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The Management of Regional Lymph Nodes in Cancer

    Br J Dermatol 149(5):919-925, 2003. © 2003 Blackwell Publishing
    Posted 12/12/2003

    Summary and Introduction

    Early clinical observation in cancer patients suggested that tumours spread in a
    methodical, stepwise fashion from the primary site to the regional lymphatics, and
    only then to distant locations. Based on these observations, the regional
    lymphatics were believed to be mechanical barriers preventing the widespread
    dissemination of tumour. Despite evidence now available disputing its validity,
    this barrier theory has guided the surgical management of the regional lymphatics
    for more than a century, influencing the use of such surgical modalities as
    therapeutic lymph node dissection, elective lymph node dissection and most
    recently sentinel lymph node biopsy. No published randomized controlled trial
    exists that demonstrates improved overall survival for patients with cancer of any
    type undergoing surgery of the regional lymphatics. We believe the presence of
    tumour in the regional lymphatics indicates the presence of systemic disease, and
    therapeutic interventions should be directed accordingly.
    Management of the regional lymph nodes (RLNs) in potentially metastatic cancer
    is fraught with controversies and misunderstandings. Early surgical oncologists
    observed many times that the RLNs were enlarged in advanced cancers before
    distant disease appeared, leading to the theory that the RLNs served as mechanical
    barriers temporarily preventing systemic dissemination of tumour. Based on this
    theory, surgeons removed these enlarged lymph nodes along with the primary
    tumour, an approach known as therapeutic lymph node dissection (TLND), in an
    attempt at surgical cure of locally advanced disease. Unacceptable cure rates,
    believed to be a result of unresected microscopic disease, led to the removal of
    clinically normal RLNs, a procedure known as elective lymph node dissection
    (ELND), in an effort to remove these nonpalpable tumour deposits. By the early
    twentieth century, routine dissections of the regional lymphatics in an effort to
    remove all microscopic disease had become the dogma of surgical oncology based
    exclusively on observation and theory rather than sound scientific evidence. This
    barrier theory of lymph node biology continues to influence the management of
    the RLNs in cancer surgery today.
    In light of current knowledge, does it make sense to perform surgical dissection of
    RLNs in patients with cancer? Through well-designed laboratory studies we know
    that the lymph nodes serve specific and important functions that aid in essential
    immunological responses. We also know that an intact immune system is critical
    for host tumour defence mechanisms. Laboratory and clinical studies have cast
    doubt on the theory that lymph nodes serve as mechanical barriers to widespread
    tumour dissemination. Furthermore, abundant randomized controlled clinical
    trials have critically evaluated the role of lymph node dissections in cancer
    management and have failed to demonstrate a significant survival advantage. This
    paper will review this evidence and will make recommendations regarding the
    management of the RLNs in cancer patients, with an emphasis on patients with
    Historical Perspective
    The theoretical value of TLND, or removal of clinically palpable lymph nodes,
    was proposed by the earliest surgical oncologists. In the late eighteenth century,
    Heister first advocated axillary dissection for the treatment of breast cancer after
    observing the clinical course of patients with advanced disease.[1] Clinical
    observation in these patients suggested that the tumour spread in an orderly
    fashion from the primary site to the RLNs, and finally to distant locations. Based
    on these observations, the prevailing theory that developed and was perpetuated
    until late in the twentieth century was that the lymph nodes served as physical
    barriers to tumour dissemination. This was tested by Halsted's experiments in
    radical mastectomies for breast cancer that entailed en bloc removal of the breast,
    the pectoralis muscles and the entire axillary contents.[2] Although Halsted initially
    reported improved survival for patients undergoing his radical surgery in 1894, he
    later retracted this conclusion after re-analysing the data in 1907.[3]
    Halsted's contemporaries argued that the reason the radical mastectomy failed to
    improve survival was that trapped, nonpalpable (microscopic) disease was left
    behind in other nondissected lymph node basins. However, attempts to improve
    on the results of the Halsted mastectomy by dissecting all regional nodal basins
    (including the supraclavicular and internal mammary nodes) were met only with
    increased operative mortality.[4,5] If more aggressive surgery failed to improve
    survival in patients with advanced disease, perhaps earlier, prophylactic lymph
    node surgery in patients with more localized disease would. The emphasis of
    cancer treatment subsequently shifted to early diagnosis in order to facilitate
    surgery in advance of the development of palpable lymphadenopathy. The
    theoretical goal of surgical oncology remained removal of trapped tumour cells
    within the lymphatics, but at a time when tumour burden was small and the
    chance of systemic dissemination was thought to be insignificant. Thus dawned
    the age of the ELND.
    The theoretical benefit of ELND seemed unassailable when considered in the
    context of the belief that the RLNs served as physical barriers to tumour
    dissemination. During a time when little else could be offered to cancer patients,
    this seemingly rational theory and the chance of a surgical cure for this dreaded
    disease captured the attention of surgeons around the world. Numerous
    retrospective and single institutional studies were published that supported the
    widespread use of ELND in nearly all forms of cancer with the potential for nodal
    metastasis including cancer of the breast, uterus, cervix, vulva, prostate, head and
    neck, penis and, of course, melanoma.[6-14] Advocates of ELND used the results of
    these uncontrolled studies to validate the theory that the RLNs were in fact
    barriers to systemic tumour dissemination. Consequently, the role of ELND in
    cancer surgery remained unchallenged in surgical oncology until late in the
    twentieth century.

