Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies.However,there is an extant void in the clinical guidelines concerning the mo...Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies.However,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion post-chemotherapy.Materials and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment.Furthermore,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen.Results:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological malignancies.Concurrently,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.展开更多
Prior research establishing that bone interacts in coordination with the bone marrow microenvironment(BMME)to regulate hematopoietic homeostasis was largely based on analyses of individual bone-associated cell populat...Prior research establishing that bone interacts in coordination with the bone marrow microenvironment(BMME)to regulate hematopoietic homeostasis was largely based on analyses of individual bone-associated cell populations.Recent advances in intravital imaging has suggested that the expansion of hematopoietic stem cells(HSCs)and acute myeloid leukemia cells is restricted to bone marrow microdomains during a distinct stage of bone remodeling.These findings indicate that dynamic bone remodeling likely imposes additional heterogeneity within the BMME to yield differential clonal responses.A holistic understanding of the role of bone remodeling in regulating the stem cell niche and how these interactions are altered in age-related hematological malignancies will be critical to the development of novel interventions.To advance this understanding,herein,we provide a synopsis of the cellular and molecular constituents that participate in bone turnover and their known connections to the hematopoietic compartment.Specifically,we elaborate on the coupling between bone remodeling and the BMME in homeostasis and age-related hematological malignancies and after treatment with bone-targeting approaches.We then discuss unresolved questions and ambiguities that remain in the field.展开更多
Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of adv...Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely curable.Over the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint inhibitors.Therapies aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor immunity.These therapies thus have shown promising results in many clinical trials alone or in combination.The efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical trials.Clinical trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC.Unfortunately,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients.To this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response.This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC.The underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.展开更多
In this editorial,we discuss the article by Agatsuma et al.We concentrate specifically on the current routinely used screening tests recommended by society guidelines and delve into the significance of early diagnosis...In this editorial,we discuss the article by Agatsuma et al.We concentrate specifically on the current routinely used screening tests recommended by society guidelines and delve into the significance of early diagnosis of colorectal cancer(CRC)and its substantial impact on both incidence and mortality rates.Screening is highly recommended,and an early diagnosis stands out as the most crucial predictor of survival for CRC patients.Therefore,it is essential to identify and address the barriers hindering adherence to screening measures,as these barriers can vary among different populations.Furthermore,we focus on screening strategy optimization by selecting high-risk groups.Patients with comorbidities who regularly visit hospitals have been diagnosed at an early stage,showing no significant difference compared to patients undergoing regular screening.This finding highlights the importance of extending screening measures to include patients with comorbidities who do not routinely visit the hospital.展开更多
In this editorial,we offer a summary of the risk associated with hepatitis B reactivation(HBVr)in the setting of both solid and hematologic malignancies treated with Bruton tyrosine kinase(BTK)inhibitors,with insights...In this editorial,we offer a summary of the risk associated with hepatitis B reactivation(HBVr)in the setting of both solid and hematologic malignancies treated with Bruton tyrosine kinase(BTK)inhibitors,with insights derived from current studies.Furthermore,we emphasize the critical need for a framework regarding robust risk evaluation in patients undergoing such treatments.This framework is essential for identifying those at increased risk of HBVr,enabling healthcare providers to implement proactive measures to prevent reactivation and ensure the safe administration of BTK inhibitor therapy.展开更多
BACKGROUND Cholecystoenteric fistula(CEF)involves the formation of a spontaneous ano-malous tract between the gallbladder and the adjacent gastrointestinal tract.Chronic gallbladder inflammation can lead to tissue nec...BACKGROUND Cholecystoenteric fistula(CEF)involves the formation of a spontaneous ano-malous tract between the gallbladder and the adjacent gastrointestinal tract.Chronic gallbladder inflammation can lead to tissue necrosis,perforation,and fistulogenesis.The most prevalent cause of CEF is chronic cholelithiasis,which rarely results from malignancy.Because the symptoms and laboratory findings associated with CEF are nonspecific,the condition is often misdiagnosed,pre-senting a challenge to the surgeon when detected intraoperatively.Therefore,a preoperative diagnosis of CEF is crucial.We present the case of a 57-year-old male with advanced gallbladder cancer(GBC)who arrived at the emergency room with persistent vomiting,abdominal pain,and diarrhea.An abdominopelvic computed tomography scan revealed a contracted gallbladder with bubbles in the fundus connected to the second por-tion of the duodenum and transverse colon.We suspected that GBC had invaded the adjacent gastrointestinal tract through a cholecystoduodenal fistula(CDF)or a cholecystocolonic fistula(CCF).He underwent multiple examinations,including esophagogastroduodenoscopy,an upper gastrointestinal series,colo-noscopy,and magnetic resonance cholangiopancreatography;the results of these tests con-firmed a diagnosis of synchronous CDF and CCF.The patient underwent a Roux-en-Y gastrojejunostomy and loop ileostomy to address the severe adhesions that were previously observed to cover the second portion of the duodenum and hepatic flexure of the colon.His symptoms improved with supportive treatment while hospitalized.He initiated oral targeted therapy with lenvatinib for further anticancer treatment.CONCLUSION The combination of imaging and surgery can enhance preoperative diagnosis and alleviate symptoms in patients with GBC complicated by CEF.展开更多
