ovarian or appendiceal origin by identifying normal ovaries and the location of the feeding vessels into the tumors. In our case, there were no lesions other than the appendix, but LAMN can metastasize to the ovary, cause pseudomyoxoma peritonei, or be an overlapping tumor with an ovarian tumor. If an appendiceal tumor is diagnosed after surgery for ovarian tumor, the intra-abdominal cavity should be searched for metastasis or dissemination, and a thorough search for ovarian lesions should be performed with the possibility of an overlapping tumor in mind.

LIMK2及miR-450a-5p在不同级别浆液性卵巢癌的表达及临床意义

目的探讨LIM激酶2(LIMK2)及微小RNA(miR)-450a-5p在不同级别浆液性卵巢癌的表达及临床意义。方法本研究为回顾性研究,选择2020年1月至2023年1月宝鸡市中心医院收治的102例浆液性卵巢癌患者作为研究对象,根据肿瘤级别分为高级别浆液性卵巢癌组(n=70)和低级别浆液性卵巢癌组(n=32)。检测所有患者病理组织中LIMK2及miR-450a-5p的表达水平;分析不同临床病理特征的浆液性卵巢癌组织中LIMK2及miR-450a-5p表达水平的差异性;使用受试者操作特征(ROC)曲线分析LIMK2及miR-450a-5p对高级别浆液性卵巢癌的鉴别诊断效能;随访12个月,记录浆液性卵巢癌患者术后复发情况,使用多因素风险评估模型分析LIMK2及miR-450a-5p与浆液性卵巢癌患者术后复发的关系。结果高级别浆液性卵巢癌组病理组织中LIMK2表达水平为5.16±1.34,高于低级别浆液性卵巢癌组(0.62±0.23),miR-450a-5p表达水平为1.12±0.45,低于低级别浆液性卵巢癌组(6.08±1.29),差异均有统计学意义(P<0.05)。浆液性卵巢癌组织中LIMK2、miR-450a-5p表达水平与手术病理分期、淋巴结转移状态有关(P<0.05),与年龄、术前糖类抗原125水平、术后残留灶大小无关(P>0.05)。经ROC曲线分析,病理组织中LIMK2联合miR-450a-5p诊断高级别浆液性卵巢癌的敏感度为92.41%,特异度为63.50%,曲线下面积(AUC)为0.931。102例浆液性卵巢癌患者,术后12个月期间,复发26例,占25.49%。复发患者病理组织中LIMK2表达水平为6.81±1.70,高于非复发患者(3.39±0.79),病理组织中miR-450a-5p表达水平为0.43±0.22,低于非复发患者(1.73±0.68),差异均有统计学意义(P<0.05)。经多因素风险评估模型分析,病理组织中LIMK2和miR-450a-5p均是浆液性卵巢癌患者术后复发的独立预测因素(P<0.05)。结论高级别浆液性卵巢癌组织中LIMK2表达上调,miR-450a-5p表达下调,两者均与手术病理分期、淋巴结转移状态有关。病理组织中LIMK2和miR-450a-5p联合诊断高级别浆液性卵巢癌的效能较好,对术后预后具有一定评估作用,值得进一步研究应用。

P21活化激酶4在胃肠道间质瘤中的表达及意义

目的通过研究不同危险度胃肠道间质瘤(gastrointestinal stromal tumor,GIST)中P21活化激酶4(P21-activated kinase 4,PAK4)的表达量,探讨PAK4与GIST危险度的关系。方法选取2020年10月至2021年4月秦皇岛市第一医院病理诊断为GIST患者24例,根据共识将患者分为高危组、中危组、低危组,通过病理切片来确定不同危险度组的PAK4的表达量,并根据Callow计算方法对不同危险度组进行评分。结果PAK4随着GIST危险度增加表达升高,并且与正常对照组织及瘤旁组织相比,GIST中的PAK4表达量升高。结论PAK4表达量与GIST危险度相关,并且随着危险度升高,表达量也升高。

