Nodal Chain Research Articles

Delineation of the Internal Mammary Nodal Chain: Utilizing a Novel Computer Assisted Program of CT Overlays and Color Coded 3D Reconstructions

Postmastectomy radiotherapy usually requires comprehensive treatment of chest wall and draining lymphatics. The internal mammary nodal chain is an important draining lymphatic pathway especially in breast cancer. However, contouring internal mammary nodes is difficult due to conflicts in: nomenclature, descriptions of anatomic locations, proximal and distal connections, and structures drained. This communication describes a novel computerized program which provides instant decision support for contouring.

The impact of IMC nodal drainage on primary breast cancer outcome

534 Background: Involvement of the internal mammary node chain (IMC) portends a poor prognosis in primary breast cancer. Theoretically, internal mammary node involvement cannot be present in the absence of primary tumor lymphatic drainage to these nodes. We examined whether the presence of IMC drainage negatively impacted regional and systemic recurrence and overall survival (OS). Methods: We performed a retrospective review of a prospective surgical database of patients with invasive breast cancer (Stage I-III) who underwent preoperative lymphoscintigraphy (LSG) with peritumoral injection and subsequent intraoperative lymphatic mapping from 1996-2002. The study was limited to 1,854 patients who demonstrated drainage on LSG and did not undergo IMC nodal biopsy. Medical records were reviewed for demographics, clinicopathologic data, and medical and surgical treatment data. Outcomes were evaluated including regional and systemic recurrence and overall survival (OS). Patients with any IMC drainage (IM+, alone or with axillary drainage) were compared to those without IMC drainage (IM-) as identified on LSG. Median follow-up was 57.9 months. Results: Three hundred forty-four (18.5%) patients showed IM drainage. Patients with IM drainage were younger and less likely to have upper outer quadrant tumors than those with non-IM drainage (p< 0.0001 for both). Tumor size and axillary sentinel node status were not significantly different between both groups (p=0.08 and p=0.39, respectively). There was no difference in IM irradiation rates of patients who were IM+ versus patients who were IM-. The 5-year systemic recurrence rate was 3.8% for IM+ patients and 2.1% for IM- patients (p=0.07). The 5-year regional recurrence rate was 0.9% for IM+ patients and 0.5% for IM- patients (p=0.46). Only one patient recurred in the IM nodal chain. There was no statistically significant difference in the 5-year OS rates of IM+ versus IM- patients in the entire study cohort as well as in the axillary node positive patients. Conclusions: A finding of IM drainage on LSG was not a significant predictor of OS during this study period. This finding needs to be confirmed at longer follow-up. Further studies are needed to determine the role of the IM sentinel node biopsy. No significant financial relationships to disclose.

Simulation of the gyroid phase in off-lattice models of pure diblock copolymer melts

Particle-based molecular simulations of pure diblock copolymer (DBC) systems were performed in continuum space via dissipative particle dynamics and Monte Carlo methods for a bead-spring chain model. This model consisted of chains of soft repulsive particles often used with dissipative particle dynamics. The gyroid phase was successfully simulated in DBC melts at selected conditions provided that the simulation box size was commensurate with the gyroid lattice spacing. Simulations were concentrated at conditions where the gyroid phase is expected to be stable which allowed us to outline approximate phase boundaries. When more than one phase was observed by varying simulation box size, thermodynamic stability was discerned by comparing the Helmholtz free energy of the competing phases. For this purpose, chemical potentials were efficiently simulated via an expanded ensemble that gradually inserts/deletes a target chain to/from the system. These simulations employed a novel combination of Bennett's [J. Comput. Phys. 22, 245 (1976)] acceptance-ratio method to estimate free-energy differences and a recently proposed method to get biasing weights that maximize the number of times that the target chain is regrown. The analysis of the gyroid nodes revealed clear evidence of packing frustration in the form of an (entropically) unfavorably overstretching of chains, a phenomenon that has been suggested to provide the structural basis for the limited region of stability of the gyroid phase in the DBC phase diagram. Finally, the G phase and nodal chain stretching were also found in simulations with a completely different DBC particle-based model.

