Diagnostic performance of nanoparticle-enhanced magnetic resonance imaging in the diagnosis of lymph node metastases in patients with endometrial and cervical cancer.

PURPOSE: Lymph node metastases affect management and prognosis of patients with gynecologic malignancies. Preoperative nodal assessment with computed tomography or magnetic resonance imaging (MRI) is inaccurate. A new lymph node-specific contrast agent, ferumoxtran-10, composed of ultrasmall particles of iron oxide (USPIO), may enhance the detection of lymph node metastases independent of node size. Our aim was to compare the diagnostic performance of MRI with USPIO against standard size criteria. METHODS: Forty-four patients with endometrial (n = 15) or cervical (n = 29) cancer were included. MRI was performed before and after administration of USPIO. Two independent observers viewed the MR images before lymph node sampling. Lymph node metastases were predicted using size criteria and USPIO criteria. Lymph node sampling was performed in all patients. RESULTS: Lymph node sampling provided 768 pelvic or para-aortic nodes for pathology, of which 335 were correlated on MRI; 17 malignant nodes were found in 11 of 44 patients (25%). On a node-by-node basis, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) by size criteria were 29%*, 99%, 56%, and 96%, and by USPIO criteria (reader 1/reader 2) were 93%/82%* (*P = .008/.004), 97%/97%, 61%/59%, and 100%/99%, respectively (where [*] indicates the statistical difference of P = x/x between the two results marked by the asterisk). On a patient-by-patient basis, sensitivity, specificity, PPV, and NPV by size criteria were 27%*, 94%, 60%, and 79%, and by USPIO criteria (reader 1/reader 2) were 100%/91%* (*P = .031/.06), 94%/87%, 82%/71%, and 100%/96%, respectively. The kappa statistic was 0.93. CONCLUSION: Lymph node characterization with USPIO increases the sensitivity of MRI in the prediction of lymph node metastases, with no loss of specificity. This may greatly improve preoperative treatment planning.     

染料法前哨淋巴结识别在宫颈癌中的初探

目的：探索宫颈癌根治术中识别前哨淋巴结的可行性，评价前哨淋巴结预测盆腔淋巴结有无肿瘤转移的准确性。方法：2002年5月～2003年6月，29例早期宫颈癌在术中于宫颈肿瘤周围注入生物染料4ml，仔细观察蓝染的淋巴管和淋巴结10分钟，记录蓝染淋巴结的部位和数目。按常规行盆腔淋巴结清扫术，根据术后病理计算前哨淋巴结预测盆腔淋巴结转移的准确性和假阴性率。结果：共有24例在术中找到蓝染的前哨淋巴结，识别率为83％(24／29)，前哨淋巴结多位于闭孔和髂内，分别位于左侧髂内组11例，右侧髂内组13例，左侧闭孔组10例，右侧闭孔组14例，3例分别有髂总和髂内二组蓝染淋巴结。24例成功识别前哨淋巴结的病例中，有淋巴结转移6例，其中5例仅有前哨淋巴结转移，1例既有前哨淋巴结转移又有非前哨淋巴结转移，18例无前哨淋巴结转移的患者也无盆腔淋巴结转移，假阴性率为0。结论：宫颈癌根治术中行染料法前哨淋巴结识别是安全可行的，前哨淋巴结能准确反映盆腔淋巴结状况。     

IV-DSA is a new diagnostic tool for axillary lymph node metastasis in breast cancer patients

BACKGROUND AND OBJECTIVE: The aim of this study is to know whether intravenous digital subtraction angiography (IV-DSA) is useful to detect axillary lymph node metastasis of breast cancer and to evaluate the anigiogenesis of lymph nodes in the axilla. PATIENTS AND METHODS: Forty three primary breast cancer patients (N0: 26 cases, N1: 5 cases, N2: 2 cases) who underwent IV-DSA between January and November 2000 were included in the study. Infinix CB apparatus (Toshiba, Japan) was used to collect IV-DSA images and when a mass became stained in the axilla, it was considered to be metastatic. The angiogenesis was studied by examining microvessel density (MVD) after lymph node immunostaining for factor VIII. Primary tumor was detected by IV-DSA in all 43 cases. RESULTS: Axillary lymph node metastases were detected by IV-DSA in 34.9% of cases (15/43), and by pathology in 37.2% (16/43). The sensitivity, specificity, and accuracy of the diagnostic method were 75.0% (12/16), 88.9% (24/27), and 83.7% (36/43), respectively. MVD, calculated after immunostaining for factor VIII, was significantly lower in the in metastatic region of lymph nodes identified by DSA (88.5 +/- 35.0) than in metastasis-free lymph nodes (141.1 +/- 34.0, P < 0.0001). CONCLUSIONS: IV-DSA is useful in the diagnosis of axillary lymph node metastasis of breast cancer. Our results suggest that the primary factors involved in the mechanism of DSA display may be different from high/low MVC values.     

