目的分析多发性骨髓瘤(MM)患者在初诊时或诊治病程中并发髓外病变(EM)的临床特征和危险因素。方法回顾性分析1993至2006年在我院住院治疗的418例 MM 患者中并发 EM的临床特征、生存率以及预后因素。结果 418例 MM 患者中,40例(9.6%)并发...目的分析多发性骨髓瘤(MM)患者在初诊时或诊治病程中并发髓外病变(EM)的临床特征和危险因素。方法回顾性分析1993至2006年在我院住院治疗的418例 MM 患者中并发 EM的临床特征、生存率以及预后因素。结果 418例 MM 患者中,40例(9.6%)并发 EM,常见受累部位前三位依次为软组织、胸(腹)膜和中枢神经系统;中位随访30个月,中位总体生存(OS)时间为28个门,初诊时25例(6%)合并 EM,初诊合并 EM组(A 组)中位 OS 时间仅为16个月,病程中有15例(3.6%)合行 EM,病程中合并 EM 组(B 组)估计中位 OS 时间为72个月,两组相比差异具有统计学意义(P=0.0045);与 A 组相比较,B 组患者初诊时骨髓浆细胞(P=0.022)及骨髓幼稚浆细胞比例(原始、幼稚浆细胞占所有浆细胞比例)(P=0.029)更高,ISS 分期较早(P=0.027)。单因素分析 MM 并发 EM 患者初诊时 C 反应蛋白(CRP)水平增高,血清乳酸脱氢酶(LDH)增高,ISS 分期为Ⅱ、Ⅲ期,Hb<110g/L。初诊时合并 EM 的 MM 预后不良,但 COX 多因素分析未显示统计学差异。结论 MM合并 EM 并不少见,最常见受累部位为软组织。CRP 增高、LDH 升高、ISS 分期晚、贫血及 EM 是 MM 不良预后指标,MM 患者并发 EM 后临床缺乏有效的治疗手段。展开更多
Background：A good postoperative alignment in total knee arthroplasty （TKA） is the key to achieving satisfactory results.We assessed the effect of femoral and tibial resection on the overall alignment after conventi...Background：A good postoperative alignment in total knee arthroplasty （TKA） is the key to achieving satisfactory results.We assessed the effect of femoral and tibial resection on the overall alignment after conventional TKA.Methods：We conducted a retrospective analysis of 212 primary TKAs in 188 patients.Intramedullary （IM）-guided resection was applied on the femoral side while extramedullary （EM）-guided resection was used on the tibial side.Using full-length X-ray,the preoperative femoral valgus angle and lower extremity alignment,as well as 2-week postoperative femoral and tibial prosthetic coronal alignment and overall lower extremity alignment,were measured.Results：Postoperatively,good prosthetic alignment was achieved in 191 cases （90.1%） on the tibial side and in 144 cases （67.9%） on the femoral side （χ^2 =5.441,P =0.02）.Multiple linear regression analysis was used to assess the effect of different alignment sides on the overall alignment in the coronal plane.Data were divided into five subgroups based on the valgus or varus status of the prostheses.The standardized regression coefficients of the femoral and tibial prosthetic alignment on the overall alignment were 0.666 and 0.414,respectively;in varus on both sides were 0.658 and 0.377,respectively;in valgus,0.555 and 0.030;femoral side varus and tibial side valgus,0.702 and 0.211;femoral side valgus and tibial side varus,-0.416 and 0.287.The study showed that the overall low extremity alignment was statistically influenced by the prosthetic alignment,except for the tibial prosthetic alignment when femoral prosthesis was in valgus （P =0.153）.Conclusions：In conventional TKA,tibial side EM-guided resection may offer satisfactory postoperative alignment,and femoral resection relying on IM guide may lead to more undesirable results.Postoperative coronal alignment is mainly affected by the femoral resection.Therefore,femoral side operation should receive adequate attention from the surgeons.展开更多
Background: Sagittal plane placement of the tibial component in total knee replacement (TKR) has important implications for maximizing the range of flexion motion, allowing collateral ligaments to function more normal...Background: Sagittal plane placement of the tibial component in total knee replacement (TKR) has important implications for maximizing the range of flexion motion, allowing collateral ligaments to function more normally, as well as providing ideal compressive loading on the tibial bone-prosthesis interface. This study attempts to quantify the normal posterior tibial slope (PTS) angle pre-operatively and post-operatively in osteoarthritic patients after using a conventional extramedullary tibial resection guide to assess its effectiveness. Methods: Forty-nine primary cementless total knee replacements in 34 osteoarthritic patients were measured radiographically pre-operatively and one year post-operatively to determine the PTS and its effect on range of motion. Lateral X-rays, using the anterior cortical line of the tibia, were employed for all measurements. Results: Pre-operative PTS measured 11.83˚ (range 5˚ - 18˚), while post-operative PTS of implanted tibial components measured 11.30o (range 4˚ - 18˚). The pre-operative range of motion of 112˚ (range 30˚ to 135˚) was improved to 119˚ (range 90˚ to 135˚) post-operatively after 1 year. Conclusions: Anterior tibial shaft referencing using a conventional extramedullary tibial resection guide provides an easy and convenient method for reproducing the anatomical PTS during TKR. This methodology provided improvement in average range of motion from 112˚ pre-operatively to 119˚ post-operatively at one year.展开更多
Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed ...Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast cancer.During this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor microenvironment.Interestingly,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic targets.Mechanistic investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of G-MDSC.On the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)subsets.In summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.展开更多
Background Interactions of tumor cells with the microenvironment were deemed to promote the tumor invasion and metastasis. CXC chemokine receptor 4 （CXCR4） and extracellular matrix metalloproteinase inducer （EMMPRI...Background Interactions of tumor cells with the microenvironment were deemed to promote the tumor invasion and metastasis. CXC chemokine receptor 4 （CXCR4） and extracellular matrix metalloproteinase inducer （EMMPRIN） had reported to participate in this process. However the roles of bone marrow microenvironment in leukemic infiltration were not well investigated. Methods A co-culture system between SHI-1 cells and bone marrow stromal cells （BMSCs） is used to simulate the interactions of leukemic cells with their microenvironment. The trans-matrigel invasion was used to detect the capability of SHI-1 cells invasion. The BMSCs and SHI-1 cells were mixed in a ratio of 1：10 and added to the millicell chamber coated with matrigel. Either the co-culture supernatant or the functional blocking peptide of CXCR4 and EMMPRIN were added to the trans-matrigel invasion system. The expressions of EMMPRIN in SHI-1 cells and BMSCs were detected by RT-PCR. The changes of the expression of matrix metalloproteinase-2, 9 （MMP-2, MMP-9）, tissue inhibitor of metalloproteinase 2 （TIMP-2）, and CXCR4 mRNA in SHI-1 cells were determined by real-time PCR. The concentration of stromal cell derived factor 1 （SDF-1） in serum free supernatant was measured by ELISA. Results Both SHI-1 cells and BMSCs express EMMPRIN. SHI-1 cells could hardly invade the matrigel membrane; the co- culture supernatant did not induce the invasion of SHI-1 cells. When contacting directly with BMSCs, SHI-1 cells invaded to the lower chamber of millicell were significantly increased. The functional blocking peptide of CXCR4 and EMMPRIN could significantly inhibit the invasion triggered by BMSCs. When co-culturing with BMSCs, the expression of CXCR4, MMP-2, MMP-9 and TIMP-2 mRNA in SHI-1 cells were significantly elevated in company with a significantly higher level of SDF-1 in the co-cultured serum-free supernatant. Conclusion The interactions of leukemic cells and BMSCs play important roles in leukemic cell infiltration.展开更多
Objective： To investigate potential prognostic factors affecting patient outcomes and to evaluate the optimal methods and effects of radiotherapy（RT） in the management of extramedullary plasmacytoma（EMP）.Methods...Objective： To investigate potential prognostic factors affecting patient outcomes and to evaluate the optimal methods and effects of radiotherapy（RT） in the management of extramedullary plasmacytoma（EMP）.Methods： Data from 55 patients with EMP between November 1999 and August 2015 were collected. The median age was 51（range, 22–77） years. The median tumor size was 3.5（range, 1.0–15.0） cm. The median applied dose was 50.0（range, 30.0–70.0） Gy. Thirty-nine patients（70.9%） presented with disease in the head or neck