The axillary lymph node status is the most important determinant of prognosis in patients with breast cancer. Sentinel lymph node (SLN) biopsy is a safe alternative for axillary clearance with an equal efficacy limiting the morbidity caused by axillary clearance.
Patient and methods
From May 1996 till September 2009, 523 clinically node negative, early breast cancer patients attending our clinic at All India Institute of Medical Sciences were included in the study. They underwent sentinel lymph node biopsy by either combined technique or blue dye alone. All patients irrespective of the axillary status underwent axillary lymph node dissection (ALND).
Of 523 patients, 267 underwent combined technique of sentinel node mapping and 256 underwent blue dye technique alone. The identification rate of sentinel lymph node was 94.3% (253/267) for combined technique and 87.8% (225/256) for blue dye alone. Of 523 patients SLN was identified in 478 patients. The identification rate was 91.3%. The sensitivity = 91.5% (141/154), false negative = 8.4% (13/154), negative predictive value = 96.14% (324/337), and accuracy being 97.2% (465/478).
Sentinel node mapping is a simple and safe technique of identifying the axillary node involvement. Sentinel lymph node biopsy is associated with less arm oedema and shoulder morbidity compared to ALND. However, the results of long term effects of sentinel node approach on tumor recurrence or patient survival are awaited.
Sentinel lymph node biopsy; Axillary lymph node dissection; Axillary node sampling; Lymphatic mapping; Early breast cancer; Immuohistochemistry
Sentinel lymph node biopsy (SLNB) is a widely accepted method to determine lymph node status in for instance breast cancer, cervical cancer, or cutaneous melanomas. Although injection of blue dyes facilitates successful detection of sentinel nodes, they have also been shown to cause adverse reactions.
A 62-year-old female patient was referred to the surgical department of the Atrium Medical Centre with a suspicious lesion located in the right breast, detected during population-based screening. Immediately after injection of patent blue V, the patient developed tachycardia on top of preexisting supraventricular tachycardia and showed an instant drop in blood pressure, after which cardiac arrest occurred. These clear symptoms of anaphylactic shock required prompt treatment, and the patient was treated accordingly.
Anaphylactic shock after injection of patent blue V remains a serious adverse event and warrants awareness. Immediate action with ephedrine, antihistamines, and subsequently corticosteroids can stabilize the patient. Tc-99m, isosulphan blue, and methylene blue can alternatively be used for SLNB, although also not without side effects.
Sentinel node; Patent blue; Anaphylactic shock; Breast cancer
There are various methods for detecting sentinel lymph nodes in breast cancer. Sentinel lymph node biopsy (SLNB) using a vital dye is a convenient and safe, intraoperatively preparative method to assess lymph node status. However, the disadvantage of the dye method is that the success rate of sentinel lymph node detection depend on the surgeon's skills and preoperative mapping of the sentinel lymph node is not feasible. Currently, a vital dye, radioisotope, or a combination of both is used to detect sentinel nodes. Many surgeons have reported successful results using either method. In this study we have analyzed breast lymphatic drainage pathways using indocyanine green (ICG) fluorescence imaging.
We examined the lymphatic courses, or lymphatic vessels, in the breast using ICG fluorescence imaging, and applied this method to SLNB in patients who underwent their first operative treatment for breast cancer between May 2006 and April 2008. Fluorescence images were obtained using a charge coupled device camera with a cut filter used as a detector, and light emitting diodes at 760 nm as a light source. When ICG was injected into the subareola and periareola, subcutaneous lymphatic vessels from the areola to the axilla became visible by fluorescence within a few minutes. The sentinel lymph node was then dissected with the help of fluorescence imaging navigation.
The detection rate of sentinel nodes was 100%. 0 to 4 states of lymphatic drainage pathways from the areola were observed. The number of sentinel nodes was 3.41 on average.
