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PubMed2000

Sentinel lymphadenectomy accurately predicts nodal status in T2 breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has emerged as a reliable, accurate method of staging the axilla for early breast cancer. Although widely accepted for T1 lesions, its use in larger tumors remains controversial. This study was undertaken to define the role of SLNB for T2 breast cancer. STUDY DESIGN: From a prospective breast sentinel lymph node database of 1,627 patients accrued between September 1996 and November 1999, we identified 223 patients with clinical T1-2N0 breast cancer who underwent 224 lymphatic mapping procedures and SLNB followed by a standard axillary lymph node dissection (ALND). Preoperative lymphatic mapping was performed by injection of unfiltered technetium 99 sulfur colloid and isosulfan blue dye. Data about patient and tumor characteristics and the status of the sentinel lymph nodes and the axillary nodes were analyzed. Statistics were performed using Fisher's exact test. RESULTS: Two hundred four of 224 sentinel lymph node mapping procedures (91%) were successful. Median tumor size was 2.0 cm (range 0.2 to 4.8 cm). One hundred forty-five of the 204 patients had T1 lesions and 59 patients had T2 lesions. There were 92 pathologically positive axillae, 5 (5%) of which were not evident either by SLNB or by intraoperative clinical examination. The false-negative rate and accuracy were not significantly different between the two groups, but axillary node metastases were observed more frequently with T2 than with T1 tumors (p = 0.005); other factors, including patient age, prior surgical biopsy, upper-outer quadrant tumor location, and tumor lymphovascular invasion were not associated with a higher incidence of false-negative SLNB in either T1 or T2 tumors. CONCLUSIONS: SLNB is as accurate for T2 tumors as it is for T1 tumors. Because no tumor or patient characteristics predict a high false-negative rate, all patients with T1-2N0 breast cancer should be considered candidates for the procedure. Complete clinical examination of the axilla should be undertaken to avoid missing palpable axillary nodal metastases.

Adult↗

PubMed1998

Analysis of malachite green and metabolites in fish using liquid chromatography atmospheric pressure chemical ionization mass spectrometry.

Malachite green (MG), a traditional agent used in aquaculture, is structurally related to other carcinogenic triphenylmethane dyes. Although MG is not approved for use in aquaculture, its low cost and high efficacy make illicit use likely. We developed sensitive and specific methods for determination of MG and its principal metabolite, leucoMG (LMG), in edible fish tissues using isotope dilution liquid chromatography atmosphere pressure chemical ionization mass spectrometry. MG and LMG concentrations were measured in filets from catfish treated with MG under putative use conditions (ca. 250 and 1000 ppb, respectively) and from commercial trout samples (0-3 and 0-96 ppb, respectively). Concentrations of LMG in edible fish tissues always exceeded those of MG. A rapid cone voltage switching acquisition procedure was used to simultaneously produce molecular ions for quantification and diagnostic fragment ions for confirmation of MG and metabolites. The accurate and precise agreement between diagnostic ion intensity ratios produced by LMG in authentic standards and incurred fish samples was used to unambiguously confirm the presence of LMG in edible fish tissue. This suggested the validity of using LMG as a marker residue for regulatory determination of MG misuse. Additional metabolites derived from oxidative metabolism of MG or LMG (demethylation and N-oxygenation) were identified in catfish and trout filets, including a primary arylamine which is structurally related to known carcinogens. The ability to simultaneously quantify residues of MG and LMG, and to confirm the chemical structure of a marker residue by using LC/MS, suggests that this procedure may be useful in monitoring the food supply for the unauthorized use of MG in aquaculture.

Aniline Compounds↗

PubMed1999

The role of sentinel lymph node biopsy in breast cancer.

