- Email: [email protected]
Experience with sentinel node localisation in a district general hospital breast unit
The Breast (2002) 11, 343–345 r 2002 Elsevier Science Ltd. All rights reserved. doi:10.1054/brst.446, available online at http://www.idealibrary.com on
SHORT REPORT
Experience with sentinel node localisation in a district general hospital breast unit P. M. Walker, M. Hussain and C. S. Humphrey Rochdale Breast Unit, Birch Hill Hospital, Rochdale OL12 9QB, UK S U M M A R Y . Intraoperative lymphatic mapping with identification of the first draining lymph node (sentinel node) is under investigation as a possible sole axillary staging procedure in breast cancer patients. The role of sentinel node biopsy in the district general hospital breast unit is currently unclear. We report a series of 122 patients undergoing sentinel node biopsy, using a blue dye technique. The sentinel node was identified in 113 patients, and accurately predicted the status of the axilla in 108 patients (96%). Of 39 patients who were node positive, the sentinel node was the only positive node in 11 cases (26%). There were five false negatives in patients who had a node-positive axilla. We therefore suggest that sentinel node biopsy may be a feasible alternative to formal axillary dissection in certain patients, and that lack of access to radioisotope facilities in a district general hospital need not preclude such an approach. r 2002 Elsevier Science Ltd. All rights reserved.
underwent sentinel node excision with subsequent axillary sampling, in combination with either mastectomy or a breast-conserving procedure. Features considered to be contraindications to the procedure were a heavy axillary tumour burden as assessed clinically, previous axillary surgery, multifocal disease and therapeutic localisation biopsy. There were relatively few mastectomies (two), in the series as in most instances excision of the sentinel node would have, required a separate axillary incision. It was felt that this could not be justified in the evaluation phase. In the first 25 patients, 1–2 ml of blue dye (patent blue V) was injected around the tumour, into the adjacent subcutaneous tissues, and intradermally. The injection took place after induction of general anaesthesia. Lymphatic uptake was then encouraged by gentle massage of the area. The breast was approached surgically first, followed by exploration of the axilla. This gave an injection to node time of approximately 25 min. Our initial experience suggested that the technique resulted in considerable contamination of the operative fields. Furthermore, it was not uncommon to find more than one blue-stained node. The technique was therefore modified and it was found that the best approach was to explore the axilla first, usually via a separate curvilinear incision. The intradermal injection was omitted, dye being infiltrated along that border of the tumour nearest the axilla. This modification reduced
INTRODUCTION Axillary node status has important prognostic implications in breast cancer.1 Intraoperative lymphatic mapping with identification of the first draining lymph node (the sentinel node) may become the surgical staging procedure of choice in the assessment of the axilla. The technique has been evaluated in a number of large centres, and a trial of the technique is currently underway (ALMANAC).2 This trial looks at sentinel node status as determined by the combined radioisotope and blue dye method of node identification. It is unclear whether sentinel node biopsy is applicable in the absence of isotope facilities, and in the district general hospital breast unit. We report a series of 122 cases performed by a single consultant surgeon with a particular interest in diseases of the breast, in a district general hospital. PATIENTS AND METHODS Between November 1998 and August 2001, 122 suitable patients, between the ages of 28 and 82 (mean age 56), Address correspondence to: Dr P. M. Walker, General Surgical Office, The Royal Oldham Hospital, Rochdale Road, Oldham OL1 2JH, Lancs, UK. Tel.: +44-161-627-8869; E-mail: [email protected] Received: 24 December 2001 Accepted: 16 April 2002
343
344
The Breast
the interval from dye injection to node identification to approximately 10 min. The sentinel node was easily visible in the majority of cases, but was not identified in a few patients. Following excision of the sentinel node (or if the node could not be identified), a formal fournode sampling was carried out. The pathological status of the sentinel node was compared with that of the axilla using histological examination of paraffin-embedded tissue.
