Draining Lymph Node Basin Research Articles

A phase 2 study to determine the pathological (path) response to neoadjuvant nivolumab (nivo) and relatlimab (rela) in stage I to III resectable Merkel cell carcinoma (Neo-MCC).

TPS9613 Background: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine cancer of the skin with viral and sun related aetiologies, and an overall mortality rate twice that observed in cutaneous melanoma (33% vs 15%). The 5-year disease specific survival is 60% to 87% for those presenting with local disease, 39% to 62% for nodal disease and 11% to 20% for metastatic disease (1). Neoadjuvant therapy (NAT) is a powerful treatment platform to rapidly assess drug activity in resectable cancers. In melanoma, using International Neoadjuvant Melanoma Consortium (INMC) path response criteria (2), a major path response to immunotherapy (≤10% viable tumor) correlates with low risk of recurrence in resectable stage III disease (Menzies et al., 2021), and improved survival and EFS when immunotherapy is given neoadjuvantly as compared to adjuvant (adj) treatment (Patel et al., 2022). In a study of NAT anti-PD1 monotherapy with nivolumab, in patients (pts) with resectable IIA-IV MCC (N=36), 47.2% of pts achieved a complete path response (pCR) (Topalian et al., 2020). Other benefits of NAT include early insight into response, feedback to pts regarding their individual response and prognosis, ability to tailor subsequent management, and collection of translational specimens to explore mechanisms of response and resistance. The Neo-MCC trial will examine whether combination PD-1 blockade plus lymphocyte-activation 3 (LAG3) checkpoint inhibition will achieve a high rate of path response with manageable toxicity in pts with resectable stage I-III MCC. Methods: Pts with histologically confirmed resectable clinical stage I (≥ 10 mm), II or III Merkel cell carcinoma, are eligible (N=20). All pts undergo complete resection (RES) at wk 6 following NAT with 2 doses of nivo (480 mg, IV) plus rela (160 mg, IV) at wk 0 and 4. Standard of care sentinel lymph node biopsy will be completed as indicated. Pts with non-path response (>50% viable tumor) or partial path response (>10% - ≤50% viable tumor) at RES will receive adj radiotherapy (RT) to all disease sites, including the draining lymph node basin. Pts with pCR (0% viable tumor) or near-pCR response (≤10% viable tumor) will receive no further adj treatment. Pts with involved RES path margins will be considered for adj RT, following multidisciplinary team consultation to determine the role of further surgery. CT, and FDG PET/CT will be performed at baseline (BL), prior to RES to measure NAT response, and 6-monthly over a 10-year follow-up period. Tumor and fecal samples are collected at BL, RES, and recurrence. Blood samples are collected at BL, wk 4, RES, and recurrence. The primary endpoint is the rate of pCR at RES after NAT using INMC response criteria. Secondary endpoints include RFS, OS, safety/tolerability, surgical outcomes, QOL, and biomarker analyses. 1. Mistry, et al., 2022. 2. Tetzlaff et al., 2018. Clinical trial information: NCT06151236 .

In transit metastases in children, adolescents and young adults with localized rhabdomyosarcoma of the distal extremities: Analysis of the EpSSG RMS 2005 study

In-transit metastases (ITM) are defined as metastatic lymph nodes or deposits occurring between the primary tumor and proximal draining lymph node basin. In extremity rhabdomyosarcoma (RMS), they have rarely been reported. This study evaluates the frequency, staging and survival of patients with ITM in distal extremity RMS. MethodsPatients with extremity RMS distal to the elbow or knee, enrolled in the EpSSG RMS 2005 trial between 2005 and 2016 were eligible for this study. ResultsOne hundred and nine distal extremity RMS patients, with a median age of 6.2 years (range 0–21 years) were included. Thirty seven of 109 (34%) had lymph node metastases at diagnosis, 19 of them (51%) had ITM, especially in lower extremity RMS. 18F-FDG-PET/CT detected involved lymph nodes in 47% of patients. In patients not undergoing 18F-FDG-PET/CT lymph node involvement was detected in 22%. The 5-yr EFS of patients with ITM vs proximal lymph nodes vs combined proximal and ITM was 88.9% vs 21.4% vs 20%, respectively (p = 0.01) and 5-yr OS was 100% vs 25.2% vs 15%, respectively (p = 0.003). ConclusionOur study showed that in-transit metastases constituted more than 50% of all lymph node metastases in distal extremity RMS. 18F-FDG-PET/CT improved nodal staging by detecting more regional and in-transit metastases. Popliteal and epitrochlear nodes should be considered as true (distal) regional nodes, instead of in-transit metastases. Biopsy of these nodes is recommended especially in distal extremity RMS of the lower limb. Patients with proximal (axillary or inguinal) lymph node involvement have a worse prognosis.