早期宫颈癌前哨淋巴结活检的临床研究

目的:评价早期宫颈癌前哨淋巴结(SLN)活检的必要性、准确性及临床应用价值.方法:将80例早期宫颈癌患者分别应用生物活性染料亚甲蓝和99Tcm-硫胶体检测SLN,阴性SLN及非SLN行CK19免疫组化检查.结果:80例患者中76例成功检测出227枚SLN,蓝染法、放射性同位素法和联合法检出率分别为80.0%、90.0%...     

下咽癌颈部及咽后淋巴结转移的CT/MRI分析

背景与目的:下咽癌早期即可出现区域淋巴结转移,然而关于下咽癌区域淋巴结尤其是咽后淋巴结转移的报道少见。本研究旨在通过对下咽癌CT/MRI扫描结果的分析,探讨下咽癌区域淋巴结特别是咽后淋巴结转移的特性,为临床治疗提供参考。方法:回顾性分析2000年8月至2009年3月我院病理证实的88例下咽癌区域淋巴结转移的CT/MRI结果。对其局部分期、各区域淋巴结转移的相互关系采用χ2检验和Logistic多因素分析研究。结果:下咽癌的区域淋巴结转移率为73.9%,Ⅱa、Ⅱb、Ⅲ区淋巴结转移发生率最高,分别为61.4%、44.3%及37.5%。Ⅰ、Ⅳ、Ⅴ、Ⅵ区及咽后淋巴结转移都较少,并且均合并Ⅱ、Ⅲ区淋巴结转移。单因素分析显示Ⅰb、Ⅲ区淋巴结转移与Ⅳ区淋巴结转移,Ⅱb区、双侧颈部淋巴结转移与咽后淋巴结转移的关系有统计学意义。多因素分析结果显示Ⅳ区淋巴结转移与Ⅵ区淋巴结转移,双侧颈部淋巴结转移与咽后淋巴结转移的关系有统计学意义。结论:下咽癌区域淋巴结转移途径遵循一定的规律,跳跃性转移少见,以Ⅱ、Ⅲ区转移最常见。双侧颈部淋巴结可能是咽后淋巴结转移的危险因素。     

Preoperative diagnosis of lymph node metastases in gastric cancer by magnetic resonance imaging with ferumoxtran-10

Background Knowledge regarding the presence and location of lymph node metastasis in gastric cancer is essential in deciding on the operative approach. Lymph node metastases have been diagnosed with imaging tests such as computed tomography (CT) and ultrasonography (US); however, the accuracy of such diagnoses, based on size and shape criteria, has not been adequate. Ferumoxtran-10 (Combidex; Advanced Magnetics) is a lymphotropic contrast agent for magnetic resonance imaging (MRI) whose efficacy for the detection of metastatic lymph nodes in various cancers has been reported by several investigators; however, its efficacy for this purpose has not been reported for gastric cancer. We investigated the efficacy of ferumoxtran-10-enhanced MRI for the diagnosis of metastases to lymph nodes in gastric cancer. Methods Seventeen consecutive patients who were diagnosed with a nonearly stage of gastric cancer were enrolled in the study. All the patients were examined by MRI (Signa Horizon 1.5 T; GE Medical; T2*-weighted images) before and 24 h after the intravenous administration of ultrasmall particles of superparamagnetic iron oxide — ferumoxtran-10 (2.6 mg Fe/kg of body weight) — and the presence or absence of metastasis was determined from the enhancement patterns. The imaging results were compared with the corresponding histopathological findings following surgery. Results Of 781 lymph nodes dissected during surgery, the imaging results of 194 nodes could be correlated with their histopathological findings. Fifty-nine lymph nodes from 11 patients had histopathological metastases. In nonaffected normal lymph nodes, we observed dark signal intensity on MRI caused by the diffuse uptake of the contrast medium by macrophages resident in the lymph nodes, which phagocytose the iron oxide particles of ferumoxtran-10. The number of phagocytic macrophages was decreased in metastatic lymph nodes, and they showed various patterns of decreased uptake of ferumoxtran-10. Three enhancement patterns were observed in lymph nodes: (A) lymph nodes with overall dark signal intensity due to the diffuse uptake of ferumoxtran-10; (B) lymph nodes with partial high signal intensity due to partial uptake; and (C) no blackening of lymph nodes due to no uptake of ferumoxtran-10. Patterns (B) and (C) were defined as metastatic. The sensitivity, specificity, positive predictive value, negative predictive value, and overall predictive accuracy of postcontrast MRI were 100% (59/59), 92.6% (125/135), 85.5% (59/69), 100% (125/125), and 94.8% (184/194), respectively. These parameters for predictive accuracy were much superior to these parameters previously evaluated by CT or US. Nodes in the retroperitoneal and paraaortic regions were more readily identified and diagnosed on the MR images than those in the perigastric region. Conclusion The present study confirmed that ferumoxtran-10-enhanced MRI is useful in the diagnosis of metastatic lymph nodes and that the use of this modality will be helpful in treatment decision-making for gastric cancer patients.     

