Occult Regional Node Metastases Research Articles

PET-CT limitations in early stage non-small cell lung cancer: to whom more aggressive approach in radiotherapy and surgery should be directed?

This editorial comments on the study by Paravati et al., which reported on the incidence of occult regional lymph node metastases in PET-CT T1T2N0 non-small cell lung cancer (NSCLC) patients. A central location and the size of the tumor were shown to be the strongest predictors of the risk of occult nodal disease. Authors comment that in view of limitations of modern imaging, as well as the reported negative predictive value (NPV) of invasive staging methods, the choice of therapeutic options as the extent of surgery (lobectomy or sublobar resection) or radiotherapy [stereotactic body radiation therapy (SBRT) or conformal radiotherapy (RT) with some forms of elective nodal irradiation (ENI)] should consider tumor's characteristics and not be based only on imaging and invasive staging modalities.

Lack of supportive evidence for the use of immunohistochemical staining to identify occult regional lymph node metastases in primary lung cancer

Immunohistochemical (IHC) staining for the identification of nodal occult metastases (OM), not detected by routine histological examination, has been proposed for improved staging, prognostication and decision of adjuvant treatment in surgically treated primary lung cancer. In a prospective study, we analysed 178 cases of primary lung cancer stage I-III (N0-N1) for OM by immunostaining lymph node tissue using a broad-spectrum anti-cytokeratin antibody. OM were found in 7 (4 %) of the 178 cases. Using Kaplan-Meier analysis, overall survival was not significantly different between cases with stage I and cases upstaged to stage II because of OM (n = 3), or between cases with stage II and cases upstaged to stage III (n = 4). Likewise, the presence of OM was not significantly correlated with overall survival in univariable or multivariable Cox proportional hazards regression models, also when disregarding OM <0.2 mm in size. Given the low frequency of OM and lack of significant impact on survival in our study, the justification for including IHC staining of lymph nodes in lung cancer in clinical practise does not appear convincing. Moreover, we report several potential pitfalls in the use of broad-spectrum cytokeratin IHC staining for OM detection, for example staining of intra-nodal mesothelial cells.

Sentinel node biopsy in soft tissue sarcoma subtypes with a high propensity for regional lymphatic spread—results of a large prospective trial

BackgroundThe role of sentinel lymph node biopsy (SLNB) in soft tissue sarcoma patients has yet to be determined. We sought to evaluate the role of SLNB in the treatment of patients with clear cell sarcoma (CCS), synovial sarcoma (SS), epithelioid sarcoma (ES) and rhabdomyosarcoma (RMS). Patients and methodsSixty-two consecutive patients without history of regional lymphatic spread or evidence of distant metastases underwent SLNB. ResultsPositive sentinel nodes were identified in 2 out of 42 patients with SS and in 6 out of 12 patients with CCS. Only two CCS patients had further metastatic nodes in regional dissection. Both of these patients, along with another CCS patient, developed distant metastases and ultimately died of disease. The remaining three CCS patients are disease-free in follow-up. One patient with SS and another with ES developed regional lymph node metastases following a negative SLNB, while a further patient with RMS developed distant metastases followed by a local recurrence with regional metastases shortly after. ConclusionsSLNB is an important diagnostic tool for patients with CCS, who appear to have a high rate of clinically occult regional lymph node metastases at diagnosis. For SS patients, SLNB appears to be of very little relevance.

Carbon coated superparamagnetic iron oxide nanoparticles for sentinel lymph nodes mapping.

