'We just need to find space for them to practice so that we can help to make a stronger society': Perceived barriers and facilitators to employing health psychologists in UK public health and clinical health settings.

INTRODUCTION: In recent years, health psychology has received significant attention within the health sector, due to its application to understanding influences on health and well-being and translation of health psychology into interventions to support behaviour change. The number of health psychologists in public health and healthcare settings is growing but remains limited, and is it unclear why. This study aimed to explore the views of potential and current employers of health psychologists, to elucidate barriers and facilitators of employing health psychologists in healthcare settings. METHODS: Semi-structured interviews were carried out to explore the experiences of working with and/or employing health psychologists. Opportunities and barriers were explored for increasing access to health psychology expertise in the NHS and public health. Interviews were analysed using inductive thematic analysis. RESULTS: Fifteen participants took part in interviews. Participants were mid-senior-level professionals working in varied healthcare settings and/or academic institutions. The majority had experience of health psychology/working with health psychologists, whilst others had limited experience but an interest in employing health psychologists. Three key themes were identified: (1) the organizational fit of health psychologists, (2) perception of competition for roles and (3) ideas for changing hearts, minds and processes. CONCLUSION: Barriers exist to employing health psychologists in healthcare settings. These barriers include misunderstandings of the role of health psychologists and the need to preserve other disciplines due to perceived competition. Recommendations for change included showcasing the benefits and skills of health psychologists and having transparent conversations with employees and multi-disciplinary colleagues about roles.

Using behavioural science in public health settings during the COVID-19 pandemic: The experience of public health practitioners and behavioural scientists.

INTRODUCTION: The emergence of COVID-19 and the importance of behaviour change to limit its spread created an urgent need to apply behavioural science to public health. Knowledge mobilisation, the processes whereby research leads to useful findings that are implemented to affect positive outcomes, is a goal for researchers, policy makers and practitioners alike. This study aimed to explores the experience of using behavioural science in public health during COVID-19, to discover barriers and facilitators and whether the rapidly changing context of COVID-19 influenced knowledge mobilisation. METHODS: We conducted a semi-structured interview study, with ten behavioural scientists and seven public health professionals in England, Scotland, Wales, The Netherlands and Canada. We conducted an inductive thematic analysis. RESULTS: We report three key themes and 10 sub-themes: 1.Challenges and facilitators of translation of behavioural science into public health (Methods and frameworks supported translation, Lack of supportive infrastructure, Conviction and sourcing of evidence and Embracing behavioural science) 2. The unique context of translation (Rapid change in context, the multi-disciplinary team and the emotional toll). 3. Recommendations to support future behavioural science translation (Embedding experts into teams, Importance of a collaborative network and showcasing the role of behavioural science). DISCUSSION: Barriers and facilitators included factors related to relationships between people, such as networks and teams; the expertise of individual people; and those related to materials, such as the use of frameworks and an overwhelming amount of evidence and literature. CONCLUSION: People and frameworks were seen as important in facilitating behavioural science in practice. Future research could explore how different frameworks are used. We recommend a stepped competency framework for behavioural science in public health and more focus on nurturing networks to facilitate knowledge mobilisation in future emergencies.

Current and historical rates of input of mercury to the Penobscot River, Maine, from a chlor-alkali plant.

Mercury inputs by surface and ground water sources to Penobscot River from a defunct Hg-cell chlor-alkali plant were measured in 2009-10 and estimated for the entire period of operation of this facility. Over the measured interval (422 days) approximately 2.3 kg (5.4 g day-1) of mercury was discharged to the Penobscot River by the two surface streams that drain the site, with most of the combined loading (1.8 kg Hg, 78%) associated with a single storm with rainfall in excess of 100 mm. Groundwater seepage rates from the site, as estimated from both a radon tracer and seepage meter methods were in the range of 3 to 4 cm day-1 and, when combined with a best estimate of the area of groundwater discharge (11,000 m2) and average seepage/porewater mercury concentration (242 ng L-1, UCL95), yielded a loading of 0.11 g day-1 for site groundwater. None of the municipal or other industrial point sources of mercury to the river between Veazie and Bucksport, Maine exceeded 1 g day-1 individually, nor was the aggregate loading of all such sources >3 g day-1 (based on State of Maine data). Mercury loadings for the three largest tributaries downstream of Veazie Dam were estimated to contribute 4.2, 3.7 and 2.5 g day-1, respectively, to the Penobscot River. Based on sampling (total Hg ~ 2 to 4 ng L-1) and historical mean discharge data (340-460 m3 s-1), the Penobscot River upstream of the plant site contributes as much as 160 g day-1 to the downstream reach depending on river discharge. Estimates of historical (1967-2012) mercury loading using both generic emission factors and measured releases ranged from 2.6 to 27 MT while the mass of mercury found in downstream sediments amounted to 9 MT.