    A turning point in this story began in 1960 when Bernard Fisher, then the director
    of the National Surgical Adjuvant Breast and Bowel Program, began an ambitious
    study that was to be the first randomized controlled trial (RCT) investigating the
    value of the ELND in breast cancer patients.[15] To the surprise of most, Fisher's
    study of 1700 patients failed to reveal any statistically significant survival
    advantage for patients undergoing ELND. Although the lymph node dissection
    group experienced fewer recurrences in the treated lymph node basin, this
    improvement in local control did not translate to a benefit in overall survival. In
    fact, when these patients did have recurrences, these were more likely to be
    distant disease. Since Fisher's landmark study, five RCTs evaluating ELND in breast
    cancer patients have failed to reveal a statistically significant survival advantage
    for patients treated with ELND.[16] The lack of evidence supporting the value of
    ELND for breast cancer patients in these five trials raised significant questions
    regarding the dogmatic but unproven traditional approach to surgical management
    in patients with cancer.

    Based on the results of Fisher's work in breast cancer, other researchers began
    critical evaluation of the value of ELND in other cancers. There have been four
    RCTs evaluating ELND in 1718 patients with cutaneous melanoma.[17-20]
    Melanoma patients randomized to ELND experienced fewer recurrences in the
    dissected lymph node basin, but none of the studies showed a statistically
    significant survival advantage. The largest of these trials, the Intergroup
    Melanoma Surgical Trial,[17] included 740 patients with melanomas 1-4 mm thick.
    As with the other three trials, there was no survival advantage for those patients
    undergoing ELND compared with those patients treated with TLND at disease
    recurrence. Even though retrospective subgroup analysis found trends in favour of
    ELND in patients less than 60 years old with nonulcerated, intermediate thickness
    melanomas (1-2 mm thick), this type of post hoc analysis attempts to discern
    therapeutic benefits in subsets of patients for which the study was not initially
    designed, and is fraught with considerable bias. For this reason, many experts
    remain hesitant to advocate ELND for their patients based on this type of
    statistical analysis.
    Published RCTs evaluating ELND in the management of other cancers are few.
    Two small RCTs of only 35 and 75 patients failed to reveal any statistically
    significant survival advantage for patients with squamous cell carcinoma of the
    oral cavity undergoing ELND.[21,22] Although statistically meaningful conclusions
    cannot be made from such a small patient population, as in breast cancer and
    melanoma patients those patients randomized to ELND experienced fewer
    regional recurrences in the dissected lymph node basin. The improvement in local
    control offered by ELND in patients with head and neck cancer may provide a
    tangible benefit in this functionally important area. Control of disease influence
    on tracheal, oesophageal and cervical neurovascular function would certainly
    maintain a high priority in disease management. This may explain why neck
    dissections remain an important tool in the treatment of patients with head and
    neck cancer despite a lack of evidence of improved overall survival for those
    undergoing such interventions.
    As sound scientific evidence accumulated to show that ELND offered no survival
    advantage for cancer patients, surgeons in the late twentieth century began to look
    for other ways to assess the status of the regional lymphatics for staging purposes.
    In 1992, Morton et al. reported the technique of sentinel lymph node (SLN)
    biopsy (SLNB) in patients with early stage melanoma.[23] As initially described,
    isosulfan blue dye was injected around the primary melanoma and soon
    afterwards the RLN basin was dissected to locate the initial or sentinel draining
    lymph node. Because of the prevailing belief in the barrier theory of the regional
    lymphatics, it was theorized that the histological status of the sentinel node would
    accurately predict whether or not the tumour had metastasized from the primary
    site. In patients with melanoma, the status of the SLN using standard histology
    became the single most accurate prognostic indicator of metastatic disease.[24]
    Now performed with the use of radiolabelled sulphur colloid, SLNB has become a
    widely used staging tool in cancers of all types with the potential for spread to the
    regional lymphatics.[25-31] In these cancers, the status of the SLN often guides
    further therapeutic interventions including completion lymphadenectomy and
    adjuvant chemotherapy or radiation therapy. However, like TLND and ELND
    before it, the theoretical value of SLNB is based on the barrier theory of the RLNs
    and remains an experimental procedure with no proven therapeutic benefit.
    The Role of the Regional Lymph Nodes
    So why are surgeons continuing to submit cancer patients to surgery of the RLNs
    without any sound scientific evidence of significant survival benefit? Perhaps
    some continue to dissect RLN basins in cancer patients based more on surgical
    tradition rather than scientific evidence. Many surgeons probably remain
    convinced that the RLNs are mechanical barriers preventing tumour dissemination
    and that design flaws in the RCTs testing ELND prevent the detection of a small
    but real benefit for patients undergoing elective node dissection. Likewise, some
    melanoma experts argue that all studies evaluating ELND in melanoma patients
    prior to the advent of SLNB are confounded by the fact that in a small but
    significant percentage of patients the wrong lymph node basin would have been
    dissected. These arguments may have some validity, but with each large-scale
    RCT published that fails to demonstrate a survival advantage for ELND,
    regardless of cancer type, it becomes more difficult to dismiss all these studies as
    scientifically flawed.
    We believe that the reason ELND does not benefit patients with cancer is because
    the RLNs are not mechanical filters or dams preventing the spread of tumour to
    the systemic circulation but are instead indicators of the presence of systemic
    metastasis. Therefore, removal of lymph nodes, even in early disease, will only
    remove the metastases that are in the RLNs, not those that simultaneously
    metastasize elsewhere. Early research by Fisher that led to the initiation of his
