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Peritumoral Injection (peritumoral + injection)
Selected AbstractsInhibitory effect of the polyinosinic-polycytidylic acid/cationic liposome on the progression of murine B16F10 melanomaEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2006Taku Fujimura Abstract Cellular proteins, retinoic acid inducible gene-I and Toll-like receptor 3, sense dsRNA including polyinosinic-polycytidylic acid (PIC) to stimulate innate immune response. The local administration of PIC has been demonstrated to be effective in anti-tumor immunotherapy. However, the effects of PIC delivered cross the cell membrane have not yet been examined. To address this issue, we used a complex of PIC and cationic liposome (PIC liposome) and examined its anti-tumor effects in vitro and in vivo. PIC liposome could directly suppress the growth of B16F10 melanoma in vitro and repeated peritumoral injections of PIC liposome inhibited melanoma growth in a dose-dependent manner. This treatment induced tyrosinase-related protein-2 (TRP-2)-tetramer+ CD8+ cells in the lymph nodes. As the mechanism for its anti-tumor immune response, we showed that the intradermal injection of PIC liposome induced the maturation of dendritic cells (DC). Moreover, the intratumoral injection of immature DC after treatment with PIC liposome significantly increased the number of TRP-2-specific IFN-,-producing cells in the lymph nodes as well as spleen, which resulted in an augmentation of the anti-tumor immune response. These studies demonstrate the potential of peritumoral injection of PIC liposome as immunotherapy for malignant melanoma. [source] Lymphoscintigraphic and intraoperative detection of the sentinel lymph node in breast cancer patients: The nuclear medicine perspectiveJOURNAL OF SURGICAL ONCOLOGY, Issue 3 2004Giuliano Mariani MD Abstract The concept of sentinel lymph node biopsy in breast cancer surgery relates to the fact that the tumor drains in a logical way via the lymphatic system, from the first to upper levels. Therefore, (1) the first lymph node met (the sentinel node) will most likely be the first one affected by metastasis, and (2) a negative sentinel node makes it highly unlikely that other nodes are affected. Sentinel lymph node biopsy would represent a significant advantage as a mini-invasive procedure, considering that, after operation, about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. Although the pattern of lymphatic drainage from a breast cancer can be very variable, the mammary gland and the overlying skin can be considered as a biologic unit in which lymphatics tend to follow the vasculature. Considering that tumor lymphatics are disorganized and relatively ineffective, subdermal, and peritumoral injection of small aliquots of radiotracer is preferred to intratumoral administration. 99mTc-labeled colloids with most of the particles in the 100,200 nm size range would be ideal for radioguided sentinel node biopsy in breast cancer. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy, as images are used to direct the surgeon to the site of the node. The sentinel lymph node should have a significantly higher count than background. After removal of the sentinel node, the axilla must be re-examined to ensure all radioactive sites are identified and removed for analysis. The success rate of radioguidance in localizing the sentinel lymph node in breast cancer surgery is about 94,97% in Institutions where a high number of procedures are performed, approaching 99% when combined with the vital blue dye technique. At present, there is no definite evidence that a negative sentinel lymph node biopsy is invariably correlated with a negative axillary status, except perhaps for T1a-b breast cancers, with size ,1 cm. Randomized clinical trials should elucidate the impact of avoiding axillary node dissection in patients with a negative sentinel lymph node on the long-term clinical outcome of patients. J. Surg. Oncol. 2004;85:112,122. © 2004 Wiley-Liss, Inc. [source] Phase I study on sentinel lymph node mapping in colon cancer: A preliminary report,JOURNAL OF SURGICAL ONCOLOGY, Issue 2 2002Yves Bendavid Abstract Background and Objectives Lymph node (LN) metastasis is one of the most significant prognostic factor in colorectal cancer. In fact, therapeutic decisions are based on LN status. However, multiple studies have reported on the limitations of the conventional pathological LN examination techniques, and therefore, the actual number of patients with LN positive colorectal cancer is probably underestimated. We assume that lymphatic tumor dissemination follows an orderly sequential route. We report here a simple and harmless coloration technique that was recently elaborated, and that allows us to identify the sentinel LN(s) (SLN) or first relay LNs in colorectal cancer patients. The main endpoint of this clinical trial is the feasibility of the technique. Methods Twenty patients treated by surgery for a colic cancer were admitted in this protocol. A subserosal peritumoral injection of lymphazurin 1% was performed 10 min before completing the colic resection. A pathologist immediately examined the specimens, harvested the colored SLN, and examined them by serial cuts (200 ,m) with H&E staining, followed by immunohistochemical staining (AE1-AE3 cytokeratin