Near-infrared-fluorescence imaging of lymph nodes by using liposomally formulated indocyanine green derivatives

Liposomally formulated indocyanine green (LP-ICG) has drawn much attention as a highly sensitive near-infrared (NIR)-fluorescence probe for tumors or lymph nodes in vivo. We synthesized ICG derivatives tagged with alkyl chains (ICG-Cn), and we examined NIR-fluorescence imaging for lymph nodes in the lower extremities of mice by using liposomally formulated ICG-Cn (LP-ICG-Cn) as well as conventional liposomally formulated ICG (LP-ICG) and ICG. Analysis with a noninvasive preclinical NIR-fluorescence imaging system revealed that LP-ICG-Cn accumulates in only the popliteal lymph node 1 h after injection into the footpad, whereas LP-ICG and ICG accumulate in the popliteal lymph node and other organs like the liver. This result indicates that LP-ICG-Cn is a useful NIR-fluorescence probe for noninvasive in vivo bioimaging, especially for the sentinel lymph node.     

Multispectral Real-time Fluorescence Imaging for Intraoperative Detection of the Sentinel Lymph Node in Gynecologic Oncology

The prognosis in virtually all solid tumors depends on the presence or absence of lymph node metastases.^1-3 Surgical treatment most often combines radical excision of the tumor with a full lymphadenectomy in the drainage area of the tumor. However, removal of lymph nodes is associated with increased morbidity due to infection, wound breakdown and lymphedema.^4,5 As an alternative, the sentinel lymph node procedure (SLN) was developed several decades ago to detect the first draining lymph node from the tumor.⁶ In case of lymphogenic dissemination, the SLN is the first lymph node that is affected (Figure 1). Hence, if the SLN does not contain metastases, downstream lymph nodes will also be free from tumor metastases and need not to be removed. The SLN procedure is part of the treatment for many tumor types, like breast cancer and melanoma, but also for cancer of the vulva and cervix.⁷ The current standard methodology for SLN-detection is by peritumoral injection of radiocolloid one day prior to surgery, and a colored dye intraoperatively. Disadvantages of the procedure in cervical and vulvar cancer are multiple injections in the genital area, leading to increased psychological distress for the patient, and the use of radioactive colloid.Multispectral fluorescence imaging is an emerging imaging modality that can be applied intraoperatively without the need for injection of radiocolloid. For intraoperative fluorescence imaging, two components are needed: a fluorescent agent and a quantitative optical system for intraoperative imaging. As a fluorophore we have used indocyanine green (ICG). ICG has been used for many decades to assess cardiac function, cerebral perfusion and liver perfusion.⁸ It is an inert drug with a safe pharmaco-biological profile. When excited at around 750 nm, it emits light in the near-infrared spectrum around 800 nm. A custom-made multispectral fluorescence imaging camera system was used.⁹.The aim of this video article is to demonstrate the detection of the SLN using intraoperative fluorescence imaging in patients with cervical and vulvar cancer. Fluorescence imaging is used in conjunction with the standard procedure, consisting of radiocolloid and a blue dye. In the future, intraoperative fluorescence imaging might replace the current method and is also easily transferable to other indications like breast cancer and melanoma.     

早期子宫颈恶性肿瘤腹腔镜手术中两种示踪剂前哨淋巴结活检结果的对比分析

目的:通过在早期子宫颈恶性肿瘤患者中应用吲哚箐绿(ICG)及纳米炭混悬液为示踪剂行腹腔镜下前哨淋巴结(sentinel lymph node,SLN)切除术,对比两种示踪剂的示踪效果,寻找临床更适宜普遍使用的示踪剂。方法:选取仁济医院妇瘤科2016.8～2019.10期间诊断明确的122例早期子宫颈恶性肿瘤患者为研究对象。随机采用ICG或纳米炭为前哨示踪剂。对两种示踪剂的显影情况和SLN的示踪效果进行分析。结果:在122例子宫颈恶性肿瘤病例中,宫颈注射ICG64例,检出SLN385枚,平均每个患者检出6.02枚SLN,检出率100%(64/64),特异度96.77%,敏感度75%。宫颈注射纳米炭混悬液58例,检出SLN265枚,平均每个患者检出4.57枚SLN,检出率96.9%(56/58),特异度96.36%,敏感度66.67%。两种示踪剂都有较好的示踪效果(P=0.9356)。结论:早期子宫颈恶性肿瘤行宫颈注射ICG或纳米炭混悬液,腹腔镜下显影的SLN均具有较高的检出率与准确率,是一种较为可行的方法,可普遍开展,值得推广。     

