Sentinel lymph node biopsy in patients with multicentric/multifocal breast cancer: low false-negative rate and lack of axillary recurrence

Background

Accuracy of sentinel lymph node biopsy (SLNB) and rate of axillary recurrence in multicentric/multifocal (MC/MF) breast cancer are reported.

Methods

From 1999 to 2006, 93 patients with MC/MF breast cancer underwent SLNB; 41 underwent axillary lymph node dissection regardless of SLN pathology (group 1), and 52 underwent axillary lymph node dissection only if an SLN was positive (group 2). Patient demographics, SLN techniques, and pathology were recorded.

Results

There were no differences between the 2 groups with respect to patient age; tumor size, grade, stage, and histology; or method of SLN detection. The incidence of axillary metastasis was greater in group 1 patients (68%) compared with group 2 patients (12%) (P < .01). In group 1, the sensitivity and specificity of SLNB were 93% and 100%, respectively, with a false-negative rate of 7%. None of the 52 patients in group 2 experienced axillary recurrence (median follow-up 4.8 years).

Conclusions

The accuracy of SLNB in MC/MF breast cancer is comparable with that observed in unifocal breast cancer. Despite a lower rate of SLN positivity in patients undergoing SLNB only, axillary recurrence was not observed.     

Surgical management of the axilla: do intramammary nodes matter?

Background

The therapeutic significance of intramammary lymph nodes is uncertain. The purpose of this study was to identify the appropriate surgical management of the axilla in intramammary node-positive patients undergoing sentinel lymph node (SLN) biopsy.

Methods

A retrospective review of consecutive patients staged between September 1996 and December 2004 was performed. Intramammary node identification and pathologic findings were compared with the status of axilla.

Results

Among 7,140 patients, intramammary nodes were identified in 151 (2%). Positive intramammary nodes were identified in 36 patients (24%). Axillary disease was identified in 61% of intramammary node-positive patients. No additional axillary disease was identified when axillary lymph node dissection was performed in intramammary node-positive patients with negative axillary SLN biopsy results.

Conclusions

The results suggest that completion axillary lymph node dissection may be based on the status of axillary SLN biopsies in clinically node negative patients when intramammary lymph node metastases are identified in the breast specimens.     

Sentinel lymph node staging of cutaneous melanoma: predictors and outcomes

Background

The authors updated their experience with sentinel lymph node (SLN) biopsy of clinically node negative (N0) melanoma to clarify indications, predictive factors, and outcomes.

Methods

A review of patients from the authors' institution's prospective database (n = 397) was performed; survival statistics were obtained from the institutional tumor registry.

Results

The SLN-positive (SLN+) rate was 16% (47 of 282) for lesions >1 mm thick; only 2 of 105 T1 lesions were SLN+. Thickness >2 mm, upper extremity primary, and ulceration predicted SLN+ status. Most SLN+ patients underwent completion node dissection; 12% had additional positive nodes. The false-negative SLN biopsy rate was 4.0%; the majority involved lower extremity and head and neck primaries. The overall complication rate was 26%; all were minor and resolved within 6 months. Overall 5-year survival rates were 73% and 92% for SLN+ and SLN-negative patients, respectively. SLN status was the most significant predictor of survival.

Conclusions

SLN status, the most important determinant of outcome for clinically N0 melanoma, correlated with T stage, ulceration, and site. Staging of T1 lesions had low yield. A minority of completion node dissections yielded additional positive nodes.     

Axillary-conserving surgery is facilitated by neoadjuvant chemotherapy of breast cancer

Background

This study examines the downstaging of breast cancer axillary lymph node (ALN) metastasis by neoadjuvant chemotherapy (NCT) and the potential facilitation of axillary-conserving surgery.

Methods

Records of breast cancer patients treated with NCT, breast surgery, and pathological ALN assessment were reviewed using the institutional breast cancer database.

