Delayed Lymph Node Dissection Research Articles

Comparison of Early Inguinal Lymph Node Dissection and Neoadjuvant Chemotherapy in Penile Cancer Patient with Bulky Nodal Metastasis: A Cohort Study.

Penile cancer is a rare malignancy, where extranodal extension in inguinal or pelvic lymph nodes is associated with decreased 5-year cancer-survival rate in this study, we try to assess survival and quality of life in a penile cancer patient with bulky lymph node. We retrospectively reviewed data from penile cancer patients with bulky lymph nodes who underwent treatment between July 2016 and July 2021 at tertiary referral hospital care. The inclusion criteria (age >18 yr, histologically proven penile cancer, and completion of last treatment 6 months prior to this study) yielded a cohort of 20 eligible penile cancer patients with bulky lymph nodes (> 4 cm/bilateral mobile/unilateral fixed). Only patients who had completed therapy at least 6 months prior to the study were included. After obtaining consent, they were asked to complete the EORTC QLQ-C30 questionnaire to evaluate the patient's quality of life. Out of 20 patients, 5 patients underwent direct ILND and 15 patients underwent chemotherapy. Median follow-up after primary diagnosis was 114+32 months in patients with early ILND and 52+11 months in patients who underwent delayed lymph node dissection. Out of 5 patients who underwent early ILND, all of them survived during follow-up, and achieved cancer-free status without residual tumor and with excellent functional outcomes (Karnofsky 90). There was no significant difference in social function (p-value = 0.551), physical function (p-value = 0.272), role function (p-value = 0.546), emotional function (p-value = 0.551), cognitive function (p-value = 0.453), and global health status (p-value = 0.893) between patient which treated with early ILND and Neoadjuvant Chemotherapy. However, patients who underwent early ILND showed a relatively better clinical outcome. Early ILND followed by adjuvant chemotherapy for penile cancer with palpable lymph nodes is more favourable than neoadjuvant TIP chemotherapy.

Validation of predictors for lymph node status in penile cancer: Results from a population-based cohort.

The ability to predict lymph node (LN) status is essential in the management of men with localized squamous cell carcinoma (SCC) of the penis. There has been limited external validation of available risk stratification tools, particularly in routine clinical care. The objective of this study was to evaluate the predictive variables of LN metastases within a large population-based cohort of patients. In this population-based cohort study, surgical pathology reports were linked to the population-based Ontario Cancer Registry to identify all patients who were diagnosed with penile cancer in Ontario, Canada. Multivariable analyses were performed to evaluate predictive variables for LN involvement. Three contemporary risk stratification schemes used to predict LN status were analyzed by logistic regression. The study included 380 localized penile SCC cases treated between 2000 and 2010. Sixty-three (17%) had pathologically confirmed LN metastases. Among these, 35 (56%) were diagnosed within three months of the initial penile SCC diagnosis and these patients had a worse five-year disease-specific survival (43%; 95% confidence interval [CI] 26-64) compared to patients who were diagnosed at a delayed LN dissection. On multivariable analysis, age (odds ratio [OR] 0.68; 95% CI 0.52-0.88), pathological stage (≥pT1b; OR 3.32; 95% CI 1.38-8.01), and tumour grade (Grade 2 OR 2.98; 95% CI 1.26-7.62; Grade 3 OR 3.97; 95% CI 1.32-11.9) were associated with an increased risk of LN metastases. Candidate risk stratification schemes demonstrated moderate to good property, with C-statistics ranging from 0.662-0.747. Using a population-based cohort of penile cancer patients with a relatively low proportion of patients with pathologically confirmed LN involvement, we confirm and externally validate the importance of age, stage, and grade of the primary tumour in predicting nodal status.

Is there a relation between type of primary melanoma treatment and the development of intralymphatic metastasis? A review of the literature.