RESULTS Infiltrating ductal carcinoma was found in 93 patients, lobular carcinoma in 16, and there was mixed differentiation in eight patients. There were two mucinous carcinomas, two papillary tumours and one case of ductal carcinoma in situ with microinvasion. Forty-nine tumours were less than 2 cm in their maximum dimension, 67 were between 2 and 3 cm and five were greater than 3 cm. There were no tumours larger than 3.5 cm, and in one case it was impossible to assess the overall size of the lesion. The tumour grades were grade 1:29 (25%), grade 2:52 (45%) and grade 3:35 (30%). There was no recorded grade in six cases (five lobular carcinomas and one DCIS with microinvasion). The sentinel lymph node was successfully identified in 113 patients (93%), and accurately predicted the axillary node status in 108 of 113 patients (96%). Thirty-nine patients were node positive, and of these the sentinel node was the only positive node in 11 (28%) cases. In 45, there was more than one sentinel node, giving an overall mean of 1.94 sentinel nodes per patient. In five patients, the node identified as sentinel was free from tumour histologically, even although another node from the axilla was positive. In the nine cases where no sentinel node was found, four patients had tumours located in the lower medial quadrant; the remainder were located centrally (three) or in the lateral lower quadrant (two).
DISCUSSION Axillary lymph node dissection provides important staging information and offers improved regional control.3 However, the procedure can be associated with significant morbidity, including infection, seroma formation and lymphoedema.4 Sentinel node excision has been reported as providing a reliable and sensitive method of predicting axillary metastases5 and can help avoid unnecessary axillary surgery in certain breast cancer patients. The ALMANAC trial is assessing the
potential of the technique across a number of centres. Our results suggest that an experienced surgeon following a period of self-assessment and audit can perform the technique successfully. There were five false negatives (4.76%) in the series but this figure approaches the staging error (2–3%) reported for a lower level II axillary dissection.6 Interestingly, the axillary sample in one of these patients revealed metastatic lobular carcinoma from what was a clinically and radiologically occult tumour. The palpable lesion that had been injected with blue dye was a ductal carcinoma. Thus, the technique was sensitive for this tumour. Multifocal tumours are not suitable for the sentinel node technique.7 In those cases where no sentinel node was found, three patients (43%) had medially sited tumours. It is possible that the sentinel node was located within the internal mammary lymph node chain, rather than in the axilla in these patients. Four of the patients were more than 70 years old, and it is recognised that lymphatic uptake is less efficient in the older patient.8 The sentinel node was often found in a surprisingly low position in the axilla. This suggests that the node might be missed during a formal axillary sampling procedure, resulting in a staging error. This, in turn, would explain the occasional regional ‘recurrence’ in a patient previously thought to have a clear axilla. It would appear that a combination of radioisotope and blue dye produces the best sentinel node localisation rate.9 Use of radioisotope also allows the detection of sentinel nodes outside the axilla. This series produced a very good localisation rate (93%) with blue dye alone however. Failure to identify a sentinel node does not, of course, prejudice a patient, for the usual axillary node sample would be carried out. Allergic reactions to the dye have been reported10 but these are very rare. One of our patients developed a generalised urticarial rash, apparent during the operation, which disappeared within 48 h. The patient was given Piriton and hydrocortisone. In our practice, it is intended to use the information obtained by sentinel node biopsy in different ways depending on the type of surgery performed. Wide local excision will be accompanied, in a clinically negative axilla, by excision of the sentinel node alone. The node will be sent for routine histological examination using haematoxylin and eosin staining of paraffin sections, and no further axillary surgery will be performed. If a sentinel node is found to contain metastases, radiotherapy will be administered to the axilla in addition to the breast. Axillary node clearance will be reserved for those patients with clinically involved nodes.
Experience with sentinel node localisation It is hoped to obviate the need for radiotherapy in a significant number of patients undergoing mastectomy by adopting a different approach to the sentinel node in this group. Frozen section analysis of the node will be performed and those patients with metastatic disease will have axillary clearance, which in many cases completes treatment of the axilla. Some reports in the literature have indicated unacceptably high false negative rates for sentinel node frozen section analysis.11 It would appear however, that this is largely as a result of failure to detect micrometastases.12 The significance of micrometastases (detected by immunocytochemistry and polymerase chain reaction) within lymph nodes remains controversial.13 A further period of audit, addressing this issue, will be required if our proposed protocols are to be established in clinical practice. References 1. Carter C L, Allen C, Henson D E. Relation to tumour size, lymph node status and survival in 24,740 breast cancer cases. Cancer 1989; 63: 181–187. 2. Manse1 R E, ALMANAC (Axillary Lymphatic Mapping Against Nodal Axillary Clearance) trial coordinator, University of Wales College of Medicine, Cardiff CF14 4XN.
