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Complications Associated With Sentinel Lymph Node Biopsy for Melanoma

From the Division of Surgical Oncology, Department of Surgery, University of Louisville, James Graham Brown Cancer Center, and Center for Advanced Surgical Technology of Norton Hospital, Louisville, Kentucky (WRW, SLW, MJE, CC, VV, KMM); Department of Mathematics, University of Louisville, Louisville, Kentucky (PBC); University of South Florida, Moffitt Cancer Center, Tampa, Florida (DSR); University of Texas, M. D. Anderson Cancer Center, Houston, Texas (MIR); and LDS Hospital, Salt Lake City, Utah (RDN).

Correspondence: Address correspondence and reprint requests to: Kelly M. McMasters, MD, PhD, University of Louisville, J. Graham Brown Cancer Center, 529 S. Jackson Street, Louisville, KY 40202; Fax: 502-629-3379; E-mail: kelly.mcmasters{at}nortonhealthcare.org

	ABSTRACT

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Background: Sentinel lymph node (SLN) biopsy has become widely accepted as a method of staging the regional lymph nodes for patients with melanoma. Although it is often stated that SLN biopsy is a minimally invasive procedure associated with few complications, a paucity of data exists to specifically determine the morbidity associated with this procedure. This analysis was performed to evaluate the morbidity associated with SLN biopsy compared with completion lymph node dissection (CLND).

Methods: Patients were enrolled in the Sunbelt Melanoma Trial, a prospective multi-institutional study of SLN biopsy for melanoma. Patients underwent SLN biopsy and were prospectively followed up for the development of complications associated with this technique. Patients who had evidence of nodal metastasis in the SLN underwent CLND. Complications associated with SLN biopsy alone were compared with those associated with SLN biopsy plus CLND.

Results: A total of 2120 patients were evaluated, with a median follow-up of 16 months. Overall, 96 (4.6%) of 2120 patients developed major or minor complications associated with SLN biopsy, whereas 103 (23.2%) of 444 patients experienced complications associated with SLN biopsy plus CLND. There were no deaths associated with either procedure.

Conclusions: SLN biopsy alone is associated with significantly less morbidity compared with SLN biopsy plus CLND.

Key Words: Melanoma • Sentinel lymph node • Morbidity • Complications • Lymph node dissection

	INTRODUCTION

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Sentinel lymph node (SLN) biopsy has become widely accepted as a method for staging the regional lymph nodes for patients with melanoma. SLN biopsy, first described by Morton et al.,¹ has reduced the need for regional lymph node dissection and has limited completion lymph node dissection (CLND) to those patients with metastatic disease found in the SLN. Since that initial report, numerous studies have demonstrated that SLN biopsy can accurately determine the nodal status of patients with clinically negative regional nodes.^2–4

The morbidity of regional node dissection is considerable. Studies have reported a complication rate from 25% to 61% after lymph node dissection.^5–11 Wound complications, lymphedema, and other complications are common. SLN biopsy is a minimally invasive procedure and is presumed to have the morbidity of a lymph node biopsy. Although SLN biopsy is purported to be less morbid than elective lymph node dissection (ELND), few data exist to substantiate this claim. This analysis was performed to compare the morbidity of SLN biopsy in a large prospective multi-institutional study.

	METHODS

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Patients were enrolled in the Sunbelt Melanoma Trial, a randomized prospective trial involving 70 institutions across the United States, between June 1997 and June 2001. The study was approved at the institutional review boards of each participating center. Patients 18 to 70 years old with cutaneous melanomas 1.0 mm Breslow thickness and clinically negative regional lymph nodes were eligible. After informed consent was obtained, patients underwent SLN biopsy with radioactive colloid and isosulfan blue dye injection. Lymphoscintigraphy was performed to identify all draining nodal basins. A handheld gamma probe, along with visualization of blue dye, was used during surgery to guide SLN detection. The protocol specified that all blue nodes and all nodes 10% of the most radioactive, or hottest, node should be removed and designated SLNs.¹² Patients with evidence of nodal metastasis underwent CLND. As defined in the protocol, some patients underwent CLND for SLNs that were positive for the presence of tumor cells only by reverse transcriptase-polymerase chain reaction analysis.