Should Sentinel Lymph Node Biopsy Status Guide Adjuvant Radiation Therapy in Patients With Merkel Cell Carcinoma?

PurposeRadiation of the draining lymph node basin remains controversial for Merkel cell carcinoma, particularly in the era of sentinel lymph node biopsy (SLNB). Methods and MaterialsBased on a 20-year experience using SLNB-guided adjuvant radiation therapy (RT), we conducted a retrospective review of clinically node-negative patients testing 2 hypotheses: (1) whether nodal RT could be safely omitted in SLNB-negative Merkel cell carcinoma and (2) whether the excised primary site should always be radiated. Clinically node-positive patients were excluded. ResultsAmong 57 clinically node-negative patients who underwent SLNB and wide local excision (WLE), 42 (74%) had a negative SLNB, and 15 (26%) had a positive SLNB. At a median follow-up of 43 months (range, 5-182), SLNB-negative patients irradiated to the primary site had improved 4-year disease-specific survival (100% vs 65%, P = .008), local recurrence-free survival (100% vs 76%, P = .009), and distant recurrence-free survival (100% vs 75%, P = .008), but not overall survival (87.5% vs 57.7%, P = .164) compared with SLNB-positive patients receiving comprehensive RT. Among SLNB-negative patients treated with WLE only, 67% (6/9) had a disease relapse, half of which were local relapses (33%). ConclusionsIn this single-institution retrospective review, after negative SLNB and WLE, RT given only to the primary site provided 100% disease control without a need for nodal RT. Among SLNB-negative patients who had WLE, omission of postoperative primary-site RT was associated with 67% cancer relapse, of which half was local.

Effect and Safety of Radiation Therapy Boost to Extramesorectal Lymph Nodes in Rectal Cancer

PurposeIn rectal cancer, the presence of extramesorectal/lateral pelvic lymph node (LPN) is associated with higher risk of locoregional and distant recurrences. LPNs are not typically resected during a standard total mesorectal excision (TME) procedure, and the optimal management for these patients is controversial. We assessed the safety and efficacy of adding a radiation therapy boost to clinically positive LPN during neoadjuvant chemoradiation therapy for rectal cancer. Methods and MaterialsWe analyzed nonmetastatic, lymph node positive rectal adenocarcinoma patients treated with neoadjuvant chemoradiation therapy followed by TME between May 2011 and February 2018. Patients without LPN involvement received external beam radiation therapy (45 Gy in 25 fractions) to the primary tumor and regional draining lymph node basins followed by a boost (5.4 Gy in 3 fractions) to gross disease. Patients with clinically positive LPN that would not be removed during TME received an additional boost (up to a total dose between 54.0 and 59.4 Gy) to the involved LPNs. We compared locoregional control, overall survival, progression-free survival, and treatment-related toxicity between these 2 groups. ResultsFifty-three patients were included in this analysis with median follow-up of 30.6 months for the LPN– group (n = 41) and 19.9 months for the LPN+ group (n = 12). There was no difference in 3-year overall survival (90.04% vs 83.33%, P = .890) and progression-free survival (80.12% vs 80.21%, P = .529) between the 2 groups. We did not observe any LPN recurrences. There were no differences in rates of acute grade 3+ or chronic toxicities. ConclusionsDespite the well-documented negative prognostic effect of LPN metastasis, we observed promising outcomes for LPN+ patients treated with an additional radiation boost. Our results suggest that radiation therapy boost to clinically involved, unresected LPN is an effective treatment approach with limited toxicity. Additional studies are needed to optimize treatment strategies for this unique patient subset.

An 18-year Study of Malignant Melanoma in Childhood and Adolescence.

