Malignant extra-gastrointestinal stromal tumor of the pancreas:Report of two cases and review of the literature

Gastrointestinal stromal tumors(GISTs)are mesenchymal tumors that arise from the gastrointestinal tract.In rare cases,these tumors are found in intra-abdominal sites unrelated to the gastrointestinal tract,such as the mesentery,omentum and retroperitoneum.However,pancreatic extra-gastrointestinal stromal tumors are extremely rare,with only 14 previous cases reported.A 61-year-old man with no clinical symptoms had a routine check-up,during which an abdominal mass located in the pancreas tail was detected.Abdominal surgery was performed with resection of the pancreas tail and the spleen,and he was diagnosed with lowrisk GISTs.Another 60-year-old man with no clinical symptoms underwent Computed tomography which revealed a well-demarcated tumor,6 cm in diameter,in the head of the pancreas.He was diagnosed with pancreatic GISTs.Here,we describe two rare cases of pancreatic GISTs and review the cases previously reported in the literature.

Giant hepatic extra-gastrointestinal stromal tumor treated with cytoreductive surgery and adjuvant systemic therapy:A case report and review of literature

BACKGROUND Primary extra-gastrointestinal stromal tumors(E-GIST)of the liver are rare.The clinical presentation may range from asymptomatic to bleeding or manifestations of mass effect.Oncologic surgery followed by adjuvant therapy with imatinib is the standard of care.However,under specific circumstances,a cytoreductive approach may represent a therapeutic option.We describe herein the case of an 84-year-old woman who presented with a tender,protruding epigastric mass.Abdominal computed tomography scan revealed a large,heterogeneous mass located across segments III,IV,V,and VIII of the liver.The initial approach was transarterial embolization of the tumor,which elicited no appreciable response.Considering the large size and central location of the tumor and the advanced age of the patient,non-anatomic complete resection was indicated.Due to substantial intraoperative bleeding and hemodynamic instability,only a near-complete resection could be achieved.Histopathology and immunohistochemical staining confirmed the diagnosis of primary E-GIST of the liver.Considering the risk/benefit ratio for therapeutic options,debulking surgery may represent a strategy to control pain and prolong survival.CASE SUMMARY Here,we present a case report of a patient diagnosed with E-GIST primary of the liver,which was indicated a cytoreductive surgery and adjuvant therapy with imatinib.CONCLUSION E-GIST primary of the liver is a rare conditional,the treatment is with systemic therapy and total resection surgery.However,a cytoreductive surgery will be necessary when a complete resection is no possible.

Primary Extra-Gastrointestinal Stromal Tumor (GIST) arising from mesentery of small bowel and presenting as abdominal mass: A rare entity

Introduction: Majority of mesenchymal tumors of gastrointestinal tract are Gastrointestinal Stromal Tumor (GIST). It is, however, a rare tumor, accounting for less than 1% of primary gastrointestinal (GI) neoplasms. Though, these tumors are refractory to conventional chemotherapy or radiotherapy but show a good response to targeted adjuvant chemotherapy with tyrosine kinase inhibitors following surgical resection. Case Report: we report here a case of primary Extra-GIST tumor arising from mesentry of small bowel near duodeno-jejunal junction in a 69 years old male patient. The patient presented with a palpable mass in upper abdomen for past 15 days. On examination, a non-tender mobile lump of size around 17 × 10 cm, with bosselated surface and firm in consistency was palpable involving epigastric, left hypochondrium and umbilical region. Contrast enhanced computed tomography of abdomen revealed a heterogenous mesentric mass. On surgical intervention a mass was found involving mesentery near dudenojejunal junction without involvement of gastrointestinal tract. Complete surgical resection of the tumor was done and adjuvant chemotherapy with Imatinib mesylate was started as HPE revealing GIST with mitotic index of >10/50 HPF and 17 × 10 cm size placed the patient in high risk category. Patient was discharged on 12th of post-operative day with advice of regular follow-up. Conclusion: GIST occurrence is not restricted to bowel but can involve unusual sites also. The mainstay of treatment remains surgical resection with adequate margin. In cases where tumour has malignant potential (high mitotic figures on histopathology) adjuvent treatment with tyrosine kinase may prevent or delay relapse.