BACKGROUND: Lymphatic mapping and sentinel lymph node (SLN) biopsy are new techniques that accurately provide crucial staging information while inflicting far less morbidity than complete axillary dissection. As these techniques continue to gain acceptance, issues such as adequacy of training, certification, and outcomes measures become increasingly important. The purpose of this paper is to report the initial lymphatic mapping experience at the H Lee Moffitt Cancer Center and Research Institute and to provide a detailed description of the technical aspects of lymphatic mapping. STUDY DESIGN: From April 1994 to April 1998, 700 patients with newly diagnosed breast cancers underwent an IRB-approved prospective trial of lymphatic mapping using a combination of Lymphazurin (USSC, Norwalk, CT) blue dye and filtered technetium 99m-labeled sulfur-colloid. Failure of the procedure was defined as the inability to detect an SLN by either radiocolloid uptake within a lymph node by the gamma probe or the inability to visualize blue staining of a lymph node. Learning curves were then generated as the failure rate versus serial number of patients for each of the 5 surgeons involved in this study. RESULTS: The SLN was identified in 665 of 700 patients (95.0%). A total of 1,348 SLNs were successfully removed, of which 238 (17.7%) were positive for metastatic disease in 176 of 665 patients (26.5%). In patients who underwent a complete axillary dissection after SLN biopsy, SLNs were identified in 173 of 186 patients (93.0%). Of the 173 patients, 53 patients (30.6%) had positive SLNs and 120 patients (69.4%) had negative SLNs. In the 120 patients with negative SLNs, one patient was found to have disease on complete dissection, for a false-negative rate of 0.83% (95% CI: 0.02%, 4.6%). A learning curve representing the mean of the 5 surgeons' experience indicates that on average 23 patients are required by an individual surgeon to achieve a 90% +/- 4.5% success rate and 53 patients are required to achieve a 95% +/- 2.3% success rate (p = 0.05). CONCLUSIONS: These data validate lymphatic mapping and SLN biopsy as indispensable tools in the surgical treatment of breast cancer. With adequate multidisciplinary training, these techniques can be readily implemented at institutions treating breast cancer.

Biopsy↗

PubMed2005

In vitro cuspal deflection and microleakage of maxillary premolars restored with novel low-shrink dental composites.

OBJECTIVES: The development of novel low-shrink resin-based composites (RBCs) may offer a potential reduction in polymerisation shrinkage stresses generated at the tooth/restoration interface compared with current methacrylate RBCs. In vitro cuspal deflection and microleakage of meiso-occlusal-distal (MOD) cavities restored with experimental oxirane and silorane (EXL596 and H1) and methacrylate (Z100 and Filtek Z250) RBCs were assessed. METHODS: Standardised pre-molar MOD cavities were prepared (n = 10) and restored with each material. The flexure of buccal and palatal cusps was recorded 0.1 h following irradiation utilising a differential transformer deflection gauge. Each restored tooth was subjected to a thermocycling regime and microleakage of tooth sections were assessed following 24 h immersion in 0.2% fuschin dye. The degree of conversion (DC) of each RBC material was also assessed using Fourier transform infrared (FTIR) spectroscopy following 0.1, 0.5, 1, 4, 24 and 48 h post-irradiation. RESULTS: A total cuspal deflection was observed for EXL596 (2.5 +/- 0.9 microm) and H1 (6.0 +/- 1.8 microm) compared with Z100 (20.0 +/- 4.7 microm) and Filtek Z250 (16.5 +/- 3.3 microm) following 0.1 h. The cavities restored with EXL596 displayed significantly higher microleakage than any other RBC and H1 exhibited non-significant and significantly decreased microleakage compared with Z100 and Filtek Z250, respectively. The DC of EXL596 and H1 was significantly decreased compared with Z100 and Filtek Z250 following 0.1, 0.5 and 1 h. SIGNIFICANCE: The 'living' polymerisation associated with the novel oxirane and silorane RBCs and the associated decrease in cuspal deflection may suggest a decrease in the magnitude of polymerisation shrinkage stress at the tooth/restoration interface. The decreased DC following 0.1 h of the oxirane compared with the methacrylate RBCs has provided information on the cure rate of cationic and free-radical polymerisation mechanisms, respectively. The inadequate marginal seal of cavities restored with EXL596 would preclude its use as a dental restorative. The reduction in cuspal deflection and decrease in microleakage of cavities restored with H1 compared with Filtek Z250 may be advantageous in terms of marginal integrity following placement. However, the non-significant difference in microleakage between the H1 and Z100 may only present modest decreases in the deleterious effects of shrinkage stress.

Bicuspid↗

PubMed2003

Tumor promotion by metanil yellow and malachite green during rat hepatocarcinogenesis is associated with dysregulated expression of cell cycle regulatory proteins.