This method using indocyanine green (ICG) fluorescence imaging may possibly improve the detection rate of sentinel lymph nodes with high sensitivity and compensates for the deficiencies of other methods. The ICG fluorescence imaging technique enables observation of breast lymph vessels running in multiple directions and easily and accurately identification of sentinel lymph nodes. Thus, this technique can be considered useful.
sentinel lymph node biopsy; breast cancer; indocyanine green; fluorescence imaging
Axillary lymph node dissection is an established procedure in breast cancer staging. However, it is associated with unpleasant side effects. A promising alternative to assess axillary lymph node status in early breast cancer patients is Sentinel Lymph Node Biopsy (SLNB). Isosulfan blue has traditionally been the dye used to identify the Sentinel Lymph Node (SLN). This article is a validation study of SLNB using methylene blue dye and radioactive sulphur colloid in early breast cancer Indian patients.
Materials & Methods
With written informed consent, 100 patients with cytology or biospy proven carcinoma breast, clinical stage T1/ T2 N0 M0, underwent SLNB using combination of methylene blue dye & radioactive technetium 99m sulphur colloid as a part of validation study from June 2003 to February 2006. After validation study, from March 2006 to February 2007, 35 patients have undergone SLNB followed by complete axillary clearance in only those patients with SLNB being positive for metastases.
In all 100 patients of the validation study SLN was identified. Total number of cases with positive axillary nodes was 27, out of which SLN was only positive node for metastases in 69% of cases. The overall sensitivity, specificity, positive predictive valve and negative predictive valve of SLNB 96.2%, 100%, 100% and 98.6% respectively with false negative rate of 3.7%. In subsequent 35 patients who underwent SLNB followed by complete axillary clearance, SLNs was identified in all the cases.
SLNB is effective in early breast cancer patients of Indian population. SLNB using combination of methylene blue dye and radio-active Tc99m sulphur colloid can stage the axilla with high accuracy & low risk of false negativity in early breast cancer patients.
Sentinel lymph node biopsy; Methylene blue dye; Tc99m radioactive sulfur colloid; Early breast cancer; Indian patients
Routine removal of the internal mammary chain (IMC) sentinel node in breast cancer patients remains a subject of discussion. The aim of this study was to determine the impact of routinely performed IMC sentinel node biopsy on the systemic and locoregional treatments plan. All patients with biopsy proven breast cancer who underwent a sentinel node procedure between 2002 and 2011 were included in a prospective database. In cases of IMC drainage, successful exploration of the IMC (i.e., sentinel node removed) and surgical complications were registered. If the removed sentinel node contained malignant cells we determined if this altered the treatment plan when practising the current guidelines. In total, 119 of the 493 included patients showed IMC drainage on lymphoscintigraphy. Exploration of the IMC was performed in 107 (89 %) patients; in 86/107 (80 %) exploration was successful. In 14/107 patients (13 %) the IMC sentinel node was tumor positive. Macro and micro metastases were found in eight and six patients, respectively. In the group of patients who underwent surgical exploration of the IMC, systemic treatment was changed in none, radiotherapy treatment in 13/107 patients (11 %). Routine sentinel node biopsy of the IMC does not alter the systemic treatment. Radiotherapy treatment is altered in a small proportion of the patients; however, solid scientific evidence for this adjustment is lacking.
Sentinel lymph node biopsy; Internal mammary chain; Breast cancer; Post-operative treatment
To evaluate the accuracy of sentinel lymph node biopsy in breast cancer patients at this institution, using combined technetium-99m (99mTc) sulphur colloid and patent blue vital dye.
From March 2007 to July 2008, 50 patients with a tumour of less than 3 cm and with clinically negative axillary lymph nodes underwent sentinel lymph node biopsy (SLNB), followed by axillary lymph node dissection (ALND). Sub-areolar 99mTc sulphur colloid injection was performed the day before surgery, and patent blue vital dye was also injected sub-areolarly at least 5 minutes before surgery. Sentinel lymph node was identified during the surgical procedure, using a gamma probe and direct vision. All sentinel nodes underwent frozen section analysis. Later haematoxylin and eosin staining and immunohistochemical analysis were performed. Finally, SLNB was compared with standard ALND for its ability to accurately reflect the final pathological status of the axillary nodes.
