OSNA-Based Novel Molecular Testing for Lymph Node Metastases in Colorectal Cancer Patients: Results from a Multicenter Clinical Performance Study in Japan

Background

Lymph node (LN) metastasis in colorectal cancer (CRC) is a critical factor in making accurate prognoses and therapeutic decisions. This study evaluated the clinical performance of the one-step nucleic acid amplification (OSNA) assay in accurately diagnosing LN metastases in CRC patients through the specific detection of cytokeratin 19 mRNA levels in LNs.

Methods

The OSNA assay was performed on 121 LNs dissected from early-stage CRC patients (pStage 0 or I) or from patients with benign colorectal disease (study 1). Separately, 385 LNs were dissected from 85 CRC patients (any stage); the OSNA assay was performed on half of each LN, and the results were compared with histopathological examination in 2-mm intervals of the other LN half (study 2).

Results

In study 1, all 121 histopathologically negative LNs were also negative by the OSNA assay (concordance rate for metastasis negative: 1.0, 95% confidence interval [95% CI]: 0.976–1.0). In study 2, the concordance rate between the OSNA assay and the 2-mm-interval histopathological examination was 0.971 (95% CI: 0.950–0.984), with a sensitivity of 0.952 (95% CI: 0.881–0.987) and a specificity of 0.977 (95% CI: 0.953–0.991).

Conclusions

The OSNA assay provided a judgment performance equivalent to a 2-mm-interval histopathological examination, a more detailed assay than the common pathological examination. Therefore, the OSNA assay is considered a new molecular examination method for the diagnosis of LN metastases in CRC patients in clinical settings.     

The performance of one-step nucleic acid amplification assay for intraoperative detection of sentinel lymph node macrometastasis in breast cancer: An updated meta-analysis

BackgroundOne-step nucleic acid amplification (OSNA) assay is a molecular diagnostic method for intraoperative detection of lymph node metastasis by amplifying cytokeratin 19 mRNA. We aim to further evaluate the performance of OSNA assay for the intraoperative diagnosis of sentinel lymph node metastasis in breast cancer.MethodsPubMed, Cochrane Library, Web of Science databases were searched to retrieve related literature published up until December 2017. This meta-analysis was performed using a random-effects model. Risks of bias and quality assessments of included studies were evaluated and subgroup analysis was performed.ResultsNineteen studies were included in this meta-analysis. For overall metastasis, the pooled sensitivity, specificity and area under the summary receiver-operating characteristic curve (AUC) were 0.90, 0.96 and 0.98, respectively. For macrometastasis, the pooled sensitivity, specificity and AUC were 0.85, 0.98 and 0.94, respectively.ConclusionOSNA assay is an accurate molecular diagnosis for intraoperative detection of sentinel lymph node macrometastasis in breast cancer.     

Intraoperative Molecular Assessment for Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma Using One-Step Nucleic Acid Amplification (OSNA) Assay

Background

Conventional intraoperative pathological examination for Sentinel node navigation surgery (SNNS) has been controversial. We evaluated the efficacy of one-step nucleic acid amplification (OSNA) assay for intraoperative diagnosis of cervical lymph node (CLN) metastasis compared with histopathological examination in patients with head and neck squamous cell carcinoma (HNSCC).

Methods

A total of 175 CLNs dissected from 56 patients with HNSCC who underwent surgery at Aichi Cancer Center, Kyorin University, Gunma University or Fukushima Medical University, between April 2008 and December 2011 were enrolled. CLN samples were sectioned into four equal pieces, with two of each used for OSNA assay and other histopathological examinations. The diagnostic value of OSNA assay in HNSCC patients in predicting the results of histopathological diagnosis was evaluated using the area under the receiver operating characteristic (AUROC) curve.

Results

OSNA assay showed acceptable efficacy in the detection of pathological CLN metastasis (AUROC 0.918, 95?% confidence interval [CI] 0.852?C0.984). Regarding the CK19mRNA cutoff value, the optimum cutoff point in HNSCC patients was 131?copies/??l (sensitivity: 82.4, 95?% CI 65.5?C93.2; specificity: 99.3, 95?% CI 96.1?C100.0; positive likelihood ratio 116.1; negative likelihood ratio 0.2].

