Jyh Cherng Yu

Prediction of Metastasis to Non-sentinel Nodes by Sentinel Node Status and Primary Tumor Characteristics in Primary Breast Cancer in Taiwan

We aimed to determine how to approach the axilla after finding a positive sentinel node (SN) for a woman with breast cancer in Taiwan. We used blue dye staining to identify the SN in 824 procedures on 811 patients with breast cancer small than 3 cm by a single surgeon. All patients underwent SN biopsy, followed by at least level II axillary dissection. All SNs were evaluated histologically and immunohistochemically with anti-cytokeratin antibodies. Non-SNs were examined by routine histology. SNs were identified in 814/824 procedures (98.8%). SN metastases were found in 286/814 (35.1%). Subsequent axillary dissections revealed tumors in non-SNs in 188 (65.7%) of these patients. There was a relatively high incidence of non-SN metastases in our population. Tumor exhibiting high nuclear grading, ER-, PR-, Erb-2/neu overexpression, lymphovascular invasion, increasing tumor size, multiple positive SNs, and macrometastatic size in SNs (> 2 mm) were all significantly correlated with non-SN metastases. Multivariate analysis showed that tumor size, the number of positive SNs, and the metastatic size in SNs were independent factors predicting the presence of positive non-SNs. Small (< 2 cm) cancers, having only micrometastatic foci in the SN and having only one SN involved are closely correlated with the tumor-free non-SNs. Our data will assist such patients regarding the need for axillary dissection after finding a positive SN.

Tartrate-Resistant Acid Phosphatase 5b Activity Is a Useful Bone Marker for Monitoring Bone Metastases in Breast Cancer Patients after Treatment

Metabolic markers of bone metabolism may be useful for the diagnosis and monitoring of bone metastasis in breast cancer patients. Serum tartrate-resistant acid phosphatase 5b (TRACP5b) activity is a novel bone resorption marker. The treatment response of serum TRACP5b activity, bone alkaline phosphatase (BAP) activity, and concentrations of NH2-terminal telopeptide of type 1 collagen (NTX) in 68 breast cancer patients with bone metastasis were determined. These patients were treated and followed up as clinically indicated. Fifty-four healthy women were recruited as control. Serum TRACP5b activity, BAP activity, and NTX level of breast cancer patients with bone metastasis were significantly higher than those of normal controls. In normal subjects, serum TRACP5b activity and NTX level are significantly correlated (P < 0.0001). Neither was correlated with BAP activity. In breast cancer patients with bone metastasis, all marker pairs correlated to each other significantly (P < 0.0001). Biomarkers were examined repeatedly in 38 patients who were evaluable for treatment response. Based on clinical criteria, 20 patients were responders and 18 were nonresponders. In the 20 responders, serum TRACP5b activity and NTX level decreased significantly (P < 0.0001 and 0.0107, respectively) after treatment. In the 18 nonresponders, only NTX level showed significant increase (P = 0.0342) after treatment; TRACP5b and BAP were unchanged. By means of multiple logistic regression with stepwise selection, we determined that TRACP5b activity has a higher probability than NTX level to indicate treatment response as a function of percent change after treatment (18 times versus 12 times). Our data support the use of either TRACP5b activity or NTX level to follow up breast cancer patients with bone metastasis after treatment instead of the prevailing BAP activity. (Cancer Epidemiol Biomarkers Prev 2006;15(3):424–8)

Role of Sentinel Lymphadenectomy Combined with Intraoperative Ultrasound in the Assessment of Locally Advanced Breast Cancer After Neoadjuvant Chemotherapy

