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European journal of cancer 154, 227-234 (2021). doi:10.1016/j.ejca.2021.05.026, Published by Elsevier, Amsterdam [u.a.]

Introduction Pelvic lymph node dissection has been the standard of care for patients with early cervical cancer. Sentinel node (SN) mapping is safe and feasible and may increase the detection of metastatic disease, but benefits of omitting pelvic lymph node dissection in terms of decreased morbidity have not been demonstrated. Materials and methods In an open-label study, patients with early cervical carcinoma (FIGO 2009 stage IA2 to IIA1) were randomly assigned to SN resection alone (SN arm) or SN and pelvic lymph node dissection (SN + PLND arm). SN resection was followed by radical surgery of the tumour (radical hysterectomy or radical trachelectomy). The primary end-point was morbidity related to the lymph node dissection; 3-year recurrence-free survival was a secondary end-point. Results A total of 206 patients were eligible and randomly assigned to the SN arm (105 patients) or SN + PLND arm (101 patients). Most patients had stage IB1 lesion (87.4%). No false-negative case was observed in SN + PLND arm. Lymphatic morbidity was significantly lower in the SN arm (31.4%) than in the SN + PLND arm (51.5%; p = 0.0046), as was the rate of postoperative neurological symptoms (7.8% vs. 20.6%, p = 0.01, respectively). However, there was no significant difference in the proportion of patients with significant lymphoedema between the two groups. During the 6-month postoperative period, the difference in morbidity decreased over time. The 3-year recurrence-free survival was not significantly different (92.0% in SN arm and 94.4% in SN + PLND arm). Conclusion SN resection alone is associated with early decreased lymphatic morbidity when compared with SN + PLND in early cervical cancer.

Background Sentinel lymph node biopsy (SNB) still remains a key procedure to appropriately stage melanoma patients and to select those who are candidate to novel treatments with immunotherapy and targeted therapy in the adjuvant setting. The impact of timing of SNB on disease-free survival (DFS) and overall survival (OS) is still unclear. Material and methods The study was conducted at 6 Italian Melanoma Intergroup (IMI) centres and included 8953 consecutive clinical stage I-II melanoma patients who were diagnosed, treated, and followed up between November 1997 and March 2018. All patients were prospectively included in dedicated IMI database. Multivariable Cox regression analyses were performed to investigate how baseline characteristics and time interval until SNB are related to DFS and OS. Results Considering the whole population, at multivariable analysis, after adjusting for age, gender, Breslow thickness, site, ulceration, and the SNB status, a delay in the timing of SNB was associated with a better DFS (adjusted hazard ratio [aHR, delayed versus early SNB] 0.98, 95% confidence interval [CI] 0.97–0.99, p, Highlights • Sentinel lymph node biopsy (SNB) is a key procedure to stage melanoma patients (MPs). • In our series, the time interval of SNB is irrelevant in MPs with positive sentinel lymph node. • A delayed SNB biopsy is not detrimental in clinically stage I-II MPs.

Purpose Optimal duration of adjuvant chemotherapy in the treatment of early-stage breast cancer remained to be investigated rigorously for the standard regimens in widespread use in North America (doxorubicin/cyclophosphamide, AC) and Europe (5-fluorouracil/epirubicin/cyclophosphamide, FEC). Whether six cycles of FEC 100 present an advantage, or not, compared with only four cycles was tested directly in a phase III prospective multicentre trial. Patients and methods Between 2002 and 2006, 1515 women between 18 and 65°years of age, with node negative N(−) high-risk early-stage breast cancer, were included in the study following breast surgery and axillary lymph node dissection or procedure by sentinel node technique. Inclusion in the study required tumour size T ≥ 1 cm and at least one of the high-risk factors: T > 2 cm, negative oestrogen receptor/progesterone receptor (ER– and PR–), Scarff-Bloom-Richardson (SBR) grade II or III and age ≤ 35°years. Patients were randomly assigned to either six FEC 100 (Arm A) or four FEC 100 (Arm B). The trial was powered to detect an absolute difference ≥6% in disease-free survival (DFS) at 5°years. Results At 6.1°years median follow-up, with 91 (12%) events recorded in Arm A versus 106 (14%) in Arm B, no statistically significant risk increase was associated with four versus six FEC 100: DFS (hazard ratio (HR) = 1.18; CI 95% [0.89–1.56], P = .24) and overall survival (OS) (HR = 1.39; CI 95% [0.91–2.13], P = .12). Conclusion Differences in chemotherapy duration did not induce notably different outcomes in our cohort of high-risk patients. Clinical trial registry number NCT00055679 , Agence National de Securite du Medicament (ANSM) – France.

