Mixed neuroendocrine and adenocarcinoma of gastrointestinal tract:A complex diagnosis and therapeutic challenge

In this editorial we comment on the manuscript describing a case of adenocarcinoma mixed with a neuroendocrine carcinoma of the gastroesophageal junction.Mixed neuroendocrine and non-neuroendocrine neoplasms of the gastrointestinal system are rare heterogeneous group of tumors characterized by a high malignant potential,rapid growth,and poor prognosis.Due to the rarity of these cancers,the standard therapy is poorly defined.The diagnosis of these tumors is based on combination of morphological features,immunohistochemical and neuroendocrine and epithelial cell markers.Both endocrine and epithelial cell components can act independently of each other and thus,careful grading of each component separately is required.These cancers are aggressive in nature and the potential of each component has paramount importance in the choice of treatment and response.Regardless of the organ of origin,these tumors portend poor prognosis with increased proportion of neuroendocrine component.Multidisciplinary services and strategies are required for the management of these mixed malignancies to provide the best oncological outcomes.The etiopathogenesis of these mixed tumors remains obscure but poses interesting question.We briefly discuss a few salient points in this editorial.

Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract

Mixed neuroendocrine non-neuroendocrine neoplasms(MiNENs)are a hetero-geneous group of malignant neoplasms that can settle in the gastroenteropan-creatic tract.They are composed of a neuroendocrine(NE)and a non-NE compo-nent in at least 30%of each tumour.The non-NE component can include different histological combinations of glandular,squamous,mucinous and sarcomatoid phenotypes,and one or both of the components can be low-or high grade malignant.Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion,and the lack of specific clinical trials is the main reason why their management is difficult.The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data.It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that,due to their low incidence,will require long recruitment periods.

Mixed adenoneuroendocrine carcinoma of gastrointestinal tract: Report of two cases

Mixed adenoneuroendocrine carcinoma(MANEC) is a rare tumor of the gastrointestinal tract that consists of a dual adenocarcinomatous and neuroendocrine differentiation, each component representing at least 30% of the tumor. To date, only seven cases have been reported in the cecum, and less than 40 in the stomach. Our first case was diagnosed in a 74-years-old female as a polypoid lesion of the cecum with direct invasion in the transverse colon, without lymph node metastases. The second case was diagnosed in the stomach of a 46-years-old male as a polypoid tumor of the antral region that invaded the pancreas and presented metastases in 22 regional lymph nodes. The metastatic tissue was represented by the glandular component. In both cases, the tumor consisted of a moderately-differentiated tubular adenocarcinoma(with mucinous component in Case 1) intermingled with neuroendocrine carcinoma. Ki67 index was lower than 20% in Case 1, respectively higher than 20% in Case 2. The neuroendocrine component was marked by synaptophysin and neuron specific enolase, being negative for Keratins 7/20. The neuroendocrine component represented 60% in Case 1, and 40% in Case 2, respectively. The glandular components were marked by carcinoembryonic antigen, maspin and keratin 20/7(Case 1/2). Both cases were proved to be microsatellite stable. Independently by the localization and tumor stage, MANECs appear to be highly malignant tumors, with high risk for distant metastases. The aggressiveness seems to depend on the endocrine component, independent of its proportion. The neuroendocrine component could be a dedifferentiated adenocarcinoma with a neuroendocrine phenotype.

Total pancreatectomy for metachronous mixed acinar-ductal carcinoma in a remnant pancreas

