Dye-guided Method Research Articles

Sentinel lymph node mapping for 385 gastric cancer patients

BackgroundThe objectives were to investigate the accuracy of sentinel lymph node (SLN) biopsy, detect the predictors for undetected or false-negative cases, evaluate the indications for SLN-navigated gastrectomy, and characterize the problems of SLN mapping in gastric cancer. The SLN concept may be applicable to early gastric cancer, particularly clinical T1N0M0 or T2N0M0 with tumor diameter ≤4 cm. MethodsA total of 385 consecutive patients diagnosed with cT1N0M0 or cT2aN0M0 operable gastric cancer from April 1999 to December 2007 underwent radical gastrectomy with SLN mapping. SLNs were identified using radio-guided and dye-guided methods. Predictors for undetected or false-negative cases on SLN mapping were examined by multivariate regression analysis. ResultsThe detection rate of hot and/or blue nodes was 96.6% (372 of 385). The accuracy of metastatic status based on SLNs was 98.9% (368 of 372) for all cases in whom SLNs could be detected. Furthermore, the accuracy of metastatic status based on SLNs was 99.1% (344 of 347) in cT1 gastric cancer and 96.0% (24 of 25) in cT2 gastric cancer. Pathologically, the tumors invaded to the muscularis propria or deeper in three of four false-negative cases. All but one case had metastatic lymph nodes within the sentinel basins. In terms of 5-y recurrence free survival, positive SLN cases (SLN(+)) had a worse prognosis than negative SLN cases (SLN(−); P = 0.008). Moreover, SLN(+) and non-SLN(−) cases (SLN(+)/non-SLN(−)) had a similar prognosis as SLN(+) and non-SLN(+) cases (SLN(+)/non-SLN(+)) (P = 0.511). On multivariate regression analysis, undetected or false-negative cases were significantly associated with the time period. ConclusionsThe present results appeared to validate the SLN concept for untreated cT1 gastric cancer with tumor diameter ≤4 cm. SLN mapping may provide an effective method of staging the lymph node status of patients undergoing minimized gastrectomy. Sentinel basin dissection guards against the possibility of leaving positive lymph nodes. Stabilization of the procedure and experience with SLN mapping in gastric cancer might decrease undetected or false-negative cases.

Preferentially examined sentinel nodes for sentinel node navigation surgery in gastric cancer.

The intraoperative examination of the sentinel nodes (SNs) is crucial for correctly performing SN navigation surgery (SNNS). Frozen-section diagnosis is ordinarily used; however, when several SNs are being assessed in gastric cancer, which has numerous regional lymph nodes, it is difficult to examine them all correctly within the short duration of surgery. In the present study, we aimed to determine the SNs that should be preferentially examined during SNNS in gastric cancer. A total of 824 SNs were examined in 113 patients with clinically determined T1-2 gastric cancer and no apparent lymph node metastasis. We focused on the accumulation of tracers expressed by hot nodes (HNs) using the radioisotope (RI) method and green nodes (GNs) using the dye-guided method and measured the radioactivity count of the HNs (RI count). We compared these parameters between 35 metastatic and 789 non-metastatic SNs. The percentage of metastasis-positive SNs that were radioactively 'hot' and dyed green was higher compared with that of the negative SNs (89 vs. 43%, respectively; P<0.01). The RI counts of the metastasis-positive SNs were higher compared with those of the negative SNs [median (range): 361 (0-10,670) vs. 53 (0-9,931), respectively; P<0.01]. The area under the receiver operating characteristic curve of the RI count was 0.69 (95% CI: 0.60-0.78). Therefore, when assessing several SNs, those with higher RI counts (HNs and GNs) should be preferentially examined. Further accumulation of cases is required to establish the cut-off value for the diagnosis of metastasis based on the RI count.

Sentinel lymph node detection using magnetic resonance lymphography with conventional gadolinium contrast agent in breast cancer: a preliminary clinical study