Correlation of tumor-associated macrophage density and proportion of M2 subtypes with the pathological stage of colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a prevalent global malignancy with complex prognostic factors.Tumor-associated macrophages(TAMs)have shown paradoxical associations with CRC survival,particularly concerning the M2 subset.AIM We aimed to establish a simplified protocol for quantifying M2-like TAMs and explore their correlation with clinicopathological factors.METHODS A cross-sectional study included histopathological assessment of paraffinembedded tissue blocks obtained from 43 CRC patients.Using CD68 and CD163 immunohistochemistry,we quantified TAMs in tumor stroma and front,focusing on M2 proportion.Demographic,histopathological,and clinical parameters were collected.RESULTS TAM density was significantly higher at the tumor front,with the M2 proportion three times greater in both zones.The tumor front had a higher M2 proportion,which correlated significantly with advanced tumor stage(P=0.04),pathological nodal involvement(P=0.04),and lymphovascular invasion(LVI,P=0.01).However,no significant association was found between the M2 proportion in the tumor stroma and clinicopathological factors.CONCLUSION Our study introduces a simplified protocol for quantifying M2-like TAMs in CRC tissue samples.We demonstrated a significant correlation between an increased M2 proportion at the tumor front and advanced tumor stage,nodal involvement,and LVI.This suggests that M2-like TAMs might serve as potential indicators of disease progression in CRC,warranting further investigation and potential clinical application.

Spatiotemporal transformable nano-assembly for on-demand drug delivery to enhance anti-tumor immunotherapy

Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.

Different types of tumor microvessels in stageⅠ-ⅢA squamous cell lung cancer and their clinical significance

BACKGROUND Lung cancer(LC)is the leading cause of morbidity and mortality among malignant neoplasms.Improving the diagnosis and treatment of LC remains an urgent task of modern oncology.Previously,we established that in gastric,breast and cervical cancer,tumor microvessels(MVs)differ in morphology and have different prognostic significance.The connection between different types of tumor MVs and the progression of LC is not well understood.AIM To evaluate the morphological features and clinical significance of tumor MVs in lung squamous cell carcinoma(LUSC).METHODS A single-center retrospective cohort study examined medical records and archival paraffin blocks of 62 and 180 patients with stage I-IIIA LUSC in the training and main cohorts,respectively.All patients underwent radical surgery(R0)at the Orenburg Regional Cancer Clinic from May/20/2009 to December/14/2021.Tumor sections were routinely processed,and routine Mayer's hematoxylin and eosin staining and immunohistochemical staining for cluster of differentiation 34(CD34),podoplanin,Snail and hypoxia-inducible factor-1 alpha were performed.The morphological features of different types of tumor MVs,tumor parenchyma and stroma were studied according to clinicopathological characteristics and LUSC prognosis.Statistical analysis was performed using Statistica 10.0 software.Univariate and multivariate logistic regression analyses were performed to identify potential risk factors for LUSC metastasis to regional lymph nodes(RLNs)and disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with and without metastases in RLNs and those with and without disease recurrence.The effectiveness of the predictive models was assessed by the area under the curve.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.A value of P<0.05 was considered to indicate statistical significance.RESULTS Depending on the morphology,we classified tumor vessels into the following types:normal MVs,dilated capillaries(DCs),atypical DCs,DCs with weak expression of CD34,"contact-type"DCs,structures with partial endothelial linings,capillaries in the tumor solid component and lymphatic vessels in lymphoid and polymorphocellular infiltrates.We also evaluated the presence of loose,fine fibrous connective tissue(LFFCT)and retraction clefts in the tumor stroma,tumor spread into the alveolar air spaces(AASs)and fragmentation of the tumor solid component.According to multivariate analysis,the independent predictors of LUSC metastasis in RLNs were central tumor location(P<0.00001),the presence of retraction clefts(P=0.003),capillaries in the tumor solid component(P=0.023)and fragmentation in the tumor solid component(P=0.009),whereas the independent predictors of LUSC recurrence were tumor grade 3(G3)(P=0.001),stage N2(P=0.016),the presence of LFFCT in the tumor stroma(P<0.00001),fragmentation of the tumor solid component(P=0.0001),and the absence of tumor spread through the AASs(P=0.0083).CONCLUSION The results obtained confirm the correctness of our previously proposed classification of different types of tumor vessels and may contribute to improving the diagnosis and treatment of LUSC.