Background:Malignant melanoma is rare in childhood and adolescence. Diagnostic uncertainty and misdiagnosis often lead to delayed treatment.Methods:We evaluated children and adolescents under 20 years of age presenting with malignant melanoma at our institution over an 18-year period. Data were collected, analyzed, and interpreted, following which findings were compared with the existing literature.Results:Twenty-four patients were included in the study with mean follow-up of 61.8 months. Males comprised 54% of cases. On presentation, 33% of children had melanoma of s thickness 2–4 mm and 34% had stage III disease. Younger children presented with thicker melanomas, differing subtypes, and more advanced stage disease compared with older children. Extremities were the most common sites affected (42%). Dissection of the draining lymph node basins was undertaken in 38% of cases. Overall survival was 92%.Conclusions:Tumor subtype, biology, hormonal influence, and lymph node status are all important prognostic factors in malignant melanoma in childhood and adolescence. Compared with adults, children presenting with thicker melanomas and more advanced stage disease generally have more favorable outcomes and a better survival. Plastic surgeons, commonly encountering skin lesion in children, must maintain a high index of suspicion so that early excision and sentinel lymph node biopsy may be promptly offered to patients with melanoma.

\u2018DURVIT\u2019: a phase-I trial of single low-dose durvalumab (Medi4736) IntraTumourally injected in cervical cancer: safety, toxicity and effect on the primary tumour- and lymph node microenvironment

BackgroundTreatment with programmed cell death receptor (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors is a promising strategy to lift tumour-induced immune response suppression. However, the current systemic treatment often causes autoimmune side effects. In more than 50% of squamous cell cervical cancer, PD-L1 expression is detected. Moreover, we observed high and interrelated rates of PD-L1 positive macrophages and regulatory T cells in metastatic lymph nodes of cervical cancer patients. As cervical cancer in general initially metastasizes to regional lymph nodes, local administration of durvalumab (a PD-L1 checkpoint inhibitor) at an early stage will deliver these antibodies exactly where they are needed, facilitating immune protection. This may result in a clinical benefit while reducing undesirable side effects.MethodsDURVIT is a non-randomized, single-arm, open-label, phase I study. Three escalating dose levels of intratumourally (i.t.) injected durvalumab will be tested, i.e. 5, 10 and 20 mg (three patients per dose level, with an additional three at the highest tolerated dose). The primary endpoint of this phase-I study is safety. Immune monitoring will consist of flow cytometric, immunohistochemical and functional T cell reactivity testing. The first patient has been included in this trial in November 2017.DiscussionEvidence of safety and biological efficacy of this locally administered checkpoint blockade may expand adjuvant therapy options for cervical cancer patients. Early metastatic spread of cervical cancer cells may thus be controlled in the draining lymph node basin, and beyond, and hopefully delay or even prevent the onset of disease recurrence.Trial registrationNTR6119, 1-nov-2016.

Visual probing of rectal neoplasia: near-infrared interrogation of primary tumors and secondary lymph nodes.

Laparoscopic and endoscopic colorectal intervention and operations have their basis in real-time, image-based decision-making and step-by-step sequenced technical progress. The capacity to visualize accurately malignant disease wherever it may be including within the primary lesion and its draining lymph node basin as well as at potential sites of metastatic harbor (i.e. peritoneum, liver and lung) would allow more accurate surgery at the time of operation and enable personalized, stratified surgical intervention. In addition, such capacity could efficiently compress the diagnostic and therapeutic stages of a patient's progress from presentation, through work-up and onto appropriate treatment, important in this era of restricted resource and increased user demand. Near-infrared endolaparoscopic illumination enables broad spectral imaging of tissue in situ, most often, at present, in conjunction with the approved safe and low-cost fluorophore indocyanine green. While additional targeted agents are in development, here we detail how this developed and available technology may be used as a visual probe of neoplasia to inform surgeons regarding functional, tissue characterization through the direct observation of metabolic and metabolomic processes within the area under inspection perhaps helping in the distinction between invasive cancer and non-invasive dysplastic lesions. This understanding can inform and accelerate development of specific agents and techniques that can better advance surgical practice into the era of surgical data science and true precision surgery.

