Sentinel Lymph Node Biopsy

Many prospective randomized controlled trials aimed to clarify this issue. The American College of Surgeons (ACOSOG) Z0011 trial showed that in women with early breast cancer (T1/T2) and metastases in 1 or 2 SLN, without extranodal extension, that undergo breast conserving important part of breast cancer treatment despite the fact the sentinel lymph node biopsy (SLNB) has revolutionized breast cancer surgery. SLNB provides the same prognostic information as ALND but with significantly less morbidity. The results of numerous trials conducted over the past 20 years have crowned SLNB as the gold standard for early breast cancer treatment. ALND represents a very standardized intervention with precise landmarks and boundaries. An accurate technique and a good knowledge of axilla’ anatomy are mandatory for a correct and complete ALND. But even with a meticulous and careful technique of dissection, a comprehensive ALND may be associated with important morbidity. Nowadays ALND indications are continuously evolving, but the procedure has still an indisputable place in breast cancer treatment.

J. Surg. Oncol. 2007;95:623–628. ß 2007 Wiley-Liss, Inc. K EY W ORDS : melanoma; sentinel lymph node biopsy; costs and cost analysis INTRODUCTION Lymphatic mapping and sentinel lymph node (SLN) biopsy have emerged as the standard method of evaluating the tumor status of the regional lymph nodes in patients with malignant melanoma. There is little doubt that SLN biopsy provides important prognostic information with relatively low morbidity. The fact that the SLN accurately reflects the status of the entire regional node field in the vast majority of cases has been well validated [1–3]. Knowledge of the SLN status provides the patient with a more reliable estimate of prognosis, and allows more accurate stratification for entry into adjuvant therapy trials. It also identifies those patients who may benefit from a completion lymphade- nectomy.

Abstract Lymphatic mapping and sentinel lymph node biopsy were first reported in 1977 by Cabanas for penile cancer. Since that time, the technique has become rapidly assimilated into clinical practice. The sentinel node concept has been validated in cutaneous melanoma and breast cancer. However, follow-up data of patients from randomised trials is needed to establish the clinical significance of sentinel lymph node biopsy before accepting the procedure as a standard of care. This technique has the potential to be utilised in all solid tumours like colon, gastric, oesophageal, lung, gynaecologic, and head and neck cancer. This paper reviews the current status of sentinel lymph node biopsy in solid tumours.

Age and body mass index Increased age and body mass index (BMI) have been linked to an increase incidence of SLNB failure [91,92]. This could have serious implications since a large propor- tion of patients with breast cancer are senior and/or over- weight. Sentinel lymph node biopsy seems to be feasible regardless of the age of the patient but the identification rate of the procedure may be impacted by increasing age and BMI. Some authors speculate that anatomical changes in the breast of elderly and obese patients, with decrease in the density of the gland and increase of fatty tissue deposit, may result in decreased lymphatic flow and increased SLNB failure rates. Furthermore, the high con- tent of subcutaneous and axillary adipose tissue makes palpation harder and the identification of the sentinel node more difficult, especially when only blue dye is uti- lized. Three multi-institutional studies found that the sen- tinel node was found less frequently in women older than 50 years of age [18,22,23], with reported identification rates of 87.6% versus 92.6% for younger patients [22], while other trials report a strong inverse relationship between increased BMI (>30) and identification rate for the SLNB [93]. The identification rate was 99% for patients with BMI < 20, 96.6% for BMI of 30 and 94.2%

5. Goyal A, Newcombe RG, Chhabra A, Mansel RE, Almanac Trialists G. Factors affecting failed localisation and false-negative rates of sentinel node biopsy in breast cancer-- results of the ALMANAC validation phase. Breast Cancer Res Treat. 2006;99(2):203-8. 6. Del Bianco P, Zavagno G, Burelli P, Scalco G, Barutta L, Carraro P, et al. Morbidity comparison of sentinel lymph node biopsy versus conventional axillary lymph node dissection for breast cancer patients: results of the Sentinella-GIVOM Italian randomised clinical trial. Eur J Surg Oncol. 2008;34(5):508-13.