Sentinel lymph node biopsy (SNB) still remains a key procedure to appropriately stage melanoma patients and to select those who are candidate to novel treatments with immunotherapy and targeted therapy in the adjuvant setting. The impact of timing of SNB on disease-free survival (DFS) and overall survival (OS) is still unclear.The study was conducted at 6 Italian Melanoma Intergroup (IMI) centres and included 8953 consecutive clinical stage I-II melanoma patients who were diagnosed, treated, and followed up between November 1997 and March 2018. All patients were prospectively included in dedicated IMI database. Multivariable Cox regression analyses were performed to investigate how baseline characteristics and time interval until SNB are related to DFS and OS.Considering the whole population, at multivariable analysis, after adjusting for age, gender, Breslow thickness, site, ulceration, and the SNB status, a delay in the timing of SNB was associated with a better DFS (adjusted hazard ratio [aHR, delayed versus early SNB] 0.98, 95% confidence interval [CI] 0.97-0.99, p 0.001) and OS (aHR 0.98, 95% CI 0.97-0.99, p = 0.001). Specifically, in patients with a negative SNB status, a beneficial impact of delayed SNB (i.e. at least 32 days after primary excision) was confirmed for DFS (aHR 0.70, 95%CI 0.63-0.79, p 0.001) and OS (aHR 0.69, 95%CI 0.61-0.78, p 0.001), whereas in those with a positive SNB status, DFS (aHR 0.96, 95%CI 0.84-1.09, p = 0.534) and OS (aHR 0.94 95%CI 0.81-1.08, p = 0.374) were not significantly different in patients with early or delayed SNB.Our study does not support a strict time interval for SNB. These results may be useful for national guidelines, for counselling patients and reducing the number of high urgency referrals.

Background Omission of completion axillary lymph node dissection (ALND) is a standard practice in patients with breast cancer (BC) and negative sentinel nodes (SNs) but has shown insufficient evidence to be recommended in those with SN invasion. Methods A retrospective analysis of a cohort of patients with BC and micrometastases (Mic) or isolated tumour cells (ITCs) in SN. Factors associated with ALND were identified, and patients with ALND were matched to patients without ALND. Overall survival (OS) and recurrence-free survival (RFS) were estimated in the overall population, in Mic and in ITC cohorts. Findings Among 2009 patients analysed, 1390 and 619 had Mic and ITC in SN, respectively. Factors significantly associated with ALND were SN status, histological type, age, number of SN harvested and absence of adjuvant chemotherapy. After a median follow-up of 60.4 months, ALND omission was independently associated with reduced OS (hazard ratio [HR] 2.41, 90 confidence interval [CI] 1.36–4.27, p = 0.0102), but not with increased RFS (HR 1.21, 90 CI 0.74–2.0, p = 0.52) in the overall population. In matched patients, the increased risk of death in case of ALND omission was found only in the Mic cohort (HR 2.88, 90 CI 1.46–5.69), not in the ITC cohort. The risk of recurrence was also significantly increased in the subgroup of matched Mic patients (HR 1.56, 90 CI 0.90–2.73). Interpretation A separate analysis of Mic and ITC groups, matched for the determinants of ALND, suggested that patients with Mic had increased recurrence rates and shorter OS when ALND was not performed. Our results are consistent with those of previous studies for patients with ITC but not for those with Mic. Randomised controlled clinical trials are still warranted to show with a high level of evidence if ALND can be safely omitted in patients with micrometastatic disease in SN.