BackgroundSentinel node (SN) biopsy for patients with locally advanced breast cancer after neoadjuvant chemotherapy results in a lower detection rate and higher false-negative rate. The aims of the study were to explore the role of SN biopsy in these patients in Taiwan and to assess the role of intraoperative ultrasound examination of the non-SN level.MethodsWe used a blue dye to identify the SNs in 127 patients with T3 locally advanced breast cancer initially treated with neoadjuvant chemotherapy. After SN biopsy, we used intraoperative ultrasound to explore the non-SN region for additional lymph nodes, followed by at least level II axillary dissection. All the SNs were evaluated histologically and immunohistochemically with anticytokeratin antibodies. All the non-SNs were examined by routine histology.ResultsSNs were identified in 116 (91.3%) of 127 procedures. SN metastases were found in 64 cases (55.2%). Subsequent axillary dissection revealed tumor involvement of non-SNs in 40 (62.5%) of 64 cases. SN biopsy results had a sensitivity of 92.8%, a specificity of 100%, and a false-negative rate of 9.6%. Furthermore, intraoperative ultrasound detected suspicious malignant nodes in the non-SN level in 39 out of 40 cases, and detected 5 cases with non-SN metastases that had false-negative SN mapping. This technique decreased the false-negative rate of SN mapping from 9.6% to only 1.39% for these cases.ConclusionsSN biopsy results combined with intraoperative ultrasonography can accurately assess the non-SN status and help breast surgeons to decide whether subsequent axillary dissection is warranted after SN biopsy has been performed.

Serum tartrate-resistant acid phosphatase 5b activity as a prognostic marker of survival in breast cancer with bone metastasis

BackgroundSerum tartrate-resistant acid phosphatase 5b (TRACP 5b) activity is a marker of osteoclast number and is elevated in breast cancer (BC) patients with extensive bone metastasis, which might in turn reflect the tumour burden. We tested the hypothesis that baseline serum TRACP 5b activity and its interval change are potential prognostic markers of survival in BC patients with bone metastasis.MethodsWe analyzed the data from previous prospective studies. A total of 100 patients with newly diagnosed bone metastasis were included. Cox proportional regression model was used to evaluate the correlation between the overall survival time (OS) and baseline serum TRACP 5b activity and its interval changes. The least significant change (LSC) of TRACP 5b was calculated from data obtained from 15 patients with early BC.ResultsEstrogen receptor status (Hazard Ratio (HR) = 0.397; p = 0.003) and visceral metastasis (HR = 0.492; p = 0.0045) were significantly correlated with OS. The OS was significantly shorter in those patients with higher baseline TRACP 5b activity based on a cut-off value to delineate the highest tertile (HR = 3.524; p < 0.0001). Further analysis demonstrated that among patients in the highest tertile, OS was significantly longer in those patients who had achieved a decrease of serum TRACP 5b activity greater than the LSC (38.59%) (p = 0.0015).ConclusionsWe found that TRACP 5b activity and its interval change after treatment bore a prognostic role in BC patients with bone metastasis and a high baseline serum TRACP 5b activity. Further prospective phase II study is necessary to confirm these results.

Sentinel Node Biopsy in Early Breast Cancer in Taiwan

The purpose of this study is to report the results of sentinel node (SN) biopsy for assessment of early breast cancer in Taiwan and to compare our results with those in other Asian countries and worldwide. We used methylene blue dye to identify SN in patients with clinically non-palpable breast mass and palpable breast mass smaller than 3 cm. We also explored the role of imprint cytology and immunochemical studies to identify metastatic cancer cells in the lymph nodes. A total of 221 procedures on 218 patients were performed by a single surgeon. The SN was identified in 85.5% of the cases. The overall accuracy of identifying tumors in SN was 97.4%, with a sensitivity of 90.9%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 96.4%. The use of immunochemical techniques helped to identify micrometasta-sis in SN or non-SN. Our results on SN biopsy with the dye method were similar to those reported from Japan and elsewhere. We concluded that sentinel node biopsy, together with the use of immunochemical techniques to identify micrometastatic foci, has allowed surgeons to decide at the time of surgery whether to perform axillary node dissection.RésuméAfin de rapporter les résultats des biopsies du ganglion sentinelle (GS) pour évaluer le cancer précoce du sein à Taiwan et de comparer nos résultats avec ceux d’autres pays asiatiques et du monde. Nous avons utilisé du bleu de méthylène pour identifier le GS chez les patientes porteuses de tumeur du sein cliniquement non-palpable ou plus petite que 3 cm. Nous avons exploré le rôle de la cytologie et des études immunochimiques pour identifier les cellules cancéreuses métastatiques dans les ganglions lymphatiques. Au total, 221 procédés chez 218 patients ont été réalisés par un seul chirurgien. On a identifié le GS dans 85.5% des cas. La précision globale pour identifier les tumeurs par la biopsie du GS a été de 97.4%, avec une sensibilité de 90.9%, une spécificité de 100%, une valeur prédictive positive de 100%, et une valeur prédictive négative de 96.4%. L’utilisation de techniques immunochimiques a permis d’identifier des micrométastases chez les patients ayant eu ou non une biopsie du GS. Nos résultats de biopsie par la méthode de coloration étaient similaires à ceux rapportés au Japon et ailleurs. Nous concluons que la biopsie du GS combinée aux techniques immunochimiques pour identifier les foyers micrométastatiques ont permis aux chirurgiens de décider s’il fallait practiquer ou pas, au moment de la chirurgie, une lymphadénectomie.ResumenEl trabajo presenta los resultados sobre el valor de las biopsias del ganglio centinela (SN), en pacientes con cáncer de mama en Taiwan, comparándolos con los obtenidos en otros paÍses de Asia y del Mundo. En pacientes con una tumoración de mama, no palpable o de un tamaño<3 cm, utilizamos para identificar el SN el azul de metileno. Se efectúan estudios citológicos e inmunoquÍmicos, para identificar las células metastásicas en los ganglios linfáticos. Un solo cirujano realizó 221 biopsias en 218 pacientes. El SN se identificó en el 85.5% de los casos. La exactitud global para la identificación de metástasis en el SN fue del 97.4%, con una sensibilidad del 90.0% y especificidad del 100%, valor predictivo del 100% y negativo del 96.4%. El empleo de técnicas inmunoquÍmicas ayuda a la detección, en los SN, de micrometástasis. Nuestros resultados en la identificación del SN mediante contraste con azul de metileno son similares a los obtenidos en Japón y en otros lugares. En conclusión, la biopsia del ganglio centinela junto con el empleo de técnicas inmunoquÍmicas para la detección de los focos micrometastásicos, permiten al cirujano decidir, durante el acto quirúrgico, si el vaciamiento axilar es o no necesario.

