DNA methylation and carcinogenesis in digestive neoplasms

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Practical hints for the diagnosis of mixed neuroendocrine-nonneuroendocrine neoplasms of the digestive system

In this editorial,a comment on the article by Díaz-López et al published in the recent issue of the 2024 is provided.We focus on the practical implications critical for providing a correct and complete diagnosis of mixed neuroendocrine-nonneuroendocrine neoplasm(MiNEN)in the gastrointestinal system.The diagnosis of MiNEN begins with the recognition of neuroendocrine features in one component of a biphasic tumor.The non-neuroendocrine counterpart can be virtually represented by any neoplastic type,even though the most frequent histologies are glandular and squamous.However,qualification of the neuroendocrine component requires histological and immunohistochemical confirmation.Neuroendocrine tumors are characterized by a peculiar architectural organization and bland nuclei with granular“salt and pepper”chromatin.Although neuroendocrine carcinomas have multiple and variable presentations,they typically show a solid or organoid architecture.The histological aspect needs to be confirmed by immunohistochemistry,and a diagnosis is confirmed whenever the expression of keratin and neuroendocrine markers is observed.Once both histopathological and immunohistochemical features of neuroendocrine neoplasms are identified,it is important to consider the three major pitfalls of MiNEN diagnostics:(1)Entrapment of neuroendocrine non-neoplastic cells within the tumor mass;(2)Differential diagnosis with amphicrine neoplasms;and(3)Differential diagnosis of tumors that partially express neuroendocrine markers.According to the current guidelines for diagnosing digestive MiNEN,each component must represent at least 30%of the entire neoplastic mass.Although the high-grade histopathological subtype frequently determines disease prognosis,both components can significantly affect prognosis.Thus,if one of the components,either neuroendocrine or non-neuroendocrine,does not fulfill the volumetric criteria,the guidelines still encourage reporting it.These strict criteria are essential for correctly recognizing and characterizing digestive MiNENs.This task is essential because it has prognostic relevance and substantial potential value for guiding further studies in this field.In the future,systematic analyses should be performed to validate or reconsider the current 30%cutoff value.

Clinical significance of CA_(19-9) in diagnosis of digestive tract tumors

IM To evaluate the clinical value of CA199 in diagnosing and differentiating the gastrointestinal tumors and in monitoring the patients treated surgically.METHODS Gastric cancer (n=70), colorectal cancer (n=90), pancreatic cancer (n=7), esophageal cancer (n=10), benign disorder (n=30), and normal adults (n=111) as control were studied. Fasting blood samples were obtained from each patient and normal adult. The serum CA199 concentration was measured with radioimmunoassay.RESULTS The mean CA199 level in gastric cancer (17069kU/L±9145kU/L) and in colorectal cancer (8721kU/L±3955kU/L) was significantly higher than that in the control (11254kU/L±600kU/L). Compared with the normal adults, the CA199 level was much higher in pancreatic cancer patients (126658kU/L±52131kU/L) (P<001). However, the CA199 concentrations in nonrecurrent gastric (1263kU/L±362kU/L) and colorectal cancers (1414kU/L±326kU/L) and benign disorders (1423kU/L±260kU/L) were similar to the control. The differences were not statistically significant (P>005). The demarcation value of CA199 between the negative and positive was <310kU/L. The sensitivity of CA199 for gastric, colorectal, pancreatic and esophageal cancers and gastrointestinal benign disorders was 473%, 500%, 833%, 200% and 0%, respectively. The specificity of CA199 for digestive system malignant diseases was all 100%.