Prognostic significance of tumor budding,desmoplastic reaction,and lymphocytic infiltration in patients with gastric adenocarcinoma

BACKGROUND Recent studies have shown that the tumor microenvironment significantly influences the behavior of solid tumors.In this context,Accumulated data suggests that pathological evaluation of tumor budding(TB),desmoplastic reaction(DR),and tumor-infiltrating lymphocytes(TILs)may be crucial in determining tumor behavior in the gastrointestinal tract.Regarding gastric adenocarcinoma(GAC),although some results suggest that TB and TILs may be effective in determining the course of the disease,the data do not agree.Moreover,very few studies have investigated the relationship between DR and survival.At present,the associations between tumor TB,DR and TILs in GAC patients have not been determined.AIM To establish the relationships between TB,DR,and TILs in patients with GAC and to assess their influence on prognosis.METHODS Our study group comprised 130 patients diagnosed with GAC.The definition of TB was established based on the International TB Consensus Conference.The DR was categorized into three groups according to the level of tumor stroma maturation.The assessment of TILs was conducted using a semiquantitative approach,employing a cutoff value of 5%.The statistical analysis of the whole group and 100 patients with an intestinal subtype of GAC was performed using SPSS version 27.RESULTS A significant correlation between peritumoral budding(PTB)and intratumoral budding(ITB)was noted(r=0.943).Tumors with high PTBs and ITBs had a greater incidence of immature DRs and low TILs(P<0.01).PTB and ITB were associated with histological subtype,lymph node metastasis(LNM),and stage(P<0.01).ITB,PTB,LNM,DR,and stage were significant risk factors associated with poor prognosis.The multivariate Cox regression analysis identified ITB,PTB,and LNM as independent prognostic variables(P<0.05).In intestinal-type adenocarcinomas,a positive correlation between PTB and ITB was noted(r=0.972).While univariate analysis revealed that LNM,stage,PTB,ITB,and DR were strong parameters for predicting survival(P<0.05),only PTB and ITB were found to be independent prognostic factors(P<0.001).CONCLUSION TB may be a potential prognostic marker in GAC.However,further studies are needed to delineate its role in pathology reporting protocols and the predictive effects of DR and TILs.

Tumor-stroma crosstalk对肝细胞癌中肝星状细胞氨基酸代谢水平的影响

目的探讨tumor-stroma crosstalk对肝星状细胞(HSC)氨基酸代谢的影响。方法分别培养人肝癌细胞系HepG2、Hep3B、Huh7,以及LX-2 HSC。分别使用LX-2 HSC条件培养基(LX2-CM)和HepG2、Hep3B、Huh7肝癌细胞混合条件培养基(Hep-CM)培养HSC,并收集细胞上清,应用氨基酸分析仪检测细胞上清氨基酸谱变化。计量资料组间比较采用t检验。结果HSC氨基酸代谢水平改变情况,与对照组(LX2-CM)相比,实验组(Hep-CM)上清中瓜氨酸(t=3. 426,P=0. 027)、缬氨酸(t=2. 892,P=0. 045)、异亮氨酸(t=4. 224,P=0. 013)、亮氨酸(t=4. 150,P=0. 014)、酪氨酸(t=3. 556,P=0. 024)、苯丙氨酸(t=4. 023,P=0. 016)、赖氨酸(t=3. 369,P=0. 028)水平降低,差异均有统计学意义。结论肿瘤微环境中,tumor-stroma crosstalk可以影响HSC的氨基酸代谢水平,这种改变可能反过来促使肝癌细胞更加适应低氧微环境。