BackgroundSentinel lymph node (SLN) mapping is the standard method for axillary lymph node staging in patients with breast cancer. Blue dye and radioisotopes are commonly used agents to localize SLNs, but both have several disadvantages. The purpose of this study was to evaluate magnetic resonance lymphography with a gadolinium-based contrast agent (Gd-MRL) in sentinel lymph node identification and metastasis detection in patients with breast cancer.MethodsSixty patients (mean age: 46.2 ± 8.8 years) with stage T1- 2 breast cancer and clinically negative axillary lymph nodes participated in this study. After 0.9 ml of contrast material and 0.1 ml of mepivacaine hydrochloride 1% were mixed and injected intradermally into the upper-outer periareolar areas, axillary lymph flow was tracked and sentinel lymph nodes were identified by Gd-MRL. After SLN biopsy and/or surgery, the efficacy of SLN identification and metastasis detection of Gd-MRL were examined.ResultsNinety-six lymph nodes were identified by Gd-MRL as SLNs (M-SLN), and 135 lymph nodes were detected by blue dye-guided methods as SLNs (D-SLN). There was a strong correlation (P < 0.001) between the SLN numbers found by these two methods. Using blue dye-guided methods as the gold standard, the sensitivity of Gd-MRL was 95.65% and the false-negative rate was 4.3% for axillary lymphatic metastasis detection. With heterogeneous enhancement and enhancement defect as the diagnostic criteria, Gd-MRL gave a sensitivity of 89.29% and specificity of 89.66% in discriminating malignant from benign SLNs.ConclusionGd-MRL offers a new method for SLN identification and metastasis detection in patients with breast cancer.

Real‐time imaging of the lymphatic channels and sentinel lymph nodes of the stomach using contrast‐enhanced ultrasonography with Sonazoid in a porcine model

The contrast-enhanced ultrasound (CEUS)-guided method in combination with Sonazoid has not been clinically or experimentally evaluated with regard to its use for identifying sentinel lymph node (SLN) in the stomach. Therefore, we attempted to evaluate the usefulness of the CEUS-guided method with Sonazoid for imaging of the lymphatic channels and SLN of the stomach in a porcine model by comparing it with the conventional Evans blue dye-guided method. Twenty-eight 2 to 3-month-old swine weighing 17-30 kg were used in this experiment. Anesthesia was maintained with 2.0-3.0% isoflurane/O(2) inhalation. Sonazoid was injected into the intra- and sub-mucosal layers of the stomach. The intragastric or transcutaneous CEUS-guided method was used to identify the lymphatic channels and SLN of the stomach. Contrast imaging using the CEUS-guided method with Sonazoid enabled us to produce clear images of the afferent lymph vessel and SLN of the stomach until 2 h after the injection of Sonazoid. In addition, intranodal flow of the microbubble agent could be clearly identified using tissue linear harmonic images of the SLN. The SLN detection rate was not significantly different between the CEUS- and dye-guided methods. However, the Evans blue dye flowed out quickly (≈ 15 min after the injection) through the true SLN into the next LN of stomach. In conclusion, the use of the CEUS-guided method with Sonazoid might be the most useful clinical procedure for producing real-time images of the SLN of the stomach, and the linear harmonic images are also useful for evaluating intranodal structure within the SLN.

Sentinel lymph node and prognostic factors in gastric cancer

We would like to respond to the letter by Hanisch and Batsis entitled ‘‘Sentinel lymph node biopsy in laparoscopic surgical oncology’’ [1] in which some interesting concerns have been raised regarding the association of minimally invasive surgery and sentinel lymph node (SLN) navigation procedure described in our case report published in the September issue of Surgical Endoscopy [2]. In fact, there are several reservations in the application of SLN mapping in gastric cancer. Unexpected anatomical skip metastases might be accounted for by aberrant drainage routes from the primary lesion [3]. Unneglectable false-negative rates have been reported due to a number of factors. The most common one is the obstruction of lymphatic vessels due to cancer invasion. In these cases, the tracer is not able to reach the initial SLN and will be deviated to second tier or false SLNs. Other risk factors associated with false-negative SLN are surgeon inexperience, male gender, and a small number of SLNs (B3) [4]. The limitations of SLN navigation have been overcome with the restriction of its indication to early-stage cases, the introduction of technical improvements like the combination of dye-guided and radio-guided methods, and sentinel lymphatic basin dissection [5]. Some Eastern authors have proposed testing the SLN navigation association with conservative visceral resection such as function-preserving gastrectomy, endoscopic mucosal resection, or endoscopic submucosal dissection [6, 7]. This way, the morbidity and functional disturbances related to not only the extended lymphadenectomy but also to total or subtotal gastric resection are avoided. The attempts to reduce the adverse effects and invasiveness of early gastric cancer surgery are also translated in the association of SLN navigation with the laparoscopic procedure [8]. Such proposals should be substantiated by more consistent data. Reading carefully the letter of Hanisch and Batsis, it is possible to surmise that they did not see the possible operational or methodological caveats of our laparoscopic SLN navigation. Their final intention was not to discuss the conceptual limitations of the SLN procedure. The ultimate topic that they were trying to address was the lack of reliable prognostic markers in gastric cancer that would enable the correct modulation of surgical radicality in early-stage disease. They conclude that basic and translational research on genomics and epigenetics would provide not only the understanding of mechanisms underlying the tumor progression but also more robust predictive factors of long-term oncological outcome of gastric cancer. Gastric carcinogenesis is a multistep process involving genetic and epigenetic alteration of protein-coding proto-oncogenes and tumorsuppressor genes. Single nucleotide variants (SNVs), present as either germline or somatic point mutations, are essential drivers of tumorigenesis and cellular proliferation in many human cancer types because they were proven to be involved in DNA repair and tumor suppression [9]. Recent discoveries have shed new light on the involvement of a class of noncoding RNA known as microRNA (miRNA) in gastric cancer [10]. Genes coding these miRNAs have been characterized as novel protooncogenes and tumor-suppressor genes based on findings that these miRNAs control malignant phenotypes of gastric cancer cells. In this sense, miRNA dysregulation promotes cell-cycle progression [11], confers resistance to apoptosis [11, 12], and enhances invasiveness and metastasis [13]. Moreover, several miRNAs have also been shown to E. Orsenigo (&) S. Kusamura C. Staudacher Department of Surgery, University Vita-Salute San Raffaele, Via Olgettina, 60-20132 Milan, Italy e-mail: orsenigo.elena@hsr.it

