What's new in sentinel node biopsy?

Sentinel node (SN) biopsy is become a standard of care in breast cancer surgical practice. However, the advent of this technique, recently discussed during the 29th San Antonio Breast Cancer Symposium 2006, revealed new questions, which the concept of the SN procedure raises: can we increase the current indications? Could be axillary lymph node dissection avoided in patients with metastatic SN? the morbidity of the biopsy of the SN, which is the prognostic value of micrometastatis discovered by the diffusion of the ultra-stadification of the SNs?     

The clinical management of Level Ⅳ lymph node and neck lymph node micrometastases in follicular thyroid carcinoma

Objective  

We evaluated the relationship between the clinical management of level VI lymph node and neck lymph node micrometastases in follicular thyroid carcinoma.     

When is a completion axillary lymph node dissection necessary in the presence of a positive sentinel lymph node?

BackgroundThe management of the axilla in the presence of positive sentinel lymph node (SLN) remains controversial. Many centres forgo completion axillary lymph node dissection (cALND) in the presence of micrometastatic disease. The American College of Surgeons Oncology Group (ACOSOG) Z0011 trialists argue for extending this to macrometastasis. The aim of this study was to correlate tumour burden in SLNs with that in the residual lymph node basin to determine the likelihood of residual disease in patients with micro- and macrometastasis in the SLN.MethodsPatients who underwent cALND following a positive SLN were analysed for histopathological features of the primary tumour and burden of axillary disease.ResultsOf 155 patients, 115 (74%) had macrometastases and 40 (26%) micrometastases in the SLNs. Residual axillary disease was detected in 55/155 (35%) patients with macrometastases and 4/40 (10%) with micrometastases. Generally, with increasing size of metastasis in the SLN there was an increasing risk of further disease in residual lymph nodes. Logistic regression analysis showed increased odds ratios for further disease for all groups when compared with the <2 mm (micrometastasis) SLN group.ConclusionPatients may be advised to forgo cALND where the SLN contains isolated tumour cells or micrometastasis. Recommendations for proceeding to cALND can be based on the size of metastasis in the SLN, which relates to the risk of further disease in the residual axillary lymph nodes and subsequent regional recurrence.     

Can we avoid axillary dissection in the micrometastatic sentinel node in breast cancer?

There is considerable interest in foregoing axillary dissection (AD) when the sentinel node (SN) is positive in early breast cancer, particularly when involvement is minimal (micrometastases or isolated tumor cells). To address this issue we analyzed outcomes in patients with a single micrometastatic SN who did not receive AD. We selected 377 consecutive patients treated at the European Institute of Oncology between 1999 and 2007 for invasive breast cancer. Classical and competing risks survival analyses were performed to estimate prognostic factors for axillary recurrence, first events and overall survival. Median age was 53?years (range 26?C80); median follow-up was 5?years (range 1?C9). Most (91.8%) patients received conservative surgery; 209 (55.4%) had only one SN (range 1?C8). Five-year overall survival was 97.3%. There were 10 local events, 2 simultaneous local and axillary events, 6 axillary recurrences and 12 distant events. The cumulative incidence of axillary recurrence was 1.6% (95% CI 0.7?C3.3). By multivariable analysis, tumor size and grade were significantly associated with axillary recurrence. The high five-year survival and low cumulative incidence of axillary recurrence in this cohort provide justification for the increasingly common practice of foregoing AD in women with minimal SN involvement, and suggest in particular that AD can safely be avoided in women with small, low-grade tumors. Nevertheless, a subset of patients might be at high risk of developing overt axillary disease and efforts should be made to identify such patients by ancillary analyses of the results of ongoing or recently published clinical trials.     

“Revertant” mammary solid papillary carcinoma in lymph node metastasis

A case of invasive carcinoma of mixed papillary and not otherwise specified ductal type with areas of solid papillary ductal carcinoma in situ(DCIS) is reported. The solid papillary areas were predominantly of low nuclear grade, but a small area of intermediate-grade solid papillary neoplasm was also seen within the tumor, together with an area suggestive of microinvasion. The massive regional nodal tumor load consisted of invasive papillary carcinoma and revertant low-grade solid papillary carcinoma with no myoepithelial cells around the circumscribed solid papillary areas. This is the first report of a solid papillary pattern simulating intraductal carcinoma in lymph nodes, and the first time that a solid papillary carcinoma is reported in association with invasive papillary carcinoma. The case suggests that mammary carcinomas with a solid papillary pattern may sometimes be of higher grade than usual, and do not always represent a DCIS, but may be invasive.     

Can we omit para-aorta lymph node dissection in endometrial cancer?

