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Clinical implications of lymph node micrometastases in patients with colorectal cancers. A case control study.

There is no unanimity about the prognostic significance of lymph node micrometastases from colorectal cancer. A case-control study of patients with recurrent and nonrecurrent colorectal cancer who were closely matched for the Dukes stage, extent of lymph node dissection, tumor size, tumor location, number of resected lymph nodes, age and gender was performed. The presence of micrometastases in a total of 1,633 lymph nodes from 44 patients (22 with and 22 without recurrence) were examined by immunohistochemistry using antibodies for cytokeratin (KL-1) and p53 (RSP53). Immunostaining with KL-1 revealed micrometastases in 15/22 patients [68%; 82/820 lymph nodes (10%)] and 15/22 patients [68%; 45/813 lymph nodes (6%)] in the recurrent and nonrecurrent groups, respectively. Immunohistochemical analysis, using RSP53, of 18 paired patients with p53-positive primary tumor revealed micrometastases in 4/9 patients [44%; (7/265 lymph nodes (2.6%)] and 4/9 patients [44%; 6/257 lymph nodes (2.3%)] with and without recurrence, respectively. Neither the micrometastatic frequencies of the patients nor the resected lymph nodes of the recurrent and nonrecurrent groups differed significantly. Micrometastases in regional lymph nodes are an interesting phenomenon, but do not influence patients' prognoses if the involved lymph nodes are removed.

Adult↗

The impact of surgical adjuvant thoracic radiation therapy for patients with nonsmall cell lung carcinoma with ipsilateral mediastinal lymph node involvement.

BACKGROUND: Previous nonsmall cell lung carcinoma studies have shown that patients with ipsilateral mediastinal (N2) lymph node involvement who underwent surgical resection have a greater local recurrence rate than those with less lymph node involvement (N0, N1). Therefore, it was hypothesized that complete surgical clearance of subclinical lymph node disease is difficult in N2 patients and that adjuvant postoperative thoracic radiotherapy (TRT) may be beneficial. METHODS: A retrospective review was performed to determine the local recurrence and survival rates for patients with N2 disease undergoing complete surgical resection with or without adjuvant TRT. Between 1987 and 1993 at the Mayo Clinic, 224 patients underwent complete resection of N2 nonsmall cell lung carcinoma. More than one mediastinal lymph node station was sampled in 98% of patients; 39% then received adjuvant TRT (median dose, 50.4 grays). RESULTS: The median follow-up time was 3.5 years for the patients who were alive at the time of the analysis. The surgery alone versus surgery plus TRT groups were well balanced with respect to gender, age, histology, tumor grade, number of mediastinal lymph node stations dissected or involved, and involved N1 lymph node number. There were slightly more patients with right lower lobe lesions (compared with other lobes), patients with multiple lobe involvement, and patients with only one N2 lymph node involved in the surgery alone group. After treatment with surgery alone, the actuarial 4-year local recurrence rate was 60%, compared with 17% for treatment with adjuvant TRT (P < 0.0001). The actuarial 4-year survival rate was 22% for treatment with surgery alone, compared with 43% for treatment with adjuvant TRT (P = 0.005). On multivariate analysis, the addition of TRT (P = 0.0001), absence of superior mediastinal lymph node involvement (P = 0.005), and fewer N1 lymph nodes involved (P = 0.02) were independently associated with improved survival rate. CONCLUSIONS: This study, which to the authors' knowledge is the largest evaluating adjuvant TRT in N2 nonsmall cell lung carcinoma, suggests that adjuvant TRT may improve local control and survival.

Carcinoma, Non-Small-Cell Lung↗

Clinicopathological characteristics of colorectal submucosal carcinoma with lymph node metastasis.