Validation study of sentinel lymph node mapping using radio- and dye-guided methods in gastric cancer: 431 cases at a single institution.

76 Background: Some papers have reported that sentinel lymph node (SLN) concept can be applied in patients with early gastric cancer, in particular clinically T1N0M0 or T2N0M0 with a tumor diameter of 4cm or less. Little is, however, available on the SLN study with the other criteria than listed above. The aim of the present work was to investigate the accuracy of the SLN biopsy of gastric cancer with various stages and evaluate the indication for SLN navigated gastrectomy. Methods: A total of 431 consecutive patients were diagnosed with operable gastric cancer during the period April 1999 through December 2007. Reasons for inclusion were, in principle, T1N0M0 or T2N0M0 gastric cancer. However, several patients diagnosed preoperatively with T3N0M0, T2N1M0, remnant gastric cancer, multiple gastric cancers and additional treatment after endoscopic therapy were also enrolled in this study according to their request. All patients underwent a radical gastrectomy with SLN mapping with an informed consent. The SLNs were identified using both radio-guided and dye-guided method. Results: Detection rate of hot and/or blue node was 95.8% (413/431). The accuracy of metastatic status based on SLN was 97.6% (403/413). In six of 10 false-negative cases, some clinical backgrounds and problems were present; scirrhous gastric cancer, the tumor penetration of serosa, multiple lesions, remnant gastric cancer after partial resection and the technical issue of tracer injection. Nine of these 10 false-negative cases had the metastatic lymph nodes within only the sentinel basins. Specifically, in the group of clinically T1N0M0 untreated gastric cancer with a tumor diameter of 4 cm or less, there were only 3 false- negative cases. In addition, all the metastatic lymph nodes of the 3 cases located within the sentinel basins. Conclusions: Our study suggested that SLN concept for untreated early gastric cancer could be validated. The sentinel basin dissection might be used to advantage to improve curativity for gastric cancer. No significant financial relationships to disclose.

Pitfalls in sentinel lymph node biopsy

Sentinel lymph node (SLN) biopsy is a common procedure to avoid unnecessary axillary lymph node dissection in breast cancer patients with negative nodes. However, there are some problems with SLN biopsy. One is the identification rate of SLNs. Many reports showed that the rate is higher with the combined dye and gamma probe-guided method than with the dye-guided method alone. Nevertheless, with the combined method, around 5% of SLNs cannot be identified. In this issue, Ando et al. studied the axillary arch consisting of a muscular anomaly. They reported the usefulness of multidetector row computed tomography (MDCT) for an anatomical diagnosis of the axillary arch that affected SLD identification. Rokutanda et al. also reported a case of retromammary lymph node metastasis with a false-negative SLN biopsy. We have to keep in mind these anatomical varieties for SLN biopsy. The other important point is the existence of false-negative SLNs. Takei et al. gave us one of the answers to this problem. They showed that an intraoperative false-negative SLN biopsy did not affect the recurrence-free survival rate of breast cancer patients. They also showed the necessity of additional axillary radiotherapy or adjuvant systemic therapy. Nakashima et al. showed that abnormal accumulation of the radiotracer close to the radioactive spot indicates lymph node metastasis surrounding radioactive SLNs. They recommended additional lymph node biopsy surrounding radioactive SLNs. We have to continue searching for the best method for SLN biopsies for patients with breast cancer.

