Pretreatment Platelet Count is a Prognostic Marker in Lung Cancer: A Danish Registry-based Cohort Study

BackgroundThrombocytosis has been associated with a poor prognosis in a wide range of malignancies. However, the results have been conflicting for lung cancer. Therefore, we evaluated the prognostic value of platelet count in a large cohort of lung cancer patients.Patients and MethodsAll lung cancer patients diagnosed in The Central Denmark Region from 2009 to 2018 were included in the study. Data from the Danish Lung Cancer Registry were combined with data from the clinical laboratory information system on pretreatment platelet count. Platelet count was defined as low, normal, or high based on being below, within, or above the reference intervals. The prognostic value of platelet count was assessed by the Cox proportional hazard model. C-statistics were conducted to investigate if the platelet count added additional prognostic value to existing prognostic markers.ResultsTotally, 6,758 patients with non–small-cell lung cancer (NSCLC) and 1150 patients with small-cell lung cancer (SCLC) were included. Low and high platelet count were significantly associated with decreased overall survival (OS) in NSCLC patients (low: adjusted hazard ratio (HR)=1.75 (95% confidence interval [CI]: 1.49-2.06); high: adjusted HR=1.24 (95% CI: 1.16-1.33)). In SCLC patients, only low platelet count was significantly associated with decreased OS (adjusted HR = 2.71 [95% CI: 2.02-3.65]). C-statistics showed that the prognostic models were significantly improved by the addition of platelet count for both NSCLC and SCLC patients (P < .0001).ConclusionLow and high platelet count were adverse prognostic factors in NSCLC patients, while only low platelet count was a prognostic marker in SCLC patients.     

Bone invasion in soft tissue sarcomas of the extremities: An underappreciated prognostic factor. Bone invasion in soft tissue sarcomas

BackgroundBone invasion is unfrequently reported in soft tissue sarcomas of the extremities (eSTS), it is difficult to assess preoperatively and its prognostic impact has not been extensively studied. The objective of this paper was to analyze the incidence and the clinical impact of histologically proven bone invasion in individuals with eSTS.MethodsA retrospective analysis was performed using the medical files patients who had eSTS and were treated between 2012 and 2016. A 5 years survival was estimated using the Kaplan-Meier method and a Cox proportional risk assessment. The outcomes of patients with and without bone invasion were compared.Results370 patients were included in the analysis. The median follow up was 25 months, the median age was 45 years (IQR 31–58). Bone invasion was found in 41 (11.08%). Median tumor size was 11.8 cm. The majority of individuals were diagnosed at stage IV (n = 116, 31.4%), followed by stage IIIB (n = 87, 23.5%). High histological grade was associated with worse OS (HR 2.23, CI 95% 1.36–3.65, p = 0.001). Absence of bone invasion was associated with better prognosis (HR 0.541, CI 95% 0.34–0.86, p = 0.009). OS was 27.3 vs 49.28 months. The disease-free survival (DFS) was 25.1 in bone invasion vs 45.23 without bone invasion.ConclusionBone invasion in individuals with eSTS is an independent adverse prognostic factor associated with lower OS and DFS; although infrequently reported, bone invasion might be considered as part of the staging in the future     

Nasopharyngeal carcinoma with bone marrow metastasis

Five of 23 patients with recurrent nasopharyngeal carcinoma (NPC) were diagnosed to have bone marrow metastasis. They all had advanced local-regional disease, and were treated with neoadjuvant chemotherapy and definitive radiotherapy after the initial diagnosis. Bone marrow metastasis developed 4-24 months later. The clinical features were anemia (5 of 5), leukopenia (3 of 5), thrombocytopenia (4 of 5), sepsis (3 of 5), tenderness of the sternum (3 of 5), and fever (4 of 5). Patients frequently had elevation of serum lactic dehydrogenase (LDH), alkaline phosphatase (ALK-P), and IgG and IgA antibody titers to Epstein-Barr viral capsid antigen when bone marrow involvement was diagnosed. However, clinical manifestations and laboratory tests were not specific. It is important that three patients had normal bone scans. All five patients had a rapid downhill course; four patients died within 23 days, and the fifth 3 months after the diagnosis of bone marrow metastasis. We concluded that bone marrow was a common metastatic site in NPC patients. Bone marrow metastasis adversely affected patients' survival and required a high index of suspicion for diagnosis. We suggested that bone marrow biopsy should be considered as a routine staging procedure in NPC patients and indicated especially when patients presented with abnormal blood counts, sepsis, bone pain, or tenderness of the sternum. It may be positive in the face of a normal bone scan.     