345
3. Fisher B, Redmond C, Fisher E R, Bauer M, Wolmark N, Wickerham D L et al. Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation. N Engl J Med 1995; 312: 674–681. 4. Ivens D, Hoe A L, Podd T J, Hamilton C R, Taylor I, Royle G T. Assessment of morbidity from complete axillary dissection. Br J Cancer 1992; 66: 13608. 5. Giuliano A E, Dale P S, Turner R R, Morton D L, Evans S W, Krasne D L. Improved axillary staging of breast cancer with sentinel lymphadenopathy. Ann Surg 1995; 222: 394–401. 6. Rosen P P, Lesser M L, Kinne D W, Beattie E J, Discontinous or ‘skip’ metastases in breast cancer. Analysis of 1228 axillary dissections. Ann Surg 1983; 197: 276–283. 7. Galimberti V, Zurrida S, Intra M, Monti S, Arnone P, Pruneri G, De Cicco C. Sentinel node biopsy interpretation: the milan experience. Breast 2000; 6: 306–309 8. Discussion on Sentinel Node Technique at Third. Milan Breast Cancer Conference, June 2001. 9. McIntosh SA, Purushotham AD. Lymphatic mapping and sentinel node biopsy in breast cancer. Br J Surg 1998; 85: 1347–1356. 10. Salvat J, Margonari H, Hardelin D. Anaphylactic shock due to patent blue used to search for the sentinel node. J Gynaecol Obstet Biol Reprod (Paris) 1999; 28: 393–394. 11. Dixon JM, Mamman U, Thomas J. Accuracy of intraoperative frozen-section analysis of axillary nodes. Edinburgh Breast Unit team. Br J Surg 1999; 86: 1092–1093. 12. Van Diest PJ, Torrenga H, Borgstein PJ, Pijpers R, Bleichrodt RP, Rahusen FD, Meijer S. Reliability of intraoperative frozen section and cytological investigation of sentinel lymph nodes in breast cancer. Histopathology 2000; 36: 185–186. 13. Yeatman TJ, Cox CE. The significance of breast cancer lymph node micrometastases. Surg Oncol N Am 1999; 8: 481–496.
SHORT REPORT
Experience with sentinel node localisation in a district general hospital breast unit P. M. Walker, M. Hussain and C. S. Humphrey Rochdale Breast Unit, Birch Hill Hospital, Rochdale OL12 9QB, UK S U M M A R Y . Intraoperative lymphatic mapping with identification of the first draining lymph node (sentinel node) is under investigation as a possible sole axillary staging procedure in breast cancer patients. The role of sentinel node biopsy in the district general hospital breast unit is currently unclear. We report a series of 122 patients undergoing sentinel node biopsy, using a blue dye technique. The sentinel node was identified in 113 patients, and accurately predicted the status of the axilla in 108 patients (96%). Of 39 patients who were node positive, the sentinel node was the only positive node in 11 cases (26%). There were five false negatives in patients who had a node-positive axilla. We therefore suggest that sentinel node biopsy may be a feasible alternative to formal axillary dissection in certain patients, and that lack of access to radioisotope facilities in a district general hospital need not preclude such an approach. r 2002 Elsevier Science Ltd. All rights reserved.
