Cervical lymph node metastases from occult squamous cell carcinoma: cut down a tree to get an apple?

PURPOSE: To review the value of extended diagnostic work-up procedures and to compare the results of comprehensive or volume-restricted radiotherapy in patients presenting with cervical lymph node metastases from clinically undetectable squamous cell carcinoma. METHODS AND MATERIALS: A systematic review was undertaken of published papers up to May 2000. RESULTS: Positron emission tomography (PET) has an overall staging accuracy of 69%, with a positive predictive value of 56% and negative predictive value of 86%. With negative routine clinical examination and computerized tomography (CT) or magnetic resonance imaging (MRI), PET detected primary tumors in 5-25% of patients, whereas ipsilateral tonsillectomy discovered carcinoma in about 25% of patients. Laser-induced fluorescence imaging with panendoscopy and directed biopsies showed some encouraging preliminary results and warrants further study. All together, the reported mucosal carcinoma emergence rates were 2-13% (median, 9.5%) after comprehensive radiotherapy and 5-44% (median, 8%) after unilateral neck irradiation. The corresponding nodal relapse rates were 8-45% (median, 19%) and 31-63% (median, 51.5%), and 5-year survival rates were 34-63% (median, 50%) and 22-41% (median, 36.5%), respectively. Retrospective single-institution comparisons between comprehensive and unilateral neck radiotherapy did not show apparent differences in outcome. Prognostic determinants for survival are the N stage, number of nodes, extracapsular extension, and histologic grade. No data were found to support the benefit of chemotherapy in this disease. CONCLUSION: Physical examination, CT or MRI, and panendoscopy with biopsies remain the standard work-up for these patients. Routine use of PET or laser-induced fluorescence imaging cannot be firmly advocated based on presently available data. Although combination of nodal dissection with comprehensive radiotherapy yielded most favorable results, its impact on the quality of life should be recognized, and the confounding effects of patient selection for various treatment modalities on therapeutic outcome cannot be ruled out. A randomized trial comparing the therapeutic value of comprehensive vs. volume-limited radiotherapy is being considered.     

Analysis of paraaortic lymph node involvement in pancreatic carcinoma: a significant indication for surgery?

BACKGROUND: Lymph node status is a key prognostic factor for pancreatic carcinoma. The paraaortic lymph nodes are the highest level of lymph nodes that can be resected safely in the abdomen for pancreatic and other gastrointestinal tumors. The pattern of paraaortic lymph node involvement and its relation with other lymph node groups were analyzed and the significance of this information relative to surgical therapy examined. METHODS: Between 1974-1996, 99 patients with invasive ductal carcinoma of the pancreas underwent pancreatectomy at the study institution. The pattern of lymph node involvement, particularly paraaortic, was evaluated by careful pathologic review of extended lymphadenectomy specimens. RESULTS. Fifty-eight of 76 patients (76%) with carcinoma in the pancreatic head (Ph) and 19 of 23 patients (83%) with carcinoma of the pancreatic body and tail (Pbt) had lymph node involvement. Fourteen patients with Ph disease (18%) and 4 with Pbt disease (17%) had paraaortic lymph node involvement. Tumor size did not correlate with paraaortic lymph node involvement. A correlation was found between Group 13 (posterior pancreaticoduodenal lymph nodes), Group 14 (lymph nodes surrounding the superior mesenteric artery), and the paraaortic lymph nodes for Ph disease. All paraaortic lymph node metastases were located in the 16M region (the region between the celiac trunk and the inferior mesenteric artery). For patients with Pbt disease, the distribution of paraaortic lymph node metastases was the same as for those with Ph disease. Only 33% of cases of paraaortic lymph node metastases were suspected preoperatively or perioperatively. The longest survival for a patient with paraaortic lymph node metastases was 36 months and 17 months, respectively, for patients with Ph and Pbt disease. CONCLUSIONS: The paraaortic lymph nodes are frequent sites of metastasis from pancreatic carcinoma, and are difficult to evaluate preoperatively or perioperatively. This situation mandates paraaortic lymph node dissection, at least in the 16M region.     

What can we learn from the phenomenon of preferential lymph node metastasis in carcinoma?