All SLNs underwent histological analysis with hematoxylin and eosin staining at multiple levels, followed by immunohistochemical staining for S-100 protein. SLNs were divided into blocks on the basis of lymph node size; at least five sections per block were evaluated by hematoxylin and eosin staining, and two sections per block were stained for S-100 protein. Frozen-section analysis of SLNs was not performed; therefore, patients undergoing CLND for positive SLNs returned to the operating room for a separate procedure at a later date.

Patients were followed up with history and physical examination at the initial postoperative visit within 2 weeks of surgery, every 3 months for the first 2 years, every 4 months for the third year, and every 6 months thereafter. Assessment of complications was performed at each visit. A prospective evaluation of complications was performed by using detailed case report forms for individual complications related to SLN biopsy or CLND, filed within 30 days of the recognition of the complication. Reports included details such as the site and severity of the complication and the extent of treatment, including the need for hospital admission or reoperation.

Complications specifically identified on the follow-up data forms included hematoma/seroma formation, lymphedema, wound separation, wound infection, deep venous thrombosis, pulmonary complications, urinary tract infection, sensory or motor dysfunction, or other complications. Guidelines for the reporting of complications, with designated case report forms, were provided to investigators. Specifically, pulmonary complications excluded minor atelectasis and stipulated that postoperative pneumonias be reported separately. Because a certain degree of numbness is expected after axillary dissection (we did not recommend sparing the intercostobrachial nerve), the expected numbness or paresthesia after axillary dissection was not considered a complication. Sensory nerve dysfunction was reported only if it was believed to be extensive or especially problematic to the patient. Lymphedema was reported as clinically significant limb swelling based on history² and physical examination.

Statistical comparison was performed by ² analysis or Fisher’s exact test, where appropriate. P values <.05 were considered significant.

	RESULTS

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A total of 2120 patients were enrolled in the study; 1676 patients underwent SLN biopsy alone, and 444 underwent SLN biopsy followed by CLND. The median follow-up for all patients was 16 months. Clinicopathologic features of the patient population are listed in Table 1. Overall, 201 (9.5%) of 2120 patients developed major or minor complications associated with their procedure.

	DISCUSSION

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The most important prognostic factor in most solid epithelial tumors is regional lymph node status. Patients with nodal metastasis in melanoma have a 40% decrease in 5-year survival as compared with node-negative patients.³ Evaluation of nodal basins in melanoma has evolved in recent years with the advent of SLN biopsy techniques. In the past, we relied on clinical staging of regional nodes or on ELND to determine the nodal status of patients with clinically negative regional nodes. SLN biopsy provides an alternative to ELND for pathologic nodal staging in such patients, and SLN biopsy has been shown to accurately predict nodal status.^2–4 SLN biopsy, therefore, provides a means of assessing lymph node status without the need for complete regional lymphadenectomy.

SLN biopsy is a less invasive procedure, in general, compared with ELND. SLN biopsy uses a small skin incision with less extensive dissection and decreased operative time compared with ELND. Although most centers have accepted the premise that SLN biopsy is less morbid compared with ELND, little evidence is available in the literature to support this claim. This is the first report regarding the complications of SLN biopsy from a large multicenter trial. The only study directly comparing the complications of SLN biopsy with those of lymphadenectomy is from Schrenk et al.,¹³ who reported the morbidity of 35 patients with breast cancer who underwent SLN biopsy and compared this with that of another group of 35 women who had level I and II axillary dissection. Formal axillary node dissection was associated with significantly increased subjective arm lymphedema, postoperative numbness, pain, and motion restriction.

Although SLN biopsy is not without morbidity, most of the complications associated with SLN biopsy are minor. One study of 200 consecutive SLN biopsies for melanoma identified a 9% complication rate.¹⁴ Our study found a somewhat lower complication rate, at 4.6%. Hematoma and seroma formation is the most frequent complication, which usually is of no long-term consequence. Ligatures or metal clips to control lymphatic channels and small blood vessels may help to minimize the incidence of hematomas and seromas. Wrone et al.¹⁵ reported five cases, or a 1.7% incidence, of lymphedema associated with SLN biopsy for melanoma. We found a .7% risk of lymphedema among patients undergoing axillary or inguinal SLN biopsy. Allergic reactions to isosulfan blue dye reportedly occur in approximately 1.5% of cases, although most are mild allergic reactions. Leong et al.¹⁶ reported a 1% incidence of anaphylaxis to isosulfan blue dye: 3 cases in a series of 406 patients during lymphatic mapping for melanoma. However, we have not identified any complications directly associated with blue dye in >2100 cases.