underwent sentinel node excision with subsequent axillary sampling, in combination with either mastectomy or a breast-conserving procedure. Features considered to be contraindications to the procedure were a heavy axillary tumour burden as assessed clinically, previous axillary surgery, multifocal disease and therapeutic localisation biopsy. There were relatively few mastectomies (two), in the series as in most instances excision of the sentinel node would have, required a separate axillary incision. It was felt that this could not be justified in the evaluation phase. In the first 25 patients, 1–2 ml of blue dye (patent blue V) was injected around the tumour, into the adjacent subcutaneous tissues, and intradermally. The injection took place after induction of general anaesthesia. Lymphatic uptake was then encouraged by gentle massage of the area. The breast was approached surgically first, followed by exploration of the axilla. This gave an injection to node time of approximately 25 min. Our initial experience suggested that the technique resulted in considerable contamination of the operative fields. Furthermore, it was not uncommon to find more than one blue-stained node. The technique was therefore modified and it was found that the best approach was to explore the axilla first, usually via a separate curvilinear incision. The intradermal injection was omitted, dye being infiltrated along that border of the tumour nearest the axilla. This modification reduced
INTRODUCTION Axillary node status has important prognostic implications in breast cancer.1 Intraoperative lymphatic mapping with identification of the first draining lymph node (the sentinel node) may become the surgical staging procedure of choice in the assessment of the axilla. The technique has been evaluated in a number of large centres, and a trial of the technique is currently underway (ALMANAC).2 This trial looks at sentinel node status as determined by the combined radioisotope and blue dye method of node identification. It is unclear whether sentinel node biopsy is applicable in the absence of isotope facilities, and in the district general hospital breast unit. We report a series of 122 cases performed by a single consultant surgeon with a particular interest in diseases of the breast, in a district general hospital. PATIENTS AND METHODS Between November 1998 and August 2001, 122 suitable patients, between the ages of 28 and 82 (mean age 56), Address correspondence to: Dr P. M. Walker, General Surgical Office, The Royal Oldham Hospital, Rochdale Road, Oldham OL1 2JH, Lancs, UK. Tel.: +44-161-627-8869; E-mail: [email protected] Received: 24 December 2001 Accepted: 16 April 2002
343
344
The Breast
the interval from dye injection to node identification to approximately 10 min. The sentinel node was easily visible in the majority of cases, but was not identified in a few patients. Following excision of the sentinel node (or if the node could not be identified), a formal fournode sampling was carried out. The pathological status of the sentinel node was compared with that of the axilla using histological examination of paraffin-embedded tissue.
RESULTS Infiltrating ductal carcinoma was found in 93 patients, lobular carcinoma in 16, and there was mixed differentiation in eight patients. There were two mucinous carcinomas, two papillary tumours and one case of ductal carcinoma in situ with microinvasion. Forty-nine tumours were less than 2 cm in their maximum dimension, 67 were between 2 and 3 cm and five were greater than 3 cm. There were no tumours larger than 3.5 cm, and in one case it was impossible to assess the overall size of the lesion. The tumour grades were grade 1:29 (25%), grade 2:52 (45%) and grade 3:35 (30%). There was no recorded grade in six cases (five lobular carcinomas and one DCIS with microinvasion). The sentinel lymph node was successfully identified in 113 patients (93%), and accurately predicted the axillary node status in 108 of 113 patients (96%). Thirty-nine patients were node positive, and of these the sentinel node was the only positive node in 11 (28%) cases. In 45, there was more than one sentinel node, giving an overall mean of 1.94 sentinel nodes per patient. In five patients, the node identified as sentinel was free from tumour histologically, even although another node from the axilla was positive. In the nine cases where no sentinel node was found, four patients had tumours located in the lower medial quadrant; the remainder were located centrally (three) or in the lateral lower quadrant (two).
DISCUSSION Axillary lymph node dissection provides important staging information and offers improved regional control.3 However, the procedure can be associated with significant morbidity, including infection, seroma formation and lymphoedema.4 Sentinel node excision has been reported as providing a reliable and sensitive method of predicting axillary metastases5 and can help avoid unnecessary axillary surgery in certain breast cancer patients. The ALMANAC trial is assessing the
potential of the technique across a number of centres. Our results suggest that an experienced surgeon following a period of self-assessment and audit can perform the technique successfully. There were five false negatives (4.76%) in the series but this figure approaches the staging error (2–3%) reported for a lower level II axillary dissection.6 Interestingly, the axillary sample in one of these patients revealed metastatic lobular carcinoma from what was a clinically and radiologically occult tumour. The palpable lesion that had been injected with blue dye was a ductal carcinoma. Thus, the technique was sensitive for this tumour. Multifocal tumours are not suitable for the sentinel node technique.7 In those cases where no sentinel node was found, three patients (43%) had medially sited tumours. It is possible that the sentinel node was located within the internal mammary lymph node chain, rather than in the axilla in these patients. Four of the patients were more than 70 years old, and it is recognised that lymphatic uptake is less efficient in the older patient.8 The sentinel node was often found in a surprisingly low position in the axilla. This suggests that the node might be missed during a formal axillary sampling procedure, resulting in a staging error. This, in turn, would explain the occasional regional ‘recurrence’ in a patient previously thought to have a clear axilla. It would appear that a combination of radioisotope and blue dye produces the best sentinel node localisation rate.9 Use of radioisotope also allows the detection of sentinel nodes outside the axilla. This series produced a very good localisation rate (93%) with blue dye alone however. Failure to identify a sentinel node does not, of course, prejudice a patient, for the usual axillary node sample would be carried out. Allergic reactions to the dye have been reported10 but these are very rare. One of our patients developed a generalised urticarial rash, apparent during the operation, which disappeared within 48 h. The patient was given Piriton and hydrocortisone. In our practice, it is intended to use the information obtained by sentinel node biopsy in different ways depending on the type of surgery performed. Wide local excision will be accompanied, in a clinically negative axilla, by excision of the sentinel node alone. The node will be sent for routine histological examination using haematoxylin and eosin staining of paraffin sections, and no further axillary surgery will be performed. If a sentinel node is found to contain metastases, radiotherapy will be administered to the axilla in addition to the breast. Axillary node clearance will be reserved for those patients with clinically involved nodes.