Sentinel Node Detection Method Using Contrast-Enhanced Ultrasonography with Sonazoid in Breast Cancer: Preliminary Clinical Study

This study aimed to evaluate the usefulness of sentinel lymph node (SLN) detection in breast cancer using contrast-enhanced ultrasonography (CEUS) with subareolar Sonazoid injection. The subjects were 20 breast cancer patients. General anesthesia was induced and 2 mL of Sonazoid was injected subareolarly. After massage of the injection site, the axillary area was observed transdermally using coded phase inversion harmonic ultrasonography with mechanical indices of 0.15 to 0.19. When contrast-enhanced lymph nodes (LNs) were seen, they were defined as CE-SLN. Two other SLN detection methods, the γ-probe-guided and dye-guided methods, were performed together. We evaluated the SLNs detected by each method to determine if they corresponded with each other and calculated the SLN detection rate. After the SLNs were resected, pathologic examinations were done. The SLN detection rate of the CEUS-guided method, the dye-guided method and the γ-probe-guided method were 70%, 75% and 100%, respectively. There was no statistically significant difference in these rates between the CEUS-guided and dye-guided methods ( p = 0.99) but the CEUS-guided method showed a significantly lower rate than the γ-probe-guided method ( p = 0.020), and dye-guided method also showed a significantly lower rate than the γ-probe-guided method ( p = 0.047). The number of CE-SLNs was 1 or 2 (average 1.1) and each took 2 to 20 (average 5.3) min to detect. The CE-SLNs corresponded grossly with SLNs detected by the γ-probe-guided and dye-guided methods. The pathologic results indicated no metastasis from the resected SLNs in 15 of 20 cases. However, the CEUS-guided method detected 12 cases of these 15 and CE-SLNs were detected in two of the remaining five metastasis cases. In summary, in breast cancer patients, after subareolar injection of Sonazoid, contrast-enhanced LNs were observed in real time with ultrasonography. In an initial clinical study of 20 cases, the detection rate of the CEUS-guided method was less than that of the γ-probe-guided method. It is suggested that the CEUS-guided method using Sonazoid may, with some improvements, be a useful new modality for sentinel node identification. (E-mail: kiyoka@jichi.ac.jp)

How should tracers be injected to detect for sentinel nodes in gastric cancer – submucosally from inside or subserosally from outside of the stomach?

BackgroundIn sentinel node (SN) detection for cases of early gastric cancer, the submucosal dye injection method appears to be more reasonable than the subserosal injection. To compare the two injection methods, we have focused on the rate of concordance between hot nodes (HNs) obtained from the radioisotope (RI) method and green nodes (GNs) obtained from the dye-guided method in addition to the number and distribution of GNs detected, and the sensitivity of metastatic detection.MethodsThe subjects of this study were 63 consecutive patients with gastric cancer (sT1–T2, sN0, tumor diameter ≦ 4 cm) in whom we attempted SN detection using a combination of RI and dye methods. 99mTc-tin colloid was injected a day before the surgery, and indocyanine green was injected either submucosally (n = 43) with endoscopes or subserosally (n = 20) by direct vision.ResultsAn average of hot and green nodes (H&G: 4 ± 3 vs. 4 ± 3), hot and non-green nodes (H&NG: 2 ± 3 vs. 1 ± 2), cold and green nodes (C&G: 2 ± 2 vs. 3 ± 4), and the rate of concordance (H&G/H&G + H&NG + C&G: 45 + 27% vs. 48 ± 30%) were not significantly different between the submucosal and subserosal injection methods. The spread of GNs to tier 2 stations (24% vs. 30%) and metastatic detection sensitivity (86% vs. 100%) were also not different between the submucosal and subserosal injection methods.ConclusionThe tracer injection sites do not have to be limited to the submucosa.

Clinical efficacy and problems with CT lymphography in identifying the sentinel node in breast cancer.