超声造影定量参数预测胰腺神经内分泌肿瘤病理分级的临床价值

目的探讨超声造影(CEUS)定量参数预测胰腺神经内分泌肿瘤(pNETs)病理分级的临床应用价值。方法选取我院经手术病理确诊的pNETs患者54例,依据WHO 2019病理分级标准分为G1/G2级组40例和G3级组14例,术前均行常规超声和CEUS检查,比较两组常规超声图像特征(肿瘤最大径、结构、位置、回声、边缘及有无主胰管扩张、内部血流情况)、CEUS图像特征(胰腺病变增强模式、动脉期增强程度、有无非增强坏死区域)及CEUS定量参数[相对峰值强度(rPI)、相对平均传输时间(rmTT)、相对上升时间(rRT)、相对达峰时间(rTTP)、相对曲线下面积(rAUC)]的差异。绘制受试者工作特征(ROC)曲线分析CEUS定量参数预测pNETs病理分级的诊断效能。结果两组常规超声图像特征、CEUS图像特征比较差异均无统计学意义。G1/G2级组rPI、rmTT、rAUC均高于G3级组,差异均有统计学意义(均P<0.05)。ROC曲线分析显示,rPI、rmTT和rAUC预测pNETs病理分级的曲线下面积分别为0.799、0.687、0.932,联合应用预测pNETs病理分级的AUC为0.980。结论CEUS定量参数可准确预测pNETs病理分级,其中rPI、rmTT和rAUC联合应用对预测pNETs病理分级具有较高的临床应用价值。

^(68)Ga-DOTATATE PETCT显像在神经内分泌肿瘤诊断及病理分级中的应用研究

目的探讨^(68)Ga-DOTATATE正电子发射断层成像(PET)/计算机断层成像(CT)在神经内分泌肿瘤(NET)诊断及病理分级中的应用价值。方法选择我院2022年1月到2023年6月期间86例疑似NET的患者为研究对象,经手术病理或病理活检结果确认74例为胃肠胰NET,12例为非NET。患者均接受多层螺旋CT(MSCT)、核磁共振成像(MRI)、^(68)Ga-DOTATATE PET-CT检查,分析患者影像学检查结果,探讨^(68)Ga-DOTATATE PET-CT显像在NET诊断及病理分级中的应用价值,按照病理诊断分级将G1级、G2级、G3级患者分别纳入A组、B组、C组,比较三组间病灶最大径、最大标准摄取值(SUV__(max))、平均标准摄取值(SUV_(mean))、肿瘤/本底比值(TBR)的差异。结果3种检查方法中,^(68)Ga-DOTATATE PETCT诊断效能最高,灵敏度为95.95%,特异度为83.33%,准确度为94.19%,kappa=0.766。三组间病灶最大径、SUV__(max)、SUV_(mean)差异有统计学意义(P<0.05);A组病灶最大径小于B组、C组,B组病灶最大径小于C组,差异有统计学意义(P<0.05);A组SUV__(max)和SUV_(mean)大于B组、C组,B组SUV__(max)和SUV_(mean)大于C组,差异有统计学意义(P<0.05)。结论^(68)Ga-DOTATATE PET-CT显像可以提高NET诊断价值,利于指导NET病理分级,有望为临床针对性治疗提供参考。

血清可溶性CD276与晚期高级别浆液性卵巢癌预后及肿瘤免疫浸润相关性分析

目的探讨血清可溶性CD276(sCD276)与晚期高级别浆液性卵巢癌(HGSOC)预后及肿瘤免疫浸润的相关性。方法将2017年3月至2020年3月资阳市第一人民医院就诊的晚期HGSOC患者73例纳入A组,选取同期入院治疗的其他类型卵巢癌患者80例纳入B组,另选择80名健康人群作为健康人群组,检测三组血清sCD276表达水平。并依据血清sCD276表达水平中位数将A组分为高表达组(≥451.26 pg/ml)与低表达组(<451.26 pg/ml)。分析血清sCD276水平变化与晚期HGSOC患者不同临床特征的关系,并采用生存曲线和Cox比例风险回归分析血清sCD276与晚期HGSOC预后的相关性。结果A组和B组血清sCD276表达水平均高于健康人群组(P<0.05),且A组血清sCD276水平高于B组(P<0.05);卵巢癌患者sCD276低表达与高表达的无病生存率比较,差异无统计学意义(P>0.05);在A组中,低表达组的无病生存率及总生存率高于高表达组(P<0.05),无病生存时间≥12月组的血清sCD276表达水平低于无病生存时间<12月组(P<0.05);A组患者中sCD276高表达组与低表达组在有无淋巴结转移、术后残余病灶、CD3^(+)阳性、FoxP3^(+)阳性等方面比较有差异统计学意义(P<0.05);经多因素COX比例风险回归分析得出,有术后残余病灶、CD3^(+)阳性、FoxP3^(+)阳性、血清sCD276≥451.26 pg/ml均是晚期HGSOC患者预后的危险因素(P<0.05);经免疫组化法对肿瘤组织检测得出,A组中有59例患者膜CD276表达为阳性,14例患者膜CD276表达为阴性,膜CD276阳性组的血清sCD276表达及FoxP3^(+)阳性比例均明显高于膜CD276阴性组(P<0.05)。结论血清sCD276在晚期HGSOC呈高表达水平,其水平升高与TILs标志物FoxP3^(+)T细胞数量均是晚期HGSOC患者复发或死亡的危险因素,与患者预后关系密切,血清sCD276为晚期HGSOC新辅助化疗期间的免疫应答监测提供了可能性。