    landmark breast cancer trial cast significant doubt on the belief that lymph nodes
    were passive filters for metastasizing cancer cells or that nodes were exposed to
    tumour before the systemic circulation. His studies in rodents demonstrated that
    tumour emboli, even when large, could pass through the draining lymphatics and
    at times bypassed the lymph node altogether.[32-35] Other studies demonstrated
    malignant cells in the venous runoff from various types of solid tumours thought
    at that time to spread only via lymphatics.[36,37] This lymph node permeability is
    due in part to abundant intranodal and lymphaticovenous shunts that can be
    demonstrated by functional studies as well as by electron microscopy.[32,35,38-42]
    If lymph nodes are not mechanical filters for tumour emboli, then what influences
    the location where a tumour metastasis develops? Recent research illustrates that
    various tumour types clearly have organ specificity for their metastases.[43-47] This
    organ specificity appears to be dictated by surface proteins called adhesion
    molecules on both the tumour cells and the tissue where the metastasis comes to
    rest. After the tumour cell breaks away from the primary lesion, it circulates
    through the lymphatic and arteriovenous system, bouncing and even rolling across
    the endothelium within various organs and tissues. As it does so, adhesion
    molecules on the tumour cell regularly come in contact with adhesion molecules
    on the endothelium of the organ or tissue in question. These adhesion molecules
    must be complementary in order for metastases to develop.[48,49] If complementary
    adhesion molecules exist, the tumour cell binds to the endothelium and may
    become a clinical metastasis if it is successful at avoiding tumour defence
    mechanisms. Consequently, if complementary adhesion molecules do not exist in
    the RLNs, tumour emboli circulating in the lymphatic system will bypass the
    RLNs while metastasizing to distant locations.[44,45,50-53] This means that the
    presence of tumour within RLNs, as in a positive SLNB, indicates only that the
    primary tumour has gained the ability to spread and that complementary adhesion
    molecules exist on both the tumour surface and the lymph node stroma. Removal
    of the RLNs at this point does nothing to counteract the systemic nature of the
    disease unless the RLNs are the only anatomical location that contains the
    necessary complementary adhesion molecules. Whether the tumour has
    disseminated to other distant locations depends on the presence of the
    corresponding adhesion molecule in the tissue in question rather than any intrinsic
    property of the RLNs.
    If lymph nodes are not passive filters for tumour emboli, then what role do they
    play in metastatic disease? We know that the lymph nodes, and other lymphoid
    organs, serve to orchestrate important immunological responses to foreign
    antigens.[54] This immunological process is important for host defence
    mechanisms in the early stages of primary tumour growth when appropriate
    antigen recognition and immunological response may prevent the widespread
    dissemination of tumour cells.[55-57] Surgical alteration of regional lymphatic
    structure and function at this early stage of tumour growth may provide the
    tumour with a growth advantage. Surgical alteration of RLN function may also
    affect future therapeutic interventions, as research in both animals and humans has
    demonstrated that removal of the tumour-draining RLNs prior to antitumour
    vaccination significantly diminishes antitumour activity.[58,59] With recent efforts
    to develop immunological therapies for many forms of cancer, the value of
    maintaining an intact RLN basin in this process will need critical evaluation.
    What then are the consequences of tumour metastases developing in the RLNs?
    When the volume of metastasis is small, the immunological effect generated
    against the primary tumour can be sufficient to control potentially lethal cells in a
    dormant state for a long period of time[60,61] and occasionally may result in cell
    death without further growth or dissemination.[38] Removal of these clinically
    irrelevant cells would be unnecessary and might even be harmful from an
    immunological standpoint. Yet, as the tumour grows, eventual
    immunosuppression is likely to develop through a variety of tumour-induced
    mechanisms.[62] Eventually, the normal lymph node architecture is destroyed
    rendering the lymph node immunologically ineffective and a possible source for
    further tumour dissemination. At this point, once the tumour has become
    biologically active and has obliterated the normal structure and function of the
    node, removal would serve to decrease tumour burden and potentially decrease
    further tumour-based immunosuppression.[38,63-65]
    Unfortunately, current technology does not permit us to determine what
    constitutes relevant nodal disease. In one breast cancer trial, 20% of the
    observation group eventually developed clinically palpable lymph node
    metastases as the site of first recurrence.[15] This is much less than the 38% of
    patients found to have microscopic tumour by standard histology after ELND,
    suggesting that an immunological response against the tumour cells may have
    prevented further growth of microscopic disease in 18% of patients. The use of
    more sensitive techniques such as serial sectioning and immunohistochemistry
    further increases the number of patients with 'positive' axillary metastases who
    never go on to develop clinically positive axillary disease: this was as high as 60%
    in one study.[66] When nodes are examined even more closely for submicroscopic
    disease via polymerase chain reaction (PCR) analysis, the results are even more
    surprising. In melanoma, 60% of patients with primary tumours < 0.75 mm thick
    had SLNs that were positive by PCR analysis.[67] This is a remarkably high
    number of patients labelled as having positive nodes by PCR in a subset of
    melanoma patients who historically have a very favourable prognosis and never
    go on to develop clinical lymph node disease. Clearly, the presence of
    microscopic and submicroscopic disease does not correlate with clinical course
    and overestimates the number of patients who will develop clinically positive
    nodal disease. Future research may allow for a determination of which patients
    among those with microscopic or submicroscopic disease contain actively
    proliferating nodal disease. Identification of these patients would create a
    classification of patients who could potentially benefit from lymph node

