Application of sentinel node biopsy to gastric cancer surgery

BACKGROUND: Sentinel node (SN) biopsy has been tried in the management of a variety of cancers with the hope that it would eliminate many unnecessary lymph node dissections, resulting in less morbidity. This important technique, however, has not been tried in gastric cancer surgery. The feasibility of SN biopsy and its accuracy in predicting the lymph node status in patients with gastric cancer were examined in the current study. PATIENTS AND METHODS: SN biopsy was performed in patients with T1 (n = 44) or T2 (n = 30) gastric cancers (ie, immediately after laparotomy, indocyanine green was injected around the primary tumor, and the green-stained nodes [SNs: 2.6 +/- 1.7 nodes per patient] were removed). Then, gastrectomy with extended lymphadenectomy was performed. The unstained nodes (non-SNs: 39 +/- 18 nodes per patient) were obtained from the resected specimens. Both SNs and non-SNs were subjected to histologic examination with hematoxylin-eosin. RESULTS: SNs could be identified in 73 of 74 patients (success rate, 99%). Of these 73 patients, 10 had lymph node metastases in SNs or non-SNs, or both; 6 in both SNs and non-SNs; 3 in SNs alone; and 1 in non-SNs alone. The sensitivity of the SN status in the diagnosis of the lymph node status of the patient was 90% (9/10) and specificity was 100% (63/63). Sensitivity was 100% in the T1 group (n = 44) and 88% in the T2 group (n = 29). CONCLUSIONS: SN biopsy using indocyanine green can be performed with a high success rate, and the SN status can predict the lymph node status with a high degree of accuracy, especially in patients with T1 gastric cancer.     

腹腔镜技术在胃癌治疗中的展望：早期胃癌的前哨淋巴结导航保留功能手术

自从腹腔镜在胃癌治疗中应用以后，短期的治疗效果与传统开腹手术相比，患者术后在生活质量上有所提高。然而，腹腔镜胃癌手术对生存质量的长期的改善作用仍在争论中。这可能由于腹腔镜下胃癌手术与开放手术有着相同的胃切除及淋巴结清扫范围造成的。为了提高胃癌手术患者长期的生存质量而又不影响复发与生存，通过腹腔镜行胃功能保留手术及最小范围的淋巴清扫使肿瘤无残留的方式是应该被考虑的。为了达到这个目的，前哨淋巴结活检（SNB）的概念被提出来。在敏感性方面SNB的结果在不同的机构是有差异性和不令人满意的，然而最近来自日本的多中心研究给我们提供了乐观的结果。目前在韩国，前哨淋巴结导航方法研究小组对应用SNB保留胃功能手术的方法进行III期试验，在这之前，参与机构在标准化及克服SNB学习曲线的质量管理研究已经在进行中。如果SNB及保留胃功能的手术可以在III期试验中证实，那么这种方式因其不影响复发与生存可能取代早期胃癌患者的标准胃切除及淋巴结清扫术，成为早期胃癌的一种更好的外科治疗选择。     

The sentinel node biopsy in early gastric cancer: a preliminary study

Background and aims Sentinel node biopsy is currently used in surgery of malignant melanoma and breast cancer. The feasibility of sentinel node mapping in gastrointestinal cancers and its diagnostic sensitivity is unclear. It could be of particular value in the management of early gastric cancer in which radical D2 lymphadenectomy may be unnecessary. Materials and methods From January 2004 to June 2005, ten patients with preoperative diagnosis of early gastric cancer and no nodal involvement (cT1N0) were submitted to sentinel node biopsy using the dual mapping procedure with endoscopic blue dye and ^99mTc radio colloid injection. All the patients underwent standard radical gastrectomy and D2 lymphadenectomy. The resected nodes were evaluated by routine (hematoxylin–eosin) histopathological examination; the sentinel (blue or hot) nodes, in addition, were evaluated with immunohistochemistry for cytokeratin. Results The detection rate of this procedure was 100%. The preliminary results and perspectives for feasibility of sentinel node biopsy and its accuracy in predicting the nodal status in early gastric cancer are discussed.     