Micronodular thymic tumor with lymphoid stroma: A case report and review of the literature

BACKGROUND Micronodular thymic tumors with lymphoid stroma include micronodular thymoma with lymphoid stroma(MNT)and micronodular thymic carcinoma with lymphoid hyperplasia(MNC),whose micromorphological features are lymphoid stromal hyperplasia and nodular arrangement of tumor epithelial cells.This type of tumor is rare;therefore,the corresponding clinical guidelines,histopathological diagnostic criteria,prognostic factors,and therapeutic regimens have not been established.CASE SUMMARY This study covers a novel presentation of MNC in a patient and summarizes the clinicopathological characteristics of this type of tumor by using pooled-analysis methods.Morphologically,this tumor type is a series of benign to malignant pedigrees.We establish the following criteria for the classification of micronodular thymic tumors with lymphoid stroma:(1)Tumor cells with moderate-to-severe dysplasia;(2)Tumor cell mitotic figures>2/10 high-power fields;(3)Appearance of neoplastic necrosis;(4)No terminal deoxynucleotidyl transferase-positive immature T lymphocytes within the tumor;(5)Tumor cells with a Ki-67 index≥10%;and(6)Tumor cells express CD5.Cases that fall into the borders of two categories in terms of morphology are attributed to atypical MNT.It is proposed that the diagnosis of MNT should be established on the diagnostic criteria mentioned above.CONCLUSION Our diagnostic algorithm can effectively distinguish malignant tumors from benign tumors and provides a potent basis for predicting a prognosis,which offers a practical reference for oncologists and pathologists.

Therapeutic strategies for targeting the ovarian tumor stroma

Epithelial ovarian cancer is the most lethal type of gynecologic malignancy. Sixty percent of women who are diagnosed with ovarian cancer present with advancedstage disease that involves the peritoneal cavity and these patients have a 5-year survival rate of less than 30%. For more than two decades, tumor-debulking surgery followed by platinum-taxane combination chemotherapy has remained the conventional first-line treatment of ovarian cancer. Although the initial response rate is 70%-80%, most patients with advancedstage ovarian cancer eventually relapse and succumb to recurrent chemoresistant disease. A number of molecular aberrations that drive tumor progression have been identified in ovarian cancer cells and intensive efforts have focused on developing therapeutic agents that target these aberrations. However, increasing evidence indicates that reciprocal interactions between tumor cells and various types of stromal cells also play important roles in driving ovarian tumor progression and that these stromal cells represent attractive therapeutic targets. Unlike tumor cells, stromal cells within the tumor microenvironment are in general geneticallystable and are therefore less likely to become resistant to therapy. This concise review discusses the biological significance of the cross-talk between ovarian cancer cells and three major types of stromal cells(endothelial cells, fibroblasts, macrophages) and the development of new-generation therapies that target the ovarian tumor microenvironment.

Tumor–stromal cross-talk modulating the therapeutic response in pancreatic cancer

