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In vivo identification of sentinel lymph nodes for clinical stage I non-small cell lung cancer for abbreviation of mediastinal lymph node dissection.

BACKGROUND: We previously reported that an identification of sentinel lymph node (SN) with a techenetium-99m (99mTc) tin colloid by ex vivo counting, i.e. the radio-activity of dissected lymph nodes, was a reliable method of establishing the first site of nodal metastasis in non-small cell lung cancer [J. Thorac. Cardiovasc. Surg. 124(2002)486]. However, for SN navigation surgery, SN should be identified before lymph node dissection (in vivo) but not after that (ex vivo). In order to reduce mediastinal lymph node dissection for clinical stage I non-small cell lung cancer (NSCLC) by SN navigation surgery, the SN identifications for hilar lymph nodes by ex vivo counting, and for mediastinal lymph nodes by in vivo, were evaluated. METHODS: Intra-operative SN identification using 99mTc tin colloid was conducted on 104 patients with clinical stage I NSCLC who had had major lung resections with mediastinal lymph node dissections. The hilar SNs were identified by ex vivo counting (after lung resection) and the mediastinal SNs were identified by in vivo counting (before lymph node dissection). To evaluate the accuracy of mediastinal SN identification by in vivo counting, it was compared with the data by ex vivo counting. RESULTS: SNs were identified in 84 patients (81%). SNs were identified at the hilum by ex vivo counting in 78 patients (93%) and at the mediastinum by in vivo counting in 40 patients (48%). While 15 patients had lymph node metastases, i.e. N1 in six and N2 in nine, the SNs could be found to have metastases during operation in 13 of the 15 patients (87%). The in vivo counting of the mediastinum missed out the mediastinal SNs identified by ex vivo counting in four of the 84 patients (5%). CONCLUSION: If the hilar SNs identified by ex vivo counting and the mediastinal SNs identified by in vivo counting had no metastases, then mediastinal lymph node dissection could be abbreviated for patients with clinical stage I NSCLC.

Aged↗

Sentinel lymph node biopsy results in less postoperative morbidity compared with axillary lymph node dissection for breast cancer.

BACKGROUND: This study was designed to compare the postoperative morbidity and socioeconomic impact of sentinel lymph node biopsy (SLNB) with axillary lymph node dissection (ALND) in patients with early stage breast cancer. METHODS: A prospective, nonrandomized, controlled study was designed to include patients who underwent breast conservation surgery and SLNB +/- ALND. Group A consisted of patients who had a negative SLNB and did not go on to completion ALND. Group B consisted of patients who underwent a SLNB followed by a completion ALND because either (1) their sentinel node contained cancer or (2) they were within the validation phase of our institution's sentinel lymph node protocol. Patients were evaluated with a questionnaire and underwent a standardized physical examination to determine arm circumference. RESULTS: Data were obtained from 96 patients with a mean follow-up period of 15 months (range 8 to 29). Significant differences were seen in subjective measurements of arm complaints and arm numbness (P <0.001), with fewer complaints reported in group A. The difference in mid-bicep and antecubital fossa circumferences was significant when comparing the ratio of the procedure arm with the nonprocedure arm and when subtracting the nonprocedure arm from the procedure arm (P <0.003 and P <0.016, respectively) in favor of group A. Axillary surgery was performed as an outpatient procedure in 88% of group A patients, compared with 15% in group B (P <0.001). Furthermore, 71% of group A patients returned to "normal activity" in less than 4 days, in comparison with 7% of group B (P <0.001). CONCLUSIONS: SLNB results in less postoperative morbidity in terms of subjective arm complaints and mid-arm swelling. Expeditious return to work or normal activity after SLNB has potentially significant socioeconomic consequences.

Aged↗

Prognostic significance of the number of lymph nodes examined in patients with lymph node-negative breast carcinoma.