Clear cell renal cell carcinoma bone metastasis: What should be considered in prognostic evaluation

IntroductionKnowledge of clear cell renal cell carcinoma bone metastasis (ccRCC-BM) remains scarce. This study depicts clinical, pathological and outcome features of the disease and provides suggestions to establish prognosis prediction system more appropriate for ccRCC-BM.Materials and methodsPatients with ccRCC-BM had clinical, pathological data collected. Kaplan-Meier survival analysis was used for outcome profiles. Prognostic risks were evaluated using MSKCC/Motzer score. Univariate and multivariate logistic regression were performed to investigate association between clinical, pathological features and prognosis.ResultsIn the series containing 106 ccRCC-BM patients with 4:1 male predominance, 44.3% of them had synchronous bone metastasis and 28.3% had multi-organ metastasis. Axial bone was prone to bone metastasis and the incidence of severe skeletal-related events was 54.7%. Curative bone lesion resection was performed in 70.7% patients. The median overall survival (mOS) time was 45 months for all and 32 months for those in unfavorable risk stratification. Shorter time to bone metastasis (TTBM) [OR 1.019, 95% CI (1.007, 1.031)], elderly age [OR 1.040, 95% CI (1.001, 1.080)], concomitant multi-organ metastasis [OR 3.883, 95% CI (1.375, 10.967)] and carbonic anhydrase (CA)-IX expression loss [OR 58.824, 95% CI (2.653, 1000)] were associated with poor prognosis.ConclusionThe outcome of ccRCC-BM remained poor in unfavorable risk stratification. Bone lesion resection accompanied by systematic therapy for selected patient could improve prognosis. Shorter TTBM, elderly age, concomitant multi-organ metastasis and the expression loss of CA-IX along with gender-bias, feasibility for surgical treatment are suggested to be incorporated in modified ccRCC-BM-specific prognosis prediction system.     

Occult tumor cells in bone marrow of patients with locoregionally restricted ovarian cancer predict early distant metastatic relapse.

PURPOSE: Based on conventional tumor staging, primary ovarian cancer is viewed as an intraperitoneal disease that rarely spreads to extraperitoneal organs. However, autopsy studies reveal a much higher rate of occult metastasis, indicating that extraperitoneal spread occurs with much greater frequency than previously appreciated. Consequently, we investigated the incidence of early hematogenous dissemination and its association with distant disease-free and overall survival. PATIENTS AND METHODS: Bone marrow aspirates from 108 patients newly diagnosed with International Federation of Gynecology and Obstetrics stage I to III ovarian cancer were prospectively analyzed with the novel anti-cytokeratin (CK) antibody A45-B/B3. We investigated the frequency of CK-positive tumor cells in bone marrow and their effect on prognosis in relation to established risk factors for tumor progression. RESULTS: Tumor cells in bone marrow were detected in 32 (30%) of 108 patients. A CK-positive finding was unrelated to established risk parameters, except for poor nuclear grading of the primary tumor. At a median follow-up of 45 months (range, 12 to 77 months), the presence of occult metastatic cells in bone marrow was associated with the occurrence of clinically overt, extraperitoneal (predominantly extraskeletal) distant metastasis (relative risk [RR], 16.5; 95% confidence interval [CI], 6.2 to 56.9; P < .0001) and death from cancer-related causes (RR, 2.3; 95% CI, 1.2 to 4.3; P = .01). Multivariate analysis identified a positive bone marrow finding as an independent prognostic factor of reduced distant disease-free survival for all patients (RR, 13.8; 95% CI, 5.4 to 52.9; P < .0001) and for the 64 stage R0-1 patients (RR, 7.3; 95% CI, 1.5 to 56.8; P = .0021). CONCLUSION: Our data signal that hematogenous dissemination of tumor cells occurs early and throughout all stages of ovarian cancer. The clinical significance of our findings is supported by the unfavorable prognosis in association with the presence of occult metastatic cells, especially in those patients who received an effective locoregional therapy.     