Background:Although bevacizumab is an important treatment for metastatic colorectal cancer(CRC),not allpatients with CRC benefit from it;in unselected patient populations,only modest survival benefits have been report...Background:Although bevacizumab is an important treatment for metastatic colorectal cancer(CRC),not allpatients with CRC benefit from it;in unselected patient populations,only modest survival benefits have been reported.Methods:We evaluated clinical outcomes in 110 patients using comprehensive molecular characterization to identifybiomarkers for a response to bevacizumab-containing treatment.The molecular analysis comprised whole-exomesequencing,ribonucleic acid sequencing,and a methylation array on patient tissues.Results:Genomic and molecularcharacterization was successfully conducted in 103 patients.Six of 103 CRC samples were hypermutated,and none ofthe non-hypermutant tumors were microsatellite unstable.Among those 103 patients,89 had adenocarcinoma(ADC),15 were diagnosed with mucinous ADC,and six had signet-ring cell carcinoma(SRCC).Consensus molecular subtype(CMS)2 was unique to ADC.Of the four SRCCs,two were CMS1,one was CMS4,and the other was CMS3.APCmutation status was a significantly enriched factor in responders to bevacizumab treatment.Fibroblast growth factorreceptor(FGFR)1/2 signaling was upregulated in non-responders,whereas cell cycle,transfer ribonucleic acidprocessing,nucleotide excision repair,and oxidative phosphorylation pathways were enriched in responders.Inaddition,IGF1 was differentially expressed in non-responders(log2 fold change=−1.43,p=4.11×10^(−5),falsediscovery rate=0.098),and FLT1 was highly methylated in non-responders(p=7.55×10^(−3)).When the molecularpathways were reanalyzed separately according to the backbone chemotherapy(FOLFOX vs.FOLFIRI),thesignificance of the molecular pathways varied according to the backbone chemotherapy.Conclusions:This studysought a subset of CRC patients with a distinct clinical response to chemotherapy containing bevacizumab.Ourresults need to be validated in a large group of homogenous patient cohort and examined according to the differentchemotherapy backbones to create personalized therapeutic opportunities in CRC.展开更多
早期肺癌患者的治疗是以治愈为目标的。针对手术可切除性和可操作性的多学科讨论模式决定了最终的局部治疗方式(手术或放疗)和相关的系统性治疗方案,从而进一步提高患者治愈的可能性。研究证据支持以顺铂为基础的辅助化疗用于切除术后,...早期肺癌患者的治疗是以治愈为目标的。针对手术可切除性和可操作性的多学科讨论模式决定了最终的局部治疗方式(手术或放疗)和相关的系统性治疗方案,从而进一步提高患者治愈的可能性。研究证据支持以顺铂为基础的辅助化疗用于切除术后,或与放疗同步使用。共识指南支持以新辅助化疗代替辅助化疗,并支持对不符合顺铂治疗条件的患者采用基于卡铂的治疗方案。由于研究设计效率低下,需要长时间随访来评估生存终点以及对晚期疾病的持续关注,将新药物(现在是IV期肺癌患者的标准药物)纳入以治愈为目标的治疗范式的工作一直滞后。目前正在研究中的替代性终点(例如病理缓解)将可能缩短研究的时间。2018年,抗程序性死亡配体(programmed cell death ligand 1,PD-L1)抗体度伐利尤单抗获批用于治疗同步放、化疗后的Ⅲ期肺癌患者,自那时起,针对早期肺癌患者的靶向治疗和免疫治疗的研究迅速发展。在本篇综述中,我们介绍了对于目前早期肺癌患者治疗方案的考虑因素,探讨并展望非转移性肺癌系统性治疗的临床研究现状和未来。展开更多
Prostate cancer (PCa) is the second most common malignancy among men in the world. Castration-resistant prostate cancer (CRPC) is the lethal form of the disease, which develops upon resistance to first line androg...Prostate cancer (PCa) is the second most common malignancy among men in the world. Castration-resistant prostate cancer (CRPC) is the lethal form of the disease, which develops upon resistance to first line androgen deprivation therapy (ADT). Emerging evidence demonstrates a key role for the PI3K-AKT-mTOR signaling axis in the development and maintenance of CRPC. This pathway, which is deregulated in the majority of advanced PCas, serves as a critical nexus for the integration of growth signals with downstream cellular processes such as protein synthesis, proliferation, survival, metabolism and differentiation, thus providing mechanisms for cancer cells to overcome the stress associated with androgen deprivation. Furthermore, preclinical studies have elucidated a direct connection between the PI3K-AKT-mTOR and androgen receptor (AR) signaling axes, revealing a dynamic interplay between these pathways during the development of ADT resistance. Thus, there is a clear rationale for the continued clinical development of a number of novel inhibitors of the PI3K pathway, which offer the potential of blocking CRPC growth and survival. In this review, we will explore the relevance of the PI3K-AKT-mTOR pathway in PCa progression and castration resistance in order to inform the clinical development of specific pathway inhibitors in advanced PCa. In addition, we will highlight current deficiencies in our clinical knowledge, most notably the need for biomarkers that can accurately predict for response to PI3K pathway inhibitors.展开更多
Gastric cancer is the fourth most common cancer,and the second-highest cause of cancer-related deaths worldwide.Despite extensive research to identify novel diagnostic and therapeutic agents,patients with advanced gas...Gastric cancer is the fourth most common cancer,and the second-highest cause of cancer-related deaths worldwide.Despite extensive research to identify novel diagnostic and therapeutic agents,patients with advanced gastric cancer suffer from a poor quality of life and poor prognosis,and treatment is dependent mainly on conventional cytotoxic chemotherapy.To improve the quality of life and survival of gastric cancer patients,a better understanding of the underlying molecular pathologies,and their application towards the development of novel targeted therapies,is urgently needed.Chemokines are a group of small proteins associated with cytoskeletal rearrangements,the directional migration of several cell types during development and physiology,and the host immune response via interactions with G-protein coupled receptors.There is also growing evidence to suggest that chemokines not only play a role in the immune system,but are also involved in the development and progression of tumors.In gastric cancer,CXC chemokines and chemokine receptors regulate the trafficking of cells in and out of the tumor microenvironment.CXC chemokines and their receptors can also directly influence tumorigenesis by modulating tumor transformation,survival,growth,invasion and metastasis,as well as indirectly by regulating angiogenesis,and tumor-leukocyte interactions.In this review,we will focus on the roles of CXC chemokines and their receptors in the development,progression,and metastasis of gastric tumors,and discuss their therapeutic potential for gastric cancer.展开更多