In October 2009, a 71-year-old female was diagnosed with a cystic tumor in the tail of the pancreas with an irregular dilatation of the main pancreatic duct in the body and tail of the pancreas. A distal pancreatectomy with splenectomy, and partial resection of the duodenum, jejunum and transverse colon was performed. In March 2011, a follow-up computed tomography scan showed a low density mass at the head of the remnant pancreas. We diagnosed it as a recurrence of the tumor and performed a total pancreatectomy for the remnant pancreas. In the histological evaluation of the resected specimen of the distal pancreas, the neoplastic cells formed an acinar and papillary structure that extended into the main pancreatic duct.Mucin5AC, α1-antitrypsin(α-AT) and carcinoembryonic antigen(CEA) were detected in the tumor cells by immunohistochemistry. In the resected head of the pancreas, the tumor was composed of both acinar and ductal elements with a mottled pattern. The proportions of each element were approximately 40% and 60%, respectively. Strongly positive α-AT cells were detected in the acinar element. Some tumor cells were also CEA positive. However, the staining for synaptophysin and chromogranin A was negative in the tumor cells. Ultimately, we diagnosed the tumor as a recurrence of mixed acinar-ductal carcinoma in the remnant pancreas. In conclusion, we report here a rare case of repeated pancreatic resection for multicentric lesions of mixed acinar-ductal carcinoma of the pancreas.

Application value of mixed reality in hepatectomy for hepatocellular carcinoma

BACKGROUND As a new digital holographic imaging technology,mixed reality(MR)technology has unique advantages in determining the liver anatomy and location of tumor lesions.With the popularization of 5 G communication technology,MR shows great potential in preoperative planning and intraoperative navigation,making hepatectomy more accurate and safer.AIM To evaluate the application value of MR technology in hepatectomy for hepatocellular carcinoma(HCC).METHODS The clinical data of 95 patients who underwent open hepatectomy surgery for HCC between June 2018 and October 2020 at our hospital were analyzed retrospectively.We selected 95 patients with HCC according to the inclusion criteria and exclusion criteria.In 38 patients,hepatectomy was assisted by MR(Group A),and an additional 57 patients underwent traditional hepatectomy without MR(Group B).The perioperative outcomes of the two groups were collected and compared to evaluate the application value of MR in hepatectomy for patients with HCC.RESULTS We summarized the technical process of MR-assisted hepatectomy in the treatment of HCC.Compared to traditional hepatectomy in Group B,MR-assisted hepatectomy in Group A yielded a shorter operation time(202.86±46.02 min vs 229.52±57.13 min,P=0.003),less volume of bleeding(329.29±97.31 mL vs 398.23±159.61 mL,P=0.028),and shorter obstructive time of the portal vein(17.71±4.16 min vs 21.58±5.24 min,P=0.019).Group A had lower alanine aminotransferas and higher albumin values on the third day after the operation(119.74±29.08 U/L vs 135.53±36.68 U/L,P=0.029 and 33.60±3.21 g/L vs 31.80±3.51 g/L,P=0.014,respectively).The total postoperative complications and hospitalization days in Group A were significantly less than those in Group B[14(37.84%)vs 35(60.34%),P=0.032 and 12.05±4.04 d vs 13.78±4.13 d,P=0.049,respectively].CONCLUSION MR has some application value in three-dimensional visualization of the liver,surgical planning,and intraoperative navigation during hepatectomy,and it significantly improves the perioperative outcomes of hepatectomy for HCC.

Goblet cell carcinoid of the appendix and mixed adenoneuroendocrine carcinoma: Report of three cases

Neuroendocrine neoplasms are the most common epithelial tumors among appendix tumors. Appendix tumors that are completely or partially composed of neuroendocrine cells are divided into two categories: Classic carcinoid tumors and goblet cell carcinoid tumors(GCCT). They are known to progress more aggressively than classic(neuro) endocrine tumors. In this study, three cases with acute appendicitis symptoms are presented, including their clinical and histopathological findings. Microscopic examination detected GCCT in two cases and mixed adenoneuroendocrine carcinoma in one case, in addition to acute appendicitis.