Ultrasonographic alterations associated with the dilatation of mammary ducts: feature analysis and BI-RADS assessment

ObjectiveThe purpose of this study was to analyse the lesion characteristics and the patterns of dilated ducts on ultrasonography (US) to determine the appropriateness of the Breast Imaging Reporting and Data System (BI-RADS) categories.Materials and methodsFrom July 2001 to June 2006, 172 consecutive pathologically proved lesions with dilated ducts on US were reviewed retrospectively. All the lesions were classified into four types according to their US features, and in combination with the size, location, margins and number of lesions, the corresponding positive predictive values (PPVs) were obtained.ResultsOf the 172 lesions, 55 (32%) were classified as type I, 68 (40%) as type II, 14 (8%) as type III and 35 (20%) as type IV. The PPVs for malignancy were 9% for type I, 13% for type II, 43% for type III and 17% for type IV. There was a significantly higher frequency of malignancy among type III lesions than among type I (43% vs 9%, respectively, Pu2009=u20090.002; χ2 test) or type II lesions (43% vs 13%, respectively, Pu2009=u20090.009; χ2 test). Lesions with a nonsubareolar location and noncircumscribed margins had a high probability of malignancy (Pu2009<u20090.001 and Pu2009=u20090.03, respectively).ConclusionThe four types of US classifications used in our study establish reliable references for the dilated duct patterns when stratified according to BI-RADS categories, and they clarify the indications for biopsy of these lesions.

The semiquantitative bone scintigraphy index correlates with serum tartrate-resistant acid phosphatase activity in breast cancer patients with bone metastasis