In spite of advances made in the management of the other more common cancers of the gastrointestinal tract,significant progress in the treatment of pancreatic cancer remains elusive.Nearly as many deaths occur from pa...In spite of advances made in the management of the other more common cancers of the gastrointestinal tract,significant progress in the treatment of pancreatic cancer remains elusive.Nearly as many deaths occur from pancreatic cancer as are diagnosed each year reflecting the poor prognosis typically associated with this disease.Until recently,the only treatment with an impact on survival was surgery.In the palliative setting,gemcitabine(Gem) has been a standard treatment for advanced pancreatic cancer since it was shown a decade ago to result in a superior clinical benefit response and survival compared with bolus 5-fluorouracil.Since then,clinical trials have explored the pharmacokinetic modulation of Gem by fixed dose administration and the combination of Gem with other cytotoxic or the biologically"targeted"agents.However,promising trial results in small phaseⅡtrials have not translated into survival improvements in larger phaseⅢrandomized trials in the advanced disease setting.Two trials have recently reported modest survival improvements with the use of combination treatment with Gem and capecitabine(United Kingdom National Cancer Research GEMCAP trial) or erlotinib(National Cancer Institute of CanadaClinical Trials Group PA.3 trial) .This review will focus on the use of systemic therapy for advanced and metastatic pancreatic cancer,summarizing the results of several recent clinical trials and discuss their implications for clinical practice.We will also discuss briefly the second-line chemotherapy options for advanced pancreatic cancer.展开更多
AIM: To investigate feasibility and accuracy of nearinfrared fluorescence imaging using indocyanine green: nanocolloid for sentinel lymph node(SLN) detection in gastric cancer.METHODS: A prospective, single-institutio...AIM: To investigate feasibility and accuracy of nearinfrared fluorescence imaging using indocyanine green: nanocolloid for sentinel lymph node(SLN) detection in gastric cancer.METHODS: A prospective, single-institution, phaseI feasibility trial was conducted. Patients suffering from gastric cancer and planned for gastrectomy were included. During surgery, a subserosal injection of 1.6 m L ICG:Nanocoll was administered around the tumor. NIR fluorescence imaging of the abdominal cavity was performed using the Mini-FLARE? NIR fluorescence imaging system. Lymphatic pathways and SLNs were visualized. Of every detected SLN, the corresponding lymph node station, signal-to-background ratio and histopathological diagnosis was determined. Patients underwent standard-of-care gastrectomy. Detected SLNs outside the standard dissection planes were also resected and evaluated.RESULTS: Twenty-six patients were enrolled. Four patients were excluded because distant metastases were found during surgery or due to technical failure of the injection. In 21 of the remaining 22 patients, at least 1 SLN was detected by NIR Fluorescence imaging(mean 3.1 SLNs; range 1-6). In 8 of the 21 patients, tumor-positive LNs were found. Overall accuracy of the technique was 90%(70%-99%; 95%CI), which decreased by higher p T-stage(100%, 100%, 100%, 90%, 0% for respectively Tx, T1, T2, T3, T4 tumors). All NIR-negative SLNs were completely effaced by tumor. Mean fluorescence signal-to-background ratio of SLNs was 4.4(range 1.4-19.8). In 8 of the 21 patients, SLNs outside the standard resection plane were identified, that contained malignant cells in 2 patients.CONCLUSION: This study shows successful use of ICG:Nanocoll as lymphatic tracer for SLN detection in gastric cancer. Moreover, tumor-containing LNs outside the standard dissection planes were identified.展开更多
AIM: To identify the clinical features and outcomes of infrequently reported leptomeningeal carcinomatosis (LMC) of gastric cancer.METHODS: We analyzed 54 cases of cytologically confirmed gastric LMC at four instituti...AIM: To identify the clinical features and outcomes of infrequently reported leptomeningeal carcinomatosis (LMC) of gastric cancer.METHODS: We analyzed 54 cases of cytologically confirmed gastric LMC at four institutions from 1994 to 2007.RESULTS: The male-to-female ratio was 32:22, and the patients ranged in age from 28 to 78 years (median,48.5 years). The majority of patients had advanced disease at initial diagnosis of gastric cancer. The clini-cal or pathologic tumor, node and metastasis stage ofthe primary gastric cancer wasin 38 patients (70%).The median interval from diagnosis of the primarymalignancy to the diagnosis of LMC was 6.3 mo, rang-ing between 0 and 73.1 mo. Of the initial endoscopic f indings for the 45 available patients, 23 (51%) of the patients were Bormann typeand 15 (33%) patientswere Bormann type. Pathologically, 94% of cases proved to be poorly differentiated adenocarcinomas. Signet ring cell component was also observed in 40% of patients. Headache (85%) and nausea/vomiting (58%) were the most common presenting symptoms of LMC. A gadolinium-enhanced magnetic resonance imaging was conducted in 51 patients. Leptomeningeal enhancement was noted in 45 cases (82%). Intrathecal (IT) chemotherapy was administered to 36 patients-primarily methotrexate alone (61%), but also in combi-nation with hydrocortisone/± Ara-C (39%). The median number of IT treatments was 7 (range, 1-18). Concomitant radiotherapy was administered to 18 patients, and concomitant chemotherapy to seven patients. Sev-enteen patients (46%) achieved cytological negative conversion. Median overall survival duration from the diagnosis of LMC was 6.7 wk (95% CI: 4.3-9.1 wk). In the univariate analysis of survival duration, hemoglobin, IT chemotherapy, and cytological negative conversion showed superior survival duration (P = 0.038, P = 0.010, and P = 0.002, respectively). However, in our multivariate analysis, only cytological negative conversion was predictive of relatively longer survival duration (3.6, 6.7 and 14.6 wk, P = 0.030, RR: 0.415, 95% CI: 0.188-0.918).CONCLUSION: Although these patients had a fatal clinical course, cytologic negative conversion by IT chemotherapy may improve survival.展开更多