Lymph nodes are the most common and earliest site of malignancies arising in epithelia. However, the reason for this pattern of preferential metastasis is not clear. This article reviews features of the metastatic process and lymph node microenvironment which might potentiate lymph node metastases. There is intriguing evidence that preferential lymph node metastasis is due to (1) the efficiency of lymph nodes as filters of the tumor cells which arrive there, and (2) the probability that adhesive interactions, normally governing the generation of different T-cell immune responses, are responsible for this efficiency and may also promote invasion and proliferation of tumor cells in the lymph node. Manipulation of the cytokine environment in a lymph node draining a primary epithelial tumor may alter both the expression of cell adhesion molecules within the node and the subsequent metastatic ability of the tumor cells arriving at it.     

Diagnostic excision of the Rosenmüller's node. Screening for occult metastases before elective regional lymph node dissection in patients with lower limb melanoma?

Elective radical groin dissection was performed on 297 consecutive patients with high-risk melanoma of the leg, Anderson Stages I, IIA, IIIA. By separate histologic examination of the so-called "Rosenmüller's node," the other inguinal, and the external iliac lymph nodes, the diagnostic excision of the Rosenmüller's node was tested as a suitable mode of screening for metastases before a planned elective regional lymph node dissection. Eighty patients (27%) presented with what was histologically determined to be occult groin metastases. Rosenmüller's node was involved in 30 of these cases; in the remaining 50, however, it was not affected; that is, 63% of the cases were false-negative. Thus, the involvement of Rosenmüller's node is not representative of metastases in the other ilioinguinal lymph nodes, but is rather a matter of chance. In women with superficial spreading melanoma the rate of occult lymph node metastases was significantly lower than that in men with melanomas of the other type. Iliac lymph node involvement was observed in 18 patients (22%) depending on clinical stage and depth of invasion of the primary tumor.     

Is metallic stenting worthwhile for biliary obstruction due to lymph node metastases?

BACKGROUND: The indications for metallic stents have widened from primary hepatobiliary cancers to the other diseases such as lymph node metastases from distant organs. The present study aimed to evaluate the results and establish the efficacy of metallic stenting in patients with obstructive jaundice due to metastatic lymph nodes. METHODS: Stent patency, survival and cost per patient until death were retrospectively compared between patients with primary carcinoma of the biliary tract (PC group; n = 71) and lymph node metastases from the gastric and colorectal carcinomas. (LN group; n = 26). RESULTS: Stent occlusion occurred in 17 patients in the PC group (24%). In contrast, stent occlusion was significantly more frequent in the LN group (P = 0.0293), occurring in 13 patients (50%). Cumulative stent patency was also significantly shorter in the LN group than that in the PC group (P = 0.0016). However, survival was almost the same between the two groups. The mean medical fee was 27% higher for the LN group than for the PC group, which was attributable to additional treatment for stent occlusion. DISCUSSION: The indications for metallic stent placement for biliary obstruction caused by lymph node metastases from the gastrointestinal tract seem limited. Further investigation of the treatments alternative to metallic stents would be required.     

Pelvic lymph node irradiation for prostate cancer: who, why, and when?

Prostate cancers are best characterized by their clinical (TNM) stage, Gleason score, and serum prostate-specific antigen (PSA) level. These 3 factors are known to influence the risk of pelvic nodal involvement. By combining these prognostic factors, nomograms and equations have been developed and are widely used in clinical practice as an accurate way of predicting the probability of a given pathological stage. Patients who have a significant risk of pelvic nodal metastasis will likely have higher biochemical failure rates. Results from the multi-institutional prospective trials have shown that patients at an intermediate to high risk for pelvic nodal involvement experience disease progression-free survival benefits from the use of whole pelvic radiotherapy combined with hormone therapy. Yet, significant biological interactions between radiation treatment volumes and timing of hormone therapy have been shown. Further study of these issues is necessary to define the best treatment for patients at significant risk of pelvic lymph node involvement.     

Expression of ALDH1 in axillary lymph node metastases is a prognostic factor of poor clinical outcome in breast cancer patients with 1–3 lymph node metastases

Background

Recently, evidence in support of the cancer stem cell (CSC) hypothesis has been accumulating. On the other hand, it has been reported that the expression of aldehyde dehydrogenase 1 (ALDH1) in primary breast cancer is a powerful predictor of a poor clinical outcome, and that breast cancer stem cells express ALDH1. According to the CSC hypothesis, development of metastases requires the dissemination of CSC that may remain dormant and be reactivated to cause tumor recurrence. In this study, we investigated whether the detection of CSC in axillary lymph node metastases (ALNM) might be a significant prognostic factor in patients with breast cancer.