Background: Pancreatic ductal adenocarcinoma(PDAC) is a highly malignant solid tumor with a dismal prognosis. The stroma component makes up to 90% of the tumor mass and is thought to be one of the main reasons for the tumor’s high chemoresistance. Cancer associated fibroblasts(CAFs) have previously been identified to be the key stromal players. This is the first time we provide detailed in vitro experiments investigating tumor–stromal interactions when exposed to three well-known chemotherapeutic agents. Methods: Monocultures, indirect and direct co-cultures of two PDAC cell lines(AsPC and Panc-1) and six primary patients derived CAFs were treated with gemcitabine, nab-paclitaxel and the γ-secretaseinhibitor(GSI) DAPT. The cell viability of each component was measured with XTT. Finally, IL-6 concentrations of the supernatants were analyzed. Results: On the contrary to PDAC cell lines, CAF monocultures hardly responded to any treatment which suggested that stroma(CAFs) itself is more resistant to standard chemo-treatments than the epithelial cancer cells. Moreover, only a weak chemotherapeutic response was observed in direct co-cultures of cancer cells with CAFs. A change in the morphology of direct co-cultures was accompanied with the chemoresistance. CAFs were observed to build cage-like structures around agglomerates of tumor cells. High levels of IL-6 were also associated with a reduced response to therapy. Indirect co-cultures make the tumor–stromal interaction more complex. Conclusions: CAFs are highly chemoresistant. Direct cell–cell contact and high levels of IL-6 correlate with a high chemoresistance.

Stem cell-derived exosomes： roles （I）CrossMarkin stromal remodeling, tumor progression,and cancer immunotherapy

Stem cells are known to maintain sternness at least in part through secreted factors that promote stem-like phenotypesin resident cells. Accumulating evidence has clarified that stem cells release nano-vesicles, known as exosomes,which may serve as mediators of cell-to-cell communication and may potentially transmit stem cell phenotypes torecipient cells, facilitating stem cell maintenance, differentiation, self-renewal, and repair. It has become apparent thatstem cell-derived exosomes mediate interactions among stromal elements, promote genetic instability in recipientcells, and induce malignant transformation. This review will therefore discuss the potential of stem cell-derivedexosomes in the context of stromal remodeling and their ability to generate cancer-initiating cells in a tumor nicheby inducing morphologic and functional differentiation of fibroblasts into tumor-initiating fibroblasts. In addition, theimmunosuppressive potential of stem cell-derived exosomes in cancer immunotherapy and their prospective applicationsin cell-free therapies in future translational medicine is discussed.

Pancreatic extragastrointestinal stromal tumor:A case report and comprehensive literature review

AIM: To provide an overview of the literature on pan-creatic extragastrointestinal stromal tumors(EGISTs).METHODS: We report a case of pancreatic EGIST and review published studies on pancreatic EGIST ac-cessed via the PubMed, MEDlInE, Google Scholar, and Google databases. The keywords used were "pancreas and GIST", "pancreas and extra GIST", "pancreas and gastrointestinal stromal tumor", and "pancreas and ex-tragastrointestinal stromal tumor". literature reviews and/or duplicate studies were excluded. The search included articles published in the English language be-tween January 1, 2000 and May 15, 2014.RESULTS: From our literature survey, 30 manuscripts on pancreatic EGISTs were considered, of which 27met the search criteria and three were excluded. The studies involved 30 patients(15 men, 15 women) with a mean age of 55.3 ± 14.3 years(range 30-84 years). The mean age of the male patients was 50.8 ± 13.7 years(range 30-84 years); that of the female patients was 59.9 ± 13.3 years(range 38-81 years). Tumor dimensions were obtained for 28 cases(mean 114.4 ± 78.6 mm; range 20-350 mm). Tumors were diagnosed incidentally in 23.3% of patients; abdominal discomfort and weight loss were the major complaints in symp-tomatic patients. Risk of aggressive behavior according to Fletcher criteria was determined in 25 of 30 patients(68%: high risk, 28%: intermediate risk, 4%: low risk). Histopathological examination revealed the presence of spindle cells in 96.1% of cases; CD117 and CD34 were present immunohistochemically in 96.6% and 84% of patients, respectively. The most common surgical pro-cedures were distal pancreatectomy with splenectomy(n = 9) and pancreaticoduodenectomy(n = 7). The to-tal follow-up period for the 28 patients ranged from 3-66 mo, during which locoregional or distant metastases were diagnosed in six patients and two patients died.CONCLUSION: Studies on EGISTs have only been published in the last decade. The lack of studies with large patient cohorts and long-term follow-up limits evidence-based commentary. In theory, each case should be assessed individually and further genetic and immunohistochemical studies are needed.