OBJECTIVEnTo determine if a correlation exists between the semiquantitative bone scintigraphy index (SQBSI) and serum tartrateresistant acid phosphatase 5b (TRACP5b) activity, a novel osteoclast marker that has been shown to be useful for monitoring bone metastasis in breast cancer (BC) patients.nnnPARTICIPANTS AND METHODSnAmong patients enrolled in 2 prospective studies conducted at Tri-Service General Hospital, Taipei, Taiwan, between December 2000 and July 2002, we identified post hoc 52 patients with both BC and bone metastasis who had detailed records of clinical condition, bone scintigraphy, and concordant serum TRACP5b levels. Between January 1, 2003, and December 31, 2005, we performed bone scintigraphy and serum TRACP5b activity assays to monitor these patients, while they were treated according to clinical need. To assess clinical condition, we obtained information from patient records, such as performance status and visual analogue pain score, as well as from selected laboratory tests for tumor markers and serum TRACP5b activity. Those patients with BC and bone metastasis who had undergone whole-body bone scintigraphy and serum TRACP5b activity determination before any therapeutic intervention were designated the pretreated group (n=30). We developed our own formula for calculating SQBSI on the basis of bone scintigraphy findings.nnnRESULTSnA significant correlation was observed between SQBSI and serum TRACP5b activity in pretreated BC patients with bone metastasis, but the strength of the correlation lessened after treatment. No significant correlation was noted between the change in serum TRACP5b activity and the change in SQBSI in treated patients. Compared with the change in SQBSI, the change in TRACP5b activity had higher sensitivity, specificity, and positive predictive value as well as a greater likelihood ratio for reflecting the clinical scenarios of bone morbidity over time.nnnCONCLUSIONnAs monitors of the response of bone metastasis in BC to treatment, serial determinations of serum TRACP5b activity and SQBSI were both shown to be useful by our preliminary findings. However, serum TRACP5b activity proved the better monitoring tool. If follow-up studies were conducted within 6 months, the combined use of SQBSI and TRACP5b would allow distinction of genuine disease progression from the flare phenomenon, in which bone metastasis can appear to progress in bone scintigraphic images although clinical symptoms improve. Larger prospective studies are needed to confirm these findings.

Spigelian hernia: Mesh or not?

OBJECTIVE: The purpose of this study was to report our experience in management and clinical result of Spigelian hernia with preperitoneal mesh repair or without mesh repair. EXPERIMENTAL DESIGN: Retrospecitve analysis. SUBJECTS: the medical records of 11 cases of Spigelian hernia with surgical treatment were reviewed. The clinical characteristic, treatment and clinical result were evaluated. RESULTS: of the 11 cases that were evaluated, 7 patients underwent open repair of hernia without extra-peritoneal mesh (group A), the other 4 patients underwent open surgery with extra-peritoneal mesh (group B). There were no significant difference in age, gender, body mass index, underlying diseases, symptoms, duration of symptoms, features of hernia sac and method of approach. No recurrence was found in these two groups. The mean follow-up time was 8.5 +/- 3.2 (years) in group A and 6.7 +/- 2.1 (years) in group B. CONCLUSIONS: whether open repair of spigelian hernia with or without extra-peritoneal mesh gives the same and well result.

Application of Intraoperative Ultrasound to Nonsentinel Node Assessment in Primary Breast Cancer

Purpose: To evaluate whether intraoperative ultrasonography can help surgeons to identify patients with breast cancer and metastases confined to the sentinel node. Experimental Design: We used blue dye to identify sentinel node during 512 procedures done on 509 patients with breast cancers of <3 cm. After sentinel node biopsy, we used intraoperative ultrasonography to explore the whole axilla followed by at least level II axillary dissection. All sentinel nodes were evaluated histologically and immunohistochemically using anti-cytokeratin antibody. All nonsentinel nodes were examined by routine histology. Multiple logistic regression was used to assess the associations of interest and to adjust for potential confounders. Receiver operating characteristic curves were used to calculate the areas under the curves of interest and for comparisons. Results: Sentinel nodes were identified in 506 of 512 (98.8%) procedures and sentinel node metastases were found in 161 of these (31.8%). Subsequent axillary dissection revealed tumor involvement in nonsentinel nodes in 93 of 161 (57.8%) procedures. Multivariate analysis showed that tumor size, number of positive sentinel nodes, and metastatic size in sentinel nodes were independent factors predicting the presence of tumor-positive nonsentinel nodes. The validity of using either node size or cortical thickness ascertained by intraoperative ultrasound to predict nonsentinel node metastases was highly significant (P < 0.0001). Intraoperative ultrasound not only detected metastatic nonsentinel nodes in 89 of 93 (95.7%) cases but also detected metastatic nonsentinel nodes in patients with false-negative sentinel node mapping. Conclusion: Sentinel node biopsy combined with intraoperative ultrasonography can help breast surgeons decide whether to perform a subsequent nonsentinel node dissection after identification of a positive sentinel node.

Distinct MR Imaging Features of Triple‐Negative Breast Cancer with Brain Metastasis

Patients with triple‐negative breast cancer (TNBC) are at increased risk of brain metastases (BMs). In this retrospective single‐institutional study, we assessed the radiographic features from a cohort of breast cancer (BC) patients with confirmed BM.