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Is there a therapeutic role for post-chemotherapy retroperitoneal lymph node dissection in metastatic transitional cell carcinoma of the bladder?

PURPOSE: We identified a subset of patients with bladder cancer (transitional cell carcinoma) and regional nodal metastasis to the retroperitoneal lymph nodes without detectable systemic dissemination. While the majority of these patients respond initially to chemotherapy, most have disease relapse at the same site within a year. We report the results of a phase II study exploring the potential benefit of retroperitoneal lymph node dissection in patients with transitional cell carcinoma of the bladder in whom disease has shown a significant response to chemotherapy. MATERIALS AND METHODS: A total of 11 patients with biopsy proven metastatic transitional cell carcinoma in the retroperitoneal lymph nodes and no evidence of visceral metastatic disease in whom disease showed a significant response to chemotherapy underwent complete bilateral retroperitoneal lymph node dissection. The end point of study was disease specific survival, calculated from the time of retroperitoneal lymph node dissection to death from transitional cell carcinoma of the bladder. RESULTS: Four patients underwent delayed retroperitoneal lymph node dissection. Seven patients underwent concurrent cystectomy, and pelvic and retroperitoneal lymph node dissection. There was no perioperative mortality. Nine patients had evidence of residual disease in the retroperitoneal nodes. Seven patients have recurrence outside of the original surgical field with a median time to recurrence of 7 months and 6 died at a median time to death of 8 months (range 5 to 14). One patient with retrocrural recurrence attained a complete response to salvage chemotherapy and remained disease-free 57 months after retroperitoneal lymph node dissection. For all 11 patients median disease specific and recurrence-free survival rates were 14 and 7 months, respectively. Four-year disease specific and recurrence-free survival rates were 36% and 27%, respectively. We stratified the patients based on the number of involved lymph nodes at retroperitoneal lymph node dissection and noted that viable tumor in no more than 2 lymph nodes correlated with greater disease specific and recurrence-free survival (p = 0.006 and 0.01, respectively). CONCLUSIONS: Retroperitoneal lymph node dissection can be safely performed for metastatic transitional cell carcinoma. Retroperitoneal lymph node dissection has curative potential, particularly in patients with viable tumor in no more than 2 lymph nodes after chemotherapy.

Carcinoma, Transitional Cell↗

Anatomical extent of lymph node dissection: impact on men with clinically localized prostate cancer.

PURPOSE: This study evaluates the influence of the anatomical extent of pelvic lymph node dissection performed at radical prostatectomy on lymph node yield, staging accuracy and time to prostate specific antigen progression. MATERIALS AND METHODS: Between February 1992 and April 2003, 2 surgeons at 1 hospital performed 2,135 and 1,865 radical prostatectomies with pelvic lymph node dissection, respectively. One surgeon routinely performed an extended lymph node dissection while the second surgeon performed a limited pelvic lymphadenectomy. The number of lymph nodes extracted and the number of patients with positive lymph nodes detected were analyzed and compared. Kaplan-Meier analysis was used to compare the biochemical recurrence-free survival between the 2 groups of patients with occult nodal disease. RESULTS: Extended lymph node dissection removed more lymph nodes (mean 11.6 vs 8.9, p<0.0001) and detected more lymph node positive disease (3.2% vs 1.1%, p<0.0001) than the more anatomically limited technique. This finding held true for patients across all pathology groups. Among men with lymph node positive disease involving less than 15% of extracted nodes, the 5-year prostate specific antigen progression-free rate for extended lymph node dissection was 43% versus 10% for the more limited lymph node dissection (p = 0.01). CONCLUSIONS: Compared to limited lymph node dissection, extended pelvic lymphadenectomy appears to identify men with positive lymph nodes more frequently. A significant benefit in biochemical recurrence-free survival may exist for certain subgroups undergoing the extended dissection. However, because the results may be influenced by stage migration, longer followup is necessary to determine whether the apparent therapeutic effect persists.

Adult↗

Trauma-hemorrhagic shock mesenteric lymph induces endothelial apoptosis that involves both caspase-dependent and caspase-independent mechanisms.

