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Lymph node dissection.

Cervical lymph nodes are involved in 43% of patients with an upper esophageal lesion, 33% of patients with a middle third tumor, and 29% with a tumor of the lower third. Conventional two-field lymph node dissection removing the abdominal and lower mediastinal lymph node groups leads to inaccurate staging and is inadequate for preventing local recurrence. Three-field lymphadenectomy involves bilateral removal of the lower cervical groups of nodes, the superior, middle, and inferior mediastinal lymph nodes and the abdominal groups. The advantages of this extended dissection are improved survival, diminished incidence of local recurrence, and more accurate staging. The benefits in terms of improved survival may accurate to patients both with and without cervical lymph node involvement. Three-field node dissection improves 5-year survival to around 35% without an increase in the mortality rate. The incidence of recurrent laryngeal nerve paralysis is increased with the operation and could be as high as 14% or more.

Carcinoma, Squamous Cell↗

[Methods of sentinel lymph node mapping].

Sentinel lymph node mapping is used as a diagnostic method in order to increase staging accuracy without the well-known morbidities of radical lymphadenectomy. The sentinel node is defined as the first node to receive lymphatic drainage from a primary tumor. The sentinel node concept postulates that if the first draining node is negative for metastasis, the remaining lymph nodes in the nodal basin can be spared. Thus one can predict the status of the nodal basin with high accuracy. It also shows that lymphatic spread seems to follow certain rules that do not concern the whole lymphatic basin. Skip metastases were proven to be rare in breast and gastric cancer. The main issue in sentinel lymph node mapping remains the improvement of staging accuracy for detection of lymph nodes most likely to develop metastasis as well as reducing morbidity by planning lymphadenectomies individually for each tumor and each patient.

Colloids↗

Laparoscopic lymph node dissection around the inferior mesenteric artery for cancer in the lower sigmoid colon and rectum: is D3 lymph node dissection with preservation of the left colic artery feasible?

BACKGROUND: When we perform laparoscopic lymph node dissection around the inferior mesenteric artery (IMA), we preserve the left colic artery (LCA) to maintain the blood supply to the proximal sigmoid colon. In this study, we present our laparoscopic D2 and D3 lymph node (LN) dissection technique and evaluate its applicability and safety. METHODS: We performed LN dissection on 23 rectal and lower sigmoid colon cancer cases from April 2002 to December 2004. For D3 LN dissection, the incision to the mesosigmoid extends to just before the root of the IMA, which is exposed with an ultrasonic cutting and coagulating surgical device to avoid bleeding. Then, the arterial wall is exposed with a dissecting electrocautery spatula down to the LCA, at least 2 cm of which is exposed. Adipose tissue surrounding the IMA and inferior mesenteric vein is dissected. For D2 LN dissection, we partially expose the IMA to confirm the location of the LCA. RESULTS: The mean times taken for D2 and D3 LN dissections were 36.2 and 68.2 min, respectively. Both procedures took longer in male patients. There was a trend for the procedure overall to take less time in female patients. However, D2 dissection took significantly longer in male than female patients (p < 0.05). In women, D3 dissection took significantly longer than D2 (p < 0.05), but this trend was not seen in men. Increased experience among surgeons with this procedure was associated with significantly faster LN dissections in men (p < 0.05), but not in women (p = 0.493). Pearson product moment analysis identified a relationship between body mass index (BMI) and the time taken for D2 LN dissection (r = 0.765), but not D3 LN dissection (r = 0.158). There was no treatment-related morbidity with this technique. CONCLUSIONS: This method was safe and feasible for all patients in this series, but takes longer to perform in male patients.

Aged↗

Is an increase in CD4/CD8 T-cell ratio in lymph node fine needle aspiration helpful for diagnosing Hodgkin lymphoma? A study of 85 lymph node FNAs with increased CD4/CD8 ratio.