Metanil yellow (MY) and malachite green (MG) are textile dyes, which, despite a ban, are used as food-coloring agents. MY and MG have promoter effects on the development of hepatic preneoplastic lesions induced by N-nitrosodiethylamine (DEN). Tumor-promoting agents are not mutagenic but may alter the expression of genes whose products are associated with hyper-proliferation, tissue remodeling, and inflammation. Cell cycle controls normally function to ensure the integrity of the genome and arrest of cells at G1/S or G2/M checkpoints until all the prerequisite events are completed. In order to understand the mechanism(s) of tumor promotion by MY and MG, we have studied the levels of PCNA, a marker of cell proliferation and cell cycle regulatory proteins, cyclin D1, and its associated kinase, cdk4, cyclin B1, and associated kinase, cdc2. Immunohistochemical staining showed an elevated level of PCNA in animals administered MY and MG subsequent to DEN treatment. Western and Northern blot hybridization showed an increased expression of both cyclin D1 and its associated kinase cdk4, and cyclin B1 and its associated kinase cdc2, in livers of rats administered MY and MG after administration of DEN as compared to untreated or DEN controls. The increased level of mRNA was due to the increased rate of transcription of these genes as studied by run-on transcription assay. These data obtained by the in vivo model of liver tumor development provide strong evidence for a link between dysregulation of the two critical checkpoints of the cell cycle as one of the possible mechanism(s) during tumor promotion by malachite green and metanil yellow.

Animals↗

PubMed2003

Sentinel node biopsy for breast cancer: using local results for estimation of risk to the patient.

BACKGROUND: Sentinel node biopsy (SNB) is being increasingly used but its place outside randomized trials has not yet been established. METHODS: The first 114 sentinel node (SN) biopsies performed for breast cancer at the Princess Alexandra Hospital from March 1999 to June 2001 are presented. In 111 cases axillary dissection was also performed, allowing the accuracy of the technique to be assessed. A standard combination of preoperative lymphoscintigraphy, intraoperative gamma probe and injection of blue dye was used in most cases. Results are discussed in relation to the risk and potential consequences of understaging. RESULTS: Where both probe and dye were used, the SN was identified in 90% of patients. A significant number of patients were treated in two stages and the technique was no less effective in patients who had SNB performed at a second operation after the primary tumour had already been removed. The interval from radioisotope injection to operation was very wide (between 2 and 22 h) and did not affect the outcome. Nodal metastases were present in 42 patients in whom an SN was found, and in 40 of these the SN was positive, giving a false negative rate of 4.8% (2/42), with the overall percentage of patients understaged being 2%. For this particular group as a whole, the increased risk of death due to systemic therapy being withheld as a consequence of understaging (if SNB alone had been employed) is estimated at less than 1/500. The risk for individuals will vary depending on other features of the particular primary tumour. CONCLUSION: For patients who elect to have the axilla staged using SNB alone, the risk and consequences of understaging need to be discussed. These risks can be estimated by allowing for the specific surgeon's false negative rate for the technique, and considering the likelihood of nodal metastases for a given tumour. There appears to be no disadvantage with performing SNB at a second operation after the primary tumour has already been removed. Clearly, for a large number of patients, SNB alone will be safe, but ideally participation in randomized trials should continue to be encouraged.

Adult↗

PubMed2001

Effect of metanil yellow and malachite green on DNA synthesis in N-nitrosodiethylamine induced preneoplastic rat livers.

Metanil yellow (MY) and malachite green (MG) are textile dyes, which, despite the ban occurs unsrupulously as food colouring agents. Accordingly they constitute a serious public health hazard and are of sufficient environmental concern. We have earlier reported that both MY and MG have tumor enhancing effects on the development of hepatic preneoplastic lesions induced by N-nitrosodiethylamine in rats. In order to understand the possible mechanisms by which MY and MG enhance tumor development, in this study we have tested the effects of MY and MG on DNA synthesis and PCNA expression in preneoplastic hepatic lesions during N-nitrosodiethylamine (DEN) induced hepatocarcinogenesis in male Wistar (WR) rats. Rats were administered 200 ppm DEN through drinking water for a period of one month. Administration of DEN for a period of one month showed an upregulation of cell cycle regulatory proteins namely cyclin D1, CDK4, cyclin E and CDK2. Accordingly, in other experiments, the animals were further administered MY and MG for a period of one month following one month DEN treatment. The effects of MY and MG were monitored on the basis of cell proliferation markers--DNA synthesis and PCNA expression both by immunohistochemical and immunoblotting. Following DEN administration, MY, MG and PB showed stimulation of DNA synthesis and increased PCNA expression when compared with either the corresponding controls or only DEN treated animals. In the present study, enhancing effect of MY, MG and PB on the cell proliferation markers during DEN-induced hepatic preneoplasia in rats was observed.