Regional Nodal Control for Head and Neck Alveolar Rhabdomyosarcoma

To assess clinical outcomes and patterns of failure, particularly regional nodal control, for pediatric patients treated with proton beam therapy (PBT) for head and neck alveolar rhabdomyosarcoma (HN-ARMS). Between 2006 and 2015, 14 patients with HN-ARMS were enrolled in a prospective registry protocol and treated with PBT at a single institution. Of the patients, 8 (57%) presented with localized disease and 6 (43%) with regional nodal metastases. All patients were treated with systemic therapy per accepted cooperativegroup regimens. All patients received PBT to the primary site and involved nodal disease with a median dose of 50.4Gy (relative biological effectiveness).Elective nodal irradiation was not delivered. The median follow-up period for surviving patients was 4.3years. The 5-year overall survival and disease-free survival rates for the cohort (N=14) were 45% and 25%, respectively. There were 10 relapses in the cohort: 7 regional nodal, 1 combination local and regional nodal, and 2 leptomeningeal. In 6 of 8 patients (75%) with no nodal disease at diagnosis, isolated regional nodal relapse developed. All nodal relapses occurred in first-echelon draining lymph node basins relative to the primary tumor site. Of 6 patients who presented with nodal metastases, 2 had regional nodal relapse; both of these nodal relapses occurred in the same nodal basin that was initially involved by disease but was not completely targeted as part of the primary treatment plan. High rates of regional nodal relapse are observed for HN-ARMS patients, including patients with no nodal disease at diagnosis. These data suggest that HN-ARMS patients may benefit from elective nodal irradiation to treat at-risk draining lymph node stations relative to the primary tumor site. We further recommend coverage of the entire nodal level for any sites of initial nodal disease at diagnosis, given the high risk of failure at these sites.

Prognostic Value of Multiple Draining Lymph Node Basins in Melanoma: A Matched-Pair Analysis Based on the John Wayne Cancer Institute Experience.

The prognostic significance of multiple draining basins is controversial in melanoma because analyses have not adequately controlled for standard prognostic variables. We hypothesized that an analysis based on prognostically matched pairs of patients with multiple versus single drainage basins would clarify any independent role of basin number. We identified patients in our 40-year prospective database, who underwent preoperative lymphoscintigraphy, intraoperative sentinel node biopsy and wide local excision for cutaneous melanoma. Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were compared in patients with multiple versus single drainage basins after matching by age, sex, Breslow depth, primary site, and stage at diagnosis. We identified 274 patients with multibasin drainage and 1,413 patients with single draining lymph node basins. Matching yielded 259 pairs (226 trunk, 27 head/neck, 6 extremity). Among matched pairs, multibasin drainage did not affect rates of lymph node metastasis (p = 0.84), OS (p = 0.23), DSS (p = 0.53), overall recurrence (p = 0.65), locoregional recurrence (p = 0.58), or distant recurrence (p = 1.0). Multivariable analysis linked higher T stage, ulceration, older age, and lymph node positivity to decreased DSS (p < 0.01) and DFS (p < 0.001). Number of drainage basins was not significant on univariable or multivariable analysis. This analysis, the first to match for standard prognostic factors, suggests that multiplebasin drainage as identified by lymphoscintigraphy has no independent biological or prognostic significance in primary cutaneous melanoma.

Histopathologic Evaluation of the Sentinel Lymph Node for Malignant Melanoma

Metastasis from malignant melanoma (MM) usually first presents in the draining lymph node basin and thus sentinel lymph node (SLN) biopsy is a staging tool used to predict risk of metastases and death in higher risk tumors and has become the standard of care. Differences in the processing and methods used in the histopathological examination of SLNs can affect the positivity rate for metastatic MM because isolated MM deposits may be small and variably distributed in the SLN. The examination of SLNs is not standardized. The authors surveyed institutions across the United States who process SLNs for MM to better characterize the current methods used and to suggest a standardized approach to improve the reliability of the SLN biopsy. A survey of 142 academic institutions in the United States regarding the methods used in the evaluation of the SLN biopsy for MM was conducted. Thirty-two institutions responded. Eighty-one percent of the institutions (26 of 32) had a protocol that they used for SLN examination. In regards to gross dissection, 28% of the responders (9 of 32) initially bivalve (cut the SLN in half), whereas 59% (19 of 32) use a bread loaf technique, cutting the SLN at even intervals without specifically commenting about orientation to the hilum. The number of levels initially cut from the SLN block varied from 1 to 8 levels per block. Thirty-nine percent of the respondents (12 of 31) routinely order immunohistochemistry before evaluation of the initial hematoxylin- and eosin-stained sections. Eighty percent of the respondents (24 of 30) report the maximum dimension of the metastatic tumor deposit. The response rate was low (22%), and most respondents did not indicate how many SLN accessions were performed at their institution each year. Histologic protocols for processing SLNs for MM vary among institutions. Different methods of handling SLNs result in varying sensitivities for detection of metastases. Data derived from these varied approaches to develop and determine prognostic and staging categories may be inconsistent. A standardized yet practical approach is needed to provide reliable information on which prognosis can be determined and therapeutic guidelines can be based. The hope is for dermatologists and those treating patients with MM to understand the intricacies and inconsistencies involved in performance and interpretation of this key staging tool.