Methods

From 1998 to 2006, 40 primary breast cancer patients with ALNM, the number of metastatic nodes varying in number from 1 to 3, underwent surgery at Okayama University; of these, 15 patients developed tumor recurrence. We retrospectively evaluated the common clinicopathological features and the expression of ER, HER2, ALDH1, and Ki67 in both the primary lesions and the ALNM, and analyzed the correlations between the expression of these biological markers and the disease-free survival (DFS).

Results

Expression of ALDH1 in the ALNM was significantly associated with the DFS (P = 0.037).

Conclusion

Evaluation of biomarker expression in ALNM could be useful for prognosis in breast cancer patients with 1–3 metastatic lymph nodes.     

The role of lymph nodes in cervical cancer: incidence and identification of lymph node metastases—a literature review

Correct identification of patients with lymph node metastasis from cervical cancer prior to treatment is of great importance, because it allows more tailored therapy. Patients may be spared unnecessary surgery or extended field radiotherapy if the nodal status can be predicted correctly. This review captures the existing knowledge on the identification of lymph node metastases in cervical cancer. The risk of nodal metastases increases per 2009 FIGO stage, with incidences in the pelvic region ranging from 2% (stage IA2) to 14–36% (IB), 38–51% (IIA) and 47% (IIB); and in the para-aortic region ranging from 2 to 5% (stage IB), 10–20% (IIA), 9% (IIB), 13–30% (III) and 50% (IV). In addition, age, tumor size, lymph vascular space invasion, parametrial invasion, depth of stromal invasion, histological type, and histological grade are reported to be independent prognostic factors for the risk of nodal metastases. Furthermore, biomarkers can contribute to predict a patient’s nodal status, of which the squamous cell carcinoma antigen (SCC-Ag) is currently the most widely used in squamous cell cervical cancer. Still, pre-treatment lymph node assessment is primarily performed by imaging, of which diffusion-weighted magnetic resonance imaging has the highest sensitivity and 2-deoxy-2-[¹⁸F]fluoro-D-glucose positron emission computed tomography the highest specificity. Imaging results can be combined with clinical parameters in nomograms to increase the accuracy of predicting positives nodes. Despite all the progress regarding pre-treatment prediction of lymph node metastases in cervical cancer in recent years, prediction rates are not robust enough to safely abandon surgical staging of the pelvic or para-aortic region yet.

     

Vulvar melanoma: is there a role for sentinel lymph node biopsy?

BACKGROUND: The objective of this study was to evaluate the author's recent, preliminary experience with the sentinel lymph node procedure in patients with vulvar melanoma and to compare this experience with treatment and follow-up of patients with vulvar melanomas who were treated previously at their institution. METHODS: From 1997, sentinel lymph node procedure with the combined technique (99mTechnetium-labeled nanocolloid and Patente Blue-V) was performed as a standard staging procedure for patients with vulvar melanoma with a thickness > 1 mm and no clinically suspicious inguinofemoral lymph nodes. For the current study, clinicopathologic data from all 33 patients with vulvar melanoma who were treated between 1978 and 2000 at the University Hospital Groningen were reviewed and analyzed. RESULTS: From January 1997 until December 2000, identification of sentinel lymph nodes was successful in all nine patients who were referred for treatment of vulvar melanoma. Three patients underwent subsequent complete inguinofemoral lymphadenectomy because of metastatic sentinel lymph nodes. In follow-up, groin recurrences (in-transit metastases) occurred in two of nine patients, both 12 months after primary treatment. Both patients had melanomas with a thickness > 4 mm and previously had negative sentinel lymph nodes. There was a trend toward more frequent groin recurrences in patients after undergoing the sentinel lymph node procedure (2 of 9 patients) compared with 24 historic control patients (0 of 24 patients; P = 0.06). Five of 33 patients developed local recurrences: Two patients had groin recurrences, and 11 patients developed distant metastases. Twelve patients died of vulvar melanoma. Seventeen patients with a median follow-up of 66 months (range, 9-123 months) are currently alive (overall survival rate, 52%). CONCLUSIONS: Although the numbers were small, this study showed that the sentinel lymph node procedure is capable of identifying patients who have occult lymph node metastases and who may benefit from lymphadenectomy for locoregional control and prevention of distant metastases. However, the data also suggest that the sentinel lymph node procedure may increase the risk of locoregional recurrences (in-transit metastases), especially in patients with thick melanomas. The potential role of the sentinel lymph node procedure as an alternative method of lymph node staging in patients with vulvar melanoma needs further investigation only within the protection of clinical trials and probably should be restricted to patients with melanomas with intermediate thickness (1-4 mm).     