BACKGROUND: Patients with endometrial cancer can present with various complicating illnesses, including obesity, diabetes mellitus, hypertension and advanced aging. These patients are at high risk of severe post-operative complications. Thus, the question of whether or not to perform systemic pelvic and para-aortic lymphadenectomy remains controversial for all patients. It is reported that external iliac lymph nodes are the most commonly involved lymph nodes in endometrial cancer, and para-aortic lymph node (PAN) metastases spread via a route shared by the common iliac lymph nodes. The aim of this study was to evaluate the potential efficacy of omitting PAN dissection when metastasis of the common iliac and external iliac lymph nodes is negative. METHODS: Between January 1994 and June 2004, a total of 101 patients at Akita University Hospital who had undergone total hysterectomy and bilateral salpingo-oophorectomy, total pelvic lymphadenectomy and para-aortic lymphadenectomy to the level of the renal vein for endometrial cancer were enrolled in this study. RESULTS: Eleven patients in all were found to have metastasis for PANs. Among 13 patients with common and/or external iliac positive lymph nodes, 10 showed PAN metastasis. Of the 88 patients with negative lymph nodes, 87 showed no PAN metastasis. Based on these data, common and/or external iliac lymph nodes had 90.9% sensitivity (10/11) and 96.7% specificity (87/90) for detecting PAN metastasis. CONCLUSION: Para-aortic lymphadenectomy might be avoided by the negativity of such lymph nodes, thereby minimizing post-operative complications.     

Sentinel lymph node biopsy in gastrointestinal malignancies-where do we stand?

Sentinel lymph nodes (SLNs) are the nodes in direct communication with the primary tumor and are therefore the first group of nodes to be involved in lymphatic metastasis. Though the role of SLN biopsy is well established in cancers of the breast and melanoma, its role in gastrointestinal malignancies is still evolving and controversial. In this paper, the literature is reviewed with respect to the status of SLN biopsy in gastrointestinal malignancies.     

What is a sentinel node? Re‐evaluating the 10% rule for sentinel lymph node biopsy in melanoma

INTRODUCTION: Many surgeons use the "10% rule" to define whether a lymph node is a sentinel node (SLN) when staging malignant melanoma. However, this increases the number of SLN removed and the time and cost of the procedure. We examined the impact of raising this threshold on the accuracy of the procedure. METHODS: We reviewed the records of 561 patients with melanoma (624 basins) who underwent SLN with technetium Tc99 labeled sulfur colloid using a definition of a SLN as 10% of that of the node with the highest counts per minute (CPM). RESULTS: Of the 624 basins, 154 (25%) were positive for metastases. An average of 1.9 nodes per basin were removed (range 1-6). Metastases were found in the hottest node in 137 cases (89% of positive basins, 97% of basins overall). Increasing the threshold above 10% decreased the number of nodes excised and the costs involved, but incrementally raised the number of false negative cases above baseline (a 4% increase for a "20% rule," 5% for a "30% rule," 6% for a "40% rule," and 7% for a "50% rule"). Taking only the hottest node would raise the false negative rate by 11%. CONCLUSIONS: Although using thresholds higher than 10% for the definition of a SLN will minimize the extent of surgery and decrease the costs associated with the procedure, it will compromise the accuracy of the procedure and is not recommended.     

Lymphoscintigraphy and gamma probe tracing in detecting breast cancer lymph node involvement: can they replace axillary lymph node dissection?

BACKGROUND: Axillary lymph node status is the most important pathological determinant of prognosis in early breast cancer. However, axillary lymph node dissection (ALND) performed for pathological assessment is not without costs and morbidity. Recently, radioisotope-guided sentinel node biopsy (SNB) has been proposed as a promising technique for staging breast cancer patients. AIM OF THE STUDY: In this study we report our experience (76 patients) in radioguided sentinel node (SN) biopsy in breast cancer. The study was divided into two phases: the first represents our learning curve, necessary to establish our guidelines for its use in clinical practice, while the second phase was aimed at assessing the feasibility of SN localization using preoperative lymphoscintigraphy and intraoperative gamma probe (GP) detection. METHODS: All patients underwent lymphoscintigraphy (LS) up to two hours after tracer delivery (99mTc-micro-nanocolloid, four i.d. injections of 200 microCi/200 miccroL around the primary lesion) 24 hours before surgery and GP tracing during surgery. Subsequently ALND was performed for pathological assessment. RESULTS: SNs were identified in 73/76 patients using LS and in 72/76 using GP. In one case the SN was detected by GP alone while in two cases GP was not able to locate the SN although it had been identified by means of LS. Thirty-three of these 73 patients had axillary node involvement. In 31/33 cases the SN was the only positive node. No positive nodes were found in the remaining 40 ALNDs where SNs were identified. Thus, according to our experience 40/73 ALNDs could have been avoided. SNB seems to be a very interesting technique but further experience in lymph node radioisotope tracing is needed.     