Results

Of 473 cases, 309 (65%) were clinically ALN-positive (cN+) and 164 (35%) were clinically ALN-negative (cN−). Pre-NCT, needle biopsy, sentinel lymph node (SLN) biopsy, or axillary dissection documented metastasis in 94% (117/124) of cN+ and 27% (13/49) of cN− patients tested. Pathological complete response of ALNs to NCT was documented in 36% (41/115) of patients. False negative SLN biopsy following NCT occurred in 4% of cases (1/28).

Conclusion

NCT downstages primary breast cancer and ALN metastasis. ALN and SLN biopsy following, rather than before, NCT facilitate both breast- and axillary-conserving surgery.     

Utility of frozen-section analysis of sentinel lymph node biopsy specimens for melanoma in surgical decision making

Background

Debate exists whether frozen-section analysis of sentinel lymph nodes (SLNs) for melanoma is an accurate method to detect disease that has metastasized to the lymph nodes. The purpose of this study was to evaluate the utility of intraoperative frozen section for SLNs in melanoma.

Methods

We reviewed 133 patients (271 nodes) who underwent SLN biopsy with frozen section for melanoma between April 2003 and September 2007. Frozen-section diagnosis was compared with final diagnosis to determine concordance between intraoperative and postsurgical diagnosis.

Results

A total of 11 nodes (8% of patients) were found to have metastatic disease. All patients underwent lymph node dissections at the time of SLN biopsy. No false-positive SLNs were found on frozen section. The false-negative rate for SLN biopsy frozen section was 8% (1 of 133 patients).

Conclusions

Intraoperative frozen section can be an accurate and reliable tool in the right setting for analysis of sentinel nodes in cutaneous melanoma and deserves further study.     

Survival in sentinel lymph node-positive pediatric melanoma

Background

Sentinel lymph node (SLN) status is the strongest predictor of survival in adult melanoma. However, the prognostic value of SLN status in children and adolescents with melanoma is unknown.

Methods

Records of 327 patients aged 12 to 86 years undergoing SLN biopsy for melanoma or other melanocytic lesions were reviewed. A literature search identified additional patients younger than 21 years undergoing SLN biopsy for the same indications and these patients were combined with our series for meta-analysis.

Results

Sentinel lymph node metastases were found in 8 (40%) of 20 patients aged 12 to 20 years compared with 55 (18%) of 307 adults (P < .05). Median follow-up was 35 and 17 months for the groups, respectively. Sentinel lymph node-positive pediatric patients did not recur, whereas 14 (25%) adults recurred within this period. Of the 55 adults, 5 (9.1%) have died of disease. Of the combined SLN-positive children and adolescents from the literature (total n = 25), only a single (4%) child recurred at 6 months. The difference in survival for adult and pediatric patients was significant.

Conclusion

Pediatric patients have a higher incidence of SLN metastases than adults yet have a lower incidence of recurrence. Sentinel lymph node status does not predict early recurrence in pediatric patients with melanoma or atypical Spitz nevi.     

Factors influencing accuracy of axillary sentinel lymph node frozen section for breast cancer

Background

Intraoperative sentinel lymph node (SLN) frozen section (FS) guides immediate axillary lymph node dissection in breast cancer patients.

Methods

The Oregon Health & Science University pathology database was searched for SLN FS From October 1999 to January 1, 2009. Slides of positive cases were reviewed and metastasis sizes measured.

Results

Of 416 cases, 129 were positive (31%) on permanent sections and immunohistochemistry, with 79 concordant and 50 false-negative FS. Accuracy was 88%, sensitivity 61%, and specificity 100%. FS accuracy for lobular carcinoma (76%) was lower than for invasive ductal carcinoma (88%) (P = .048). FS accuracy significantly differed by size of nodal tumor. For 49 cases of tumor ≤ 2 mm (isolated tumor cells plus micrometastases), the accuracy of FS was 18%; for 77 cases of >2-mm metastases, accuracy was 90% (P < .0001).

Conclusions

False-negative FS were predominantly small nodal tumor deposits not sampled at FS. Although accuracy was lower, SLN FS is still beneficial in lobular carcinoma, but not ductal carcinoma in situ.     