Tidal fluxes of mercury and methylmercury for Mendall Marsh, Penobscot River estuary, Maine.

Tidal marshes are both important sites of in situ methylmercury production and can be landscape sources of methylmercury to adjacent estuarine systems. As part of a regional investigation of the Hg-contaminated Penobscot River and Bay system, the tidal fluxes of total suspended solids, total mercury and methylmercury into and out of a regionally important mesohaline fluvial marsh complex, Mendall Marsh, were intensively measured over several tidal cycles and at two spatial scales to assess the source-sink function of the marsh with respect to the Penobscot River. Over four tidal cycles on the South Marsh River, the main channel through which water enters and exits Mendall Marsh, the marsh was a consistent sink over typical 12-h tidal cycles for total suspended solids (8.2 to 41 g m-2), total Hg (9.2 to 47 µg m-2), total filter-passing Hg (0.4 to 1.1 µg m-2), and total methylmercury (0.2 to 1.4 µg m-2). The marsh's source-sink function was variable for filter-passing methylmercury, acting as a net source during a large spring tide that inundated much of the marsh area and that is likely to occur during approximately 17% of tidal cycles. Additional measurements on a small tidal channel draining approximately 1% of the larger marsh area supported findings at the larger scale, but differences in the flux magnitude of filter-passing fractions suggest a highly non-conservative transport of these fractions through the tidal channels. Overall the results of this investigation demonstrate that Mendall Marsh is not a significant source of mercury or methylmercury to the receiving aquatic systems (Penobscot River and Bay). While there is evidence of a small net export of filter-passing (<0.4 µm pore size) methylmercury under some tidal conditions, the mass involved represents <3% of the mass of filter-passing methylmercury carried by the Penobscot River.

Assessment of DNA methylation status in early stages of breast cancer development.

BACKGROUND: Molecular pathways determining the malignant potential of premalignant breast lesions remain unknown. In this study, alterations in DNA methylation levels were monitored during benign, premalignant and malignant stages of ductal breast cancer development. METHODS: To study epigenetic events during breast cancer development, four genomic biomarkers (Methylated-IN-Tumour (MINT)17, MINT31, RARß2 and RASSF1A) shown to represent DNA hypermethylation in tumours were selected. Laser capture microdissection was employed to isolate DNA from breast lesions, including normal breast epithelia (n=52), ductal hyperplasia (n=23), atypical ductal hyperplasia (n=31), ductal carcinoma in situ (DCIS, n=95) and AJCC stage I invasive ductal carcinoma (IDC, n=34). Methylation Index (MI) for each biomarker was calculated based on methylated and unmethylated copy numbers measured by Absolute Quantitative Assessment Of Methylated Alleles (AQAMA). Trends in MI by developmental stage were analysed. RESULTS: Methylation levels increased significantly during the progressive stages of breast cancer development; P-values are 0.0012, 0.0003, 0.012, <0.0001 and <0.0001 for MINT17, MINT31, RARß2, RASSF1A and combined biomarkers, respectively. In both DCIS and IDC, hypermethylation was associated with unfavourable characteristics. CONCLUSION: DNA hypermethylation of selected biomarkers occurs early in breast cancer development, and may present a predictor of malignant potential.

Aberrant hypermethylation in primary tumours and sentinel lymph node metastases in paediatric patients with cutaneous melanoma.