A computerized literature search was performed using Ovid, Medline, Embase, and PubMed databases using the terms “melanoma,” “head and neck neoplasms,” “head and neck cancer,” “sentinel lymph node” and “sentinel lymph node biopsy.” The results were limited to English publications from 2010 to September 13, 2013. Once duplicates were identified and removed, the retrieved articles were then reviewed to ensure their relevance for our review. Once all articles to be included were identified, the references of all included articles were reviewed to identify any additional applicable publications that may have been missed by our original search.

Discussion The aim of our pilot study was to assess the technical fea- sibility of sentinel lymph node biopsy with a radiotracer in patients presenting with uninodular thyroid disease sus- picious for malignancy. As we were conducting a techni- cal feasibility study for a procedure and not a clinical out- come trial, not only patients with proven papillary carci- nomas, but also a series of patients with uninodular thy- roid neoplasms, were included. SLN biopsy has been in- troduced in the field of malignant melanoma, breast can- cer, oral squamous cell carcinoma and other tumors with great reliability and accuracy [1, 12, 17, 26, 28]. It allows the histological staging of the lymphatic drainage without excising the whole lymphatic basin. By doing this, pa- tients who benefit from extended lymphatic dissection can be selected, and the others can be spared the risks and costs of this procedure. In contrast to most other malignancies with preferentially lympatic spread, the stage of lymph node involvement seems not to be a general prognostica- tor in differentiated thyroid cancer [4, 16, 24]. Therefore, we can not expect any benefit with regard to survival from disclosing occult metastatic neck disease by SLN biopsy in all patients. However, more recent studies have come up demonstrating an elevated regional failure rate and prog- nostic impact of neck metastases in a subset of high-risk patients [6, 10, 14, 16, 21, 22, 23, 25, 29]. Unfortunately, all these studies only address palpable or imaging-detectable lymph nodes or macrometastatic disease as discovered by neck dissection. The impact of occult metastatic lymph node involvement on recurrence and survival has not yet been elucidated prospectively. The question still remains:

If you had breast surgery, your nurse will give you the resource titled Exercises After Your Sentinel Lymph Node Biopsy or.. Lumpectomy (www.mskcc.org/pe/exercises_slnb_lumpectomy).[r]

The management of lymph nodes in nonmelanoma skin cancer patients is currently still debated. Merkel cell carcinoma (MCC), squamous cell carcinoma (SCC), pigmented epithelioid melanocytoma (PEM), and other rare skin neoplasms have a well-known risk to spread to regional lymph nodes. The use of sentinel lymph node biopsy (SLNB) could be a promising procedure to assess this risk in clinically N0 patients. Metastatic SNs have been observed in 4.5–28% SCC (according to risk factors), in 9–42% MCC, and in 14–57% PEM. We observed overall 30.8% positive SNs in 13 consecutive patients operated for high-risk nonmelanoma skin cancer between 2002 and 2011 in our institution. These high rates support recommendation to implement SLNB for nonmelanoma skin cancer especially for SCC patients. Completion lymph node dissection following positive SNs is also a matter of discussion especially in PEM. It must be remembered that a definitive survival benefit of SLNB in melanoma patients has not been proven yet. However, because of its low morbidity when compared to empiric elective lymph node dissection or radiation therapy of lymphatic basins, SLNB has allowed sparing a lot of morbidity and could therefore be used in nonmelanoma skin cancer patients, even though a significant impact on survival has not been demonstrated.