Intra-operative lymphatic mapping and sentinel lymph-adenectomy (LM/SL) maps the lymphatic path from the primary tumor to the regional nodes and permits selective excision of the first sentinel lymph nodes. It is a well established technique to detect occult regional node metastases for melanoma patients and breast cancer patients. In continuing attempts to improve accuracy, most surgeons now combine a dye (such as carbon particles) and radiopharmaceuticals when performing LM/SL. We developed a proto-type of carbon coated superparamagnetic iron oxide nanoparticles (SPIO@C) for sentinel lymph nodes mapping. Compared with combining carbon particles and radiopharmaceuticals for performing LM/SL, there are a number of advantages with our approach: I. SPIO is an MRI contrast agent, thus pre-operative MRI may be used for LM/SL instead of gamma camera. There is no radiation associated with MRI, and MRI offers good tissue contrast and detailed cross-sectional images. II. There will be only needed one injection of SPIO@C nanoparticles, instead of administrating two successive injections of radiopharmaceuticals and carbon particles. III. During the operation, an intra-operative MRI scanner can be used, or more conveniently by a simple magnetometer.

How Should We View the Results of the Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1)?

Prior to the release of the initial findings of the Multicenter Selective Lymphadenectomy Trial-1 (MSLT-1), SLN biopsy had already been generally embraced by the worldwide surgical community as a valuable staging tool and as a minimally invasive way to accurately identify patients with clinically occult regional lymph node metastases. The application of regional lymph node dissection only for patients with positive SLNs–termed “selective lymphadenectomy”–effectively minimizes the development of clinical nodal disease and spares node-negative patients the morbidity of a formal lymph node dissection. This management strategy has been promoted as a rational alternative to the two prior popularized approaches of elective lymph node dissection (ELND) or nodal observation. At the same time, a relatively vocal minority argued that a survival advantage from SLN biopsy should be demonstrated before the routine use of this procedure was endorsed.

Completion Lymphadenectomy for Melanoma Patients With a Positive Sentinel Node Biopsy Remains Standard of Care

In many parts of the world, sentinel node biopsy (SNB) for high-risk primary cutaneous melanoma (‡1 mm in thickness) is now considered reasonable care, particularly since the initial results of the Multicenter Selective Lymphadenectomy Trial (MSLT) were presented. 1 This study set out to resolve the issue of whether SNB could reliably and accurately identify the 20% of melanoma patients with occult regional lymph node metastases who might benefit from a completion lymph node dissection (CLND). In summary, no survival difference was found between patients randomized to SNB (with completion lymphadenectomy if positive) and those randomized to standard care with observation and lymphadenectomy if a regional recurrence occurred. However, and particularly germane to the study presented by Wong et al. 2 in this issue of the Journal, patients with a positive SNB who underwent an immediate CLND had significantly superior survival compared with patients randomized to the control arm who underwent lymphadenectomy after symptomatic presentation (5-year survival rates were 71% vs. 55%; P = .0033). The implications of this observation are clear; resection of low-volume micrometastatic disease early in the course of the disease is superior to resection of symptomatic later-stage higher-volume disease. Because a fundamental aim of the MSLT was to select the subgroup of patients likely to benefit from lymphadenectomy, CLNDwas mandated in the

Fluorodeoxyglucose Positron Emission Tomography for Melanoma Staging: Refining the Indications