BACKGROUND: An elevated CD4/CD8 T-cell ratio on flow cytometry (FCM) analysis has been reported in the literature to be associated with Hodgkin lymphoma (HL). The purpose of our study was to determine the diagnostic significance of an elevated CD4/CD8 ratio in lymph node fine needle aspiration (FNA) specimens. DESIGN: Between 1996 and 2002, out of 837 lymph node FNAs submitted for flow cytometry analysis, 85 cases showed an elevated CD4/CD8 ratio, defined as greater than or equal to 4, without definitive evidence of a lymphoproliferative disorder. The cytologic diagnoses of these 85 cases were grouped into four categories: reactive, atypical, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL). Histologic follow-up was available in 17/85 (20%) of the cases. RESULTS: 5 of the 64 cases in which FCM and cytology did not reveal evidence of a lymphoproliferative disease had tissue follow-up because of persistent lymphadenopathy and high clinical suspicion. 3/5 (60%) confirmed the diagnosis of reactive lymphadenopathy. The two remaining cases (40%) were positive for lymphoma (1HL, 1NHL). 8/15 cases called atypical on cytology had histologic follow-up. 7/8 (87.5%) cases were positive for lymphoma (3HL, 4NHL). 3/4 cases called HL on cytology had tissue follow-up and all 3 (100%) confirmed the diagnosis of HL. One case diagnosed as NHL on cytology was found to be a diffuse large B-cell lymphoma. In summary, out of 17 cases with histologic follow-up 4/17 (24%) were reactive with CD4/CD8 T-cell ratio of 4.1-29, 7/17 (41%) were HLs with CD4/CD8 T-cell ratio of 5.3-11, and 6/17 (35%) were NHLs with CD4/CD8 T-cell ratio of 4.2-14. CONCLUSION: An elevated CD4/CD8 ratio on FCM is a nonspecific finding which may be seen in both reactive and lymphoproliferative disorders. The cytomorphologic features of the smear are more relevant than the sole flow cytometric finding of an elevated CD4/CD8 ratio.

Journal Article↗

Axillary staging using positron emission tomography in breast cancer patients qualifying for sentinel lymph node biopsy.

Axillary lymph node dissection (ALND) is the standard of care for nodal staging of patients with invasive breast cancer. Due to significant somatic and psychological side effects, replacement of ALND with less invasive techniques is desirable. The goal of this study was to evaluate the clinical usefulness of axillary lymph node (ALN) staging by means of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in breast cancer patients qualifying for sentinel lymph node biopsy (SLNB). FDG-PET was performed within 1 week before surgery in 24 clinically node-negative breast cancer patients with tumors smaller than 3 cm. Sentinel lymph nodes (SLNs) were identified by preoperative lymphoscintigraphy following peritumoral technetium 99m-labeled colloid albumin injection, and by intraoperative gamma detector and blue dye localization. Following SLNB, a standard ALND was performed. Serial sectioning and immunohistochemistry of the SLN as well as standard histologic examination of the non-SLN was performed. FDG-PET detected all primary breast cancers. Staging of ALNs by PET was accurate in 15 of 24 patients (62.5%), whereas PET staging was false negative in 8 of 10 node-positive patients and false-positive in 1 patient. The sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET for nodal status was 20%, 93%, 67%, and 62%, respectively. The mean diameter of false-negative ALN metastases was 7.5 mm (range 1-15 mm). Lymph node staging using FDG-PET is not accurate enough in clinically node-negative patients with breast cancer qualifying for SLNB and should not be used for this purpose.

Adult↗

The contemporary incidence of lymph node metastases in prostate cancer: implications for laparoscopic lymph node dissection.

The incidence of lymphatic metastases in 229 consecutive patients with clinically localized prostatic cancer was assessed. Only 13 patients had nodal metastases, for an incidence of 5.7%. A monoclonal prostatic specific antigen value of more than 40 ng./ml. correlated with a positive predictive value of 53% for nodal metastases. Routine laparoscopic node dissection is unnecessary considering the low incidence of nodal metastases.

Humans↗

Adenovirus vector-mediated gene transfer to regional lymph nodes.