Experience with sentinel node localisation It is hoped to obviate the need for radiotherapy in a significant number of patients undergoing mastectomy by adopting a different approach to the sentinel node in this group. Frozen section analysis of the node will be performed and those patients with metastatic disease will have axillary clearance, which in many cases completes treatment of the axilla. Some reports in the literature have indicated unacceptably high false negative rates for sentinel node frozen section analysis.11 It would appear however, that this is largely as a result of failure to detect micrometastases.12 The significance of micrometastases (detected by immunocytochemistry and polymerase chain reaction) within lymph nodes remains controversial.13 A further period of audit, addressing this issue, will be required if our proposed protocols are to be established in clinical practice. References 1. Carter C L, Allen C, Henson D E. Relation to tumour size, lymph node status and survival in 24,740 breast cancer cases. Cancer 1989; 63: 181–187. 2. Manse1 R E, ALMANAC (Axillary Lymphatic Mapping Against Nodal Axillary Clearance) trial coordinator, University of Wales College of Medicine, Cardiff CF14 4XN.
345
3. Fisher B, Redmond C, Fisher E R, Bauer M, Wolmark N, Wickerham D L et al. Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation. N Engl J Med 1995; 312: 674–681. 4. Ivens D, Hoe A L, Podd T J, Hamilton C R, Taylor I, Royle G T. Assessment of morbidity from complete axillary dissection. Br J Cancer 1992; 66: 13608. 5. Giuliano A E, Dale P S, Turner R R, Morton D L, Evans S W, Krasne D L. Improved axillary staging of breast cancer with sentinel lymphadenopathy. Ann Surg 1995; 222: 394–401. 6. Rosen P P, Lesser M L, Kinne D W, Beattie E J, Discontinous or ‘skip’ metastases in breast cancer. Analysis of 1228 axillary dissections. Ann Surg 1983; 197: 276–283. 7. Galimberti V, Zurrida S, Intra M, Monti S, Arnone P, Pruneri G, De Cicco C. Sentinel node biopsy interpretation: the milan experience. Breast 2000; 6: 306–309 8. Discussion on Sentinel Node Technique at Third. Milan Breast Cancer Conference, June 2001. 9. McIntosh SA, Purushotham AD. Lymphatic mapping and sentinel node biopsy in breast cancer. Br J Surg 1998; 85: 1347–1356. 10. Salvat J, Margonari H, Hardelin D. Anaphylactic shock due to patent blue used to search for the sentinel node. J Gynaecol Obstet Biol Reprod (Paris) 1999; 28: 393–394. 11. Dixon JM, Mamman U, Thomas J. Accuracy of intraoperative frozen-section analysis of axillary nodes. Edinburgh Breast Unit team. Br J Surg 1999; 86: 1092–1093. 12. Van Diest PJ, Torrenga H, Borgstein PJ, Pijpers R, Bleichrodt RP, Rahusen FD, Meijer S. Reliability of intraoperative frozen section and cytological investigation of sentinel lymph nodes in breast cancer. Histopathology 2000; 36: 185–186. 13. Yeatman TJ, Cox CE. The significance of breast cancer lymph node micrometastases. Surg Oncol N Am 1999; 8: 481–496.