region. Twelve patients received RT alone, 9 received surgery（S） alone, 3 received chemotherapy（CT） alone, and 3 patients did not receive any treatment. Combination therapies were applied in 28 patients.Results：The median follow-up duration was 56 months.The 5-year local recurrence-free survival（LRFS）,multiple myeloma-free survival（MMFS）,progression-free survival（PFS）and overall survival（OS）rates were 79.8%,78.6%,65.2% and 76.0%,respectively.Univariate analysis revealed that RT was a favourable factor for all examined endpoints.Furthermore,head and neck EMPs were associated with superior LRFS,MMFS and PFS.Tumor size〈4 cm was associated with superior MMFS,PFS and OS;serum M protein negativity was associated with superior MMFS and PFS;age≥50 years and local recurrence were associated with poor MMFS.The dose≥45 Gy group exhibited superior 5-year LRFS,MMFS and PFS rates（94.7%,94.4%,90.0%,respectively）,while the corresponding values for the dose〈45 Gy group were 62.5%（P=0.008）,53.3%（P=0.036）and 41.7%（P〈0.001）.Conclusions：Involved-site RT of at least 45 Gy should be considered for EMP.Furthermore,patients with head and neck EMP,tumor size〈4 cm,age〈50 years and serum M protein negativity had better outcomes.展开更多
BACKGROUND Plasma-cell neoplasms rarely involve the gastrointestinal tract and manifest as gastrointestinal bleeding. Plasmablastic myeloma is an aggressive plasma cell neoplasm associated with poor outcomes. A small ...BACKGROUND Plasma-cell neoplasms rarely involve the gastrointestinal tract and manifest as gastrointestinal bleeding. Plasmablastic myeloma is an aggressive plasma cell neoplasm associated with poor outcomes. A small number of cases with gastrointestinal involvement is reported in the literature and therefore high index of suspicion is essential for avoiding delays in diagnosis and treatment.CASE SUMMARY Our aim is to present our experience of a 70-year-old patient with a secondary presentation of plasmablastic myeloma manifesting as unstable upper gastrointestinal bleeding and to review the literature with the view to consolidate and discuss information about diagnosis and management of this rare entity. In addition to our case, a literature search(Pub Med database) of case reports of extramedullary plasma cell neoplasms manifesting as upper gastrointestinal bleeding was performed. Twenty-seven cases of extramedullary plasmacytoma(EMP) involving the stomach and small bowel presenting with upper gastrointestinal bleeding were retrieved. The majority of patients were males(67%). The average age on diagnosis was 62.7 years. The most common site of presentation was the stomach(41%), followed by the duodenum(15%). The most common presenting complaint was melena(44%). In the majority of cases, the EMPs were a secondary manifestation(63%) at the background of multiple myeloma(26%), plasmablastic myeloma(7%) or high-grade plasma cell myeloma(4%). Oesophagogastroscopy was the main diagnostic modality and chemotherapy the preferred treatment option for secondary EMPs.CONCLUSION Despite their rare presentation, upper gastrointestinal EMPs should be considered in the differential diagnosis of patients with gastrointestinal bleeding especially in the presence of systemic haematological malignancy.展开更多
BACKGROUND Direct infiltration of the pancreas by acute myeloid leukemia(AML)with acute pancreatitis(AP)as an initial symptom is extremely rare.Only once in the literature,the leukemia cells in AML have been implicate...BACKGROUND Direct infiltration of the pancreas by acute myeloid leukemia(AML)with acute pancreatitis(AP)as an initial symptom is extremely rare.Only once in the literature,the leukemia cells in AML have been implicated as the cause of AP.Pancreatitis caused by a rare predisposing factor is often misdiagnosed as idiopathic pancreatitis or pancreatitis of other common causes.Severe AP(SAP)progresses rapidly with a high fatality rate.Therefore,it is important to identify the predisposing factors in the early stage of SAP,evaluate the condition,determine