Differential analysis of lymph node metastasis in histological mixed-type early gastric carcinoma in the mucosa and submucosa

AIM To investigate the relationship between histological mixed-type of early gastric cancer(EGC) in the mucosa and submucosa and lymph node metastasis(LNM).METHODS This study included 298 patients who underwent gastrectomy for EGC between 2005 and 2012. Enrolled lesions were divided into groups of pure differentiated(pure D), pure undifferentiated(pure U), and mixed-type according to the proportion of the differentiated and undifferentiated components observed under a microscope. We reviewed the clinicopathological features, including age, sex, location, size, gross type, lymphovascular invasion, ulceration, and LNM, among the three groups. furthermore, we evaluated the predictors of LNM in the mucosa-confined EGC.RESULTS Of the 298 patients, 165(55.4%) had mucosa-confined EGC and 133(44.6%) had submucosa-invasive EGC. Only 13(7.9%) cases of mucosa-confined EGC and 30(22.6%) cases of submucosa-invasive EGC were observed to have LNM. The submucosal invasion(OR = 4.58, 95%CI: 1.23-16.97, P = 0.023), pure U type(OR = 4.97, 95%CI: 1.21-20.39, P = 0.026), and mixedtype(OR = 5.84, 95%CI: 1.05-32.61, P = 0.044) were independent risk factors for LNM in EGC. The rate of LNM in mucosa-confined EGC was higher in the mixedtype group(P = 0.012) and pure U group(P = 0.010) than in the pure D group, but no significant difference was found between the mixed-type group and pure U group(P = 0.739). Similarly, the rate of LNM in the submucosa-invasive EGC was higher in the mixedtype(P = 0.012) and pure U group(P = 0.009) than in the pure D group but was not significantly different between the mixed-type and pure U group(P = 0.375). Multivariate logistic analysis showed that only female sex(OR = 5.83, 95%CI: 1.64-20.70, P = 0.028) and presence of lymphovascular invasion(OR = 13.18, 95%CI: 1.39-125.30, P = 0.020) were independent risk factors for LNM in mucosa-confined EGC, while histological type was not an independent risk factor for LNM in mucosa-confined EGC(P = 0.106).CONCLUSION for mucosal EGC, histological mixed-type is not an independent risk factor for LNM and could be managed in the same way as the undifferentiated type.

Neuroendocrine carcinoma of the common hepatic duct coexisting with distal cholangiocarcinoma:A case report and review of literature

BACKGROUND Neuroendocrine carcinoma(NEC)of the extrahepatic bile duct is very rare,and the treatment and prognosis are unclear.Herein,we report the case of a middleaged female with primary large cell NEC(LCNEC)of the common hepatic duct combined with distal cholangiocarcinoma(dCCA).Additionally,after a review of the relevant literature,we summarize and compare mixed neuroendocrine-nonneuroendocrine neoplasm(MiNEN)and pure NEC to provide a reference for selecting the appropriate treatment and predicting the prognosis of this rare disease.CASE SUMMARY A 62-year-old female presented to the hospital due to recurrent abdominal pain for 2 months.Physical examination showed mild tenderness in the upper abdomen and a positive Courvoisier sign.Blood tests showed elevated liver transaminase and carbohydrate antigen 199 levels.Imaging examination revealed node dissection was performed,and hepatic duct tumours were unexpectedly found during surgery.Pathology suggested poorly differentiated LCNEC(approximately 0.5 cm×0.5 cm×0.4 cm),Ki-67(50%),synaptophysin+,and chromogranin A+.dCCA pathology suggested moderately differentiated adenocarcinoma.The patient eventually developed lymph node metastasis in the liver,bone,peritoneum,and abdominal cavity and died 24 months after surgery.Gene sequencing methods were used to compare gene mutations in the two primary bile duct tumours.CONCLUSION The prognosis of MiNEN and pure NEC alone is different,and the selection of treatment options needs to be differentiated.