The changing role of surgery in the current era of head and neck oncology

As in all fields of scientific endeavor, the nature and role of surgery for treatment of neoplastic disease in the head and neck has evolved since the publication of the first textbook on head and neck surgery by Levi Cooper Lane in 1896 [1]. After the discovery that ionizing radiation could destroy malignant tissue, this modality became a preferred treatment for head and neck cancer because it avoided the massive tissue ablation, infection and other morbidities associated with extirpation of head and neck tumors in the pre-antibiotic era. The initial promise of radiation treatment proved to be disappointing, and by the mid 20th century, ablative surgery with en bloc resection of tumors including wide margins of surrounding normal tissue and the draining lymph node basin could be performed with relative safety and became the preferred standard either as initial treatment or for treatment of irradiation failure [2]. The introduction of megavoltage radiotherapy units in the 1950s and subsequent continuous advances in the fields of radiotherapy technology, radiobiology and drug design led to increased use of irradiation and systemic therapy over time [3]. This paper was written by members of the International Head and Neck Scientific Group (www.IHNSG.com).

A low-risk tumour, at a high-risk site? Basal cell carcinoma of the nipple-areola complex

Funding sources: none. Conflicts of interest: none declared. Madam, A 42‐year‐old caucasian man presented with a lesion on the right nipple–areola complex (NAC), highly suspicious clinically of recurrent basal cell carcinoma (BCC). His past medical history was significant for Gorlin syndrome and a renal transplant for end‐stage renal failure secondary to glomerulonephritis. His regular medications comprised ciclosporin and prednisolone. In 2009 a biopsy‐proven primarily superficial BCC affecting the right nipple and areola region was treated, at that time successfully, with two cycles of photodynamic therapy. In July 2011, however, a 33 × 21 mm poorly defined plaque affecting the right upper outer quadrant of the NAC was noted (Fig. 1). Repeat biopsies confirmed this to be a multifocal BCC with a mixed superficial and nodular growth pattern. Clinical examination revealed no puckering or tethering of the NAC itself and no lymphadenopathy in the draining lymph node basin. In view of the ill‐defined clinical margins, the recurrent nature of the tumour and the need for tissue preservation in this cosmetically sensitive site, Mohs micrographic surgery (MMS) was performed. Tumour‐free margins were achieved following one stage and two sections and the resulting 36 × 23 mm defect (Fig. 2) closed primarily with an excellent cosmetic outcome at review 3 months later.

Evaluation of mobile gamma camera imaging in sentinel lymph node biopsy for melanoma independent of pre-operative lymphscintigraphy.

e19062 Background: Sentinel lymph node biopsy (SLNB) is the standard method for staging cutaneous melanoma and involves identifying the first node(s) draining a tumor, by detecting an intradermally-injected radioactive colloid tracer. Intra-operatively the sentinel node(s) are identified with a hand-held gamma probe. Pre-operative lymphoscintigraphy is obtained to identify draining lymph node basins, but requires coordinating schedules between nuclear medicine and the operating room. A pilot study utilizing Mobile Gamma Camera (MGC) devices in conjunction with conventional lymphoscintigraphy for intraoperative sentinel node localization provided clinical benefit in 20% of patients. However, utilizing MGC devices to localize lymph node basins at the time of surgery independent of conventional lymphoscintigraphy with a fixed gamma camera (FGC) has not been adequately studied. Here, we present the results of a clinical trial utilizing MGC devices to localize lymph node basins in a manner blinded to the FGC images in order to compare the modalities directly. Methods: In 2011-12 18 patients underwent Tc99 sulfur colloid lymphoscintigraphy, and MGC survey immediately pre-operative by the study surgeon. The study surgeon established an operative plan using the MGC survey, while blinded to lymphoscintigraphy results. SLNB was then performed with use of a gamma probe and intra-operative MGC imaging. Results: 22 lymph node basins were detected in 18 imaged patients by lymphoscintigraphy. All of these basins were identified by the study surgeon using the MGC device in the pre-operative setting prior to un-blinding. In every case the operative plan established based on pre-operative MGC imaging was confirmed by the FGC images. In two cases, additional information from the MGC images aided surgical decision-making. 5 of 22 lymph node basins were positive for metastasis. All of these basins were identified by pre-operative MGC imaging, and all individual positive nodes were identified by intra-operative MGC imaging. Conclusions: Pre-operative MGC imaging in sentinel lymph node biopsy can provide comparable information for operative planning, compared to standard FGC imaging.