ARHGAP8在中低位局部进展期直肠癌新辅助化疗疗效预测中的应用

目的分析ARHGAP8对中低位局部进展期直肠癌新辅助化疗疗效预测的敏感性,为进展期直肠癌的治疗提供精准依据。方法通过生物信息学分析筛选,获得差异基因ARHGAP8。选取68例原发性直肠癌患者的直肠癌组织及直肠组织标本,应用实时荧光定量PCR、Western blot和免疫组织化学方法分别对ARHGAP8的表达强度进行验证,并收集患者性别、年龄、分期、肿瘤大小、分化程度、病理类型等临床病理特征进行功能验证;选取44例行新辅助化疗的中低位局部进展期直肠癌患者,采用免疫组织化学方法检测新辅助化疗前后ARHGAP8的表达情况,分析ARHGAP8在新辅助化疗前后、不同疗效组之间的表达情况。结果生物信息学结果显示,ARHGAP8在癌组织及直肠组织中的表达差异有统计学意义(P<0.001),且ARHGAP8的表达水平与肿瘤分期(P=0.024)、淋巴结转移(P=0.007)、年龄(P=0.005)等临床特征相关。实时荧光定量PCR结果显示,ARHGAP8 mRNA在癌组织中的表达显著高于直肠组织(P<0.001);Western blot和免疫组织化学结果显示,ARHGAP8蛋白在癌组织中的表达显著高于直肠组织(P=0.011);ARHGAP8的表达与肿瘤大小(P=0.010)、病理分期(P=0.005)密切相关,而与肿瘤分化程度、淋巴结转移、肝转移、Ki-67、微卫星不稳定性的表达程度无相关性。44例接受新辅助化疗的患者中TRG 0级13例、1级8例、2级8例、3级15例,其中65.91%(29/44)的患者新辅助化疗有效,新辅助化疗有效患者治疗后ARHGAP8的表达显著下降(P<0.001),ARHGAP8蛋白低表达患者的有效率为92.86%,显著高于ARHGAP8蛋白高表达者(53.33%)(P=0.033)。结论ARHGAP8在直肠癌组织中高表达,ARHGAP8低表达的中低位局部进展期直肠癌患者对XELOX方案新辅助化疗更为敏感,ARHGAP8可作为直肠癌发生发展的潜在生物学指标,同时可作为中低位局部进展期直肠癌XELOX方案新辅助化疗疗效评估的重要参考指标。

APT-联合DCE-MRI术前预测成人型弥漫性胶质瘤病理分级及IDH基因突变型

目的:探讨氨基质子转移(APT)成像联合DCE-MRI对成人型弥漫性胶质瘤病理分级和IDH基因型的术前预测价值。方法:将2020年10月-2023年10月在本院诊治且经病理证实的78例脑胶质瘤患者纳入本研究。患者手术前均进行APT成像和DCE-MRI检查。依据肿瘤的组织病理学分级将患者分为2组:低级别组(Ⅱ~Ⅲ级)36例,高级别组(Ⅳ级)42例;依据患者IDH基因表达情况将患者分为2组:IDH野生型组31例,IDH突变型组47例。比较高、低病理分级组及不同IDH分型组之间病灶的APT图像信号等级(分为1~5级)和DCE-MRI参数(K_(trans)、V_(e)、rCBV、V_(p)、K_(ep)和rCBF)值的差异,对组间差异有统计学意义的指标,采用ROC曲线分析其诊断效能。结果:IDH突变型和野生型组之间年龄、性别、主诉、神经系统体征差异均无统计学意义(P>0.05);高级别组和低级别组之间年龄、性别、主诉、神经系统体征差异均无统计学意义(P>0.05),但是高级别组中IDH野生型占比更高(P<0.05)。78例病灶的APT信号分级:1级有19例,2级3例,3级14例,4级6例,5级36例。高级别组APT图像上肿瘤的信号等级高于低级别组,IDH野生型组患者APT图像等级高于突变型组,差异有统计学意义(P<0.05)。DCE-MRI参数的组间比较结果显示,高级别组与低级别组之间,以及IDH突变型与IDH野生型之间,K_(trans)、V_(e)和rCBV值的差异均有统计学意义(P<0.05)。APT信号等级鉴别高、低级别胶质瘤及IDH状态的AUC分别为0.782和0.714,K_(trans)、V_(e)和rCBV鉴别高、低级别胶质瘤的AUC分别为0.982、0.793和0.898,鉴别IDH状态的AUC分别为0.963、0.803和0.873。结论:APT成像联合DCE-MRI定量参数能在术前较准确地预测成人型弥漫性胶质瘤的病理分级和IDH基因分型。