The sentinel lymph node (SLN) was identified in 48 of 50 patients (96%). The number of sentinel lymph nodes ranged from one to four (mean 1.48) and non-sentinel nodes ranged from seven to 27 (mean 14.33). Of the 48 patients with successfully identified SLNs, 29.17% (14/48) were histologically positive. Sensivity of the SLN to predict axilla was 93.75%; accuracy was 97.96%. The SLN was falsely negative in one patient—6.25% (1/16).
The SLNB represents a major advance in the surgical treatment of breast cancer as a minimally invasive procedure predicting the axillary lymph node status. This validation study demonstrates the accuracy of the SLNB and its reasonable false negative rate when performed in our institute. It can now be used as the standard method of staging in patients with early breast cancer at this institution.
Axillary clearance provides important prognostic information but is associated with significant morbidity. Sentinel node biopsy can provide staging .141 patients with node negative early breast cancers-tumour size less than 1.5 cm measured clinically or by imaging had guided axillary sampling (sentinel lymph node biopsy in combination with axillary sampling). Four node axillary sampling improved the detection rate of axillary node metastases by 13.6% as compared to blue dye sentinel node biopsy alone. Positive sampled nodes strongly indicated the likelihood of further metastatic being revealed by axillary dissection (67%). Negative sampled nodes in combination with a positive sentinel node biopsy were associated with a much lower rate of further nodal involvement in the axillary clearance (8%).
Early breast cancer; sentinel node biopsy; axillary sampling; guided axillary sampling
The purpose of this study was to evaluate the occurrence of lymphatic drainage to non-axillary sentinel nodes and to determine the implications of this phenomenon. A total of 549 breast cancer patients underwent lymphoscintigraphy after intratumoural injection of 99mTc-nanocolloid. The sentinel node was intraoperatively identified with the aid of intratumoural administered patent blue dye and a gamma-ray detection probe. Histopathological examination of sentinel nodes included step-sectioning at six levels and immunohistochemical staining. A sentinel node outside level I or II of the axilla was found in 149 patients (27%): internal mammary sentinel nodes in 86 patients, other non-axillary sentinel nodes in 44 and both internal mammary and other non-axillary sentinel nodes in nineteen patients. The intra-operative identification rate was 80%. Internal mammary metastases were found in seventeen patients and metastases in other non-axillary sentinel nodes in ten patients. Staging improved in 13% of patients with non-axillary sentinel lymph nodes and their treatment strategy was changed in 17%. A small proportion of clinically node negative breast cancer patients can be staged more precisely by biopsy of sentinel nodes outside level I and II of the axilla, resulting in additional decision criteria for postoperative regional or systemic therapy.
British Journal of Cancer (2002) 87, 705–710. doi:10.1038/sj.bjc.6600359 www.bjcancer.com
© 2002 Cancer Research UK
breast cancer; lymphoscintigraphy; sentinel node; staging
For accurate nodal staging, all blue and radioactive lymph nodes should be sampled during the sentinel lymph node biopsy for breast cancer. We report a case of anomalous drainage in which one of the sentinel lymph nodes was unexpectedly found in the level III axillary space.
A 40-year-old female underwent mastectomy for extensive high-grade ductal carcinoma in-situ (DCIS) with micro-invasion. The index lesion was located in the right upper inner quadrant. Lymphoscintigraphy was performed on the morning of surgery. Two sentinel lymph nodes were identified. At operation, 5 mls of isosulfan blue dye was injected at the same site of the radio-colloid injection. The first sentinel lymph node was found at level I and was blue and radioactive. The second sentinel node was detected in an unexpected anomalous location at level III, medial to the pectoralis minor. Both sentinel nodes were negative.