The clinicopathological characteristics of colorectal submucosal carcinoma with lymph node metastasis are described. Lymph node positive metastasis was found in 10 (11%) of 87 cases. The depth of submucosal invasion was classified as sm1, sm2 or sm3. Lymph node positive metastases were found in 18% of the cases at sm2 or more, in 31% of those without adenomatous components, in 39% of those with positive lymphatic permeation, in 41% of those with positive budding, and in 56% of all the moderately differentiated adenocarcinomas. These characteristics are risk factors and are important for the prediction of lymph node metastasis from colorectal submucosal carcinoma. Bowel resection with lymphadenectomy is indicated in the presence of any one or more risk factors.

Adult↗

Sentinel lymph node mapping in breast cancer.

Sentinel lymph node (SLN) biopsy is a rapidly emerging treatment option for patients with early-stage invasive breast cancer and a clinically negative axilla. In the era of mammographic detection, SLN biopsy has the potential to eliminate axillary dissection for the enlarging cohort of breast cancer patients who are node-negative. Using radioisotope, blue dye, or both methods, experienced surgeons can successfully localize SLNs in more than 90% of cases. The effects of isotope and blue dye may be additive. Sentinel lymph node biopsy reliably predicts axillary node status in 98% of all patients and 95% of those who are node-positive. The operation is best learned under a formalized protocol in which a backup axillary dissection is performed to validate the technique during the surgeon's early experience. Enhanced pathologic analysis, including serial sections and immunohistochemical (IHC) staining, is an essential element of the procedure. In experienced hands, SLN biopsy has less morbidity and greater accuracy than conventional axillary dissection.

Axilla↗

[Proportion of B- and T-lymphocytes in lymph nodes removed from patients with Hodgkin's disease].

The proportions of T and B lymphocytes were determined in lymph nodes removed from 30 patients with Hodgkin's disease and in 18 control lymph nodes. In all lymph nodes obtained from patients with Hodgkin's disease histological examination demonstrated presence of typical granulation tissue of type Ns, Mc, Ld (changes of Lp type were not found). In the control lymph nodes no neoplastic changes or inflammatory reactions were observed. For identification of T cells the rosette test E was used and for identification of B cells --- the EAC rosette test and tests for presence of Ig on their surface by the immunofluorescent method (L Ig+). It was found that the proportions of T and B cells in the lymph nodes obtained from patients with Hodgkin's disease were not different from those in control lymph nodes. The percent values of T and B cells were similar in all three histological types of changes in Hodgkin's disease. Early radiotherapy was not connected with a change in T and B cell proportions in the irradiated lymph nodes.

B-Lymphocytes↗

[Lymph node documentation and lymphadenectomy in bronchial carcinomas. Results of a survey in Germany].

A number of different mapping systems have been published for the lymph-node staging in lung cancer. The use of a reproducible map is an essential prerequisite for correct determination of the TNM status and comparing the surgical results. In order to evaluate the current status of lymph-node mapping and lymph-node dissection in Germany, we performed a mail survey involving 90 hospitals performing operations for lung cancer. Responses were obtained from 61 (67.7%) hospitals. Currently, the majority of the departments (43%) use the German staging system (according to the Deutsche Gesellschaft für Thorax-, Herz- und Gefässchirurgie/Pneumologie), 23% lymph-node mapping according to Naruke, and 25% an individual description of the resected lymph nodes. The number of resected lymph nodes is reported in 75% of the departments, the quotient of involved/not involved lymph nodes in 33%. Mediastinal lymph-node sampling guided by the intraoperative aspect of lymph nodes is performed in 59% of the departments. A systematic mediastinal "enbloc" resection is accomplished in 41%. The results of this survey represent the current status of lymph-node mapping and lymphadenectomy in lung cancer in Germany and might be useful for the development of a uniform staging system.