Use of Indocyanine Green for Detecting the Sentinel Lymph Node in Breast Cancer Patients: From Preclinical Evaluation to Clinical Validation

Assessment of the sentinel lymph node (SLN) in patients with early stage breast cancer is vital in selecting the appropriate surgical approach. However, the existing methods, including methylene blue and nuclides, possess low efficiency and effectiveness in mapping SLNs, and to a certain extent exert side effects during application. Indocyanine green (ICG), as a fluorescent dye, has been proved reliable usage in SLN detection by several other groups. In this paper, we introduce a novel surgical navigation system to detect SLN with ICG. This system contains two charge-coupled devices (CCD) to simultaneously capture real-time color and fluorescent video images through two different bands. During surgery, surgeons only need to follow the fluorescence display. In addition, the system saves data automatically during surgery enabling surgeons to find the registration point easily according to image recognition algorithms. To test our system, 5 mice and 10 rabbits were used for the preclinical setting and 22 breast cancer patients were utilized for the clinical evaluation in our experiments. The detection rate was 100% and an average of 2.7 SLNs was found in 22 patients. Our results show that the usage of our surgical navigation system with ICG to detect SLNs in breast cancer patients is technically feasible.     

Minimally Invasive Electro-Magnetic Navigational Bronchoscopy-Integrated Near-Infrared-Guided Sentinel Lymph Node Mapping in the Porcine Lung

BackgroundThe use of near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) for sentinel lymph node (SN) mapping has been investigated in lung cancer; however, this has not been fully adapted for minimally invasive surgery (MIS). The aim of our study was to develop a minimally invasive SN mapping integrating pre-operative electro-magnetic navigational bronchoscopy (ENB)-guided transbronchial ICG injection and intraoperative NIR thoracoscopic imaging.MethodsA NIR thoracoscope was used to visualize ICG fluorescence. ICG solutions in a 96-well plate and ex vivo porcine lungs were examined to optimize ICG concentrations and injection volumes. Transbronchial ICG injection (n=4) was assessed in comparison to a traditional transpleural approach (n=3), where after thoracotomy an ICG solution (100μL at 100μg/mL) was injected into the porcine right upper lobe for SN identification. For further translation into clinical use, transbronchial ICG injection prior to thoracotomy followed by NIR thoracoscopic imaging was validated (n=3). ENB was used for accurate targeting in two pigs with a pseudo-tumor.ResultsThe ICG fluorescence at 10 μg/mL was the brightest among various concentrations, unchanged by the distance between the thoracoscope and ICG solutions. Injected ICG of no more than 500μL showed a localized fluorescence area. All 7 pigs showed a bright paratracheal lymph node within 15 minutes post-injection, with persistent fluorescence for 60 minutes. The antecedent transbronchial ICG injection succeeded in SN identification in all 3 cases at the first thoracoscopic inspection within 20 minutes post-injection. The ENB system allowed accurate ICG injection surrounding the pseudo-tumors.ConclusionsENB-guided ICG injection followed by NIR thoracoscopy was technically feasible for SN mapping in the porcine lung. This promising platform may be translated into human clinical trials and is suited for MIS.     

Uniform silica coated fluorescent nanoparticles: synthetic method, improved light stability and application to visualize lymph network tracer

Background

The sentinel lymph node biopsy (SLNB) was developed as a new modality in the surgical diagnosis of lymph node metastases. Dye and radioisotope are major tracers for the detection of sentinel lymph nodes (SLN). Dye tends to excessively infiltrate into the interstitium due to their small size (less than several nanometers), resulting in difficulties in maintaining clear surgical fields. Radioisotopes are available in limited number of hospitals. Fluorescent nanoparticles are good candidates for SLN tracer to solve these problems, as we can choose suitable particle size and fluorescence wavelength of near-infrared. However, the use of nanoparticles faces safety issues, and many attempts have been performed by giving insulating coats on nanoparticles. In addition, the preparation of the uniform insulating layer is important to decrease variations in the quality as an SLN tracer.