Sentinel node staging can lead to unexpected patterns of lymphatic drainage. For accurate staging, it is important to survey all potential sites of nodal metastasis either with preoperative lymphoscintigraphy and/or rigorous examination of regional nodal basins with the intra-operative gamma probe.
Sentinel lymph node biopsy is emerging as the new standard for axillary staging in breast cancer. Intra-operative assessment of the sentinel lymph nodes allows immediate completion of axillary dissection during the same anaesthetic. This project was a quality assurance practice to establish feasibility, time-to-report, as well as accuracy of performing intra-operative assessment of sentinel lymph nodes using touch imprint cytology in our centre.
PATIENTS AND METHODS
This prospective audit included 146 sentinel lymph nodes from 74 consecutive patients with invasive breast cancer. All patients underwent axillary sentinel lymph node biopsy using combined blue dye and radiocolloid technique. Results of intra-operative touch imprint cytology using haematoxylin and eosin staining were compared with the definitive histopathology results.
Mean time to report touch imprint cytology was 25.7 ± 6.4 min (range, 15–40 min). Histopathology demonstrated metastasis in 25 sentinel nodes from 17 (23%) patients. Intra-operative touch imprint cytology detected 15 nodes in 11 patients, giving a sensitivity of 60% (nodes) and 66.7% (patients) and specificity of 99.2% (nodes) and 98.2% (patients) based on the number of nodes and patients involved, respectively. Touch imprint cytology failed to show metastatic involvement in 10 nodes from 6 patients; of these, five nodes had micrometastasis (< 2 mm) and the other five had macrometastasis. One touch imprint cytology positive node contained isolated tumour cells only. Using intra-operative touch imprint cytology made a change in treatment of 11(14.9%) patients, and spared second axillary procedure in 7 (9.4%) patients.
Intra-operative sentinel lymph node assessment using touch imprint cytology is feasible within a busy NHS practice. We now offer touch imprint cytology to patients following appropriate counselling.
Touch imprint cytology; Sentinel lymph node; Breast cancer
The widespread adoption of sentinel lymph node biopsy to stage the axilla has led to decrease in arm and shoulder morbidity. Sentinel lymph node biopsy is suitable for patients with clinically/radiologically node negative invasive breast cancer and selected patients with DCIS (those with clinical/radiological mass or extensive lesions requiring mastectomy). The combined isotope-blue dye injection technique gives the best results. We inject the isotope intra-dermally preoperatively and blue dye dye subdermally after anesthetic induction into the tumour quadrant peri-areolar tissue. Lymphoscintiscan is not necessary but is useful during the learning phase. Sentinel node biopsy can be performed through a small transverse or vertical axillary incision (∼3 cm) appropriately placed to allow axillary lymph node clearance if needed.
Breast cancer; Blue dye; Sentinel lymph node biopsy; Radioisotope
This paper describes a simple technique of axillary and breast massage which improves the successful identification of blue sentinel nodes using patent blue dye alone.
Patent blue dye was injected in the subdermal part of the retroaroelar area in 167 patients having surgical treatment for invasive breast cancer. Three stage axillary lymphatic massage was performed prior to making the axillary incision for sentinel lymph node biopsy. All patients had completion axillary sampling or clearance.
A blue lymphatic duct leading to lymph nodes of the first drainage was identified in 163 (97%) of the patients. Results are compared with 168 patients who had sentinel lymph node biopsy using blue dye without axillary massage. Allergic reactions were observed in four patients (1.2%).
Three stage axillary lymphatic massage improves the successful identification of a blue sentinel lymph node in breast cancer patients.
Sentinel lymph node biopsy (SLNB) is now considered a standard of care in early breast cancers with N0 axillae; however, its role in locally advanced breast cancer (LABC) after neo-adjuvant chemotherapy (NACT) is still being debated. The present study assessed the feasibility, efficacy and accuracy of sentinel lymph node biopsy (SLNB) using "dye alone" (methylene blue) method in patients with LABC following NACT.