Animals↗

PubMed2000

Heterogeneous distribution of tumor blood supply affects the response to chemotherapy in patients with head and neck cancer.

OBJECTIVE: To evaluate if the heterogeneous distribution of tumor blood supply affects the response to chemotherapy in patients with head and neck cancer. METHODS: We treated 25 stage III/IV patients with an intraarterial cisplatinum-bleomycin regimen. Prior to treatment, a blue dye was injected directly to tumors through the catheter. Well-stained areas were considered as profusely perfused areas whereas poorly stained areas were considered as poorly perfused areas. Biopsies of both areas of each tumor were taken prior to and after the treatment and the histopathological response was evaluated with the following grading: I, tumor disappearance; II, destruction of some tumor nests; III, no changes. RESULTS: Grade I responses were attained in 13/25 (52%) of profusely perfused areas against 1/25 (4%) of poorly perfused areas (p < 0.001). Moreover, there were significant differences (p < 0.001) in the overall responses: 21/25 (84%) in the profusely perfused areas versus 7/25 (28%) in the poorly perfused areas; and in grade III responses (4/25, 16% vs. 18/25, 72%). To determine a possible correlation between the histopathological responses obtained in profusely perfused and in poorly perfused areas of each tumor, we then calculated the Kendall's tau-b statistics, obtaining a tau value of 0.279 (p = 0.145). This data indicated that histopathological responses to chemotherapy of profusely perfused and poorly perfused areas were independent in each tumor. CONCLUSIONS: Heterogeneity in the distribution of tumor blood supply affects the response to chemotherapy by influencing the intratumoral delivery of therapeutic agents. After the administration of effective doses of anticancer drugs to a tumor, cells in profusely perfused areas receive enough to destroy them while cells in the poorly perfused areas are exposed to lower drug concentrations and, therefore, survive. This phenomenon could explain in part the difficulty in the treatment of human solid tumors.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

[Interest of periareolar injection for colorimetric detection of sentinel node in breast cancer].

Most teams working on sentinel node biopsy in the treatment of breast cancer inject either radioactive colloid or vital blue dye around the primary tumour. Many anatomical studies and lymphoscintigraphical studies, some very old, have shown that the lymphatic drainage of the breast is collected first in the periareolar plexus of Sappey, then routed to the axilla in 95% of cases, via one or two primary collectors. In a series of 94 breast cancers measuring less than 3 cm, with any palpable axillary lymph node, 2 ml of patent blue was injected intradermally around the areola, at the two meridians around the tumor. The sentinel node was identified in 89 cases (94,7%), regardless of the location of the primary tumor. All the sentinel nodes were located in the lower axilla. An average of 1.6 nodes were found per patient. In 41 cases, axillary lymph node dissection was performed either immediately (5 technical failures, 9 positive frozen section) or delayed only if the sentinel node was positive, either on standard H&E staining or on immunohistochemistry (27 cases). Thus, axillary lymph node dissection was not performed in 48 patients (55%). In positive node patient, the sentinel node was the only positive lymph node in 20 patients (55%). For 5 positive node patients, axillary lymph node dissection was not performed: poor vital status (2 micro-metastatic nodes) or by decision of patient (3 IHC positive nodes). With this periareolar injection procedure, the rate of detection is highly satisfactory and is comparable to that usually published with peritumoral injection. This procedure seems appropriate in all cases, regardless of the topography, the size or the multifocality of breast cancer.

Axilla↗

PubMed2002

Increased false negative rates in sentinel lymph node biopsies in patients with multi-focal breast cancer.