OBJECTIVE: To determine the mechanism by which gut-derived factors present in mesenteric lymph from rats subjected to trauma-hemorrhagic shock (T/HS) induce endothelial cell death. SUMMARY BACKGROUND DATA: Intestinal ischemia after hemorrhagic shock results in gut barrier dysfunction and the subsequent production of biologically active and tissue injurious factors by the ischemic gut. These factors are carried in the mesenteric lymph and reach the systemic circulation via the mesenteric lymph, thereby ultimately resulting in distant organ injury. Although studies have established that trauma-hemorrhagic (T/HS) shock but not trauma-sham-shock (T/SS) mesenteric lymph is cytotoxic to endothelial cells, whether T/HS lymph-induced endothelial cell death occurs via an apoptotic or a necrotic pathway is unknown. The mechanisms underlying T/HS lymph-induced cytotoxicity are likewise unknown. METHODS: Human umbilical vein endothelial cell (HUVEC) monolayers were incubated with medium, sham-shock, or post shock mesenteric lymph (5%) for 4 hours, after which the mode of cell death (ie, apoptosis versus necrosis) was determined using morphologic (confocal microscopy), biochemical (nucleosomal release), and DNA-based (gel electrophoresis) assays. To clarify the cellular pathways involved in T/HS lymph-induced HUVEC cell death, caspase-3, caspase-9, caspase-8, and BID activity was measured as was the ability of the pan-caspase inhibitor z-VAD-fmk to prevent T/HS lymph-induced cell death. RESULTS: T/HS, but not T/SS, mesenteric lymph or medium was cytotoxic and caused the appearance of the classic morphologic signs of apoptosis, including membrane blebbing, cell shrinkage, and apoptotic body formation. Nucleosomal release and a DNA laddering pattern was also observed in the HUVECs incubated with T/HS lymph. These signs of apoptosis were associated with increased caspase activity as reflected in activation of the pro-apoptotic caspases, caspase-8, -9, and -3, as well as the pro-apoptotic bcl-2-related protein BID. However, since the broad-spectrum caspase inhibitor z-VAD-fmk delayed T/HS lymph-induced HUVEC cell death, but did not prevent it fully, it appears that other factors besides caspases are involved in the endothelial cell toxicity of T/HS lymph. CONCLUSIONS: Gut-derived factors in T/HS, but not T/SS, mesenteric lymph cause endothelial cell death via an apoptotic mechanism that involves both caspase-dependent and caspase-independent pathways.

Animals↗

Lymphoid cells in afferent and efferent intestinal lymph: lymphocyte subpopulations and cell migration.

Gut wall emigrating cells have been characterized in the intestinal lymph. The intestinal lymph duct was cannulated in 6-month-old minipigs. Under non-restraining conditions the efferent lymph from the mesenteric lymph nodes was collected in seven normal animals. Lymph coming directly from the gut (afferent lymph) was also collected in 18 pigs after resection of the mesenteric lymph node chains 3 months previously. The intestinal lymph flow was similar in both groups (around 18 ml/h). The lymphoid cell yield was 1.2 +/- 1.0 x 10(6)/h in control animals, while in mesenteric lymph node resected pigs it was around 20 times higher (26.2 +/- 17.6 x 10(6)/h). In the gut-derived lymph 76.5 +/- 8.8% T lymphocytes were observed (CD4+, 48.1 +/- 15.5%; CD8+, 53.6 +/- 12.7%). The percentage of immunoglobulin-positive cells was lower (IgM+, 10.1 +/- 4.5; IgA+, 1.7 +/- 1.1). In 14 mesenteric lymph node resected pigs a mean of 5.6 +/- 3.1 x 10(8) lymphocytes from the gut lymph were labelled in vitro with a fluorescent dye and retransfused. The labelling index of fluorescent cells in the intestinal lymph increased rapidly and remained at a high level until 44 h after cell transfusion. A four-to-ten times lower labelling index was found in the spleen, various lymph nodes and Peyer's patches. Most of the recovered lymphocytes were T cells. This model provides access to the cell pool leaving the gut wall, thus allowing an examination of its role in the gastrointestinal tract and other mucosal-lined organs.

Animals↗

Lymph flow pattern in the intact thoracic duct in sheep.

1. To study the lymph flow dynamics in the intact thoracic duct, we applied an ultrasound transit-time flow probe in seven anaesthetized and four unanaesthetized adult sheep (approximately 60 kg). In unanaesthetized non-fasting animals we found that lymph flow in the thoracic duct was always regular pulsatile (pulsation frequency, 5.2 +/- 0.8 min-1) with no relation to heart or respiratory activity. At baseline the peak level of the thoracic duct pulse flow was 11.6-20.7 ml min-1 with a nadir of 0-3.6 ml min-1. Mean lymph flow was 5.4 +/- 3.1 ml min-1. The flow pattern of lymph in the thoracic duct was essentially the same in the anaesthetized animals. 2. In both the anaesthetized and unanaesthetized animals, the lymph flow response to a stepwise increase in the outflow venous pressure showed interindividual variation. Some were sensitive to any increase in outflow venous pressure, but others were resistant in that lymph flow did not decrease until outflow venous pressure was increased to higher levels. This resistance was also observed in the high lymph flow condition produced by fluid infusion in the anaesthetized animal and mechanical constriction of the caudal vena cava in the unaesthetized animals. Pulsation frequency of the thoracic duct flow initially increased and then decreased with a stepwise increase in the outflow venous pressure. This initial increase might be a compensatory response to maintain lymph flow against elevated outflow venous pressure. 3. To test the effect of long-term outflow venous pressure elevation in unanaesthetized sheep, outflow venous pressure was increased by inflation of a cuff around the cranial vena cava for 1, 5 or 25 h. The cuff was inflated to a level where lymph flow was reduced. Lymph flow remained low or decreased further during the entire cuff-inflation period. We calculated the lymph debt caused by the outflow venous pressure elevation and the amount 'repaid' when venous pressure returned to normal. Lymph debt for 25 h was 6400 ml but only 200 ml was repaid. Since we observed no visible oedema formation in the lower body of the sheep, the non-colloidal components of the lymph must have been reabsorbed into the bloodstream, most likely in the lymph nodes.