Objective The one-step nucleic acid amplification (OSNA) assay can assess an entire lymph node and detect clinically relevant metastases quantified based on cytokeratin 19 (CK19) mRNA copy number. The OSNA assay of all sentinel lymph nodes (SNs) and non-sentinel nodes (non-SNs) allows for the accurate measurement of tumour burden in either situation. We aim to reveal the usefulness of the OSNA assay regarding the prediction of non-SN metastasis. Methods The subjects consisted of 185 breast cancer patients who underwent axillary dissection after a metastatic SN biopsy and whose SNs and non-SNs were examined using the OSNA whole-node assay between 2009 and 2011. The non-SN tumour burden was classified as macrometastasis (CK19 mRNA ⩾5000 copies/μl) or micrometastasis (250–5000 copies/μl). The relationship between SN and non-SN tumour burdens and predictors of non-SN metastasis were investigated. Results Among these 185 patients, 38 patients (20.5%) had macrometastasis and 58 (31.4%) had micrometastasis only in the non-SNs. Non-SN macrometastasis rates increased in direct proportion to the SN copy number: approximately 5% in patients with SNs with 250–500 copies; 20%, 500–5000 copies and 30%, ⩾5000 copies. However, non-SN micrometastasis rates were approximately 30% regardless of the SN copy number. In multivariate analyses, the mean SN copy number, number of macrometastatic SN and lymphovascular invasion were significant for identifying non-SN macrometastases. Conclusions The SN tumour burden quantified using the OSNA assay predicts non-SN metastases. A novel mathematical model to predict the non-SN tumour burden can be generated using the results of the OSNA assay.

Background The Z0011-study, a landmark randomised controlled trial (RCT) challenged the benefits of complete axillary lymph node dissection (ALND) compared with sentinel lymph node dissection only (SLND) in breast cancer patients with positive sentinel nodes. The study, however, has been criticised for lack of power and low applicability. The aim of this review was to systematically assess the evidence on the comparative benefits and harms of ALND versus SLND for sentinel node positive breast cancer patients. Methods We systematically searched PubMed, Embase, the Cochrane Library, and reference lists of pertinent review articles from January 2006 to August 2011. We dually reviewed the literature and rated the risk of bias of each study. For effectiveness, we included RCTs and observational studies of at least 1year follow-up. In addition, we considered studies conducted in sentinel node-negative women to assess the risk of harms. If data were sufficient, we conducted random effects meta-analysis of outcomes of interest. Results Meta-analysis of three studies with 50,120 patients indicated similar 5-year survival and regional recurrence rates between patients treated with ALND or SLND, although prognostic tumour characteristics varied among the 3 study-populations. Results from 6 studies on more than 11,500 patients reported a higher risk for harms for ALND than SLND. Long-term evidence on pertinent health outcomes is missing. Conclusion The available evidence indicates that for some women with early invasive breast cancer SLND appears to be a justifiable alternative to ALND. Surgeons need to discuss advantages and disadvantages of both approaches with their patients.

Item does not contain fulltext AIM: Sentinel lymph node (SLN) biopsy is an accepted alternative to axillary lymph node dissection to assess the axillary tumour status in breast cancer patients. Memorial Sloan-Kettering Cancer Center (MSKCC) developed a nomogram to predict the likelihood of SLN metastases in breast cancer patients. Nomogram performance was tested on a Dutch population. METHODS: Data of 770 breast cancer patients who underwent successful SLN biopsy were collected. SLN metastases were present in 222 patients. A receiver operating characteristic (ROC) curve was drawn and the area under the curve was calculated to assess the discriminative ability of the MSKCC nomogram. A calibration plot was drawn to compare actual versus nomogram-predicted probabilities. RESULTS: The area under the ROC curve for the predictive nomogram was 0.67 (95% confidence interval 0.63-0.72) as compared to 0.75 in the original population. The nomogram was well-calibrated in the Dutch population. CONCLUSIONS: In a Dutch population, the MSKCC nomogram estimated risk of sentinel node metastases in breast cancer patients well (i.e. calibration) with reasonable discrimination (area under ROC curve). Nomogram performance on core needle biopsy data has to be evaluated prospectively.

Isolated tumour cells and micrometastases represent two different staging categories and are often dealt with differently when identified in sentinel lymph nodes of breast cancer patients. The reproducibility of these categories was found to be suboptimal in several studies. The new edition of the TNM (Tumour Node Metastasis) is expected to improve the reproducibility of these categories. Fifty cases of possible low-volume nodal involvement were represented by one to four digital images and were analysed by members of the European Working Group for Breast Screening Pathology (EWGBSP). The kappa value for interobserver agreement of the pN (TNM) staging categories and of the isolated tumour cells category were 0.55 and 0.56 reflecting moderate reproducibility, and the kappa of the micrometastatic category (0.62) reflected substantial reproducibility. This is an improvement over the results gained on the basis of the previous edition of the TNM. Maximal adherence to the category definitions supplemented by explanatory texts in the staging manual should result in more homogeneous nodal staging of breast cancer.