Bone marrow involvement in anaplastic small cell lung cancer. Diagnosis, hematologic features, and prognostic implications

The hematologic changes and prognostic implications of bone marrow involvement in small cell lung cancer (SCLC) were examined in 133 patients undergoing staging procedures including bone marrow aspiration and trephine biopsy. Bone marrow involvement was found to be present in 27 of 133 (20%) at diagnosis. In most instances bone marrow involvement was associated with the presence of other metastases but in five patients (4%) the bone marrow was the sole site of metastasis. Bone marrow biopsy proved superior (14%) to bone marrow aspiration (5%) in detecting marrow infiltration. Peripheral blood hematologic changes were infrequent even in patients with positive bone marrow biopsy results. Although patients with bone marrow involvement had a shorter median survival (9 weeks) than bone marrow-negative patients (33 weeks) the adverse effect on survival appears to have been mainly due to the presence of concomitant metastases at other sites. Intensive chemotherapy was tolerated to the same degree by bone marrow-positive and bone marrow-negative patients.     

Bone marrow involvement in small cell lung cancer. Clinical significance and correlation with routine laboratory variables

Of 129 patients with small cell lung cancer (SCLC) who underwent bone marrow examination for staging, 39 (30%) had bone marrow involvement. Only three of 129 patients (2.3%) had bone marrow involvement as the only site of metastatic disease. When patients with bone marrow metastasis were compared with patients whose bone marrow was normal, there were significant differences in serum levels of lactate dehydrogenase (LDH), glutamic oxalacetic transaminase (SGOT), glutamic pyruvic transaminase (SGPT), alkaline phosphatase (AP), albumin, and sodium (Na). We found no clinically significant difference in survival between patients with extensive disease with or without bone marrow involvement. Serum Na, albumin, SGOT, and uric acid were important prognostic determinants of survival. Based on the results of this study, we do not recommend routine bone marrow examinations in the staging of SCLC.     

Matrix metalloproteinase activity, bone matrix turnover, and tumor cell proliferation in prostate cancer bone metastasis.

BACKGROUND: The metastasis of prostate cancer to bone is associated with a substantial increase in bone matrix turnover. Matrix metalloproteinases (MMPs) play roles in both normal bone remodeling and invasion and metastasis of prostate cancer. This study was designed to determine the role of MMP activity in prostate cancer that has metastasized to bone. METHODS: Single human fetal bone fragments were implanted subcutaneously in immunodeficient mice. Four weeks later, PC3 human prostate cancer cells were injected directly into some of the implants, and daily treatment was begun with batimastat (a broad-spectrum MMP inhibitor). There were six mice (i.e., six implants) in each of four experimental arms: bone alone with and without batimastat and bone injected with PC3 cells with and without batimastat. Bone implants were harvested after 14 days of treatment and analyzed for MMP expression, bone histomorphometry, osteoclast counts, blood vessel density, and tumor cell proliferation and apoptosis. Complementary data were obtained from bone biopsy samples from patients and a bone organ coculture system. All statistical tests were two-sided. RESULTS: MMPs were detected in tumor and stromal cells of clinical specimens and experimental bone implants. In vivo, MMP inhibition reduced the number of osteoclasts per millimeter in PC3-injected implants-from 8.2 (95% confidence interval [CI] = 7.9 to 8.5) to 3.0 (95% CI = 2.3 to 3.7) (P =.006). In addition, it prevented degradation of marrow trabeculae within the bone implants (cross-sectional area of implant occupied by mineralized trabeculae: untreated implant = 29.1% [95% CI = 27.1% to 31.1%], PC3-injected implant = 14.0% [95% CI = 10.9% to 17.1%] [P =.005 versus untreated], and batimastat-treated PC3-injected implant = 27.2% [95% CI = 22.4% to 32.0%] [P =.03 versus PC3 injected alone]). MMP inhibition reduced proliferating tumor cells from 20.8% (95% CI = 19.9% to 21.7%) to 7.4% (95% CI = 5.2% to 9.6%) (P =.006), without affecting angiogenesis or apoptosis. In vitro, MMP inhibition had no toxic effect on PC3 cells but prevented calcium release from bone fragments cocultured with PC3 cells. CONCLUSIONS: MMP activity appears to play an important role in bone matrix turnover when prostate cancer cells are present in bone. Bone matrix turnover and metastatic tumor growth appear to be involved in a mutually supportive cycle that is disrupted by MMP inhibition.     