Intralymphatic metastases (ILM) originate from tumor cell emboli entrapped in dermal lymphatics between primary tumor and regional lymph node basin. Because of this origin, sentinel lymph node biopsy (SLNB) might increase ILM by restricting lymph flow. Pubmed, Embase, Cochrane and Medline were searched for articles on ILM between 1980 and September 2014. ILM Incidences were calculated after wide local excision (WLE), excision with elective lymph node dissection (ELND) or therapeutic lymph node dissection (TLND), WLE with SLNB with or without completion lymph node dissection (CLND) and delayed lymph node dissection (DLND) for patients developing nodal metastasis during follow-up. In 36 studies, 14,729 patients underwent WLE, 1682 patients WLE/ELND, 362 patients WLE/DLND and 11,201 patients WLE/SLNB. On meta-analysis, ILM occurrence was 3.4% (95% CI 2.8-4.2%). ILM occurred most frequently in the WLE/DLND group (5.5%, 95% CI 3.5-8.7%), followed by WLE/ELND (4.7%, 95% CI 3.1-7.0%), WLE/SLNB (4.5%, 95% CI 3.5-5.7%) and WLE alone (1.9%, 95% CI 1.4-2.7%). 1330 SLNB+ patients were identified and 5783 SLNB- patients. For these groups, on meta-analysis, ILM recurrence was 13.2% (95% CI 10.8-16.2%) and 3.4% (95% CI 2.5-4.5%), respectively (p=0.01). In this review SLNB is associated with an increase of ILM with an incidence of 1.9% for WLE vs. 3.4% for SNLB-. Selection bias in this review cannot be excluded. However, ILM occur four times more frequently after SLNB+ than SLNB- procedures and more often after SLNB+/CLND than WLE/DLND or WLE/ELND. ILM should therefore be viewed as a bio-marker of aggressive primary disease. Sentinel lymph node biopsy is thought to increase intralymphatic metastasis by restricting lymph flow. This review demonstrates that there is an increase in metastasis, but this result has to be interpreted with caution due to possible selection bias. Aggressive tumor characteristics are likely the cause of this increase.

5116 Treatment of small invasive breast cancer with ultrasound-guided radiofrequency ablation followed by immediate resection

Intralymphatic metastases (ILM) originate from tumor cell emboli entrapped in dermal lymphatics between primary tumor and regional lymph node basin. Because of this origin, sentinel lymph node biopsy (SLNB) might increase ILM by restricting lymph flow.Pubmed, Embase, Cochrane and Medline were searched for articles on ILM between 1980 and September 2014. ILM Incidences were calculated after wide local excision (WLE), excision with elective lymph node dissection (ELND) or therapeutic lymph node dissection (TLND), WLE with SLNB with or without completion lymph node dissection (CLND) and delayed lymph node dissection (DLND) for patients developing nodal metastasis during follow-up.In 36 studies, 14,729 patients underwent WLE, 1682 patients WLE/ELND, 362 patients WLE/DLND and 11,201 patients WLE/SLNB. On meta-analysis, ILM occurrence was 3.4% (95% CI 2.8–4.2%). ILM occurred most frequently in the WLE/DLND group (5.5%, 95% CI 3.5–8.7%), followed by WLE/ELND (4.7%, 95% CI 3.1–7.0%), WLE/SLNB (4.5%, 95% CI 3.5–5.7%) and WLE alone (1.9%, 95% CI 1.4–2.7%). 1330 SLNB+ patients were identified and 5783 SLNB− patients. For these groups, on meta-analysis, ILM recurrence was 13.2% (95% CI 10.8–16.2%) and 3.4% (95% CI 2.5–4.5%), respectively (p = 0.01).In this review SLNB is associated with an increase of ILM with an incidence of 1.9% for WLE vs. 3.4% for SNLB−. Selection bias in this review cannot be excluded. However, ILM occur four times more frequently after SLNB+ than SLNB− procedures and more often after SLNB+/CLND than WLE/DLND or WLE/ELND. ILM should therefore be viewed as a bio-marker of aggressive primary disease.Sentinel lymph node biopsy is thought to increase intralymphatic metastasis by restricting lymph flow. This review demonstrates that there is an increase in metastasis, but this result has to be interpreted with caution due to possible selection bias. Aggressive tumor characteristics are likely the cause of this increase.