Conclusions

We demonstrated that OSNA assay is useful in intraoperative diagnosis for CLN metastasis in patients with HNSCC. OSNA assay could be applied for SNNS in HNSCC patients.     

Prognostic significance of histomorphologic features of lymph node metastases in prostate cancer patients treated with radical prostatectomy: A single center study

ObjectiveWe assessed the prognostic value of histomorphologic features of lymph node (LN) metastases in patients with prostate cancer treated with radical prostatectomyMaterials and MethodsWe evaluated the effect of the features of LN metastasis on the risk of biochemical recurrence (BCR) in 280 LN-positive patients who underwent radical prostatectomy between 2006 to 2018. LN specific parameters recorded included number of metastatic LNs, size of the largest metastatic focus, Gleason Grade (GG) of the metastatic focus, and extranodal extension (ENE).ResultsA solitary positive LN was found in 166/280 (59%), 95/280 (34%) patients had 2-4 positive LNs, and 19/280 (7%) had 5 or more positive LNs. The size of the largest metastatic focus > 2 mm (macrometastasis) in 154/261 (59%). GG of the metastatic focus was as follows: GG 1-2: 29/224 (13%); GG 3: 27/224 (12%); and GG 4-5: 168/224 (75%). ENE was identified in 99/244 (41%). We found the number of LNs positive (2-4 vs. 1 Hazard ratio (HR) = 1.60; 95% CI: 1.02 to 2.5; P = 0.04) and GG of the metastatic focus (GG 4&5 vs. 1-3 HR = 1.90; 95% CI: 1.14-3.2; P= 0.014) to be independent predictors of the risk of BCR after surgery on multivariate analysis.ConclusionsOur study showed the number of LNs positive and GG of the LN metastatic focus to be significant independent predictors of BCR after radical prostatectomy. We recommend reporting histomorphologic parameters of LN metastasis as they may help in defining BCR risk categorization.     

Total tumor load assessed by one-step nucleic acid amplification assay as an intraoperative predictor for non-sentinel lymph node metastasis in breast cancer

BackgroundThis study aimed to determine the relationship between CK19 mRNA copy number in sentinel lymph nodes (SLN) assessed by one-step nucleic acid amplification (OSNA) technique, and non-sentinel lymph nodes (NSLN) metastization in invasive breast cancer. A model using total tumor load (TTL) obtained by OSNA technique was also constructed to evaluate its predictability.MethodsWe conducted an observational retrospective study including 598 patients with clinically T1-T3 and node negative invasive breast cancer. Of the 88 patients with positive SLN, 58 patients fulfill the inclusion criteria.ResultsIn the analyzed group 25.86% had at least one positive NSLN in axillary lymph node dissection. Univariate analysis showed that tumor size, TTL and number of SLN macrometastases were predictive factors for NSLN metastases. In multivariate analysis just the TTL was predictive for positive NSLN (OR 2.67; 95% CI 1.06–6.70; P = 0.036). The ROC curve for the model using TTL alone was obtained and an AUC of 0.805 (95% CI 0.69–0.92) was achieved. For TTL >1.9 × 10⁵ copies/μL we got 73.3% sensitivity, 74.4% specificity and 88.9% negative predictive value to predict NSLN metastases.ConclusionWhen using OSNA technique to evaluate SLN, NSLN metastases can be predicted intraoperatively. This prediction tool could help in decision for axillary lymph node dissection.     

The prognostic value of different node staging systems in patients with ≤15 lymph nodes following surgery for gastric adenocarcinoma

Aim: Lymph node (LN) status is an important prognostic indicator in patients with gastric cancer (GC). Although American Joint Committee on Cancer/International Union against Cancer (AJCC/UICC) is the most widely used staging system, there is a challenge in predicting survival of patients when the number of total harvested LNs is ≤15. Our aim was to investigate the prognostic performances of seventh edition AJCC/UICC, lymph-node ratio (LNR), and log odds of metastatic lymph nodes (LODDS) on the overall survival (OS) of GC patients with ≤15 examined LNs after gastric resection.

Material and method: A total of 74 patients who underwent curative resection for gastric adenocarcinoma and had ≤15 LNs at the final histopathological examination were included in the study. The prognostic ability of three node staging models to predict OS was assessed using the area under the curve (AUC).