BackgroundCombining a radioisotope with a dye-guided method is the best method for identification of the sentinel lymph nodes (SNs) in breast cancer. However, some institutions are limited to use of a dye-guided method alone. Recently, computed tomographic lymphography (CTLG) employing a nonionic contrast medium has achieved SN identification.Patients and methods218 patients with primary breast cancer and no clinical evidence of lymph node metastasis were studied. SN identification was performed by CTLG and a dye-guided method. The SN identification rate was analyzed for correlations with the clinicopathological findings.ResultsThe SN identification rates were 96% with CTLG, 92% with the dye-guided method and 99% with both methods combined. The identification rates with CTLG and the combined method were significantly lower in node-positive patients compared to node-negative patients, and significantly lower with the combined method in vascular invasion-positive patients compared to negative patients. In addition, the SN identification rate with the dye-guided method was significantly lower in patients with a body mass index (BMI) of ≥ 25, whereas the BMI did not affect the identification rate with CTLG or the combined method. Multiple SNs were detected in approximately 20% of the patients.ConclusionCombined performance of CTLG and a dye-guided method enables identification of SNs prior to breast cancer surgery. That SN identification is easier compared with by the dye-guided method alone, and the identification rate is improved compared with either method alone. The combination of methods was especially useful in obese patients. For patients with multiple SNs, the combination has the further advantage of enabling accurate SN biopsy. CTLG may yield false-negative findings in node-positive patients and patients with lymph vessel obstruction.

New method of sentinel node detection using a combination of contrast-enhanced ultrasound and dye guidance: an animal study.

To determine whether a combination of contrast-enhanced ultrasound-guided methods and dye-guided methods can identify sentinel lymph nodes in animals. Seven pigs were put under general anesthesia and injected subcutaneously in the neck: three with 2 ml saline and four with 2 ml fluid comprising 0.4 ml 5% patent blue violet solution and 1.6 ml of hydroxyethylated starch (Salinhes) solution (PB + HS). The regional lymph nodes were observed by ultrasound; blue-stained regional lymph nodes found after the skin was cut were situated as ultrasound had shown they would be. The regional lymph nodes of the pigs given saline were unchanged, but in the pigs receiving PB + HS, the echo level in the lymph nodes nearest the injection site was altered, producing a clear contrast with the surrounding tissues. The area of the relevant regional lymph node in each PB + HS-injected pig increased significantly (t-test, P < 0.01; from 25.7, 39.6, 9.36, 70.2 mm(2), and mean, 36.2 mm(2); to 50.7, 65.5, 21.1, 98.3 mm(2), and mean, 58.9 mm(2), respectively). These enlarged regional lymph nodes were easily found by contrast-enhanced ultrasonography. When excised under ultrasound guidance, all were stained blue, indicating that they were sentinel lymph nodes. These results suggest that this combination of contrast-enhanced ultrasound-guided and dye-guided methods warrants use as a quick, simple procedure for detecting sentinel lymph nodes.

Maturation of dendritic cells and T‐cell responses in sentinel lymph nodes from patients with breast carcinoma

Methods for identifying sentinel lymph nodes (SNs) and their clinical significance have been established. Recent advances in molecular immunology have enabled the analysis of precise immune responses. The objective of the current study was to clarify the dendritic cell (DC) maturation, T-helper type 1 (Th-1) and Th-2 responses, and regulatory T-cell responses of SNs in patients with breast carcinoma. SNs and non-SNs were identified by radioguided and blue dye-guided methods in 70 consecutive patients with clinically lymph node negative (N0) breast carcinoma. Lymphocytes were collected from SNs and non-SNs and were subjected to flow cytometric analysis (FCM) using antibodies of CD83-fluorescein isothiocyanate (FITC), CD80-phycoerythrin (PE), CD86-PE, CD40-PE, human leukemic D-related antigen (HLA-DR)-FITC, CD4-FITC, and CD25-PE. Total RNA was extracted from SNs and non-SNs, and the expression of CD83, interleukin 12p40 (IL-12p40), interferon gamma (IFN-gamma), IL-4, IL-10, and Foxp3 was evaluated by using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The immunologic status of SNs was analyzed further with regard to micrometastases, which were identified as negative microscopically but positive according to an RT-PCR analysis that was specific for mammaglobin. SNs were detectable in 70 of 71 consecutive patients (98.6%) with clinically N0 breast carcinoma. Fourteen of 70 patients (20.0%) had positive metastasis in SNs. When SNs were compared with non-SNs in 56 metastasis-negative patients, FCM revealed that HLA-DR-positive, CD80-positive, CD86-positive, and CD40-positive cell populations were decreased significantly in SNs. RT-PCR analysis demonstrated that, among 44 patients with metastasis-negative SNs, the expression levels of CD83 and IFN-gamma mRNA were significantly lower in SNs compared with non-SNs. Immunologic parameters also were compared between 44 metastasis-negative SNs and 14 metastasis-positive SNs. The metastasis-positive SNs demonstrated significantly higher expression of CD83, IL-12p40, IFN-gamma, IL-10, and Foxp3 mRNA than the metastasis-negative SNs. Correction of micrometastasis detected by mammaglobin enhanced these differences consistently. In patients with breast carcinoma, cellular immune responses, from DC maturation to Th-1 responses, appeared to be less active in SNs compared with non-SNs before metastasis developed. Once metastasis was established in SNs, DC maturation was triggered and was followed by the up-regulation of Th-1 responses, which may reflect antigen-specific immune responses in SNs. Unlike DC maturation and Th-1 responses after metastasis in SNs, up-regulation of Th-2 and regulatory T-cell responses developed in parallel.