Activity Cycles↗

Catalytic enzyme activity concentration in thoracic duct, liver, and intestinal lymph of the dog, the rabbit, the rat and the mouse. Approach to a quantitative diagnostic enzymology, II. Communication.

In the mixed body lymph of the thoracic duct and in the defined organ lymph of the liver and the intestine, the catalytic activity concentrations of up to sixteen enzymes and the concentrations of albumin and protein were determined, as well as the transport rate of these substances and their lymph/plasma ratio. Thoracic duct lymph specimens were obtained from an extracorporeal lymph shunt in anaesthetized and conscious dogs and from short-term fistulas in anaesthetized rabbits, rats and mice. Additionally, rabbits and rats underwent passive motion of the hind limbs in another experimental trial. Thoracic duct flow in anaesthetized dogs is only half that seen in conscious dogs, due to bypassed muscular lymph. A similar flow change is seen during passive motion of hind limbs in anaesthetized rabbits and rats. From a literature review of flow in the four main lymphatics of the body, it is concluded that the thoracic duct flow should account for 50-70% of total body lymph flow. In the anaesthetized state, flow is mainly of visceral origin. In the conscious state and during passive motion the increased flow is of muscular origin. In the latter case, the catalytic activities of enzymes like lactate dehydrogenase, malate dehydrogenase, creatine kinase, aldolase and phosphohexose isomerase, increase in lymph as does their lymph/plasma ratio. These enzymes have high catalytic activities in muscle. Their transport into the blood increases 2-3-fold, due to a doubling of lymph flow. Reported data for anaesthetized and immobile animals therefore far underestimate the significance of thoracic duct enzyme transport. Liver lymph was obtained from anaesthetized dogs and rabbits. Our finding that lymph catalytic activity for several enzymes is higher than in plasma is not compatible with the proposed delivery of plasma proteins directly into the sinusoidal space without prior mixing with the Space of Disse. Enzymes in liver lymph should derive from parenchymal and endothelial lining cells. Their site of delivery from the hepatocyte seems different from that of proteins. Liver lymph is an important transport route of enzymes into the blood. Intestinal lymph was sampled from anaesthetized dogs, rabbits and rats. It was shown that most enzymes from the intestine are primarily released into the interstitial space and from there are transported via the lymph into the blood.

Anesthesia↗

Variability in the detection of enlarged mediastinal lymph nodes in staging lung cancer: a comparison of contrast-enhanced and unenhanced CT.

OBJECTIVE: Because CT protocols for staging lung cancer vary and little information exists regarding the diagnostic importance of using i.v. contrast material, our intent was to evaluate intra- and interobserver agreement in the detection of enlarged mediastinal lymph nodes, comparing i.v. contrast-enhanced and unenhanced CT. SUBJECTS AND METHODS: Fifty patients with known or suspected bronchogenic carcinoma underwent unenhanced thoracic CT followed by contrast-enhanced CT. Three observers noted enlarged lymph nodes (> 10 mm in the short axis) and assigned the enlarged nodes to American Thoracic Society nodal station designations. Enlarged lymph nodes were grouped two ways: by assigning the exact number of enlarged lymph nodes found (zero, one, two, three, four or more), and by assigning whether at least one, or no, enlarged mediastinal lymph nodes were found at a station ("one or none"). Agreement levels were determined for inter- and intraobserver interpretations using weighted kappa statistics and the McNemar test. RESULTS: The number of enlarged lymph nodes with enhanced CT was 11% higher than on unenhanced studies (418 versus 377; p = .044). Numbers of enlarged lymph nodes were different for five stations; however, the numbers were small except for the right upper paratracheal station (2R) (contrast-enhanced, 68 enlarged lymph nodes; unenhanced, 44 enlarged lymph nodes; p = .014). With regard to all stations together, intraobserver agreement between contrast-enhanced and unenhanced studies was almost perfect (kappa range, .85-.94), and no difference was found for any observer in the proportion of patients with at least one enlarged lymph node. Interobserver agreement was substantial or almost perfect for the total number of enlarged lymph nodes. For specific stations, the lowest kappa value was .48 at 2R. One observer reported more patients with at least one enlarged lymph node with contrast enhancement at station 2R (p = .031). Greater agreement existed between two observers at station 2R with contrast enhancement versus no enhancement (kappa = .85 versus .48; p = .02). Conclusions matched, and calculations of estimated kappa values gave similar results for determination of the specific number of enlarged lymph nodes at a station and the "one or none" category. CONCLUSION: We found high agreement for intra- and interobserver interpretations for contrast-enhanced and unenhanced CT, although contrast-enhanced CT revealed more enlarged lymph nodes, especially at station 2R.