Results: Of the 74 patients, 15 (20.3%) had no LN metastasis whereas 59 (79.7%) had nodal involvement. The median OS was 26 months. When assessed as a continuous variable, LNR was the strongest staging system to stratify GC patients on the basis of LN status. LODDS had superiority on other node staging models when the number of LNs retrieved was modeled as categorical variable.

Conclusions: LNR (continuous) and LODDS (categorical) were the strongest indicators of OS in GC when the number of LN harvested was ≤15. Therefore, they may be considered as an alternative nodal staging systems for GC.     

La densidad de los ganglios linfáticos en la linfadenectomía retroperitoneal como marcador novel para predecir la recurrencia en pacientes con cáncer testicular de células germinales: estudio de casos y controles y experiencia clínica a largo plazo de un hospital de referencia terciario

Introduction and objectivesIn this retrospective study, we aimed to evaluate lymph node (LN) density in retroperitoneal lymph node dissection (RPLND) to analyze whether residual mass after chemotherapy might behave as predicting factor for recurrence in patients with germ cell testicular cancer (GCTC).Materials and methodsThe data of 185 patients that were operated between 12/2004 and 02/2017 because of GCTC were reviewed retrospectively. LN density was calculated. The patients were compared statistically in terms of demographic features, tumor characteristics, serum tumor marker levels, treatment strategies, and pathological results according to GCTC subtypes. Correlation analysis was performed to determine the parameters related to recurrent disease.ResultsThe median follow-up was 79 (31-179) months and the median age of the patients was 23 (16-71). The median tumor size was 4 (1-18) cm. Five (2.7%) patients had metastatic disease at initial diagnosis. Seminoma, non-seminomatous-GCT and mix type-GCTC was detected in 62 (33.5%), 60 (32.4%) and 63 (34.1%) patients, respectively. Following inguinal orchiectomy, 48 (25.9%) patients underwent follow-up, 126 (68.1%) patients underwent chemotherapy and 11 (5.9%) patients underwent radiotherapy. A total of 21 (11.4%) patients underwent post-chemotherapy RPLND. Early and late recurrence was seen in 3 (1.6%) and 2 (1.1%) of the patients, respectively. A mild to moderate, negative, but significant correlation was found between the recurrence and the number of LNs containing metastatic deposits and LN density (r= –0.490, P=.024 and r= –0.450, P=.041, respectively).ConclusionsThere was a negative correlation between the number of LNs containing metastatic deposits and LN density and recurrent disease.     

逆转录-聚合酶链反应检测乳腺癌腋淋巴结微转移的研究

目的探讨乳腺癌患者淋巴结内癌微转移灶的临床意义。方法采用逆转录－聚合酶链反应技术,扩增细胞骨架角蛋白１９（ＣＫ１９）,对１５例乳腺癌患者的癌组织及其６１个腋窝淋巴结进行检测。结果１５例患者乳腺癌组织均有ＣＫ１９ｍＲＮＡ表达,５个正常淋巴结均无表达。６１个淋巴结同时进行逆转录－聚合酶链反应（ＲＴ－ＰＣＲ）及组织学检查,７个淋巴结病理证实有转移,其ＣＫ１９ｍＲＮＡ亦都表达阳性;病理未发现转移的５４个淋巴结中有１２个ＣＫ１９ｍＲＮＡ表达阳性。结论ＣＫ１９ＲＴ－ＰＣＲ方法检测乳腺癌腋淋巴结癌微转移比组织学检查敏感（χ２检验,Ｐ＜０．０１）,特别在筛选组织学检查淋巴结阴性而具有高度复发危险性的患者具有实用价值。     

Intraoperative assessment of sentinel lymph node by one-step nucleic acid amplification in breast cancer patients after neoadjuvant treatment reduces the need for a second surgery for axillary lymph node dissection