Pancreatic carcinomas with acinar differentiation are rare,accounting for 1%-2% of adult pancreatic tumors; they include pancreatic acinar cell carcinoma(PACC),pancreatoblastoma,and carcinomas of mixed differentiation...Pancreatic carcinomas with acinar differentiation are rare,accounting for 1%-2% of adult pancreatic tumors; they include pancreatic acinar cell carcinoma(PACC),pancreatoblastoma,and carcinomas of mixed differentiation. Patients with PACC have a prognosis better than pancreatic ductal adenocarcinomas but worse than pancreatic neuroendocrine tumors. Reports of overall survival range from 18 to 47 mo. A literature review on PACCs included comprehensive genomic profiling and whole exome sequencing on a series of more than 70 patients as well as other diagnostic studies including immunohistochemistry. Surgical resection of PACC is the preferred treatment for localized and resectable tumors. The efficacy of adjuvant treatment is unclear. Metastatic PACCs are generally not curable and treated with systemic chemotherapy. They are moderately responsive to chemotherapy with different regimens showing various degrees of response in case reports/series. Most of these regimens were developed to treat patients with pancreatic ductal adenocarcinomas or colorectal adenocarcinomas. Review of PACC's molecular profiling showed a number of gene alterations such as: SMAD4,BRAF,BRCA2,TP53,RB1,MEN1,JAK-1,BRCA-1,BRCA-2,and DNA mismatch repair abnormalities. PACCs had multiple somatic mutations with some targetable with available drugs. Therefore,molecular profiling of PACC should be an option for patients with refractory PACC.展开更多
AIM: The Lewis b (Leb) antigen has been implicated as a possible binding site for attachment of Helicobacter pylori (H pylori)to gastric mucosa. However, studies both supporting and denying this association have been ...AIM: The Lewis b (Leb) antigen has been implicated as a possible binding site for attachment of Helicobacter pylori (H pylori)to gastric mucosa. However, studies both supporting and denying this association have been reported in the literature. Differences in secretor (Se)genotype have been suggested as a possible reason for previous discrepancies. Therefore, we investigated the relationship between Le and Se genotypes and H pylori infection rates in people with peptic ulcer or gastric cancer.METHODS: Peripheral blood samples were obtained from 347 patients with endoscopic evidence of peptic ulcer disease (235 cases of duodenal ulcer, 62 of gastric ulcer,and 50 of combined duodenal ulcer/gastric ulcer) and 51patients with gastric cancer on endoscopy. Peripheral blood specimens from 101 unrelated normal volunteers were used as controls. Lewis phenotype was determined using an antibody method, whereas Le and Se genotypes were determined by DNA amplification and restriction enzyme analysis. Gastric or duodenal biopsies taken from patients with endoscopic evidence of peptic ulcer or gastric cancer were cultured for H pylori. Isolates were identified as H pylori by morphology and production of urease and catalase. The H pylori infection status was also evaluated by rapid urease test (CLO test), and urea breath test (13C-UBT). Results of studies were analyzed by chi-square test (taken as significant).RESULTS: H pyloriwas isolated from 83.7% (303/347)of patients with peptic ulcer disease. Statistical analysis did not show any significant difference in Lewis phenotype or genotype between patients with and without H pylori infection. No significant association was found between Lewis genotype and peptic ulcer or gastric cancer.CONCLUSION: Lewis blood genotype or phenotype may not play a role in the pathogenesis of H pyloriinfection.However, bacterial strain differences and the presence of more than one attachment mechanism may limit the value of epidemiological studies in elucidating this matter.展开更多
Colon cancer continues to be one of the leading causes of mortality and morbidity throughout the world despite the availability of reliable screening tools and effective therapies.The majority of patients with colon c...Colon cancer continues to be one of the leading causes of mortality and morbidity throughout the world despite the availability of reliable screening tools and effective therapies.The majority of patients with colon cancer are diagnosed at an early stage(stages I to III),which provides an opportunity for cure.The current treatment paradigm of early stage colon cancer consists of surgery followed by adjuvant chemotherapy in a select group of patients,which is directed at the eradication of minimal residual disease to achieve a cure.Surgery alone is curative for the vast majority of colon cancer patients.Currently,surgery and adjuvant chemotherapy can achieve long term survival in about two-thirds of colon cancer patients with nodal involvement.Adjuvant chemotherapy is recommended for all patients with stage III colon cancer,while the benefit in stage II patients is not unequivocally established despite several large clinical trials.Contemporary research in early stage colon cancer is focused on minimally invasive surgical techniques,strategies to limit treatment-related toxicities,precise patient selection for adjuvant therapy,utilization of molecular and clinicopathologic information to personalize therapy and exploration of new therapies exploiting the evolving knowledge of tumor biology.In this review,we will discuss the current standard treatment,evolving treatment paradigms,and the emerging biomarkers,that will likely help improve patient selection and personalization of therapy leading to superior outcomes.展开更多
Acute myelogenous leukemia(AML)can involve the gastrointestinal tract but rarely involves the appendix. We report a male patient who had 1 year partial remission from AML and who presented with apparent acute appendic...Acute myelogenous leukemia(AML)can involve the gastrointestinal tract but rarely involves the appendix. We report a male patient who had 1 year partial remission from AML and who presented with apparent acute appendicitis as the initial manifestation of leu-kemia relapse.Pathological findings of the appendix revealed transmural infiltrates of myeloblasts,which indicated a diagnosis of leukemia.Unfortunately,the patient died from progression of the disease on the 19th d after admission.Although leukemic cell infiltration of the appendix is uncommon,patients with leu-kemia relapse can present with symptoms mimicking acute appendicitis.展开更多
基金National Natural Science Foundation of China(No.82370164)Sanming Project of Medicine in Shenzhen(No.SZSM202011004)Shenzhen Science and Technology Innovation Commission(JCYJ20180307150419435 and JCYJ20210324123004011).