Clinical importance of micrometastasis in sentinel lymph nodes

Introduction

We evaluated the incidence of micrometastasis and nonsentinel lymph node metastasis as well as local and axillary recurrence rates after level I-II axillary lymph node dissection.

Materials and methods

Patients (n = 760) with early-stage breast cancer underwent sentinel lymph node biopsy, and 45 patients (6.0%) with micrometastasis (0.2-2.0 mm) were included in this study. Data concerning tumor, patients’ characteristics and adjuvant treatments were recorded.

Results

The median age was 46 (26-67) years, median breast tumor size was 20 (1-50) mm, and median number of excised sentinel lymph nodes were 2 (1-5). All patients with micrometastasis underwent further level I-II axillary lymph node dissection. Eleven of 45 (24.4%) patients with micrometastasis in their sentinel lymph node biopsy had nonsentinel lymph node metastasis after an axillary lymph node dissection. There was no factor related to nonsentinel lymph node metastasis. Stage migration occurred in 4 of 45 patients (8.8%) due to the detection of micrometastases or macrometastases in nonsentinel lymph nodes.

Discussion

The classical treatment after detection of micrometastasis in sentinel lymph nodes is further axillary dissection. However, nonrandomized, nonprospective studies with 4-5 years follow up showed 0.6% axillary recurrence without further axillary lymph node dissection, although we still need the results of randomized controlled studies.     

The use of touch preparation for the evaluation of sentinel lymph nodes in breast cancer

Background

This study was undertaken to evaluate the accuracy of touch preparation (touch prep) in the evaluation of sentinel lymph nodes (SLNs).

Methods

We performed a retrospective review of 402 breast cancer patients who underwent SLN biopsy.

Results

A SLN was identified in 381 patients. Of 61 patients with a true positive result, 59 underwent axillary node dissection, and in 22 the SLN was the only node with metastases. Thirty-six (9.44%) had at least 1 false negative result. Twenty-five with a false negative results were due to macrometastases, with 17 (2.4%) false negatives occurring in patients with invasive ductal and 6 (5.5%) in those with invasive lobular histology, P = .04. Touch prep had an overall sensitivity of 62.89% and specificity of 98.94%.

Conclusions

Touch prep for the evaluation of SLNs in breast cancer compares favorably to reported results for frozen section. False negative findings are more likely with micrometastases and invasive lobular histology.     

Hypersensitivity reaction against patent blue during sentinel lymph node removal in three melanoma patients

Background

In order to identify the sentinel lymph node (SLN) in melanoma patients intradermal injection of a radiocolloid tracer and a blue dye are commonly used. Life-threatening side effects such as allergic reactions to the injected dye have been described. We report 3 cases with systemic allergic reactions.

Methods

Three patients suffering from systemic reactions such as hypotension and rash during SLN biopsy were tested for sensitisation against patent blue and methylene blue with skin prick, scratch, and intradermal test.

Results

All 3 patients showed positive skin tests to patent blue confirming allergic reaction to the injected dye. In addition, all patients showed positive skin tests with methylene blue indicating immunologic cross-reactivity between patent blue and methylene blue.

Conclusions

Although allergic reactions to blue dye during SLN biopsy are rare, they may be life threatening. It is important that the attending anesthetist is aware of this.     

Scientific Impact Award: Axillary reverse mapping (ARM) to identify and protect lymphatics draining the arm during axillary lymphadenectomy

Introduction

The axillary reverse mapping (ARM) procedure distinguishes lymphatics draining the arm from those draining the breast. The aim of this study was to assess the ability of ARM to identify and preserve lymphatics draining the arm and the impact on lymphedema.

Methods

This study included 220 patients undergoing sentinel lymph node (SLN) biopsy (SLNB) with or without axillary lymph node dissection (ALND) from May 2006 to September 2008. After SLN localization with a radioactive tracer, blue dye was used to map ARM lymphatics. Data were collected on identification and variations in lymphatic drainage, crossover rate, the incidence of metastases, and nodal status.