Prognostic value of the lymph node ratio in stage Ⅲ colorectal cancer

The nodal stage of colorectal cancer is based on the number of positive nodes.It is inevitably affected by the number of removed lymph nodes,but lymph node ratio can be unaffected.We investigated the value of lymph node ratio in stage Ⅲ colorectal cancer in this study.The clinicopathologic factors and follow-up data of 145 cases of stage Ⅲ colorectal cancer between January 1998 and December 2008 were analyzed retrospectively.The Pearson and Spearman correlation analyses were used to determine the correlation coefficient,the Kaplan-Meier method was used to analyze survival,and the Cox proportional hazard regression model was used for multivariate analysis in forward stepwise regression.We found that lymph node ratio was not correlated with the number of removed lymph nodes(r =-0.154,P = 0.065),but it was positively correlated with the number of positive lymph nodes(r = 0.739,P 0.001) and N stage(r = 0.695,P 0.001).Kaplan-Meier survival analysis revealed that tumor configuration,intestinal obstruction,serum carcinoembryonic antigen(CEA) concentration,T stage,N stage,and lymph node ratio were associated with disease-free survival of patients with stage Ⅲ colorectal cancer(P 0.05).Multivariate analysis showed that serum CEA concentration,T stage,and lymph node ratio were prognostic factors for disease-free survival(P 0.05),whereas N stage failed to achieve significance(P = 0.664).We confirmed that lymph node ratio was a prognostic factor in stage Ⅲ colorectal cancer and had a better prognostic value than did N stage.     

What is new about sentinel lymph node biopsy in breast cancer?

Sentinel lymph node biopsy concept was described in several reports since 1994. Technical and identification procedure, false negative risk, learning curve criteria and benefits concerning cancer stadification and postoperative morbidity were assessed. Peroperative and postoperative pathologic examination procedures are improving progressively but remains still under debate. Classification for micro-metastasis, isolated cells and macro-metastasis in sentinel lymph node was suggested but their immunohistochimic detection and prognostic impact are unclear. These parts are discussed in this article.     

Sentinel lymph node in oesophageal cancer—a systematic review and meta-analysis

Background

Sentinel lymph nodes (SLNs) have been used to predict regional lymph node metastasis in patients with melanoma and breast cancer. However, the validity of the SLN hypothesis is still controversial for oesophageal cancer. We performed this meta-analysis to evaluate the feasibility and accuracy of radio-guided SLN mapping for oesophageal cancer.

Methods

A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane library, Google scholar, Science Direct, and Web of Science. Original data was abstracted from each study and used to calculate a pooled event rates and 95% confidence interval (95% CI).

Results

The search identified 23 relevant articles. The overall detection rate was 0.93 (95% CI: 0.894-0.950), sensitivity 0.87 (95% CI: 0.811-0.908), negative predictive value 0.77 (95% CI: 0.568-0.890) and the accuracy was 0.88 (95% CI: 0.817-0.921). In the adenocarcinoma cohort, detection rate was 0.98 (95% CI: 0.923-0.992), sensitivity 0.84 (95% CI: 0.743-0.911) and the accuracy was 0.87(95% CI: 0.796-0.913). In the squamous cell carcinoma group, detection rate was 0.89 (95% CI: 00.792-0.943), sensitivity 0.91 (95% CI: 0.754-0.972) and the accuracy was 0.84 (95% CI: 0.732-0.914).

Conclusions

It is possible to identify and obtain a SLN before neoadjuvant therapy in oesophageal cancer. However, further work is needed to optimize radiocolloid type, refine the technique and develop a quick and accurate way to determine SLN status intraoperatively. This technique has to be further evaluated before it can be applied widely.     

Will we need lymph node dissection at all in the future?