Progression of hepatic hyperperfusion disorders revealed during follow-up CT scan of digestive system neoplasm

Objective： The aim of this study was to investigate progression of hepatic hyperperfusion disorders revealed during follow-up contrast material-enhanced multi-slice spiral computed tomography （MSCT） scan of digestive system neoplasm. Methods： Three-phase contrast material-enhanced MSCT were performed during the follow-up in patients with digestive system malignant tumor confirmed histologically. The progression of hepatic hyperperfusion disorders revealed on contrast material-enhanced CT image were investigated at the 2 years follow-up with approximately 6 months interval. Results： The hepatic hyperperfusion disorders were showed in 39 patients on follow-up contrast material-enhanced MSCT scans. Among the 39 patients, initial hyperperfusion disorders were revealed in 6 （15.38%）, 26 （66.67%）, and 7 （17.95%） patients in 6, 12, and 18 months during follow-up respectively. The initial hyperperfusion disorders revealed in 12 months were more frequent than those revealed in 6 months （X2 = 14.82, P 〈 0.05） and 18 months （X2 = 15.02, P 〈 0.05）. Among the 39 patients, the hyperperfusion disorders progressed into liver metastasis based on typical CT findings in 37 （94.87%） patients, and were not obvious changes in 2 （5.13%） patients. Among the 37 patients, the hyperperfusion disorders progressed into metastasis in 10 （25.64%） patients in 6 months after the hyperperfusion disorders were revealed, and in 27（69.23%） patients in 12 months. The hyperperfusion disorders developing into metastasis were more in 12 months than those in 6 months （X2= 14.98, P 〈 0.05）. Conclusion： Most hepatic hyperperfusion disorders revealed at the follow-up of digestive system neoplasm may be early manifestations of liver metastasis. The careful follow-up of hepatic hyperperfusion disorders is necessary.

Retrospective study on mixed neuroendocrine non-neuroendocrine neoplasms from five European centres

BACKGROUND Mixed neuroendocrine non-neuroendocrine neoplasm(MiNEN)is a rare diagnosis,mainly encountered in the gastro-entero-pancreatic tract.There is limited knowledge of its epidemiology,prognosis and biology,and the best management for affected patients is still to be defined.AIM To investigate clinical-pathological characteristics,treatment modalities and survival outcomes of a retrospective cohort of patients with a diagnosis of MiNEN.METHODS Consecutive patients with a histologically proven diagnosis of MiNEN were identified at 5 European centres.Patient data were retrospectively collected from medical records.Pathological samples were reviewed to ascertain compliance with the 2017 World Health Organisation definition of MiNEN.Tumour responses to systemic treatment were assessed according to the Response Evaluation Criteria in Solid Tumours 1.1.Kaplan-Meier analysis was applied to estimate survival outcomes.Associations between clinical-pathological characteristics and survival outcomes were explored using Log-rank test for equality of survivors functions(univariate)and Cox-regression analysis(multivariable).RESULTS Sixty-nine consecutive patients identified;Median age at diagnosis:64 years.Males:63.8%.Localised disease(curable):53.6%.Commonest sites of origin:colon-rectum(43.5%)and oesophagus/oesophagogastric junction(15.9%).The neuroendocrine component was;predominant in 58.6%,poorly differentiated in 86.3%,and large cell in 81.25%,of cases analysed.Most distant metastases analysed(73.4%)were occupied only by a poorly differentiated neuroendocrine component.Ninety-four percent of patients with localised disease underwent curative surgery;53%also received perioperative treatment,most often in line with protocols for adenocarcinomas from the same sites of origin.Chemotherapy was offered to most patients(68.1%)with advanced disease,and followed protocols for pure neuroendocrine carcinomas or adenocarcinomas in equal proportion.In localised cases,median recurrence free survival(RFS);14.0 months(95%CI:9.2-24.4),and median overall survival(OS):28.6 months(95%CI:18.3-41.1).On univariate analysis,receipt of perioperative treatment(vs surgery alone)did not improve RFS(P=0.375),or OS(P=0.240).In advanced cases,median progression free survival(PFS);5.6 months(95%CI:4.4-7.4),and median OS;9.0 months(95%CI:5.2-13.4).On univariate analysis,receipt of palliative active treatment(vs best supportive care)prolonged PFS and OS(both,P<0.001).CONCLUSION MiNEN is most commonly driven by a poorly differentiated neuroendocrine component,and has poor prognosis.Advances in its biological understanding are needed to identify effective treatments and improve patient outcomes.