Melanoma patients with advanced disease are often considered for major therapeutic surgical interventions. Accurate identification of all sites of metastatic disease is critical, because only patients rendered completely free of disease are likely to experience disease-free intervals or a potential survival benefit from surgery. Metabolic imaging with fluorine 18–labeled deoxyglucose (FDG)-positron emission tomography (PET) has recently become more widely applied in a variety of human malignancies. Several reports show FDG-PET to be a more sensitive indicator of metastatic melanoma than conventional diagnostic imaging modalities, particularly in patients with recurrent disease. However, various design shortcomings in early reports may have overestimated the utility of PET. Recent studies focusing on specific clinical scenarios are providing information to develop guidelines for the effective use of PET in patients with melanoma. In this issue of Annals of Surgical Oncology, Brady et al. provide a thoughtful report of their investigations of the clinical utility of preoperative PET imaging in patients planned for surgery for high-risk or recurrent/metastatic melanoma. Their work provides further evidence that PET has a role in management of the complex advanced melanoma patient. Although this study showed FDG-PET to be more sensitive than conventional imaging for detection of metastatic disease, the combination of PET and conventional imaging had a greater effect on clinical decision making than either modality alone. The authors showed that the addition of PET to computed tomographic (CT) imaging affected clinical decision making in one third of patients. Collectively, this and other studies show that properly selected patients with metastatic/recurrent melanoma may benefit from adjunctive PET imaging. Should FDG-PET imaging be obtained in all melanoma patients? The collective literature clearly does not support this practice. Prospective studies of preoperative FDG-PET imaging in stage I and II melanoma patients do not show a significant clinical effect. FDG-PET imaging is very unlikely to upstage early-stage melanoma patients already staged by conventional staging protocols that include sentinel node biopsy. Our group found that PET was only 21% sensitive for identification of occult regional lymph node metastases compared with sentinel node biopsy. Preoperative FDG-PET was not useful in predicting the histology of the residual lymph node basin after a positive sentinel node. Most importantly, FDG-PET rarely predicts the presence of occult distant metastases in this population. Increased FDG uptake at a site of possible distant metastatic disease was 10 times more likely to be false positive than true positive. Despite increasing use of FDG-PET in melanoma, it is important to point out that FDG-PET is not generally considered to be the single most sensitive Received December 2, 2005; accepted December 20, 2005; published online February 24, 2006. Address correspondence and reprint requests to: Jeffrey D. Wagner, MD, Wagner and Associates Plastic and Reconstructive Surgery Consultants, Suite 570, 8040 Clearvista Parkway, Indianapolis, IN 46256; E-mail: jdwagner@insightbb.com.

The Risk of In-Transit Melanoma Metastasis Depends on Tumor Biology and Not the Surgical Approach to Regional Lymph Nodes

Although the majority of patients newly diagnosed with cutaneous melanoma present with clinically negative regional nodal basins, many of these patients harbor occult regional lymph node metastases. Historically, the initial treatment strategy for patients with clinically negative regional lymph nodes has been controversial. Treatments have included elective dissection, the goal of which was improved survival, and observation followed by dissection when clinical relapse developed. A more rational selective approach, involving lymphatic mapping and sentinel lymph node biopsy (SLNB), has now been widely adopted. SLNB is a minimally invasive technique for identifying the approximately 20% of patients who harbor occult metastatic disease and who may therefore benefit from comple

Sentinel lymph node biopsy in the management of patients with primary cutaneous melanoma: review of a large single-institutional experience with an emphasis on recurrence.

To analyze the authors' experience with sentinel lymph node biopsy (SLNB) and the subsequent incidence and pattern of recurrence in patients with positive and negative nodes. Lymphatic mapping with SLNB has become widely accepted in the management of patients with melanoma who are at risk for occult regional lymph node metastases. Because this procedure is relatively new, the pattern of recurrence after SLNB is not yet clear. All patients with primary cutaneous melanoma who underwent SLNB from 1991 through 1998 were identified from a prospective single-institution melanoma database. Three hundred fifty-seven consecutive patients with localized primary cutaneous melanoma who underwent SLNB were identified. The sentinel node was identified in 332 patients (93%) and was positive in 56 (17%). Fourteen percent of patients had developed a recurrence at a median follow-up of 24 months. The median time to recurrence was 13 months. The 3-year relapse-free survival rates for patients with positive and negative nodes were 56% and 75%, respectively. SLN status was the most important predictor of disease recurrence. The site of first recurrence in patients with negative and positive nodes was more commonly locoregional than distant. Reexamination of the SLN in 11 patients with negative nodes with initial nodal and in-transit recurrence showed evidence of metastases in 7 (64%). Patients with positive sentinel nodes have a significantly increased risk for recurrence. The early pattern of first recurrence for patients with negative and positive results is characterized by a preponderance of locoregional sites, similar to that reported in previous series of elective lymph node dissection. These data underscore the need for careful pathologic analysis of the SLN as well as a careful, directed locoregional physical examination in the follow-up of these patients.