When is a completion axillary lymph node dissection necessary in the presence of a positive sentinel lymph node?

BackgroundThe management of the axilla in the presence of positive sentinel lymph node (SLN) remains controversial. Many centres forgo completion axillary lymph node dissection (cALND) in the presence of micrometastatic disease. The American College of Surgeons Oncology Group (ACOSOG) Z0011 trialists argue for extending this to macrometastasis. The aim of this study was to correlate tumour burden in SLNs with that in the residual lymph node basin to determine the likelihood of residual disease in patients with micro- and macrometastasis in the SLN.MethodsPatients who underwent cALND following a positive SLN were analysed for histopathological features of the primary tumour and burden of axillary disease.ResultsOf 155 patients, 115 (74%) had macrometastases and 40 (26%) micrometastases in the SLNs. Residual axillary disease was detected in 55/155 (35%) patients with macrometastases and 4/40 (10%) with micrometastases. Generally, with increasing size of metastasis in the SLN there was an increasing risk of further disease in residual lymph nodes. Logistic regression analysis showed increased odds ratios for further disease for all groups when compared with the <2 mm (micrometastasis) SLN group.ConclusionPatients may be advised to forgo cALND where the SLN contains isolated tumour cells or micrometastasis. Recommendations for proceeding to cALND can be based on the size of metastasis in the SLN, which relates to the risk of further disease in the residual axillary lymph nodes and subsequent regional recurrence.     

Is there a role of sentinel lymph node biopsy in ductal carcinoma in situ?: analysis of 587 cases

SummaryBackground The role of sentinel lymph node biopsy (SLNB) in patients with a core needle-biopsy diagnosis of ductal carcinoma in situ (DCIS) has been intensely debated. Core needle-biopsy has an inherent sampling error leading to histologic underestimation of invasive disease. If SLNB is not performed at the time of the definitive operative procedure, patients found to have an invasive cancer, will require a second operative procedure. The study was designed to determine when the risk of finding invasive disease on final pathology in patients with an initial diagnosis of DCIS was sufficiently high to justify the use of SLNB.Methods We identified 587 women with an initial core needle-biopsy diagnosis of DCIS in the prospective Breast Test Wales (BTW) database from 1995 through 2005. A variety of clinical, mammographic and histologic features were identified and correlated with the presence of invasion at excision using univariate and multivariate analyses.Results Median age of patients at the time of diagnosis was 58 years (range 41 to 83 years). 201 patients (36%) were treated by mastectomy and 354 (64%) by breast conservation surgery. 220 of 587 patients (38%) were found to have invasive disease on final pathology. On univariate analysis, the rate of upstaging was related to the presence of a clinically palpable mass and size of the mass (both p<0.0001, Mann–Whitney test); mammographic presence of a mass and size of the mass (both p<0.0001, Mann–Whitney test). Multivariate logistic regression analysis revealed 2 independent predictors of invasive cancer on final pathology: mass on clinical examination (odds ratio [OR], 5.09; p<0.0001) and mammographic mass (OR, 7.37; p<0.0001). Age, grade of DCIS, microinvasion and presence of comedonecrosis did not help in distinguishing between patients with DCIS and those upstaged to invasive carcinoma at definitive surgery. Axillary nodal staging (four node sampling or clearance) was done at the time of surgery in 269 patients. Axillary nodal metastases were found in 35 of 269 patients (13%). All 35 patients had invasive carcinoma on final pathology.Conclusion The indiscriminate use of SLNB in patients with DCIS seems excessive. Our study suggests that patients with a mass on clinical examination or mammogram have an increased risk of invasive disease at the time of definitive operative procedure and should undergo SLNB at the initial procedure. In addition, SLNB should be performed in patients undergoing mastectomy because mastectomy precludes SLNB if invasive disease is subsequently discovered.Presented at the 28^th Annual San Antonio Breast Cancer Symposium, San Antonio, Texas, December 8–11, 2005     

Cervical lymph node relapses of head-and-neck squamous cell carcinoma: is brachytherapy a therapeutic option?

Purpose: To report the results of interstitial brachytherapy (IBT) without salvage surgery for isolated cervical lymph node relapses.

Patients and Methods: From 1970 to 1989, 84 patients were treated; 76 patients had relapsed in sites of previous external beam radiation. In 72 patients, IBT was sole salvage treatment (mean, 56.5 Gy). In 12 patients IBT (mean, 38 Gy) was combined with further external beam radiotherapy (mean, 41 Gy).