Low-Grade B-Cell Lymphomas With Plasmacytic Differentiation Lack PAX5 Gene Rearrangements

The chromosomal translocation t(9;14)(p13;q32) has been reported in association with lymphoplasmacytic lymphoma (LPL). Although this translocation involving the paired homeobox-5 (PAX5) gene at chromosome band 9p13 and the immunoglobulin heavy chain (IgH) gene at 14q32 has been described in approximately 50% of LPL cases, the actual number of cases studied is quite small. Many of the initial cases associated with t(9;14)(p13;q32) were actually low-grade B-cell lymphomas with plasmacytic differentiation other than LPL. Thus, we analyzed a series of low-grade B-cell lymphomas for PAX5 gene rearrangements. We searched records from the Department of Pathology, Stanford University Medical Center for low-grade B-cell lymphomas, with an emphasis on plasmacytic differentiation, that had available paraffin blocks or frozen tissue. We identified 37 cases, including 13 LPL, 18 marginal zone lymphomas (nodal, extranodal, splenic, and alpha-heavy chain disease), and 6 small lymphocytic lymphomas. A novel dual-color break-apart bacterial artificial chromosome probe was designed to flank the PAX5 gene, spanning previously described PAX5 breakpoints, and samples were analyzed by interphase fluorescence in situ hybridization. All cases failed to demonstrate a PAX5 translocation, indicating that t(9;14)(p13;q32) and other PAX5 translocations are uncommon events in low-grade B-cell lymphomas with plasmacytic differentiation. This study also confirms recent reports that found an absence of PAX5 rearrangements in LPL, suggesting the reassessment of PAX5 rearrangements in LPL.

Internal mammary lymph node (IMN) coverage by standard radiation tangent fields in patients showing IMN drainage on lymphoscintigraphy: therapeutic implications.

The purpose of this report is to evaluate the variability in coverage of the internal mammary nodal chain (IMN) by standard radiation tangential fields in those patients with medial drainage on lymphoscintigraphy. Twenty-two patients who showed lymphoscintigraphic IMN drainage underwent radiation simulation planned with computed tomography (CT). Standard tangent fields were placed and CT scans were reviewed to assess IMN inclusion and correlation with presternal fat thickness. Of the 22 patients who showed IMN drainage on lymphoscintigraphy, 10 (45%) had lateral primary lesions, 9 (41%) had medial lesions and 3 (14%) had subareolar lesions. Of these 22 women, 4 (19%) had the IMN completely within the standard tangent fields. Twelve women (55%) had only partial coverage of the IMN and the remaining 6 women (27%) had the IMN region completely outside. Presternal fat thickness greater than 10 mm was less likely associated with complete IMN coverage than fat thickness 10 mm or less, P = 0.001. Lymphoscintigram drainage to the IMN in breast cancer patients may suggest an increased risk of IMN involvement. Our data show that a majority (73%) of these patients had complete or partial incidental inclusion of the IMNs with standard tangents, which may in part explain the historically low IMN failure rate.

Clinical and anatomical guidelines in pelvic cancer contouring for radiotherapy treatment planning.

Many observations on potential inadequate coverage of tumour volume at risk in advanced cervical cancer (CC) when conventional radiation fields are used, have further substantiated by investigators using MRI, CT or lymphangiographic imaging. This work tries to obtain three dimensional margins by observing enlarged nodes in CT scans in order to improve pelvic nodal chains clinical target volumes (CTVs) drawing, and by looking for corroborative evidence in the literature for a better delineation of tumour CTV. Eleven consecutive patients (seven males, four females, mean age 62 years, range 43-78) with CT diagnosis of nodal involvement caused by pathologically proved carcinoma of the cervix (n = 2), carcinoma of the rectum (n = 2), carcinoma of the prostate (n = 2), non-Hodgkin lymphoma (n = 2), Hodgkin lymphoma (n = 1), carcinoma of the penis (n = 1) and carcinoma of the corpus uteri (n = 1) were retrospectively reviewed. Sixty CT scans with 67 enlarged pelvic nodes were reviewed in order to record the more proximal structures (muscle, bone, vessels, cutis or subcutis and other organs) to each enlarged node or group of nodes according to the four surfaces (anterior, lateral, posterior and medial) in a clockwise direction. A summary of the observations of each nodal chain and the number of occurrences of every marginal structure on axial CT slices is presented. Finally, simple guidelines are proposed. Tumour CTV should be based on individual tumour anatomy-mainly for lateral beams as it results from sagittal T2 weighted MRI images. Boundaries of pelvic nodes CTVs can be derived from observations of enlarged lymph nodes in CT scans.

