Esophageal and Esophagogastric Junction Cancers, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

Cancers originating in the esophagus or esophagogastric junction constitute a major global health problem. Esophageal cancers are histologically classified as squamous cell carcinoma (SCC) or adenocarcinoma, which differ in their etiology, pathology, tumor location, therapeutics, and prognosis. In contrast to esophageal adenocarcinoma, which usually affects the lower esophagus, esophageal SCC is more likely to localize at or higher than the tracheal bifurcation. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability status, and the expression of programmed death-ligand 1, has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, ipilimumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with locally advanced esophageal or esophagogastric junction cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on the management of recurrent or metastatic disease.

Development of LOX-1 Antibody Modified Immuno-liposomes as Drug Carriers to Macrophages in Atherosclerotic Lesions.

We developed a drug delivery system for atherosclerotic lesions using immuno-liposomes. We focused on enhancing the delivery efficiency of the liposomes to macrophages in atherosclerotic lesions by antibody modification of lectinlike oxidized low-density lipoproteins (LDL) receptor 1 (LOX-1). The cellular accumulation of the liposomes in foam cells induced by oxidized LDL (oxLDL) in Raw264 mouse macrophages was evaluated. The cellular accumulation of LOX-1 antibody modified liposomes in oxLDL-induced foam cells and untreated Raw264 cells was significantly higher compared with that of unmodified liposomes. The liposomes were also administered intravenously to Apoeshl mice as an atherosclerosis model. Frozen sections were prepared from the mouse aortas and observed by confocal laser microscopy. The distribution of LOX-1 antibody modified liposomes in the atherosclerotic regions of Apoeshl mice was significantly greater compared with that of unmodified liposomes. The results suggest that LOX-1 antibody modified liposomes can target foam cells in atherosclerotic lesions, providing a potential route for delivering various drugs with pharmacological effects or detecting atherosclerotic foci for the diagnosis of atherosclerosis.

Pancreatic Tumor Microenvironment Factor Promotes Cancer Stemness via SPP1-CD44 Axis.

BACKGROUND & AIMS: Tumor-microenvironment factors and cancer stem cells (CSCs) play a critical role in the aggressiveness of pancreatic cancer (PC). However, the degree to which tumor-microenvironment factors promote stemness remains unexplored. Here, we examined whether cancer-associated fibroblasts (CAFs) promote CSC features in PC. METHODS: PC cells were treated long-term (30, 60, and 90 days) with conditioned media (CM)-derived from normal human fibroblasts (NFs) and CAFs. The stemness features of tumorsphere formation and stemness populations, along with CSCs markers, were analyzed using 2-dimensional and 3-dimensional sodium alginate bead-based co-culture models. Immunohistochemistry and immunofluorescence staining were performed for CSCs and fibroblast markers in autochthonous KrasG12D/+; Trp53R172H/+; Pdx1-Cre mice and human pancreatic tumors. Polymerase chain reaction array and gene knockdown were performed to identify the mechanism of stemness enrichment. RESULTS: Long-term treatment of PC cells with CAF-CM enriched stemness, as indicated by significantly higher CD44+, ALDH+, and AF+ populations in PC cells. Increased tumorsphere formation and elevated CSC, self-renewal, and drug-resistance markers in CAF-CM-treated PC cells were observed. In addition, CAFs co-cultured with PC cells in the 3-dimensional model showed a substantial increase in stemness features. CD44 and α-smooth muscle actin were positively correlated and their expressions progressively increased from the early to late stages of KrasG12D/+; Trp53R172H/+; Pdx1-Cre mouse and human pancreatic tumors. Osteopontin/secreted phosphoprotein 1 was identified as the top differentially overexpressed gene in CAF-CM-treated PC cells and knockdown of osteopontin/secreted phosphoprotein 1 significantly reduced stemness characteristics in CAF-CM-treated PC cells. CONCLUSIONS: Our data uncovered novel insight into the interplay between CAF and enrichment of stemness population through the osteopontin/secreted phosphoprotein 1-CD44 axis in PC.