BACKGROUND: Debate on how to manage paediatric patients with cutaneous melanoma continues, particularly in those with sentinel lymph node (SLN) metastases who are at higher risk of poor outcomes. Management is often based on adult algorithms, although differences in clinical outcomes between paediatric and adult patients suggest that melanoma in paediatric patients differs biologically. Yet, there are no molecular prognostic studies identifying these differences. OBJECTIVES: We investigated the epigenetic (methylation) regulation of several tumour-related genes (TRGs) known to be significant in adult melanoma progression in histopathology(+) SLN metastases (n = 17) and primary tumours (n = 20) of paediatric patients with melanoma to determine their clinical relevance. METHODS: Paediatric patients (n = 37; ≤ 21 years at diagnosis) with American Joint Committee on Cancer stage I-III cutaneous melanoma were analysed. Gene promoter methylation of the TRGs RASSF1A, RARß2, WIF1 and APC was evaluated. RESULTS: Hypermethylation of RASSF1A, RARß2, WIF1 and APC was found in 29% (5/17), 25% (4/16), 25% (4/16) and 19% (3/16) of histopathology(+) SLNs, respectively. When matched to adult cutaneous melanomas by Breslow thickness and ulceration, hypermethylation of all four TRGs in SLN(+) paediatric patients with melanoma was equivalent to or less than in adults. With a median follow-up of 55 months, SLN(+) paediatric patients with melanoma with hypermethylation of > 1 TRG vs. ≤ 1 TRG had worse disease-free (P = 0·02) and overall survival (P = 0·02). CONCLUSIONS: Differences in the methylation status of these TRGs in SLN(+) paediatric and adult patients with melanoma may account for why SLN(+) paediatric patients have different clinical outcomes. SLN biopsy should continue to be performed; within SLN(+) paediatric patients with melanoma, hypermethylation of TRGs can be used to identify a subpopulation at highest risk for poor outcomes who warrant vigilant clinical follow-up.

Histopathologic assessment of the sentinel lymph node in breast cancer.

Thorough pathologic examination of the sentinel lymph node (SLN) improves the accuracy of breast cancer staging and reduces the rate of false-negative results. Intraoperative examination of the SLN with cytological or frozen section techniques remains problematic. Diagnostic difficulties encountered on hematoxylin and eosin paraffin sections in general are easily resolved with cytokeratin immunohistochemistry, but the finding of minute metastases may lead to diagnostic and therapeutic dilemmas. Pathologic characteristics of the primary tumor and SLN metastasis determine the risk of non-SLN metastasis in the same lymphatic basin.

Carbon dye histologically confirms the identity of sentinel lymph nodes in cutaneous melanoma.

BACKGROUND: False-negative results from lymphatic mapping and sentinel lymphadenectomy (LM/SL) are associated with technical failures in nuclear medicine and surgery or with erroneous histologic evaluation. Any method that can confirm sentinel lymph node (SN) identity might decrease the false-negative rate. Carbon dye has been used as an adjunct to assist lymphadenectomy for some tumors, and the authors hypothesized that it could be used for the histologic verification of SNs removed during LM/SL. The current study assessed the clinical utility of carbon dye as a histopathologic adjunct for the identification of SNs in patients with melanoma and correlated the presence of carbon particles with the histopathologic status of the SNs. METHODS: LM/SL was performed using carbon dye (India ink) combined with isosulfan blue dye and sulfur colloid. Blue-stained and/or radioactive lymph nodes (two times background) were defined as SNs. Lymph nodes were evaluated for the presence of carbon particles and melanoma cells. If an SN lacked carbon dye in the initial histologic sections, four additional levels were obtained with S-100 protein and HMB-45 immunohistochemistry. Completion lymph node dissection (CLND) was performed if any SN contained melanoma cells. RESULTS: One hundred patients underwent successful LM/SL in 120 lymph node regions. Carbon particles were identified in 199 SNs from 111 lymph node regions of 96 patients. Sixteen patients had tumor-positive SNs, all of which contained carbon particles. The anatomic location of the carbon particles within these tumor-positive SNs was found to be correlated with the location of tumor cells in the SNs. The presence of carbon particles appeared to be correlated with blue-black staining (P = 0.0001) and with tumor foci (P = 0.028). All 35 non-SNs that were removed during LM/SL were tumor-negative, and only 2 contained carbon particles. Of the 272 non-SNs removed during CLND, 5 contained metastases; 3 of these 5 were the only non-SNs that had carbon particles. The use of carbon particles during LM/SL was found to be safe and nontoxic. CONCLUSIONS: Carbon dye used in LM/SL for melanoma permits the histologic confirmation of SNs. Carbon particles facilitate histologic evaluation by directing the pathologist to the SNs most likely to contain tumor. The location of carbon particles within SNs may assist the pathologist in the detection of metastases, thereby decreasing the histopathologic false-negative rate of LM/SL and subsequently reducing the same-basin recurrence rate.