Hepatic gastrointestinal stromal tumor: Systematic review of an exceptional location

BACKGROUND A minor subset of primary gastrointestinal stromal tumors(GIST)can also arise outside the gastrointestinal tract,which is known as an extra-GIST(E-GIST).Primary GIST of the liver is an exceptional location.AIM To characterize epidemiological,clinical and pathological features and options of treatments.METHODS We performed a systematic review to search for articles on primary hepatic GIST.RESULTS This review shows that right hepatic lobe was the most frequent location.Regarding pathological and immunohistochemical features,mitotic count was≥5/50 High Power Fields in more than 50%;and CD117 was negative in only 1 patient.More than 70%of patients had a lesion with high risk of malignancy.CONCLUSION The diagnosis of E-GIST must be considered in a liver mass.Rendering an accurate diagnosis is a challenge,as well as the confirmation of their primary or metastatic nature.

Primary Hepatic Extra-gastrointestinal Stromal Tumors:Molecular Pathogenesis,Immunohistopathology,and Treatment

Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract.They originate from the interstitial cells of Cajal and are usually found in extrahepatic gastrointestinal sites.However,a small subset are derived from the liver and are known as primary hepatic gastrointestinal stromal tumors(PHGIST).They have a poor prognosis and are historically difficult to diagnose.Our objective was to review and update the latest evidence-based knowledge concerning PHGIST,with a focus on epidemiology,etiology,pathophysiology,clinical presentation,histopathology,and treatment.These tumors are usually found incidentally,occur sporadically,and are associated with mutations of KIT and PDGFRA genes.PHGIST is a diagnosis of exclusion,as it has the same molecular,immunochemistry and histological appearance as gastrointestinal stromal tumors(GIST).Thus,imaging,such as positron emission tomography-computed tomography(PET-CT)must be used to rule out metastatic GIST before a diagnosis can be made.However,with mutation analysis and pharmacological advances,tyrosine kinase inhibitors are typically pursued with or without surgical intervention.Other potential treatments include transcatheter arterial chemoembolization and tumor ablation.However,these are typically considered palliative options.As there are only a limited number of publications regarding PHGIST,data concerning morbidity and mortality are not yet available.Immunohistopathology can help develop screening guidelines and evaluating resistance to treatment.

Advances in the study of the effect of tumor stromal cells on oral cancer

Oral squamous cell carcinoma (OSCC) is the most common malignant tumour in oral and maxillofacial region. The interaction between stromal cells and tumor cells is involved in the proliferation, differentiation, apoptosis, adhesion and migration of tumor cells, and is closely related to the malignant degree and prognosis of tumors. The development of OSCC is of great significance to the treatment of OSCC. This paper summarizes the sources of several important stromal cells and their effects on tumor cells, which provides a theoretical basis for the treatment of OSCC.

How the interplay among the tumor microenvironment and the gut microbiota influences the stemness of colorectal cancer cells

Colorectal cancer(CRC)remains the third most prevalent cancer disease and involves a multi-step process in which intestinal cells acquire malignant characteristics.It is well established that the appearance of distal metastasis in CRC patients is the cause of a poor prognosis and treatment failure.Nevertheless,in the last decades,CRC aggressiveness and progression have been attributed to a specific cell population called CRC stem cells(CCSC)with features like tumor initiation capacity,self-renewal capacity,and acquired multidrug resistance.Emerging data highlight the concept of this cell subtype as a plastic entity that has a dynamic status and can be originated from different types of cells through genetic and epigenetic changes.These alterations are modulated by complex and dynamic crosstalk with environmental factors by paracrine signaling.It is known that in the tumor niche,different cell types,structures,and biomolecules coexist and interact with cancer cells favoring cancer growth and development.Together,these components constitute the tumor microenvironment(TME).Most recently,researchers have also deepened the influence of the complex variety of microorganisms that inhabit the intestinal mucosa,collectively known as gut microbiota,on CRC.Both TME and microorganisms participate in inflammatory processes that can drive the initiation and evolution of CRC.Since in the last decade,crucial advances have been made concerning to the synergistic interaction among the TME and gut microorganisms that condition the identity of CCSC,the data exposed in this review could provide valuable insights into the biology of CRC and the development of new targeted therapies.

