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Sentinel lymph node biopsy has no benefit for patients with primary cutaneous melanoma metastatic to a lymph node: an assertion based on comprehensive, critical analysis: part I.

The thesis is set forth in this treatise that there is no place in the routine practice of medicine for the procedure for melanoma known conventionally and universally as sentinel node biopsy. Our assertion is based on assessment of the extensive body of literature devoted to the subject of treatment of melanoma before any metastasis has manifested itself clinically and of that dedicated to therapy for overt metastatic melanoma by a variety of modalities, chief among those addressed here being elective lymph node dissection and sentinel lymph node biopsy. In this era of sentinel lymph node biopsy, elective lymph node dissection has been modified to include only patients with metastasis of melanoma to lymph nodes, a procedure now termed "selective complete lymph node dissection." Among adjuvant medical therapies, the most popular today is interferon alpha-2B. Critical, incisive scrutiny of the literature leads to the conclusion, incontrovertibly, that elective lymph node dissection has no benefit for a patient and that all modifications of it also are devoid of value. The reason, logically, for the lack of utility of elective lymph node dissection becomes apparent by virtue of the route taken by cells of melanoma as they metastasize; those cells proceed in the same fashion as does lymph, bacteria, foreign material (including vital dyes and radioactive tracers), and other kinds of cells, to wit, by passing rapidly through nodes, including the sentinel one, and even bypassing entirely the nodes. In reality, cells of metastatic melanoma are not held up in nodes for any significant period of time, contrary to what is asserted repeatedly, but without any basis in fact, by many students of the subject. Moreover, not a single adjuvant medical therapy available currently is effective against metastatic melanoma and, therefore, none of them should be invoked to justify performance of sentinel node biopsy. Even if the sentinel node is found to house cells of melanoma, which, as a rule, conveys a grim message regarding the future, the finding in an individual patient is meaningless; a particular patient may live in harmony with metastases of melanoma for more than 30 years and even die of an unrelated malady. In short, no surgeon, pathologist, or oncologist is a seer, diviner, or prophet when it comes to predicting accurately the outcome for a patient with metastasis of melanoma; the end could come in weeks, months, or decades. If, however, a sentinel node is found to contain nary a cell of metastatic melanoma, it, too, means nothing for an individual patient because the existence of metastases widely is not excluded by that finding. In short, sentinel node biopsy cannot be considered the standard of care in the daily practice of medicine; it is woefully substandard because it is without benefit. There is no justification, whatsoever, for the procedure, scientifically or practically, and for that reason it should be abandoned, without delay, now.

Female↗

Lymph-borne dendritic leucocytes do not recirculate, but enter the lymph node paracortex to become interdigitating cells.

Peripheral lymph contains constitutively major histocompatibility complex (MHC) class II-positive, dendritic leucocytes (DL) with a veiled (VC) or dendritic (DC) shape. On the basis of phenotypic similarities to the interdigitating cells (IDC) of T-dependent areas of lymphoid tissues, they are believed, but not yet proven, to be IDC precursors that develop into mature IDC within the draining lymph nodes. In order to determine the relationship between VC/DC and IDC, highly purified radiolabelled peripheral lymph DL (collected by thoracic duct cannulation of mesenteric lymphadenectomized congenitally athymic, nude rats) were reinjected into the veins or footpads of syngeneic recipients. Later, host blood and lymph were collected and the tissues were biopsied and processed for scintillation counting or for light microscopic autoradiography combined with electron microscopy of neighbouring sections. The intravenously injected VC/DC did not enter lymph nodes or Peyer's patches directly from blood and did not re-enter the lamina propria of the gut, but became localized largely in the liver and the spleen. From the liver some of the cells proceeded via afferent lymphatics to the liver and the spleen. From the liver some of the cells proceeded via afferent lymphatics to the coeliac lymph nodes. Similarly, some of the locally injected cells were carried with peripheral lymph to the draining popliteal lymph nodes, although most were retained in the footpads. In the spleen the VC/DC entered the periarteriolar lymphoid sheaths and in the coeliac and popliteal lymph nodes they became localized in the paracortex, where they acquired the morphology of mature IDC.

Animals↗

Intrathoracic sources of caudal mediastinal lymph node efferent lymph in sheep.