Examination of bone marrow biopsy specimens and staging of small cell lung cancer

Bone marrow biopsy specimens were evaluated retrospectively in 63 of 88 (72%) patients with small cell lung cancer (SCLC). Significant differences were not found between extensive disease (ED) patients with or without bone marrow metastases in survival nor in nadirs of leucocytes or platelets subsequent to chemotherapy. A panel of antibodies was used to investigate whether immunohistochemical analysis on routinely processed bone marrow biopsy specimens could detect marrow metastases more effectively than conventional microscopy. In histologically proven marrow metastases and in control SCLC sections a combination of an antibody against cytokeratin 8, 18 and 19 (NCL5D3) and an antibody against neurone specific enolase was validated for detection of metastases. In histologically negative marrow biopsy samples, however, this combination did not yield any additional tumour positive cases. Therefore, histological evaluation of a bone marrow biopsy specimen, even when analysed by immunohistochemistry, does not contribute information relevant for staging, therapy evaluation or prognosis in SCLC.     

Clinicopathological Significance of Micropapillary Pattern in Lung Adenocarcinoma

The aim of this study was to elucidate the clinicopathological characteristics of the micropapillary (MP) subtype and its correlation with survival in lung adenocarcinoma. We investigated the clinicopathological characteristics, including the incidence, sex, smoking history, tumor size, lymph node metastasis, lymphovascular invasion, distant metastasis, genetic alteration, and prognosis in lung adenocarcinoma with the MP pattern through a meta-analysis. From 48 eligible studies, 19,502 lung adenocarcinomas were included. The incidence rate of the MP pattern was 0.101 [95% confidence interval (CI) 0.075–0.136]. There was no significant difference between stage I and III tumors. Lung adenocarcinoma with the MP pattern showed higher rates of lymphatic invasion (0.526, 95% CI 0.403–0.645). MP pattern was found in 0.150 (95% CI 0.008–0.790) of lung adenocarcinoma with distant metastasis. In lung adenocarcinoma with the MP pattern, the estimated rates of ALK, EGFR, and KRAS mutations were 0.102 (95% CI 0.027–0.322), 0.620 (95% CI 0.444–0.769), and 0.118 (95% CI 0.027–0.393), respectively. The MP pattern of lung adenocarcinoma was significantly correlated with worse overall and disease-free survival rates (hazard ratio 1.704, 95% CI 1.216–2.387, and 2.082, 95% CI 1.541–2.813, respectively). Taken together, identification of the MP pattern in lung adenocarcinoma is useful for prediction of clinicopathological characteristics and prognosis of patients.     