Sentinel node identification and the ability to detect metastatic tumor to inguinal lymph nodes in squamous cell cancer of the vulva

Objectives The goal of this study was to identify one or more inguinal sentinel nodes in patients with primary squamous cell carcinoma of the vulva and to determine the ability of the sentinel node to predict metastasis to the inguinal lymphatic basin. Methods Techniques employing technetium-99m (Tc-99m) sulfur colloid and isosulfan blue dye were utilized to identify sentinel nodes in the inguinal lymphatic beds. Technetium-99m sulfur colloid was injected intradermally at the tumor margins 90–180 min preoperatively followed by a similar injection of isosulfan blue dye 5–10 min before the groin dissection. A handheld collimated gamma counter was employed to identify Tc-99m-labeled sentinel nodes. Lymphatic tracts that had taken up blue dye and their corresponding sentinel node were also identified and retrieved. A completion inguinal dissection was then performed. Each sentinel node was labeled as hot and blue, hot and nonblue, or cold and blue. The sentinel nodes were subjected to pathologic examination with step sections and nonsentinel nodes were evaluated in the standard fashion. Results Twenty-one patients with a median age of 79 were entered onto protocol and a total of 31 inguinal node dissections were performed. A sentinel node was identified in 31/31 (100%) groin dissections with the use of Tc-99m. Isosulfan blue dye identified a sentinel node in 19/31 (61%) groin dissections. Surgical staging revealed 7 patients with stage I disease, 5 with stage II disease, 5 with stage III disease, and 4 with stage IV disease. Lymph nodes in 9 groin dissections were found to have metastatic disease, and in 4 of these dissections, the sentinel node was the only positive node. Lymph nodes in 22 groin dissections had no evidence of metastasis. No false-negative sentinel lymph nodes were obtained (sentinel node negative and a nonsentinel node positive). Conclusion Tc-99m sulfur colloid is superior to isosulfan blue dye in the detection of sentinel nodes in inguinal dissections of patients with vulvar cancer. A sentinel node dissection utilizing Tc-99m alone can identify a sentinel node in all inguinal dissections. Pathologic examination with step sections has shown the sentinel node to be an accurate predictor of metastatic disease to the inguinal nodal chain.

Internal mammary sentinel nodes in primary breast cancer

SUMMARYFor over a century, there has been considerable interest in the management of regional lymph node metastasis in patients with primary breast cancer. Since the advent of sentinel lymph node biopsies, there has been renewed interest in the management of patients with metastasis to the internal mammary nodes. The appropriate management of these patients has not yet been established. Some investigators propose that biopsy of the internal mammary sentinel node may provide additionalprognostic information which might be used to guide the administration of systemic adjuvant therapy. Additionally, it has been suggested that patients with metastasis to the internal mammary sentinel node may benefit from radiotherapy to the internal mammary nodal chain. Clinical trials are needed to resolve these issues. Internal mammary sentinel node biopsy in patients with primary breast cancer should be considered investigational, and conducted only in the context of clinical trials.

Merkel cell carcinoma arising in the head and neck: optimizing therapy.

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine dermal neoplasm. Because of the limited number of cases described in the literature (approximately 600 to date), statistically significant data regarding treatment are difficult to obtain. The majority of MCC cases affect the head and neck and are thought to be caused by the actinic damage associated with sun exposure. This study evaluates cases of head and neck MCC at Naval Medical Center San Diego (NMCSD) and compares the treatment regimens and outcomes from multiple institutions. This study is a retrospective outcomes analysis of all cases of head and neck MCC seen at NMCSD, between January 1, 1988 and June 30, 1998. The records of the NMCSD Tumor Registry were searched for patients with that diagnosis, and supplemental information was retrieved from the Radiation Oncology and Head & Neck Surgery Clinic charts. Eight of nine patients in this study were treated with either wide-local excision or Mohs microsurgery. The surgical margins were free of disease in all eight patients. One patient presented with distant metastatic disease, and two others were subsequently found to have nodal involvement. Subsequent therapy varied among the patients. Survey of the available literature revealed inconsistency in terms of which treatment regimens are optimal. Tumor resections are recommended by most groups to include a 2-cm to 3-cm tumor-free margin around the primary lesion when possible, but this is often difficult to achieve in the head and neck. Data, which do not reach statistical significance, suggest improved outcomes with tumor-free margins. Treatment of the regional draining lymph nodes is also recommended in most series. Prophylactic lymph node dissection or radiation therapy to the nodal chain may decrease local recurrence but does not consistently affect overall survival. Adjuvant chemotherapy is advocated by most groups in the treatment of metastatic disease because MCC is pathologically similar to small-cell lung carcinoma. However, no chemotherapy protocol has been shown to improve survival. Head and neck MCC is a rare and aggressive dermal tumor of neuroendocrine origin that requires multimodality therapy, including surgery, radiation therapy, and possibly adjuvant chemotherapy. Multiinstitutional studies are crucial to obtain sufficiently large populations to investigate and optimize therapy in this disease.