We investigated the intrathoracic contributions to the caudal mediastinal lymph node (CMN) efferent lymph in 12 anesthetized sheep after removing possible systemic contributions from below the diaphragm. We interrupted various pathways that may send lymph to the CMN (chest wall, esophagus, lung). Because the experiment is destructive, we did the resections in various combinations and waited 1 h between steps. Base-line CMN efferent lymph flow averaged 0.90 +/- 0.52 g/15 min (mean +/- SD). Cutting the pulmonary ligaments bilaterally caused lymph flow to decrease by an average of 58%. In five sheep, cauterizing around the lung hila reduced lymph flow by 16% of base line, cauterizing along the esophagus reduced lymph flow by 18% of base line, and cauterizing along the chest wall increased lymph flow by 6% of base line. After complete isolation of the node, except for the bronchoesophageal artery, dorsal mediastinal vein, and CMN efferent duct, 14% of base-line flow remained. The lymph-to-plasma total protein concentration ratios did not change significantly with any procedure. Under the conditions of our experiments, approximately 74% of base-line intrathoracic CMN efferent flow comes from the lung.

Abdominal Muscles↗

[Tumor size and regional lymph node metastasis in patients with M0 renal cell carcinoma: analysis in those having regional lymph node dissection].

We evaluated the relationship between regional lymph node metastasis and tumor size in patients with M0 renal cell carcinoma who received regional lymph node dissection. The study involved 234 of the 247 patients with localized renal cell carcinoma who underwent radical nephrectomy with lymph node dissection at our institute between 1985 and 1999. Patients were arbitrarily classified into 3 groups by the greatest diameter of the tumor on preoperative computed tomography (CT): 4.0 cm or less (group A), 4.1 to 7.0 cm (group B), and 7.1 cm or more (group C). The incidence of lymph node metastasis was assessed in each group. The current study showed that 11 (4.7%) of the 234 patients with lymph node dissection together with radical nephrectomy were lymph node positive. The incidences of lymph node metastasis were 4.0% in group A, 2.3% in group B, and 8.4% in group C (p = 0.79). Of these 11 patients with lymph node metastasis, 2 (18.2%) have so far survived for over 5 years following surgery. Although the role of regional lymph node dissection with radical nephrectomy might be limited and controversial in renal cell carcinoma, urological surgeons should always be aware of possible metastasis for any tumor size.

Adult↗

[Study of para-aortic lymph node metastasis for advanced gastric cancer on consecutive lymph node slices].

Para-aortic lymph nodes (No. 16) from 21 patients with advanced gastric cancer who underwent extensive lymph node dissection, were sliced consecutively at intervals of 50 mu to study minute metastasis of No. 16 lymph nodes. Twenty-six of 30 metastatic lymph nodes had minute involvement, in which carcinoma cells were detected in marginal sinus of lymph node, microscopically. The rate of the metastases to No. 16 lymph nodes was 19% among N0-3 cases by conventional method (not consecutive slices). On the contrary, the percentage of metastasis to No. 16 lymph nodes by consecutive slices was 33% among N0-3 cases. Therefore, No. 16 nodes are involved in metastasis at high rate at operation and the extensive lymph node dissection including No. 16 nodes (R4) will be recommended to prevent lymph node recurrence caused by such a minute metastasis.

Aorta↗

Lymph node-revealing solution: simple new method for detecting minute lymph nodes in colon carcinoma.

PURPOSE: Detection of metastatic lymph nodes in colon cancer is essential for determining stage and, thus, therapeutic modalities. However, very small lymph nodes can easily be missed during routine examination. The aim of this study is to describe a new and easy technique for detecting tiny nodes in colonic specimens. METHODS: Thirty problematic cases, in which an unsatisfactory number of lymph nodes was found by the traditional method, were investigated. The entire mesocolonic fat was immersed for six hours in a lymph node-revealing solution (LNRS) composed of various traditional fixatives and fatty solvents. After six hours, the lymph nodes stood out as white, chalky nodules on the background of yellow fat. They were then excised, processed. and stained. RESULTS: Total number of lymph nodes found by the traditional method in the 30 cases was 88. After LNRS, 258 additional lymph nodes, measuring from 0.5 to 7 mm in largest diameter, were found. Of the 12 cases in which no lymph nodes were found by the traditional method, 8 became N0 and 4 became N1. Of the 14 cases first classified as N0, 4 became N1; of the 4 classified at first as N1, 2 became N2 after LNRS. Upstaging from Dukes B to C occurred in eight cases. Quality of the sections and histochemical and immunohistochemical stains after LNRS was similar to that of formalin-fixed tissues. CONCLUSIONS: LNRS is an easy, rapid, and inexpensive technique for detecting very small lymph nodes. These may contain metastases, a fact that changes the stage of disease and influences the mode of therapy.