Results

Crossover (ARM = SLN) occurred in 6 patients (2.8%). ARM lymphatics were near or in the SLN field in 40.6% of patients, placing it at risk for disruption during lymphadenectomy. ARM lymphatics juxtaposed to the hot SLNB (n = 12 [5.6%]) were preserved. Fifteen ARM nodes were excised and were negative even in positive axillae. There were no cases of lymphedema at 6-month follow-up where ARM nodes were preserved.

Conclusion

Confluence of the arm and breast drainage is rarely the SLN, and none of these nodes contained metastases. Preserving the ARM nodes may translate into a lower incidence of postoperative lymphedema.     

Stage migration with sentinel node biopsy in breast cancer

Background

Axillary staging provides the single most important piece of prognostic information in breast cancer patients. This retrospective study was performed to document the phenomenon of stage migration.

Methods

Of 392 patients, 5 (1%) failed identification of sentinel lymph nodes (SLNs) and therefore underwent axillary lymph node dissection (ALND). Four patients (80%) had metastatic lymph nodes, 302 (77%) patients had negative SLNs, 47 (15%) underwent ALND, 85 (22%) had positive SLNs, 11 (13%) received adjuvant radiation treatment to the axilla, and 74 (87%) underwent completion ALND.

Results

The median (quartiles) follow-up period was 29 months (19-46 mo). Twenty of 392 (5%) patients had disease relapse; 2 of which were local (.5%) and the rest were systemic. Earlier relapse was related significantly to lymph node status, tumor grade, and tumor size. SLN-negative patients who did not receive ALND had a relapse rate of 2.3% (6 of 256) compared with 0% in those who were truly negative based on confirmatory ALND. SLN-positive patients who did not receive ALND had a 9% (1 of 11) relapse rate.

Discussion

The stage-matched pattern of relapse between SLN biopsy and ALND patients revealed lower relapse rates in SLN biopsy-staged patients, documenting the stage migration phenomenon.     

The clinical impact and outcomes of immunohistochemistry-only metastasis in breast cancer

Background

Modern surgical and pathological techniques can detect small-volume axillary metastases in breast cancer with unknown clinical significance.

Methods

A retrospective database review from 1996 through 2004 identified all patients with immunohistochemical (IHC)-only sentinel node (IHC-SN) metastases and compared them with negative controls (Neg-SN).

Results

When comparing the 232 IHC-SN patients with the 252 Neg-SN controls, the IHC-SN patients had larger tumors, more lobular histology, a higher grade, and more HER2/neu positivity. They also received more systemic therapy. With a median follow-up of 5 years, there were no differences in recurrence-free survival or overall survival. In 123 IHC-SN patients treated with axillary dissection (axillary lymph node dissection), 16% had positive non-SLNs. Patients with positive non-SLNs tended to have worse outcomes.

Conclusions

IHC-only sentinel lymph node (SLN) metastases were associated with worse prognostic features and higher rates of systemic therapy. However, no outcomes differences were noted.     

Long-term follow-up results of breast cancer patients with sentinel lymph node biopsy using periareolar injection

Background

Areolar injection for sentinel lymph node biopsy (SLNB) in breast cancer surgery has been adopted by many institutions. However, only one study has reported the follow-up results for patients whose SLNB was performed with this injection method alone.

Methods

Three hundred eighty patients with breast cancer underwent SLNB with periareolar injection of both blue dye and radiotracer. The follow-up consisted of a physical examination every 3 months and annual mammography.

Results

Of 380 patients with SLNB, 261 were found to have negative sentinel lymph nodes so that no ALND was performed. At a median follow-up of 39 months (range 13-74), 2 of the 261 patients developed axillary recurrence for an axillary relapse incidence of .77%. Five-year distant disease-free survival was 96.9%, and overall survival was 99.4%.

Conclusions

The incidence of axillary recurrence for the areolar injection method was low and consistent with that reported in other observational studies using other injection methods.     