Is a Lymph Node Detected by the Dye-Guided Method a True Sentinel Node in Gastric Cancer?

A sentinel node is defined as the initial lymph node, to which cancer cells metastasize from a primary tumor. Recently, sentinel node navigation surgery has been done using the dye-guided method. However, no study has shown that a lymph node detected by the dye-guided method is the true sentinel node from the viewpoint of micrometastasis. Micrometastases of lymph nodes, in which no metastasis was found by H&E staining, were examined to establish whether a lymph node detected by the dye-guided method is the true sentinel node. Isosulfan blue was injected endoscopically as the dye-guided method at a submucosal lesion of early gastric cancer. Total 345 lymph nodes, including 150 blue-dyed lymph nodes and 195 nondyed lymph nodes were collected from 57 patients and each was quartered. Two quarters were examined histologically by H&E staining and cytokeratin staining. The other specimens were used for quantitative reverse transcription-PCR of CEA and CK20 mRNAs. Lymph node disease was not found in any of 345 lymph nodes from the 57 patients by routine H&E staining. By contrast, either CEA or CK20 mRNA expression was detected in 21 of 345 lymph nodes obtained from the 10 (18%) of 57 patients by quantitative reverse transcription-PCR. Eight of the 21 micrometastasis-positive lymph nodes were confirmed to be positive for cytokeratin staining. Although micrometastasis of nondyed lymph nodes was found in three cases, these were included in the 10 cases with micrometastasis of blue-dyed nodes, such that there was no patient who only had micrometastasis in nondyed nodes. Six of 10 cases were micrometastasis-positive in a single node; all six were blue-dyed nodes. A lymph node detected by the dye-guided method should be a true sentinel node to which cancer cells metastasize initially.

Sentinel lymph node biopsy in breast cancer: an overview of the Japanese experience.

This paper reviews the Japanese literature regarding sentinel lymph node (SLN) biopsy in an attempt to provide an overview of existing controversies and to suggest a method for the identification of the SLN and the detection of micrometastases in the SLN to eliminate unnecessary axillary lymph node dissection (ALND). The combined dye- and gamma probe-guided method resulted in the accurate identification of the SLN in 96% of patients, compared with 80% when the dye-guided method alone was used. Although neither 99m-Tc sulfur colloid nor 99m-Tc colloidal albumin is commercially available in Japan, 99m-Tc stannous phytate and 99m-Tc rhenium colloid appear to be ideal tracers for identifying SLNs. Moreover, subdermal injection over the primary tumor or subareolar injection was found to enhance SLN identification, although these injection routes do not lead to detection of internal mammary SLNs. Furthermore, the accuracy of SLN diagnosis using frozen sections as well as imprint cytology improved with an increase in the number of sections, and could attain a sensitivity comparable to that obtained with routine histologic examination of permanent sections. As a result, several surgeons have begun to offer the option of forgoing ALND to patients with negative SLN. Although subsequent relapse in the axilla has not yet been reported, longer follow-up periods are needed to assess accurately the incidence of axillary failure in these negative SLN patients.

A multicenter validation study of sentinel lymph node biopsy by the Japanese Breast Cancer Society.