Methodology/Principal Findings

We herein succeeded in coating fluorescent polystyrene nanoparticles of 40 nm with uniform silica layer of 13 nm by the modified Stöber method. The light stability of silica coated nanoparticles was 1.3-fold greater than noncoated nanoparticles. The popliteal lymph node could be visualized by the silica coated nanoparticles with injection in the rat feet.

Conclusions/Significance

The silica coated nanoparticles in lymph nodes could be observed by transmission electron microscope, suggesting that our silica coating method is useful as a SLN tracer with highly precise distribution of nanoparticles in histological evaluation. We also demonstrated for the first time that a prolonged enhancement of SLN is caused by the phagocytosis of fluorescent nanoparticles by both macrophages and dendritic cells.     

Visualisation of Sentinel Lymph Node with Indium-Based near Infrared Emitting Quantum Dots in a Murine Metastatic Breast Cancer Model

Due to its non-invasiveness, high temporal resolution and lower cost, fluorescence imaging is an interesting alternative to the current method (blue dye and radiocolloid) of sentinel lymph node (SLN) mapping in breast cancer. Near-infrared (NIR) emitting cadmium-based Quantum Dots (QDs) could be used for this purpose; however, their wide application is limited because of the toxicity of heavy metals composing the core. Our recent work demonstrated that indium-based QDs exhibit a weak acute local toxicity in vivo compared to their cadmium-based counterparts. In the present study we confirmed the weak toxicity of CuInS(2)/ZnS QDs in different in vitro models. Further in vivo studies in healthy mice showed that In-based QDs could be visualised in SLN in a few minutes after administration with a progressive increase in fluorescence until 8 h. The quantity of indium was assessed in selected organs and tissues by inductively coupled plasma - mass spectroscopy (ICP-MS) as a function of post-injection time. QD levels decrease rapidly at the injection point in the first hours after administration with a parallel increase in the lymph nodes and to a lesser extent in the liver and spleen. In addition, we observed that 3.5% of the injected indium dose was excreted in faeces in the first 4 days, with only trace quantities in the urine. Metastatic spread to the lymph nodes may hamper its visualisation. Therefore, we further performed non-invasive fluorescence measurement of QDs in SLN in tumour-bearing mice. Metastatic status was assessed by immunohistology and molecular techniques and revealed the utmost metastatic invasion of 36% of SLN. Fluorescence signal was the same irrespective of SLN status. Thus, near-infrared emitting cadmium-free QDs could be an excellent SLN tracer.     

吲哚菁绿联合亚甲蓝在乳腺癌前哨淋巴结活检中的临床应用

目的:探讨吲哚菁绿(indocyanine green,ICG)联合亚甲蓝在乳腺癌前哨淋巴结活检(sentinel lymph node biopsy,SLNB)中的临床应用价值。方法:共入组39例乳腺癌患者,在光学分子影像手术导航系统(surgical navigation system,SNS)的引导下,使用ICG联合亚甲蓝实施SLNB。快速冰冻病理证实前哨淋巴结(sentinel lymph node,SLN)转移者,即刻行腋窝淋巴结清扫(axillary lymph node dissection,ALND);SLN阴性者免于ALND。结果:联合法实施SLNB检出率95%,成功检出SLN125个,平均检出3.2个SLN,准确率95.0%,灵敏度100%,假阴性率0%;蓝染法检出率87.2%,成功检出SLN71个,平均检出1.8个SLN,准确率89.7%,灵敏度93.7%,假阴性率为6.3%;统计结果采用x2检验,检验结果具有统计学意义。结论:ICG联合亚甲蓝实施乳腺癌SLNB成功率高,假阴性率低,临床效果不亚于亚甲蓝,是实施SLNB的新方法。     

Ex vivo localization and immunohistochemical detection of sentinel lymph node micrometastasis in patients with colorectal cancer can upgrade tumor staging