Patients With Merkel Cell Carcinoma Tumors ≤ 1.0 cm in Diameter Are Unlikely to Harbor Regional Lymph Node Metastasis

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine cutaneous malignancy. Current recommendations include offering regional lymph node evaluation by either sentinel lymph node biopsy (SLNB) or complete lymph node dissection (CLND) to all patients with MCC; however, we hypothesized a cohort of low-risk patients may exist for whom regional nodal metastasis would be unlikely. A retrospective review of the Department of Veterans Affairs national health care database was performed. Patients undergoing resection of primary MCC were identified; and demographic, medical, and social history; tumor characteristics; nodal status; and recurrence events were recorded. Between 1995 and 2006, 346 patients were diagnosed with MCC. Of these, 213 underwent resection of the primary lesion and evaluation of the draining lymph node basin. Fifty-four patients (25%) had tumors < or = 1.0 cm in diameter. Average tumor diameter was 0.7 cm, and 63% were located on the head or neck. Only two patients (4%) with tumors < or = 1.0 cm had regional lymph node metastasis, compared with 51 (24%) of 213 patients with tumors more than 1.0 cm (P < .0001). Both patients had clinically evident nodal disease at presentation and underwent CLND. Both have remained recurrence-free for 40 months. Thirteen (25%) of 51 patients with nodal metastasis and tumors more than 1 cm had occult nodal metastasis. In this series, patients with MCC < or = 1.0 cm were unlikely to have regional lymph node metastasis, suggesting that regional nodal evaluation may reasonably be avoided in these patients. However, these data support SLNB for MCC more than 1 cm in diameter.

The need for a revised staging system of metastatic (M) colorectal cancer (CRC): Evidence from a national perspective on survival following surgically treated (HPX) liver metastases

4099 Background: AJCC V.6 (2002) places all patients with MCRC beyond the lymph node basin of the primary tumor in a homogenous Stage 4. Patients with inoperable hepatic MCRC can be made operable with curative intent with chemotherapy yet remaining in Stage 4. Via the linkage of routine health datasets across England this population-based study sought to determine the impact of HPX for MCRC on stage-matched survival at initial presentation. Methods: All patients between 1998–2001 undergoing surgery for CRC in England were identified via the national-linked cancer registry HES dataset. All care episodes in the 3 years following initial colorectal surgery were examined to determine the frequency of subsequent HPX. Kaplan-Meier curves and log- rank tests were used to examine 5-year survival following HPX for MCRC compared to all Stage 3 and Stage 4 at presentation. Survival was calculated from the date of resection of each patient's primary colorectal tumor. Results: 68,307 individuals were identified as undergoing surgery for primary CRC over the study period. 20,298 were Stage 3 at presentation. 1,483 (2.2%) subsequently underwent HPX &lt;3 years of their colorectal operation. 55 patients died within 30 days of HPX (mortality rate: 3.7%). Crude 5-year survival of patients who underwent HPX was 41.6% (95%CI 39.0–44.1%) from time of initial colectomy. This survival rate was significantly better than that for both Stage 3 (38.6% (95%CI 37.9%-39.2%, P&lt;0.01) and 4 (6.1% 95%CI 5.3–6.9%, P&lt;0.01) overall. Conclusions: 5-year survival following HPX for MCRC is better than that seen overall for all Stage 3 patients (with MCRC confined to the regional draining lymph node basin) following initial colectomy. Our data support the hypothesis that all MCRC that is potentially resectable with curative intent should be stratified within Stage 3, and Stage 4 should only contain those MCRC patients for whom surgery is not an option. If further evidence emerges to support this theory then a revision of the current staging system will be required. [Table: see text]