Mixed neuroendocrine carcinoma of the gastric stump: A case report

BACKGROUND Gastric stump cancer,also known as gastric remnant cancer(GRC),is one of the main complications of postgastrectomy syndrome,which usually occurs following Billroth II reconstruction.The predominant histological subtype of GRC is adenocarcinoma,whereas neuroendocrine carcinoma is relatively rare.In particular,there are few recently reported cases of mixed neuroendocrine carcinoma(MNEC)in the English literature.Here,we present an extremely rare case of MNEC of the gastric stump.CASE SUMMARY A 59-year-old patient presented to our department owing to chronic constipation.He had undergone subtotal gastric resection 35 years prior to admission because of benign peptic ulcer.After admission,the patient underwent several tests,and gastroendoscopy showed evidence of Billroth II gastrectomy and local thickening of the gastric stump mucosa at the gastrojejunostomy site,with bile reflux;pathological biopsy revealed adenocarcinoma.He was then diagnosed with GRC and underwent total gastrectomy,D2 Lymphadenectomy,and esophagojejunal Roux-en-Y reconstruction.Histopathological examination of the specimen identified MNEC comprising MNEC(60%),adenocarcinoma(30%),and squamous cell carcinoma(10%).Postoperative adjuvant chemotherapy was initiated on September 17,2020.Taxol plus cisplatin was administered for only one cycle because of severe liver function damage,and the regimen was changed to etoposide plus cisplatin on October 10,2020 for five cycles.The patient recovered,with no recurrence after 6 mo of follow-up.CONCLUSION Gastric MNECs(GMNECs)is a rare type of GRC.This study presented the unusual occurrence of GMNEC in the gastric stump.This case will contribute to improvements in our understanding of the carcinogenesis,biology,pathology,and behavior of GMNEC and GRC.

Mixed epithelial endocrine neoplasms of the colon and rectum–An evolution over time:A systematic review

BACKGROUND Mixed tumors of the colon and rectum,composed of a combination of epithelial and endocrine elements of benign and malignant potential are rare neoplasms.These can occur anywhere in the gastrointestinal tract and are often diagnosed incidentally.Though they have been a well-documented entity in the pancreas,where the exocrine-endocrine mixed tumors have been known for a while,recognition and accurate diagnosis of these tumors in the colon and rectum,to date,remains a challenge.This is further compounded by the different terminologies that have been attributed to these lesions over the years adding to increased confusion and misclassification.Therefore,dedicated literature reviews of these lesions in the colon and rectum are inconsistent and are predominantly limited to case reports and case series of limited case numbers.Though,most of these tumors are high grade and of advanced stage,intermediate and low grade lesions of these mixed tumors are also increasingly been reported.There are no established independent consensus based guidelines for the therapeutic patient management of these unique lesions.AIM To provide a comprehensive targeted literature review of these complex mixed tumors in the colon and rectum that chronicles the evolution over time with summarization of historical perspectives of terminology and to further our understanding regarding their pathogenesis including genomic landscape,clinicoradiological features,pathology,treatment,prognosis,the current status of the management of the primary lesions,their recurrences and metastases.METHODS A comprehensive review of the published English literature was conducted using the search engines PubMed,MEDLINE and GOOGLE scholar.The following search terms[“mixed tumors colon”OR mixed endocrine/neuroendocrine tumor/neoplasm/lesion colon OR adenocarcinoma and endocrine/neuroendocrine tumor colon OR mixed adenocarcinoma and endocrine/neuroendocrine carcinoma colon OR Amphicrine tumors OR Collision tumors]were used.Eligibility criteria were defined and all potential relevant items,including full articles and/or abstracts were independently reviewed,assessed and agreed upon items were selected for in-depth analysis.RESULTS In total 237 full articles/abstracts documents were considered for eligibility of which 45 articles were illegible resulting in a total of 192 articles that were assessed for eligibility of which 139 have been selected for reference in this current review.This seminal manuscript is a one stop article that provides a detailed outlook on the evolution over time with summarization of historical perspectives,nomenclature,clinicoradiological features,pathology,treatment,prognosis and the current status of the management of both the primary lesions,their recurrences and metastases.Gaps in knowledge have also been identified and discussed.An important outcome of this manuscript is the justified proposal for a new,simple,clinically relevant,non-ambiguous terminology for these lesions to be referred to as mixed epithelial endocrine neoplasms(MEENs).CONCLUSION MEEN of the colon and rectum are poorly understood rare entities that encompass an extensive range of heterogeneous tumors with a wide variety of combinations leading to tumors of high,intermediate or low grade malignant potential.This proposed new revised terminology of MEEN will solve the biggest hurdle of confusion and misclassification that plagues these rare unique colorectal neoplasms thus facilitating the future design of multi institutional prospective randomized controlled clinical trials to develop and evaluate newer therapeutic strategies that are recommended for continued improved understanding and personal optimization of clinical management of these unique colorectal neoplasms.