    One can conclude from this discussion that the RLNs are biologically important
    organs that play a vital role in tumour defence mechanisms. The presence of
    metastases in the RLNs is an indication that the tumour has gained the ability to
    spread and that the stroma of the lymph node contains the necessary surface
    proteins to facilitate tumour attachment. The RLNs should no longer be
    considered mechanical filters or barriers preventing the systemic dissemination of
    metastatic tumour. In fact, tumour dissemination and ultimately tumour metastasis
    is a much more active process than once believed, and results from a dynamic
    interaction between the tumour cell and the surface of the endothelium of the
    organ where the metastasis eventually develops. Traditional surgical management
    of the RLNs for most of the twentieth century was based on the theory that the
    lymph nodes served to limit the systemic spread of tumour metastasis. We now
    know this theory to be false and we have demonstrated that no scientific evidence
    exists to support the routine elective removal of clinically uninvolved lymph
    nodes in any cancer in an attempt to prolong survival.
    Based on the arguments presented in this article, specific recommendations
    regarding the management of the regional lymphatics in cancer can be made.
    When no effective adjuvant therapy exists for metastatic disease, close clinical
    follow-up and TLND at disease recurrence is an acceptable approach in patient
    management. TLND in this case allows for improved local control and may on
    occasion even salvage a small number of patients. ELND in this patient
    population may also improve local control and assist with staging procedures but
    this potential benefit should be weighed against the risks of the procedure, and in
    patients who desire more prognostic information SLNB may be a more
    appropriate intervention. When proven effective adjuvant therapy exists for
    patients with cancer, SLNB can be used as a staging tool to determine those
    patients eligible for adjuvant treatment. Staging information obtained from lymph
    node dissection, whether used for prognostic purposes or for decisions about
    adjuvant therapy, should be interpreted with caution and an understanding that the
    presence or absence of metastatic disease in the RLNs is unrelated to the presence
    of metastatic disease in other organs.