Acetic Acid↗

[A clinical study of 76 cases in carcinoma of the colon and rectum with metastasis to the peri-aortic lymph nodes. With particular reference to the skip metastasis in carcinoma of the sigmoid colon to the peri-aortic lymph nodes].

The therapeutic result by tumorous site were evaluated in 76 cases of carcinoma of the colon and rectum with the confirmed presence of metastasis to the peri-aortic lymph nodes. The results revealed that significant good out-comes were noted in the relatively non-curative cases of carcinoma of the sigmoid colon, with particularly good prognosis being found in six cases with skip metastasis. There was a 26.1% (6/23) incidence of the skip metastasis in carcinoma of the sigmoid colon with the peri-aortic lymph nodes metastasis. We confirmed two lymphatic routes of the skip metastasis; one route was from the lymph nodes near the tumor to the para-aortic lymph nodes directly, and the other was from the lymph nodes near the tumor to the lymph nodes at the aortic diffract directly and finally to the para-aortic lymph nodes. In the all six cases, the peri-aortic lymph nodes metastasis occurred only in inferior site of the inferior mesenteric artery. The average number of the peri-aortic lymph nodes metastasis were as few as 1.7 in these cases. The prognosis was favorable with three of the six cases scoring a three-year survival and included a five-year survival case.

Adult↗

[Cytokinetics of lymph nodes in lymph nodes in lymphatic system diseases (author's transl)].

Untreated malignant lymphatic system diseases are characterized by a preponderance of cell new formation (proliferation) against the destruction of lymphatic cells. If the lymph nodes are enlarged during these diseases, then cell new formation occurs largely or mostly in these lymph nodes. The proliferating cells of the lymph node are bigger than small lyphocytes and have, in general, a mean diameter of the nucleus of 10 mu and more. In normal lymph nodes they belong morphologically to the big lymphocytes, immunoblasts and plasmoblasts. In pathological lymph nodes they have to be looked for among the bigger cells of the disease-specific cell population. Whereas in healthy lymph nodes and in chronic lymphatic leukemia only about 1% of lymph node cells was found to proliferate, they amount on the average to 5% in lymphomas of lymphogranulomatosis and mostly to 30--50% in the lympho-reticulosarcoma (lymphoblast and immunoblast sarcoma, corresponding to large-cell, poorly differentiated lymphomas). The proliferating cells often appear as foci in the lymphomas. The generation times of the proliferating cells both in normal and pathological lymph nodes are about 24 hrs. or slightly longer. In lymphatic proliferation, apart from plasma cells big and smallymphocytes are produced in the normal lymph node; in CLL, big and small lymphocytes, in lymphogranulomatosis, big and small lymphocytes and Hodgkin-cells, and in poorly differentiated lymphomas, the corresponding lymphoma cells are produced. The clinicist is at the beginning of drawing conclusions from prevalent kinetic disturbances.

Cell Division↗

Lymph pathways of the medial retropharyngeal lymph node in dogs.

In dogs, lymph drains from tissues throughout the head, including the tonsils, along lymphatic vessels to the facial, parotid, lateral retropharyngeal and mandibular lymph nodes. From the mandibular lymph nodes, lymph may flow to the ipsilateral medial retropharyngeal lymph nodes, or along anastomotic connections to the contralateral node. Afferent lymphatics convey lymph from these nodes to defined areas in the medial retropharyngeal nodes. They divide over the surface of the node, and within trabeculae. Terminal afferent lymphatics are connected to the subcapsular and trabecular sinuses either through circular or oval holes in the vessel wall, or terminate at the sinus where the vessel contains a valve adjacent to the point of entry. The subcapsular sinus surrounds the entire node, and is continuous with an interconnecting network of trabecular and cortical sinuses which convey lymph through the cortex. Connective tissue septa extend through the sinuses and lymph flows freely between adjacent sinuses through holes in the septal walls. Initial efferent lymphatic vessels, which arise from the medullary sinuses between medullary cords, converge towards and unite within the network of medullary trabeculae. Other vessels, which contain valve-like flaps, drain lymph from the subcapsular sinus. Efferent vessels emerge along the hilus and coalesce to form the tracheal trunk. The tracheal trunk has several layers of smooth muscle cells, well developed elastic laminae and connective tissue, surrounding the lymphatic endothelium.

Animals↗

Mini-laparotomy pelvic lymph node dissection minimizes morbidity, hospitalization and cost of pelvic lymph node dissection.