Telomere,telomerase and digestive cancer

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Endoscopic submucosal tunnel dissection for largesuperficial esophageal squamous cell neoplasms

Endoscopic submucosal dissection(ESD)is a wellestablished treatment for superficial esophageal squamous cell neoplasms(SESCNs)with no risk of lymphatic metastasis.However,for large SESCNs,especially when exceeding two-thirds of the esophageal circumference,conventional ESD is time-consuming and has an increased risk of adverse events.Based on the submucosal tunnel conception,endoscopic submucosal tunnel dissection(ESTD)was first introduced by us to remove large SESCNs,with excellent results.Studies from different centers also reported favorable results.Compared with conventional ESD,ESTD has a more rapid dissection speed and R0 resection rate.Currently in China,ESTD for large SESCNs is an important part of the digestive endoscopic tunnel technique,as is peroral endoscopic myotomy for achalasia and submucosal tunnel endoscopic resection for submucosal tumors of the muscularis propria.However,not all patients with SESCNs are candidates for ESTD,and postoperative esophageal strictures should also be taken into consideration,especially for lesions with a circumference greater than three-quarters.In this article,we describe our experience,review the literature of ESTD,and provide detailed information on indications,standard procedures,outcomes,and complications of ESTD.

Advances in the diagnosis and treatment of MET-variant digestive tract tumors

The receptor tyrosine kinase encoded by the MET gene plays an important role in various cellular processes such as growth,survival,migration and angiogenesis,and its abnormal activation is closely related to the occurrence and development of various tumors.This article reviews the recent advances in diagnosis and treatment of MET-variant digestive tract tumors.In terms of diagnosis,the application of next-generation sequencing technology and liquid biopsy technology makes the detection of MET variants more accurate and efficient,providing a reliable basis for individualized treatment.In terms of treatment,MET inhibitors such as crizotinib and cabotinib have shown good efficacy in clinical trials.In addition,the combination of immunotherapy and MET inhibitors also demonstrated potential synergies,further improving the therapeutic effect.However,the complexity and heterogeneity of drug resistance mechanisms are still one of the difficulties in current research.In the future,it is necessary to further deepen the understanding of the mechanism of MET variation and explore new combination treatment strategies to improve the overall survival rate and quality of life of patients.The diagnosis and treatment of MET-variant digestive tract tumors are moving towards precision and individualization,and have broad application prospects.

Characterics of upper digestive tract diseasesin fishermen of the Bohai Bay

AIM To study the characteristics of upper digestive tract diseases (UDTDs) in the fishermen of the Bohai Bay. METHODS An investigation was carried out in 1488 fishermen with symptoms of UDTDs except liver, biliary and pancreatic diseases during the period from December 1991 to February 1995, which included medical history inquiry, physical, gastroscopic and pathological examinations, detection of Helicobacter pylori ( H. pylori) infection, and nitrate content in their drinking water. RESULTS Among the 1488 subjects investigated, 1467 suffered from one or more diseases among 14 kinds of UDTDs, most of which were chronic atrophic gastritis (CAG, 1103 cases), peptic ulcer (268 cases), and cancer of the upper digestive tract (25 cases). CONCLUSION Incidence rate of UDTDs tends to be high among the fishermen, especially CAG, peptic ulcer and upper digestive tract cancer, and complicated state of illness due to their special life habits, and high nitrate content in their drinking water, etc, and UDTDs in fishermen is significantly different from that in inland residents in clinical manifestations.