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.

Clinicopathological features and prognostic factors associated with gastroenteropancreatic mixed neuroendocrine non-neuroendocrine neoplasms in Chinese patients

BACKGROUND The incidence of mixed neuroendocrine-non-neuroendocrine neoplasms(MiNEN)is low.To improve our understanding of this rare tumor type and optimally guide clinical treatment,associated risk factors,clinical manifestations,and prognosis must be explored.AIM To identify risk factors that influence the prognosis of patients with gastroenteropancreatic MiNEN(GEP-MiNEN).METHODS We retrospectively analyzed the clinical data of 46 patients who were diagnosed with GEP-MiNEN at the First Affiliated Hospital of Bengbu Medical College(Anhui,China)between January 2013 and December 2017.Risk factors influencing the prognosis of the patients were assessed using Kaplan-Meier curves and cox regression models.We compared the results with 55 randomly selected patients with gastroenteropancreatic GEP neuroendocrine tumors,47 with neuroendocrine carcinomas(NEC),and 58 with poorly differentiated adenocarcinoma.RESULTS Among the 46 patients with GEP-MiNEN,thirty-five had gastric tumors,nine had intestinal tumors(four in the small intestine and five in the colon and rectum),and two had pancreatic tumors.The median age of the patients was 66(41-84)years,and the male-to-female ratio was 2.83.Thirty-three(71.7%)patients had clinical stage III and IV cancers.Distant metastasis occurred in 14 patients,of which 13 had metastasis to the liver.The follow-up period was 11-72 mo,and the median overall survival was 30 mo.Ki-67 index≥50%,high proportion of NEC,lymph node involvement,distant metastasis,and higher clinical stage were independent risk factors affecting the prognosis of patients with GEP-MiNEN.The median overall survival was shorter for patients with NEC than for those with MiNEN(14 mo vs 30 mo,P=0.001),but did not significantly differ from those with poorly differentiated adenocarcinoma and MiNEN(30 mo vs 18 mo,P=0.453).CONCLUSION A poor prognosis is associated with rare,aggressive GEP-MiNEN.Ki-67 index,tumor composition,lymph node involvement,distant metastasis,and clinical stage are important factors for patient prognosis.

Mixed neuroendocrine-non-neuroendocrine neoplasms of the digestive system:A mini-review

Mixed neuroendocrine-non-neuroendocrine neoplasms(MiNENs)are rare mixed tumors containing both neuroendocrine(NE)and non-NE components.Each component must occupy at least 30%of the tumor volume by definition.Recent molecular evidence suggests MiNENs are clonal neoplasms and potentially harbor targetable mutations similar to conventional carcinomas.There have been multiple changes in the nomenclature and classification of MiNENs which has created some confusion among pathologists on how to integrate the contributions of each component in a MiNEN,an issue which in turn has resulted in confusion in communication with front-line treating oncologists.This mini review summarizes our current understanding of MiNENs and outline diagnosis,prognosis,and management of these neoplasms.The authors emphasize the importance of treating the most aggressive component of the tumor regardless of its percentage volume.

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.

Mixed epithelial and stromal tumour with extension to vesicoureteric junction

Mixed epithelial and stromal tumour(MEST)is an uncommon renal tumour with a tendency to protrude into the collecting system.We present a 50-year-old woman with a renal tumour extending up to the vesicoureteric junction(VUJ)who was suspected to have an upper tract transitional cell carcinoma for which a nephroureterectomy was performed.Histopathologic examination revealed a MEST arising from the kidney and extending up to the VUJ.To the best of our knowledge,this is the first report of a renal MEST with extension to the VUJ.