Adult↗

Association between lymph node size and metastasis in dogs with oral malignant melanoma: 100 cases (1987-2001).

OBJECTIVE: To determine the association between lymph node size and metastasis and to assess measurement of lymph node size as an accurate and reliable means of tumor staging in dogs with oral malignant melanoma. DESIGN: Retrospective study. ANIMALS: 100 dogs with histologically confirmed oral malignant melanoma. PROCEDURE: Clinical records for dogs with oral malignant melanoma were reviewed. Data regarding size and results of cytologic or histologic examination of lymph nodes were evaluated. The association between lymph node size and metastasis was determined. RESULTS: Forty-seven (47%) dogs, of which 23 (49%) had enlarged mandibular lymph nodes, had no cytologic or histologic evidence of metastasis. Of 53 (53%) dogs with cytologic or histologic evidence of mandibular lymph node metastasis, 37 (70%) had enlarged mandibular lymph nodes, and 16 (30%) had mandibular lymph nodes of normal size. Overall, 16 of the 40 (40%) dogs with normal-sized lymph nodes had microscopic evidence of metastatic disease. Sensitivity and specificity of lymph node size as a predictor of metastasis were 70 and 51%, respectively, and the positive and negative predictive values were 62 and 60%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Although a significant relationship was identified between lymph node size and metastasis to the lymph node, this association did not appear strong enough to be clinically relevant. Results suggest that lymph node size alone is insufficient for accurate clinical staging of oral malignant melanoma in dogs; cytologic or histologic examination of regional lymph nodes should routinely be performed, regardless of size of those nodes.

Animals↗

The role of popliteal lymph nodes in differentiating rheumatoid arthritis from osteoarthritis by using CE 3D FSPGR MR imaging: relationship of the inflamed synovial volume.

OBJECTIVE: We wanted to assess the role of the popliteal lymph nodes for differentiating rheumatoid arthritis (RA) from osteoarthritis (OA), and we also wanted to investigate the relationship between the popliteal lymph nodes and the inflamed synovial volume (ISV) by using contrast enhanced (CE), fat suppressed, three dimensional-fast spoiled gradient echo (3D-FSPGR) MR imaging. MATERIALS AND METHODS: Contrast enhanced 3D-FSGPR MR imaging of 94 knees (21 with RA and 73 with OA) was analyzed. A lymph node was defined as being 'observed' if it could be seen in at least two planes of the three orthogonal reformatted planes. The number of observed lymph nodes, the mean of the smallest dimension of each lymph node and the existence of central fatty change were recorded. The OA group was graded according to the ISV calculated by a segmentation method: grade I was < 20 cm(3); grade II ranged from 20 cm(3) to 40 cm(3); and grade III was > 40 cm(3). Statistical analysis of the number and the mean size of the popliteal lymph nodes among the four groups (the RA group and the grade I-III OA groups) was performed. RESULTS: The prevalence of the observed popliteal lymph nodes was significantly different between all the OA groups or between the grade III OA group and the RA group (p < 0.0001, 0.0001, respectively). The popliteal lymph node was observed in 32 out of 73 OA cases, whereas it was visible in all of the 21 RA cases. The number (mean +/- standard deviation) of lymph nodes in the grade I OA group, the grade II OA group, the grade III OA group and the RA group was 1.2 +/- 0.4, 1.2 +/- 0.4, 1.3 +/- 0.5, and 2.7 +/- 1.1, respectively. The mean size (mean +/- standard deviation) of the lymph nodes was 3.8 +/- 1.0 mm, 3.6 +/- 1.1 mm, 4.1 +/- 0.8 mm, and 5.4 +/- 1.3 mm, respectively. The incidence of central fatty changes was significantly lower in the RA group than in all the OA groups and the grade III OA group. When differentiating RA from OA, and when the differentiation was confined to the RA group and grade III OA group, respectively, the criteria of the number of lymph nodes, their size, their central fatty change and a combination of all these three criteria showed statistical significance (Az values for the former were 0.869, 0.847, 0.776, and 0.942; Az values for the latter were 0.855, 0.799, 0.712, and 0.916). The number and mean size of the lymph nodes correlated with the ISVs (r = 0.49, p < 0.001; 0.50, 0.001, respectively). CONCLUSION: The number, size and central fatty changes in the popliteal lymph nodes observed on the MR images might serve as simple and useful markers in differentiating RA disease from OA disease. These markers would be particular helpful in cases of severe synovial enhancement where the ISVs of both RA and OA overlap. The number and mean size of the lymph nodes also correlated well with the ISV.