Interstitial irradiation by 192Ir seed assemblies in fixed cervical lymph node metastases

Eleven patients with fixed cervical lymph node metastases were treated using external irradiation followed by interstitial implants, 137Cs needles were used for one patient and 192Ir seed-assemblies for 10 patients. The local tumor responses were 4 CR, 6 PR and 1 NC. Acute tolerance was good, and there were no major late injuries except for one case of severe subcutaneous fibrosis. No morbidities such as local infection, bleeding or pulmonary injuries were encountered. Clear-cut dose control relationships were demonstrated; the local control of the nodes treated with intervals of more than one month between external and interstitial irradiation was poor. It is considered that adequate treatment is to give 40 Gy over 4 weeks by external irradiation first, then, after an interval of 2 weeks, to give 40-50 Gy over 4-5 days using 192Ir interstitial implants. The interstitial implants appeared to provide an improvement in local control and in the therapeutic ratio of fixed cervical lymph node metastases.     

中晚期宫颈癌腹主动脉旁淋巴结转移治疗的临床研究

目的:研究中晚期（Ⅱb-Ⅲb期）宫颈癌腹主动脉旁淋巴结(PALN)转移采用手术和放疗治疗的疗效。方法:选择中晚期（Ⅱb-Ⅲb期）腹主动脉旁淋巴结转移的宫颈癌患者76例,观察组43例,行腹主动脉旁淋巴结清扫术,术后行同步放化学治疗。对照组33例,行宫颈癌同步放化学治疗。分析与患者3年生存率有关的临床病理因素,探讨影响患者预后的因素。结果:手术分期、病理分级、SCCA水平、局部肿瘤大小、腹主动脉旁淋巴结大小、治疗方法与患者的3年生存率有关。多因素分析表明影响患者生存期的因素是分期、分级、局部肿瘤大小、腹主动脉旁淋巴结大小、治疗方法。结论:中晚期宫颈癌腹主动脉旁淋巴结转移,行腹主动脉旁淋巴结切除并辅以术后延伸放疗联合同期化疗,对于病人治疗有重要意义。     

Sentinel lymph node detection using computed tomography lymphography is accurate after neoadjuvant chemotherapy for breast cancer

For breast cancer patients who have undergone neoadjuvant chemotherapy (NAC), a sentinel lymph node biopsy (SLNB) has not been recommended until recently. This is due to the possible lymph-flow interruption caused by fibrotic changes following chemotherapy and possible increases in false-negative cases. We investigated the changes in the lymph-flow and the detection of sentinel lymph nodes (SLNs) using computed tomography (CT) lymphography before and after NAC. We enrolled 53 patients with breast cancer who had undergone CT lymphography between May 2004 and April 2006. In total, 75 examinations were performed; 44 before NAC and 31 just after NAC. The CT lymphography procedures were approved by the medical ethics committee of our university. After a comprehensive explanation, written informed consent was obtained from all the patients, prior to enrollment in the study. Differences in changes in the lymph-flow, detection of SLNs, and changes in the number of detected SLNs were examined before and after NAC. Differences in the categoric variables were analyzed using the Chi-square test or Fisher's exact test. The identification rate (90.5%) of the SLNs following NAC was higher than the one before NAC (79.5%). However, no statistically significant difference was noted. No interruptions to the lymph-flow prevented the detection of SLNs by NAC. By performing CT lymphography before and after NAC, the interruption to the lymph-flow can be checked and the site of SLNs can be identified prior to surgery. We found that SLNB is recommended for breast cancer patients with or without NAC.     