Carcinoma of the uterine cervix: a 3D – CT analysis of dose to the internal, external and common iliac nodes in tandem and ovoid applications

Purpose: To describe external, internal and common iliac dose rates estimated with 3D-computed tomography (CT) based dose calculations in tandem and ovoid brachytherapy. Materials and methods: Thirty patients with carcinoma of the uterine cervix received low dose rate brachytherapy with a CT-compatible Fletcher–Suit–Deldos device. A total of 36 implants were performed with axial CT images used to identify internal iliac, external iliac, and common iliac vessels. Dose rates on the surfaces of these vessels were calculated for the purpose of estimating the dose to their associated lymph nodes. Results: In 22 out of 72 comparisons, point B overestimated the maximum dose with the external iliac nodes. In 21 out of 72 comparisons, point B overestimated the maximum dose with the internal iliac nodes. In all cases, Point B overestimated the minimum dose to the internal and external iliac nodal chains. Conclusion: It was found that Point B dose is similar to the maximum common iliac nodal dose. Patient to patient variability, of Point B dose, warrants further study of dose distributions to the nodal chains. The minimum dose to the external iliac nodal chain at the bifurcation of the nodal chains may provide a useful measure of ‘pelvic side wall dose’ and deserves further study to see if it can be correlated with pelvic side wall control and complications.

Sentinel node biopsy and internal mammary lymphatic mapping in breast cancer

Background: Currently outer quadrant breast tumors are not felt to have significant drainage to the internal mammary nodal chain. We evaluated the incidence of internal mammary sentinel nodes (IMSN) found with lymphoscintigraphy for all breast quadrants. Methods: Eighty women were prospectively studied by technitium-sulfur colloid injection, nuclear medicine imaging, and intraoperative gamma probe identification of sentinel nodes. IMSN detected were surgically removed. Results: Ten of 80 ( 12%) patients had IMSN identified in addition to axillary sentinel nodes (AXSN). Four tumors were located medially, 6 (60%) were in the outer quadrants. Metastatic disease was present in 3 of 10 women. Patients with positive IMSN also had positive AXSN. Conclusions: Patients undergoing lymphatic mapping for the management of breast cancer should have radiolabelled tracer and gamma probe sentinel node identification regardless of tumor location in the breast.

Peritoneal carcinomatosis: natural history and rational therapeutic interventions using intraperitoneal chemotherapy.

The rationale and the treatment strategies for peritoneal carcinomatosis have gained prominence over the last decade. Their definite contribution to the management of gastrointestinal cancer has been established. The significant contributions are summarized in Table 7.

Factors determining survival in resected N2 lung cancer.

This retrospective study was based on 237 patients with non-small cell lung cancer (NSCLC) and nodal N2 disease. All accessible mediastinal lymph nodes (LN) were removed and classified according to their anatomical location in LN chains. The pulmonary resections performed were: pneumonectomy (n = 187), lobectomy (n = 44) and segmentectomy (n = 4). There was solitary nodal chain involvement by metastasis in 141 cases, two chains in 72 cases and three or more in 24; "skip" metastases were present in 26.6%. N2 disease would have been missed in 45 cases of single chain involvement (31.9%) if routine removal of mediastinal nodes had not been performed. The overall 5-year survival rate was 18.8%. Survival was not influenced by site, size or extension (T) of tumor, tumor histology or the presence of vascular invasion. The prognosis was significantly worsened by the presence of microscopic residual disease (30 cases) and of satellite nodules (23 cases). Survival was significantly improved when metastases involved a single LN chain (26.3 versus 8.3%, P = 0.0003). The location and number of involved nodes in the chain, "skip" metastases and the presence of extracapsular spread of carcinoma did not influence the prognosis. Routine mediastinal LN dissection is necessary to improve survival and for classification of lung cancer. Anatomic description allows better understanding of N2 disease which is not a contraindication to surgery when a gross complete resection can be achieved.