Lymphoscintigraphy and lymphatic mapping for identification of sentinel lymph nodes.

The recently introduced technique of sentinel lymph node dissection (SLND) may replace complete axillary lymph node dissection for axillary staging of early breast cancer. Successful SLND is predicated on meticulous delineation of the lymphatic pathway and sentinel node(s). Currently employed lymphatic mapping materials include vital blue dyes and radioactive tracers. Techniques of intraoperative lymphatic mapping and SLND using dye, tracer, or both have high success rates in the hands of experienced investigators, but their routine and widespread use awaits resolution of questions about the timing, dose, and type of radioactive tracer; the optimal lymphatic mapping technique; indications and contraindications for SLND; and certification of qualified surgeons, pathologists, and nuclear medicine physicians.

Pathologic examination of sentinel lymph node for breast carcinoma.

Comprehensive pathologic evaluation of the sentinel lymph node using step sections and cytokeratin immunohistochemistry enhances detection of micrometastases and optimizes the staging of breast carcinoma. This review discusses our current understanding of the pathologic and molecular techniques for sentinel node examination.

Molecular staging of early colon cancer on the basis of sentinel node analysis: a multicenter phase II trial.

PURPOSE: Approximately 30% of patients with American Joint Committee on Cancer stage I or II colorectal cancer (CRC) develop systemic disease. We hypothesized that multimarker reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of sentinel lymph nodes (SNs) draining a primary CRC could detect micrometastases not detected by conventional histopathologic analysis. PATIENTS AND METHODS: In a multi-institutional study, 40 patients with primary CRC underwent dye-directed lymphatic mapping at the time of colon resection. Each dye-stained SN was tagged, and the tumor and regional nodes were resected en bloc. All lymph nodes were examined by conventional hematoxylin and eosin (HE) staining. In addition, each SN was cut into multiple sections for cytokeratin immunohistochemical (CK-IHC) staining and for RT-PCR and electrochemiluminescent detection of three markers: beta-chain human chorionic gonadotropin, hepatocyte growth factor receptor, and universal melanoma-associated antigen. Whenever possible, RT-PCR assay was also performed on primary tumor tissue. The detection sensitivity of individual markers was 10(-3) to 10(-4) microg of RNA and one to five tumor cells in 10(7) lymphocytes of healthy donors. RESULTS: One to three SNs were identified in each patient. An average of 15 nodes were removed from each CRC specimen. No nonsentinel (untagged) node contained evidence of tumor if all tagged (sentinel) nodes in the same specimen were histopathology tumor-negative. HE staining of SNs identified tumor in 10 patients (25%), and CK-IHC of SNs identified occult micrometastases in four patients (10%) whose SNs were negative by HE. Of the remaining 26 patients with no evidence of SN involvement by HE or CK-IHC, 12 (46%) had positive RT-PCR results. The number of markers expressed in each SN correlated (P <.04) with the T stage of the primary tumor. There was 79% concordance in marker expression for the respective pairs (n = 38) of primary tumor and histopathologically positive SNs, and 86% (12 of 14) concordance between RT-PCR positive and histopathologically positive SNs. CONCLUSION: Identification and focused examination of the SN is a novel method of staging CRC. CK-IHC and RT-PCR identified occult micrometastases in 53% of patients whose SNs were negative by conventional staging techniques. These ultrasensitive assays of the SN can identify patients who may be at high risk for recurrence of CRC and therefore are more likely to benefit from systemic adjuvant therapy.