早期胃癌与前哨淋巴结

胃癌的淋巴结转移状况是预后的最重要因素之一。转移淋巴结的清扫,尤其是微转移灶的清除,是胃癌根治的关键。广泛性淋巴结清扫(extended lymph node dessiction, ELND)一直深受胃肠肿瘤外科学者的推崇,随着胃癌早期诊断技术水平的提高,如纤维胃镜的广泛应用,近年早期     

前哨淋巴结活检在早期胃癌淋巴结转移评估中的应用

1977年,Cubanas在对阴茎癌的研究中,首先提出了前哨淋巴结（sentinel lymph node,SLN）的概念。1992年,Morton将染色剂注入黑色素瘤体后,发现染色剂从原发肿瘤经淋巴管流入第1站淋巴结。通过对恶性黑色素瘤和乳腺癌病人的研究,人们给SLN下了以下定义,即最先接受原发肿瘤淋巴引流的淋巴结和首先可能发生微转移的一个或一组淋巴结。如果SLN阴性则其他区域淋巴结也较少发生转移,因此SLN的检测结果可作为是否行淋巴结清扫的依据。     

Same-day lymphoscintigraphy and sentinel node biopsy for early breast cancer

Background: Lymphoscintigraphy and sentinel node biopsy are currently being assessed as an alternative to axillary dissection for staging in early breast cancer. However, little is known about the optimum timing of surgery following injection of the radio­isotope into the breast. The aim of the present study was to establish whether lymphoscintigraphy on the morning of surgery allowed efficacious and accurate sentinel node identification and biopsy. Methods: We reviewed our experience of 216 consecutive cases of lymphoscintigraphy in early breast cancer using peritumoural injections of technetium^99m antimony sulphide colloid and subsequent sentinel node biopsy using a hand‐held gamma probe and blue dye. The time interval between radioisotope injection and successful intraoperative identification of the sentinel node was assessed and whether this was associated with certain clinical and histological variables. Results: The sentinel node was identified by lymphoscintigraphy in 160 cases (74%) at a median time duration of 40 min post injection. The median time duration between isotope injection and surgery was 5 h. Of the 160 cases where the sentinel node was visualized at lymphoscintigraphy, sentinel node biopsy was successfully performed in 155 cases (97%). This compares with 25/56 (45%) cases where lymphoscintigraphy failed to localize the sentinel node (P < 0.0001). There was no association found between the injection of the radioisotope greater or less than 5 h before surgery and the successful intraoperative identification of the sentinel node. Failure to identify the sentinel node at lymphoscintigraphy beyond 3 h was associated with a low intraoperative identification rate. There was no correlation found between intraoperative identification of the sentinel node according to the duration of isotope injection in relation to surgery and the various clinical and histological factors assessed. Conclusions: In our experience, the chance of identifying the sentinel node at the time of surgery does not increase with longer isotope injection duration using technetium^99m antimony sulphide colloid. As soon as a sentinel node is identified at lymphoscintig­raphy, one can proceed to surgery. Scanning beyond 3 h does not appear to be effective in sentinel node localization. Given that the median time for successful lymphoscintigraphic mapping was only 40 min, lymphoscintigraphy can easily be completed during the morning to allow surgery to take place the same day.     

Laparoscopically assisted total gastrectomy with sentinel node biopsy for early gastric cancer: preliminary results