Prediction of non-sentinel node status and outcome in sentinel node-positive melanoma patients

Sentinel lymph node (SLN) -positive melanoma patients are usually recommended completion lymph node dissection (CLND) with the aim to provide regional disease control and improve survival. Nevertheless, only 20% these patients have additional metastases in non-sentinel lymph nodes (NSLN), indicating that CLND may be unnecessary in the majority of patients. In this retrospective study, we (i) sought to identify clinico-pathological features predicting NSLN status, as well as disease-free (DFS) and -specific (DSS) survival and (ii) evaluated the applicability of previously published algorithms, which were able to define a group of patients at zero-risk for NSLN-metastasis. This analysis included 504 consecutive melanoma patients stage I and II who underwent successful SLN-biopsy (SLNB) at our institute between 1998 and 2005. Metastatic SLN were re-evaluated for tumor burden and categorized according to two different micro-anatomic classifications and the S/U-score (Size of the sentinel node metastasis > 2 mm/Ulceration of the primary melanoma) was assessed. DFS and DSS were calculated for all analyses. Out of 504 melanoma patients stage I or II, 85 (17%) were SLN-positive and 18 of 85 (21%) were found with positive NSLN in the CLND specimen. Median follow-up was 31 months. Neither primary tumor characteristics (age, gender, Clark level, Breslow thickness, ulceration of the primary melanoma, site and histological subtype of the primary melanoma), nor features of the sentinel node tumor (number and site of draining lymph node basins, number of positive sentinel nodes and size of sentinel node tumor (< 2 mm vs. > or = 2 mm) were able to predict additional positive lymph nodes in the CLND specimen. Likewise the implementation of published algorithms was not able to identify patients at negligible risk for harboring NSLN metastases. Upon univariate analysis, disease-free survival in SLN-positive patients was correlated with Breslow thickness, sentinel node tumor size > 2 mm and S/U score. In respect to disease-specific survival the significant prognostic parameters were Breslow thickness, ulceration, sentinel node tumor size > 2 mm and the S/U score. After a median follow-up of 31 months recurrence rates (37% vs. 78%, p=0.02) and death from disease (24% vs. 50%, p<0.01) were significantly different in patients with SLN-metastasis only as compared to patients with NSLN-metastasis. NSLN status cannot be predicted in this data analysis by using clinico-pathological characteristics. Therefore, CLND is recommended for all patients after positive SLNB pending the results of the second Multicenter Selective Lymphadenectomy Trial.

Immediate dynamic lymphoscintigraphy delivers no additional value to lymphoscintigraphy 3 hr after tracer injection in sentinel lymph node biopsy in breast cancer patients

Immediate dynamic imaging enables accurate definition of sentinel lymph nodes, whereas imaging 3 hr after tracer injection may lead to overestimation of the number of sentinel lymph nodes. A study was performed to define the value of lymphoscintigraphy immediately versus 3 hr after tracer injection in sentinel lymph node biopsy for breast cancer management. In 165 sentinel lymph node biopsy procedures preoperative immediate and 3 hr post-injection lymphoscintigraphy was performed after intraparenchymal tracer administration. Lymph node visualization occurred in 63 immediate procedures (38%) versus in 163 procedures 3 hr post-injection (99%). In 17 procedures (10%) in which immediate lymphoscintigraphy had visualized sentinel lymph nodes, additional nodes had been seen on 3 hr post-injection lymphoscintigraphy. In eight of these procedures (5%) all nodes were detected in the same draining lymph node basin. Non-axillary sentinel lymph nodes were identified by preoperative lymphoscintigraphy in 28 procedures (17%) and improved staging in three patients (5%). The only impact of immediate lymphoscintigraphy was the possible omission of removal of 1-2 sec-echelon nodes per patient in 5% of patients. We consider this yield too low to continue immediate lymphoscintigraphy in breast cancer patients.