Hepatic angiomyolipoma-misdiagnosis as hepatocellular carcinoma:A report of 14 cases

Angiomyolipoma (AML) is a rare benign mesenchymal tumor of the liver, composed of a varying heterogeneous mixture of three tissue components: blood vessels, smooth muscle, and adipose cells. It has recently been proposed that the perivascular epithelial cell (PEC) is the common progenitor[1，2] Since its first description by Ishak in 1976[3], there have been more than 100 cases reported in the English literature[4-6]. With the advance of radiological techniques, many more tumors are being diagnosed by the means. But radiological findings of AML may only be suggestive of the lesion; its definitive diagnosis requires histological confirmation[9-19]. Some authors regard renal and hepatic AMLs, pulmonary and soft tissue lymphangiomyomatosis[2], pulmonary and pancreatic clear cell “sugar” tumor, and cardiac rhabdomyoma as closely related groups of tumors, based on their morphologic overlap and common immunoreactivity for HMB-45[l]. They show different microscopic appearances, however, according to their organ of origin. The goals of this study were to highlight more subtle morphology and to gain possible insights into the differential diagnosis that could provide important information about this disease.

Giant low-grade appendiceal mucinous neoplasm: A case report

BACKGROUND Appendiceal mucinous neoplasm (AMN) is extremely rare. Since the disease does not manifest a characteristic profile of clinical symptoms, it is easy to misdiagnose and still difficult to diagnose without operation. Here, we report a case of low-grade AMN (LAMN) and summarize its clinical features, diagnosis, and treatment. CASE SUMMARY A 63-year-old postmenopausal woman presented with a history of right lower abdominal mass. The patient underwent laparotomy, which showed an appendiceal mucocele originating from the apex of the appendix, and a simple appendectomy was performed. The subsequent histological assessment identified an LAMN with no lymph node involvement and negative surgical margin. The patient received six cycles of chemotherapy after surgery, and to date, more than a year after the surgery, the patient remains in good health. CONCLUSION A unified, standardized, detailed, and accurate pathological diagnosis is needed for LAMN, to facilitate selection of an appropriate surgical plan. In addition, the surgeon should record the details of the tumors in the surgical records in order to facilitate follow-up after surgery.

Intraductal papillary mucinous neoplasm originating from a jejunal heterotopic pancreas:A case report

BACKGROUND Intraductal papillary mucinous neoplasm(IPMN)is a rare pancreatic tumor and has the potential to become malignant.Surgery is the most effective treatment at present,but there is no consensus on the site of resection.Heterotopic pancreas occurs in the gastrointestinal tract,especially the stomach and duodenum but is asymptomatic and rare.We report a case of ectopic pancreas with IPMN located in the jejunum.CASE SUMMARY A 56-year-old male patient suffered from severe pain,nausea and vomiting due to a traffic accident and sought emergency treatment at our hospital.Contrast-enhanced computed tomography of the whole abdomen suggested splenic congestion,which was considered to be splenic rupture.Emergency laparotomy was performed,and the ruptured spleen was removed during the operation.Unexpectedly,a cauliflower-like mass of about 2.5 cm×2.5 cm in size was incidentally found about 80 cm from the ligament of Treitz during the operation.A partial small bowel resection was performed,and postoperative pathology confirmed the small bowel mass as heterotopic pancreas with low-grade IPMN.CONCLUSION Ectopic pancreas occurs in the jejunum and is pathologically confirmed as IPMN after surgical resection.

Strengthen international academic cooperation and exchanges:prospects in the 21st century:Summary of the First World Chinese Congress of Digestion

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Nodular fasciitis in the mesentery, a differential diagnosis of peritoneal carcinomatosis

Nodular fasciitis is a benign proliferative lesion composed of fibroblast-like cells that affects various sites in the body.We describe a patient with nodular fasciitis in the mesentery,encountered during laparotomy for the treatment of ascending colon cancer.The nodular fasciitis in our patient resembled peritoneal dissemination of malignancy on macroscopic observation.Because the treatment options change with concomitant peritoneal dissemination of gastrointestinal tract malignancy,recognition of this rare condition and preparation for unexpected nodular lesions are crucial.