ABSTRACT: BACKGROUND: It is not clear if sentinel lymph node (SLN) mapping can improve outcomes in patients with colorectal cancers. The purpose of this study was to determine the prognostic values of ex vivo sentinel lymph node (SLN) mapping and immunohistochemical (IHC) detection of SLN micrometastasis in colorectal cancers. METHODS: Colorectal cancer specimens were obtained during radical resections and the SLN was identified by injecting a 1% isosulfan blue solution submucosally and circumferentially around the tumor within 30 min after surgery. The first node to stain blue was defined as the SLN. SLNs negative by hematoxylin and eosin (HE) staining were further examined for micrometastasis using cytokeratin IHC. RESULTS: A total of 54 patients between 25 and 82 years of age were enrolled, including 32 males and 22 females. More than 70% of patients were T3 or above, about 86% of patients were stage II or III, and approximately 90% of patients had lesions grade II or above. Sentinel lymph nodes were detected in all 54 patients. There were 32 patients in whom no lymph node micrometastasis were detected by HE staining and 22 patients with positive lymph nodes micrometastasis detected by HE staining in non-SLNs. In contrast only 7 SLNs stained positive with HE. Using HE examination as the standard, the sensitivity, non-detection rate, and accuracy rate of SLN micrometastasis detection were 31.8% (7/22), 68.2% (15/22), and 72.2%, respectively. Micrometastasis were identified by ICH in 4 of the 32 patients with HE-negative stained lymph nodes, resulting in an upstaging rate 12.5% (4/32). The 4 patients who were upstaged consisted of 2 stage I patients and 2 stage II patients who were upstaged to stage III. Those without lymph node metastasis by HE staining who were upstaged by IHC detection of micrometastasis had a significantly poorer disease-free survival (p = 0.001) and overall survival (p = 0.004). CONCLUSION: Ex vivo localization and immunohistochemical detection of sentinel lymph node micrometastasis in patients with colorectal cancer can upgrade tumor staging, and may become a factor affecting prognosis and guiding treatment.     

Clinical relevance of novel imaging technologies for sentinel lymph node identification and staging

The sentinel lymph node (SLN) concept has become a standard of care for patients with breast cancer and melanoma, yet its clinical application to other cancer types has been somewhat limited. This is mainly due to the reduced accuracy of conventional SLN mapping techniques (using blue dye and/or radiocolloids as lymphatic tracers) in cancer types where lymphatic drainage is more complex, and SLNs are within close proximity to other nodes or the tumour site. In recent years, many novel techniques for SLN mapping have been developed including fluorescence, x-ray, and magnetic resonant detection. Whilst each technique has its own advantages/disadvantages, the role of targeted contrast agents (for enhanced retention in the SLN, or for immunostaging) is increasing, and may represent the new standard for mapping the SLN in many solid organ tumours. This review article discusses current limitations of conventional techniques, limiting factors of nanoparticulate based contrast agents, and efforts to circumvent these limitations with modern tracer architecture.     

High Prevalence of Human Cytomegalovirus Proteins and Nucleic Acids in Primary Breast Cancer and Metastatic Sentinel Lymph Nodes

Background

Breast cancer is a leading cause of death among women worldwide. Increasing evidence implies that human cytomegalovirus (HCMV) infection is associated with several malignancies. We aimed to examine whether HCMV is present in breast cancer and sentinel lymph node (SLN) metastases.

Materials and Methods

Formalin-fixed paraffin-embedded tissue specimens from breast cancer and paired sentinel lymph node (SLN) samples were obtained from patients with (n = 35) and without SLN metastasis (n = 38). HCMV immediate early (IE) and late (LA) proteins were detected using a sensitive immunohistochemistry (IHC) technique and HCMV DNA by real-time PCR.

Results

HCMV IE and LA proteins were abundantly expressed in 100% of breast cancer specimens. In SLN specimens, 94% of samples with metastases (n = 34) were positive for HCMV IE and LA proteins, mostly confined to neoplastic cells while some inflammatory cells were HCMV positive in 60% of lymph nodes without metastases (n = 35). The presence of HCMV DNA was confirmed in 12/12 (100%) of breast cancer and 10/11 (91%) SLN specimens from the metastatic group, but was not detected in 5/5 HCMV-negative, SLN-negative specimens. There was no statistically significant association between HCMV infection grades and progesterone receptor, estrogen receptor alpha and Elston grade status.

Conclusions

The role of HCMV in the pathogenesis of breast cancer is unclear. As HCMV proteins were mainly confined to neoplastic cells in primary breast cancer and SLN samples, our observations raise the question whether HCMV contributes to the tumorigenesis of breast cancer and its metastases.     