Is the node of Cloquet the sentinel node for the iliac/obturator node group?

PURPOSE: Some surgeons question the survival advantage of ilioinguinal lymphadenectomy for metastatic melanoma because they believe that deep nodal involvement signifies a poor prognosis that is unchanged by surgery. However, several series, including our own, have reported 5-year survival rates reaching 30%. New adjuvant therapies may further improve survival after ilioinguinal lymphadenectomy, but this applies only to nodal basins with metastatic disease. We hypothesized that the node of Cloquet accurately reflects the pathologic status of the iliac/obturator nodes, allowing deep pelvic lymphadenectomy to be selectively performed. PATIENTS AND METHODS: Between 1972 and 1998, 691 patients with primary cutaneous melanoma underwent both elective and therapeutic complete (superficial and deep) ilioinguinal lymphadenectomy. Of the 204 (30%) patients with tumor-positive inguinal and/or iliac/obturator nodes, 68 had a node of Cloquet identified during pathologic review of the lymphadenectomy specimen. Chart and computer database review of these 68 patients was undertaken to determine the association between the tumor status of Cloquet's node and that of deep pelvic nodes. Immunohistochemical analysis was performed on eight of 11 negative Cloquet's nodes in patients with positive iliac/obturator nodes. Paraffin blocks of the other three negative nodes of Cloquet were unavailable for immunohistochemistry, and they were excluded from analysis. RESULTS: Tumor-positive deep nodes were identified in the lymphadenectomy specimen from 20 of 30 (67%) patients with a positive Cloquet's node and from eight of 35 (23%) patients with a negative Cloquet's node (P = 0.0019). Re-examination of these eight tumor-negative Cloquet's nodes using immunostaining with S-100 and HMB45 identified tumor in 3 nodes, increasing the sensitivity of Cloquet's node for predicting deep nodal metastases from 71% to 82%. The 6.8 odds ratio of positive iliac/obturator nodes given a positive node of Cloquet increased to 12.4 after immunohistochemical analysis. The positive and negative predictive values were also enhanced from 67% to 70% and 77% to 84%, respectively. DISCUSSION: The tumor status of the node of Cloquet significantly reflects the tumor status of the iliac/obturator nodes, particularly when Cloquet's node is examined by immunohistochemical analysis. The node of Cloquet assumes the role of the sentinel node in patients whose superficial inguinal lymph nodes drain through Cloquet's node to the iliac/obturator nodes.

Focused examination of sentinel lymph nodes upstages early colorectal carcinoma.

Approximately 30 per cent of patients with early colorectal carcinoma (CRC) develop systemic disease. A subgroup of these patients may harbor occult micrometastatic disease and might benefit from adjuvant chemotherapy. We investigated sentinel lymph node (SLN) mapping and focused pathologic examination of the SLN as a means of detecting nodal micrometastases. Between 1996 and 2000 SLN mapping was performed in 50 consecutive patients undergoing colectomy for CRC. All lymph nodes in the resection specimen were examined via routine hematoxylin and eosin (H&E) staining. In addition multiple sections of each SLN were examined via both H&E and cytokeratin immunohistochemistry. At least one SLN was identified in 47 patients (94%). In seven patients (14%) SLN mapping identified aberrant drainage that altered the planned resection. The SLN(s) correctly predicted nodal basin status in 44 of 47 (94%) cases; there were three falsely negative SLNs. Sixteen cases had positive SLNs by conventional H&E staining. An additional 10 (20%) cases were upstaged by a focused examination of the SLNs. Micrometastases were identified in three cases by H&E staining of multiple sections of the SLN and in seven only by cytokeratin immunohistochemistry. In nine cases the SLN was the only node containing tumor cells. In this study, SLN mapping demonstrated aberrant nodal drainage patterns that altered the surgical resection in patients with CRC. Focused examination of SLNs may detect micrometastases missed by conventional techniques and thereby identify patients who might benefit from adjuvant therapy.