Sentinel lymphonodectomy does not increase the risk of loco-regional cutaneous metastases of malignant melanomas

With regard to malignant melanoma, the impact of lymph node surgery on the development of loco-regional cutaneous metastases (LCM) has not yet been adequately addressed. However, this aspect is of interest, since sentinel lymphonodectomy (SLNE) has been suspected of causing LCM by inducing entrapment of melanoma cells. We analysed 244 patients with SLNE and compared the data with 199 patients treated with delayed lymph node dissection (DLND) for clinically palpable metastases. Analysis of both groups commenced at the time of excision of the primary tumour, using the Kaplan–Meier method. LCM that appeared as a first recurrence, as well as the overall probability of developing LCM, were recorded. For sentinel-negative patients with a primary melanoma >1 mm thick, the 5-year probability of developing LCM as a first recurrence was 6.9 ± 0.02% (±standard error of the mean (SEM)). The probability was 17.6 ± 0.03% in the DLND group. Comparing the two node-positive subgroups, the probability of developing LCM as a first recurrence was significantly higher in patients with positive SLNE (27.3 ± 0.05%, P = 0.03). However, the 5-year overall probability of developing LCM did not differ significantly in the node-positive groups (33.3% in the DLND group vs. 33.7% in patients with positive sentinel lymph nodes (SLNs)). Since early excision of lymphatic metastases by SLNE avoids nodal recurrences, thereby prolonging the recurrence-free interval, the chance of LCM to manifest as a first recurrence should inevitably increase. However, the overall in-transit probability is not increased after SLNE.

Sentinel lymphonodectomy and s-classification: a successful strategy for better prediction and improvement of outcome of melanoma.

The most successful strategies in the management of melanoma have always been based on early diagnosis and timely surgical removal. Sentinel lymphonodectomy (SLNE) is the most reliable technique for the detection of melanoma micrometastases in regional lymph nodes. The micromorphometric S-classification, a routinely determinable surrogate of tumor burden in the sentinel lymph node (SLN), has high prognostic relevance. SIII metastases, defined by a depth of invasion (d) greater than 1 mm below the capsular level, imply a risk of more than 50% for the presence of nonsentinel lymph node metastases in the same basin and for the emergence of distant metastases within 5 years of follow-up. Corresponding risks with SI metastases (d </= 0.3 mm) and SII metastases (0.3 mm < d </= 1 mm) do not exceed 15%. The survival curve for patients with SIII metastases approaches that of patients in the pre-SLNE era who underwent delayed lymph node dissection for subsequently detected nodal macrometastases. The survival of patients with initially removed SI and SII metastases is much better, similar to that of patients with S0 metastases. This explains the significant survival benefit of SLN-guided surgery in the entire population of patients with melanomas thicker than 0.75 mm, although the outcome of the subgroup without nodal metastases is not influenced by SLNE.

Patients with lymphatic metastasis of cutaneous malignant melanoma benefit from sentinel lymphonodectomy and early excision of their nodal disease

Early versus delayed excision of lymph node metastases is still being assessed in malignant melanoma. In the present retrospective, multicentre study, the outcome of 314 patients with positive sentinel lymphonodectomy (SLNE) was compared with the outcome of 623 patients with delayed lymph node dissection (DLND) of clinically enlarged lymph node metastases. In order to avoid the lead-time bias, survival was generally calculated from the excision of the primary tumour. Survival curves were constructed using the Kaplan–Meier product-limit estimate. Cox's proportional hazards model was used to perform a multivariate analysis of factors related to overall survival. Compared with SLNE and early performed complete lymph node dissection, DLND yielded a significantly higher number of lymph node metastases. Median and mean tumour thickness were nearly identical in the two therapy groups. The estimated 3-year overall survival rate was 80.1±2.8% (±standard error of the mean (SEM)) in patients with positive SLNs, and 67.6±1.9% in patients with DLND (5-year survival rates 62.5±5.5 and 50.2±5.4%, respectively). The difference between the two survival curves was statistically significant (P=0.002). Using multifactorial analysis, SLNE (P=0.000052), American Joint Committee on Cancer (AJCC) Breslow thickness category (P<0.000001), age (P=0.01) and gender (P=0.028) were independent predictors of overall survival. The location of the primary tumour (P=0.59) was non-significant. Considering only those centres with sufficient data for epidermal ulceration, this risk factor was also significant. In cutaneous malignant melanoma, early excision of lymphatic metastases, directed by the sentinel node procedure, provides a highly significant overall survival benefit.