文摘Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies.However,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion post-chemotherapy.Materials and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment.Furthermore,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen.Results:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological malignancies.Concurrently,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.
基金supported by awards from the National Institute of Health R21AR069789&R01 AG059775(to LX),R01 AG076786&R01 AG079556The Henry and Marilyn Taub Foundation+4 种基金the Edward P.Evans Foundationthe Mangurian Foundationthe National Aeronautics and Space Administration(to LMC)NIH R21 AR081050,R01 AR056702,P30 AR069655&P50 AR072000(to EMS)University of Rochester Aging Institute and the Dresner MDS foundation(to SY)。
文摘Prior research establishing that bone interacts in coordination with the bone marrow microenvironment(BMME)to regulate hematopoietic homeostasis was largely based on analyses of individual bone-associated cell populations.Recent advances in intravital imaging has suggested that the expansion of hematopoietic stem cells(HSCs)and acute myeloid leukemia cells is restricted to bone marrow microdomains during a distinct stage of bone remodeling.These findings indicate that dynamic bone remodeling likely imposes additional heterogeneity within the BMME to yield differential clonal responses.A holistic understanding of the role of bone remodeling in regulating the stem cell niche and how these interactions are altered in age-related hematological malignancies will be critical to the development of novel interventions.To advance this understanding,herein,we provide a synopsis of the cellular and molecular constituents that participate in bone turnover and their known connections to the hematopoietic compartment.Specifically,we elaborate on the coupling between bone remodeling and the BMME in homeostasis and age-related hematological malignancies and after treatment with bone-targeting approaches.We then discuss unresolved questions and ambiguities that remain in the field.
基金Supported by IU Simon Comprehensive Cancer Center grant,No.5P30CA082709-24.
文摘Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely curable.Over the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint inhibitors.Therapies aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor immunity.These therapies thus have shown promising results in many clinical trials alone or in combination.The efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical trials.Clinical trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC.Unfortunately,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients.To this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response.This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC.The underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.
文摘In this editorial,we discuss the article by Agatsuma et al.We concentrate specifically on the current routinely used screening tests recommended by society guidelines and delve into the significance of early diagnosis of colorectal cancer(CRC)and its substantial impact on both incidence and mortality rates.Screening is highly recommended,and an early diagnosis stands out as the most crucial predictor of survival for CRC patients.Therefore,it is essential to identify and address the barriers hindering adherence to screening measures,as these barriers can vary among different populations.Furthermore,we focus on screening strategy optimization by selecting high-risk groups.Patients with comorbidities who regularly visit hospitals have been diagnosed at an early stage,showing no significant difference compared to patients undergoing regular screening.This finding highlights the importance of extending screening measures to include patients with comorbidities who do not routinely visit the hospital.
文摘In this editorial,we offer a summary of the risk associated with hepatitis B reactivation(HBVr)in the setting of both solid and hematologic malignancies treated with Bruton tyrosine kinase(BTK)inhibitors,with insights derived from current studies.Furthermore,we emphasize the critical need for a framework regarding robust risk evaluation in patients undergoing such treatments.This framework is essential for identifying those at increased risk of HBVr,enabling healthcare providers to implement proactive measures to prevent reactivation and ensure the safe administration of BTK inhibitor therapy.
文摘BACKGROUND Cholecystoenteric fistula(CEF)involves the formation of a spontaneous ano-malous tract between the gallbladder and the adjacent gastrointestinal tract.Chronic gallbladder inflammation can lead to tissue necrosis,perforation,and fistulogenesis.The most prevalent cause of CEF is chronic cholelithiasis,which rarely results from malignancy.Because the symptoms and laboratory findings associated with CEF are nonspecific,the condition is often misdiagnosed,pre-senting a challenge to the surgeon when detected intraoperatively.Therefore,a preoperative diagnosis of CEF is crucial.We present the case of a 57-year-old male with advanced gallbladder cancer(GBC)who arrived at the emergency room with persistent vomiting,abdominal pain,and diarrhea.An abdominopelvic computed tomography scan revealed a contracted gallbladder with bubbles in the fundus connected to the second por-tion of the duodenum and transverse colon.We suspected that GBC had invaded the adjacent gastrointestinal tract through a cholecystoduodenal fistula(CDF)or a cholecystocolonic fistula(CCF).He underwent multiple examinations,including esophagogastroduodenoscopy,an upper gastrointestinal series,colo-noscopy,and magnetic resonance cholangiopancreatography;the results of these tests con-firmed a diagnosis of synchronous CDF and CCF.The patient underwent a Roux-en-Y gastrojejunostomy and loop ileostomy to address the severe adhesions that were previously observed to cover the second portion of the duodenum and hepatic flexure of the colon.His symptoms improved with supportive treatment while hospitalized.He initiated oral targeted therapy with lenvatinib for further anticancer treatment.CONCLUSION The combination of imaging and surgery can enhance preoperative diagnosis and alleviate symptoms in patients with GBC complicated by CEF.
基金supported by a grant of the Korean Health Technology R&D Project through the Korean Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(Grant Number:HR20C0025).