BACKGROUND: A recent report suggested that the number of lymph nodes examined was a strong predictor of survival in patients with lymph node-negative breast carcinoma. Among women who had >or= 20 lymph nodes examined, the risk of dying from breast carcinoma within 5 years was increased nearly 4-fold compared with women who had fewer lymph nodes examined. Because these findings were based on a relatively small cohort of patients, corroborative studies with larger patient populations were needed. METHODS: The authors studied the relation between the number of lymph nodes examined and breast carcinoma survival among 911 women with lymph node-negative breast carcinoma with a median length of follow-up of 84 months. The association between other prognostic indicators and survival and the number of lymph nodes examined also was investigated. RESULTS: The number of lymph nodes examined was not found to be associated with either 5-year or long-term survival. The proportion of women dying from breast carcinoma was the same (8%) in both groups (those patients with >or= 20 lymph nodes examined vs. those in whom < 20 lymph nodes were examined) and the hazard ratio was 0.98 (95% confidence interval, 0.58-1.64). CONCLUSIONS: In this larger study population, the authors failed to confirm the findings of an earlier investigation in which having a larger number of lymph nodes examined was associated with poorer survival. This finding suggests that it is unlikely the number of lymph nodes examined is an important prognostic indicator in patients with lymph node-negative breast carcinoma.

Adult↗

[Sentinel lymph node biopsy in breast cancer patients--results and experience after 500 sentinel lymph node biopsies].

INTRODUCTION: Sentinel lymph node biopsy (SLNB) is a widely used technique for axillary staging in breast cancer patients. The principle to evaluate the axillary status of a breast cancer patient with a less invasive surgery than axillary lymph node dissection (ALND) meets the new minimally invasive concept in breast cancer surgery. Some breast cancer centers proceed to SLNB without ALND in SLN-negative patients. PATIENTS AND METHODS: Between March 1998 and March 2002, 500 SLNBs were performed. After a learning period with SLNB and ALND in 75 patients with a sensitivity of 96.2% and a false-negative rate of 3.8%, SLNB alone without further ALND was performed in a group of patients. In addition, the feasibility of SLNBin patients with locally advanced breast cancer, in patients after neoadjuvant chemotherapy and in patients with multicentricity was evaluated. The combined method with blue dye and technetium-99m-labeled human albumin for identification of SLNs was applied. RESULTS: 500 SLNBs were performed. The identification rate was 86.2%. After exclusion of patients with neoadjuvant chemotherapy and patients with multicentricity, the identification rate was 94.5%. SLNs were positive in 41.3% of patients and negative in 58.7% of patients. DISCUSSION: SLNB is an excellent method for axillary stag-ing and an alternative for ALND in a certain group of breast cancer patients.

Axilla↗

The role of axillary lymph node dissection in breast cancer patients with sentinel lymph node micrometastases.

AIM: To identify by means of clinical and histopathological features a subset of breast cancer patients with sentinel lymph-node (sN) micrometastases and metastatic disease confined only to the sN in order to spare them an unnecessary axillary lymph node dissection (ALND). MATERIALS AND METHODS: From January 1998 to December 2004, 116 patients with sN micrometastases underwent standard ALND for early-stage (T1-2 N0 M0) invasive breast cancer; clinical and histopathologic parameters were prospectively collected and evaluated by means of univariate and logistic regression analysis in order to identify which patients with sN micrometastases were free of metastasis in axillary non-sN. RESULTS: Sixteen of 116 patients with sN micrometastases had tumour involvement of non-sN, with six and 10 patients having non-sN micrometastases and macrometastases, respectively. None of 19 patients with primary tumour measuring </= 10 mm had tumour-positive non-sN; moreover, none of 15 patients with G1 tumours had non-sN metastases. The mean tumour size in patients with non-sN involvement was 21.3 mm (range, 12-40 mm). Univariate test of association between clinical and histopathologic features and non-sN status showed that the primary tumour size (P=0.005) and the presence of lymphovascular invasion (P=0.000) were the only significant predictors of non-sN involvement. By logistic regression, primary tumour size (P=0.011), lymphovascular invasion (P=0.001), and size of sN micrometastases were the only variables remaining into the model, although the latter parameter was not statistically significant. CONCLUSIONS: In patients with sN micrometastases, primary tumour size and lymphovascular invasion significantly predict non-sN status; notably, no patient with T1a-T1b and/or G1 tumours had non-sN metastases so that they could be spared an unnecessary ALND.