胃癌细胞侵犯骨髓患者临床实验室检查特点分析

  目的  分析胃癌骨髓侵犯患者临床实验室检测结果的特点,筛选对胃癌细胞骨髓侵犯具有提示意义的实验室指标。  方法  回顾性分析2013年1月至2021年3月河北医科大学第四医院收治的30例胃癌发生骨髓侵犯患者,收集血常规、凝血功能、免疫、生化及骨髓等临床指标检测结果资料。分析上述患者与未发生骨髓侵犯的Ⅳ期胃癌患者临床实验室检测结果的差异,并制作受试者工作特征（receiver operating characteristic,ROC）曲线评价各指标在提示胃癌细胞骨髓侵犯中的意义。  结果  与未发生骨髓侵犯的Ⅳ期胃癌患者相比较,发生骨髓侵犯的患者血小板（Plt）计数、凝血酶原时间（PT）、凝血酶时间（TT）、乳酸脱氢酶（LDH）、D二聚体（D-DIMER）、纤维蛋白原降解产物（FDP）、CEA及CA72-4等指标的检测结果差异均具有统计学意义（均P<0.05）。其中FDP的ROC曲线下面积最大（AUC=0.988）,且阳性似然比最高。同时,两组患者外周血幼红、幼粒细胞检出率差异具有统计学意义（P<0.01）。  结论  胃癌骨髓侵犯患者的部分临床实验室检测指标较未发生骨髓侵犯患者异常检出率更高且变化更为明显,上述指标对骨髓侵犯具有提示意义。     

Bone marrow micrometastases in 109 breast cancer patients: Correlations with clinical and pathological features and prognosis

Background: The presence in bone marrow of cells which react with monoclonal antibodies against tumor-associated antigens has been proposed over the last few years as a new prognostic factor in breast cancer patients. Patients and methods: Bone marrow aspirates were obtained from 109 stage I and II breast cancer patients during or 2–4 weeks after primary surgery. The samples were processed for leukocyte separation on a Ficoll-Hypaque gradient and then used to prepare cytospin slides for immunocytochemical analysis. The slides were stained with a pool of monoclonal antibodies (MoAbs) which recognize tumor associated antigens, using the alkaline phosphatase anti-alkaline phosphatase method. The median follow-up was 36 months (range 15–62); 22 patients relapsed and 7 died. Results: Thirty-four of the 109 patients (31.1%) had MoAb positive bone marrow cells. The bone marrow was positive in 28/74 (37.9%) patients who had the aspirate taken during surgery and in 6/35 (17.1%) who had it taken after surgery (p = 0.055). No association was found between bone marrow positivity and tumour size, nodal status, menopausal status, estrogen receptor positivity or the proliferative index. No association was found between bone marrow and prognosis: the log-rank test was 0.291 (p > 0.5) for OS and 0.023 for DFS; the hazard ratio (positive vs negative) was 1.51 for OS (95% CI: 0.33–6.86) and 0.93 for DFS (95% CI: 0.35–2.45). Conclusions: In our series, bone marrow positivity did not correlate with prognostic parameters or prognosis. Of interest is the relative excess of positivity when the bone marrow was obtained during surgery.     

The prognosis and clinicopathology of CXCR4 in gastric cancer patients: a meta-analysis

The chemokine receptor 4 (CXCR4) has been widely investigated in diagnosis and prognosis of gastric cancer (GC). However, the impact of CXCR4 on GC patients remains controversial; Here, we conducted a meta-analysis to obtain the precise role of CXCR4 in GC prognosis and clinicopathology. Thirteen published studies with a total of 1,936 patients were included. Original data included the hazard ratio (HR) of overall survival (OS) and odds ratio (OR) in GC patients. We combined HR/OR with 95 % confidence interval (CI) to estimate the hazard. In this study, OS was significantly related to CXCR4 expression, with the HR 2.63 (95 % CI 1.69–4.09; p?<?0.0001), and a significant correlation was also revealed between CXCR4 expression and stage (I?+?II, +) (OR 0.52, 95 % CI 0.32–0.83; p?=?0.007), depth of invasion (T1/T2, +) (OR 0.44, 95 % CI 0.27–0.73; p?=?0.001), lymph node metastasis (LN, +) (OR 2.30, 95 % CI 1.57–3.36; p?<?0.0001), as well as vascular invasion (vas.inv, +) (OR 0.72, 95 % CI 0.53–0.98; p?=?0.04). Heterogeneity was observed among the included studies with OS (I ²?=?51 %), stage (I ²?=?78 %), depth of invasion (I ²?=?74 %), lymph node metastasis (I ²?=?64 %), and histology differentiation (I ²?=?79 %). No publication bias was observed. In conclusion, this meta-analysis showed CXCR4 expression indicates poor prognosis in GC patients with advanced stage or deep invasion in GC tissues, which also implied lymph node metastasis and vascular invasion. Thus, CXCR4 could help predict patient prognosis and guide clinical diagnosis and treatment.     