文摘Background:Although bevacizumab is an important treatment for metastatic colorectal cancer(CRC),not allpatients with CRC benefit from it;in unselected patient populations,only modest survival benefits have been reported.Methods:We evaluated clinical outcomes in 110 patients using comprehensive molecular characterization to identifybiomarkers for a response to bevacizumab-containing treatment.The molecular analysis comprised whole-exomesequencing,ribonucleic acid sequencing,and a methylation array on patient tissues.Results:Genomic and molecularcharacterization was successfully conducted in 103 patients.Six of 103 CRC samples were hypermutated,and none ofthe non-hypermutant tumors were microsatellite unstable.Among those 103 patients,89 had adenocarcinoma(ADC),15 were diagnosed with mucinous ADC,and six had signet-ring cell carcinoma(SRCC).Consensus molecular subtype(CMS)2 was unique to ADC.Of the four SRCCs,two were CMS1,one was CMS4,and the other was CMS3.APCmutation status was a significantly enriched factor in responders to bevacizumab treatment.Fibroblast growth factorreceptor(FGFR)1/2 signaling was upregulated in non-responders,whereas cell cycle,transfer ribonucleic acidprocessing,nucleotide excision repair,and oxidative phosphorylation pathways were enriched in responders.Inaddition,IGF1 was differentially expressed in non-responders(log2 fold change=−1.43,p=4.11×10^(−5),falsediscovery rate=0.098),and FLT1 was highly methylated in non-responders(p=7.55×10^(−3)).When the molecularpathways were reanalyzed separately according to the backbone chemotherapy(FOLFOX vs.FOLFIRI),thesignificance of the molecular pathways varied according to the backbone chemotherapy.Conclusions:This studysought a subset of CRC patients with a distinct clinical response to chemotherapy containing bevacizumab.Ourresults need to be validated in a large group of homogenous patient cohort and examined according to the differentchemotherapy backbones to create personalized therapeutic opportunities in CRC.
基金supported in part by an NIH grant P30 CA008748 to Memorial Sloan Kettering Cance。
文摘早期肺癌患者的治疗是以治愈为目标的。针对手术可切除性和可操作性的多学科讨论模式决定了最终的局部治疗方式(手术或放疗)和相关的系统性治疗方案,从而进一步提高患者治愈的可能性。研究证据支持以顺铂为基础的辅助化疗用于切除术后,或与放疗同步使用。共识指南支持以新辅助化疗代替辅助化疗,并支持对不符合顺铂治疗条件的患者采用基于卡铂的治疗方案。由于研究设计效率低下,需要长时间随访来评估生存终点以及对晚期疾病的持续关注,将新药物(现在是IV期肺癌患者的标准药物)纳入以治愈为目标的治疗范式的工作一直滞后。目前正在研究中的替代性终点(例如病理缓解)将可能缩短研究的时间。2018年,抗程序性死亡配体(programmed cell death ligand 1,PD-L1)抗体度伐利尤单抗获批用于治疗同步放、化疗后的Ⅲ期肺癌患者,自那时起,针对早期肺癌患者的靶向治疗和免疫治疗的研究迅速发展。在本篇综述中,我们介绍了对于目前早期肺癌患者治疗方案的考虑因素,探讨并展望非转移性肺癌系统性治疗的临床研究现状和未来。
基金supported by the National Institute on Aging(R03AG064374)the Ohio State University Comprehensive Cancer Center+3 种基金supported by the National Institute on Aging(R01AG059711)supported by the National Institute on Aging(R03AG056439,K76AG064431)the University of California,San Francisco Helen Diller Family Comprehensive Cancer CenterThe Cancer and Aging Research Group also supported this review(R33AG059206).
文摘癌症常见于老年人。初诊为恶性肿瘤的患者的中位年龄为66岁,癌症相关死亡的中位年龄为72岁[1]。老年人是癌症患病率增长最快的人群之一[2]。免疫治疗的发展,尤其是免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)的问世,彻底改变了所有年龄层包括老年人在内的肿瘤患者的常规治疗方案。细胞毒性T淋巴细胞相关抗原4、程序性死亡受体1(programmed death receptor-1,PD-1)及其配体(programmed death-ligand 1,PD-L1)的抑制剂可改善多种肿瘤患者的总生存期(overall survival,OS)[3],且部分患者可获得持续缓解[4]。
文摘Prostate cancer (PCa) is the second most common malignancy among men in the world. Castration-resistant prostate cancer (CRPC) is the lethal form of the disease, which develops upon resistance to first line androgen deprivation therapy (ADT). Emerging evidence demonstrates a key role for the PI3K-AKT-mTOR signaling axis in the development and maintenance of CRPC. This pathway, which is deregulated in the majority of advanced PCas, serves as a critical nexus for the integration of growth signals with downstream cellular processes such as protein synthesis, proliferation, survival, metabolism and differentiation, thus providing mechanisms for cancer cells to overcome the stress associated with androgen deprivation. Furthermore, preclinical studies have elucidated a direct connection between the PI3K-AKT-mTOR and androgen receptor (AR) signaling axes, revealing a dynamic interplay between these pathways during the development of ADT resistance. Thus, there is a clear rationale for the continued clinical development of a number of novel inhibitors of the PI3K pathway, which offer the potential of blocking CRPC growth and survival. In this review, we will explore the relevance of the PI3K-AKT-mTOR pathway in PCa progression and castration resistance in order to inform the clinical development of specific pathway inhibitors in advanced PCa. In addition, we will highlight current deficiencies in our clinical knowledge, most notably the need for biomarkers that can accurately predict for response to PI3K pathway inhibitors.