prognosis,formulate treatment plans,and prevent a recurrence.Here,we describe a case of SAP due to AML.CASE SUMMARY A 61-year-old man presented to the hospital with fever and persistent abdominal pain.Blood analysis presented significantly elevated serum amylase and severe thrombocytopenia.Computed tomography examination of the abdomen revealed peripancreatic inflammatory effusion.The patient had no common etiologies and risk factors for AP,but the concurrent severe thrombocytopenia could not be explained by pancreatitis.Finally,the bone marrow aspirate and biopsy inspection revealed the underlying reason for pancreatitis,AML(M2 type based on the French-American-British classifications system).CONCLUSION Direct infiltration of the pancrease by acute leukemia,particularly AML cells,is an infrequent cause of AP.Therefore,although AP is a rare extramedullary infilt-ration characteristic for AML patients,it should be considered when determining the etiology of AP.展开更多
BACKGROUND Extramedullary blast crisis in chronic myeloid leukemia(CML)is an uncommon occurrence of leukemic blast infiltration in regions other than the bone marrow.Malignant infiltration of the serosal membranes sho...BACKGROUND Extramedullary blast crisis in chronic myeloid leukemia(CML)is an uncommon occurrence of leukemic blast infiltration in regions other than the bone marrow.Malignant infiltration of the serosal membranes should be considered in cases where CML presents with ascites or pleural effusion.CASE SUMMARY A 23-year-old female with CML presented with progressively worsening ascites and pleural effusion despite first-line tyrosine kinase inhibitor treatment.Her blood work indicated leukocytosis with myelocyte bulge and 2%blasts.Analysis of the patient’s bone marrow confirmed the chronic phase of CML.Abdominal ultrasound revealed hepatosplenomegaly with ascites.The fluid investigation of both ascites and pleural effusion revealed a predominance of neutrophils with exudate.However,no acid-fast bacilli or growth was observed after culturing.Although hydroxyurea reduced cell counts,there was no observed effect on ascites or pleural effusion.Repeat investigation of the ascitic and pleural fluid revealed a polymorphous myeloid cell population consisting of myelocytes,metamyelocytes,band forms,neutrophils and a few myeloblasts.Extramedullary blast crisis was suspected,and mutation analysis was performed.We switched the patient to dasatinib.The patient’s symptoms were relieved,and ascites and pleural effusion diminished.CONCLUSION Serosal membrane involvement in CML is extremely rare.In this case,the patient responded well to dasatinib treatment.展开更多
BACKGROUND: Extramedullary pancreatic plasmacytoma treated with bortezomib is rarely reported. METHODS: We admitted a 53-year-old woman with an asymptomatic mass above the left clavicle for over three months, then an ...BACKGROUND: Extramedullary pancreatic plasmacytoma treated with bortezomib is rarely reported. METHODS: We admitted a 53-year-old woman with an asymptomatic mass above the left clavicle for over three months, then an asymptomatic swelling of the pancreas was found. A biopsy on the mass and a fine needle aspiration of the pancreas were performed. The diagnosis of extramedullary plasmacytoma (EMP) was made. The patient was initially treated with combination chemotherapy consisting of vincristine, doxorubicin and dexamethasone (VAD regimen). She progressed to painless jaundice during the chemotherapy. Then she was treated with bortezomib and hyper-dose dexamethasone. As a result, she had a near complete remission. RESULTS: The data demonstrated that the diagnosis was EMP of the pancreas. The patient responded very well to bortezomib, while failing to respond to the traditional chemotherapy regimen of VAD. CONCLUSION: EMP of the pancreas is rare. This case gives evidence for an excellent response of EMP of the pancreas to bortezomib. (Hepatobiliary Pancreat Dis Int 2009; 8: 329-331)展开更多