This study sought to describe a procedure involving laparoscopically assisted total gastrectomy (LATG) with sentinel node biopsy (SNB) and to evaluate the results of the first three patients. LATG for early gastric cancer was performed with sentinel node (SN) identification using a combined patent blue-violet dye and 99mtechnetium-labeled tin colloid technique. Laparoscopically resected SNs were processed for frozen section examination by routine hematoxylin and eosin (H&E) and immunohistochemical cytokeratin (IHC-CK) stains. LATG consists of a four-surgical port technique, removal of the specimen through a small 5-cm laparotomy, and stapled Roux-en-Y esophagojejunostomy. Five patients were candidates for LATG with SNB between March 2001 and June 2003; two had open surgery because of a tumor extending the serosal surface and peritoneal dissemination, whereas in the remaining three, SNs were successfully identified and evaluated with no evidence of sentinel node (micro) metastases intraoperatively. Based on the results of SNB, three patients underwent LATG with adequate lymphadenectomy. Mean operative time and blood loss were 375 min and 219 mL, respectively. No dissected lymph nodes had evidence of metastasis by H&E and IHC-CK on permanent sections. LATG with SNB followed by adequate lymphadenectomy is technically feasible, and with its acceptable operative time and blood loss, presents an excellent therapeutic option for early gastric cancer; while SNB and subsequent frozen section analysis by H&E and IHC-CK staining is a rapid and reliable diagnostic method for intraoperative detection of SN (micro) metastasis. This combination treatment is a promising alternative to laparoscopic gastrectomy with conventional lymphadenectomy.     

Lymphatic mapping and sentinel node biopsy in gastric cancer

BACKGROUND: To determine the feasibility and significance of lymphatic mapping and sentinel lymph node biopsy (SLNB) in patients with gastric cancer. METHODS: From August 1999 to January 2002, 27 gastric cancer patients underwent lymphatic mapping and sentinel lymph node biopsy using isosulfan blue dye. RESULTS: The success rate of SLNB was 96.3% (26 of 27). Accuracy, sensitivity, and specificity were 100%. There were no false negatives. In 26 successful cases, 8 patients had positive sentinel lymph nodes and 18 had negative sentinel nodes. Of 8 patients with positive sentinel nodes, 6 had positive sentinel nodes only at N1 lymph node station, 1 only at N2 station, and 1 had positive sentinel nodes at both N1 and N2 stations. Of 18 patients with negative sentinel lymph nodes, 9 patients had sentinel nodes only at N1, 3 only at N2, 5 at both N1 and N2, and 1 at both N1 and N3. There were no cases in which sentinel lymph nodes were the only sites of metastases. CONCLUSIONS: Sentinel lymph node biopsy using isosulfan blue dye in gastric cancer is a feasible procedure with high sensitivity and accuracy. Sentinel lymph nodes demonstrate the varied lymphatic drainage. If the sentinel nodes at N2 are positive, it will guide surgeons to do a more extended lymph node dissection in early stage gastric cancer.     

Video-assisted breast surgery and sentinel lymph node biopsy guided by three-dimensional computed tomographic lymphography

Background Video-assisted breast surgery (VABS) is a less invasive and aesthetically better option for benign and malignant breast diseases and for sentinel lymph node biopsy (SLNB). The authors have performed 150 VABS procedures since December 2001. They have examined the usefulness of three-dimensional computed tomographic (3D-CT) lymphography for detecting sentinel lymph nodes (SLNs) precisely, as well as the cosmetic and treatment results of VABS. Methods In this study, VABS was performed with a 2.5-cm skin incision in the axilla or periareola (1 cm in the axilla for SLNB), using a retraction method, for mammary gland resection, SLNB, axillary lymph node dissection, and breast reconstruction under video assistance. On the day before the surgery, 3D-CT lymphography was performed to mark SLN on the skin. Above the tumor and near the areola, 2 ml of Iopamiron 300 was injected subcutaneously. A 16-channnel multidetector-row helical CT scan image was taken after 1 min and reconstructed to produce a 3D image. Sentinel lymph node biopsy was performed by the VABS technique using the Visiport. Results The VABS procedure was performed for 19 benign and 131 malignant diseases, and 115 SLNBs (74 with 3D-CT) were performed. The SLNs were shown precisely by 3D-CT lymphography, as proved by a case of lymph node metastasis, in which accurate relationships between lymph ducts and SLNs were shown. These were classified into four patterns: a single duct to single node (40 cases), multiple ducts to a single node (13 cases), a single duct to multiple nodes (1 case), and multiple ducts to multiple nodes (12 cases). The SLNB procedure can be performed safely by 3D-CT lymphography and less invasively by VABS. Conclusions The findings show that 3D-CT lymphography is useful for performing precise SLNB using VABS. An erratum to this article can be found at     