Carcinoma, Bronchogenic↗

Initial metastatic, including micrometastatic, sites of lymph nodes in esophageal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: It is important to identify the initial lymph node metastasis when performing less invasive surgery. The purpose of the present study was to analyze locations of solitary lymph node metastasis and micrometastasis in esophageal carcinoma. METHODS: We retrospectively analyzed the initial sites of lymph node metastasis in esophageal cancer. Sixty-five consecutive patients with solitary lymph node metastasis, and 33 pN0 patients with only lymph node micrometastasis detected by immunohistochemistry, were classified according to tumor location and tumor depth. RESULTS: The location of lymph node metastasis in the 22 patients with superficial cancer was limited to recurrent nerve nodes (RN) in the upper thoracic esophagus; RN, paraesophageal nodes (PE), or perigastric nodes (PG) in the middle or lower thoracic esophagus. Thirty-six patients with advanced cancer had lymph node metastasis at RN, PE, or PG locations, while in the remaining seven, lymph node metastasis was found in areas far from the primary tumor. Regarding the 33 patients with lymph node micrometastasis, the locations of micrometastasis were similar to those of solitary metastasis. CONCLUSIONS: Although less invasive surgery, such as reduction of lymphadenectomy, may be suitable for superficial cancer, it should be performed with special care in advanced cancer.

Aged↗

Sentinel lymph node mapping with GI cancer.

Precise evaluation of lymph node status is one of the most important factors in determining clinical outcome in treating gastro-intestinal (GI) cancer. Sentinel lymph node (SLN) mapping clearly has become highly feasible and accurate in staging GI cancer. The lunchtime symposium focused on the present status of SLN mapping for GI cancer. Dr. Kitigawa proposed a new strategy using sentinel node biopsy for esophageal cancer patients with clinically early stage disease. Dr. Uenosono reported on whether the SLN concept is applicable for gastric cancer through his analysis of more than 180 patients with cT1-2, N0 tumors. The detection rate was 95%, the false negative rate of lymph node metastasis including micro-metastasis was 4%, and accuracy was 99% in gastric cancer patients with cT1N0. Dr. Bilchik recommended the best technique for identifying SLNs in colorectal cancer: a combination of radiotracer and blue dye method, emphasizing that this technique will become increasingly popular because of the SLN concept, with improvement in staging accuracy. He stressed that this novel procedure offers the potential for significant upstaging of GI cancer. Dr. Saha emphasized that SLN mapping for colorectal cancer is highly successful and accurate in predicting the presence or absence of nodal disease with a relatively low incidence of skip metastases. It provided the "right nodes" to the pathologists for detailed analysis for appropriate staging and treatment with adjuvant chemotherapy. Although more evidence from large-scale multicenter clinical trials is required, SLN mapping may be very useful for individualizing multi-modal treatment for esophageal cancer and might be widely acceptable even for GI cancer.

Antineoplastic Agents↗

Use of electrical impedance scanning in the differentiation of sonographically suspicious and highly suspicious lymph nodes of the head-neck region.

Sonographic differentiation between inflammatory and malignant lymph nodes is difficult, due in part to almost unchanged morphology of small lymph node metastases; however, as cancer cells exhibit altered dielectric properties, measurement of local electrical field distortions may be useful as adjunct to ultrasound in detection of malignancy. In this study, we evaluated the ability of electrical impedance scanning (EIS) to differentiate cervically located sonographically suspicious or highly suspicious lymph nodes. Seventy patients with 106 sonographically suspicious lymph nodes (mean size 20 x 13 x 13 mm, mean depth 8 mm) were examined using TransScan TS2000 (Siemens, Erlangen, Germany; manufactured by TransScan Research and Development Co., Israel). Included in the study were cervical ( n=64), inframandibular/periparotideal ( n=32) and nuchal/supraclavicular ( n=10) nodes. The EIS results were compared with histopathological ( n=100) and serological ( n=6) findings. Sixty-two of 64 malignant lymph nodes were correctly detected using EIS; 19 of 42 inflammatory/benign lymph nodes were correctly identified as benign (true positive 96.9%, true negative 45.2%; accuracy 71.3%, negative predictive value 90.5%, positive predictive value 59.6%). The high tumour detection rate achieved in this study suggests that EIS may be of value as an adjunctive technique in differentiation of lymph nodes of the head-neck region. Software changes to reduce the high number of false-positive markers are, however, necessary to improve the value in the evaluation during a regular clinical routine.