Cutaneous malignant melanoma of the head and neck with intermediate tumor thickness: the role of elective lymph node dissection for clinical stage I

At present a tendency towards a more limited surgery in the treatment of clinical stage I and II melanoma exists. The controversy of elective lymph node dissections (ELND) in stage-I-melanoma with intermediate tumor thickness continues to be discussed. The sentinel lymph node biopsy may provide improved staging accuracy. It was the aim of this study to examine whether extent of surgical treatment particularly the ELND in case of intermediate tumor thickness has prognostic significance. Metastatic pattern of these malignant melanoma were analyzed to form a basic for routine sentinel lymph node biopsy. No prognostic difference could be shown in clinical stage I melanoma with intermediate tumor thickness between "local excision" (no lymph node dissection) or "wait and see" (delayed lymph node dissection because of clinical suspicion) respectively and "local excision with elective neck dissection". The 5-year survival was 67 %, 67 % and 69 %. It ran to 53 % in case of therapeutical lymph node dissection as primary therapy. Occult nodal metastases occur in 15 % and "skip"-metastases in 6 %. No therapeutic value for ELND in clinical stage I malignant melanoma of the head and neck with intermediate tumor thickness could be shown. The low incidence of occult nodal metastases and "skip"-metastases represents the basic for sentinel lymph node biopsy.

The impact of surgery on the course of melanoma.

Skin melanoma, unlike other cancers, occurs on the body surface: it can be detected and treated before it reaches the stage where it can metastasise; the impact of surgery is unrivalled, but only while it is at this early stage. In melanomas more than 0.75-1.00 mm thick, an increasing proportion acquire metastatic properties. There is today evidence showing that wide excision does not help, and that the effect of surgery is limited to local control of the disease. According to randomised trials, the territory of early spread--without concomitant distant micrometastases--that can be eradicated by surgery is shrinking. It has been demonstrated that resection margins of 3-4 cm are no better in terms of recurrence and survival than margins of 1 or 2 cm. Most melanomas can now be adequately resected without skin grafting. Regional elective lymph node dissection for high-risk melanoma (1.5 mm thick or more) does not improve survival over that obtained with delayed lymph node dissection performed when clinical metastases appear. By analogy, prophylactic isolated limb perfusion with melphalan reduces the rate of in-transit metastases but does not improve survival. Sentinel node biopsy allows early detection of regional lymph node metastases with minimally invasive surgery. On-going randomised studies will show whether it can have any impact on survival. Considering the experience with elective lymph node dissection, it seems unlikely that selective--as opposed to elective--lymph node dissection, of positive sentinel nodes, will influence survival. The already extensive experience with sentinel node biopsy provides a death risk hierarchy: one N2 node (with clinical metastasis), one N1 node--or sentinel node--with micrometastasis and one N0 node with no histologically detectable micrometastasis but PCR positive give, respectively, 50%, 60% and 70% 5-year survival rates. In other words, the earlier the detection of metastasis, the longer the survival. In terms of growth kinetics, the earlier the detection of metastasis, the longer the time to death, with no evidence that surgery would have an impact. There is just one, as yet unpredictable, subset of pa- tients with lymph node-confined disease in whom surgery might have an impact. It is hoped that, in the future, gene expression profiles of primary melanoma will help to pick out these patients. Multivariate analysis has shown that the sentinel node status is the most powerful prognostic factor in primary melanoma. Sentinel node biopsy is a valuable tool for selecting patients for adjuvant treatments within the frame of clinical trials, in which micrometastatic and clinically involved lymph nodes are entered separately. In-transit metastases can be eradicated in 50% of cases by isolated limb perfusion with melphalan under mild hyperthermia. When in-transit metastases are recurrent, deep seated, or bulky, the combination of tumour necrosis factor (TNF) with melphalan and interferon gamma yields a complete response rate of around 80%. This is the first antiangiogenic treatment of cancer that is effective in clinical practice, but it has no effect on survival. Current better knowledge of melanoma biology indicates that local, limited surgery has an impact on local or regional spread only.