Adult↗

A morphological study of antibody transport in the transparent fluid flowing form the lymph-folds of the copulatory organ into the cloacal lumen of the cock (Gallus domesticus).

The lymph of the copulatory organ of the cock is produced mainly in the lymphobulbus phalli. The lymph fluid passes the secretory duct with its branching lymph capillaries and discharges into the lymph-fold. From here, it is released into the interstitial tissue through gaps of the lymph capillaries but also through the intercellular spaces between the endothelial cells of the lymph capillaries. A minor portion of the lymph is produced also in the lymph-fold from where it is transported in the interstitial tissue either by transfer vesicles of the circulatory blood capillaries or by pores and fenestrae of the transudatory blood capillaries. During the erection of the copulatory organ the lymph is pressed through the intercellular spaces of the epithelial covering the lymph-fold which is cylindrical and multistratified in shape. From here, it reaches the cloacal lumen in the form of transparent fluid (TF). TF was collected by different methods. It contains immunoglobulins which arise from plasma cells of the lymph-fold. Juxtaluminally, the lymph passage takes place via zonulae pseudooccludentes. The epithelial covering secretes a mucoid substance which is added to the TF prior to its following the spermatic phase as the final fraction of the ejaculate. Plasma cells and lymphocytes migrate along the lymph flow in the intercellular spaces of the epithelial covering of the lymph-fold. After an experimental application of antigen the sub- and intraepithelial cells and lymphocytes increase in number with their portion of active cells exceeding the less active ones. The increase coincides with the increase in antibodies detected in the TF where they may cause a local immunisation.

Animals↗

[Optimal lymph node dissection for carcinoma of the biliary tract].

To clarify the optimal lymph node dissection for carcinoma of the biliary tract, we analyzed the mode of lymphatic spread in 86 resected cases with carcinoma of the gallbladder and 139 with carcinoma of the extrahepatic bile duct, and investigated long-term results after resection based on the degree of lymph node metastasis. Of the 86 patients with carcinoma of the gallbladder, 62 (72.1%) had lymph node metastasis. Patients with m and mp tumors (n = 9) had no lymph node metastasis, whereas ss tumors (n = 13) had 23.1% lymph node metastasis. Those with se, si tumors (n = 64) had greater lymph node involvement (92.2%). In 4 patients with advanced carcinomas (ss or more) who survived more than 5 years, only one (limited to periportal lymph nodes) of them had lymph node metastasis. Of the 139 patients with carcinoma of the extrahepatic bile duct, 58 (41.7%) had lymph node metastasis. There was no lymph node metastasis in 15 patients with m or fm tumors. The frequency of metastasis in the ss (n = 39) and se, si (n = 85) tumors was 17.9% and 60.0%, respectively. Twenty-four patients with advanced tumors survived more than 5 years. Curative resection was achieved in all 24 and lymph node metastasis was n0 in 19, n1 in 4 and n2 in 1 patients. Satisfactory long-term result can be achieved in carcinoma of the biliary tract after resection when lymph node metastasis is limited to nodes in the hepatoduodenal ligament. In view of our surgical results and the lymphatic drainage system of the biliary tract, systemic dissection of the regional lymph nodes, including periportal, posterior pancreato-duodenal, and celiac nodes, is necessary in patients with N0-N2 (limited to lymph nodes in the hapatoduodenal ligament) tumors in whom it contributes to good prognosis.

Biliary Tract Neoplasms↗

Extended pelvic lymphadenectomy in patients undergoing radical prostatectomy: high incidence of lymph node metastasis.