基金Supported by Basic Science Research Program through the National Research of Korea(NRF)funded by the Ministry of Education,Science and Technology,NRF-2009-0076540,NRF-2009-0067256
文摘Gastric cancer is the fourth most common cancer,and the second-highest cause of cancer-related deaths worldwide.Despite extensive research to identify novel diagnostic and therapeutic agents,patients with advanced gastric cancer suffer from a poor quality of life and poor prognosis,and treatment is dependent mainly on conventional cytotoxic chemotherapy.To improve the quality of life and survival of gastric cancer patients,a better understanding of the underlying molecular pathologies,and their application towards the development of novel targeted therapies,is urgently needed.Chemokines are a group of small proteins associated with cytoskeletal rearrangements,the directional migration of several cell types during development and physiology,and the host immune response via interactions with G-protein coupled receptors.There is also growing evidence to suggest that chemokines not only play a role in the immune system,but are also involved in the development and progression of tumors.In gastric cancer,CXC chemokines and chemokine receptors regulate the trafficking of cells in and out of the tumor microenvironment.CXC chemokines and their receptors can also directly influence tumorigenesis by modulating tumor transformation,survival,growth,invasion and metastasis,as well as indirectly by regulating angiogenesis,and tumor-leukocyte interactions.In this review,we will focus on the roles of CXC chemokines and their receptors in the development,progression,and metastasis of gastric tumors,and discuss their therapeutic potential for gastric cancer.
文摘In spite of advances made in the management of the other more common cancers of the gastrointestinal tract,significant progress in the treatment of pancreatic cancer remains elusive.Nearly as many deaths occur from pancreatic cancer as are diagnosed each year reflecting the poor prognosis typically associated with this disease.Until recently,the only treatment with an impact on survival was surgery.In the palliative setting,gemcitabine(Gem) has been a standard treatment for advanced pancreatic cancer since it was shown a decade ago to result in a superior clinical benefit response and survival compared with bolus 5-fluorouracil.Since then,clinical trials have explored the pharmacokinetic modulation of Gem by fixed dose administration and the combination of Gem with other cytotoxic or the biologically"targeted"agents.However,promising trial results in small phaseⅡtrials have not translated into survival improvements in larger phaseⅢrandomized trials in the advanced disease setting.Two trials have recently reported modest survival improvements with the use of combination treatment with Gem and capecitabine(United Kingdom National Cancer Research GEMCAP trial) or erlotinib(National Cancer Institute of CanadaClinical Trials Group PA.3 trial) .This review will focus on the use of systemic therapy for advanced and metastatic pancreatic cancer,summarizing the results of several recent clinical trials and discuss their implications for clinical practice.We will also discuss briefly the second-line chemotherapy options for advanced pancreatic cancer.
文摘AIM: To investigate feasibility and accuracy of nearinfrared fluorescence imaging using indocyanine green: nanocolloid for sentinel lymph node(SLN) detection in gastric cancer.METHODS: A prospective, single-institution, phaseI feasibility trial was conducted. Patients suffering from gastric cancer and planned for gastrectomy were included. During surgery, a subserosal injection of 1.6 m L ICG:Nanocoll was administered around the tumor. NIR fluorescence imaging of the abdominal cavity was performed using the Mini-FLARE? NIR fluorescence imaging system. Lymphatic pathways and SLNs were visualized. Of every detected SLN, the corresponding lymph node station, signal-to-background ratio and histopathological diagnosis was determined. Patients underwent standard-of-care gastrectomy. Detected SLNs outside the standard dissection planes were also resected and evaluated.RESULTS: Twenty-six patients were enrolled. Four patients were excluded because distant metastases were found during surgery or due to technical failure of the injection. In 21 of the remaining 22 patients, at least 1 SLN was detected by NIR Fluorescence imaging(mean 3.1 SLNs; range 1-6). In 8 of the 21 patients, tumor-positive LNs were found. Overall accuracy of the technique was 90%(70%-99%; 95%CI), which decreased by higher p T-stage(100%, 100%, 100%, 90%, 0% for respectively Tx, T1, T2, T3, T4 tumors). All NIR-negative SLNs were completely effaced by tumor. Mean fluorescence signal-to-background ratio of SLNs was 4.4(range 1.4-19.8). In 8 of the 21 patients, SLNs outside the standard resection plane were identified, that contained malignant cells in 2 patients.CONCLUSION: This study shows successful use of ICG:Nanocoll as lymphatic tracer for SLN detection in gastric cancer. Moreover, tumor-containing LNs outside the standard dissection planes were identified.
基金Supported by The Dong-A University Research Fund and the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST R13-2002-044-05001-0)
文摘AIM: To identify the clinical features and outcomes of infrequently reported leptomeningeal carcinomatosis (LMC) of gastric cancer.METHODS: We analyzed 54 cases of cytologically confirmed gastric LMC at four institutions from 1994 to 2007.RESULTS: The male-to-female ratio was 32:22, and the patients ranged in age from 28 to 78 years (median,48.5 years). The majority of patients had advanced disease at initial diagnosis of gastric cancer. The clini-cal or pathologic tumor, node and metastasis stage ofthe primary gastric cancer wasin 38 patients (70%).The median interval from diagnosis of the primarymalignancy to the diagnosis of LMC was 6.3 mo, rang-ing between 0 and 73.1 mo. Of the initial endoscopic f indings for the 45 available patients, 23 (51%) of the patients were Bormann typeand 15 (33%) patientswere Bormann type. Pathologically, 94% of cases proved to be poorly differentiated adenocarcinomas. Signet ring cell component was also observed in 40% of patients. Headache (85%) and nausea/vomiting (58%) were the most common presenting symptoms of LMC. A gadolinium-enhanced magnetic resonance imaging was conducted in 51 patients. Leptomeningeal enhancement was noted in 45 cases (82%). Intrathecal (IT) chemotherapy was administered to 36 patients-primarily methotrexate alone (61%), but also in combi-nation with hydrocortisone/± Ara-C (39%). The median number of IT treatments was 7 (range, 1-18). Concomitant radiotherapy was administered to 18 patients, and concomitant chemotherapy to seven patients. Sev-enteen patients (46%) achieved cytological negative conversion. Median overall survival duration from the diagnosis of LMC was 6.7 wk (95% CI: 4.3-9.1 wk). In the univariate analysis of survival duration, hemoglobin, IT chemotherapy, and cytological negative conversion showed superior survival duration (P = 0.038, P = 0.010, and P = 0.002, respectively). However, in our multivariate analysis, only cytological negative conversion was predictive of relatively longer survival duration (3.6, 6.7 and 14.6 wk, P = 0.030, RR: 0.415, 95% CI: 0.188-0.918).CONCLUSION: Although these patients had a fatal clinical course, cytologic negative conversion by IT chemotherapy may improve survival.