Immunolymphoscintigraphy for the detection of lymph node metastases from breast cancer

The presence of metastases in the regional lymph nodes is the major prognostic factor in breast cancer in the absence of overt distant metastases and is also an important indicator of the need for adjuvant therapy in "early" breast cancer. Currently, the accurate assessment of axillary lymph node status requires axillary dissection which has an associated morbidity. An alternative method of identifying patients who are "node positive" has been developed by means of immunolymphoscintigraphy with s.c. administered radioiodinated monoclonal antibody. The 131I-labeled anti-breast cancer antibody (RCC-1; 400 micrograms) and cold iodine-labeled "blocking" antibody (Ly-2.1; 2 mg which is nonreactive with breast cancer) were injected s.c. into both arms and scintigraphy images were obtained 16-18 h after the injection, using the axilla contralateral to the side of the breast cancer as the control. Studies were reported as positive (and therefore indicative of lymph node metastases) if the amount of background-subtracted radioactive count in the axilla of interest exceeded the normal side by a radio equal to or greater than 1.5:1.0 as assessed by computer analysis. In 38 of 40 patients the findings on scintigraphy were correlated with operative and histopathological findings on the axillary dissection specimen or cytological findings of fine needle aspiration of axillary lymph nodes. In a prospective study of 26 patients, the method is more sensitive (86%) and specific (92%) than preoperative clinical assessment (57% sensitivity, 58% specificity) in the detection of axillary lymph node metastases; and by combining both modalities of assessment, there was an improvement in the sensitivity (100%) but a deterioration in the specificity (50%). There was no significant complication from this essentially outpatient procedure and only 1 of 40 patients developed a human anti-mouse antibody response. This novel and safe method of imaging may become a most useful adjunct in the surgical management of breast cancer.     

Intensity-modulated radiotherapy for cervical lymph node metastases from unknown primary cancer

PURPOSE: To compare the effectiveness of intensity-modulated radiotherapy (IMRT) and conventional (two-dimensional) radiotherapy in the treatment of cervical lymph node metastases from unknown primary cancer (UPC). METHODS AND MATERIALS: Between February 2003 and September 2006, 23 patients with UPC of squamous cell carcinoma were treated with IMRT. Extended putative mucosal and bilateral nodal sites were irradiated to a median dose of 66 Gy. In 19 patients, IMRT was performed after lymph node dissection, and in 4 patients primary radiotherapy was given. The conventional radiotherapy group (historical control group) comprised 18 patients treated to a median dose of 66 Gy between August 1994 and October 2003. RESULTS: Twenty patients completed treatment. As compared with conventional radiotherapy, the incidence of Grade 3 acute dysphagia was significantly lower in the IMRT group (4.5% vs. 50%, p = 0.003). By 6 months, Grade 3 xerostomia was detected in 11.8% patients in the IMRT group vs. 53.4% in the historical control group (p = 0.03). No Grade 3 dysphagia or skin fibrosis was observed after IMRT but these were noted after conventional radiotherapy (26.7%, p = 0.01) and 26.7%, p = 0.03) respectively). With median follow-up of living patients of 17 months, there was no emergence of primary cancer. One patient had persistent nodal disease and another had nodal relapse at 5 months. Distant metastases were detected in 4 patients. The 2-year overall survival and distant disease-free probability after IMRT did not differ significantly from those for conventional radiotherapy (74.8% vs. 61.1% and 76.3% vs. 68.4%, respectively). CONCLUSIONS: Use of IMRT for UPC resulted in lower toxicity than conventional radiotherapy, and was similar in efficacy.     

Retroperitoneal lymph node resection in patients with cervical cancer

OBJECTIVE: To determine predictive factors precluding complete resection of metastatic lymph nodes identified by pre-operative imaging in patients with cervical cancer. METHODS: Retrospective clinical review of patients with cervical cancer with suspected metastases to pelvic and/or periaortic lymph nodes who underwent lymph node dissection by laparotomy at The University of Texas M.D. Anderson Cancer Center from September 1990-December 2004. RESULTS: A total of 104 patients were the subject of this analysis. Post-operatively, 25 patients (24%) had negative lymph nodes, 62 patients (60%) had macroscopically positive lymph nodes, one patient had microscopically positive (1%) and 16 patients (15%) had unresectable lymph nodes. Body mass index did not have any impact on successful resection of lymph nodes. On univariate analysis age (p=0.049) and size and location of the largest lymph node were associated with resection status (p=0.001 and 0.020). Logistic regression confirmed that chance of achieving a successful resection decreases with increasing age (p=0.046) and size of largest lymph node (0.002). CONCLUSIONS: The ability to completely resect suspected metastatic lymph nodes at the time of extraperitoneal lymph node dissection in patients with cervical cancer is associated with size and location of largest lymph node.     