应用亚甲蓝行乳腺癌前哨淋巴结活检276例分析

目的 探讨以亚甲蓝作为示踪剂行乳腺癌前哨淋巴结(SLN)活检的临床应用及影响因素.方法 分析了276例临床T1-T2 N0-M0乳腺癌患者前哨淋巴结活检(SLNB)结果,对SLN检出率及假阴性率影响因素进行了初步分析.结果 276例患者中,成功检出SLN者246例(检出率为89.1%).共检出SLN 423枚,每例1～4枚.前哨淋巴结对腋窝淋巴结转移情况预测的敏感性为77.3%(68/88),假阴性率为8.1%(20/246),假阳性率为0,准确率为91.9%(226/246).临床T2N0M0SLNB成功率高于临床T1N0M0乳腺癌患者(P=0.046);年龄<50岁者SLNB检出成功率高于年龄≥50岁病例(P=0.000),SLNB假阴性率年龄<50岁者显著低于高龄患者(P=0.037);外上象限和外下象限肿瘤SLNB检出成功率明显高于其他象限(P=0.000).内上象限肿瘤SLNB假阴性率高于外上及外下象限(P=0.018).临床TMN分期、EB、PR表达情况及病理类型对SLNB成功率及假阴性率无影响.结论 以亚甲蓝作为示踪剂行乳腺癌SLNB,患者年龄、临床TNM分期、肿瘤部位对SLN检出率有一定影响,患者年龄、肿瘤部位可影响SLNB假阴性率.     

Laparoscopy-assisted distal gastrectomy with laparoscopic sentinel lymph node biopsy after endoscopic mucosal resection for early gastric cancer

Background There has been a trend toward minimally invasive treatment of early gastric cancer. We report the preliminary results of laparoscopy-assisted distal gastrectomy with laparoscopic sentinel lymph node biopsy after endoscopic mucosal resection. Methods Six patients underwent laparoscopy-assisted distal gastrectomy after endoscopic mucosal resection between February 2002 and October 2005 at Mie University Hospital. These patients first underwent laparoscopic sentinel lymph node biopsy and then laparoscopy-assisted distal gastrectomy with lymphadenectomy. Results No patient underwent conversion to open surgery during the operation. None of the patients had any postoperative complications. The mean length of postoperative hospital stay was 11.3 days. Sentinel lymph nodes were identified laparoscopically in five patients. There were 20 sentinel and 85 nonsentinel lymph nodes in the six patients. Postoperatively, tissue sections showed that none of the lymph nodes were metastasized. Immunohistochemistry with D2-40 antibody showed that there were normal lymphatics in the submucosal layer with mucosal defects at the endoscopic mucosal resection site. No patients had any tumor recurrence during followup. Conclusions Laparoscopy-assisted distal gastrectomy after endoscopic mucosal resection was a safe and curative procedure. Endoscopic mucosal resection before sentinel lymph node biopsy was acceptable for early gastric cancer.     

Lymphatic mapping and sentinel node biopsy during laparoscopic gastrectomy for early cancer

BACKGROUND/AIMS: Intraoperative lymphatic mapping and sentinel node (SN) biopsy can potentially be combined with minimally invasive surgery, but there are few reports of laparoscopic lymphatic mapping for gastrointestinal cancer. We examined the feasibility and accuracy of laparoscopic lymphatic mapping in predicting lymph node status in patients with gastric cancer. METHODS: Seventeen patients with gastric cancer invading the mucosal or submucosal layers (T1) underwent laparoscopic gastrectomy with lymphatic mapping between March 2001 and May 2002. The day before surgery, a technetium-99m-labelled tin colloid solution was injected endoscopically around the tumor. Immediately after the pneumoperitoneum, patent blue was injected. Gastrectomy was performed in all patients, and blue-stained or radioactive nodes were defined as SNs. Fresh SNs were immediately processed for frozen-section examination by hematoxylin-eosin (H and E) and immunohistochemical (IHC) staining. All non-SNs harvested from resected specimens were subjected to histological examination with H and E. RESULTS: SNs were detected in all patients by combination of the two kinds of tracers. Three patients had lymph node metastases in their final examination, and SNs in these 3 were operatively diagnosed as positive by H and E or IHC staining. Lymphatic mapping and SN biopsy under laparoscopic surgery were performed with 100% accuracy. CONCLUSION: Our preliminary study shows the feasibility of intraoperative lymphatic mapping in laparoscopic gastrectomy for T1 gastric cancer.     