Clinical and pathological characteristics and prognosis of 132 cases of rectal neuroendocrine tumors

BACKGROUND Neuroendocrine tumors(NETs)frequently occur in the gastrointestinal tract,lung,and pancreas,and the rectum and appendix are the sites with the highest incidence.Epidemiology statistics show that an estimated 8000 people every year in the United States are diagnosed with NETs occurring in the gastrointestinal tract,including the stomach,intestine,appendix,colon,and rectum.The pathological changes and clinical symptoms of NETs are not specific,and therefore they are frequently misdiagnosed.AIM To investigate the clinical symptoms,pathological characteristics,treatment,and prognosis of rectal neuroendocrine tumors(RNETs)by analyzing the clinical and pathological data of 132 RNET cases at our hospital.METHODS All RNETs were graded according to Ki-67 positivity and mitotic events.The tumors were staged as clinical stages I,II,III,and IV according to infiltrative depth and tumor size.COX proportional hazard model was used to assess the main risk factors for survival.RESULTS These 132 RNETs included 83 cases of G1,21 cases of G2,and 28 cases of G3(neuroendocrine carcinoma)disease.Immunohistochemical staining showed that 89.4%of RNETs were positive for synaptophysin and 39.4%positive for chromogranin A.There were 19,85,23,and 5 cases of clinical stages I,II,III,and IV,respectively.The median patient age was 52.96 years.The diameter of tumor,depth of invasion,and pathological grade were the main reference factors for the treatment of RNETs.The survival rates at 6,12,36,and 60 mo after operation were 98.5%,94.6%,90.2%,and 85.6%,respectively.Gender,tumor size,tumor grade,lymph node or distant organ metastasis,and radical resection were the main factors associated with prognosis of RNETs.Multivariate analysis showed that tumor size and grade were independent prognostic factors.CONCLUSION The clinical symptoms of RNETs are not specific,and they are easy to misdiagnose.Surgery is the main treatment method.The grade and stage of RNETs are the main indices to evaluate prognosis.

Clinical characteristics and outcome of primary hepatic neuroendocrine tumors after comprehensive therapy

BACKGROUND Primary hepatic neuroendocrine tumors(PHNETs),a group of neuroendocrine neoplasms,are extremely rare.There are only few case reports about PHNETs in the literature.The lack of large samples and multicenter research results in poor diagnostic and therapeutic approaches.AIM To discuss the clinical characteristics,diagnosis,and treatment of PHNETs and risk factors related to survival.METHODS We retrospectively analyzed the clinical data,imaging features,immunohistochemistry data,and treatment efficacy of 40 patients who were pathologically diagnosed with PHNETs and admitted to The First Affiliated Hospital of Zhengzhou University from January 1,2014 to November 15,2019.Finally,survival analysis was performed to identify the risk factors for survival.RESULTS The main symptoms and signs included intermittent abdominal pain(19 patients,47.5%)and bloating(8 patients,20.0%).The positive rates of tested tumor markers were recorded as follows:Carbohydrate antigen 19-9(CA19-9)(6 patients,15.0%),CA72-4(3 patients,7.5%),carcinoembryonic antigen(7 patients,17.5%),and alpha-fetoprotein(6 patients,15.0%).Immunohistochemical staining results showed positivity for Syn in 38(97.4%)of 39 patients,for chromogranin A in 17(65.4%)of 26 patients,for CD56 in 35(94.6%)of 37 patients,for AE1/AE3 in 28(87.5%)of 32 patients,and for Ki-67 in all 40(100.0%)patients.The overall survival rate was significantly related to the tumor grade,AE1/AE3,and Ki-67.tumor number,tumor size,metastasis,and treatment)and overall survival.CONCLUSION Higher grade,negative AE1/AE3,and higher Ki-67 are associated with a worse survival rate.Kinds of treatment and other parameters have no significant influence on overall survival.