文摘Pancreatic carcinomas with acinar differentiation are rare,accounting for 1%-2% of adult pancreatic tumors; they include pancreatic acinar cell carcinoma(PACC),pancreatoblastoma,and carcinomas of mixed differentiation. Patients with PACC have a prognosis better than pancreatic ductal adenocarcinomas but worse than pancreatic neuroendocrine tumors. Reports of overall survival range from 18 to 47 mo. A literature review on PACCs included comprehensive genomic profiling and whole exome sequencing on a series of more than 70 patients as well as other diagnostic studies including immunohistochemistry. Surgical resection of PACC is the preferred treatment for localized and resectable tumors. The efficacy of adjuvant treatment is unclear. Metastatic PACCs are generally not curable and treated with systemic chemotherapy. They are moderately responsive to chemotherapy with different regimens showing various degrees of response in case reports/series. Most of these regimens were developed to treat patients with pancreatic ductal adenocarcinomas or colorectal adenocarcinomas. Review of PACC's molecular profiling showed a number of gene alterations such as: SMAD4,BRAF,BRCA2,TP53,RB1,MEN1,JAK-1,BRCA-1,BRCA-2,and DNA mismatch repair abnormalities. PACCs had multiple somatic mutations with some targetable with available drugs. Therefore,molecular profiling of PACC should be an option for patients with refractory PACC.
文摘AIM: The Lewis b (Leb) antigen has been implicated as a possible binding site for attachment of Helicobacter pylori (H pylori)to gastric mucosa. However, studies both supporting and denying this association have been reported in the literature. Differences in secretor (Se)genotype have been suggested as a possible reason for previous discrepancies. Therefore, we investigated the relationship between Le and Se genotypes and H pylori infection rates in people with peptic ulcer or gastric cancer.METHODS: Peripheral blood samples were obtained from 347 patients with endoscopic evidence of peptic ulcer disease (235 cases of duodenal ulcer, 62 of gastric ulcer,and 50 of combined duodenal ulcer/gastric ulcer) and 51patients with gastric cancer on endoscopy. Peripheral blood specimens from 101 unrelated normal volunteers were used as controls. Lewis phenotype was determined using an antibody method, whereas Le and Se genotypes were determined by DNA amplification and restriction enzyme analysis. Gastric or duodenal biopsies taken from patients with endoscopic evidence of peptic ulcer or gastric cancer were cultured for H pylori. Isolates were identified as H pylori by morphology and production of urease and catalase. The H pylori infection status was also evaluated by rapid urease test (CLO test), and urea breath test (13C-UBT). Results of studies were analyzed by chi-square test (taken as significant).RESULTS: H pyloriwas isolated from 83.7% (303/347)of patients with peptic ulcer disease. Statistical analysis did not show any significant difference in Lewis phenotype or genotype between patients with and without H pylori infection. No significant association was found between Lewis genotype and peptic ulcer or gastric cancer.CONCLUSION: Lewis blood genotype or phenotype may not play a role in the pathogenesis of H pyloriinfection.However, bacterial strain differences and the presence of more than one attachment mechanism may limit the value of epidemiological studies in elucidating this matter.
文摘Colon cancer continues to be one of the leading causes of mortality and morbidity throughout the world despite the availability of reliable screening tools and effective therapies.The majority of patients with colon cancer are diagnosed at an early stage(stages I to III),which provides an opportunity for cure.The current treatment paradigm of early stage colon cancer consists of surgery followed by adjuvant chemotherapy in a select group of patients,which is directed at the eradication of minimal residual disease to achieve a cure.Surgery alone is curative for the vast majority of colon cancer patients.Currently,surgery and adjuvant chemotherapy can achieve long term survival in about two-thirds of colon cancer patients with nodal involvement.Adjuvant chemotherapy is recommended for all patients with stage III colon cancer,while the benefit in stage II patients is not unequivocally established despite several large clinical trials.Contemporary research in early stage colon cancer is focused on minimally invasive surgical techniques,strategies to limit treatment-related toxicities,precise patient selection for adjuvant therapy,utilization of molecular and clinicopathologic information to personalize therapy and exploration of new therapies exploiting the evolving knowledge of tumor biology.In this review,we will discuss the current standard treatment,evolving treatment paradigms,and the emerging biomarkers,that will likely help improve patient selection and personalization of therapy leading to superior outcomes.
文摘Acute myelogenous leukemia(AML)can involve the gastrointestinal tract but rarely involves the appendix. We report a male patient who had 1 year partial remission from AML and who presented with apparent acute appendicitis as the initial manifestation of leu-kemia relapse.Pathological findings of the appendix revealed transmural infiltrates of myeloblasts,which indicated a diagnosis of leukemia.Unfortunately,the patient died from progression of the disease on the 19th d after admission.Although leukemic cell infiltration of the appendix is uncommon,patients with leu-kemia relapse can present with symptoms mimicking acute appendicitis.