Molecular staging of prostatic cancer with RT-PCR assay for PSA in peripheral blood and lymph nodes. Comparison with standard histological staging and immunohistochemical assessment of occult regional lymph node metastases.

Molecular staging of prostatic cancer with RT-PCR assay for PSA in peripheral blood and lymph nodes. Comparison with standard histological staging and immunohistochemical assessment of occult regional lymph node metastases

The immunohistochemical assessment of occult regional lymph node metastases in patients with T3pN0 M0 prostate cancer before definitive radiotherapy

The immunohistochemical assessment of occult regional lymph node metastases in patients with T3pN0 M0 prostate cancer before definitive radiotherapy

The immunohistochemical assessment of occult regional lymph node metastases in patients with T3pN0M0 prostate cancer before definitive radiotherapy.

To detect occult regional lymph node metastases in patients with T3pN0M0 prostate cancer not recognized by routine haematoxylin and eosin staining, and to evaluate the clinical relevance of this finding. Formalin-fixed and paraffin-embedded pelvic lymph nodes (1118) from 92 patients were evaluated by immunohistochemistry using antibodies for prostate specific antigen (PSA) and pancytokeratin (AE1/AE3). Of the tumours, 14% were well, 69% moderately and 17% poorly differentiated. The extent of tumour was categorized as T3pN0M0 in all patients, who were referred for definitive radiotherapy after pelvic staging lymphadenectomy. The median (range) serum PSA value before treatment was 18.5 (0.4-342) microg/L. After radiotherapy, the patients were followed by assessing biochemical progression, pelvic recurrence and/or development of distant metastases. The median (range) observation time for all patients was 61 (16-136) months. Occult lymph node metastases were detected in four (4.4%) of the 92 patients. Patients with or without occult metastases had similar serum PSA levels and histological grades. None of the four patients with occult metastases progressed, compared with 37 of the 88 (42%) with no such metastases. Using immunohistochemistry the detection rate of occult lymph node metastases in patients with T3pN0M0 prostate cancer is low. The occurrence of such metastases is probably unrelated to the serum PSA value before treatment. The short-term outcome of patients subsequently treated with definitive radiotherapy does not seem to be associated with the finding of occult lymph node metastases, but long-term follow-up is needed. So far, the results do not justify the search for occult lymph node metastases as a routine procedure in these patients

Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial

The use of elective regional node dissection in patients with cutaneous melanoma without any clinical evidence of metastatic spread is still debated. Our aim was to evaluate the efficacy of immediate node dissection in patients with melanoma of the trunk and without clinical evidence of regional node and distant metastases. An international multicentre randomised trial was carried out by the WHO Melanoma Programme from 1982 to 1989. The trial included only patients with a trunk melanoma 1.5 mm or more in thickness. After wide excision of primary melanoma, patients were randomised to either immediate regional node dissection or a regional node dissection delayed until appearance of regional-node metastases. Of the 252 patients entered, 240 (95%) were eligible and evaluable for analysis. 122 of these were randomised to immediate node dissection. 5-year survival observed in patients who had delayed node dissection was 51.3% (95% CI 41.7-60.1) compared with 61.7% (52.0-70.1) of patients who had immediate node dissection (p=0.09). 5-year survival rate in patients with occult regional node metastases was 48.2% (28.0-65.8) and 26.6% (13.4-41.8, p=0.04) in patients in whom the regional node dissection was delayed until the time of appearance of regional node metastases. Multivariate analysis showed that routine use of immediate node dissection had no impact on survival (hazard ratio 0.72, 95% CI 0.5-1.02), whilst the status of regional nodes affected survival significantly (p=0.007). The patients with regional nodes that became clinically and histologically positive during follow-up had the poorest prognosis. Node dissection offers increased survival in patients with node metastases only. Sentinel node biopsy may become a tool to identify patients with occult node metastases, who could then undergo node dissection.