Preclinical Evaluation of a Humanized, Near-Infrared Fluorescent Antibody for Fluorescence-Guided Surgery of MUC16-Expressing Pancreatic Cancer.

Surgery remains the only potentially curative treatment option for pancreatic cancer, but resections are made more difficult by infiltrative disease, proximity of critical vasculature, peritumoral inflammation, and dense stroma. Surgeons are limited to tactile and visual cues to differentiate cancerous tissue from normal tissue. Furthermore, translating preoperative images to the intraoperative setting poses additional challenges for tumor detection, and can result in undetected and unresected lesions. Thus, pancreatic ductal adenocarcinoma (PDAC) has high rates of incomplete resections, and subsequently, disease recurrence. Fluorescence-guided surgery (FGS) has emerged as a method to improve intraoperative detection of cancer and ultimately improve surgical outcomes. Initial clinical trials have demonstrated feasibility of FGS for PDAC, but there are limited targeted probes under investigation for this disease, highlighting the need for development of additional novel biomarkers to reflect the PDAC heterogeneity. MUCIN16 (MUC16) is a glycoprotein that is overexpressed in 60-80% of PDAC. In our previous work, we developed a MUC16-targeted murine antibody near-infrared conjugate, termed AR9.6-IRDye800, that showed efficacy in detecting pancreatic cancer. To build on the translational potential of this imaging probe, a humanized variant of the AR9.6 fluorescent conjugate was developed and investigated herein. This conjugate, termed huAR9.6-IRDye800, showed equivalent binding properties to its murine counterpart. Using an optimized dye:protein ratio of 1:1, in vivo studies demonstrated high tumor to background ratios in MUC16-expressing tumor models, and delineation of tumors in a patient-derived xenograft model. Safety, biodistribution, and toxicity studies were conducted. These studies demonstrated that huAR9.6-IRDye800 was safe, did not yield evidence of histological toxicity, and was well tolerated in vivo. The results from this work suggest that AR9.6-IRDye800 is an efficacious and safe imaging agent for identifying pancreatic cancer intraoperatively through fluorescence-guided surgery.

Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability (MSI) status, and the expression of programmed death-ligand 1 (PD-L1), has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with localized gastric cancer. This selection from the NCCN Guidelines for Gastric Cancer focuses on the management of unresectable locally advanced, recurrent, or metastatic disease.

Human splenic myeloid derived suppressor cells: Phenotypic and clustering analysis.

Myeloid derived suppressor cells (MDSCs) can be subset into monocytic (M-), granulocytic (G-) or polymorphonuclear (PMN-), and immature (i-) or early MDSCs and have a role in many disease states. In cancer patients, the frequencies of MDSCs can positively correlate with stage, grade, and survival. Most clinical studies into MDSCs have been undertaken with peripheral blood (PB); however, in the present studies, we uniquely examined MDSCs in the spleens and PB from patients with gastrointestinal cancers. In our studies, MDSCs were rigorously subset using the following markers: Lineage (LIN) (CD3, CD19 and CD56), human leukocyte antigen (HLA)-DR, CD11b, CD14, CD15, CD33, CD34, CD45, and CD16. We observed a significantly higher frequency of PMN- and M-MDSCs in the PB of cancer patients as compared to their spleens. Expression of the T-cell suppressive enzymes arginase (ARG1) and inducible nitric oxide synthase (i-NOS) were higher on all MDSC subsets for both cancer patients PB and spleen cells as compared to MDSCs from the PB of normal donors. Similar findings for the activation markers lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), program death ligand 1 (PD-L1) and program cell death protein 1 (PD-1) were observed. Interestingly, the total MDSC cell number exported to clustering analyses was similar between all sample types; however, clustering analyses of these MDSCs, using these markers, uniquely documented novel subsets of PMN-, M- and i-MDSCs. In summary, we report a comparison of splenic MDSC frequency, subtypes, and functionality in cancer patients to their PB by clustering and cytometric analyses.