Magnetic resonance imaging to detect bone marrow metastases in the initial staging of small cell lung carcinoma and breast carcinoma

BACKGROUND: Bone marrow is a common site of metastases in patients with small cell lung carcinoma (SCLC) and female breast carcinoma (FBC). Metastatic bone marrow involvement is found in approximately 50% of SCLC patients and up to 85% of FBC patients at autopsy. Initial staging procedures detect malignant bone marrow lesions in only 2-30% of patients with these tumors. This study was performed to assess whether MRI can improve the detection rate of bone marrow metastases in tumors with a high incidence of skeletal involvement. METHODS: Fifty-two patients with histologically verified SCLC (25 with limited stage disease and 27 with extensive stage disease) and 33 women with FBC were entered into a prospective study. The MRI protocol was comprised of coronal slices in the pelvic region and sagittal slices of the whole spine utilizing a T1-weighted spin echo sequence with a field of view of 50 cm. All patients underwent initial routine diagnostic staging procedures including bone scintigraphy, unilateral crest biopsy, and plain film radiography of suspicious skeletal areas. RESULTS: Only in two SCLC patients, MRI was positive in 25 cases. All SCLC patients with bone marrow lesions histologically verified, diagnosed by crest biopsy (six patients) or by bone scan (seven patients) had the correct diagnosis of metastases by MRI. In addition MRI revealed hypointense bone marrow foci in 14 cases. In contrast, 28 of 33 FBC patients examined during the initial staging procedure showed no evidence of bone marrow involvement. MRI was not superior compared with bone scintigraphy in FBC patients. CONCLUSIONS: The staging results obtained in SCLC and FBC patients are different, although both tumors have a high incidence of bone marrow metastases. It may be assumed that the biologic behavior of these tumors is reflected by the initial bone marrow involvement. Because of its superiority compared with biopsy and bone scan, the authors believe MRI should become an integral part of the initial staging procedures in patients with SCLC. When staging patients with FBC, MRI should be applied only in clinically indicated cases.     

Prognostic factors associated with local recurrence, metastases, and tumor-related death in patients with synovial sarcoma

Prognostic factors associated with local recurrence, metastases, and tumor-related death in synovial sarcoma were studied in 51 patients in the Scottish Bone Tumor Registry from 1955 to 1999. In a multivariate analysis, the presence of poorly differentiated (PD) areas was the strongest prognostic factor associated with local recurrence (Hazard ratio [HR] = 11.3, 95% CI 2.3, 122.5, p = 0.033), metastases (HR = 16.9, 95% CI 2.3,122.5, p = 0.005), and tumor-related death (HR = 6.9, 95% CI 1.1,41.8, p = 0.036). Other significant independent risk factors included bone invasion (HR = 16.6, 95% CI 1.1, 252.5, p = 0.043) and necrosis (HR = 5.1, 95% CI 1.4, 18.99, p = 0.016) for metastases and bone invasion (HR = 17.6, 95% CI 1.2, 253.2, p = 0.035) for tumor-related death. Increasing percentages of PD areas and necrosis were associated with increasing hazard ratios for metastases and death. In the univariate analysis, PD areas, tumor size, and a mitotic count over 10/10 high-power fields were significantly associated with recurrence, whereas necrosis, vascular invasion, and age more than 25 years were additional risk factors for metastases and death. Local recurrence was significantly associated with increased risks for metastases (OR = 6.8, 95% CI 1.6, 28.7, p = 0.006), and death (all cases). Histologic features such as PD areas, necrosis, vascular invasion, and bone invasion should be considered when deciding about adjuvant therapy.     