Traditionally in the treatment of primary breast cancer, axillary lymph node dissection (ALND) plays an important role. However, a substantial and increasing percentage of patients appear to have no nodal involvement and have been subjected to ALND unnecessarily. The first reason to perform an ALND is axillary nodal staging. After reviewing the literature, it can be concluded that in clinically node-negative patients an adequately conducted lymphatic mapping by sentinel node procedure is equal to ALND for this purpose. The second reason to perform an ALND is to establish the extent of nodal involvement, which might have an impact on adjuvant treatment recommendations. However, there is no evidence available that patients with extensive nodal involvement (= 4 positive nodes) benefit more from adjuvant systemic treatment (either standard or high dose) in terms of reduction of odds of recurrence and mortality compared to patients with limited nodal involvement and optimally administered so-called standard adjuvant treatment. The third reason to perform an ALND is to ensure axillary tumor control. Reviewing the different treatment options, it can be concluded that in clinically node-negative patients axillary control after axillary radiotherapy appears to be similar to axillary control after ALND. In clinically overt axillary involvement, ALND (with or without adjuvant radiotherapy) may result in an improved regional control. In the near future, ALND will not be the standard of care but will be reserved for those patients with proven axillary lymph node involvement. In microscopic disease, radiotherapy may be an alternative with equal control and less morbidity.     

Positive sentinel node biopsy in breast cancer: is axillary surgery necessary in all cases?

Our retrospective study analyzes various factors to evaluate the risk of invasion of the not sentinel node when the sentinel node biopsy is positive in the infiltrated breast cancers. We compared in single varied then multivaried analysis, various parameters between two groups: positive not sentinel nodes and negative not sentinel nodes among 180 cases of positive sentinel node biopsy between 2001 and 2004. At the time of the single varied analysis, seem to be risk factors of non sentinel node involvement: the histopronostic SBRIII rank, positive a HER2neu status, the presence of extracapsulal node extension and infiltration of the sentinel node by a macrometastasis. The tumoral embol, the absence of hormonal receivers, a tumoral size > 10 mm and the number of sentinel node taken appear at the limit of the significativity. In multivaried analysis, SBRIII rank and the presence of an extracapsular node extension remain related to non sentinel node involvement. The histological type, association with a CIS, the size of the sentinel nodes, the number of positive sentinel nodes and the year of surgery are nonsignificant. Additional axillairy clearing out at the time of a positive node sentinel biopsy should be discussed according to different criteria determined by a precise histological analysis.     

Expression of ALDH1 in axillary lymph node metastases is a prognostic factor of poor clinical outcome in breast cancer patients with 1–3 lymph node metastases

Background

Recently, evidence in support of the cancer stem cell (CSC) hypothesis has been accumulating. On the other hand, it has been reported that the expression of aldehyde dehydrogenase 1 (ALDH1) in primary breast cancer is a powerful predictor of a poor clinical outcome, and that breast cancer stem cells express ALDH1. According to the CSC hypothesis, development of metastases requires the dissemination of CSC that may remain dormant and be reactivated to cause tumor recurrence. In this study, we investigated whether the detection of CSC in axillary lymph node metastases (ALNM) might be a significant prognostic factor in patients with breast cancer.

Methods

From 1998 to 2006, 40 primary breast cancer patients with ALNM, the number of metastatic nodes varying in number from 1 to 3, underwent surgery at Okayama University; of these, 15 patients developed tumor recurrence. We retrospectively evaluated the common clinicopathological features and the expression of ER, HER2, ALDH1, and Ki67 in both the primary lesions and the ALNM, and analyzed the correlations between the expression of these biological markers and the disease-free survival (DFS).

Results

Expression of ALDH1 in the ALNM was significantly associated with the DFS (P = 0.037).

Conclusion

Evaluation of biomarker expression in ALNM could be useful for prognosis in breast cancer patients with 1–3 metastatic lymph nodes.     

Can axillary dissection be avoided in patients with sentinel lymph node metastasis?

BACKGROUND: Who should undergo a completion dissection following identification of a +sentinel lymph node (SLN) is controversial. METHODS: The records of 1,133 patients who underwent SLN mapping were reviewed. The association between patient, tumor, and treatment characteristics and the presence of +SLNs and +nonSLNs was analyzed using two-way tables of frequency counts and Pearson chi2 test. Possible predictors of +SLNs and +nonSLNs were analyzed using simple and multiple logistic regression. RESULTS: One thousand one hundred forty-eight SLN procedures were performed. 367 procedures (32%) yielded +SLNs. For patients with a +SLN, on multiple logistic regression analysis LVSI, increasing numbers of +SLNs, decreasing numbers of negative SLNs, and increasing size of the largest SLN metastasis were statistically significantly associated with increased likelihood of nonSLN involvement. No subgroup was identified that did not have a significant rate of nonSLN involvement on completion axillary dissection, except those who had a large number of negative SLNs (> or =3) and small size of the largest SLN metastasis (<10 mm). CONCLUSIONS: A definitive answer to the question of who needs a completion axillary dissection awaits the results of ongoing trials. In the interim, our data does not support eliminating dissection for any subgroup of patients with +SLNs.