Lymphedema after axillary or inguinal lymphadenectomy is not uncommon and is perhaps the most dreaded complication associated with nodal staging procedures. The incidence of lymphedema after a formal lymph node dissection in the axilla or groin is substantial and is related to the extent of lymphatic disruption and the number of lymph nodes removed.^5–11 In this study, the rates of lymphedema after axillary and inguinal CLND were 4.6% and 31.5%, respectively—these are within the ranges reported in other studies.

The only complication resulting in readmission was wound infections that required intravenous antibiotics. The incidence of wound infections after regional lymph node dissection has been reported from 6% to 29%.^6,8 Our data are consistent with this and revealed a 7% incidence of wound infection after CLND. Our series reports a 1% rate of wound infection in the SLN biopsy group, which is comparable to that of a clean operative procedure and is significantly less than that of the CLND group. The Sunbelt Melanoma Trial did not require the use of prophylactic perioperative antibiotics, and, therefore, the study did not capture data related to antibiotic use. The indications for the use of antibiotics, as well as the specific drug and dosage, were dictated by surgeon preference. There is evidence that prophylactic antibiotic use reduces the incidence of wound infection for patients undergoing axillary dissection,¹⁷ however, and the rate of wound infection associated with CLND in this study suggests that prophylactic antibiotic use may be appropriate in such cases.

Our study also included patients with melanoma in the head and neck region undergoing SLN biopsy involving the parotid basin. Although some surgeons have suggested that SLN biopsy may limit complications associated with parotid dissection—in particular, facial nerve injury—others have refuted this argument because the facial nerve is not exposed properly, and, therefore, unintentional injury could occur because of the limited dissection field. The morbidity associated with SLN biopsy of the parotid has been reported to be 2.6% to 4%.^18,19 These complications were related to transient facial nerve paresis and seroma formation. In this study, we found only one minor complication associated with parotid SLN biopsy, and there were no cases of facial nerve injury or paresis.

Some caveats regarding this analysis should be mentioned. First, the comparison in this study was not between SLN biopsy and ELND, but between SLN biopsy alone and SLN biopsy followed by CLND. Although it is possible that CLND after SLN biopsy, which involves two operative procedures, is more morbid than ELND alone, the rate of complications in the SLN plus CLND group in this study was similar to that reported for ELND in other studies. Furthermore, although lymphedema, if it occurred, was attributed to the SLN or CLND procedure, wide local excision of extremity melanomas could contribute to this incidence of lymphedema. In addition, lymphedema was not evaluated in this study by prospective evaluation of limb volume or circumference, but was defined as clinically apparent swelling of the extremity on the basis of history and physical examination. Although we believe that, given the careful and frequent follow-up required in this prospective study, this has captured the clinically meaningful cases of lymphedema, it is possible that some cases of minor limb swelling were missed. Finally, the median follow-up for the study was 16 months, and we believe that most operative complications were captured during this follow-up period. However, certainly lymphedema, cellulitis, and potentially other complications can become apparent during longer follow-up.

	CONCLUSIONS

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This is the first report of the complications associated with SLN biopsy from a large prospective multi-institutional study. The rate of complications associated with SLN biopsy was significantly less than that associated with SLN biopsy followed by CLND. Most complications of SLN biopsy were minor and easily managed. Lymphedema can result from SLN biopsy alone in rare cases.

	ACKNOWLEDGMENTS

 
Supported by a grant from Schering Oncology-Biotech and the Center for Advanced Surgical Technologies of Norton Hospital, Louisville, KY. The authors thank Carla Shelton; Sherri Matthews, CCRC, CCRP; and Diana Simpson, RN, for their continued dedication to the data management and coordination of this study. The authors are also deeply appreciative of the ongoing efforts of the members of the Sunbelt Melanoma Trial Investigators.

The acknowledgments are available online at www.annalssurgicaloncology.org.

	FOOTNOTES

 
W.W.R. and S.L.W. contributed equally to this work.

Complications associated with sentinel lymph node (SLN) biopsy were compared with those associated with completion lymph node dissection (CLND). SLN biopsy is associated with significantly less morbidity compared with CLND.