The competent sentinel node: an association with an axillary presentation and an occult or a small primary invasive breast carcinoma

The concept of the sentinel node describes a primary or sentinel lymph node (SLN), which exists and through which tumour cells from a primary tumour in a particular location must first travel to spread to a particular regional lymph node group. In this series we present three patients presenting with a pathological axillary node associated with either an occult or very small primary breast cancer. In each case the primary tumour was found to have metastasised to the palpable node, however despite the significant enlargement of this node, no other axillary nodes were found to be affected on axillary node clearance. This has led us to postulate that the SLN in some cases contains unique characteristics that enable it to prevent further spread of the tumour up the lymphatic chain. Hence the term the competent sentinel node.     

初诊腋窝淋巴结阳性乳腺癌新辅助化疗后对腋窝淋巴结转阴性前哨活检的影响分析

摘要 目的：探究对初诊腋窝淋巴结阳性乳腺癌行新辅助化疗患者开展腋窝前哨淋巴结活检的临床意义。方法：选择2017年1月至2020年10月于我院接受改良根治术或保乳术治疗的100例初诊腋窝淋巴结阳性乳腺癌患者,将其中50例病理检测II B、III期行4~8个疗程新辅助化疗后实施前哨淋巴结活检患者设为研究组,将50例I、II A期直接行前哨淋巴结活检患者设为对照组,对比两组患者前哨淋巴结检出率、准确率、假阴性率和灵敏度,同时就患者病理特征与前哨淋巴结检出率的相关性开展分析。结果：（1）比较显示研究组患者与对照组患者在前哨淋巴结检出数、前哨淋巴结检出率以及前哨淋巴结假阴性率方面组间差异不大（P>0.05）;（2）病理学特征分析显示肿瘤直径以及临床N分期同新辅助化疗后患者前哨淋巴结检出阳性率密切相关（P<0.05）。结论：对初诊腋窝淋巴结阳性行新辅助化疗乳腺癌患者实施前哨淋巴结活检具有较显示的临床意义,能够较好的预测患者腋窝淋巴结状况,同时化疗前肿瘤直径、临床N分期是影响前哨淋巴结检出率的重要影响因素。     

Diagnostic value of intraoperative histopathological examination of the sentinel nodes in breast cancer and skin melanoma—Preliminary results of single centre retrospective study

Objective

Intraoperative histopatological examination of the sentinel nodes enables selection of patients who need dissection of the regional lymphatic system during the same operation. The aim of this study is to evaluate the diagnostic value of intraoperative histopathological examination of the sentinel nodes in breast cancer and skin melanoma. Intraoperative histopathology of the sentinel nodes as a diagnostic method is used in patients with melanoma and breast cancer. Recent studies have proved it to be an effective method for evaluating the nodes in the final histopathology. Intraoperative histopathological examination of the sentinel nodes is not performed routinely and there is no clear position on this issue. In this paper we try to prove that intraoperative test gives patients the simultaneous benefits of removal of regional lymph nodes metastases and earlier initiation of adjuvant therapy.

Methods

The study comprises 137 patients with breast cancer and 35 patients with malignant skin melanoma. Sentinel nodes were intraoperatively sectioned and examined by means of the imprint method and frozen section evaluation. The patients with positive sentinel nodes underwent immediate dissection of regional lymph nodes. Those with negative sentinel nodes diagnosed in the intraoperative examination, but positive in final pathologic results, underwent subsequent dissection of regional lymph nodes.

Results

60 sentinel lymph nodes were found in 35 patients with skin melanoma. In 3 patients, 3 sentinel lymph nodes were false negative in the intraoperative histopathological examination. No false positive sentinel lymph nodes were found. 249 sentinel lymph nodes were found in the intraoperative histopathological examination in 137 patients with breast cancer. There were no false positive sentinel nodes, but there were 7 false negative sentinel nodes. In this study, only 5 (3.6%) patients with breast cancer and 3 (8.5%) patients with skin melanoma required another regional operation.

Conclusion

The method of intraoperative histopathological evaluation of the sentinel nodes enables identification of metastases in these lymph nodes and gives a possibility to carry out a one-step regional lymphadenectomy and start the adjuvant therapy earlier.     