Adult↗

Presence of human papilloma virus DNA in pelvic lymph nodes can predict unexpected recurrence of cervical cancer in patients with histologically negative lymph nodes.

Patients without any evidence of lymph node metastases are supposed to have a fair prognosis, but some of these patients develop recurrent disease unexpectedly after surgery. The object of this study is to examine whether the detection of human papilloma virus (HPV) DNA could be used as a diagnostic marker to predict such recurrences. Two hundred and thirty-six patients undergoing radical hysterectomy and pelvic lymphadenectomy for stage Ib and II cervical cancer at Okayama University Hospital (Japan) from 1988-1994 were reviewed, and only those cases positive for HPV-16 or HPV-18 in primary sites were included in this survey. The E6-E7 region of the HPV genome was amplified by a sensitive nested PCR from archival pelvic lymph node specimens. HPV sequences identical to those of the primary sites were detected in histologically confirmed negative lymph nodes, regardless of histological type or HPV type of the primary lesion, in 9 of 10 patients who recurred within 4 years of surgery. In contrast, histologically confirmed negative lymph nodes from 12 patients with stage IIb disease without evidence of recurrent disease were all negative for the presence of HPV, except for 1 lymph node. The presence of HPV DNA in histologically negative nodes implies the possibility of early nodal involvement or coexistence of undetectable hematogenic dissemination and could therefore be used as a diagnostic marker to predict the unexpected recurrence of these patients.

Adult↗

[Diagnosis of retroperitoneal lymph node swelling by computed tomography in advanced testicular cancer patients, with special reference to retrocrural lymph node swelling].

We tried to divide anatomically the retroperitoneal space into three areas on computed tomography, infrahilar, suprahilar and retrocrural spaces, and investigated the relationship between frequency of lymph node swelling in each space and clinical picture in 15 patients with testicular cancer of stage II or III, particularly focusing on the lymph node swelling in the retrocrural space. Lymph node swelling was found in the infrahilar space in 11 cases (73.3%), in the suprahilar space in 7 cases (46.7%) and in the retrocrural space in 6 cases (40.0%). Retrocrural or suprahilar lymph node swelling was always accompanied by suprahilar or infrahilar lymph node swelling. Most of the patients with retrocrural lymph node swelling had bulky tumors in the infrahilar level and frequently cervical lymph node swelling. Retrocrural lymph node swelling did not necessarily affect the patient's prognosis. The retrocrural lymph node seems to be a sentinel node for retroperitoneal lymph node swelling not only in the case of testicular cancer but also in the cancer of urogenital malignancies.

Adult↗

Quality control of lymph node dissection in the Dutch randomized trial of D1 and D2 lymph node dissection for gastric cancer.