Carcinoma, Squamous Cell↗

Ultrasound-guided fine needle aspiration cytology prior to sentinel lymph node biopsy in melanoma patients.

BACKGROUND: Sentinel lymph node biopsy (SLNB) allows early detection of metastases, thereby enabling early treatment in melanoma patients likely to benefit from adjuvant therapies. This prospective study analyzes the possible benefits of additional ultrasound (US) and fine needle aspiration cytology (FNAC) of sentinel nodes (SN) prior to SLNB. METHOD: Over a 2-year period 127 melanoma patients with 151 SN were scheduled for SLNB. All SN were initially identified with lymphoscintigraphy, then identified and evaluated by US and the cells aspirated for cytology (FNAC). US findings and FNAC results were compared to surgical findings. RESULTS: Of 127 patients, 114 had one SN each, 12 had two, and one had three. In vivo US achieved a sensitivity of 79% (95% CI: 62-91%) and a specificity of 72% (95% CI: 62-81%). FNAC showed a sensitivity of 59% (95% CI: 41-76%) and a specificity of 100% (95% CI: 95-100%). The combination of these two in vivo methods achieved an overall sensitivity of 82% (95% CI: 65-93%) and an overall specificity of 72% [95% CI: 62-81%]. CONCLUSION: Combined US and FNAC provides important information prior to SLNB in that both procedures identify metastases in the lymph nodes (sensitivity > 80%). Patients with positive FNAC may proceed directly to complete lymph node dissection (cLND) instead of having initial SLNB. Thus, combined US and FNAC may prevent unnecessary anesthesia and surgical management as well reduce costs. In our study 16% (19/121) fewer SLNB procedures were carried out, subsequently replaced by cLND. For patients with a negative combination of in vivo US and FNAC, SLNB remains the best diagnostic option.

Adult↗

Autotransplantation of lymph node fragments. Structure and function of regenerated tissue.

In pigs slices of autologous lymph nodes were implanted in the subcutaneous fat, under the muscular fascia or under the kidney capsule to study the regeneration of autotransplanted lymph node tissue. The regenerated nodules consisted of all the normal compartments found in lymph nodes and there was evidence that afferent lymphatics reached these nodules. Superficial inguinal lymph nodes regenerated more often and with a better structure than mesenteric lymph nodes. The sites under the kidney capsule and the fascia of muscles were found to be a less stimulating microenvironment for regeneration than the subcutaneous tissue. Regeneration of transplanted lymph node tissue was observed in pigs which had been operated on as young piglets or as adults. The regeneration of autotransplanted lymph node tissue might be a useful model for draining lymphedema, especially from the extremities.

Aging↗

Stages of the development of immunologic response in regional lymph nodes draining breast cancer.

During the studies of regional lymph nodes originating from 50 patients with breast cancer, there were distinguished four stages in development of immune response. The first, stage of induction of the response concerned patients with non-infiltrating carcinoma. The second stage of the active immune response was observed in 1/3 of the patients with infiltrating cancer without metastases. In these cases, in the pattern of regional lymph nodes predominated medium sized lymphocytes within the thymus-dependent inner cortex, while in outer areas there was an increased number of small active follicles. Within the sinusoidal structures there predominated proliferating prohistiocytes growing in interaction with small lymphocytes. The third stage of immune response was characterized by weak activity and progressive cortical strophy of the lymph nodes and it was observed in 2/3 of the patients with invasive cancer. The fourth stage of immunologic response concerned the patients with minute-metastases within the regional lymph nodes. In these cases one group of the lymph nodes showed unstimulated pattern while the other a highly stimulated pattern with the presence of giant follicles.