不同病理亚型胃印戒细胞癌的临床预后分析

目的探讨不同病理亚型胃印戒细胞癌(GSRC)患者的临床病理特征、预后及其影响因素。方法回顾性收集2016年1月-2018年12月兰州大学第二医院收治的经病理确诊的232例GSRC患者的临床资料。按照WHO诊断标准进行分类,其中胃纯印戒细胞癌(pGSRC)36例,胃混合印戒细胞癌(mGSRC)196例,随访截至2022年9月30日。应用Kaplan-Meier法进行生存分析,单因素及多因素Cox回归分析影响GSRC患者预后的危险因素。结果pGSRC和mGSRC患者中位生存时间分别为41.0(6.0~70.0)个月、24.0(2.0~74.0)个月。Kaplan-Meier生存分析显示,合并糖尿病、合并贫血、神经侵犯、脉管侵犯、T分期、N分期、GSRC病理类型、CA125和肿瘤直径可影响GSRC患者根治术后总生存期(OS)(P<0.05),而Her-2、是否接受化疗等对GSRC患者根治术后OS无明显影响(P>0.05)。单因素Cox回归分析显示,合并糖尿病(P=0.031)、合并贫血(P=0.028)、肿瘤直径>5 cm(P=0.009)、神经侵犯(P=0.002)、脉管侵犯(P=0.002)、病理类型为mGSRC(P=0.039)、T_(2)-T_(4)分期(P=0.001)、N_(1)-N_(4)分期(P=0.004)、p TNMⅢ期(P=0.044)、淋巴结清扫数目>30个(P=0.044)和CA125阳性(P=0.009)是GSRC患者根治术后预后的影响因素。多因素Cox回归分析显示,mGSRC病理类型(P=0.035)、T_(2)-T_(4)分期(P=0.003)和CA125阳性(P=0.010)是GSRC患者根治术后预后不良的独立危险因素。结论与pGSRC相比,mGSRC在确诊时pTNM分期较高,侵袭性较强,中位生存时间较短。mGSRC病理类型、T_(2)-T_(4)分期和CA125阳性是GSRC患者预后不良的独立危险因素。

结直肠癌组织miR-331-3p、MLLT10 mRNA表达变化及其临床意义

目的观察结直肠癌(CRC)组织微小RNA-331-3p(miR-331-3p)、混合谱系白血病转位辅因子10(MLLT10)mRNA表达变化,并探讨其表达与临床病理特征和上皮间质转化的关系。方法选择CRC患者156例,取术中获取的CRC组织及其配对的癌旁正常组织,采用实时荧光定量聚合酶链反应检测miR-331-3p、MLLT10mRNA表达以及上皮间质转化相关基因E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)、锌指转录因子Snail mRNA表达。比较CRC组织与癌旁正常组织miR-331-3p及MLLT10、E-cadherin、N-cadherin、Snail mRNA表达;分析CRC组织miR-331-3p、MLLT10 mRNA表达与临床病理特征的关系,二者表达的关系及其与E-cadherin、N-cadherin、Snail mRNA表达的关系。结果CRC组织MLLT10、N-cadherin、Snail mRNA相对表达量均高于癌旁正常组织,miR-331-3p、E-cadherin mRNA相对表达量均低于癌旁正常组织(P均<0.01)。CRC组织miR-331-3p、MLLT10 mRNA表达与TNM分期、淋巴结转移有关(P均<0.05),而与性别、年龄、肿瘤最大径、肿瘤位置、组织分化程度无关(P均>0.05)。Pearson相关分析显示,CRC组织miR-331-3p表达与MLLT10 mRNA表达呈负相关(r=-0.678,P<0.05);CRC组织miR-331-3p表达与E-cadherin mRNA表达呈正相关(r=0.589,P<0.05),与N-cadherin、Snail mRNA表达呈负相关(r分别为-0.712、-0.654,P均<0.05);CRC组织MLLT10 mRNA表达与E-cadherin mRNA表达呈负相关(r=-0.549,P<0.05),与N-cadherin、Snail mRNA表达呈正相关(r分别为0.668、0.714,P均<0.05)。结论CRC组织miR-331-3p低表达、MLLT10 mRNA高表达,二者表达与TNM分期、淋巴结转移以及上皮间质转化密切相关。