    For patients with melanoma, the above guidelines also apply. The routine use of
    ELND offers patients no survival advantage vs. observation and TLND upon
    nodal recurrence, and should be abandoned. However, TLND is a useful tool in
    the clinical management of patients with recurrent nodal disease and will serve to
    improve local control.[68-74] The use of SLNB is a valuable prognostic tool, but
    attempts to justify this procedure as standard of care in patients with melanoma
    are premature. As no proven effective adjuvant therapy exists for patients with
    metastatic melanoma, the additional prognostic information gained by SLNB
    should be weighed against the small but real risks of the procedure. As SLNB
    remains an experimental procedure, we believe that the use of the procedure in
    patients with melanoma should only be performed within the confines of a
    controlled experimental protocol. Furthermore, the use of ultrasensitive diagnostic
    techniques such as serial sectioning, immunohistochemistry and PCR, made
    technically more practical with SLNB, may serve to upstage patients with nodal
    disease that will never become biologically meaningful. These techniques should
    be considered experimental until evidence exists that validates their use in routine
    patient management.

    References from:
    The Management of Regional Lymph Nodes in Cancer

    D.B. Pharis; J.A. Zitelli
    Br J Dermatol 149(5):919-925, 2003

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    More studies on lymph node surgery:

    Nippon Geka Gakkai Zasshi 2001 Jun;102(6):465-72 Related Articles, Books

    Management of axillary and internal mammary lymph nodes in primary breast

    Masuda N, Tamaki Y, Noguchi S.

    Department of Surgery and Clinical Oncology, Graduate School of Medicine,
    Osaka University, Suita, Japan.