markers), when serial sections were classified as cancer free. Results The preoperative identification of the SLN was impossible in at least 50 of the cases, however, SLNs were identified by the pathologist in 90% of cases. In two patients (10%) SLN was never identified. The average number of SLN was 3.9. Immunohistochemical analysis of the SLN has potentially changed the initial staging (from Dukes B to Dukes C) for 5 of the 20 patients (25%). On the other hand, there was one patient (5%) with hepatic metastasis from adenocarcinoma for whom SLN pathology was negative for metastasis (skip metastasis). Conclusions SLN biopsy is readily feasible with identification of SLN in at least 90% of patients with colorectal cancers. Our results indicate that 45% of patients initially staged as Dukes B had tumor cells identified in their SLN when these were subjected to our protocol. This represented a 25% upgrading rate when our complete study population is considered. However, controversy persist about the clinical significance and metastatic potential of these often very small clusters of tumor cells. J. Surg. Oncol. 2002;79:81,84. © 2002 Wiley-Liss, Inc. [source] Sentinel Lymph Node Biopsy: A Rational Approach for Staging T2N0 Oral Cancer,THE LARYNGOSCOPE, Issue 12 2005Nestor Rigual MD Abstract Objectives/Hypothesis: For oral cancer patients, the presence of neck nodal metastases is the most important disease prognosticator. However, a significant proportion of clinically N0 patients harbor occult microscopic nodal metastasis. Our objective was to determine the feasibility and accuracy of sentinel node biopsy (SNB) in the staging of T2N0 oral carcinoma patients. Study Design: Prospective analysis. Methods: Twenty patients with previously untreated N0 oral cavity squamous cell carcinoma were studied. Each patient had an SNB performed using preoperative technetium sulfur colloid lymphoscintigraphy, intraoperative gamma probe guidance, and intraoperative peritumoral injection of 1% isosulfan blue. All patients underwent neck dissection. The sentinel lymph nodes (SLNs) were sectioned in 2- to 3-mm intervals, formalin fixed, and sectioned at three levels. The non-SLNs were sectioned in a routine manner for histologic examination. Results: SLNs were identified in all patients (100%) and accurately predicted the pathologic nodal status in 18 of 20 patients (90%). Tumor was found exclusively in the SLNs in six patients (30%). Two patients had positive SLNs at multiple neck levels. Two patients had a negative SLN and a positive non-SLN (false-negative findings). Occult nodal metastases were present in 60% of the cohort. Conclusions: SNB is a technically feasible and accurate procedure for staging the neck in oral carcinoma patients. However, SNB accuracy is lower for floor of the mouth lesions. The rate of occult nodal metastases identified in this cohort is higher than previously reported in the literature. These results suggest that SNB warrants further multi-institutional studies. [source] Candidate's Thesis: The Application of Sentinel Node Radiolocalization to Solid Tumors of the Head and Neck: A 10-Year Experience,THE LARYNGOSCOPE, Issue 1 2004James C. Alex MD Abstract Objectives/Hypothesis The goals of the research study were to develop an easily mastered, accurate, minimally invasive technique of sentinel node radiolocalization with biopsy (SNRLB) in the feline model; to compare it with blue-dye mapping techniques; and to test the applicability of sentinel node radiolocalization biopsy in three head and neck tumor types: N0 malignant melanoma, N0 Merkel cell carcinoma, and N0 squamous cell carcinoma. Study Design Prospective consecutive series studies were performed in the feline model and in three head and neck tumor types: N0 malignant melanoma (43 patients), N0 Merkel cell carcinoma (8 patients), and N0 squamous cell carcinoma (20 patients). Methods The technique of sentinel node radiolocalization with biopsy was analyzed in eight felines and compared with blue-dye mapping. Patterns of sentinel node gamma emissions were recorded. Localization success rates were determined for blue dye and sentinel node with radiolocalization biopsy. In the human studies, all patients had sentinel node radiolocalization biopsy performed in a similar manner. On the morning of surgery, each patient had sentinel node radiolocalization biopsy of the sentinel lymph node performed using an intradermal or peritumoral injection of technetium Tc 99m sulfur colloid. Sentinel nodes were localized on the skin surface using a handheld gamma detector. Gamma count measurements were obtained for the following: 1) the "hot" spot/node in vivo before incision, 2) the hot spot/node in vivo during dissection, 3) the hot spot/node ex vivo, 4) the lymphatic bed after hot spot/node removal, and 5) the background in the operating room. The first draining lymph node(s) was identified, and biopsy of the node was performed. The radioactive sentinel lymph node(s) was submitted separately for routine histopathological evaluation. Preoperative lymphoscintigrams were performed in patients with melanoma and patients with Merkel cell carcinoma. In patients with head and neck squamous cell carcinoma, the relationship between the sentinel node and the remaining lymphatic basin was studied and all patients received complete neck