BACKGROUND: Variability among surgeons and reduced protocol adherence threaten the conduct and outcome of surgical multicenter trials. We introduced, in the Dutch Gastric Cancer Trial of D1 and D2 (extended) lymph node dissection for gastric cancer, a novel way of managing instruction, quality control, and evaluation of protocol adherence.METHODS: Of 1078 patients entered in the Dutch trial, 711 patients with potentially curative resections were evaluated. Numbers and locations of lymph nodes detected at pathological investigation were compared according to the guidelines of the Japanese Research Society for the Study of Gastric Carcer. Non-compliance indicated inadequate removal of lymph node stations, whereas contamination indicated that lymph nodes were detected outside the intended level of dissection. Protocol adherence during the course of the trial, and the impact on complications, hospital mortality, and survival were evaluated.RESULTS: Major non-compliance was noted in 15.3% of D1 and 25.9% of D2 patients. Contamination was present in 22.9% of D1 and 23.5% of D2 patients, and was limited to one or two lymph node stations only. Intensification of quality control resulted in only a marginal improvement in protocol adherence and in the number of lymph nodes detected. There was no association between protocol adherence and the occurrence of complications or long term survival.CONCLUSIONS: Contamination proved an important parameter to substantiate protocol adherence by the surgeon, whereas non-compliance had a multifactorial cause. Non-adherence to the protocol did not lead to increased hospital morbidity and mortality, but also had no impact on long term survival.

Journal Article↗

Sentinel lymph node biopsy examination for breast cancer patients with clinically negative axillary lymph nodes after neoadjuvant chemotherapy.

BACKGROUND: The feasibility and accuracy of sentinel lymph node (SLN) biopsy examination for breast cancer patients with clinically node-negative breast cancer after neoadjuvant chemotherapy (NAC) have been investigated under the administration of a radiocolloid imaging agent injected intradermally over a tumor. In addition, conditions that may affect SLN biopsy detection and false-negative rates with respect to clinical tumor response and clinical nodal status before NAC were analyzed. METHODS: Seventy-seven patients with stages II and III breast cancer previously treated with NAC were enrolled in the study. All patients were clinically node negative after NAC. The patients then underwent SLN biopsy examination, which involved a combination of intradermal injection over the tumor of radiocolloid and a subareolar injection of blue dye. This was followed by standard level I/II axillary lymph node dissection. RESULTS: The SLN could be identified in 72 of 77 patients (identification rate, 93.5%). In 69 of 72 patients (95.8%) the SLN accurately predicted the axillary status. Three patients had a false-negative SLN biopsy examination result, resulting in a false-negative rate of 11.1% (3 of 27). The SLN identification rate tended to be higher, although not statistically significantly, among patients who had clinically negative axillary lymph nodes before NAC (97.6%; 41 of 42). This is in comparison with patients who had a positive axillary lymph node before NAC (88.6%; 31 of 35). CONCLUSIONS: The SLN identification rate and false-negative rate were similar to those in nonneoadjuvant studies. The SLN biopsy examination accurately predicted metastatic disease in the axilla of patients with tumor response after NAC and clinical nodal status before NAC. This diagnostic technique, using an intradermal injection of radiocolloid, may provide treatment guidance for patients after NAC.

Adult↗

Micrometastases in sentinel lymph node in a multicentric study: predictive factors of nonsentinel lymph node involvement--Groupe des Chirurgiens de la Federation des Centres de Lutte Contre le Cancer.

PURPOSE: To determine the rate of nonsentinel lymph node (NSN) involvement at axillary lymph node dissection (ALND) and predictive factors of this involvement following detection of micrometastasis in sentinel nodes (SN). METHODS: We analyzed 700 observations of SN micrometastases with additional ALND with the characteristics of the patients, tumors, and SN. RESULTS: Involvement of SN was diagnosed 388 times by serial sections (55.4%) with standard hemoxylin and eosin staining (HES) and 312 times solely on immunohistochemical analysis (IHC; 44.6%). The accurate size of the micrometastases was indicated in 488 cases: 301 larger than 0.2 mm (61.7%) and 187 < or = 0.2 mm (38.3%). Ninety-four patients (13.4%) presented an NSN involvement with only one NSN involved in 62 cases (66%). Predictive factors of NSN involvement were in univariate analysis (pT stage [P < .000], menopausal status [P = .048], T stage [P = .006], grade [P = .013], lymphovascular invasion [LVI; P = .013], histologic tumor type [P = .017], and method of micrometastasis detection, by HES or IHC [P = .015]) and in multivariate analysis (pT stage < or = or > 20 mm [odds ratio, 2.54], micrometastases detected by HES or IHC [odds ratio,1.734], presence or absence of LVI [odds ratio, 1.706]). Micrometastasis size < or = or greater than 0.2 mm was not predictive. CONCLUSION: This study confirms the value of serial sections and the vital role played by IHC in screening for small micrometastases. Omission of additional ALND may be envisaged with minimal risk for pT1a and pT1b tumors, and pT1a-b-c tumors corresponding to tubular, colloidal, or medullar cancers.