Several pilot studies have indicated that SLN biopsy can be used to identify axillary lymph node metastases in patients with breast cancer. To confirm this finding, a multicenter study in a variety of practice settings was performed. A total of 674 patients with breast cancer at five institutions were enrolled. The techniques of SLN identification included the vital dye-guided and the vital dye- and gamma probe-guided methods. The SLN was removed, and complete axillary lymph node dissection (ALND) was performed. SLN and ALND specimens were examined separately. The SLN was successfully identified in 214 (94%) of 227 patients using the combined dye- and gamma probe-guided methods. The SLN was identified in 332 (74%) of 447 patients using vital dye-guided method alone. Patient age of at least 21 years, medially located primary tumor, and clinically positive nodes were correlated with failure to identify the SLN. The accuracy of SLN biopsy for the detection of metastatic disease was 96% (522 of 546), and the sensitivity was 90% (203 of 226). Accuracy of 100% was achieved in the patients with tumors less than 1.6 cm in diameter. All 23 false negative results occurred with larger primary tumors. SLN biopsy can accurately predict the presence or absence of axillary lymph node metastases, particularly in patients with small (< or = 1.5 cm) breast cancers.

Intraoperative sentinel lymph node examination by imprint cytology and frozen sectioning during breast surgery.

The purpose of the present study was to evaluate the usefulness of intraoperative imprint cytology and frozen sectioning of sentinel lymph nodes in patients with clinically node-negative breast cancer. Sentinel node biopsy was performed in 101 patients with stage I or II breast cancer with clinically negative nodes using a dye-guided method. Intraoperative evaluation of sentinel node involvement by imprint cytology and frozen sectioning was compared with the final histopathological results of permanent sections. Tumour-negative nodes in paraffin sections stained by haematoxylin and eosin were further studied using an anticytokeratin antibody. The results of imprint cytology and frozen-section analysis were compared with those of haematoxylin and eosin-stained sections. The sensitivity, specificity and overall accuracy of imprint cytology were 96.0, 90.8 and 92.1 per cent respectively, and those of frozen-section examination were 52.0, 100 and 88.1 per cent. Ten sentinel nodes were tumour positive on imprint cytology and tumour negative on stained paraffin sections. Micrometastasis was found in eight of these nodes on immunohistochemistry. Taking these immunohistological results into consideration, the final sensitivity, specificity and overall accuracy of imprint cytology were 90.9, 98.5 and 96.0 per cent respectively. Intraoperative imprint cytology is a useful method for evaluating the status of sentinel nodes and is more accurate than frozen-section analysis. In addition, imprint cytology can detect micrometastasis more accurately than conventional haematoxylin and eosin-stained sectioning.

Dye- and gamma probe-guided sentinel lymph node biopsy in breast cancer patients: using patent blue dye and technetium-99m-labeled human serum albumin

Sentinel lymph node (SLN) biopsy is a promising method for the diagnosis of the axillary nodal status. We examined the availability of the SLN biopsy using two mapping procedures: the dye- and gamma probe-guided method, and preoperative lymphoscintigraphy by gamma camera imaging. We enrolled 48 patients with breast cancer. Technetium-99m-labeled human serum albumin was injected into the subdermal tissue above the primary tumor or biopsy cavity, and preoperative gamma camera imaging was performed. After induction of general anesthesia, patent blue dye was injected into the peritumoral area prior to the surgical procedure. A handheld gamma-detection probe was used to assist in SLN detection. Careful dissection was performed to identify blue-stained afferent lymphatic vessels and nodes. An SLN was defined as any blue and/or radioactive node, and was excised. After SLN biopsy, axillary lymph node dissection of level I, II, and III was completed, in order to confirm the diagnostic ability of the SLN biopsy. Intraoperative SLN identification of axillary lesions was successful in 43 of 48 patients (90%). The dye- and gamma probe-guided method was successful in 25 patients (52%), the dye-guided method alone succeeded in 11 patients (23%), and the gamma probe-guided method alone succeeded in 7 patients (15%). Preoperative lymphoscintigraphy revealed axillary focal accumulations in 29 of 48 patients (60%). All patients who underwent successful preoperative SLN identification by lymphoscintigraphy had successful intraoperative SLN identification. A diagnostic accuracy of 95%, a sensitivity of 89%, and a specificity of 100% were achieved in the diagnosis of axillary metastasis. Internal mammary SLNs were identified in four patients intraoperatively, but we could not detect cancer metastasis in the internal mammary SLNs. The dye-guided and gamma probe-guided methods were complementary. Preoperative lymphoscintigraphy was useful to predict intraoperative SLN identification. Further study is necessary to assess the role of SLN biopsy of the internal mammary lymph nodes.

Sentinel node biopsy guided by indocyanine green dye in breast cancer patients.