Distribution, speciation, and transport of mercury in stream-sediment, stream-water, and fish collected near abandoned mercury mines in southwestern Alaska, USA.

Concentrations of total Hg, Hg (II), and methylmercury were measured in stream-sediment, stream-water, and fish collected downstream from abandoned mercury mines in southwestern Alaska to evaluate environmental effects to surrounding ecosystems. These mines are found in a broad belt covering several tens of thousands of square kilometers, primarily in the Kuskokwim River basin. Mercury ore is dominantly cinnabar (HgS), but elemental mercury (Hg degrees) is present in ore at one mine and near retorts and in streams at several mine sites. Approximately 1400 t of mercury have been produced from the region, which is approximately 99% of all mercury produced from Alaska. These mines are not presently operating because of low prices and low demand for mercury. Stream-sediment samples collected downstream from the mines contain as much as 5500 microg/g Hg. Such high Hg concentrations are related to the abundance of cinnabar, which is highly resistant to physical and chemical weathering, and is visible in streams below mine sites. Although total Hg concentrations in the stream-sediment samples collected near mines are high, Hg speciation data indicate that concentrations of Hg (II) are generally less than 5%, and methylmercury concentrations are less than 1% of the total Hg. Stream waters below the mines are neutral to slightly alkaline (pH 6.8-8.4), which is a result of the insolubility of cinnabar and the lack of acid-generating minerals such as pyrite in the deposits. Unfiltered stream-water samples collected below the mines generally contain 500-2500 ng/l Hg; whereas, corresponding stream-water samples filtered through a 0.45-microm membrane contain less than 50 ng/l Hg. These stream-water results indicate that most of the Hg transported downstream from the mines is as finely-suspended material rather than dissolved Hg. Mercury speciation data show that concentrations of Hg (II) and methylmercury in stream-water samples are typically less than 22 ng/l, and generally less than 5% of the total Hg. Muscle samples of fish collected downstream from mines contain as much as 620 ng/g Hg (wet wt.), of which 90-100% is methylmercury. Although these Hg concentrations are several times higher than that in fish collected from regional baseline sites, the concentration of Hg in fish is below the 1000 ng/g action level for edible fish established by the US Food and Drug Administration (FDA). Salmon contain less than 100 ng/g Hg, which are among the lowest Hg contents observed for fish in the study, and well below the FDA action level.

Measuring the impact of onychomycosis on patient quality of life.

According to survey research, onychomycosis, a fungal infection of the toenail or fingernail, affects quality of life including physical and social functioning and emotional health. We developed an onychomycosis disease-specific questionnaire (ODSQ) that sensitively assessed symptom distress, functional impact, and social stigma associated with the disease. Samples of patients enrolled in a randomized controlled clinical trial were used for the psychometric evaluations. The multi-item scales were internally consistent (alpha > or = 0.80) and reproducible (ICC > 0.85). Interscale correlations between the ODSQ and generic scales were moderate and consistent with the hypothesized magnitude and directions. Construct validation, employing known groups analysis, supported the hypothesized impact of onychomycosis on three domains of quality of life: physical functioning, emotional health, and social functioning. Significant differences were found between clinically "cured", "improved", or "failed" patients, and between mycologically "eradicated" and "persistent" patients. The ODSQ was responsive to clinical change and more sensitive than derived Medical Outcomes Study Short Form-36 scales. The ODSQ provides reliable, validated and responsive information about the consequences of onychomycosis and its treatment.

Pathologic features associated with nonsentinel lymph node metastases in patients with metastatic breast carcinoma in a sentinel lymph node.

BACKGROUND: To the authors' knowledge it has not yet been determined which patients with primary breast carcinoma and an axillary sentinel lymph node (SN) metastasis have additional metastases in nonsentinel lymph nodes. METHODS: Pathologic features of the primary breast carcinoma and its SN metastasis were examined in 194 patients and correlated with the tumor status of the non-SNs in the same axillary basin. Two-level cytokeratin immunohistochemistry was applied to the SNs and to non-SNs of cases that were negative by standard hematoxylin and eosin examination. RESULTS: Lymph node staging based on SN findings, size of the primary tumor, and presence of peritumoral lymphatic vascular invasion (LVI) were associated with non-SN metastasis. The majority (63%) of the 101 patients with SN macrometastases had non-SN metastases. Extranodal hilar tissue invasion in conjunction with SN involvement also was strongly associated with non-SN metastasis (P = 0.0001) but was present in only 65% of patients (35 of 54 patients) with non-SN macrometastases. Approximately 26% of patients (24 of 93 patients) with SN micrometastases (

Prospective observational study of sentinel lymphadenectomy without further axillary dissection in patients with sentinel node-negative breast cancer.