宫颈癌盆腔淋巴结转移调强放射治疗的疗效分析

目的 探讨调强放射治疗(IMRT)对宫颈癌盆腔淋巴结转移患者的临床疗效.方法 回顾性分析94例宫颈癌患者的临床资料,将47例行IMRT方法治疗的患者作为IMRT组,将47例行普通放疗方法治疗的患者作为普通放疗组.分析比较两组患者治疗3个月后的近期疗效、急性不良反应和3年的生存情况.结果 治疗3个月后,IMRT组盆腔淋巴结完全消失和缩小消退的比例均高于普通放疗组(P﹤0.05).IMRT组3年死亡29例,累积生存率为38.3%,普通放疗组3年死亡34例,累积生存率为27.7%,IMRT组和普通放疗组的中位生存时间分别为29(23~35)个月和13(7~20)个月,IMRT组中位生存时间长于普通放疗组(P﹤0.05).IMRT组消化系统和骨髓抑制等急性不良反应均较普通放疗组明显减少,差异有统计学意义(P﹤0.01),且IMRT组均未出现3级不良反应.结论 I MRT不仅可以提高瘤体组织的放射剂量,还可以提高治疗的疗效,减少急性不良反应的发生,延长患者治疗后3年的中位生存时间.     

Ultrasound detection of axillary lymph node metastases in breast cancer

Presence or absence of lymph node metastases is the most accurate prognostic indicator in breast cancer. Clinical examination is unreliable in detecting involved nodes. Preoperative ultrasound scan of the axilla has been performed in 140 consecutive women with breast cancer. The sensitivity for involved nodes was 66% which was significantly higher than clinical examination (42%) (P = less than 0.01). However ultrasound gave more false positives than clinical examination and thus no overall improvement in prognostic information was achieved.     

Risk of bilateral cervical lymph node metastases in papillary thyroid cancer

We evaluated the risk of bilateral or contralateral cervical lymph node metastases in 135 patients with papillary thyroid cancer who underwent bilateral neck dissection. We confirmed that bilateral jugular lymph node metastases were frequent in patients with obvious carcinoma in both lobes of the gland, in those with cancers arising in the isthmus, in those with clinically detectable bilateral lymphadenopathy, and in those with recurrent thyroid cancer. However, only 24% of the patients who had cancer clinically confined to one lobe with no bilateral or contralateral lymphadenopathy had histologically detected bilateral or contralateral jugular lymph node metastases. But the occurrence of contralateral jugular lymph node metastases was significantly correlated with both clinical lymphadenopathy in the ipsilateral neck and contralateral paratracheal lymph node metastases. Bilateral lymph dissection might be beneficial for these patients. © 1993 Wiley-Liss, Inc.     

Tumor carbonic anhydrase 9 expression is associated with the presence of lymph node metastases in uterine cervical cancer

Tumor hypoxia has a pronounced effect on malignant progression and metastatic spread of human tumors. As carbonic anhydrases (CA) 9 and 12 are induced by the low-oxygen environment within tumors, we investigated the relationship between the expression of these two CA and the presence of metastatic lymph nodes (LN) in uterine cervical cancer. CA9/CA12 expression was evaluated histochemically in primary cervical cancer tissues of 73 patients who underwent laparoscopic LN staging and two patients with clinical staging before definitive radiotherapy at the National Cancer Center, Korea. We also evaluated CA9 expression in 33 patients with pathologically confirmed metastatic LN. CA9 expression in the primary tumors was significantly associated with LN metastasis (P = 0.03) and poorer disease-free survival (relative risk, 6.1; 95% confidence interval, 1.3-28.3, P = 0.02, multivariate analysis), whereas CA12 expression did not show such a relationship. In addition, 21 of 24 metastatic LN revealed similar CA9 expression (P = 0.001), suggesting that CA9-expressing tumor cells had a higher metastatic potential. CA9 was expressed in 45 of 75 (60%) primary tumors, with positive tumor cells observed predominantly in the area away from the blood vessels. In contrast, CA12 expression was observed in only 29 of 74 primary tumors (39%), without a specific pattern. These findings indicate that expression of CA9, but not CA12, in tumors is associated with the presence of LN metastases and poorer prognosis. Selective application of new treatment modalities based on CA9 expression to prevent LN metastases may improve overall treatment outcome in patients with uterine cervical cancer.