PURPOSE: Lymphadenectomy for prostate cancer is limited to obturator and external iliac lymph nodes, although the internal lymph nodes represent the primary landing zone of lymphatic drainage. We performed anatomically adequate extended pelvic lymphadenectomy to assess the incidence of lymph node metastasis in cases of clinically localized prostate cancer. MATERIALS AND METHODS: A total of 103 consecutive patients underwent extended pelvic lymphadenectomy at radical retropubic prostatectomy comprising 9 selective fields, namely the external iliac, internal iliac, obturator and common iliac lymph nodes bilaterally, and the presacral lymph nodes. Histopathological findings were compared with serum prostate specific antigen (PSA), histopathological stage, preoperative biopsy and postoperative prostatectomy Gleason score. Extended pelvic lymphadenectomy was compared with radical retropubic prostatectomy and standard lymphadenectomy in 100 consecutive patients in terms of complications, the number of lymph nodes dissected and operative time. RESULTS: There were no significant differences in age, preoperative PSA or mean biopsy Gleason score in patients who underwent extended pelvic and standard lymphadenectomy. Metastases were diagnosed in 27 of the 103 patients (26.2%) who underwent the extended procedure. A mean of 28 lymph nodes (range 21 to 42) were dissected. Metastases were identified in the internal iliac and presacral regions despite negative obturator lymph nodes. Of the 27 patients 1 to 3 lymph nodes involved with metastasis were detected in 15, 9 and 1, respectively. In 26 of the 27 patients (95.8%) with lymph node metastasis PSA was greater than 10.5 ng./ml. and preoperative biopsy Gleason sum was 7 or greater. A low risk of 2% for lymph node disease was noted in patients with serum PSA less than 10.5 ng./ml. and biopsy Gleason sum less than 7. There were no significant differences in regard to intraoperative and postoperative complications, lymphocele formation or blood loss in the 2 groups. CONCLUSIONS: Extended pelvic lymphadenectomy is associated with a high rate of lymph node metastasis outside of the fields of standard lymphadenectomy in cases of clinically localized prostate cancer. Lymphadenectomy including the internal iliac lymph nodes should be performed in all patients with prostate cancer who are at high risk for lymph node involvement, as indicated by PSA greater than 10.5 ng./ml. and biopsy Gleason sum 7 or greater. In the low risk group pelvic lymphadenectomy can be omitted.

Aged↗

[Influence of the number of lymph node metastasis on survival and significance of postoperative radiotherapy for esophageal carcinoma].

OBJECTIVE: To analyze the influence of the number of lymph node metastasis on survival and prophylactic postoperative radiotherapy after radical resection of thoracic esophageal carcinoma. METHODS: Four hundred and ninety-five patients with thoracic esophageal squamous cell cancer who had undergone radical resection were randomly divided into surgery group alone (S, 275) and surgery plus radiotherapy group (S + R, 220). The patients were classified into three groups: Group A: 234 patients (47.2%) without lymph node involvement; Group B: 146 patients (29.5%) with 1 to 2 involved lymph nodes and Group C: 115 patients (23.2%) with >or= 3 involved lymph nodes. RESULTS: 1. The 5-year survival rate in Groups A, B and C for the same T stage (T3) was 52.6%, 28.8% and 10.9%, respectively (P = 0.0000); the 5-year survival rate in group C was 0% in S group and 19.3% in S + R group (P = 0.0336); 2. In the positive lymph node group, the metastatic rate of intra-thoracic and supraclavicular lymph node was 35.9% and 21.2% in S group and 19.7% and 4.4% in S+R group (P = 0.014 and P = 0.000). In the negative lymph node group, the metastatic rates of intra-thoracic lymph node was 27.8% in S group and 10.3% in S + R group (P = 0.003). The metastatic rate of intra-abdominal lymph node in Groups A, B and C was 3.9%, 9.4% and 17.5%, respectively (P = 0.0000). The occurrence of hematogenous metastasis was most frequent in group C (27.8%) with >or= 3 positive lymph nodes. CONCLUSION: 1. The number of metastatic lymph node is one of the important factors which affects the survival of thoracic esophageal carcinoma. 2. Chemotherapy might be given to the patients with three or more lymph nodes involved who have the possibility of developing hematogenous metastasis. Postoperative radiotherapy can reduce the occurrence of intra-thoracic and supraclavicular lymph node metastasis and improve the survival of patients with three or more lymph nodes involvement.

Adult↗

[Interferon production in lymph nodes draining breast carcinoma and its augmentation by OK-432].