Materials and methods
Thirty, biopsy proven cases of LABC that had received three cycles of neo-adjuvant chemotherapy (cyclophosphamide, adriamycin, 5-fluorouracil) were subjected to SLNB (using methylene blue dye) followed by complete axillary lymph node dissection (levels I-III). The sentinel node(s) was/were and the axilla were individually assessed histologically. The SLN accuracy parameters were calculated employing standard definitions. The SLN identification rate in the present study was 100%. The sensitivity of SLNB was 86.6% while the accuracy was 93.3%, which were comparable with other studies done using dual lymphatic mapping method. The SLN was found at level I in all cases and no untoward reaction to methylene blue dye was observed.
This study confirms that SLNB using methylene blue dye as a sole mapping agent is reasonably safe and almost as accurate as dual agent mapping method. It is likely that in the near future, SLNB may become the standard of care and provide a less morbid alternative to routine axillary lymph node dissection even in patients with LABC that have received NACT.
One of the most exciting and talked about new surgical techniques in breast cancer surgery is the sentinel lymph node biopsy. It is an alternative procedure to standard axillary lymph node dissection, which makes possible less invasive surgery and side effects for patients with early breast cancer that wouldn't benefit further from axillary lymph node clearance. Sentinel lymph node biopsy helps to accurately evaluate the status of the axilla and the extent of disease, but also determines appropriate adjuvant treatment and long-term follow-up. However, like all surgical procedures, the sentinel lymph node biopsy is not appropriate for each and every patient.
In this article we review the absolute and relative contraindications of the procedure in respect to clinically positive axilla, neoadjuvant therapy, tumor size, multicentric and multifocal disease, in situ carcinoma, pregnancy, age, body-mass index, allergies to dye and/or radio colloid and prior breast and/or axillary surgery.
Certain conditions involving host factors and tumor biologic characteristics may have a negative impact on the success rate and accuracy of the procedure. The overall fraction of patients unsuitable or with multiple risk factors that may compromise the success of the sentinel lymph node biopsy, is very small. Nevertheless, these patients need to be successfully identified, appropriately advised and cautioned, and so do the surgeons that perform the procedure.
When performed by an experienced multi-disciplinary team, the SLNB is a highly effective and accurate alternative to standard level I and II axillary clearance in the vast majority of patients with early breast cancer.
The best method of pathological evaluation of sentinel lymph node in breast cancer has not been agreed upon. Immunohistochemical (IHC) techniques have shown a greater sensitivity over conventional histology for the detection of micrometastais. The aim of the study was to determine whether IHC for Epithelial Membrane Antigen (EMA) on the sentinel node could be more sensitive than conventional histology for diagnosing micrometastasis in sentinel lymph nodes. Eighty-four clinically node negative breast cancer patients underwent sentinel node biopsy at time of surgery for breast cancer. The node was subjected to conventional histopathology as well as IHC for EMA. The sensitivity of histology viz a viz IHC for EMA for detection of sentinel node metastasis was 88% and the specitficity was 96%. The overall diagnostic accuray of histology viz a viz IHC was 93%. There were 4 patients with micrometastasis (<2.0 mm), which were positive on IHC but negative on histology. Two patients with poorly differentiated breast cancer had a false negative IHC for EMA result as compared to histology. Immunohistochemistry for Epithelial Membrane Antigen can increase the detection rate of micrometastasis in sentinel lymph node. This can have important bearing on deciding the need of adjuvant systemic therapy. A false negative result for EMA may be seen in patients with poorly differential cancer. Therefore the best policy seems to employ both histopathology and IHC for EMA for the comprehensive evaluation of sentinel lymph node in breast cancer.