Clinicopathological features of giant cell carcinoma of the pancreas

BACKGROUND: Giant cell carcinoma of the pancreas (GCCP) as a tumor of high malignancy, large size, and inflammatory reaction occupies 2.1%-12.8% of all cases of pancreatic malignancies. This study was to analyze cases of GCCP collected in 8 years at our hospital in an attempt to describe some features of GCCP in Chinese people. METHODS: The clinicopathological features of 19 patients who had been pathologically diagnosed as having GCCP from 1021 patients with pancreatic malignancies collected by Pancreatic Disease Research Group (PDRG) of Chang- hai Hospital were retrospectively analyzed compared with those of 96 patients with common pancreatic carcinoma (PC) who were randomly selected from 1002 patients with pancreatic carcinoma. The differences of location, clinical symptoms, imagings, laboratory test, operation and the prognosis of these two groups were defined. RESULTS: Tumors in the head of the pancreas were found in 8 patients (42.1%), and those in the body or tail of the pancreas in 11 (57.9%). The initial symptom was abdomi- nal pain in most patients (57.9%). Abdominal pain (73.7%), dyspepsia (63.2%), weight loss (36.8%) but jaun- dice were common at the time of diagnosis. The abnormal rates of routine laboratory tests in the GCCP group were lower than those in the common PC group. The assay of tumor markers between the groups of GCCP and common PC was approximately the same. The sensitivity and accu- racy of ultrasonography, spiral computed tomography and magnetic resonance imaging were considerably high. Large carcinoma in stage was seen in 9 patients or 47.4% of the GCCP group, a rate higher than that in the common PC group. Osteoid formation was found microscopically in some patients, and poorly differentiated tumor cells were found in most patients. The 1-year survival rate was 17.6%, which was lower than that in the common PC group. CONCLUSION: The clinicopathological features of GCCP are different from those of common PC. Imaging tests can be used together with the assay of tumor markers to diag- nose GCCP as early as possible and to improve the progno-sis of GCCP patients.

Clinicopathologic Observation of 6 Cases with Neuroendocrine Carcinoma of the Urinary Bladder

OBJECTIVE To discuss the pathologic characteristics and theprognosis of neuroendocrine carcinoma of the bladder(NECB)in order to assist in making a precise diagnosis and to effectivelytreat the disease.METHODS Clinicopathologic features of the 6 cases with NECBwere analyzed retrospectively.The personal data of the patientsand the pathologic and immunohistochemical characteristics ofthe tumor were investigated.The follow-up of these patients wasconducted over a time period ranging from 3 months to 9 years.RESULTS Transurethral resection of the bladder tumorwas performed in all 6 patients.Based on the results of thepathologic examination,4 of the cases were diagnosed as smallcell neuroendocrine carcinoma and the other 2 were diagnosedas atypical carcinoid tumor.On immunohistochemical stainingall tumors expressed neuroendocrine markers includingneuronspecific enolase(CD56),synaptophysin(Syn)andchromogranin(CgA).In patients receiving partial cystectomyfollowed by postoperative chemotherapy,relapse was found in 4of the 6 cases on follow up.CONCLUSION NECB is a rare entity and a tumor with highmalignant potential and characteristic pathologic features.Hematuria is the cardinal symptom of NECB.Metastasis mayoccur at an early stage and the prognosis of the disease is poor.Final diagnosis of NECB depends on histopathologic examinationand immunohistochemical assays.Surgical excision combinedwith radiotherapy and chemotherapy is considered an effectivetreatment.