Radio-guided sentinel node detection for gastric cancer

BACKGROUND: Radio-guided detection of sentinel nodes (SNs) has been used to predict regional metastases in patients with malignant melanoma and breast cancer. However, the validity of the SN hypothesis is still controversial for gastrointestinal cancers including gastric cancer. The aim of this study was to test the feasibility and accuracy of radio-guided mapping of SNs for gastric cancer. METHODS: Some 145 consecutive patients with gastric cancer diagnosed as T1 or T2 and evaluated clinically as N0 were enrolled. Endoscopic injection of technetium-99m-radiolabelled tin colloid was performed before operation and radioactive SNs were identified with a gamma probe. Standard radical gastrectomy with lymphadenectomy was performed in all patients and all resected nodes were evaluated by routine histopathological examination. RESULTS: Using radio-guided methods, SNs were detected in 138 (95.2 per cent) of 145 patients. The SN was positive in 22 of 24 patients with lymph node metastasis. The incidence of metastasis in the SNs (7.8 per cent) was significantly higher than that in the non-SNs (0.3 per cent) (P < 0.01). The diagnostic accuracy according to SN status was 98.6 per cent (136 of 138). CONCLUSION: Radio-guided SN mapping is an accurate diagnostic procedure for detecting lymph node metastasis in patients with early-stage gastric cancer.     

Internal mammary sentinel node biopsy for breast cancer

Background

The purpose of this study was to determine the value of lymphoscintigraphy (LS) for internal mammary sentinel node (IMSN) identification, the metastatic rate, and the change in staging and treatment.

Methods

Between 2001 and 2007 a prospective database was obtained of all patients undergoing IMSN biopsies using an open or thoracoscopic approach. Radiotracer injection was peritumoral.

Results

Thirty-four patients were included. There was one man. Three had ductal carcinoma in situ. LS showed IMSN in 47.1%. The IMSN biopsy success rate was 91.2%. Seven of the 28 successfully biopsied invasive cancer patients had metastatic IMSNs (25%). Positive IMSNs were associated with positive axillary nodes in 71.4% (P = .036). All patients with positive IMSNs were upstaged and received radiation to the internal mammary chain. In 4 of 28 patients (14%) the chemotherapy plans were probably altered. In univariate and multivariate analyses tumor size, location, nuclear grade, estrogen receptors, progesterone receptors, Her-2, and histology were not significant predictors of positivity.

Conclusions

IMSNs were positive in 25% of the invasive cancer patients. All had treatment changes. LS identified less than 50% of IMSNs. There are no good tumor-related predictors of IMSN positivity.     

乳腺癌前哨淋巴结活检的研究进展

腋窝淋巴结清扫（axillary lymph nodes dissection，ALND）一直是乳腺癌外科治疗中不可缺少的组成部分，对乳腺癌临床分期、判断预后、指导治疗和防止局部复发具有重要的临床价值。但随着腋窝淋巴结阴性的早期乳腺癌发病比例逐年增高，ALND的治疗意义也逐渐下降，还可导致术后许多并发症，影响了患者的肢体功能和生活质量。因此，越来越多的学者对乳腺癌常规行ALND的必要性提出质疑。随着对前哨淋巴结活检（sentinel lymph node biopsy，SLNB）技术研究的不断深入，已有越来越多的医生和医疗机构接受了这一全新的概念和技术。     

Detection of early lymph node metastases in prostate cancer by laparoscopic radioisotope guided sentinel lymph node dissection