In breast cancer patients on whom modified radical mastectomy is performed, relatively more of the regional lymph nodes draining the breast carcinoma remain in comparison with standard radical mastectomy. Therefore, investigation of the functions of lymph nodes draining breast carcinoma has become important. Lymphocyte subsets of 33 axillary lymph nodes from 19 breast cancer patients were analysed using flow cytometry. In axillary lymph nodes, both OKT-3(+) cells and OKT-8(+) cells were decreased in comparison with those in peripheral blood. However, the OKT 4/8 ratio was increased in axillary lymph nodes. These findings suggest that axillary lymph nodes are immunologically more functional against cancer spread than peripheral blood. OK-M1(+) cells, Leu-7(+) cells and Leu-11a(+) cells were decreased in axillary lymph nodes in comparison with peripheral blood. The ability of IFN production in axillary lymph nodes and peripheral blood was analysed using the cytopathic effect of VSV-sindbis virus. After 72 hours incubation, IFN production of axillary lymph nodes showed maximum titer. When lymph nodes were co-cultured with OK-432, IFN production of axillary lymph nodes was strongly augmented. IFN production of axillary lymph nodes draining breast carcinoma were increased in comparison with peripheral blood. Axillary lymph nodes draining breast carcinoma would thus seem to be important as cytokine-producing organs. IFN has been found to be an activator of NK cells, cytotoxic T cells and IL-2 production. Axillary lymph nodes may therefore play an important role against the spread of breast cancer.

Axilla↗

[Clinical evaluation of cervical and superior mediastinal lymph node dissection for intrathoracic esophageal carcinoma].

From 1985 to 1989, 257 cases of carcinoma of the thoracic esophagus underwent esophagectomy and lymph node dissection with right thoracotomy based on preoperative staging. Bilateral cervical lymph node dissection was selected in cases in which preoperative examinations (CT, US, EUS, etc) revealed metastasis to cervical or superior mediastinal lymph nodes and cervical or superior mediastinal lymph nodes and in cases of tumors of the upper intrathoracic esophagus. All cases were classified into 3 groups according to region of lymph node dissection. In addition to dissection of the lymph node in the mediastinum and abdomen, group A (102 cases) underwent bilateral cervical and extensive superior mediastinal lymph node dissection (en bloc removal of tissue from the upper mediastinum), group B (61 cases) underwent extensive superior mediastinal lymph node dissection with or without left side cervical dissection and group C (94 cases) underwent standard dissection. Group A contained more advanced cases and cases with metastasis to the upper mediastinal lymph nodes compared to groups B and C. Postoperative complications were also more frequent in group A than groups B or C and were slightly more frequent in group C than group B. Recurrent nerve palsy was recognized in 21% of group A cases. Operative death (within 30 days) was highest in the group A (5.8%) particularly in the elderly group aged over 70 y or absolutely non-curatively resected cases, while in group C the operative mortality was 2.2%. Apart from absolutely non-curatively resected cases, there was no significant difference in the survival curves of the 3 groups, and there was no difference between group A and B cases with no cervical metastasis and group C cases. Also, this selection showed a favorable survival curve following esophagectomy in the period since 1985 compared to the earlier period (1980-1984), excluding absolutely non-curative cases and early stage cases (ep, mm cancer). The results suggest our evaluation methods and selection criteria were appropriate. All absolutely non-curatively resected cases had poor survival rates without significant difference among the 3 groups. In this category of cases, bilateral cervical lymph node dissection of absolutely non-curative cases was not effective. In cases with 1-3 metastatic lymph nodes of all, there was a significant difference in prognosis between group A and groups B and C, but there was no significant difference in cases with more than 4 metastatic lymph nodes. Those results suggest that when 1-3 lymph nodes are metastatic, it is necessary to dissect bilateral cervical lymph nodes.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Modified clearing technique to identify lymph node metastases in post-irradiated surgical specimens from rectal adenocarcinoma.

The aim of this study is to describe a modification of the original method of clearing lymph nodes in specimens from rectal adenocarcinoma and its yield in comparison to a control group whose specimens were studied by a manual technique. There were 32 consecutive patients with locally advanced rectal adenocarcinoma. All patients received preoperative radiation therapy (PRT) at doses of 45 Gy, concomitant with 5-fluorouracil at the doses of 450 mg/m2 IV bolus, days 1-5 and 28-33 of PRT; 4-8 weeks later radical surgery with a curative intent was performed. Twenty two specimens were studied by a manual technique consisting of fixation in 10% formalin. Ten specimens were studied with the modified clearing technique consisting of administration through the inferior mesenteric artery of methylene blue; fixation with 10% formalin plus 0.01% of methylene blue; clearing the fat with a sequence of 95% alcohol-100% acetone-100% xylene. In the 32 specimens, 413 lymph nodes were found. Using the manual technique 104 lymph nodes were found (average 4.7 lymph nodes per specimen); 309 lymph nodes by the modified clearing technique (average 30.9 lymph nodes per specimen), (p < 0.0001). Using the manual technique 23 out of 104 lymph nodes (22%) contained metastases. All metastatic lymph nodes measured > 5 mm; 18 out of 23 metastatic lymph nodes were located on the perirectal area (level 2); and five were located in the root of the inferior mesenteric artery (level 5). Using the modified clearing technique 278 out of 309 (89%) lymph nodes measured < 5 mm; 15 out of 309 (4.8%) lymph nodes contained metastases; 9 out of 15 (60%) measured > 5 mm and were located on levels 2 and 5; and six, located on level 5, measured < 5 mm. The modified clearing technique is a quick, easy and reproducible method for identifying lymph nodes in post-irradiated surgical specimens. In comparison to the traditional manual method of searching for lymph nodes, it improves in the detection of small lymph nodes (< 5 mm), allowing better staging in patients with rectal adenocarcinoma.