Discussion The aim of our pilot study was to assess the technical fea- sibility of sentinel lymph node biopsy with a radiotracer in patients presenting with uninodular thyroid disease sus- picious for malignancy. As we were conducting a techni- cal feasibility study for a procedure and not a clinical out- come trial, not only patients with proven papillary carci- nomas, but also a series of patients with uninodular thy- roid neoplasms, were included. SLN biopsy has been in- troduced in the field of malignant melanoma, breast can- cer, oral squamous cell carcinoma and other tumors with great reliability and accuracy [1, 12, 17, 26, 28]. It allows the histological staging of the lymphatic drainage without excising the whole lymphatic basin. By doing this, pa- tients who benefit from extended lymphatic dissection can be selected, and the others can be spared the risks and costs of this procedure. In contrast to most other malignancies with preferentially lympatic spread, the stage of lymph node involvement seems not to be a general prognostica- tor in differentiated thyroid cancer [4, 16, 24]. Therefore, we can not expect any benefit with regard to survival from disclosing occult metastatic neck disease by SLN biopsy in all patients. However, more recent studies have come up demonstrating an elevated regional failure rate and prog- nostic impact of neck metastases in a subset of high-risk patients [6, 10, 14, 16, 21, 22, 23, 25, 29]. Unfortunately, all these studies only address palpable or imaging-detectable lymph nodes or macrometastatic disease as discovered by neck dissection. The impact of occult metastatic lymph node involvement on recurrence and survival has not yet been elucidated prospectively. The question still remains: is a cN0 neck that turns out to be a pN+ (mi) (sn) [9] neck rather comparable to a pN0 neck or to a pN+ neck? Or, in other words, is occult metastatic lymph node disease in high-risk groups an independent prognosticator that should be therapeutically addressed? Though the high-risk cohort of patients with advanced age, gross tumor extent, distant metastases or large tumor size might be the group to study for a potential benefit of SLN biopsy, the trial to resolve this question is very unlikely to succeed. With regard to the high cure rate and the slow growing pattern of papil- lary thyroid cancer, the number of patients and the dura- tion of such a study probably exceeds by far what is feasi- ble. Further, occult metastases as an independent prognos- ticator would have to compete in this high-risk setting with all the aforementioned strong prognosticators. In con- clusion, we think that the benefit of SLN biopsy is hard to prove, but it could be the way to go for those who believe

Lymphoscintigraphy Abstract Sentinel lymph node biopsy has become a well-established and commonplace prac- tice in many oncologic disease sites as a means to stage the regional lymphatics, avoid unnec- essary surgery and decrease patient morbidity. In the head and neck, its role is well established for cutaneous melanoma with proven fidelity and survival benefit. Its role in use for other sites such as oral cavity carcinoma continues to develop with promising results from several recent trials. Although not widely adopted, the potential benefits of sentinel lymph node biopsy in the management of oral cavity carcinoma are apparent. Refinements in tech- nology and protocols including development of novel radiopharmaceutical tracers, routine incorporation of detailed anatomic imaging, increasing surgeon experience and development of new intraoperative identification aids will likely lead to improvements in the use and accu- racy of this technique.

DCIS is a disease devoid of invasive behaviour and thus without potential for spread to the axillary lymph nodes. Current practice is to perform sentinel lymph node biopsy (SLNB) only in selected patients with DCIS when there is substantial risk of upgrade of the lesion at final pathology, such as a mass lesion highly suggestive of invasive cancer at imaging and physical examination, patients with a large area of DCIS at imaging (5 cm or greater), or when mastec- tomy is indicated 8 . However, evidence for this recommen- dation is inadequate because of the sparsity of data analysed in the literature, also characterized by a lack of long-term

Breast cancer treatment has evolved over recent decades due to advances in techniques for early detection of the disease, with consequent decreases in the mortality rate 1,2 and morbidity rate that result from less aggressive surgeries. The status of axillary lymph nodes determines whether the treatment should be more or less invasive, indicating either axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB), 3–5 respectively. Surgical injuries resulting from ALND cause obstruction of the primary route of lymphatic drainage of the arm, 5,6 leading to postoperative complications, such as hemorrhage, infection, seroma, axillary web syndrome, chronic pain, paraesthesia caused by intercostobrachial nerve damage, reduced range of motion and muscle weakness on the shoulder ipsilateral to the surgery, and, especially, lymphedema. 7,8 More conservative intraoperative techniques to approach the axillary chain, such as SLNB have been used