Background MMPs and TIMPs play important roles in tumor angiogenesis and invasion. Studies have shown that TIMP- 2 has two roles in tumor invasion. However, its role in leukemic infiltration has not been well investig...Background MMPs and TIMPs play important roles in tumor angiogenesis and invasion. Studies have shown that TIMP- 2 has two roles in tumor invasion. However, its role in leukemic infiltration has not been well investigated. This study explored the roles of TIMP-2 in extramedullary infiltration of acute monocytic leukemic SHI-1 cells both in vitro and in vitro. Methods A retroviral vector carrying the human TIMP-2 cDNA was constructed and transfected into the monocytic leukemic cell line SHI-I. The expression of TIMP-2 in the positive clones was determined. The proliferation of SHI-1 cells was examined by MTT assay. Trans-Matrigel invasion assays were used to investigate the infiltration ability in vitro. SHI-1 cells were intravenously injected into pre-traated nu/nu mice to investigate the infiltration ability feature in vitro. Results The expression of TIMP-2 on the cell membrane was significantly elevated in SHI-1/TIMP-2 cells. Over- expression of TIMP-2 promoted the cells proliferation and the invasions in vitro. The SHI-1/TIMP-2 cells demonstrated higher infiltration ability when intravenously injected into nu/nu mice. Conclusion Over-expression of TIMP-2, especially on the cell membrane, may play important roles in promoting the proliferation and infiltration of SHI-1 leukemic cells.展开更多
文摘目的分析多发性骨髓瘤(MM)患者在初诊时或诊治病程中并发髓外病变(EM)的临床特征和危险因素。方法回顾性分析1993至2006年在我院住院治疗的418例 MM 患者中并发 EM的临床特征、生存率以及预后因素。结果 418例 MM 患者中,40例(9.6%)并发 EM,常见受累部位前三位依次为软组织、胸(腹)膜和中枢神经系统;中位随访30个月,中位总体生存(OS)时间为28个门,初诊时25例(6%)合并 EM,初诊合并 EM组(A 组)中位 OS 时间仅为16个月,病程中有15例(3.6%)合行 EM,病程中合并 EM 组(B 组)估计中位 OS 时间为72个月,两组相比差异具有统计学意义(P=0.0045);与 A 组相比较,B 组患者初诊时骨髓浆细胞(P=0.022)及骨髓幼稚浆细胞比例(原始、幼稚浆细胞占所有浆细胞比例)(P=0.029)更高,ISS 分期较早(P=0.027)。单因素分析 MM 并发 EM 患者初诊时 C 反应蛋白(CRP)水平增高,血清乳酸脱氢酶(LDH)增高,ISS 分期为Ⅱ、Ⅲ期,Hb<110g/L。初诊时合并 EM 的 MM 预后不良,但 COX 多因素分析未显示统计学差异。结论 MM合并 EM 并不少见,最常见受累部位为软组织。CRP 增高、LDH 升高、ISS 分期晚、贫血及 EM 是 MM 不良预后指标,MM 患者并发 EM 后临床缺乏有效的治疗手段。
文摘Background：A good postoperative alignment in total knee arthroplasty （TKA） is the key to achieving satisfactory results.We assessed the effect of femoral and tibial resection on the overall alignment after conventional TKA.Methods：We conducted a retrospective analysis of 212 primary TKAs in 188 patients.Intramedullary （IM）-guided resection was applied on the femoral side while extramedullary （EM）-guided resection was used on the tibial side.Using full-length X-ray,the preoperative femoral valgus angle and lower extremity alignment,as well as 2-week postoperative femoral and tibial prosthetic coronal alignment and overall lower extremity alignment,were measured.Results：Postoperatively,good prosthetic alignment was achieved in 191 cases （90.1%） on the tibial side and in 144 cases （67.9%） on the femoral side （χ^2 =5.441,P =0.02）.Multiple linear regression analysis was used to assess the effect of different alignment sides on the overall alignment in the coronal plane.Data were divided into five subgroups based on the valgus or varus status of the prostheses.The standardized regression coefficients of the femoral and tibial prosthetic alignment on the overall alignment were 0.666 and 0.414,respectively;in varus on both sides were 0.658 and 0.377,respectively;in valgus,0.555 and 0.030;femoral side varus and tibial side valgus,0.702 and 0.211;femoral side valgus and tibial side varus,-0.416 and 0.287.The study showed that the overall low extremity alignment was statistically influenced by the prosthetic alignment,except for the tibial prosthetic alignment when femoral prosthesis was in valgus （P =0.153）.Conclusions：In conventional TKA,tibial side EM-guided resection may offer satisfactory postoperative alignment,and femoral resection relying on IM guide may lead to more undesirable results.Postoperative coronal alignment is mainly affected by the femoral resection.Therefore,femoral side operation should receive adequate attention from the surgeons.