PurposeSentinel lymph node (SLN) biopsy has been shown to be both accurate and feasible for women who receive neoadjuvant chemotherapy (NAC). Intraoperative assessment of SLN by frozen sections can produce false negative results. The aim of this study was to compare two different techniques of intraoperative assessment of SLN in breast cancer patients treated with NAC: frozen section (FS) and molecular assay (OSNA).MethodsA multicenter cohort of 320 consecutive breast cancer patients treated with NAC between 2010 and 2014 was analyzed. FS was performed intraoperatively in 166 patients (H&E cohort) and OSNA in 154 patients (OSNA cohort).ResultsA mean of 2.15 SLNs by FS and 1.22 SLNs by OSNA was assessed (p = 0.03). SLN metastasis was found in 44 patients (26.5%) by FS and in 48 (31.2%) by OSNA (p = 0.4). There was no statistical significance in rates of macrometastasis (75%), micrometastasis (20.5%) or ITCs (4.5%) when assessed by FS compared to OSNA (52.3%, 36.3% and 11.4%, respectively) (p = 0.06). There were 10 patients in the H&E cohort with positive-SLN in the definitive pathology assessment with negative intraoperative FS. When OSNA and definitive pathology were compared, there were no differences in rates of macrometastasis (61.1%), micrometastasis (33.3%) nor ITCs (5.6%) (p = 0.5). Fifty-four patients in the H&E cohort and 44 in the OSNA cohort had ALND after positive-SLNs. ALND was performed in a second surgery in 10 patients (18.5%) in the H&E cohort for intraoperative FS false negative results, 90% being micrometastasis. 42 out of 44 patients (95.5%) in the OSNA cohort had an ALND in the same surgery (p = 0.03).ConclusionsOSNA assay detects SLNs metastases as accurately as conventional pathology in the NAC setting. Intraoperative definitive assessment of the SLN by OSNA reduces the need for a second surgery for ALND in 18.5% of breast cancer patients with a positive-SLN after NAC.     

Sentinel and nonsentinel lymph node assessment using a combination of one-step nucleic acid amplification and conventional histological examination

BackgroundClinical significance of intraoperative sentinel lymph node (SLN) metastases detection using one-step nucleic acid amplification (OSNA) has not been thoroughly investigated. The aim of this study was to assess the usefulness of using a combination of OSNA and conventional histological examinations.Materials and methodsWe included 772 consecutive patients with clinical node-negative cTis-cT3 primary breast cancer who underwent SLN biopsy with intraoperative OSNA and multi-section histological examination at our institution. We estimated the concordance rate and compared SLN metastases detection rates between the two methods. We also compared non-SLN metastasis detection rate between patients who tested positive in OSNA and those who tested positive in histology.ResultsAmong 772 patients, SLN metastases were intraoperatively detected in 211 (26.4%) by either OSNA or histology, in 168 (21.8%) by OSNA, and in 150 (19.4%) by histology. The concordance rate between OSNA and histological examination was 89.2%, but only 123 (58.8%) patients tested positive in both OSNA and histology; 45 were positive in OSNA only and 43 were positive in histology only.SLN status as per both OSNA and histology was significantly correlated with the presence of non-SLN metastases and multivariate analysis-identified independent predictive factors of non-SLN metastases.ConclusionsIntraoperative SLN metastases detection may be more accurate with a combination of OSNA and histological examination than with OSNA or histological examination alone. By using both methods, we can reduce the risk of false negative rate in SLN biopsy, and may prevent physicians from overlooking patients with non-SLN metastases.     

淋巴结清扫总数和阴性淋巴结数对根治性远端胃大部切除胃癌患者预后的影响

目的 探讨淋巴结清扫总数和阴性淋巴结数目对根治性远端胃大部切除胃癌患者预后的影响.方法 1995年1月至2004年11月,对634例胃癌患者施行根治性远端胃大部切除手术(R0切除).分析淋巴结清扫总数与阴性淋巴结数目的相关性;对预后因素进行单因素及多因素分析;分析淋巴结清扫总数、阴性淋巴结数目与术后5年生存率的关系.结果 本组591例(93.2%)获得随访,时间5～14年,其中位生存期为62.0个月,术后5年生存率为57.6%.淋巴结清扫总数与阴性淋巴结数目的相关性具有统计学意义(P＜0.05).肿瘤浸润深度、阳性及阴性淋巴结数目和淋巴结清扫总数是影响本组患者预后的独立因素.相同TNM分期中,患者的术后5年生存率有随淋巴结清扫总数和阴性淋巴结数目增加而增高的趋势且具有统计学意义(P＜0.05).线性回归预测,淋巴结清扫总数每增加l0枚,患者术后5年生存率都有不同程度的提高:全组为13.1%、Ⅰ期为14.2%、Ⅱ期为20.5%、Ⅲ期为17.5%和Ⅳ期为10.9%;而每多清扫10枚阴性淋巴结,患者术后5年生存率亦可提高:全组为19.2%、Ⅰ期为20.1%、Ⅱ期为18.8%、Ⅲ期为18.4%和Ⅳ期为18.0%.结论 淋巴结清扫总数和阴性淋巴结数目可反映胃癌淋巴结清扫的程度并预测患者预后,应努力增加根治性远端胃大部切除胃癌患者的淋巴结清扫总数和阴性淋巴结数目,以提高远期疗效.     