We aimed to evaluate whether dye-guided sentinel node biopsy is a useful indicator of axillary node involvement in breast cancer patients and whether clinicopathological features affect its success in identifying sentinel nodes. Sentinel node biopsy was performed in patients with stage I or II breast cancer using an indocyanin green dye-guided method. We could identify sentinel nodes in 127 (73.8%) of 172 patients. The mean number of sentinel nodes per patient was 1.7 (range, 1-8) and the mean node size was 9.3 mm (range, 3.0-28.0 mm). Of the 127 patients, 40 (31.5%) also had axillary node involvement. In 16 (40.0%) of these, the sentinel node was the only node involved. There was concordance between sentinel node and axillary node status in 122 (96.1%) of the 127 patients. Success in identifying sentinel nodes was not affected by tumor size, operative procedure, histological type of tumor or tumor location; however, the success rate was significantly lower in patients with axillary node involvement (65.7 vs 79.0% in axillary node-negative patients, p = 0.039) and the presence or absence of lymphatic or vascular invasion in the tumor (63.8 vs 78.9% in patients without lymphatic or vascular invasion, p = 0.043). Sentinel nodes could also be identified significantly more frequently in patients under 50 years old (83.3%) than in those over 50 years old (64.8%, p = 0.009). Sentinel node biopsy guided by indocyanin green dye is an easy technique with an acceptable success rate in detecting sentinel nodes and predicting axillary nodal status. Axillary node status, the presence or absence of lymphatic or vascular invasion in the tumor and patient age affect its success in identifying sentinel nodes.

Computed Tomography for Preoperative Evaluation of Axillary Nodal Status in Breast Cancer.

BACKGROUND: We prospectively evaluated axillary lymph node metastasis by preoperative thin-slice computed tomography (CT) and compared those results with theresults of dye-guided sentinel lymph node biopsy (SNB). PATIENTS AND METHODS: Fifty-one breast cancer cases were examined. Preoperative axillary CT, dyeguided SNB and complete axillary lymph node dissection were performed. We prospectively diagnosed lymph node metastasis in the whole axillaryregion and qualitatively predicted the sentinel lymph node (SN) status with thepreoperative CT images. Based on the results of SNB and the pathological nodal status as revealed by complete axillary dissection, we evaluated the usefulness of preoperative axillary CT as a predictor of axillary node metastasis, and we also investigated the qualitative diagnostic value of the SN predicted by CT. RESULTS: For the whole axillary region, the results of CT diagnosis showed anaccuracy of 71% and a sensitivity of 60%. The SN predicted by CT correlated with the SN identified by the dye-guided method in 86% of all cases. The SN status predicted by CT had an accuracy of 81%, a sensitivity of 78%, and a negative predictive value of 79%. The dye-guided methods resulted in three false-negative SNcases, however, CT predicted one of those cases as positive. CONCLUSIONS: Diagnosis of axillary lymph node metastasis by CT alone is inadequate. However, CT achieves a comparatively high rate of identification of axillary SN. The combined use of dye-guided SNB and preoperative CT will facilitate identification of the SN and also lower the false-negative rate.

Sentinel Node Biopsy in Breast Cancer Patients with Clinically Negative Lymph-Nodes.

BACKGROUND: The purpose of the present study is to evaluate the usefulness ofdye-guided sentinel node biopsy in breast cancer patients with clinically negative nodes and to clarify the anatomic distribution of sentinel nodes in the axilla. METHODS: Sentinel node biopsy was performed in patients with T1 or T2 breast cancer who had clinically negative nodes, using an indocyanin green dye-guided method. Thereafter, complete axillary dissection was performed. Sentinel node andcomplete axillary lymph-node dissection specimens were examined separately, andthe incidence of metastases was compared. RESULTS: We identified sentinel nodes in 115 (76.7%) of 150 patients with clinically negative nodes. The mean number of sentinel nodes was 1.7 (range, one toeight nodes). The mean size of sentinel nodes was 9.0 mm (range, 2.0 to 28.0 mm). Of the 31 patients who had a tumor-positive sentinel node, 14 (45.2%) patients had only the sentinel node involved. There was concordance on histological examination between sentinel node and axillary node status in 111 (96.5%) of 115 cases. Of the sentinel nodes 89.1% were located cranially to the intercostobrachial nerve and within 2 cm of the lateral edge of the pectoralis minor muscle. CONCLUSIONS: Sentinel node biopsy guided by indocyanin green dye is an easy technique with an acceptable detection rate of sentinel nodes for breast cancer patients with clinically negative nodes. Most of the sentinel nodes were locatednear the lateral edge of the pectoralis minor muscle and cranial to the intercostobrachial nerve.