卵巢-附件报告和数据系统超声2022版(O-RADS US v2022)及其联合恶性风险指数4鉴别附件良、恶性肿瘤

目的观察卵巢-附件报告和数据系统超声2022版(O-RADS US v2022)及其联合恶性风险指数4(RMI4)鉴别附件良、恶性肿瘤的价值。方法回顾性分析126例手术病理诊断为附件肿瘤患者,根据O-RADS US v2022将1~3类归为良性病变、4~5类归为恶性病变,以450为RMI4分类的临界值,基于二者进行联合分类。以病理结果为金标准,绘制受试者工作特征(ROC)曲线,计算曲线下面积(AUC),评估单一O-RADS US v2022、RMI4及其联合鉴别附件良、恶性肿瘤的效能。结果126例附件肿瘤中,良性94例、恶性32例。O-RADS US v2022鉴别附件良、恶性肿瘤的敏感度、特异度、准确率及AUC分别为78.13%、80.85%和80.16%、0.795,RMI4分别为71.88%、84.04%和80.95%、0.780;二者联合的特异度及准确率(93.62%、92.06%)均高于单一O-RADS US v2022(χ^(2)=7.322、5.967,P=0.007、0.015)或RMI4(χ^(2)=4.625、5.331,P=0.032、0.021),而敏感度及AUC(87.50%、0.906)差异均无统计学意义(P均>0.05)。结论O-RADS US v2022能有效鉴别附件良、恶性肿瘤,联合RMI4可提高鉴别特异度及准确率。

超声造影在不同分子分型乳腺癌鉴别诊断中的应用

目的 探讨超声造影(CEUS)特征预测乳腺癌分子分型的价值。资料与方法 回顾性分析2020年1月—2022年7月于内蒙古医科大学附属医院术前行乳腺肿块常规超声检查及CEUS,术后病理诊断为乳腺癌,并获得免疫组化结果的122例患者,根据免疫组化结果分为Luminal A、Luminal B、人表皮生长因子受体-2(HER-2)过表达型及三阴性(TNBC)乳腺癌,分析不同分子分型乳腺癌CEUS特征及参数的差异。结果 不同分子分型乳腺癌患者年龄、Ki-67表达量差异有统计学意义(F=12.856,χ^(2)=211.370,P均<0.05),HER-2型平均年龄最大,Luminal B型、TNBC型以Ki-67占比更高多见。CEUS特征提示,Luminal A型、Luminal B型增强程度呈高增强、等或低增强分别为17例、15例,28例、27例,HER-2型、TNBC型高增强(16例、12例)占比更高(χ^(2)=3.235,P=0.039);灌注峰值时边界Luminal A型、Luminal B型、HER-2型以不清晰为主(17例、31例、16例),TNBC型以清晰为主(13例);HER-2型以灌注缺损(14例)和周围穿支血流(11例)多见,Luminal A型、Luminal B型以周围汇聚征(24例、41例)多见。时间-强度曲线参数:不同分子分型乳腺癌ΔPeak、ΔAUC差异有统计学意义(H=12.558、22.683,P均<0.05),其中HER-2过表达型ΔPeak和ΔAUC均高于其他亚型(P<0.05),可作为HER-2过表达型的预测指标,而不同分子分型乳腺癌ΔTP、ΔSharpness差异均无统计学意义(P>0.05)。结论 不同分子分型乳腺癌CEUS具有一定特征性,CEUS典型图像特征可协助鉴别乳腺癌的分子分型。

原发性气管支气管腺样囊性癌的研究进展

原发性气管支气管腺样囊性癌(primary tracheobronchial adenoid cystic carcinoma, TACC)是一种罕见的非小细胞肺癌,仅占所有肺恶性肿瘤的0.1%~0.2%。按照2021版世界卫生组织(world health organization, WHO)肺肿瘤组织学分类,该肿瘤属于唾液腺型肿瘤。该疾病临床表现及影像学无特异性,易被延误诊治,确诊需病理,分期尚无公认标准,治疗首选手术,术后或不能手术者可行放疗,单纯全身治疗(化疗、靶向、免疫)效果差。该文对TACC从命名和组织学分类、临床特征、影像学、病理、分期、治疗和预后共七个方面进行了综述。