文摘Background: Sagittal plane placement of the tibial component in total knee replacement (TKR) has important implications for maximizing the range of flexion motion, allowing collateral ligaments to function more normally, as well as providing ideal compressive loading on the tibial bone-prosthesis interface. This study attempts to quantify the normal posterior tibial slope (PTS) angle pre-operatively and post-operatively in osteoarthritic patients after using a conventional extramedullary tibial resection guide to assess its effectiveness. Methods: Forty-nine primary cementless total knee replacements in 34 osteoarthritic patients were measured radiographically pre-operatively and one year post-operatively to determine the PTS and its effect on range of motion. Lateral X-rays, using the anterior cortical line of the tibia, were employed for all measurements. Results: Pre-operative PTS measured 11.83˚ (range 5˚ - 18˚), while post-operative PTS of implanted tibial components measured 11.30o (range 4˚ - 18˚). The pre-operative range of motion of 112˚ (range 30˚ to 135˚) was improved to 119˚ (range 90˚ to 135˚) post-operatively after 1 year. Conclusions: Anterior tibial shaft referencing using a conventional extramedullary tibial resection guide provides an easy and convenient method for reproducing the anatomical PTS during TKR. This methodology provided improvement in average range of motion from 112˚ pre-operatively to 119˚ post-operatively at one year.
基金supported by the Postdoctoral Research Funds of Hebei Medical University(30705010016-3759)Natural Science Foundation of China(32272328)+4 种基金Natural Science Foundation of Hebei Province(B2022321001)National Key Research Project of Hebei Province(20375502D)Postdoctoral Research Project of Hebei Province(B2022003031)Science and Technology Research Program of Hebei Provincial Colleges(QN2023229)Hebei Provincial Key Laboratory of Nutrition and Health(2023YDYY-KF05)。
文摘Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast cancer.During this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor microenvironment.Interestingly,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic targets.Mechanistic investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of G-MDSC.On the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)subsets.In summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.
基金This work was supported by the grants from Naiional Natural Science Foundation of China （No. 30800490） and ＂Jinggang Star＂ Young Scientist Training Program of Jiangxi Province.
文摘Background Interactions of tumor cells with the microenvironment were deemed to promote the tumor invasion and metastasis. CXC chemokine receptor 4 （CXCR4） and extracellular matrix metalloproteinase inducer （EMMPRIN） had reported to participate in this process. However the roles of bone marrow microenvironment in leukemic infiltration were not well investigated. Methods A co-culture system between SHI-1 cells and bone marrow stromal cells （BMSCs） is used to simulate the interactions of leukemic cells with their microenvironment. The trans-matrigel invasion was used to detect the capability of SHI-1 cells invasion. The BMSCs and SHI-1 cells were mixed in a ratio of 1：10 and added to the millicell chamber coated with matrigel. Either the co-culture supernatant or the functional blocking peptide of CXCR4 and EMMPRIN were added to the trans-matrigel invasion system. The expressions of EMMPRIN in SHI-1 cells and BMSCs were detected by RT-PCR. The changes of the expression of matrix metalloproteinase-2, 9 （MMP-2, MMP-9）, tissue inhibitor of metalloproteinase 2 （TIMP-2）, and CXCR4 mRNA in SHI-1 cells were determined by real-time PCR. The concentration of stromal cell derived factor 1 （SDF-1） in serum free supernatant was measured by ELISA. Results Both SHI-1 cells and BMSCs express EMMPRIN. SHI-1 cells could hardly invade the matrigel membrane; the co- culture supernatant did not induce the invasion of SHI-1 cells. When contacting directly with BMSCs, SHI-1 cells invaded to the lower chamber of millicell were significantly increased. The functional blocking peptide of CXCR4 and EMMPRIN could significantly inhibit the invasion triggered by BMSCs. When co-culturing with BMSCs, the expression of CXCR4, MMP-2, MMP-9 and TIMP-2 mRNA in SHI-1 cells were significantly elevated in company with a significantly higher level of SDF-1 in the co-cultured serum-free supernatant. Conclusion The interactions of leukemic cells and BMSCs play important roles in leukemic cell infiltration.