Is OSNA better than imprint cytology for intraoperative diagnosis of cancer involvement of axillary sentinel node in breast cancer?

ObjectiveThe study aim was to establish Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value (NPV), and Accuracy Values of both imprint cytology (IC) and the OSNA assay for intraoperative assessment of axillary sentinel node (SN) cancer involvement in breast cancer. Specifically, we wished to find out if true positive and false negative results of IC were associated to axillary lymphadenectomy (ALND). Also, we addressed a comparative cost analysis between techniques.Methods244 patients treated for breast cancer in the Breast Unit of Hospital Germans Trias i Pujol from 2011 to 2015 were prospectively included. A transversal, consecutive design was applied to assess IC compared to the reference test (OSNA). Inclusion criteria were: T1 and T2 tumors with negative nodes, both clinically and on ultrasound.ResultsSensitivity of IC for macrometastases was 70%. The NPV of IC for macrometastases was 95,75%. Accuracy of IC was 96,12%. In the comparative cost analysis, the release time of results for OSNA doubled that of IC and was associated with an increased cost of € 370.ConclusionsIC has been stated as a good technique for intraoperative cancer involvement SN with high sensitivity and NPV compared to the OSNA assay. It allows keeping the whole node tissue and thus the possibility of improved histopathological evaluation, which can be useful for adjuvant, and offers the advantage of being less time consuming. Cost analysis shows a higher cost for OSNA, which may exceed the benefit of sorting out false negatives from IC.     

Use of touch preps for intraoperative diagnosis of sentinel lymph node metastases in breast cancer

Background: Intraoperative touch prep (TP) is highly accurate for determining positive breast cancer margins and thereby reducing the need for second surgeries. It also may be useful in determining the status of the sentinel lymph node (SLN) during the initial surgical resection. The objective of this study was to test the ability of intraoperative TP to predict metastatic disease and, thus, the necessity for axillary lymph node dissection (ALND) at the time of SLN biopsy. Methods: Fifty-five patients with invasive breast cancer were entered in the SLN biopsy protocol. The SLN was identified by gamma probe, dissected, and sent to pathology for TP and permanent sections. Level I and II ALND was then performed. Any radiolabeled LN in the lymphadenectomy specimen also was sent for TP and permanent sections. Results: A total of 124 radiolabeled lymph nodes (LNs) were submitted for TP; of these, 93 (75%) were SLNs. Pathologic diagnosis by TP was correct compared with permanent sections for 99.2% of the nodes. There were no false positives. There was one (0.8%) false negative. The positive predictive value was 100% and the negative predictive value was 99%. Sensitivity was 95.7% and specificity was 100%. Conclusions: TP is a simple, quick, and accurate method for detecting metastatic disease in the SLN and, when used intraoperatively, enables the surgeon to determine whether or not an ALND is necessary at the time of the initial surgery.     

Clinical impact of lymphadenectomy extent in resectable gastric cancer of advanced stage

Background Advanced, but potentially still curable gastric cancer (stages IIIA, IIIB, or stage IV M0) is associated with very high recurrence rates after gastrectomy. The value of an extended lymph node dissection (ELND) remains unclear in this setting. Methods A resected gastric cancer data set was created through structured queries to the SEER 1973–2000 database. Relationships between the number of lymph nodes (LNs) examined and survival outcomes were analyzed for the stage subgroups characterized by the N categories N2 or N3, and transmural tumor extension (T categories T2b or T3). Results The study group encompassed 1,377 patients, including T2b/3N2 (n = 1,076) and T2b/3N3 stage subgroups (n = 301). Total LN count (or number of negative LNs examined; P < 0.0001), number of positive LNs (P < 0.0001), age (P < 0.0001), primary site (P = 0.0002), T category (P = 0.0271), race (P = 0.0301) and gender (P = 0.0261) were independent prognostic survival predictors. A cut point analysis yielded the ability to detect significant survival differences for LN numbers up to 30 (N2) or up to 40 (N3), always in favor of the higher number of LNs examined. Best long-term survival outcomes were observed with negative LN counts of more than 15 (N2) or more than 20 (N3). Conclusions Even in transmural or serosa-positive gastric cancer with advanced nodal involvement, more extensive LN dissection and analysis influences survival. Stage-based survival prediction depends on total LN number and number of negative LNs. The mechanism remains uncertain, but is not limited to stage migration. ELND during potentially curative gastrectomy is recommended even for advanced gastric cancer.     