    Axillary lymph node dissection (ALND) is an effective staging procedure and
    is essential for local control of breast cancer. The regimen of the adjuvant
    systemic therapy is largely based on the number of nodes involved. There is
    as yet no evidence of survival benefit from axillary treatment by either
    surgery or radiotherapy, but this issue remains controversial. In general,
    the standard treatment of the axilla is surgical clearance of nodes from
    level I and II (partial ALND). If these nodes are involved, the clearance of
    level III nodes (complete ALND) is indispensable from the viewpoint of local
    control. Because a high rate of adverse events is observed, the extent of
    ALND should be determined by considering the balance between side effects and
    therapeutic benefit on a case-by-case basis. For the management of internal
    mammary nodes, most reports on randomized trials indicate that neither
    surgical treatment nor radiotherapy influences survival. However, the
    prognostic significance of internal mammary node status is high and a
    selected biopsy of lymph nodes with adenopathy should be considered for
    staging purposes. The significance of local control in this region is still
    controversial at present. About 30% to 40% of all invasive breast cancers are
    node positive. Thus, in most cases, the potential morbidity of ALND could be
    avoided if the status of the axillary nodes was ascertained with a less
    invasive procedure. The technique of sentinel lymph node biopsy may
    eventually prove to decrease the need for standard ALND. The randomized trial
    NSABP-B32 is ongoing and the results should indicate the clinical need for

    Surg Clin North Am 1999 Oct;79(5):1061-73

    Management of the axilla in primary breast cancer.

    Jatoi I.

    Department of Surgery, Uniformed Services University of the Health Sciences,
    Bethesda, Maryland, USA.

    Treatment of the axilla with either radiotherapy or surgery remains an
    integral part of the management of patients with invasive breast cancer. In
    general, the standard treatment of the axilla involves a partial ALND
    (surgical clearance of axillary nodes from levels I and II). There is as yet
    no evidence that axillary treatment improves survival, but the issue
    remains controversial. Axillary lymph node dissection is an effective staging
    procedure and is essential for local control of disease in the axilla,
    although, with increased emphasis on mammographic screening and early
    detection, the incidence of node-positive breast cancers is decreasing.
    Today, only about 30% to 40% of all invasive breast cancers are
    node-positive. Thus, in most cases, the potential morbidity of ALND could be
    avoided if the status of the axillary nodes were ascertained with a less
    invasive procedure. The SLNB may eventually prove to be a preferred
    alternative to routine ALND. It must first be demonstrated, however, that
    SLNB (without completion ALND) does not adversely affect outcome. Randomized
    controlled trials must address these concerns, and surgeons must await
    completion of these studies before accepting SLNB as the standard of care.

    Langenbecks Arch Surg 2000 Jul;385(4):236-45

    Lymph-node dissection in breast cancer.

    Bembenek A, Schlag PM.

    Surgery and Surgical Oncology, Robert-Rossle-Klinik, Charite
    Humboldt-University, Berlin, Germany.

    BACKGROUND: Along with the ongoing modifications in treatment of primary
    breast cancer, the purpose and extent of lymph-node dissection has changed.
    The following is an overview of the current knowledge and practice of
    lymph-node dissection in breast cancer, with special regard to expected
    developments in the near future. Axillary dissection is described as a
    ten-step procedure, including dissection of level-I and -II and Rotter's
    nodes, without level-III nodes, providing at least ten lymph nodes for
    accurate staging information. DISCUSSION: Axillary dissection still offers
    the most efficient local control in node-positive patients, whereas, in
    primarily node-negative patients, irradiation seems to be equally effective.
    In general, lymph-node dissection does not alter overall survival but there
    is no doubt that surgical therapy still contributes to cure in
    early-breast-cancer patients and seems to be curative for certain patients
    with stage-I carcinoma. The lymph node status of the axilla is crucial for
    the indication of adjuvant therapy in early invasive breast cancer, but an
    increasing number of clinical node-negative patients could be managed with
    information based on features of the primary tumor, regardless of the nodal
    status. The most promising new concept for the selection of node-positive
    patients, while avoiding unnecessary morbidity of axillary dissection in
    early-breast-cancer patients, is the sentinel-node concept. The principle is
    based on the identification of the first "sentinel" lymph node reached by
    lymphatic flow. Thus, only proven node-positive patients undergo axillary
    dissection. Local failure of internal mammary lymph nodes is rarely
    recognized; however, internal mammary lymph nodes seem to have an
    underestimated prognostic significance in about 10-20% of axillary
    node-negative patients. This may lead to the withholding of systemic therapy
    for patients with early breast cancer. Nevertheless, there is no indication
    for a routine parasternal dissection today. The sentinel-node concept may
    also support the selection of diagnostic internal lymph-node biopsy and
    subsequent adjuvant therapy in cases with no axillary lymph-node metastases
    but with internal lymph-node metastases.