Adult↗

The local lymph node assay: an interlaboratory evaluation of interleukin 6 (IL-6) production by draining lymph node cells.

The murine local lymph node assay is a predictive method for the identification of skin-sensitizing chemicals in which activity is measured as a function of proliferative activity induced in lymph nodes draining the site of exposure. In the present study, the induction by topically applied chemicals of draining lymph node cell (LNC) production of the cytokine interleukin 6 (IL-6) has been evaluated as an alternative endpoint for the local lymph node assay. In addition, results derived from studies of IL-6 production by LNC performed independently in two separate collaborating laboratories have been compared. Of the nine skin sensitizing chemicals examined, six provoked detectable levels (> 150 pg ml-1) of IL-6 production by draining LNCs (as measured by enzyme-linked immunosorbent assay) following exposure of mice to at least one test concentration of the material in both of the laboratories. Three other sensitizing chemicals failed to induce measurable IL-6 production at any test concentration in either one or both of the participating laboratories. Both of the non-sensitizing chemicals evaluated (sodium lauryl sulphate and methyl salicylate) also failed to result in detectable IL-6 synthesis. There was a high level of agreement between the two laboratories. The rank order of chemicals with respect to IL-6 production by LNCs was identical in both cases, as was the dose-response relationship observed with each test material. These data reveal that, although inducible IL-6 production by draining LNCs provides a robust approach to the measurement of strong sensitizing activity, as performed here the method is of insufficient sensitivity for the routine identification of skin allergens.

Allergens↗

[Computerized tomography of the soft tissue of the neck. Lymph nodes and their differential diagnosis. II: Clinical value of CT in lymph node staging].

Basing on an analyses of pretherapeutic CT examinations of 333 patients suffering from squamous cell carcinomas of the head and neck region (206 of these had lymph node metastases), the clinical diagnostic value of CT for lymph node staging was determined. CT criteria for metastatic infestation of the lymph nodes were the lymph node size (greater than 15 mm) and structural characteristics (inhomogenity, central hypdensity with rim enhancement), and it became evident that CT with its 93% sensitivity and 89% accuracy was superior to clinical palpation, where the sensitivity was only 64% and the accuracy 72%. It can be concluded from these results that CT provides a reliable basis for a therapeutic approach.

Adolescent↗

Tumor status of lymph nodes in early endometrial cancer in relation to lymph node size.

A retrospective analysis of 36 patients with metastatic nodes out of 209 consecutively managed patients with a clinically stage I endometrial cancer was carried out. Of the 1023 lymph nodes removed, 154 nodes were found to be metastatic. The mean number of the involved nodes was 4.27 (range: 1-29). Of the 154 positive nodes, 3 had nodal diameters < or = 3 mm (1.9%), 84 had diameters of 4-10 mm (54.6%), 60 had diameters of 11-20 mm (39.0%) and 7 had diameters more than 20 mm (4.5%). With increasing lymph node size, the frequency of tumoral involvement varies from 1.0% in nodes < or = 3 mm to 63.6% in nodes bigger than 20 mm. In terms of patients, nine of them were found to have a single metastatic node ranging from 6 mm to 10 mm in diameter. In the remaining 27 patients with multiple metastatic nodes, the biggest nodes encountered were 6-10 mm in 4 (14.8%), 11-20 mm in 17 (62.9%) and more than 20 mm in 6 (22.2%) patients. Since mere sampling of the lymphatic tissue directed particularly to the enlarged nodes may not show the true incidence of positive nodes, a complete lymphadenectomy is advocated in order to obviate an understaging problem.