SentiDose : a dose optimizing study with SiennaXP, a superparamagnetic iron oxide for sentinel node detection

To investigate if the tumour infiltrating lymphocytes (TILs) are able to predict the sentinel lymph node (SLN) positivity, the disease-free survival (DFS) and overall survival (OS) in clinical stages I-II AJCC primary cutaneous melanoma (PCM).The study included consecutive patients with PCM, all diagnosed, treated and followed up prospectively. Logistic regression was used to investigate the association between DFS, OS, SLN positivity and Breslow thickness, Clark level, TIL, ulceration, lesion site, gender, regression and age.From November 1998 to October 2008, 1251 consecutive patients with PCM were evaluated. Median age was 51 (range 15-96) with 32.2% (N=393) of them older than 60; 44.8% of them were males. Of the whole series, a total of 404 patients with primary vertical growth phase (VGP) melanoma and no clinical evidence of metastatic disease underwent SLN biopsy. Of these, 74 (18.8%) had a positive SLN. In a multivariate analysis, primary melanoma on the extremities versus that on the axial locations (truncal and head/neck) (OR 0.49, 95% CI 0.25-0.98, p 0.04) and TILs (TILs versus no TILs) (OR 0.47, 95%CI 0.25-0.90, p 0.02) were predictive for lower probability of SLN involvement, while thickness (4mm versus 0-1mm) (OR 24, 19, 95% CI 4.91-119.13, p.001) was predictive for higher risk of SLN positivity. A multivariate stepwise analysis confirmed these results. The histological status of the SLN was the most significant predictor of DFS and OS. Patients with a negative SLN had a 5-year DFS of 75.9%, compared with 35.2% in patients with a positive SLN (p.0001) and a 5-year OS of 88.7% versus 42.9%, respectively (p.0001).Our study demonstrates that the absence of TILs predicts SLN metastasis, in multivariate analysis the SLN positivity predicts DFS and OS.

Ductal carcinoma in situ (DCIS) of the breast is defined as a proliferation of malignant epithelial cells within breast ducts without evidence of invasion through the basement membrane. The detection rate of DCIS of the breast has dramatically increased since the mid-1980s as the result of the widespread use of screening mammography. DCIS currently represents about 15-25% of all breast cancers detected in population screening programmes. Although inherently a non-invasive disease, occult invasion with the potential of lymph node metastases may occur. Where performing an axillary lymph node dissection-or-not for DCIS used to be an important dilemma, the same now holds for the sentinel node biopsy. This article reviews the potential role of the sentinel node biopsy (SNB) in patients with DCIS. We conclude that based on the current literature, there is in general no role for a SNB in DCIS. A SNB should only be considered in patients with an excisional biopsy diagnosis of high risk DCIS (grade III with palpable mass or large tumour area by imaging) as well as in patients undergoing mastectomy after a core or excisional biopsy diagnosis of DCIS, although SNB may be contraindicated in many of the latter patients because of lesion size and/or multifocality. Even in these patients the value of a positive SN, containing mostly isolated tumour cells, is questionable.

This study has analyzed the incidence of in transit/local recurrences (IT/LR) in melanoma patients after sentinel node (SLN) biopsy; completion lymph node dissection (CLND) that was performed due to positive node; and therapeutic LND (TLND) due to clinically detected node metastases and factors influencing IT/LR. Between May 1995 and May 2004, 1187 consecutive patients underwent SLN biopsy (median Breslow thickness 2.5 mm) and 224 of them had subsequent CLND. During the same time period, 306 patients had TLND (median Breslow 3.9 mm). The excision margin of primaries was > or =1cm. At median follow-up time of 37.5 months, we analyzed the incidence of IT/LR as the first site of relapse and clinicopathological parameters affecting these recurrences. In SLN-negative cases, IT/LR as the site of the first recurrence were rare (46/963; 4.8%) and; in SLN+/-CLND IT/LR were detected in 45/224 cases (20.1%). IT/LR in SLNB group correlated with presence of SLN metastases (P

Sentinel node biopsy in patients with breast carcinoma accurately predicts the axillary nodal status. However, in some 6% of patients with negative sentinel nodes the remaining axillary nodes harbour metastases. Our purpose was to observe a large number of patients who did not undergo an axillary dissection after a negative sentinel node biopsy for the appearance of overt axillary metastases. 953 patients treated from 1996 to 2000, with negative sentinel nodes not submitted to axillary dissection, were followed-up to 7 years, with a median follow-up of 38 months. Fifty-five unfavourable events occurred among the 953 patients, 37 (4%) related to the primary breast carcinoma. Three cases of overt axillary metastases were found: they received total axillary dissection and are presently alive and well. The 5 year overall survival rate of the whole series was 98%. Patients with negative sentinel node biopsies not submitted to axillary dissection show during follow-up a rate of overt axillary metastases that is lower than that expected.