Key words: breast cancer, excisional biopsy, sentinel lymph-node biopsy, accuracy «L’ ACCURATEZZA DEL LINFONODO SENTINELLA DOPO BIOPSIA ESCISSIONALE DEL CARCINOMA DELLA MAMMELLA » Riassunto. Scopo: La biopsia del linfonodo sentinella (BLS) nel carcinoma della mammella con linfonodi ascellari clinicamente negativi è considerato la migliore scelta per stadiare il cavo ascellare. Inizialmente una precedente biopsia escissionale del carcinoma era considerata una controindicazione. Esaminiamo il tasso di successo della BLS e la incidenza della recidiva a livello ascellare in pazienti con carcinoma della mammella precedentemente sottoposti a biopsia escissionale del tumore. Pazienti e metodi: 858 pazienti con carcinoma della mammella sono stati sottoposti a BLS e i pazienti con linfonodi sentinella metastatici a svuotamento del cavo ascellare; 82 pazienti erano stati sottoposti precedentemente a biopsia escissionale del tumore. Ri- sultati: Il linfonodo sentinella è stato identificato nel 100% dei casi, è risultato indenne nel 74,4% e meta- statico nel 23,1%. La dissezione del cavo ascellare è stata effettuata in tutti i casi con linfonodi sentinella me- tastatici e nel 74% dei casi non si sono ritrovati altri linfonodi ascellari metastatici. Il follow-up mediano è stato di 63,5 mesi e non si sono osservate recidive ascellari. Conclusioni: L’accuratezza del BLS in pazienti con carcinoma della mammella sottoposte precedentemente a biopsia escissionale è uguale a quella dei pazienti non sottoposti a biopsia.

ABSTRACT Objectives: To evaluate feasibility, accuracy and technique of sentinel lymph node biopsy in the management of early breast cancer. Methods: A retrospective study of sentinel lymph node biopsy was done at King Abdulaziz University Hospital from June 2007– to –June 2013. Total of 110 patients were studied, these patients underwent lumpectomy + Sentinel lymph node biopsy. Patients records were studied by looking file, electronic records, OPD records and data was collected regarding previous surgery, location of mass in breast, size of mass, site of breast, pre or postmenopausal, previous axillary surgery, radiological evaluation, radiotherapy, type of surgery done, adjuvant or neo-adjuvant

Timothy M. Johnson, MD 5 ; and Carol R. Bradford, MD 1 BACKGROUND: Sentinel lymph node biopsy (SLNB) has emerged as a widely used staging procedure for cutaneous melanoma. However, debate remains around the accuracy and prognostic implications of SLNB for cutaneous mela- noma arising in the head and neck, as previous reports have demonstrated inferior results to those in nonhead and neck regions. Through the largest single-institution series of head and neck melanoma patients, the authors set out to demonstrate that SLNB accuracy and prognostic value in the head and neck region are comparable to other sites. METHODS: A prospectively collected database was queried for cutaneous head and neck melanoma patients who underwent SLNB at the University of Michigan between 1997 and 2007. Primary endpoints included SLNB result, time to recurrence, site of recurrence, and date and cause of death. Multivariate models were constructed for analyses. RESULTS: Three hundred fifty-three patients were identified. A sentinel lymph node was identified in 352 of 353 patients (99.7%). Sixty-nine of the 353 (19.6%) patients had a positive SLNB. Seventeen of 68 patients (25%) under- going completion lymphadenectomy after a positive SLNB result had at least 1 additional positive nonsentinel lymph node. Patients with local control and a negative SLNB failed regionally in 4.2% of cases. Multivariate analysis revealed positive SLNB status to be the most prognostic clinicopathologic predictor of poor outcome; hazard ratio was 4.23 for SLNB status and recurrence-free survival ( P < .0001) and 3.33 for overall survival (P < .0001). CONCLUSIONS: SLNB is accurate and its results are of prognostic importance for head and neck melanoma patients. Cancer 2012;118:1040-7. V C 2011 American Cancer Society.