Localization of Malignant Melanoma Using Monoclonal Antibodies

Finding a screening test to evaluate patients with cancer for occult metastatic disease, as well as imaging all known disease, is a goal of research efforts. Twenty-nine evaluable patients with deeply invasive (stage I), regional nodal (stage II), or systemic (stage III) melanoma underwent imaging by administration of a preparation of the antimelanoma antibody labeled with technetium 99m. Scan results indicated that 28 of 32 confirmed metastatic sites were imaged with this technique (88% sensitivity). Analysis of the individual positive sites revealed that nodal basins and visceral metastases accounted for the highest percentage of metastatic sites imaged, with 14 (88%) of 16 nodal basin metastases and all four visceral metastases being detected through imaging. Occult nodal disease was detected in the iliac nodal chain in two of the 29 patients. The imaging of benign tumors and nodal basins not containing disease accounted for a confirmed false-positive rate of 21%. Three (10%) of the 29 scan results were confirmed to be false-negative. In vivo tumor localization with monoclonal antibodies showed a sensitivity similar to that of other roentgenographic procedures for identifying metastatic disease and was useful in two of three patients in identifying occult iliac nodal disease, a region that is difficult to evaluate with physical examination and other imaging modalities.

Lymphoscintigraphy for Melanoma

Therapeutic decision making in treating patients with melanoma is difficult, with very few investigative tools and a lack of treatment options. Surgical extirpation remains the best method for cure and supports discussion in favor of prophylactic regional node dissection for subgroups of patients with stage I disease. In melanoma of the trunk or head and neck, lymphoscintigraphy has reliably provided guidance for resecting the regional lymphatics draining the involved site. This article describes a patient with a melanoma of the posterior neck, with metachronous metastases to the right and left posterior cervical triangles. Lymphoscintigraphy performed in the context of clinically negative nodal regions did not show drainage to either cervical nodal chain. Several explanations are presented, although a false-negative lymphoscintigraphic finding is the only plausible explanation. To our knowledge, this dilemma has not been previously reported, and raises the question of the infallibility of lymphoscintigraphy in predicting lymphatic basin mapping.

Filling of the Obturator Nodes in Pedal Lymphangiography: Fact or Fiction

The value of pedal lymphangiography as a staging procedure for carcinoma of the prostate and the bladder continues to be debated because of the fact that the obturator lymph nodes apparently are not visualized during this diagnostic technique. This study involves 25 patients who have undergone pedal lymphangiography followed by fine needle aspiration. Pelvic lymph node dissection was performed and pelvic x-rays were taken once the external iliac nodes had been excised, leaving the obturator nodes behind. The next step was the removal of the remaining nodes in the obturator fossa, after which another x-ray was obtained. With this technique we could prove whether these obturator lymph nodes opacified on routine pelvic x-ray. In a review of the radiography consistent filling of the obturator nodal chain was noted in all of the cases, as well as the consistent prediction of the location of these lymph nodes before fine needle aspiration.

Lymphography and Percutaneous Lymph Node Biopsy in Clinically Localized Carcinoma of the Prostate

Accurate staging of prostatic carcinoma requires determination of the status of the regional draining lymph nodes. Pelvic lymphadenectomy is the definitive examination but has certain morbidity and even mortality. Lymphography is safe but may not be sufficiently accurate. A total of 41 patients with clinically localized disease and abnormal or suspicious lymphograms underwent percutaneous lymph node biopsy. Ten of 11 patients (91 per cent) with abnormal lymphograms and 14 of 30 (47 per cent) with suspicious lymphograms had positive cytology studies. Of the suspicious defects an unopacified void in a nodal chain most frequently was positive. Of 22 potentially curable patients with stages A and B1 disease 12 had metastatic disease.

Value of anterior mediastinotomy in bronchogenic carcinoma of the left upper lobe

Neoplasms of the left upper lobe may spread directly to the anterior mediastinal group of nodes without involving the inferior tracheobronchial, superior tracheobronchial, or paratracheal nodal chain. Routine cervical mediastinoscopy does not sample the anterior mediastinal node group. Parasternal anterior mediastinotomy was performed in 28 patients with left upper lobe carcinoma and normal findings from cervical mediastinoscopy. Despite the normal findings at cervical mediastinoscopy, 10 of the 28 patients were deemed to have inoperable disease because of spread of the neoplasm to the anterior nodal group or because of direct neoplastic involvement of the aorta or main pulmonary artery. All patients in whom results of anterior mediastinotomy were normal had resectable lesions at thoracotomy. Fourteen of the 16 patients who came to thoracotomy had normal hilar nodes. Parasternal anterior mediastinotomy, introduced by Chamberlain, should be performed in addition to standard cervical mediastinoscopy if the nodal drainage of left upper lobe neoplasms is to be more completely evaluated. Combining these two procedures samples all major drainage pathways except the posterior mediastinal nodal chain.