肿瘤间质比在口腔鳞状细胞癌患者预后评估中的价值分析

目的:分析肿瘤间质比(tumor-stroma ratio,TSR)在口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)患者预后中的价值。方法:收集2015年1月~2017年12月在蚌埠医学院第一附属医院接受根治性切除术的OSCC患者为研究对象,并收集临床及病理资料。TSR以50%为界限,将其分为高间质比组(≥50%)及低间质比组(<50%)。分析TSR和OSCC患者的无病生存期及总生存期之间的关系。结果:术后随访及临床资料完整的98例患者中,高间质比患者42例,低间质比患者56例。高间质比组OSCC患者的5年总生存率以及5年无病生存率分别为31.0%(13/42)、26.2%(11/42);低间质比组OSCC患者的5年总生存率以及5年无病生存率分别为73.2%(41/56)、67.9%(38/56)。肿瘤发病部位与患者的5年总生存率(χ^(2)=1.327,P=0.932)及5年无病生存率(χ^(2)=3.113,P=0.683)无关;肿瘤临床分期、TSR与患者的5年总生存率5年无病生存率显著相关(P<0.001)。单因素COX分析结果显示,年龄、肿瘤T分期、淋巴结转移、TSR与OSCC患者总体生存率以及无病生存率有关。而通过多因素COX研究显示,肿瘤T分期、淋巴结转移以及TSR是影响OSCC患者总生存率与无病生存率的独立危险因素(P<0.05)。结论:TSR可作为OSCC患者术后预后的影响因素,可为OSCC患者术后辅助治疗方法的选择提供参考依据。

Pancreatic cancer stroma:understanding biology leads to new therapeutic strategies

Pancreatic ductal adenocarcinoma(PDA)is among the deadliest cancers in the United States and in the world.Late diagnosis,early metastasis and lack of effective therapy are among the reasons why only 6%of patients diagnosed with PDA survive past 5 years.Despite development of targeted therapy against other cancers,little progression has been made in the treatment of PDA.Therefore,there is an urgent need for the development of new treatments.However,in order to proceed with treatments,the complicated biology of PDA needs to be understood first.Interestingly,majority of the tumor volume is not made of malignant epithelial cells but of stroma.In recent years,it has become evident that there is an important interaction between the stromal compartment and the less prevalent malignant cells,leading to cancer progression.The stroma not only serves as a growth promoting source of signals but it is also a physical barrier to drug delivery.Understanding the tumor-stroma signaling leading to development of desmoplastic reaction and tumor progression can lead to the development of therapies to decrease stromal activity and improve drug delivery.In this review,we focus on how the current understanding of biology of the pancreatic tumor microenvironment can be translated into the development of targeted therapy.

Tumor stem cell, or its niche, which plays a primary role in tumorigenesis?

Cancer research over the past decades has focused on neoplastic cells, or a fraction of them, i.e. tumor stem cells, as the ultimate causes of tumorigenesis. However, during recent years, scientists have come to realize that tumorigenesis is not a solo act of neoplastic cells, but rather a cooperative process in which the roles of numerous types of non-neoplastic cells should be recognized. These tumor-residing non-neoplastic cells constitute the so-called tumor-associated stroma, which in certain cases even greatly surpasses the neoplastic cellular compartment that was previously thought of as a sole determiner leading to a seemingly autonomous growth pattern. In this review, we summarize several recent research highlights that have unveiled many previously unappreciated roles for microenvironmental factors, especially during the initiation stage of tumorigenesis. It is becoming increasingly clear that the stroma’s regulatory effects constitute not only an essential force for maintaining tumor growth, but also primary causes initiating tumorigenesis.