PURPOSE: Radioisotope guided sentinel lymph node (SLN) dissection (SLND) for prostate cancer has been shown to increase the sensitivity of detecting early metastases in open pelvic lymph node dissection. We developed a technique that allows SLND to be performed by laparoscopy in conjunction with laparoscopic radical prostatectomy. MATERIALS AND METHODS: In 71 consecutive patients SLND was performed by 1 surgeon preceding laparoscopic radical prostatectomy. Mean preoperative prostate specific antigen was 8.88 ng/ml (range 2.1 to 25.4). At 24 hours prior to surgery 3 ml (200 MBq) Tc labeled human albumin colloid were injected into the prostate gland under transrectal ultrasound guidance. An especially designed laparoscopic gamma probe was used to measure radioactivity during surgery. SLNs were identified and removed. If frozen section analysis showed metastases, extended pelvic lymph node dissection was performed. RESULTS: Radioactivity was detected on 2, 1 and no sides in 50 (70.4%), 19 (26.7%) and 2 patients (2.8%), respectively. In 81 of the 142 pelvic side walls (54.7%) SLNs were exclusively outside of the obturator fossa. Histopathological examination showed metastases to SLNs in 9 patients (12.9%). Eight of the 11 detected metastases (72.7%) were outside of the obturator fossa. Lymph node metastases were exclusively found in Tc marked lymph nodes. Mean tumor size was 1.7 mm (range 0.2 to 3.9). CONCLUSIONS: SLND is feasible by laparoscopy. It detects micrometastases outside of the obturator fossa in a significant number of patients. We noted that the transperitoneal approach allowing wide exposure and a gamma probe with a 90-degree lateral energy window is the most important factor to enable successful laparoscopic SLND.     

Clinical significance of sentinel node navigation surgery in the treatment of early gastric cancer]

Radical lymphadenectomy is the standard surgical approach even for early-stage gastric cancer with a relatively low incidence of lymph node metastasis because of the limited sensitivity of diagnostic imaging to detect micrometastasis in regional lymph nodes. The sentinel node (SN) concept is one topic among novel diagnostic procedures for micrometastasis. The SN is defined as the first draining node from the primary lesion and it would be the first site of micrometastasis. SN biopsy has been clinically validated and applied for the surgical treatment of malignant melanoma and breast cancer. Although the feasibility of this technique in other solid tumors including gastric cancer is still controversial, there are several reports demonstrating the diagnostic significance of SN mapping in early gastric cancer. We have established radio-guided SN mapping for early gastric cancer, and the diagnostic accuracy using this procedure in cT1N0 cases reached 98%. The radio-guided method allows us to detect the SN in endoscopic surgery quantitatively and reproducibly. Validation of the SN concept in gastric cancer in a multi-centric clinical trial is essential for clinical application of this procedure, including the establishment of a novel, minimally invasive approach for early-stage gastric cancer.     

前哨淋巴结活检在结直肠癌根治术中的应用研究

目的探讨前哨淋巴结活检（SLNB）在结直肠癌根治术中临床应用的可行性及其价值。方法应用美蓝对67例结直肠癌患者行前哨淋巴结（SLN）定位活检,分体内、体外组,采用HE染色病理检查法、CK-20免疫组化染色（SP法）检测SLN中转移癌。结果共检出淋巴结660枚,其中SLN130枚,检出率19．7％。腹腔镜结直肠癌根治术和开腹结直肠癌根治术对SLN的检出差异无统计学意义（P=0．742）;体内、体外两种SLN的标记方法差异无统计学意义（P=0．564）;SP法检测SLN癌转移的敏感性明显高于HE染色,而假阴性率明显低于后者;肿瘤细胞在SLN的转移率明显高于区域淋巴结的转移率（P〈0．01）。结论结直肠癌根治术中体内、体外SLN定位方法均可以获得成功,均具有切实的可行性,与手术方式无关,并能够预测区域淋巴结的转移状况;通过SP法检查有助于明确结直肠癌的病理分期,有利于判断预后和个体化治疗方案的制定。