The clinical and radiological response to chemotherapy was evaluated after 4 treatment cycles and at the end of chemo- therapy. Axillary lymph node dissection was performed 3 to 4 weeks after chemotherapy. Histological analysis of sen- tinel lymph node biopsies and axillary lymph node dissections were studied for each patient. Results: Eighty nine pa- tients had sentinel lymph node biopsy. The identification rate for sentinel lymph nodes was 98.9%. The sentinel lymph node biopsies were metastatic in 44 of 88 patients. Axillary lymph nodes were metastatic in 12 cases. The negative pre- dictive value was 91.1% [95%CI: 85.1% - 97.1%]. Conclusion: Identification rate and negative predictive value of sen- tinel lymph node biopsy prior to neoadjuvant chemotherapy confirm that the procedure is suitable with its use in stan- dard practice. This approach comprises two surgical procedures, but allows a better nodal status evaluation.

What does a sentinel lymph node biopsy involve? It involves a surgical procedure usually under a general anaesthetic (with you asleep) to remove one or more of the nodes the lymph fluid drains into first and which are closest to the area where the melanoma has been found. For example, if the original melanoma is on the right calf of your leg, the sentinel lymph node is likely to be in your right groin. On the other hand, if the melanoma was on your right arm, the sentinel lymph node is likely to be in your right armpit. In areas like the trunk or head and neck, there may be more than one group of lymph nodes involved.

MATERIALS AND METHODS Protocol development and overview. A protocol was developed for undertaking systematic reviews of test accuracy, diagnostic and therapeutic impact. Scoping searches for relevant systematic reviews were conducted in MEDLINE, EMBASE and the Cochrane Library. Systematic reviews were carried out using established methods (Higgins and Green, 2011; Diagnostic Test Accuracy Working Group, 2012). Presentation of results is according to the PRISMA guidelines (Moher et al, 2009). Inclusion of studies, data extraction and quality assessment were carried out in duplicate using predesigned and piloted data extraction sheets with differences resolved by consensus and/or arbitration involving a third reviewer. A two-stage process was used, firstly by screening titles and abstracts. For all references categorised as ‘include’ or ‘uncertain’ by both reviewers, full text was retrieved wherever possible and final inclusion decisions were made on the full paper. Search strategy, inclusion and exclusion criteria and quality assessment. Comprehensive searches from the inception of database to 25 October 2013 were conducted in MEDLINE, Embase, Science Citation Index, the Cochrane Library, MEDION, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, the Health Technology Assessment Database, Clinical Trials.com as well as a search of internet resources (UK Clinical Research Network Portfolio, specialist search gateways (OMNI and the National Cancer Institute), Google and Copernic) to identify relevant published and unpublished studies and studies in progress. Electronic searches were supplemented by checking reference lists, handsearching the journal Gynecologic Oncology and contact with authors of included studies for information on any relevant published or unpublished studies. No language restrictions were applied. Search strategies were designed from a series of test searches and discussions of the results of searches among the review team. Both MESH terms and text words were used and included ‘vulva cancer’, ‘sentinel lymph node biopsy’ and ‘lymphoscintigraphy’.

American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol 2005, 23:7703 – 7720. 2. Cox CE, Nguyen K, Gray RJ, Salud C, Ku NN, Dupont E, Hutson L, Peltz E, Whitehead G, Reintgen D, Cantor A: Importance of lymphatic mapping in ductal carcinoma in situ (DCIS): why map DCIS? Am Surg 2001, 67:513 – 519. discussion 519 – 521.