文摘Objective： To investigate potential prognostic factors affecting patient outcomes and to evaluate the optimal methods and effects of radiotherapy（RT） in the management of extramedullary plasmacytoma（EMP）.Methods： Data from 55 patients with EMP between November 1999 and August 2015 were collected. The median age was 51（range, 22–77） years. The median tumor size was 3.5（range, 1.0–15.0） cm. The median applied dose was 50.0（range, 30.0–70.0） Gy. Thirty-nine patients（70.9%） presented with disease in the head or neck region. Twelve patients received RT alone, 9 received surgery（S） alone, 3 received chemotherapy（CT） alone, and 3 patients did not receive any treatment. Combination therapies were applied in 28 patients.Results：The median follow-up duration was 56 months.The 5-year local recurrence-free survival（LRFS）,multiple myeloma-free survival（MMFS）,progression-free survival（PFS）and overall survival（OS）rates were 79.8%,78.6%,65.2% and 76.0%,respectively.Univariate analysis revealed that RT was a favourable factor for all examined endpoints.Furthermore,head and neck EMPs were associated with superior LRFS,MMFS and PFS.Tumor size〈4 cm was associated with superior MMFS,PFS and OS;serum M protein negativity was associated with superior MMFS and PFS;age≥50 years and local recurrence were associated with poor MMFS.The dose≥45 Gy group exhibited superior 5-year LRFS,MMFS and PFS rates（94.7%,94.4%,90.0%,respectively）,while the corresponding values for the dose〈45 Gy group were 62.5%（P=0.008）,53.3%（P=0.036）and 41.7%（P〈0.001）.Conclusions：Involved-site RT of at least 45 Gy should be considered for EMP.Furthermore,patients with head and neck EMP,tumor size〈4 cm,age〈50 years and serum M protein negativity had better outcomes.
文摘BACKGROUND Plasma-cell neoplasms rarely involve the gastrointestinal tract and manifest as gastrointestinal bleeding. Plasmablastic myeloma is an aggressive plasma cell neoplasm associated with poor outcomes. A small number of cases with gastrointestinal involvement is reported in the literature and therefore high index of suspicion is essential for avoiding delays in diagnosis and treatment.CASE SUMMARY Our aim is to present our experience of a 70-year-old patient with a secondary presentation of plasmablastic myeloma manifesting as unstable upper gastrointestinal bleeding and to review the literature with the view to consolidate and discuss information about diagnosis and management of this rare entity. In addition to our case, a literature search(Pub Med database) of case reports of extramedullary plasma cell neoplasms manifesting as upper gastrointestinal bleeding was performed. Twenty-seven cases of extramedullary plasmacytoma(EMP) involving the stomach and small bowel presenting with upper gastrointestinal bleeding were retrieved. The majority of patients were males(67%). The average age on diagnosis was 62.7 years. The most common site of presentation was the stomach(41%), followed by the duodenum(15%). The most common presenting complaint was melena(44%). In the majority of cases, the EMPs were a secondary manifestation(63%) at the background of multiple myeloma(26%), plasmablastic myeloma(7%) or high-grade plasma cell myeloma(4%). Oesophagogastroscopy was the main diagnostic modality and chemotherapy the preferred treatment option for secondary EMPs.CONCLUSION Despite their rare presentation, upper gastrointestinal EMPs should be considered in the differential diagnosis of patients with gastrointestinal bleeding especially in the presence of systemic haematological malignancy.
文摘BACKGROUND Direct infiltration of the pancreas by acute myeloid leukemia(AML)with acute pancreatitis(AP)as an initial symptom is extremely rare.Only once in the literature,the leukemia cells in AML have been implicated as the cause of AP.Pancreatitis caused by a rare predisposing factor is often misdiagnosed as idiopathic pancreatitis or pancreatitis of other common causes.Severe AP(SAP)progresses rapidly with a high fatality rate.Therefore,it is important to identify the predisposing factors in the early stage of SAP,evaluate the condition,determine prognosis,formulate treatment plans,and prevent a recurrence.Here,we describe a case of SAP due to AML.CASE SUMMARY A 61-year-old man presented to the hospital with fever and persistent abdominal pain.Blood analysis presented significantly elevated serum amylase and severe thrombocytopenia.Computed tomography examination of the abdomen revealed peripancreatic inflammatory effusion.The patient had no common etiologies and risk factors for AP,but the concurrent severe thrombocytopenia could not be explained by pancreatitis.Finally,the bone marrow aspirate and biopsy inspection revealed the underlying reason for pancreatitis,AML(M2 type based on the French-American-British classifications system).CONCLUSION Direct infiltration of the pancrease by acute leukemia,particularly AML cells,is an infrequent cause of AP.Therefore,although AP is a rare extramedullary infilt-ration characteristic for AML patients,it should be considered when determining the etiology of AP.