PURPOSE: Immediate complete axillary lymphadenectomy (ALND) after sentinel lymphadenectomy (SLND) has confirmed that tumor-negative sentinel nodes accurately predict tumor-free axillary nodes in breast cancer. Therefore, we hypothesized that SLND alone in patients with tumor-negative sentinel nodes would achieve axillary control, with minimal complications. PATIENTS AND METHODS: Between October 1995 and July 1997, 133 consecutive women who had primary invasive breast tumors clinically

Intraoperative examination of the sentinel lymph node for breast carcinoma staging.

Intraoperative pathologic examination of the sentinel lymph node (SLN) draining a primary breast carcinoma allows an SLN-positive patient to undergo complete axillary lymphadenectomy as part of the same surgical procedure. However, the optimal technique for rapid SLN assessment has not been determined. We reviewed our results with imprint cytology (IC) and frozen section (FS) examination of SLNs from 278 patients. Compared with H&E-stained paraffin sections, IC and FS had an overall accuracy of 93.2%. The false-reassurance rate (false-negative results/all negative results) was 8.4%. It correctly identified 98% of macrometastases but only 28% of micrometastases. There were no false-positive results. Compared with paraffin-section cytokeratin immunohistochemistry results, the IC-FS false-reassurance rate increased to 25.8%. The false-reassurance rate decreased with smaller primary tumor size (T1 vs T2/3) and ductal type, smaller diameter of the SLN (< or = 2.0 cm), and greater pathologist experience. IC combined with 2-level FS reliably identifies SLN macrometastases but commonly fails to detect SLN micrometastases. If SLN micrometastasis is used to determine the need for further lymphadenectomy, more sensitive intraoperative methods will be needed to avoid a second operation.

Prognostic significance of occult metastases detected by sentinel lymphadenectomy and reverse transcriptase-polymerase chain reaction in early-stage melanoma patients.

PURPOSE: Detection of micrometastases in the regional tumor-draining lymph nodes is critical for accurate staging and prognosis in melanoma patients. We hypothesized that a multiple-mRNA marker (MM) reverse transcriptase-polymerase chain reaction (RT-PCR) assay would improve the detection of occult metastases in the sentinel node (SN), compared with hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC), and that MM expression is predictive of disease relapse. PATIENTS AND METHODS: Seventy-two consecutive patients with clinical early-stage melanoma underwent sentinel lymphadenectomy (SLND). Their SNs were serially sectioned and assessed for MAGE-3, MART-1, and tyrosinase mRNA expression by RT-PCR, in parallel with H&E staining and IHC, for melanoma metastases. MM expression in the SNs was correlated with H&E and IHC assay results, standard prognostic factors, and disease-free survival. RESULTS: In 17 patients with H&E- and/or IHC-positive SNs, 16 (94%) expressed two or more mRNA markers. Twenty (36%) of 55 patients with histopathologically negative SNs expressed two or more mRNA markers. By multivariate analysis, patients at increased risk of metastases to the SN had thicker lesions (P =.03), were 60 years of age or younger (P <.05), and/or were MM-positive (P <.001). Patients with histopathologically melanoma-free SNs who were MM-positive, compared with those who were positive for one or fewer mRNA markers, were at increased risk of recurrence (P =.02). Patients who were MM-positive with histopathologically proven metastases in the SN were at greatest risk of disease relapse (P =. 01). CONCLUSION: H&E staining and IHC underestimate the true incidence of melanoma metastases. MM expression in the SN more accurately reflects melanoma micrometastases and is also a more powerful predictor of disease relapse than are H&E staining and IHC alone.