Results: Local control in the neck was 49% at 1 year, 31% at 2 years, and 0% at 5 years. Overall survival was 33% at 1 year, 13% at 2 years, and 1% at 5 years. Significant toxicity occurred in 35% (7% fatal). Multivariate analysis shows survival after salvage was better for patients who had achieved initial control for ≥18 months before relapse (0% vs. 13% at 3 years, p < 0.0002). Lymph node control was better for patients who received total salvage dose ≥60 Gy (0% vs. 56% at 3 years, p = 0.0004).

Conclusion: Given its poor efficiency and its toxicity, IBT must be considered only when surgery is contraindicated and if lymph node relapse occurs after a minimal interval of 18 months.     

Occipital lymph node metastasis from nasopharyngeal carcinoma：a special case report and literature review

Cervical lymph node metastasis is common in patients with nasopharyngeal carcinoma (NPC), but occipital lymph node metastasis in NPC patients has not yet been reported. In this case report, we describe an NPC patient with occipital lymph node metastasis. The clinical presentation, diagnostic procedure, treatment, and outcome of this case were presented, with a review of the related literature.     

Is lymph node dissection necessary for staging while undergoing nephrectomy in patients with renal cell carcinoma?

Objective: The essential treatment for patients with renal cell carcinoma is nephrectomy. As no lymph node dissection (LND) could be performed in the majority of these patients, healthy staging could not be carried out. In this study, we investigated the impact of LND during nephrectomy on patient survival. Methods: A total of 181 patients—58 (32%) were female and 123 (68%) were male—were included in the study. Median follow-up period was 48 months. The patients were separated into 4 groups according to their stage during diagnosis; group 1 (T1–3N0M0), group 2 (T1–3NXM0), group 3 (T1–3N1M0), and group 4 (T1–4N0/XM1). The disease-free survival of nonmetastatic patients and the overall survival of all groups were calculated. Results: Mean age was 58.4 ± 12.0 years. Median survival for Group 1 could not be reached. Median survival was 89 months in Group 2, 50 months in Group 3, and 39 months in Group 4 (P <0.001). There was no statistically significant difference between the N1 and M1 groups (P = 0.297). For the NX patient group without LND, median survival was 89 months, which is worse than the N0 group and better than the N1 group (P = 0.002). Conclusions: Our study presumes that the patients without LND are not staged sufficiently, NX patients have worse survival rates when compared with N0 patients, node-positive patients have poor survival rates as do the metastatic patients, and it should be defined as TNM stage4.     

Scalene lymph node dissection in locally advanced cervical carcinoma: is it reasonable or unnecessary?

AIMS AND BACKGROUND: The aim of this study was to evaluate the routine use of scalene lymph node dissection to determine the degree of disease spread in women with stage IIB-IVA cervical cancer treated at our hospital. METHODS AND STUDY DESIGN: Patients with locally advanced cervical carcinoma underwent para-aortic lymph node dissection via the extraperitoneal approach. Patients with clinical evidence of scalene or supraclavicular node metastasis were excluded. If their para-aortic nodes were tumor-positive, patients underwent scalene lymph node dissection. RESULTS: Twenty-eight scalene lymph node samplings were performed. Three patients had microscopically positive scalene lymph nodes (10.7%). In one patient the thoracic duct was injured. CONCLUSION: Patients with cervical carcinoma whose only extrapelvic site of metastases is the para-aortic lymph nodes may be eligible for scalene lymph node dissection as part of their pretreatment assessment, especially if extended field radiation is considered.     

Is there a role for sentinel lymph node biopsy in the management of sarcoma?

Is there a role for sentinel lymph node (SLN) biopsy in the management of sarcoma? Sentinel node biopsy has dramatically changed the management of melanoma and breast cancer, helping surgeons avoid radical lymphadenectomies in node negative patients who would previously have undergone a more morbid operation with little benefit, or remained pathologically unstaged. Many investigators have explored the use of lymphatic mapping for malignancies other than breast cancer or melanoma. Lymphatic mapping and sentinel node biopsy has not been investigated in the management of sarcomas, which is not surprising given that the majority of sarcomas spread by local extension or hematogenously. Regional lymph node metastases are rare; developing in about 3-10% of patients with localized disease. However, among certain subtypes of high-grade sarcomas there is a propensity for regional lymph node metastases. These include rhabdomyosarcoma, epithelioid sarcoma, clear cell sarcoma, synovial sarcoma, and vascular sarcomas. It is in these particular subtypes that there may be a benefit to SLN biopsy.