Assessment of value of the sentinel lymph node biopsy in melanoma in children and adolescents and applicability of subcutaneous infusion anesthesia

Background/Purpose

The management of pediatric melanoma is controversial but equates that of adults. Lymphatic mapping with sentinel lymph node (SLN) biopsy is proposed as standard of care for patients with primary melanoma. The operation can be done with general or local anesthesia in adults. The goal of this study was to determine the applicability of subcutaneous infusion anesthesia (SIA) for SLN biopsy in children and adolescents, as well as to assess complications of this procedure and to document outcome of patients with melanoma in this particular age group after SLN biopsy.

Methods

Charts of patients with melanomas on the trunk and extremities who underwent lymphatic mapping and SLN biopsy in SIA between November 2000 and January 2006 revealed 13 patients with age 21 years or less. Tumescent solutions with lidocaine (0.2%) were used for SLN biopsy. Patient demographics, tumor thickness, Clark level, location of primary melanoma, ulceration, number of SLNs, number of positive nodes, and follow-up of patients were included.

Results

In 13 patients (age range, 12-21), SLN biopsy was performed. Mean tumor thickness was 1.8 mm (range, 1.0-7.0), none of these melanomas showed ulceration. The operation was tolerated in SIA by all patients; none had any associated complications. Of 13 patients, 5 (38.5%) had positive sentinel nodes. Three patients underwent completion lymph node dissection, and no further positive nodes were found. After a mean follow-up of 29.2 months (range, 13-68), all patients were found disease-free.

Conclusions

Sentinel lymph node biopsy in SIA can safely be performed in children and adolescents with primary melanomas. Further studies are necessary to determine the prognostic information and therapeutic implications of SLN biopsy in this patient group.     

Prognostic factors and patterns of recurrence in esophageal cancer assert arguments for extended two-field transthoracic esophagectomy

Background

High recurrence rates determine the dismal outcome in esophageal cancer. We reviewed our experiences and defined prognostic factors and patterns of recurrences after curatively intended transthoracic esophagectomy.

Methods

Between January 1991 and December 2005, 212 consecutive patients underwent a radical transthoracic esophagectomy with extended 2-field lymphadenectomy. Recurrence rates, survival, and prognostic factors were analyzed (minimal follow-up period, 2 y).

Results

Radicality was obtained in 85.6%. The median follow-up period was 26.6 months. The overall recurrence rate at 1, 3, and 5 years was 28%, 44%, and 64%, respectively, and locoregional recurrence rate was 17%, 27%, and 43%, respectively. Overall survival rates, including postoperative deaths, were 45% and 34% at 3 and 5 years, respectively. pT stage and lymph node (LN) ratio greater than .20 were independent prognostic factors for survival and recurrences. Radicality was most prognostic for survival, and for N+ greater than 4 positive LN for recurrences.

Conclusions

Radicality and LN ratio are strong prognostic factors. High radicality and adequate nodal assessment are guaranteed by an extended transthoracic approach.     

The effect of neoadjuvant chemoradiation therapy on the prognostic value of lymph nodes after rectal cancer surgery

Background

Neoadjuvant therapy may affect the prognostic impact of total lymph node harvests and lymph node positivity after surgery for rectal cancer.

Methods

We performed a retrospective review of 390 consecutive patients with histologically confirmed rectal cancer. Postoperative follow-up evaluation and survival were confirmed via medical record review. The impacts of lymph node positivity and total lymph node harvest on survival and recurrence are reflected as proportional hazard ratios (HRs).

Results

A total of 221 patients underwent neoadjuvant therapy, of whom 75 had positive nodes. Node-positive patients showed a significantly shorter survival time (HR, 2.89; P = .002) and time to local recurrence (HR, 6.36; P = .031) compared with patients without positive nodes. Survival and recurrence were not significantly different between patients with a total harvest of fewer than 12 nodes and patients with a higher lymph node harvest.