Absence of Tumor-Infiltrating Lymphocyte Is a Reproducible Predictive Factor for Sentinel Lymph Node Metastasis: A Multicenter Database Study by the Brazilian Melanoma Group

Aims

The aim of this study is to confirm the function of tumor-infiltrating lymphocytes (TILs) in sentinel lymph node (SLN) metastasis.

Materials and Methods

This retrospective study included 633 patients with invasive melanoma who underwent sentinel lymph node biopsy in 7 referral centers certified by the Brazilian Melanoma Group. Independent risk factors of sentinel node metastasis (SNL) were identified by multiple logistic regression.

Results

SLN metastasis was detected in 101 of 633 cases (16.1%) and in 93 of 428 patients (21.7%) when melanomas ≤ 1mm were excluded. By multiple logistic regression, the absence of TILs was as an independent risk factor of SLN metastasis (OR = 1.8; 95%CI: 1.1–3.0), in addition to Breslow index (greater than 2.00 mm), lymph vascular invasion, and presence of mitosis.

Conclusion

SLNB can identify patients who might benefit from immunotherapy, and the determination of predictors of SLNB positivity can help select the proper population for this type of therapy. The absence of TILs is a reproducible parameter that can predict SLNB positivity in melanoma patients, since this study was made with several centers with different dermatopathologists.     

Sentinel lymph node detection by combining nonradioactive techniques with contrast agents: State of the art and prospects

The status of sentinel lymph nodes (SLNs) has a substantial prognostic value because these nodes are the first place where cancer cells accumulate along their spreading route. Routine SLN biopsy (“gold standard”) involves peritumoral injections of radiopharmaceuticals, such as technetium-99m, which has obvious disadvantages. This review examines the methods used as “gold standard” analogs to diagnose SLNs. Nonradioactive preoperative and intraoperative methods of SLN detection are analyzed. Promising photonic tools for SLNs detection are reviewed, including NIR-I/NIR-II fluorescence imaging, photoswitching dyes for SLN detection, in vivo photoacoustic detection, imaging and biopsy of SLNs. Also are discussed methods of SLN detection by magnetic resonance imaging, ultrasonic imaging systems including as combined with photoacoustic imaging, and methods based on the magnetometer-aided detection of superparamagnetic nanoparticles. The advantages and disadvantages of nonradioactive SLN-detection methods are shown. The review concludes with prospects for the use of conservative diagnostic methods in combination with photonic tools.     

Apport de la TEMP/TDM pour la détection du ganglion sentinelle dans les cancers du col utérin et de l’endomètre

The sentinel lymph node procedure is still under evaluation for the management of cervical and endometrial carcinomas. The aim of our study was to determine the diagnostic accuracy of single-photon emission computed tomography/computed tomography (SPECT/CT) for preoperative sentinel lymph node mapping in uterine cancers. Sixty-eight patients with cervical (n = 42) or endometrial carcinoma (n = 26) underwent preoperative lymphoscintigraphy for sentinel node mapping. Sentinel node detection rate with conventional planar imaging was similar to that of SPECT/CT (87.1 versus 91.8 %) in the whole cohort. However, SPECT/CT detected a higher number of sentinel nodes in more than one third of patients, affected by either cervical or endometrial carcinoma. The rate of non or insufficiently contributive procedures (lack of uptake or unilateral uptake) in endometrial carcinomas was 47 % with conventional planar imaging, and 30 % with SPECT/CT. Sensitivity of both procedures for the detection of metastatic nodes was 81.8 %, compared to 100 % for the intraoperative combined detection (gamma probe sonde and blue dye). The impact of SPECT/CT for the sentinel lymph node detection in cervical and endometrial carcinomas needs further evaluation. Nevertheless, SPECT/CT may provide additional information when conventional planar imaging detects only unilateral uptake, may improve identification of atypical localizations, and facilitate surgical approach.     