There are few data about the reliability of sentinel node biopsy in patients with multi-focal breast cancer. The aim of this study was to determine the factors affecting the identification and accuracy of the sentinel node, comparing multifocality with other variables, using peritumoral isosulfan blue dye injection technique alone. Between 1998 and 2001, 122 patients with clinically negative nodes from a single institute were eligible for sentinel lymph node biopsies (SLNBs). All patients underwent conventional axillary lymph node dissection (ALND). SLNs were identified in 111 of 122 (91%) cases, and analyzed by hematoxylin and eosin. Twenty-one patients with multifocal breast cancer were determined by clinical or pathologic examination (gross or microscopic). Success in locating the sentinel node was unrelated to patient's age, tumor size, type, location, histological or nuclear grade, multifocality, or a previous surgical biopsy. SLNBs accurately predicted the status of the axilla in 104 of the 111 patients (93.7%), while 18 of the 21 patients with multi-focal breast cancer (85.7%) had successful lymphatic mapping. The false negative (FN) rate was 11.3% among patients with successful SLNBs. Multifocality and tumor size (>2 cm) were associated significantly with decreased accuracy and increased FN rates (for multifocality, p = 0.007 and p = 0.006, and for tumor size >2 cm, p = 0.04 and p = 0.05, respectively) in binary logistic regression analysis, whereas excisional biopsy, tumor location in the upper outer quadrant and patient's age did not significantly affect the accuracy and FN rates in univariate analysis. These results suggest sentinel lymph node biopsy using peritumoral isosulfan blue injection method alone can accurately predict axillary status in patients with clinically negative nodes, but patients with multi-focal disease and large tumor size may not be ideal candidates.

Adult↗

PubMed2004

Laparoscopic sentinel node procedure for cervical cancer: impact of neoadjuvant chemoradiotherapy.

BACKGROUND: SN detection based on combined blue dye and radiocolloid labeling can reliably show lymph node status in cervical cancer, but the influence of prior neoadjuvant chemoradiotherapy has not yet been reported. The aim of this study was to evaluate the effect of neoadjuvant chemoradiotherapy on the accuracy of a dual-labeling laparoscopic sentinel node (SN) procedure in patients with cervical cancer. METHODS: Between July 2001 and June 2003, 26 patients (mean age, 50.3 years) with cervical cancer underwent a laparoscopic SN procedure based on dual labeling with patent blue and radiocolloid. After the SN procedure, all the patients underwent complete laparoscopic pelvic lymphadenectomy and laparoscopic radical hysterectomy (n=19), the Schauta-Amreich operation (n=5), or trachelectomy (n=2). The results of the SN procedure were compared between 11 patients who received neoadjuvant chemoradiotherapy and 15 patients who did not receive neoadjuvant treatment. RESULTS: The SN identification rates were 100% in the 11 patients who underwent neoadjuvant chemoradiotherapy and 93.3% in the 15 patients who did not receive adjuvant therapy. A total of 59 SNs were removed. Eight SNs (13.6%) from five patients (19.2%) were found to be metastatic at the final histological assessment. Three SN involvements were detected by hematoxylin and eosin staining of the SN. Immunohistochemical studies identified five metastatic SNs in three patients. There were no false-negative SN results. CONCLUSIONS: This study suggests that SN detection with a combination of radiocolloid and patent blue is feasible and accurate in patients with cervical cancer undergoing neoadjuvant chemoradiotherapy or primary surgery. The combination of laparoscopy and the SN procedure permits minimally invasive management of cervical cancer.

Chi-Square Distribution↗

PubMed1999

Initial experience in a community hospital with sentinel lymph node mapping and biopsy for evaluation of axillary lymph node status in palpable invasive breast cancer.

BACKGROUND AND OBJECTIVES: To determine the sentinel node detection rate and the accuracy with which the sentinel node histology reflects that of the axilla in a series of patients with palpable invasive breast cancer. METHODS: Forty-four patients with clinically node-negative palpable invasive T1 or T2 breast tumors underwent sentinel node biopsy using isosulfan blue dye, followed immediately by either local excision of the primary lesion with standard axillary lymph node dissection or modified radical mastectomy. All surgeries were performed at Northwest Hospital, Seattle, Washington, between January 1996 and October 1997. RESULTS: The sentinel node was successfully identified in 73% of the patients (32/44). The frequency of sentinel node detection was greater for tumors in the outer quadrants than the inner quadrants (z-test, P < 0.001). Of the 32 patients in whom a sentinel node was identified, 10 (31%) had histologically positive sentinel nodes: 5 (16%) by frozen section, 2 additional patients (6%) after permanent hematoxalin-eosin (H&E) stained sections, and the remaining 3 (9%) after immunohistochemical stains for cytokeratins when the FS and permanent H&E-stained sections were benign. Twenty patients had benign axilla. The sentinel node was falsely negative in 2 patients, yielding an accuracy of 93.8%, sensitivity of 83.3%, and negative predictive value of 91%. CONCLUSIONS: Lymphatic mapping is technically feasible for patients with small (T1 or T2) palpable invasive breast tumors. The sentinel node can be reliably identified in the majority of these patients, and its histology reflects that of the axilla with a high degree of accuracy. Immunohistochemical stains and permanent H&E-stained sections of the sentinel node increased the test's ability to correctly identify axillary metastases. Improving this sensitivity remains a primary goal, however, if benign sentinel node histology is to be used as a criterion to preclude axillary dissection.