Sentinel node; Breast cancer; Immunohistochemistry
On a pathological specimen of breast cancer cells, retraction artifact during histological processing mimics true lymphovascular invasion (LVI). The accurate determination of the presence or absence of LVI is a factor in determining risk of having a positive sentinel node, or having additional positive axillary nodes after a positive sentinel node biopsy in women with early-stage breast cancer. The determination of nodal risk influences the decision of the treating physicians as to whether a sentinel node biopsy or completion axillary dissection is necessary. On slide preparation, ideal factors favoring true LVI include: a definite endothelial lining, with endothelial nuclei that seem to protrude into the lymphatic space; invasion in one lymphatic vessel (LV) lumen with nearby cancer glands that have minimal or no retraction; a tumor embolus in a LV clear lumen with outside nearby tumor bulk; a tumor embolus that is different in shape than its surrounding clear LV space; and a positive stain for fibrin, CD31, or CD34 on tumor embolus periphery.
Breast neoplasms; Diagnosis; Pathology
The concept of sentinel lymph node surgery is to determine whether the cancer has spread to the very first lymph node or sentinel node. If the sentinel node does not contain cancer, then there is a high likelihood that the cancer has not spread to other lymph nodes. The sentinel node technique has been proven to be effective in different types of cancer. In this study we want to determine whether a sentinel node procedure in patients with ovarian cancer is feasible when the tracers are injected into the ovarian ligaments.
Patients with a high likelihood of having an ovarian malignancy in whom a median laparotomy and a frozen section analysis is planned and patients with endometrial cancer in whom a staging laparotomy is planned will be included.
Before starting the surgical staging procedure, blue dye and radioactive colloid will be injected into the ligamentum ovarii proprium and the ligamentum infundibulo-pelvicum. In the analysis we calculate the percentage of patients in whom it is feasible to identify sentinel nodes. Other study parameters are the anatomical localization of the sentinel node(s) and the incidence of false negative lymph nodes.
Approval number: NL40323.068.12
Name: Medical Ethical Committee Maastricht University Hospital, University of Maastricht
Affiliation: Maastricht University Hospital
Board Chair Name: Medisch Ethische Commissie azM/UM
Sentinel node; Ovarian cancer
Sentinel node biopsy is a minimally invasive technique to select patients with occult lymph node metastases who may benefit from further regional or systemic therapy. The sentinel node is the first lymph node reached by metastasising cells from a primary tumour. Attempts to remove this node with a procedure based on standard anatomical patterns did not become popular. The development of the dynamic technique of intraoperative lymphatic mapping in the 1990s resulted in general acceptance of the sentinel node concept. This hypothesis of sequential tumour dissemination seems to be valid according to numerous studies of sentinel node biopsy with confirmatory regional lymph node dissection. This report describes the history and the validation of the technique, with particular reference to breast cancer.
history; lymphatic dissemination; review; sentinel node
Sentinel lymph node biopsy (SLNB) is a simple technique that uses subdermal or peri-tumoral injection of vital blue dye and/or radioactive isotope to identify the first lymph node(s) draining the primary tumor. It has been shown to accurately predict axillary node status in patients with clinically node negative breast cancer. The SLNB is emerging as a new standard of care in patients with early breast cancer. However, the use of methylene blue (MB) dye can be associated with a number of local complications due to its tissue reactive properties. We report a rare case of skin and fat necrosis followed by a dry gangrene of the skin in a female patient with breast cancer who underwent SLNB localization using peri-tumoral injection of MB dye in another institution. This case and literature review suggest that the use of MB dye for SLNB identification should be avoided and replaced with alternative types of blue dye such as Patent Blue V preferably in conjunction with a radioactive isotope tracer.
Sentinel lymph node; methylene blue dye; breast cancer; skin necrosis
Maximisation of the potential of sentinel lymph node biopsy as a minimally invasive method of axillary staging requires sensitive intraoperative pathological analysis so that rates of re-operation for lymphatic metastases are minimised. The aim of this study was to describe the test parameters of the frozen section evaluation of sentinel node biopsy for breast cancer compared to the gold standard of standard permanent pathological evaluation at our institution.