Sentinel node biopsy (SNB) is rapidly emerging as the preferred technique for nodal staging in breast cancer. When radioactive colloid is used, a preoperative lymphoscintiscan is obtained to ease sentinel lymph node (SN) identification. This study evaluates whether preoperative lymphoscintigraphy adds diagnostic accuracy to offset the additional time and cost required. 823 breast cancer patients underwent SNB based on lymphoscintigraphy, intraoperative gamma probe detection, and blue dye mapping using 99 mTc-nanocolloid and Patent Blue V injected peritumourally. The SNB was followed by standard axillary treatment at the same operation. Preoperative lymphoscintigraphy was performed around 3 h after the radioisotope injection. Preoperative lymphoscintigraphy revealed SNs in 593 (72%) of the 823 patients imaged. SN visualisation on lymphoscintigraphy was less successful in large tumours and tumours involving the upper outer quadrant of the breast (P=0.046, P

Forty three years after Gould's first description of the sentinel lymph node (SN) technique in malignant tumours of the parotid, sentinel lymph node biopsy (SLNB) has become an invaluable tool for the treatment of solid tumours. In some tumour types, it has been shown to reliably reflect the lymph node (LN) status of the tumour-draining LN basin. In melanoma and breast cancers, it has become a widely accepted element in the routine surgical management of these malignant diseases. In gastrointestinal tumours, the technique is currently under intense investigation. First reports on its application in other solid tumours like non-small cell lung cancer, thyroid carcinoma, oropharyngeal carcinoma, vulvar carcinoma, and Merkel Cell carcinoma of the skin were published more recently. In the following review, we will give a synopsis of the fundamentals of the SN concept and will then proceed to an overview of recent advances of SLNB in gastrointestinal cancers.

INTRODUCTION The aims of this study were to investigate the practice of axillary lymph node management within different units throughout the UK, and to assess changes in practice since our previous survey in 2004. SUBJECTS AND METHODS A structured questionnaire was sent to 350 members of the British Association of Surgical Oncology. RESULTS There were 177 replies from respondents who managed more than 100 patients a year with breast cancer. Of these: 12 did not perform axillary ultrasound at all in their centre; 17 (10%) employed axillary node clearance (ANC) on all patients; 122(69%) performed sentinel node biopsy (SNB) with dual localisation; and 111 respondents had attended the New Start Course. Radioisotope was most frequently injected 2 h or more before operation. Just 13 surgeons were convinced of the value of dissecting internal mammary nodes visualised on a scan. Reasons for not using dual localisation included lack of nuclear medicine facilities, no local ARSAC licence holder, no probe, and no funding. Sixty-six surgeons stated that, if they had an ARSAC licence and could inject the radioactivity in theatre, this would be a major improvement. In addition, 83 (47%) did not perform SLNB in patients receiving neo-adjuvant chemotherapy. CONCLUSIONS Despite significant changes since 2004, substantial variation remains in management of the axilla. A number of surgeons are practicing outwith current guidelines.

Currently, axillary lymph node dissection is increasingly being replaced by the sentinel node procedure. This method is time-consuming and the full immunohistochemical evaluation is usually only first known postoperatively. This study was designed to evaluate the accuracy of preoperative ultrasound-guided fine needle aspirations (FNAs) for the detection of non-palpable lymph node metastases in primary breast cancer patients. We evaluated the material of 183 ultrasound-guided FNAs of non-palpable axillary lymph nodes of primary breast cancer patients. The cytological results were compared with the final histological diagnosis. Ultrasound-guided FNA detected metastases in 44% (37/85) of histologically node-positive patients, in 20% of the total patient population studied. These pecentages are likely to be higher when women with palpable nodes are included. Cytologically false-negative and false-positive nodes were seen in 28 (15%) and three cases (1.6%), respectively. Interestingly 25% (n=7) of the false-negative nodes, revealed micrometastases on postoperative histology. The sensitivity was 57%, the specificity 96%. We conclude that ultrasound-guided FNA of the axillary lymph nodes is an effective procedure that should be included in the preoperative staging of all primary breast cancer patients. Whether lymph nodes are palpable or not, it will save considerable operating time by selecting those who need a complete axillary lymph node dissection at primary surgery and would save a significant number of sentinel lymph node dissections (SLNDs).