Endometrial Neoplasms↗

Immediate preoperative injection of 99m-Tc sulfur colloid is effective in the detection of breast sentinel lymph nodes.

Sentinel lymph node (SLN) biopsy is an accurate technique to determine the metastatic status of lymph nodes. Radionuclide guidance makes the procedure easier and improves the success rate. Coordinating the operating room and nuclear medicine schedules causes delays when same-day radionuclide injection is used. We hypothesized that injection of 99m-Tc sulfur colloid immediately preoperatively is effective in SLN detection. We analyzed a prospective database of 70 patients treated at Harbor-UCLA Medical Center. The first 39 patients underwent completion axillary dissection (Group A) and subdermal injection of sulfur colloid immediately before surgery. A second group of 31 patients (Group B) had intraparenchymal injection immediately before surgery. We used isosulfan blue in all cases. SLNs were identified in 97 per cent of cases. SLNs were radioactive in 94 per cent and blue in 90 per cent. In Group A the accuracy and the positive and negative predictive values of SLN biopsy were 100 per cent. SLN counts per second ranged from 22 to 1700. The mean count per second was 290 +/- 281 (mean +/- standard deviation). Subdermal and intraparenchymal injections were equally successful (93% vs 92%). In conclusion injection of radiocolloid and isosulfan blue immediately preoperatively is highly successful and accurate in the detection of SLNs in breast cancer. It avoids operating room schedule delays.

Adult↗

Benefits of D2 lymph node dissection for patients with gastric cancer and pN0 and pN1 lymph node metastases.

A retrospective immunohistological analysis of 100 patients with pT1-3 N0 and pT1-3 N1 gastric adenocarcinoma demonstrated a high frequency of micro-involvement in the removed lymph nodes. The presence of three or more tumour cells in more than 10 per cent of the lymph nodes was of significant prognostic value in the pN0 cases. Multivariate analysis identified micro-involvement as an independent prognostic factor. The results explain why patients benefit from lymphadenectomy even if the removed lymph nodes are not involved by tumour (pN0) in routine histological examination. The frequent occurrence of micro-involvement is a strong argument favouring routine D2 lymph node dissection in gastric cancer surgery in patients with lymph node metastasis.

Adult↗

[Adenocarcinoma of the esophagus: prognostic comparison between transthoracic esophageal resection with expanded 2-field lymph node dissection and trans-hiatal esophageal dissection with abdominal lymph node excision].

A retrospective analysis should compare the two operative approaches, transhiatal or transthoracic resection in patients suffering from adenocarcinoma of the esophagus. Between 1985 and 2002 123 cases were presented with adenocarcinoma of the esophagus, treated in 65% by transhiatal resection including abdominal lymph node dissection and in 35% by the transthoracic approach with standardized extended mediastinal and abdominal lymph node dissection. Hospital mortality was 14% (6/43) after transthoracic resection and 3.8% (3/80) after transhiatal resection (ns). Die number of removed and examined abdominal lymph nodes following transhiatal resection was 14.1 (mean) versus 12.3 (mean) after transthoracic resection (ns). Die number of removed and examined mediastinal lymph nodes by transhiatal resection was 6.3 (mean) versus 19.7(mean) after transthoracic resection (p < 0.001). The median survival after transthoracic approach was 19 months versus 20 months after transhiatal approach (ns). Median survival of curatively resected patients (R0) were in both operative procedures similar (21 months). A more differentiated analysis referred to the UICC stages also demonstrated no differences in the survival between transthoracic and transhiatal resection. With respect to less mortality and less morbidity after transhiatal resection and because of the not detectable prognostic advantage of the transthoracic resection we suggest the transhiatal approach as the treatment of choice in patients with adenocarcinoma of the esophagus.

Abdomen↗