Adult↗

[Clinical study on papillary thyroid carcinoma presenting with lymph node metastasi].

Papillary thyroid carcinoma (PTC) may metastasize to cervical lymph nodes. It is, however, uncommon for a palpable neck node alone to lead to the diagnosis of this disease when it is not apparent at presentation. Standard treatment for such cases has not yet been established. We retrospectively analyzed clinical courses in 8 patients with thyroid papillary carcinoma presenting with palpable lymph node metastasis at Hokkaido University Hospital between 1990 and 2003. Three had high thyrogloblin in cervical cystic lesions, leading to the diagnosis of PTC with lymph node metastasis. In 4, PTC was diagnosed by pathological examination of cervical lymph nodes initially diagnosed as lateral cervical cysts. Preoperative examination did not indicate PTC within the gland in any case. All 8 were alive at the last visit after follow-up from 23 to 150 months (mean: 78 months). Total thyroidectomy was done on 4 and thyroid lobectomy on 3. Pathological examination of resected thyroid glands confirmed multifocal papillary carcinoma from 4 mm to 15 mm in diameter. Six underwent unilateral neck dissection and 1 chose bilateral dissection. The other patient received no additional surgery on either the thyroid or neck after the single enlarged lymph node initially diagnosed as a lateral cervical cyst was resected. Postoperative radioiodine treatment was done in 2 undergoing total thyroidectomy. Recurrence in the cervical area were observed in 1 whose neck dissection was insufficient. Based on these observations, we concluded that patients who undergo thyroid lobectomy and adequate neck dissection may enjoy longer survival than those treated with total thyroidectomy without sacrificing thyroid and parathyroid function. We therefore propose a prospective study on the effectiveness of thyroid lobectomy with neck dissection including positive nodes in patients with occult PTC presenting with lymph node metastasis.

Adult↗

Ultrasonography and fine needle aspirate cytology of the mesenteric lymph node in normal domestic ferrets (Mustela putorius furo).

The large mesenteric lymph node of 28 normal ferrets was imaged with ultrasound. The large node, located in the mid-abdomen at the root of the mesentery, was round to ovoid and uniformly hyperechoic. Mean ultrasonographic dimensions of the lymph node were 12.6 +/- 2.6 mm by 7.6 +/- 2.0 mm. Fine needle aspirates of 20 lymph nodes were obtained either using ultrasound guided free-hand techniques or at necropsy. The cytological descriptions were compared to histological descriptions of 13 lymph node core biopsies obtained during laparotomy or necropsy as well as 10 peripheral blood smear differentials. The large mesenteric lymph node of ferrets could be easily imaged and measured by ultrasound and evaluated by fine needle aspirate cytology. Normal lymph node cytology may include an eosinophilic infiltrate.

Animals↗

Laparoscopy-assisted pylorus-preserving gastrectomy with quality controlled lymph node dissection in gastric cancer operation.

BACKGROUND: Pylorus-preserving gastrectomy (PPG) with extensive lymph node dissection is useful for treatment of early gastric cancer with preservation of function. This technique could be improved by using laparoscopy-assisted gastrectomy. STUDY DESIGN: Between September 2000 and September 2004, 109 patients with T1 gastric cancer underwent surgical treatment; 72 underwent laparoscopy-assisted PPG (LAPPG) and 37 underwent conventional PPG (CPPG). Total numbers of dissected lymph nodes, retrieval at each lymph node station, intraoperative blood loss, and operation times were used as measures of the quality of lymph node dissection to compare the procedures. Continuous data are summarized as mean +/- SE. RESULTS: Operation times with the LAPPG procedure (279 +/- 6 minutes) were significantly, but only 20 minutes, longer than with CPPG (259 +/- 8 minutes) (p = 0.047), although estimated blood loss for LAPPG patients (153 +/- 13 mL) was not significantly different for those undergoing CPPG (184 +/- 13 mL, p = 0.13). Mean total number of dissected lymph nodes was 32.3 +/- 1.6 in the LAPPG group and 28.5 +/- 2.2 in the CPPG group (p = 0.16). There was no significant difference in the number of lymph nodes retrieved for any of the nodal stations between the LAPPG and CPPG procedures. CONCLUSIONS: Clinical outcomes of surgical treatment were comparable for gastric cancer patients who underwent LAPPG and those treated with CPPG in terms of station-dependent lymph node dissection and estimated blood loss.