The accuracy of intraoperative frozen section (FS) of sentinel nodes was determined in 94 consecutive women undergoing surgery for clinically node negative, invasive breast cancer (37:T1 disease; 43:T2; 14:T3). Definitive evidence of lymphatic spread on FS indicated immediate level II axillary clearance while sentinel node "negativity" on intraoperative testing led to the operation being curtailed to allow formal H&E analysis of the remaining sentinel nodal tissue.
Intraoperative FS correctly predicted axillary involvement in 23/30 patients with lymphatic metastases (76% sensitivity rate) permitting definitive surgery to be completed at the index operation in 87 women (93%) overall. All SN found involved on FS were confirmed as harbouring tumour cells on subsequent formal specimen examination (100% specificity and positive predictive value) with 16 patients having additional non-sentinel nodes found also to contain tumour. Negative Predictive Values were highest in women with T1 tumours (97%) and lessened with more local advancement of disease (T2 rates: 86%; T3: 75%). Of those with falsely negative FS, three had only micrometastatic disease.
Intraoperative FS reliably evaluates the status of the sentinel node allowing most women complete their surgery in a single stage. Thus SN can be offered with increased confidence to those less likely to have negative axillae hence expanding the population of potential beneficiaries.
Sentinel lymph node (SLN) biopsy has emerged as a preferred method for axillary lymph node staging of breast cancer, and imaging the SLN in three-dimensional space is a prerequisite for the biopsy. Conventional SLN mapping techniques based on the injection of an organic dye or a suspension of radioactive colloids suffer from invasive surgical operation for visual detection of the dye or hazardous radioactive components and low spatial resolution of Geiger counters in detecting the radioactive colloids. This work systematically investigates the use of gold nanocages (AuNCs) as a novel class of optical tracers for noninvasive SLN imaging by photoacoustic (PA) tomography in a rat model. The transport of AuNCs in a lymphatic system and uptake by the sentinel lymph node were evaluated by PA tomography on the axillary region of a rat. Quantification of AuNCs accumulated in the lymph node was achieved by correlating the data from PA imaging with the results from inductively-coupled plasma mass spectrometry. Several parameters were systematically evaluated and optimized, including the concentration, size, and surface charge of the AuNCs. These results are critical to the further development of this AuNC-based PA tomography system for noninvasive SLN imaging, providing valuable information for metastatic cancer staging.
gold nanocages; sentinel lymph node; photoacoustic tomography; metastatic cancer staging
Sentinel node surgery was designed to minimize side effects of lymph node surgery but still offer outcomes equivalent to axillary dissection. The aims of NSABP Protocol B-32 were to determine whether sentinel node resection in breast cancer patients achieves the same survival and regional control as axillary dissection but with fewer side effects.
5611 women with invasive breast cancer were randomly assigned to sentinel node resection plus axillary dissection (Group 1) or to sentinel node resection alone with axillary dissection only if sentinel nodes were positive (Group 2). Random assignment was done at the NSABP Biostatistical Center and accomplished via using a biased coin minimization approach. Stratification variables were age at entry (≤ 49,≥ 50), clinical tumor size (≤ 2.0 cm, 2.1 – 4 cm, ≥ 4.1 cm), and surgical plan (lumpectomy, mastectomy). Sentinel node resection was done using blue dye and radioactive tracer. As pre-specified in the protocol, analyses of endpoint data were performed according to the randomized group assignments on patients who were assessed at the time of randomization as having pathologically negative sentinel nodes (3989 patients). The endpoint analyses were performed on all such patients who had follow-up information regardless of their eligibility status (3986 patients). The primary endpoint for the study was overall survival. All deaths regardless of cause were included. The mean time on study for the 3986 sentinel node-negative patients with follow-up information was 95.6 months (range: 70.1 – 126.7 months).