The Role of No. 10 Lymphadenectomy for Advanced Proximal Gastric Cancer Patients Without Metastasis to No. 4sa and No. 4sb Lymph Nodes

Background

There is no consensus in the impact of No. 10 lymph node dissection (LND) for advanced proximal gastric cancer (APGC) and the status of negative No. 4sa and No. 4sb lymph nodes (No. 4s LNs) is reportedly associated with no metastasis to No. 10 LN. We aimed to evaluate the role of No. 10 LND in APGC patients with negative No. 4s LNs and the diagnostic accuracy of intraoperative pathologic examination.

Methods

We analyzed data on 727 patients with APGC who had undergone D2 lymphadenectomy with No. 10 LND (n?=?380) or without No. 10 LND (n?=?347) between January 2005 and December 2010. Additionally, from January to July 2014, we prospectively enrolled 48 patients with APGC and examined their No. 4s LNs intraoperatively.

Results

The negative predictive efficacy of No. 4s LN status for no metastasis to No. 10 LN was 98.09 %. Operation time, blood loss, time to first solid diet, hospital stay, and postoperative complication rate differed significantly between patients with negative No. 4s LNs who underwent No. 10 LND (n?=?260) and those who did not undergo No. 10 LND (n?=?243). Differences between the two groups in 5-year overall and disease-free survival were not statistically significant. The sensitivity, specificity, and accuracy of intraoperative pathological examination of LNs were 93.42, 96.56, and 95.86 %, respectively.

Conclusions

The No. 10 lymphadenectomy may not be recommended in patients with APGC who are found by intraoperative pathological examination to have negative No. 4s LNs.

     

How many lymph nodes are enough? Assessing the adequacy of lymph node yield for staging in favorable histology wilms tumor

PurposeCurrent investigational priorities in the treatment of favorable histology Wilms tumor (FHWT) center on accurate staging and risk-stratification. The extent of lymph node (LN) sampling has not been clearly defined; its importance cannot be overstated as it guides adjuvant therapy. The identification of a minimum LN yield to minimize the risk of harboring occult metastatic disease could help development of surgical guidelines. This study focuses on using the beta-binomial distribution to estimate the risk of occult metastatic disease in patients with FHWT.Materials & methodsThe National Cancer Database was queried for patients with unilateral FHWT from 2004 to 2013. Data were used to characterize nodal positivity for patients who underwent surgery and had ≥ 1 positive LN and ≥ 2 LNs examined. The probability of missing a positive LN (i.e., false negative) for a given LN yield was calculated using an empirical estimation and the beta-binomial model. Patients were then stratified by tumor size.Results422 patients met study criteria. To limit the chance of missing a positive LN to ≤ 10%, the empirical estimation and beta-binomial model estimated that 6 and 10 LNs needed to be sampled, respectively. Tumor size did not influence the result. Internal validation showed little variation to maintain a false negative rate ≤ 10%.ConclusionsUsing mathematical modeling, it appears that the desired LN yield in FHWT to reduce the risk of false-negative LN sampling to ≤ 10% is between 6 and 10. The current analysis represents an objective attempt to determine the desired surgical approach to LN sampling to accurately stage patients with FHWT.Level of evidenceII     