Received for publication October 3, 2001. Accepted for publication March 7, 2003.

	REFERENCES

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1. Morton DL, Wen DR, Wong JH, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 1992; 127: 392–9.[Abstract/Free Full Text]
2. Reintgen DS, Cox EB, McCarthy KM. Efficacy of elective lymph node dissection in patients with intermediate thickness primary melanoma. Ann Surg 1983; 198: 379–85.[Medline]
3. Reintgen DS, Balch CM, Kirkwood J, Ross MI. Recent advances in the care of the patient with malignant melanoma. Ann Surg 1997; 225: 1–14.[CrossRef][Medline]
4. Holmes EC, Mosley HS, Morton DL, Clark W, Robinson D, Urist MM. A rational approach to the surgical management of melanoma. Ann Surg 1977; 186: 481–90.[Medline]
5. Baas PC, Schraffordt KH, Hockstra HJ, van Bruggen JJ, van der Weele LT, Oldhoff J. Groin dissection in the treatment of lower extremity melanoma. Short term and long term morbidity. Arch Surg 1992; 127: 281–6.[Abstract/Free Full Text]
6. Beitsch P, Balch C. Operative morbidity and risk factor assessment in melanoma patients undergoing inguinal lymph node dissection. Am J Surg 1992; 164: 462–5.[Medline]
7. Ingvar C, Erichsen C, Jonsson PE. Morbidity following prophylactic and therapeutic lymph node dissection for melanoma—a comparison. Tumori 1984; 70: 529–33.[Medline]
8. Urist MM, Maddox WA, Kennedy JE, Balch CM. Patient risk factors and surgical morbidity after regional lymphadenectomy in 204 melanoma patients. Cancer 1983; 51: 2152–6.[CrossRef][Medline]
9. Karakousis CP, Stahl L, Moore R, Holyoke ED. Lymph node dissection in malignant melanoma. J Surg Oncol 1980; 13: 245–52.[Medline]
10. Bland K, Klamer T, Polk H Jr, Knutson C. Isolated regional lymph node dissection: morbidity, mortality and economic considerations. Ann Surg 1981; 193: 372–6.[Medline]
11. Hughes TM, Thomas JM. Combined inguinal and pelvic lymph node dissection for stage III melanoma. Br J Surg 1999; 86: 1493–8.[CrossRef][Medline]
12. McMasters KM, Reintgen DS, Ross MI, et al. Sentinel lymph node biopsy for melanoma: how many radioactive nodes should be removed? Ann Surg Oncol 2001; 8: 192–7.[Abstract/Free Full Text]
13. Schrenk P, Rieger R, Shamiyeh A, Wayand A. Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast carcinoma. Cancer 2000; 88: 608–14.[CrossRef][Medline]
14. Jansen L, Nieweg OE, Peterse JL, et al. Reliability of sentinel lymph node biopsy for staging melanoma. Br J Surg 2000; 87: 484–9.[CrossRef][Medline]
15. Wrone DA, Tanabe KK, Cosimi AB, et al. Lymphedema after sentinel lymph node biopsy for cutaneous melanoma: a report of 5 cases. Arch Dermatol 2000; 136: 511–4.[Abstract/Free Full Text]
16. Leong SP, Donegan E, Heffernon W, Dean S, Katz JA. Adverse reactions to isosulfan blue during selective sentinel lymph node dissection in melanoma. Ann Surg Oncol 2000; 7: 361–6.[Abstract/Free Full Text]
17. Bold RJ, Mansfield PF, Berger DH, et al. Prospective, randomized, double-blind study of prophylactic antibiotics in axillary lymph node dissection. Am J Surg 1998; 176: 239–43.[CrossRef][Medline]
18. Wagner JD, Park HM, Coleman JJ, Love C, Hayes JT. Cervical sentinel lymph node biopsy for melanomas of the head and neck and upper thorax. Arch Otolaryngol Head Neck Surg 2000; 126: 313–21.[Abstract/Free Full Text]
19. Ollila DW, Foshag LJ, Essner R, Setern SL, Morton DL. Parotid region lymphatic mapping and sentinel lymphadenectomy for cutaneous melanoma. Ann Surg Oncol 1999; 6: 150–4.[Abstract]

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