Regional lymph nodes (RLNs) possess important immune functions and represent a major pathway of metastasis for solid tumors. Given these facts, the ability to transfer exogenous genes to the RLNs with the goal of manipulating the local immunological milieu would be desirable. On the basis of the hypothesis that a significant proportion of adenovirus (Ad) gene transfer vectors traffic through the lymphatics, E1-E3- Ad vectors were injected into the hind footpad of C3H/He mice and the RLNs assessed for vector trafficking and transgene expression. A low dose (10(9) particles) of an Ad vector encoding the firefly luciferase gene (Ad-CMV.Luc) resulted in luciferase expression only in the injection site and RLNs, with no detectable systemic (liver, spleen, lung) expression. At a higher dose (10(11) particles), some expression could be detected systemically in addition to the RLNs, but at levels in liver 14-fold less than in the RLNs. Transgene expression in the RLNs was transient, peaking at 1 day, decreasing markedly by 7 days. At high doses (10(11) particles), interruption of draining lymphatics decreased the amount of systemic dissemination 22-fold, suggesting that a large proportion of the vector trafficks through the lymphatics before reaching the systemic circulation. Administration of a vector encoding the jellyfish green fluorescent protein gene (AdCMV.GFP, 10(11) particles) showed that transgene expression in the RLNs was primarily in the cortical area. After footpad injection of a fluorescent-labeled Ad vector (Cy3-AdCMV.Null), fluorescent virions were visualized in the draining lymph. Regional lymph collected from animals injected in the footpad with AdCMV.Luc (10(11) particles) contained functional vector. Augmentation of local immune function in the RLNs was achieved by footpad administration of an Ad vector encoding murine IL-12, resulting in high mIL-12 and IFN-gamma levels in the regional, but not distant, nodes. These data demonstrate that expression of exogenous genes in RLNs is easily accomplished with Ad vectors, Ad vector dissemination occurs primarily via the lymphatics after footpad administration in mice, and basic immune functions in the RLNs can be manipulated by Ad-mediated gene transfer in vivo.

Adenoviridae↗

[Could lymph node microangiopathy play a part in the immunodeficiency of diabetes? Histological and immunohistochemical study of lymph nodes from 4 patients with long-term insulin-dependent diabetes mellitus subjected to autopsy examination].

The reason of increased susceptibility to frequent and protracted infections in diabetic patients is still unclear, although a multitude of "in vitro" studies have focused on the metabolic and functional modifications of the immune cells. From the literature immune abnormalities have been demonstrated "in vitro models" in genetic (type 1), autoimmune (type 2) and metabolic (type 1 and type 2) insulin-dependent diabetes mellitus (IDDM), and concisely referred in this paper. Diabetes microangiopathy, which is a peculiar alteration of the disease has been extensively described on many sites such as retina, renal glomeruli, skin etc, but as far as we know, not yet in the lymph-nodes. Therefore we report our histological and immunohistochemical observations in lymph-nodes removed from four patients with long-term IDDM, submitted to autoptic examination. On the clinical history all had shown, in the last years, lymphocytopenia and several infective diseases. The peculiar microangiopatic modifications appear joint to lymphodepletion of B and T cell dependent areas with marked reduction of follicular dendritic reticulum cells. The microangiopathy of thin intranodal capillaries besides compromise the diapedesis and traffic of the T and B lymphocytes could prevent the transformation of endothelial cells into dendritic reticulum cells. Indeed from the recent literature the dendritic reticulum cells should appear derived from transformed endothelial cells. This histological and immunohistochemical report could thence provide some additional knowledge about the complex problem of the immunodeficiency in diabetic patients.

Adult↗

Migration inhibition of lymph node lymphocytes as an in vitro assay for cell-mediated immunity in the draining lymph nodes of parenterally immunized mice.

This paper describes a method for in vitro measurement of specific cell-mediated immunity in the mouse. Animals were immunized parenterally with ovalbumin in Freund's incomplete or complete adjuvant, and a direct migration inhibition assay was performed, using lymphoid cells from the draining lymph nodes. Migration inhibition was found to be antigen specific, correlated with systemic delayed-type hypersensitivity measured in vivo by skin testing, and had a high degree of sensitivity for ovalbumin. The migrating cells were identified as lymphocytes. Lymph node lymphocyte migration inhibition provides a reliable in vitro assay for regional CMI in the mouse.