Prognostic factors of overall survival in patients with delayed lymph node dissection for cutaneous malignant melanoma.

To date, no study of melanoma patients who have undergone delayed lymph node dissection (DLND) has focused on the independent prognostic factors of overall survival, as calculated from surgery on the primary. Using Kaplan-Meier estimates and Cox's proportional hazard model, the significance of prognostic factors was evaluated in 173 patients who developed clinically apparent regional lymph node metastases. When calculated from excision of the primary tumour (median Breslow thickness 3.0 mm), the median survival was 38 months. When calculated from DLND, the median survival was 19 months. Multifactorial analysis revealed that the number of nodes involved at the time of DLND significantly affected both survival calculated from primary tumour excision (P = 0.0002) and survival calculated from DLND (P < 0.0001). In contrast, the well-known risk factors of primary melanoma did not significantly influence overall survival or survival after DLND. However, the remission duration between surgery on the primary and DLND clearly depended on epidermal ulceration (P = 0.001), Breslow thickness (P = 0.009) and the site of the primary melanoma (P = 0.048). Thus, in patients submitted to DLND, the risk factors of primary melanoma influence the early period of the disease, until metastatic lymph nodes become palpable. With regard to overall survival, only the extent of nodal disease determines the prognosis of these patients.

Sentinel node detection in malignant melanoma.

The initial application of intraoperative lymphatic mapping and sentinel lymphadenectomy followed by selective complete lymphadenectomy (LM/SL/SCLND) was in melanoma. This arose as a solution to the ongoing debate concerning immediate vs. delayed lymph node dissection. Acceptance of the concept and advances in nuclear medicine, surgery, and pathology aspects of the sentinel node procedure have brought it into widespread use for melanoma and have expanded its application for other solid tumors that progress through the lymphatic route. Although the diagnostic accuracy of the procedure has been demonstrated in multicenter trials, caution should be exercised regarding therapeutic aspects until definitive benefit can be shown from well-designed clinical trials. Current issues of active discussion and debate are reviewed including ideal nomenclature, clinical significance of occult metastatic disease, quality assurance, and the role of LM/SL/SCLND outside high-volume melanoma centers.

Superior mediastinal dissection in the treatment of Hürthle cell carcinoma of the thyroid

Background: Hürthle cell carcinoma of the thyroid frequently metastasizes to regional lymph nodes. Delayed lymph node dissection may become necessary, adding little risk to patient survivability; however, metastatic disease to the superior mediastinum that cannot be promptly detected, represents a survival threat that deserves special attention. The purpose of this study is to review our experience in managing Hürthle cell carcinoma of the thyroid and make recommendations for appropriate treatment. Patients and Methods: A retrospective review of 371 thyroid neoplasms seen between 1987 and 1994 yielded six patients with Hürthle cell carcinoma of the thyroid gland. These include three cases treated with thyroidectomy and transcervical superior mediastinal dissection (SMD) as initial treatment and three cases treated with thyroidectomy alone. Results: Of the three patients treated with SMD as part of their initial treatment, one had occult micrometastases to the superior mediastinum. All three patients remain alive and disease free at least 3 years later, whereas all three patients treated with thyroidectomy alone developed superior mediastinal metastases and died of their disease. Conclusion: We propose that at the time of initial surgery, a transcervical SMD may prevent spread to the superior mediastinum and therefore, improve survivability.

Penile cancer—Is lymphadenectomy necessary in all cases?

This retrospective study examines the need for lymphadenectomy in all cases of penile cancer. Thirty-six patients were followed up regularly by the same person between 1986 and 1992. Nine (25%) patients presented with positive groin lymph nodes and underwent immediate ilioinguinal node dissection. Of the 27 (75%) patients who presented with negative groin lymph nodes, 10 had a delayed lymph node dissection. Four of these patients are alive at 3.7 years. Three died within 1 year of surgery and 3 are lost to follow-up. Seventeen patients (47%) did not require lymphadenectomy and 14 (82%) of these patients are alive at 3.8 years, the other 3 being lost to follow-up. A careful, closely monitored, follow-up protocol can eliminate the need for lymphadenectomy in select patients with penile cancer.