Adult↗

PubMed2001

Clinical relevance of internal mammary node mapping as a guide to radiation therapy.

BACKGROUND: The surgical management of breast cancer has changed markedly with the development of lymphatic mapping and sentinel lymph node (SLN) biopsy. Lymphatic mapping technique varies with respect to injection method, mapping agent, and surgical technique. The decision to pursue the internal mammary nodes (IMN) is another source of controversy. METHODS: From April 1998 to November 2000, 1,470 patients underwent lymphatic mapping for breast cancer and were prospectively entered into the breast database. The combined technique method was used, consisting of both isosulfan blue dye and technetium-99 labeled sulfur colloid. Patients with inner quadrant lesions and suspicion for internal mammary metastasis had preoperative lymphoscintigraphy. Those with internal mammary radioactivity noted by either lymphoscintigraphy or gamma probe underwent removal of the internal mammary sentinel nodes. RESULTS: Thirty-six of the 1,470 (2.4%) patients mapped had at least 1 internal mammary lymph node removed. Inner quadrant lesions were present in 24 of the 36 (67%) IMN mapped patients. Of the 36 patients mapping to the IM area, 5 (14%) had at least 1 IM node positive. Two of the 5 (40%) had only IM metastasis, with 1 of these patients having 5 of 5 IMN positive and no disease detected in her axilla. A total of 2 of the 5 (40%) IM positive patients had more than 1 IMN positive. Twenty-eight of the 36 (78%) IM node harvested patients had preoperative lymphoscintigraphy, with 18 (64%) IMN appearing on imaging. Complications occurred in 3 of the 36 (8%) IMN mapped patients, without clinical significance. CONCLUSIONS: Mapping to the IMN basin with the finding of metastasis results in N3 disease by the current staging system. The consequence for these patients is radiation therapy to the IMN basin. It is significant to note that 14% (5 of 36) were upstaged as result of IMN detection and 40% (2 of 5) had multiple positive IMNs. Substantial disease was detected in these 5 patients necessitating additional radiation therapy while avoiding IM radiation and its attendant complications in 86% of patients mapping to the IM basin.

Breast Neoplasms↗

PubMed1989

Ability of prostaglandin to reduce ethanol injury to dispersed chief cells from guinea pig stomach.

To determine whether prostaglandin exerts a direct action on individual gastric epithelial cells that protects them from ethanol-induced injury, dispersed chief cells from guinea pig stomach were pretreated with 16,16-dimethyl-prostaglandin E2 (dmPGE2) or placebo before incubation with ethanol or control. Cell injury was assessed in terms of exclusion of Fast Green dye, release of lactate dehydrogenase, alterations of ultrastructure, and pepsinogen secretion stimulated by a variety of secretagogues. Of chief cells 60 +/- 2% were stained by Fast Green if incubated with 10% ethanol for 1 h after pretreatment with placebo, whereas only 38 +/- 1% of cells showed Fast Green staining when pretreated with 2.6 microM dmPGE2 before ethanol exposure. Similarly, 63 +/- 2% of cellular lactate dehydrogenase was released from chief cells pretreated with placebo compared with 36 +/- 4% of lactate dehydrogenase released from cells pretreated with 2.6 microM dmPGE2 (P less than 0.01). The prostaglandin's protective effect persisted throughout a 6-h incubation with ethanol. Scanning and transmission electron micrographs demonstrated disintegration of chief cells pretreated with placebo before ethanol exposure, whereas ultrastructural architecture was relatively preserved among chief cells pretreated with dmPGE2. Preincubation with 8 or 10% ethanol inhibited the subsequent stimulation of pepsinogen secretion caused by carbachol, cholecystokinin, A23187, 12-O-tetradecanoylphorbol 13-acetate, forskolin, or 8-bromoadenosine 3',5'-cyclic monophosphate. Pretreatment with dmPGE2 did not reduce the ethanol-induced inhibition of secretion stimulated by any of these secretagogues. These data indicate that dmPGE2 significantly reduces ethanol-induced damage to dispersed chief cells in terms of alterations of membrane permeability and ultrastructure but does not prevent the ethanol-induced impairment of pepsinogen secretion. These findings provide evidence that dmPGE2 exerts a direct but limited protective action on the gastric chief cell, independent of vascular, paracrine, or neural actions.