    Am Surg. 2003 Mar;69(3):209-11; discussion 212.

    Sentinel lymph node biopsy lowers the rate of lymphedema when
    compared with standard axillary lymph node dissection.

    Golshan M, Martin WJ, Dowlatshahi K.

    Department of Surgery, Rush University, Rush Presbyterian St. Luke's Medical Center,
    Chicago, Illinois, USA.

    Arm edema occurs in 20 to 30 per cent of patients who undergo axillary lymph node
    dissection (ALND) for carcinoma of the breast. Sentinel lymph node biopsy (SLNB) in
    lieu of ALND for staging of breast cancer significantly lowers this morbidity. We
    hypothesized that SLNB would have a lower lymphedema rate than conventional
    axillary dissection. Patients who underwent SLNB were compared with those who
    underwent level I and II axillary node dissection. A total of 125 patients were evaluated
    with 77 patients who underwent SLNB and 48 patients who underwent ALND. The arm
    circumference 10 cm above and 10 cm below the olecranon process was measured on
    both arms. In this series a difference in arm circumference greater than 3 cm between
    the operated and nonoperated side was defined as significant for lymphedema.
    Lymphedema was seen in two of 77 (2.6%) patients in the SLNB group as compared
    with 13 of 48 (27%) ALND patients. Given the above data patients who underwent
    sentinel lymph node biopsy show a significantly lower rate of lymphedema than those
    who had axillary lymph node dissection. This has an important impact on long-term
    postoperative management of patients with breast cancer.

    Cancer. 2005 Feb 1;103(3):492-500.

    Predicting the status of axillary sentinel lymph nodes in 4351 patients with invasive
    breast carcinoma treated in a single institution.

    Viale G, Zurrida S, Maiorano E, Mazzarol G, Pruneri G, Paganelli G, Maisonneuve P,
    Veronesi U.

    Department of Pathology and Laboratory Medicine, European Institute of Oncology and
    University of Milan,
    Milan, Italy.

    BACKGROUND: Reliable predictors of metastatic involvement would enable a better
    selection of candidate patients for sentinel lymph node biopsy (SLNB) and possibly allow
    identification of patients with such a lowrisk of axillary sentinel lymph node (SLN)
    involvement to be even spared SLNB. METHODS: The authors evaluated 4351
    consecutive patients surgically treated for breast carcinoma who also underwent SLNB.
    Clinicopathologic features significantly associated with SLN metastases by univariate
    analysis wereincluded in a multivariate model. RESULTS: By multivariate analysis, the
    prevalence of SLN metastaseswas associated directly with tumor size, multifocality, and
    with the occurrence of peritumoral vascular invasion (PVI; all P &lt; 0.0001), and was
    associated inversely with a favorable histotype (P = 0.0007) and lackof progesterone
    receptors (P = 0.004). A predictive model based on the features more closely
    associatedwith SLN status documented that the patients with a favorable tumor type &lt;/=
    1 cm in size and without PVI(n = 178 [4% of the population]) had the lowest risk of SLN
    metastases (9.5%) whereas patients with tumors &gt;2 cm and with PVI (n = 250 [5.7% of the
    population]) had the highest risk (77.2%) of SLN involvement.

    CONCLUSIONS: Tumor size and PVI emerged as the most powerful independent predictors
    of SLN metastases. Although no combination of features identified patients with a 9.5%
    risk of SLN metastases,the current data may be used to tailor the management of patients
    with breast carcinoma with the aim of minimizing as much as possible the diagnostic and
    therapeutic procedures, thus improving the quality of life of the patients without any
    adverse effect on their survival rates. (c) 2004 American Cancer Society
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