A total of 309 deaths were reported in the 3986 sentinel node-negative patients with follow-up information. Log-rank comparison of overall survival in Groups 1 and 2 yielded an unadjusted hazard ratio of 1.20 (95% confidence interval [CI]; 0.96 –1.50, P = 0.12). Eight-year Kaplan-Meier estimates for overall survival are 91.8% in Group 1 and 90.3% in Group 2. Treatment comparisons for disease-free survival yielded an unadjusted hazard ratio of 1.05 (95% CI: 0.90 – 1.22, P=0.54). Eight-year Kaplan-Meier estimates for disease-free survival are 82.4% in Group 1 and 81.5% in Group 2. There were 8 regional node recurrences as first events in Group 1 and 14 in Group 2 (P=0.22). Patients are continuing follow up for longer term evaluation of survival and regional control.
Overall survival, disease-free survival, and regional control were statistically equivalent between groups. When the sentinel node is negative, sentinel node surgery alone with no further axillary dissection is an appropriate, safe, and effective therapy for breast cancer patients with clinically negative lymph nodes.
sentinel node; breast cancer; randomized trial; survival; axillary dissection
We present an unusual case of severe anaphylaxis to Patent Blue dye with atypical clinical features during sentinel lymph node biopsy (SLNB). The medical personnel involved with sentinel node biopsies should be alert, and familiar with this unusual entity. We also present current data from the literature.
During a wide local excision for primary breast cancer and SLNB, and early during the operation, the patient became severely tachycardic and hypotensive without any signs of urticaria, rash, oedema, or bronchospasm. Resuscitation required the addition of noradrenaline infusion followed by an overnight admission to the intensive care unit. Raised serum tryptase levels supported the diagnosis of anaphylactic shock while skin tests showed a severe reaction to Patent Blue dye.
Severe, life-threatening anaphylaxis to Patent Blue dye may present without obvious previous exposure to the dye and without the cardinal signs of oedema, urticaria and bronchospasm making the diagnosis and management of such cases challenging. Correct diagnosis and identification of the causative factor is important and requires a specific set of laboratory tests that are not commonly requested in every-day medical practice. It is not clear from the literature whether the condition is common enough to justify pre-operative prophylactic or diagnostic measures.
Patent Blue; Isosulphan Blue; Anaphylaxis; Sentinel lymph node biopsy
Synchronous bilateral Paget’s disease of the nipple is extremely rare. In the present study, we report a case of synchronous bilateral Paget’s disease in a 45-year-old woman who had a medical history of gastric cancer. The patient presented with a 6-month history of eczema and itching in both nipples. Mammography and ultrasonography did not reveal any mass lesions in the bilateral breast, and computed tomography and bone scintigraphy showed no site of distant metastasis. The patient was scheduled for mastectomy and sentinel node biopsy. The histological diagnosis was Paget’s disease of the breast with no evidence of underlying invasive ductal carcinoma or ductal carcinoma in situ of the breast tissue. There was no metastasis in either of the sentinel nodes. Immunohistochemical staining showed a negative expression of oestrogen and progesterone receptors. The patient has not received chemotherapy, radiotherapy or hormonal therapy. The patient has been disease-free for 7 months following surgery.
Paget’s disease; breast cancer; bilateral; synchronous
The sentinel node is the first lymph node to receive lymphatic drainage from a tumour and is usually the first site of metastases. Today, the sentinel node is used for tumour staging. Here, we focus on its immunological role and investigate lymphocytic function in sentinel nodes, identified intraoperatively by peritumoural dye injection, from 15 patients with colon cancer. Tumour infiltrating lymphocytes, sentinel and nonsentinel lymph node cells and peripheral blood leukocytes were studied by flow cytometry, proliferation assays and interferon-γ secretion after activation with autologous tumour homogenate. Whereas tumour-infiltrating lymphocytes were nonresponsive in the proliferation assays, lymphocytes from sentinel nodes proliferated dose dependently and secreted interferon-γ upon stimulation with tumour homogenate. The responses were of varying magnitude and tended to be weaker in metastatic sentinel nodes. Sentinel node lymphocytes represents an enriched source of tumour reactive lymphocytes, and may be useful in future trials of adoptive immunotherapy.
sentinel node; colon cancer; adoptive immunotherapy; tumour reactive lymphocytes