含有印戒细胞成分胃癌的临床病理特征及预后的研究进展

胃癌作为一项全球性健康挑战,特别是印戒细胞癌(SRCC)这一亚型,正呈现出不断上升的发病趋势。根据世界卫生组织(WHO)的标准,SRCC主要由超过50%的印戒细胞(SRC)构成。然而,临床上常见的胃癌往往只含有较少的SRC,进而形成了所谓的混合印戒细胞癌(mSRCC)。这种病变日益影响到年轻群体,尤其是年轻女性。研究显示,与SRCC相比,mSRCC患者的平均年龄通常更高。此外,性别因素在此类疾病中也显得格外重要,年轻女性更易患有胃SRCC和mSRCC。从生物学角度来看,胃纯SRCC与mSRCC之间差异显著,高SRC比例的胃癌拥有更好的肿瘤浸润深度、癌症分期、淋巴结转移、周围组织侵犯和切除率等多个方面。相比之下,胃mSRCC的预后通常不如纯SRCC。对于仅限于黏膜的早期胃SRCC,其淋巴结和远处转移风险较低,而晚期胃SRCC则显示出更强的侵袭性和较差的预后,SRC的百分比被强调为晚期胃癌的一个独立预后因素。本文综述了近年来关于含SRC成分的胃癌的临床与病理特征、预后等方面的研究进展,旨在为含SRC胃癌的深入研究和临床治疗策略提供基于证据的深入见解,以期为发展针对含有SRC的胃癌的更有效的综合治疗策略和定制化治疗方案提供科学依据和策略指导。

RIP1、MLKL蛋白在未分化甲状腺癌中的表达及临床意义

目的探讨受体相互作用蛋白激酶1(RIP1)、混合系激酶区域样蛋白(MLKL)在未分化甲状腺癌(ATC)中的表达及其临床意义。方法选取48例ATC患者为研究对象,检测手术标本组织中RIP1、MLKL的表达,收集患者临床病理参数并随访,统计分析RIP1、MLKL在ATC组织标本中的表达模式及对患者预后的影响。培养人未分化型甲状腺癌THJ-11T、THJ-16T、THJ-21T、ASH-3、BHT101细胞系、分化型甲状腺癌细胞系CAL-62、PDTC-1、正常人甲状腺细胞系Nthy-ori 3-1、HTORI-3,利用Western blot法及RT-PCR检测细胞系中RIP1、MLKL的蛋白mRNA的表达水平。结果(1)RT-PCR及Western blot检测显示,与正常人甲状腺细胞系及分化型甲状腺癌细胞系相比,未分化甲状腺癌细胞系中RIP1、MLKL蛋白和mRNA相对表达水平明显更高。(2)48例ATC患者中,14例起源于乳头状甲状腺癌(PTC),34例起源于滤泡状甲状腺癌(FTC)。肿瘤细胞表现出明显的多形性。形态学特征包括梭形细胞为主的肉瘤样及鳞状细胞样。(3)免疫组化染色显示,RIP1表达主要定位于ATC细胞膜。48例ATCs中有24例(50.0%)RIP1染色阳性。组织中含有混合岛状或低分化癌成分。MLKL阳性细胞核表达清晰,48例ATC患者中有29例(60.4%)患者MLKL染色阳性。(4)Kaplan-Meier生存分析显示,RIP1和MLKL过度表达会缩短ATC患者的无病生存期(DFS)(P<0.05),但对患者的总体生存率(OS)无明显影响(P>0.05)。Cox多因素分析显示,RIP1高表达、MLKL高表达、N分期、M分期均是影响ATC患者DFS的独立性危险因素(P<0.05)。结论RIP1、MLKL高表达与ATC的发生及DFS密切相关,或可作为ATC潜在的治疗靶点及预后预测的生物学标记物。