Annexin A1 is a potential biomarker of bone metastasis in small cell lung cancer

Small cell lung cancer (SCLC) is a subtype of lung cancer with a poor prognosis, with bone metastasis being one of the main causes of treatment failure. Therefore, investigating new biomarkers associated with bone metastasis may result in positive treatment outcomes. The present study detected the expression levels of annexin A1 (ANXA1) in the serum of 82 patients with SCLC using ELISA. ANXA1 expression in patients with SCLC with bone metastasis was significantly higher compared with that in patients without bone metastasis. Receiver operating characteristic analysis revealed that ANXA1 expression was significant in the diagnosis of bone metastasis in SCLC. ANXA1 was inhibited in SBC-5 cells and overexpressed in SBC-3 cells. Results revealed that ANXA1 was able to enhance SCLC cell proliferation, invasion, migration and bone adhesion in vitro. In vivo xenograft bone metastasis assays indicated that ANXA1 had the potential to promote the bone-metastasis ability of SCLC cells in NOD/SCID mice. Furthermore, ANXA1 increased parathyroid hormone-related protein secretion and enhanced Smad2 phosphorylation following TGF-β treatment in SCLC cells. Overall, ANXA1 may be involved in the pathogenesis of bone metastasis in SCLC and may be a potential biomarker for the diagnosis of SCLC.     

非霍奇金淋巴瘤骨髓侵犯69例临床分析

目的：探讨非霍奇金淋巴瘤（NHL）骨髓侵犯患者的临床特点、病理类型、细胞形态特征、治疗效果与预后。方法：对404例经病理学确诊为非霍奇金淋巴瘤患者行血常规,骨髓细胞学检查,分析其骨髓侵犯发生率、细胞形态特征、病理类型、临床表现、分期、疗效及预后的关系。结果：例患者中骨髓侵犯69例．404NHL（17．1％）,形态学特征与原发肿瘤一致,年龄35岁以下者多见（53．6％）,病理类型以B细胞淋巴瘤为主（78．2％）,骨髓侵犯晚期多见,其侵犯程度越重,临床症状越重,化疗效果差,缓解率低,预后不良。结论：NHL骨髓侵犯程度与临床症状严重程度、病理类型、治疗与预后等密切相关,骨髓侵犯程度重,临床分期晚,疗效及预后差。     

Prognostic significance of an increased number of micrometastatic tumor cells in the bone marrow of patients with first recurrence of breast carcinoma

BACKGROUND: Using cytokeratin (CK) as a histogenetic marker of epithelial tumor cells in the bone marrow of patients with primary breast carcinoma, a subgroup of patients with decreased survival can be identified. This study was designed to evaluate the frequency and prognostic relevance of such cells in patients with recurrent breast carcinoma. METHODS: Bone marrow aspirates from 65 patients were analyzed immunocytochemically for the presence of CK positive cells. A quantitative immunoassay with monoclonal anti-CK antibody A45-B/B3 was used and 2 x 10(6) bone marrow cells per patient were evaluated. For prognostic evaluation the authors calculated a cutoff value of micrometastatic tumor cells by analogy to classification and regression tree (CART) analysis. Patients were monitored prospectively for a median of 37 months (range, 11-63 months). RESULTS: Bone marrow micrometastases were present in 5 of 32 patients (16%) with locoregional recurrence and in 24 of 33 patients (73%) with distant recurrence. The bone marrow status yielded no prognostic indication for patients with locoregional recurrence. In contrast, a cutoff value of 2.5 tumor cells per 1 million bone marrow cells analyzed (2.5 x 10(-6) tumor cells) correlated with a significantly different prognosis for women with distant disease. Patients with metastatic disease and a micrometastatic tumor load of > 2.5 x 10(-6) tumor cells survived for a mean of 6 months (95% confidence interval [95% CI], 2.0-9.1) compared with 17 months (95% CI, 11.6-22.0) for patients with < or = 2.5 x 10(-6) tumor cells (P < 0.0001). Multivariate analysis, allowing for hormone receptor status, disease free interval prior to recurrence, manifestation site of metastases, age, and micrometastases in bone marrow, revealed that bone marrow involvement was an independent risk factor, with a hazard ratio of 7.4 (95% CI, 1.6-13.3) for disease-related death. CONCLUSIONS: An increased number of micrometastases identified in the bone marrow of patients with metastatic breast carcinoma represents an independent prognostic factor that may influence future therapeutic strategies for patients with metastatic breast carcinoma.