Approximately one-third of node-negative colon cancers will recur, possibly due to understaging and inadequate pathological examination of lymph nodes (LNs). We evaluated the sensitivity, accuracy and feasibility of staging based on lymphatic mapping, focused examination, and molecular analysis of the sentinel node (SN) in patients with primary colorectal carcinoma. Between 1996 and 2000, 100 patients with colon carcinoma (CRC) underwent lymphatic mapping immediately after peritumoral injection of 1.0 cc of isosulphan blue dye. All LNs in the CRC specimen were examined by routine haematoxylin and eosin (H&E) staining. Sentinel nodes were examined by step serial sectioning, cytokeratin immunohistochemistry (CK-IHC) and/or reverse transcriptase-polymerase chain reaction (RT-PCR) analysis in an attempt to identify occult micrometastatic disease. Lymphatic mapping was successful in 97% of the cases. There were 5 false-negative cases, predominately associated with T3/T4 tumours. Aberrant lymphatic drainage was identified in 8 patients (8%) altering the operative approach. 26 patients had H&E-positive LNs. In 74 patients who were node-negative by routine H&E, 18 (24%) had occult nodal micrometastases missed on routine H&E examination, but detected by focused analysis of the SN. RT-PCR analysis of the SN was performed in 40 patients, 26 of which were negative by H&E and CK-IHC. In 12/26 (46%) of these patients, there was additional evidence of micrometastatic disease. In this study, focused examination of the SN in conjunction with RT-PCR analysis identified micrometastatic disease in a significant number of node-negative patients. This may have important implications when selecting patients for adjuvant treatment protocols.

The aims of the study were to determine how often four node axillary sampling (4NAS) encompasses the sentinel node (SN) and to compare the relative sensitivity of 4NAS with sentinel node biopsy (SNB) for axillary node staging. 200 patients with breast cancer were preoperatively injected with 27 MBq 99m-Tc-labelled colloid adjacent to the tumour. At operation, standard 4NAS was performed. Each node was counted ex vivo using a probe. A search was then made to find a node with higher counts in vivo directed by the probe. If found, it was excised. Each node was submitted separately to pathology. A SN was identified in 191 patients (96%). The SN was contained in the 4NAS in 153 patients (80%) and identified separately in 38 patients (20%). Of 60 node-positive patients, 49 were positive by 4NAS and SNB, the SN was not identified in 2 and in 8 the SN was falsely negative compared with 4NAS. For 1 patient, the SN was positive and the 4NAS negative. SNB performed using radiolabelled colloid has no advantage over 4NAS when nodes are assessed by standard histological technique.

The aim of this study was to discuss the role of preoperative ultrasound (US) scanning and sentinel node biopsy (SNB) in melanoma patients. 100 patients underwent SNB following preoperative US scan and lymphoscintigraphy; patent blue dye (PBD) was injected before biopsy. Intra-operative lymphoscintigraphy (IL) was performed in 51 basins. All nodes were examined with histology and immunohistochemistry. Sensitivity and specificity of US scanning was 33% and 100%, respectively; 7% were true positives. The low sensitivity was mainly due to the resolution power of the US scanner (2 mm) which was unable to identify all the patients with microdeposits. PBD associated with IL identified SNs in all cases. In all patients with Breslow >1.5 mm and in all cases with two metastatic SNs, further positive additional nodes were found. The mean counts per 10 s (CP10S) ratio for SN and non-SN values was 5.62 (1.29–23.51) and 3.09 (1.03–10.99) in the intra-operative and extra-operative phases, respectively. US scanning and preoperative lymphoscintigraphy associated with PBD allows preoperative patient selection and accurate SN(s) identification. Breslow thickness and the number of metastatic SN(s), but not their type, are correlated with disease spread; CP10S contributed to the differentiation amongst the nodes and the determining of procedure's completion.