16,16-Dimethylprostaglandin E2↗

PubMed2000

Sentinel node localization in primary melanoma: preoperative dynamic lymphoscintigraphy, intraoperative gamma probe, and vital dye guidance.

BACKGROUND: Sentinel node (SN) biopsy can be used to select patients with primary melanoma for therapeutic lymphadenectomy. The aim of the study was to assess the efficacy of 3 methods to locate the SN: preoperative dynamic lymphoscintigraphy, intraoperative patent blue dye (PBD), and gamma-detecting probe (GDP). METHODS: We studied 133 patients with cutaneous melanoma and clinically negative lymph nodes. Within 24 hours before surgery, colloid labeled with technetium 99m was injected intradermally around the site of the primary melanoma. The patients were studied before their operations by using dynamic lymphoscintigraphy. A total of 208 SNs were found in 164 lymph node basins. In addition, all the patients had PBD injected immediately before the surgical procedure. When the blue-stained node was identified intraoperatively, its radioactivity level was measured with the GDP. In the absence of blue coloration, the GDP was used to trace the SN. RESULTS: Of 208 SNs, 168 (80.8%) were identified in the regional draining basin during intraoperative lymphatic mapping by using PBD. By using the GDP method, 202 (97.1%) of 208 were identified (GDP vs PBD; P < .01). By combining the 2 methods, 206 (99%) of 208 SNs were detected. Of the 133 patients, 29 (21.8%) had pathologically positive SNs, and were subsequently subjected to regional lymphadenectomy. In 26 (89.7%) of 29 patients, the SN was the only node with metastasis. Three cases (10.3%) of recurrence in patients with microscopic SN metastasis and 7 cases (6.7%) of recurrence in patients without SN metastasis were found during a median follow-up of 566 days. CONCLUSIONS: Preoperative dynamic lymphoscintigraphy and intraoperative mapping with PBD and GDP offer simple and reliable methods of staging regional lymph nodes without subjecting every patient to a regional lymphadenectomy.

Adolescent↗

PubMed2000

Sentinel lymphadenectomy for staging patients with intermediate-level melanoma.

Sentinel lymph node dissection (SLND) as originally described by D.L. Morton et al. (Surg Oncol Clin North Am 1992;1:247-59), is currently being used at most tertiary institutions for staging patients with intermediate-level melanomas. Identification and subsequent surgical resection of occult metastasis before the development of clinical disease may improve survival in these patients. This study is a retrospective review of patients with intermediate melanomas treated by the senior author (P.S.D.). Isosulfan blue dye and a radioactive technetium-labeled dye were used to identify the sentinel node. Sentinel nodes were evaluated by routine hematoxylin and eosin staining, immunohistochemical staining for S-100 and HMB-45, and later in the study with multipanel reverse transcriptase-polymerase chain reaction analysis. All patients were followed closely. Fifty-seven patients with primary melanoma were evaluated between December 1995 and June 1998. Thirty-two patients underwent SLND; two patients underwent SLND on two separate drainage basins, for a total of 34 procedures. The median age was 49 years (range, 19-77). There were 11 females and 21 males. The locations of the primary melanoma were: head and neck, seven; extremity, 8; and trunk, 18; 1 patient had a dual primary melanoma at presentation. Clark's levels of invasion among the patients were level III, 5; and level IV, 27; median Breslow thickness was 1.4 mm (range, 0.45-3.8 mm). A sentinel node was not identified in four procedures (11.1%). Twenty-two nodes (73%) were negative by all methods, and eight (27%) were positive by at least one method. All positive patients underwent complete lymphadenectomy, and routine hematoxylin and eosin stains identified no additional positive nodes. Median follow-up was 21 months (6-36 months). Two patients developed recurrent disease. The other 30 patients remain disease free at last follow-up. SLND is a low-morbidity technique that accurately stages patients with intermediate-level melanoma. Early intervention with complete therapeutic lymphadenectomy and possible interferon therapy may improve the survival of patients with stage III melanoma. A complete discussion of the technique for SLND and an update of this data is presented.