Conclusions

After neoadjuvant treatment and total mesorectal excision, lymph node positivity is associated with significantly shorter survival and time to local recurrence in rectal cancer patients, whereas absolute total lymph node harvests likely have little impact on prognosis.     

Clinicopathologic features of peripheral squamous cell carcinoma of the lung

Background

The clinicopathologic features are still unknown in peripheral squamous cell carcinoma of the lung, unlike centrally located carcinomas. In this retrospective study, we investigated the clinicopathologic characteristics of patients with peripheral squamous cell carcinomas.

Methods

Of 1,381 primary lung carcinomas surgically resected at the National Cancer Center Hospital, Tokyo, from 1995 through 2001, 70 (5.1%) peripheral squamous cell carcinomas of 3.0 cm or less in diameter were studied retrospectively in terms of clinicopathologic characteristics such as age, sex, past history, smoking, tumor size, mode of operation, extent of lymph node dissection, pathologic lymph node status, mode of recurrence, and cause of death.

Results

These patients ranged in age from 49 to 82 years, with a mean age of 69.2 years. Thirty-nine patients (56%) were at increased risk preoperatively. The incidence of lymph node metastasis was 25%, and larger tumors tended to be associated with a higher prevalence, although this difference was not significant (p = 0.12). None of the patients with N2 disease had skipping metastasis. Recurrence was observed in 13 patients (19%). There was no significant correlation between recurrence and the extent of lymphadenectomy or the mode of operation. The 5-year overall and disease-specific survival rates were 73.4% and 85.9%, respectively. The cause of death was recurrence in 53% and other disease in 47%.

Conclusions

We propose that mediastinal hilar lymphadenectomy should be routinely conducted as a curative operation for low-risk patients with small peripheral squamous cell carcinoma. We further propose that for patients who may have difficulty tolerating this procedure, pathologic examination of intraoperative frozen sections from the hilar node could be useful for planning a surgical strategy.     

A Comparative Validation of Primary Surgical Versus Post-neo-adjuvant Chemotherapy Sentinel Lymph Node Biopsy for Stage III Breast Cancers

Introduction

Sentinel lymph node biopsy (SLNB) is the standard of care for staging N0 primary early breast cancers (EBC). Patients in developing countries mostly present with large (LOBC) or locally advanced cancers (LABC) and are treated with neo-adjuvant chemotherapy (NACT). Accuracy of SLNB in staging stage III N0 and post-NACT N0 patients is uncertain. This prospective validation study on LOBC/LABC patients compared the accuracy of SLNB between primary versus post-NACT surgery.

Materials and methods

Fifty T3/T4, N0 patients undergoing primary surgery (Group I) and 70 LOBC/LABC (index stage) treated with NACT and N0 at the time of surgery (Group II) were inducted. Validation SLNB was performed using low-cost methylene-blue and ^99mTc-Antimony colloid. SLN identification (IR) and false-negative (FNR) rates were compared between the groups. Sub-group analysis was done in Group II per index tumor and nodal stage to identify factors predicting SLN IR and FNR in post-NACT patients. SLN IR and FNR in both groups were compared with those in previously published SLN validation study and meta-analysis in EBC.

Results

Using combination of blue-dye and radio-colloid, post-NACT SLN IR and FNR (82.9, 13.5 %) were far inferior to T3/T4 primary surgery group (94, 7.7 %; p values 0.034, 0.041) and in EBC. SLN IR using blue-dye alone was dismally low in post-NACT LABCs. Factors predicting unidentified post-NACT SLN and false-negative SLNB included young age, LVI, skin infiltration, extra-nodal spread or N2a stage, and UOQ tumors.

Conclusions

Accuracy of SLNB in T3, N0 tumors undergoing primary surgery is comparable to that of SLNB for N0 EBC. In post-NACT patients, SLNB IR are lower and FNR are higher. Factors predictive of non-identification and false-negative SLNB include pre-NACT skin involvement (T4b), N2a stage or extra-nodal invasion and LVI, and to a lesser extent, young age and UOQ location of the tumor.