CK19mRNA测定在乳腺癌腋淋巴结微转移诊断中的应用

研究敏感的方法检测乳腺癌腋窝淋巴结微转移。方法:对15例乳腺癌者的61个腋淋巴结和5个正常对照淋巴结同时进行HE染色组织学检查和CKl9逆转录-聚合酶链式反应(CK19RT-PCR)检测。结果:15例乳腺癌组织均有CK19mRNA表达,而5个正常淋巴结中均末见表达。61个腋窝淋巴结中7个组织学检查证实转移,其CK19mRNA亦表达阳性。组织学检测无转移的54个淋巴结中有12个CK19RT-PCR表达阳性,42个阴性;提示该12个淋巴结存在微转移只能用CK19RT-PCR方法检测出。经统计学分析,CK19RT-PCR与组织学检查二者有显著差异(X~2检验,P<0.01)。结论:CK19表达于恶性乳腺细胞,正常淋巴细胞无表达,CK19能作为组织特异基因进行RT-PCR扩增以检测乳腺癌腋淋巴结微转移。CK19 RT-PCR方法比组织学方法更敏感,特别对在筛选组织学检查淋巴结阴性而具有高度复发危险性的病人将有实用价值。     

Critical analysis of the 2010 TNM classification in patients with lymph node–positive bladder cancer: Influence of lymph node disease burden

ObjectivesIn 2010, a new TNM staging system was published by American Joint Committee on Cancer, changing the nodal classification to include the presence of common iliac lymph node (LN) involvement as N3 category. The objective of this study was to define the capability of the current TNM nodal classification to separate patients with different prognostic stages and to evaluate the effect of LN disease burden.Methods and materialsA total of 93 patients with metastatic LNs after radical cystectomy and extended LN dissection for urothelial carcinoma of the bladder between 1999 and 2012 were included. The median follow-up was 21.5 months. The correlation between N3 and indicators of LN disease burden was analyzed using the Spearman correlation coefficient. Recurrence-free survival (RFS) and overall survival (OS) analysis was performed using the Kaplan-Meier and Cox proportional hazards methods.ResultsThe presence of N3 disease was associated with higher number of metastatic LNs (7 vs. 2, P<0.01); however, this was highly variable and correlation coefficients between common iliac metastatic LNs and other lymphatic disease burden indicators demonstrated weak association (0.39–0.63). Patients with N1 lesions were found to have a distinct RFS and OS (P<0.01 and P = 0.01, respectively). A trend toward worse RFS (P = 0.07) and OS (P = 0.08) was observed in patients with N3 lesions. However, no difference in RFS or OS was found between patients with N2 and N3 lesions (P = 0.83 and 0.50, respectively).ConclusionsThe N3 category in the current TNM classification defines a group of patients with high but heterogeneous disease burden. This may be the explanation for its lack of prognostic stratification when compared with N2 category bladder cancer.     

脾门区血管后方淋巴结清扫在进展期近端胃癌根治术中应用价值研究

目的 探讨进展期近端胃癌行全胃切除并D2淋巴结清扫术时是否需要清扫脾门区血管后方（No.10p）淋巴结。方法 回顾性分析2010年1月至2014年12月间在福建医科大学附属协和医院胃外科接受腹腔镜全胃切除术并D2淋巴结清扫术404例近端胃癌病人资料，其中有行脾门区血管后方淋巴结清扫者68例，称No.10p组，仅行脾门区血管前方淋巴结清扫者336例，称nNo.10p组，对比两组病人淋巴结清扫情况和远期疗效的差异。结果 与nNo.10p组相比，No.10p淋巴结清扫更易出现于较年轻、体重指数（BMI）较小、分散型、脾叶血管分支少和胰尾邻近脾下极的病人（P＜0.05）。两组病人平均淋巴结清扫数目和平均阳性淋巴结数目差异均无统计学意义（P＞0.05）；虽然No.10p组获取的脾门淋巴结数目较多（P＜0.05），而两组脾门淋巴结转移发生率和阳性脾门淋巴结数目均相似（P＞0.05）。生存分析显示，No.10p组与nNo.10p组的远期预后差异无统计学意义（P＞0.05），而且不论脾门淋巴结是否转移，No.10p淋巴结清扫均不能提高病人5年存活率（P＞0.05），并且No.10p淋巴结清扫亦不能提高脾门淋巴结清扫的治疗指数。结论 No.10p淋巴结清扫虽能获得更多的脾门淋巴结，但并不能增加脾门淋巴结转移发生率和阳性淋巴结数目，亦未能提高病人的远期预后；故对于进展期近端胃癌行脾门淋巴结清扫时，可无须常规清扫No.10p淋巴结。