dissections. The accuracy of sentinel node radiolocalization with biopsy, the micrometastatic rate, the false-negative rate, and long-term recurrence rates were reported for each of the head and neck tumor types. In the melanoma study, the success of sentinel node localization was compared for sentinel node radiolocalization biopsy, blue-dye mapping, and lymphoscintigraphy. In the Merkel cell carcinoma study, localization rates were evaluated for sentinel node radiolocalization biopsy and lymphoscintigraphy. In the head and neck squamous cell carcinoma study, the localization rate of sentinel node radiolocalization biopsy and the predictive value of the sentinel node relative to the remaining lymphatic bed were determined. All results were analyzed statistically. Results Across the different head and neck tumor types studied, sentinel node radiolocalization biopsy had a success rate approaching 95%. Sentinel node radiolocalization biopsy was more successful than blue-dye mapping or lymphoscintigraphy at identifying the sentinel node, although all three techniques were complementary. There was no instance of a sentinel node-negative patient developing regional lymphatic recurrence. In the head and neck squamous cell carcinoma study, there was no instance in which the sentinel node was negative and the remaining lymphadenectomy specimen was positive. Conclusion In head and neck tumors that spread via the lymphatics, it appears that sentinel node radiolocalization biopsy can be performed with a high success rate. This technique has a low false-negative rate and can be performed through a small incision. In head and neck squamous cell carcinoma, the histological appearance of the sentinel node does appear to reflect the regional nodal status of the patient. [source] Sentinel lymph node biopsy as guidance for central neck dissection in patients with papillary thyroid carcinomaCANCER, Issue 7 2008Jong-Lyel Roh MD Abstract BACKGROUND. Occult lymph node metastasis of papillary thyroid carcinoma (PTC) can be detected by sentinel lymph node (SLN) biopsy, but studies in larger patient cohorts undergoing complete central neck dissection may be required to assess the diagnostic accuracy of SLN. Therefore, the authors prospectively assessed the usefulness of SLN biopsy for the detection of central lymph node metastasis in patients with differentiated PTC who had no suspicious cervical lymphadenopathy. METHODS. After peritumoral injection of methylene blue, SLN biopsy was performed in 50 patients with newly diagnosed PTC who had no palpable or ultrasound (US)-detected lymph node involvement. After SLN biopsy, all patients underwent total thyroidectomy and central neck dissection. The diagnostic accuracy of intraoperative SLN sampling was calculated by comparison with the final pathologic diagnosis. RESULTS. SLNs were identified in 46 of 50 patients (92%); of these, 14 SLNs were positive and 32 SLNs were negative on intraoperative frozen sections. One patient had a positive SLN in the jugular region and subsequently underwent modified radical neck dissection. Final pathologic examination revealed that 18 patients (36%), including 4 who had negative SLNs, had central lymph node metastasis. Thus, the sensitivity, specificity, accuracy, and positive and negative predictive values of SLN biopsy were 77.8%, 100%, 92%, 100%, and 88.9%, respectively. Temporary and permanent hypocalcemia developed in 19 patients and 1 patient, respectively. There were no direct complications of SLN sampling. CONCLUSIONS. SLN biopsy in patients with PTC without gross clinical or US lymph node involvement was able to detect occult metastasis with high accuracy and may have the potential to select patients who require central neck dissection. Cancer 2008. © 2008 American Cancer Society. [source] Inhibitory effect of the polyinosinic-polycytidylic acid/cationic liposome on the progression of murine B16F10 melanomaEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2006Taku Fujimura Abstract Cellular proteins, retinoic acid inducible gene-I and Toll-like receptor 3, sense dsRNA including polyinosinic-polycytidylic acid (PIC) to stimulate innate immune response. The local administration of PIC has been demonstrated to be effective in anti-tumor immunotherapy. However, the effects of PIC delivered cross the cell membrane have not yet been examined. To address this issue, we used a complex of PIC and cationic liposome (PIC liposome) and examined its anti-tumor effects in vitro and in vivo. PIC liposome could directly suppress the growth of B16F10 melanoma in vitro and repeated peritumoral injections of PIC liposome inhibited melanoma growth in a dose-dependent manner. This treatment induced tyrosinase-related protein-2 (TRP-2)-tetramer+ CD8+ cells in the lymph nodes. As the mechanism for its anti-tumor immune response, we showed that the intradermal injection of PIC liposome induced the maturation of dendritic cells (DC). Moreover, the intratumoral injection of immature DC after treatment with PIC liposome significantly increased the number of TRP-2-specific IFN-,-producing cells in the lymph nodes as well as spleen, which resulted in an augmentation of the anti-tumor immune response. These studies demonstrate the potential of peritumoral injection of PIC liposome as immunotherapy for malignant melanoma. [source] |