文摘BACKGROUND Extramedullary blast crisis in chronic myeloid leukemia(CML)is an uncommon occurrence of leukemic blast infiltration in regions other than the bone marrow.Malignant infiltration of the serosal membranes should be considered in cases where CML presents with ascites or pleural effusion.CASE SUMMARY A 23-year-old female with CML presented with progressively worsening ascites and pleural effusion despite first-line tyrosine kinase inhibitor treatment.Her blood work indicated leukocytosis with myelocyte bulge and 2%blasts.Analysis of the patient’s bone marrow confirmed the chronic phase of CML.Abdominal ultrasound revealed hepatosplenomegaly with ascites.The fluid investigation of both ascites and pleural effusion revealed a predominance of neutrophils with exudate.However,no acid-fast bacilli or growth was observed after culturing.Although hydroxyurea reduced cell counts,there was no observed effect on ascites or pleural effusion.Repeat investigation of the ascitic and pleural fluid revealed a polymorphous myeloid cell population consisting of myelocytes,metamyelocytes,band forms,neutrophils and a few myeloblasts.Extramedullary blast crisis was suspected,and mutation analysis was performed.We switched the patient to dasatinib.The patient’s symptoms were relieved,and ascites and pleural effusion diminished.CONCLUSION Serosal membrane involvement in CML is extremely rare.In this case,the patient responded well to dasatinib treatment.
文摘BACKGROUND: Extramedullary pancreatic plasmacytoma treated with bortezomib is rarely reported. METHODS: We admitted a 53-year-old woman with an asymptomatic mass above the left clavicle for over three months, then an asymptomatic swelling of the pancreas was found. A biopsy on the mass and a fine needle aspiration of the pancreas were performed. The diagnosis of extramedullary plasmacytoma (EMP) was made. The patient was initially treated with combination chemotherapy consisting of vincristine, doxorubicin and dexamethasone (VAD regimen). She progressed to painless jaundice during the chemotherapy. Then she was treated with bortezomib and hyper-dose dexamethasone. As a result, she had a near complete remission. RESULTS: The data demonstrated that the diagnosis was EMP of the pancreas. The patient responded very well to bortezomib, while failing to respond to the traditional chemotherapy regimen of VAD. CONCLUSION: EMP of the pancreas is rare. This case gives evidence for an excellent response of EMP of the pancreas to bortezomib. (Hepatobiliary Pancreat Dis Int 2009; 8: 329-331)
基金This work was supported by the Grant from National Natural Science Foundation of China （No. 30670905）.
文摘Background MMPs and TIMPs play important roles in tumor angiogenesis and invasion. Studies have shown that TIMP- 2 has two roles in tumor invasion. However, its role in leukemic infiltration has not been well investigated. This study explored the roles of TIMP-2 in extramedullary infiltration of acute monocytic leukemic SHI-1 cells both in vitro and in vitro. Methods A retroviral vector carrying the human TIMP-2 cDNA was constructed and transfected into the monocytic leukemic cell line SHI-I. The expression of TIMP-2 in the positive clones was determined. The proliferation of SHI-1 cells was examined by MTT assay. Trans-Matrigel invasion assays were used to investigate the infiltration ability in vitro. SHI-1 cells were intravenously injected into pre-traated nu/nu mice to investigate the infiltration ability feature in vitro. Results The expression of TIMP-2 on the cell membrane was significantly elevated in SHI-1/TIMP-2 cells. Over- expression of TIMP-2 promoted the cells proliferation and the invasions in vitro. The SHI-1/TIMP-2 cells demonstrated higher infiltration ability when intravenously injected into nu/nu mice. Conclusion Over-expression of TIMP-2, especially on the cell membrane, may play important roles in promoting the proliferation and infiltration of SHI-1 leukemic cells.