PURPOSE: We compared efficacy, morbidity and cost of mini-laparotomy pelvic lymph node dissection and laparoscopic pelvic lymph node dissection. MATERIALS AND METHODS: A total of 40 patients underwent mini-laparatomy, laparoscopic or standard pelvic lymph node dissection during a 24-month period. Nodal yield, complications, hospitalization and postoperative analgesic requirements were retrospectively evaluated. Operative expenses and the cost of postoperative hospitalization were standardized to a base cost for comparison. RESULTS: Mini-laparotomy pelvic lymph node dissection has an operative time (90 minutes) and nodal yield (9) similar to those of standard pelvic lymph node dissection, and morbidity and postoperative hospitalization (1.3 days) are comparable to those of laparoscopic pelvic lymph node dissection. The expense of the mini-laparotomy procedure is approximately 50% that of the laparoscopic procedure due primarily to the prolonged operative time (190 minutes) and disposable instrument costs ($665) of laparoscopic pelvic lymph node dissection. CONCLUSIONS: Mini-laparotomy pelvic lymph node dissection competes successfully with laparoscopic pelvic lymph node dissection in terms of efficacy and morbidity at significant cost savings.

Aged↗

Intraoperative, radio-guided sentinel lymph node mapping in laparoscopic lymph node dissection for Stage I testicular carcinoma.

BACKGROUND: The management of regional lymph nodes in patients with clinical Stage I testicular carcinoma is a controversial problem. The authors investigated the feasibility and accuracy of radio-guided mapping of sentinel lymph nodes (SLNs) for men with clinical Stage I testicular tumors. METHODS: Twenty-two patients with clinical Stage I testicular carcinoma were enrolled in the study. One day before surgery, (99m)Technetium-labeled phytate was injected around the testicular tumor. After undergoing radical orchiectomy, patients underwent laparoscopic retroperitoneal lymph node dissection (L-RPLND). All radioactive lymph nodes were marked in the L-RPLND procedure, and three-dimensional SLN maps were made. All resected lymph nodes were evaluated by routine histopathologic examination, and the clinical significance of intraoperative SLN mapping was evaluated. RESULTS: SLNs were detected in 21 of 22 patients (95%). Nearly all SLNs were detected at the ventral or lateral side of the vena cava or at the aorta between the levels of the aortic bifurcation. All SLNs were detected easily in a surgical procedure. Only 1 radio-positive area per patient was identified in 15 patients, and approximately 2-4 positive areas were detected in 6 patients. Two patients had micrometastasis only in SLNs. In 2 patients who had seminoma, lymph node recurrences (at the level of the renal vein and in the obturator lymph node area) occurred at 10 months and 20 months after surgery. CONCLUSIONS: Radio-guided mapping of SLNs with laparoscopy was feasible, and nearly all SLNs were detected accurately by the procedure. In the near future, the standard retroperitoneal lymph node dissection may be avoided in most patients with clinical Stage I testicular carcinoma by utilizing focused examination of SLNs.

Adult↗

Effect of venous and lymphatic congestion on lymph capillary pressure of the skin in healthy volunteers and patients with lymph edema.

The aim of the present study was to assess the influence of venous and lymphatic congestion on lymph capillary pressure (LCP) in the skin of the foot dorsum of healthy volunteers and of patients with lymph edema. LCP was measured at the foot dorsum of 12 patients with lymph edema and 18 healthy volunteers using the servo-nulling technique. Glass micropipettes (7-9 microm) were inserted under microscopic control into lymphatic microvessels visualized by fluorescence microlymphography before and during venous congestion. Venous and lymphatic congestion was attained by cuff compression (50 mm Hg) at the thigh level. Simultaneously, the capillary filtration rate was measured using strain gauge plethysmography. The mean LCP in patients with lymph edema increased significantly (p < 0.05) during congestion (15.7 +/- 8.8 mm Hg) compared to the control value (12.2 +/- 8.9 mm Hg). The corresponding values of LCP in healthy volunteers were 4.3 +/- 2.6 mm Hg during congestion and 2.6 +/- 2.8 mm Hg during control conditions (p < 0.01). The mean increase in LCP in patients with lymph edema was 3.4 +/- 4.1 mm Hg, and 1.7 +/- 2.0 mm Hg in healthy volunteers (NS). The maximum spread of the lymph capillary network in patients increased from 13.9 +/- 6.8 mm before congestion to 18.8 +/- 8.2 mm during thigh compression (p < 0.05). No increase could be observed in healthy subjects. In summary, venous and lymphatic congestion by cuff compression at the thigh level results in a significant increase in LCP in healthy volunteers as well as in patients with lymph edema. The increased spread of the contrast medium in the superficial microlymphatics in lymph edema patients indicates a compensatory mechanism for lymphatic drainage during congestion of the veins and lymph collectors of the leg.

Adult↗