Adenocarcinoma↗

Use of technetium-99m tin colloid for sentinel lymph node identification in non-small cell lung cancer.

BACKGROUND: To test the reliability of sentinel lymph node identification in non-small cell lung cancer, sentinel nodes were localized with a radioactive colloid in patients undergoing surgery. METHODS: Forty-six patients with non-small cell lung cancer undergoing curative resection with mediastinal lymph node dissection were examined. The day before surgery, technetium-99m ((99m)Tc) tin colloid was injected into the peritumoral region. At operation, the radioactivity of the lymph nodes was counted with a handheld gamma counter before (in vivo) and after (ex vivo) dissection. Lymph nodes with an ex vivo radioactive count more than 10 times the background value were identified as sentinel nodes. The correlation between the in vivo and ex vivo results was examined. RESULTS: Lymphoscintigraphy revealed that it took longer than 6 hours for sufficient (99m)Tc tin colloid to reach the sentinel nodes. Sentinel nodes could be identified in 40 patients (87%). Patients whose sentinel nodes could not be identified had a significantly lower ratio of forced expiratory volume in 1 second to forced vital capacity than did those with identifiable sentinel nodes (P =.03). No false-negative sentinel nodes were detected in 14 patients with N1 or N2 disease (0%). In the hilar lymph node stations, the lobar lymph nodes were most frequently identified as sentinel nodes (as often as 85% of the time). Fourteen patients (35%) had sentinel nodes in the mediastinum, the distribution of which depended on the lobe. In vivo and ex vivo counting showed 88% concurrence for the identification of sentinel nodes in mediastinal lymph node stations. CONCLUSION: The identification of sentinel nodes with (99m)Tc tin colloid is a reliable method of establishing the first site of nodal metastasis in non- small cell lung cancer. Sentinel nodes could be hardly identified in patients with a low ratio of forced expiratory volume in 1 second to forced vital capacity because of such conditions as chronic obstructive pulmonary disease. In vivo identification of sentinel nodes in the mediastinum could be useful approach to guide mediastinal lymph node sampling or dissection.

Adult↗

Experimental study of lymph node auto-transplantation in rats.

OBJECTIVE: To observe the restoration of structure and function of auto-transplanted lymph nodes. METHODS: Inguinal lymph nodes in Spregue-Dawley (SD) rats were auto-transplanted by free implantation, or with an intact vascular pedicle, or by free transplantation with microvascular anastomosis, to the popliteal fossa where lymph nodes were removed. The observation methods included emission computerized tomographic (ECT) scanning, staining of China ink and methylthionine chloride to observe the histological changes. RESULTS: After four weeks, these vascularized nodes showed normal histological appearances and spontaneously reestablished afferent and efferent lymphatic reconnection with the surrounding lymphatic vessels. ECT lymphoscintigraphy with 99mTc-Dx showed that vascularized lymph nodes had restored their normal function. CONCLUSION: Vascularized lymph node transplantation is a useful method for draining extremity lymph edema.

Animals↗

Laparoscopic pelvic lymph node dissection.

The infiltration of pelvic lymph nodes by carcinoma of the prostate or carcinoma of the bladder is an important factor in disease staging. Until now, this could be accurately assessed only by means of open surgery, an undesirable option as an investigation. Recent advances in laparoscopic instruments and camera systems have allowed the performance of laparoscopic pelvic lymph node dissection. A series of dissections in 14 patients is reported.

Aged↗