Animals↗

Concomitant endometrial adenoacanthoma and bilateral (inguinal) lymph node endometriotic adenoacanthomas or nodal metastases of the endometrial adenoacanthoma? A case report with a literature survey of the histogenetic aspects of endometriotic foci in pelvic lymph nodes.

This case report depicts an interesting association of well-differentiated adenocarcinoma of the endometrium with benign squamous metaplastic foci confined to the fundus uteri, superficially invading the myometrium and with concomitant bilateral pelvic lymph node endometriotic adenoacanthomas. Right inguinal lymphadenopathy was detected during the first hospitalization. A lymph node biopsy from the right groin, carried out at Nahariyya, revealed apparent metastatic adenoacanthoma regarded most probably as endometrial in origin. Fractionated curettage later showed a stage Ia G1 adenocarcinoma of the endometrium with benign squamous metaplastic elements (adenoacanthoma). At Rambam Hospital, Haifa, left groin node enlargement was noted as well. The Gynecologic Oncology Unit confirmed the previous histologic findings. At exploratory laparotomy total abdominal hysterectomy and bilateral salpingo-oophorectomy, paraaortic, and bilateral pelvic lymph node sampling as well as appendectomy were performed. Bilateral groin node dissection was then carried out. Out of 37 nodes examined tumor was found in only one node, namely that of the left groin. The paper includes an extensive survey of the literature on the subject of the histopathogenesis of endometriotic foci in pelvic lymph nodes and the discussion is designed to elucidate the diagnostic problem involved in this case report.

Adenocarcinoma↗

Flow cytometry in breast cancer: prognostic and surgical indications of the sparing of axillary lymph node dissection.

The lymph node status is still regarded as the most important prognostic factor in breast cancer. However, the utility of axillary lymph node dissection in clinically node-negative patients with breast cancer as a therapeutic approach rather than a pathologic staging procedure has been recently discussed. DNA index (DI) and S-phase fraction (SPF), evaluated by flow cytometric analysis, are two prognostic factors used especially in the assessment of the adjuvant therapy in stage N0 tumors. By studying a large number of cases, the authors aimed to assess the potential role of flow cytometry in predicting lymph node status. Two hundred eleven patients with breast cancer were included. Each tumor specimen was freshly analyzed by flow cytometry to assess DI and SPF. The authors also evaluated TNM status of patients, estrogen- and progesterone-receptor (ER and Pgr) status, and histologic grades. A group of patients with negative axillary lymph nodes was identified by means of association of tumor size of 2 cm or less, DI of 1, and SPF less than 7%. The ER and PgR status as well as histologic grade were significantly more favorable in this group of patients. These findings indicate that association of DI, SPF value, and tumor size may be predictive of axillary lymph node status in breast cancer.

Axilla↗

Surgical pathological staging of breast cancer by sentinel lymph node biopsy with special emphasis on the histological work-up of axillary sentinel lymph nodes.

Axillary nodal status assessed by traditional histological methods is a proven independent prognostic factor in breast cancer. Sentinel lymph node biopsy is a surgical pathologic staging procedure that not only allows the selective removal of the most likely sites of lymphogenic metastases, but also enables upstaging of breast carcinoma by detecting nodal involvement undetected by standard methods of nodal staging. This review highlights the upstaging potential of sentinel node biopsy. It also suggests that incomplete reporting of the pathological methods may make the comparisons of results from different studies difficult. The article also describes a few methods that have been claimed optimal but are probably not, and it formulates basic considerations for building up a histological protocol that can identify all metastases larger than 2 mm, which are of unquestionable prognostic relevance. These considerations are also useful for the detection of micrometastases. Issues of pathological reporting of sentinel nodal findings are also highlighted, with emphasis on the lack of standardization and on the differentiation of isolated tumor cells from micrometastases. Finally the stepwise building up of our current histology protocol and our experience gained since the introduction of sentinel node biopsy in 1997 is also briefly summarized.

Breast Neoplasms↗