Accuracy of lymphatic mapping and sentinel lymph node biopsy after previous wide local excision in patients with primary melanoma

Sentinel lymph node (SLN) status is the most important prognostic factor with respect to the survival of patients with primary cutaneous melanoma. However, lymphatic mapping and SLN biopsies (LM/SLNBs) performed in patients who have had a wide local excision (WLE) may not accurately reflect the pathologic status of the draining lymph node basins. The purpose of this study was to assess the feasibility and accuracy of LM/SLNB in patients who have had a previous WLE. A single-institution database was examined to identify patients who had a WLE before LM/SLNB and patients who had a concomitant LM/SLNB. Primary clinicopathologic features (age, tumor thickness, and ulceration), SLN identification rate, SLN pathologic status, and the incidence and sites of recurrences were compared between patients with and without prior WLE. Of the 1395 patients identified, 104 had WLE before LM/SLNB. The mean preoperative WLE radial margin was 1.4 cm (median, 1.0 cm). LM/SLNB was successful in 103 of 104 (99%) patients. Age, tumor thickness, incidence of ulceration, and incidence of SLN positivity in the group with prior WLE were similar to those of the cohort of patients who had concomitant LM/SLNB and WLE (n = 1291). In 97 (93%) of the 104 prior-WLE patients, the surgical defects were closed by either primary closure or skin graft; 7 patients (7%) had rotational flaps. The median follow-up of these 104 patients was 51 months. Among the prior-WLE group, 19 patients (18%) had a positive SLNB; of these 19 patients, 4 (21%) had recurrences (3 distant failures and 1 local and distant failure). There were no lymph node recurrences-in a mapped or unmapped basin-in these 104 patients with a negative or positive SLNB. SLNs can be successfully identified and accurately reflect the status of the regional lymph node basin in carefully selected melanoma patients with a previous WLE. Prior WLE does not appear to adversely impact the ability to detect lymphatic metastases, although the utility of LM/SLNB in patients who have undergone extensive reconstruction of the primary excision site remains to be defined. Because more extensive surgery may be required to accomplish accurate lymph node staging in patients who have undergone prior WLE-including the possible removal of SLNs from additional lymph node basins and an additional surgical procedure-to minimize morbidity and cost, concomitant WLE and LM/SLNB is strongly preferred whenever possible.

A Preliminary Study of the Draining Lymph Node Basin in Advanced Lower Rectal Cancer Using a Radioactive Tracer

This study was designed to examine the draining lymph node basin at highest risk of metastasis in lower rectal cancer using 99 mTc-tin colloid. In 43 patients, the area with highest hot nodes density was defined as the draining lymph node basin using a gamma probe. Metastatic states of all removed lymph nodes were examined histologically. A total of 203 hot nodes were identified in 39 patients (91 percent) with a mean of 5.2 nodes. The number of removed lymph nodes was 808 nodes: 670 nodes in the mesorectum, and 138 nodes in the pelvis. In 21 patients, the metastatic states of 119 nodes were investigated histologically. From the distribution of the identified hot nodes, the draining lymph node basins were classified into two patterns: lateral type (n = 17), and mesorectal type (n = 22). Only 20 (17 percent) of 119 positive nodes were identified as hot node. Tumor cells that occupied the lymph node diffusely or massively probably interfered with the exact diagnosis of metastasis. Lymph node metastasis in the pelvis was observed in 5 patients (13 percent). One false negative was of the mesorectal type with diffuse metastases in the para-aortic lymph nodes. The remaining four patients were of the lateral type and all positive lymph nodes, including positive nonhot nodes, were located within the draining lymph node basin. Consequently, in 20 (95.2 percent) of 21 patients with lymph node metastasis, all positive lymph nodes were located within the draining lymph node basin of the tumor. Two types of the draining lymph node basin of advanced lower rectal cancer were identified using this method. The concordance between lymph node metastases and the draining lymph node basin is good.

Diagnosis of lymphoma in the draining lymph node basin at the time of in-transit metastasis of cutaneous melanoma

The association between cutaneous melanoma and non-Hodgkin's lymphoma (NHL) has been described. Herein we describe two cases in which lymphoma was detected in the draining lymph node basin at the time of the finding of in-transit metastasis of cutaneous melanoma. In both of these cases, sentinel lymph node biopsy at the time of the excision of the primary melanoma showed no evidence of metastatic melanoma or lymphoma. The temporal and spatial correlation of melanoma and NHL in these two cases suggests the possibility of a local failure in immune surveillance.