Adult↗

PubMed2026

Use of indocyanine green fluorescence versus patent blue V dye for sentinel lymph node biopsy in early breast cancer, a randomized controlled trial.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is standard for axillary staging in early breast cancer. While the combination of radioisotope and blue dye (e.g., patent blue V, PBV) remains the standard, it has limitations including logistics, variable identification rate (IR), and allergic potential. Indocyanine green (ICG) fluorescence is a promising alternative, but high-quality comparative evidence is needed. METHODS: This was a single-center, prospective, randomized controlled trial. Forty patients with early-stage, node-negative breast cancer were allocated to SLNB using either ICG (n = 20) or PBV (n = 20). All patients subsequently underwent completion level I-II axillary lymph node dissection (ALND) as the pathological reference standard for diagnostic performance assessment. Primary outcome was sentinel lymph node (SLN) IR. Secondary outcomes included detection time, number of SLNs retrieved, false-negative rate (FNR), and safety. RESULTS: Baseline characteristics were comparable between groups. The SLN IR was significantly higher with ICG (100% [20/20]) than with PBV (75% [15/20], p = 0.047). ICG was associated with a significantly shorter median detection time (14.5 vs. 24.0 min, p < 0.001) and retrieved more SLNs (mean: 3.6 vs. 2.4, p = 0.002). Most critically, ICG demonstrated 100% sensitivity, specificity, negative predictive value (NPV), and overall diagnostic accuracy, with a 0% FNR. In contrast, PBV achieved a sensitivity of 75%, an overall diagnostic accuracy of 90%, and an FNR of 25%. No ICG-related adverse events occurred. PBV caused skin discoloration in 75% of patients and one (5%) allergic reaction. CONCLUSION: ICG fluorescence achieved a higher SLN IR, shorter detection time, higher sensitivity, lower FNR, and fewer tracer-related adverse events than PBV as a single tracer for SLNB in patients with early-stage breast cancer. These findings suggest that ICG is a promising standalone tracer when radioisotope mapping is unavailable. Larger multicenter studies are required before widespread adoption can be recommended.

Humans↗

PubMed2001

Multicenter trial of sentinel node biopsy for breast cancer using both technetium sulfur colloid and isosulfan blue dye.

OBJECTIVE: To determine the factors associated with false-negative results on sentinel node biopsy and sentinel node localization (identification rate) in patients with breast cancer enrolled in a multicenter trial using a combination technique of isosulfan blue with technetium sulfur colloid (Tc99). SUMMARY BACKGROUND DATA: Sentinel node biopsy is a diagnostic test used to detect breast cancer metastases. To test the reliability of this method, a complete lymph node dissection must be performed to determine the false-negative rate. Single-institution series have reported excellent results, although one multicenter trial reported a false-negative rate as high as 29% using radioisotope alone. A multicenter trial was initiated to test combined use of Tc99 and isosulfan blue. METHODS: Investigators (both private-practice and academic surgeons) were recruited after attending a course on the technique of sentinel node biopsy. No investigator participated in a learning trial before entering patients. Tc99 and isosulfan blue were injected into the peritumoral region. RESULTS: Five hundred twenty-nine patients underwent 535 sentinel node biopsy procedures for an overall identification rate in finding a sentinel node of 87% and a false-negative rate of 13%. The identification rate increased and the false-negative rate decreased to 90% and 4.3%, respectively, after investigators had performed more than 30 cases. Univariate analysis of tumor showed the poorest success rate with older patients and inexperienced surgeons. Multivariate analysis identified both age and experience as independent predictors of failure. However, with older patients, inexperienced surgeons, and patients with five or more metastatic axillary nodes, the false-negative rate was consistently greater. CONCLUSIONS: This multicenter trial, from both private practice and academic institutions, is an excellent indicator of the general utility of sentinel node biopsy. It establishes the factors that play an important role (patient age, surgical experience, tumor location) and those that are irrelevant (prior surgery, tumor size, Tc99 timing). This widens the applicability of the technique and identifies factors that require further investigation.

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