Lymph flow guided irradiation of regional lymph nodes in patients with cervical cancer: Preliminary analysis of scintigraphic data

PurposeTo evaluate patterns of lymph flow from primary lesions in patients with cervical cancer and to determine how useful for radiotherapy planning this information can be.Materials and methodsSPECT–CT visualization of sentinel (SLN) lymph nodes (LNs) was performed in 36 primary patients with IB-IIB cervical cancer. The acquisition started 120–240 min after 4 peritumoral injections of 99mTc-radiocolloids (150–300 MBq in 0.4–1 ml). We determined localization of LN with uptake of radiocolloids, type of lymph flow (mono-, bi-lateral) and lymph flow patterns (supraureteral paracervical, infraureteral paracervical and directly to para-aortic LNs).ResultsSLNs were visualized in 31 of 36 women. Bilateral lymph-flow was detected in 22 (71%), monolateral – in the other 9 (29%) cases. The distribution of SLNs was as follows: external iliac – 64.5%, internal iliac – 54.8%, obturator – 32.2%, common iliac – 35.5% and pre-sacral 3.2%. Para-aortic LNs were visualized in 5 (16.1%) patients. The supraureteral paracervical pattern of lymph flow was identified in 22, infraureteral paracervical – in 4 and their combination – in the other 5 women.ConclusionVisualization of an individual pattern of lymph flow from primary cervical cancer can be considered as a promising tool for optimization of the volume of irradiated regional LNs.     

Étude de faisabilité du ganglion sentinelle dans le cancer de la prostate par cœlioscopie : premiers résultats

Objectives

The standard lymphadenectomy is currently a challenge in the management of prostate cancer. The aim of this prospective study was to evaluate the performance of the sentinel lymph node (SLN) by laparoscopy in patients with localized prostate cancer, candidates for local treatment.

Patients and methods

Patients were injected transrectal ultrasound-guided with 0.3 mL/100MBq 99^mTc-Sulfur rhenium colloid in each prostatic lobe, the day before surgery. Lymphoscintigraphy was performed after 2 hours. The detection was realized intraoperatively with a laparoscopic probe (Gamma Sup Clerad^®) followed by extensive dissection. Counts of SLN were performed in vivo and confirmed ex vivo. The histological analysis was performed by HPS staining and followed by immunochemistry if SLN was free.

Results

Seventy patients with carcinoma of the prostate at intermediate or high risk of lymph node metastases (D’Amico), PSA median 9.5 ng/mL [6–130], were included in the study. The lymphoscintigraphic detection rate was 94.2% (66/70) and intraoperative of 97.0% (68/70). Fourteen patients had lymph node metastases, six only in SLN. The false negative rate was 2/14 (14.0%). The internal iliac region is the first metastatic site (40.9%). Limited or standard lymph node dissection would have ignored respectively 72.7% and 59.0% of lymph node metastases.

Conclusion

The laparoscopy is adapted to a broad identification of SLN and targeted dissection of these lymph nodes significantly limits the risk of surgical extended dissection while maintaining the accuracy of the information.     

Intérêt de l’injection péritumorale de nanocolloïdes technétiés pour la détection du ganglion sentinelle mammaire interne

ObjectivesUntil now, the effectiveness of sentinel lymph-node biopsy (SLNB) has only been demonstrated for the detection of axillary lymphatic involvement in early breast cancer (cT1N0). The purpose of this study was to evaluate whether the detection of an extra-axillary internal mammary sentinel lymph node (SLN), using peritumoral injection of radiolabelled nanocolloids (NC), can lead to a modification in management for these patients.Materials and methodsA total of 538 consecutives SLNB was analysed from a cohort of 529 patients. Peri- and infratumoral injections of radiolabelled NC were made under ultrasound control.ResultsA SLN was identified on 524 occasions, 147 (28.1%) of which were located in the internal mammary chain (IMC). In 10 cases, the SLN in the IMC was not associated with an axillary SLN. One hundred and thirty-five surgical biopsies of the IMC SLN were performed without significant morbidity. Sixteen patients demonstrated local involvement of an IMC SLN, which on seven occasions was isolated to this region. For six of these patients, the finding of SLN involvement led to a recommendation for adjuvant chemotherapy. For 308 patients, for lack of IMC involvement, the adjuvant IMC radiotherapy could have been avoided (i.e.: 95% of the theoretical indications for adjuvant radiotherapy).ConclusionsPeritumoral injection of radiolabelled NC, associated with a systematic IMC SLN biopsy, enabled the rationalisation of management in patients with stage cT1 breast cancer and did not affect the usual performance of the technique nor led to a significant increase in morbidity. The long-term survival and morbidity outcomes of these therapeutic modifications, particularly with regards to radiotherapy, will need to be demonstrated.