The approach to the clinically negative regional lymph node basin presents a challenging problem in the clinical management of patients with early-stage melanoma (stage I and II). As a group, stage I and stage II patients generally have a good prognosis following surgical excision of the primary tumour; however, the presence of clinically undetectable nodal disease is an important prognostic factor. Traditionally, these patients are either monitored closely for development of palpable metastases at which time a therapeutic lymphadenectomy would be performed or, have been offered early elective lymphadenectomy that is performed immediately at the time of wide excision of the primary tumour. The high rate of morbidity and lack of proven survival impact for immediate elective lymphadenectomy limit its use. Lymphatic mapping and sentinel node biopsy allow a more selective approach to regional lymph node dissections. Only node-positive patients undergo lymphadenectomy, thereby avoiding the morbidity associated with the procedure for patients without nodal disease. Several studies have confirmed that lymphatic mapping identifies the lymph node most likely to contain disease and confirms the orderly progression of lymphatic metastases. Use of radioactive colloid and a hand-held gamma probe improves the localisation of the sentinel lymph node. Because adjuvant systemic therapy has been proven to prolong survival in patients with nodal involvement, lymphatic mapping and sentinel node biopsy, by identifying patients with clinically negative, but pathologically positive disease, may improve their outcome.

Breast cancer remains the most common cause of cancer in women and is the second leading cause of cancer death. The surgical management of breast cancer has evolved over the last 40 years from radical ablative procedures to breast conservation as the preferred method of treatment for early stage disease. The presence of axillary lymph node metastases remains the best prognostic indicator for patients with breast cancer and the mainstay of surgical management of breast cancer has included the removal of Level I, II and at times III axillary lymph nodes. The presence of axillary nodal metastases is often used to identify patients who would benefit from adjuvant treatment or a more aggressive adjuvant therapy regimen. However, over the last 10 years, the need for adjuvant therapy has often been based on the primary tumour characteristics and an increasing number of node-negative women are offered adjuvant therapy. This has led some to question the need for axillary surgery. Several methods have been used to identify breast cancer patients at risk of nodal metastases; however, none has been able to replace the need for histological evaluation of axillary lymph nodes. Fisher and colleagues [1] demonstrated that approximately 35% of nodes considered normal on physical examination contained carcinoma and 25% of enlarged suspicious lymph nodes on examination did not contain metastastic cells; therefore, clinical exam alone is not an accurate assessment of nodal status. Other radiological modalities such as computerised tomography, magnetic resonance imaging and mammography present similar difficulties with respect to determining the tumour status of lymph nodes. Positron emission tomography can identify nodal metastases larger than 1 cm, but its use would have limited value in the majority of patients [2]. In 1955, Berg popularised the anatomical subdivision of the axillary lymph nodes into three functional levels related to the pectoralis minor muscle [3]. Lymph nodes lateral and inferior to the pectoralis minor muscle are classified as Level I nodes, those located behind the pectoralis minor muscle are Level II nodes and nodes superior and medial to the pectoralis minor muscle are Level III nodes. Several types of axillary dissections are therefore defined by the Berg levels removed. A low axillary dissection removes Berg level I nodes, while a partial axillary node dissection removes Berg I and II levels and a total axillary node dissection removes all three Berg levels. Lesser procedures termed axillary sampling refer to the random biopsy of low axillary lymph nodes without anatomical reference [4]. The United States National Institutes of Health Consensus Conference in 1991 recommended that a Level I and II axillary lymph node dissection (ALND) be performed in patients with early breast cancer [5]. This is because axillary staging associated with this procedure is very accurate and has less than a 2% false-negative rate [6,7]. However, the ability to achieve this level of accuracy is at the expense of considerable morbidity: the most devastating to patients is chronic lymphoedema, which has been reported to occur in as many as 20–30% of patients in some series [8–10]. Because only approximately one-third of patients who present with breast cancer have nodal metastases, routine axillary nodal dissection places a substantial number of patients at risk for operative morbidity without any known benefit from the operative procedure. Attempts to reduce the morbidity of axillary node dissection with lesser procedures such as low ALND or axillary sampling have been abandoned due to high false-negative rates. There is a 40% false-negative rate with random axillary nodal sampling and a 10–15% false-negative rate with excision of Level I nodes alone [10–15]. The recent introduction of the sentinel node biopsy (SNB) provides a less invasive, but highly accurate, alternative of axillary assessment to axillary node dissection.