Adenocarcinoma↗

Lymphatic mapping and sentinel lymph node biopsy in the management of primary cutaneous melanoma: report of a single-centre experience.

AIMS AND BACKGROUND: Lymphatic mapping and sentinel lymph node biopsy provide important prognostic data in patients with early stage melanoma and are crucial in guiding the management of the tumor. We report our experience with lymphatic mapping and sentinel lymph node biopsy in a group of patients with primary cutaneous melanoma and discuss recent concepts and controversies on its use. PATIENTS AND METHODS: A total of 111 patients with stage I-II AJCC primary cutaneous melanoma underwent lymphatic mapping and sentinel lymph node biopsy from December 1999 through December 2004 using a standardized technique of preoperative lymphoscintigraphy and biopsy guided by blue dye injection in addition to a hand-held gamma probe. After removal, sentinel lymph nodes were submitted to serial sectioning and permanent preparations for histological and immunohistochemical examination. Complete lymph node dissection was performed only in patients with tumor-positive sentinel lymph nodes. RESULTS: Sentinel lymph nodes were identified and removed in all patients (detection rate of 100%), and metastases were found in 17 cases (15.3%). The incidence of metastasis in sentinel lymph nodes was 2.1%, 15.9%, 35.2%, and 41.6% for melanomas < or 1.0, 1.01-2.0, 2.01-4.0, and > 4.0 mm in thickness, respectively. Complete lymph node dissection was performed in 15 of 17 patients with positive sentinel lymph nodes, and metastases in non-sentinel lymph nodes were detected in only 2 cases (11.7%). Recurrences were more frequently observed in patients with a positive than in those with negative sentinel lymph node (41.1% vs. 5.3% at a median follow-up of 31.5 months, P < 0.001). The false-negative rate was 2.1%. CONCLUSIONS: Our study confirms that lymphatic mapping and sentinel lymph node biopsy allow accurate staging and yield relevant prognostic information in patients with early stage melanoma.

Adult↗

Evaluation of immunohistochemistry and multiple-level sectioning in sentinel lymph nodes from patients with breast cancer.

CONTEXT: Previous investigations on sentinel lymph node biopsies have demonstrated their importance in nodal staging of patients with breast cancer. However, sentinel node biopsy in breast cancer is currently a controversial procedure and continues to provoke debate. OBJECTIVES: We designed our study to determine the usefulness of a standard protocol for evaluating sentinel lymph node metastases and to assess the value of sentinel node biopsy as the only procedure in nodal staging in breast cancer patients. MATERIALS AND METHODS: A retrospective analysis of 84 breast cancer patients with sentinel node biopsies, who also underwent axillary dissection, was conducted using a standard protocol (3 levels of immunohistochemical stains for keratin and 2 levels of hematoxylin-eosin (HE) stains on the first 3 negative lymph nodes). RESULTS: Hematoxylin-eosin staining identified 20 patients (23.8%) with sentinel node metastases. The remaining 64 negative patients (76.1%) were tumor free on sentinel lymph nodes at level 1 HE. Additional immunohistochemical stains for keratin and HE stains on specimens from these 64 patients showed an additional 5 patients (7.8%) to be positive for lymph node micrometastases (<2 mm). The total percentage of cases with sentinel lymph node metastases detected by HE staining and immunohistochemistry was 29.7%. Of the remaining 59 cases that were negative on HE and immunohistochemistry, axillary dissection revealed 3 cases that had metastases in the axillary lymph nodes. The false-negative rate was 10.7%. The concordance rate between sentinel lymph nodes and axillary lymph nodes was 96.4%. The sensitivity was 89% and specificity was 100%. CONCLUSION: Immunohistochemistry and multiple-level sectioning increased detection of metastases by 7.8% in sentinel lymph nodes. Caution should be used in accepting sentinel node biopsy alone as the only procedure for staging due to a high false-negative rate (10.7%). A predictive value of 96.4% confirms that sentinel lymph node biopsy is most likely to contain metastatic carcinoma. Sentinel lymph node examination with the protocol we describe, combined with axillary dissection, increased the yield of metastatic disease by identifying 8 additional cases of nodal metastatic disease (an increase of 28%), as compared to standard axillary nodal dissection and single-section sentinel lymph node examination alone.

Adult↗