CXCR2 signaling promotes secretory cancer-associated fibroblasts in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most challenging malignancies. Desmoplasia and tumor-supporting inflammation are hallmarks of PDAC. The tumor microenvironment contributes significantly to tumor progression and spread. Cancer-associated fibroblasts (CAFs) facilitate therapy resistance and metastasis. Recent reports emphasized the concurrence of multiple subtypes of CAFs with diverse roles, fibrogenic, and secretory. C-X-C motif chemokine receptor 2 (CXCR2) is a chemokine receptor known for its role during inflammation and its adverse role in PDAC. Oncogenic Kras upregulates CXCR2 and its ligands and, thus, contribute to tumor proliferation and immunosuppression. CXCR2 deletion in a PDAC syngeneic mouse model produced increased fibrosis revealing a potential undescribed role of CXCR2 in CAFs. In this study, we demonstrate that the oncogenic Kras-CXCR2 axis regulates the CAFs function in PDAC and contributes to CAFs heterogeneity. We observed that oncogenic Kras and CXCR2 signaling alter CAFs, producing a secretory CAF phenotype with low fibrogenic features; and increased secretion of pro-tumor cytokines and CXCR2 ligands, utilizing the NF-κB activity. Finally, using syngeneic mouse models, we demonstrate that oncogenic Kras is associated with secretory CAFs and that CXCR2 inhibition promotes activation of fibrotic cells (myofibroblasts) and impact tumors in a mutation-dependent manner.

Esophageal and Esophagogastric Junction Cancers, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. Squamous cell carcinoma is the most common histology in Eastern Europe and Asia, and adenocarcinoma is most common in North America and Western Europe. Surgery is a major component of treatment of locally advanced resectable esophageal and esophagogastric junction (EGJ) cancer, and randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival. Targeted therapies including trastuzumab, ramucirumab, and pembrolizumab have produced encouraging results in the treatment of patients with advanced or metastatic disease. Multidisciplinary team management is essential for all patients with esophageal and EGJ cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on recommendations for the management of locally advanced and metastatic adenocarcinoma of the esophagus and EGJ.

Management of asymptomatic, well-differentiated PNETs: results of the Delphi consensus process of the Americas Hepato-Pancreato-Biliary Association.

BACKGROUND: Variation in the management of PNETs exist due to the limited high-level evidence to guide clinical practice. The aim of this work is to generate consensus guidelines with a Delphi process for managing PNETs. METHODS: A panel of experts reviewed the surgical literature and scored a set of clinical case statements using a web-based survey to identify areas of agreement and disagreement. Results of the survey were discussed after each round of review. This cycle was repeated until no further likelihood of reaching consensus existed. RESULTS: Twenty-two case statements related to surgical indications, preoperative biopsy, extent of resection, type of surgery, and tumor location were scored. Using a pre-defined definition of consensus, the panel achieved consensus on the following: i) resection is not recommended for <1 cm lesions; ii) resection is recommended for lesions greater than 2 cm; iii) lymph node dissection is recommended for radiographically-suspicious nodes with splenectomy for distal lesions; iv) tumor enucleation and central pancreatectomy are acceptable when technically feasible. No consensus was reached regarding issues of preoperative biopsy or 1-2 cm tumors. CONCLUSIONS: Using a structured, validated system for identifying consensus, an expert panel identified areas of agreement regarding critical management decisions for patients with PNET. Issues without consensus warrant additional clinical investigation.

Indocyanine green loaded hyaluronan-derived nanoparticles for fluorescence-enhanced surgical imaging of pancreatic cancer.

Pancreatic ductal adenocarcinoma is highly lethal and surgical resection is the only potential curative treatment for the disease. In this study, hyaluronic acid derived nanoparticles with physico-chemically entrapped indocyanine green, termed NanoICG, were utilized for intraoperative near infrared fluorescence detection of pancreatic cancer. NanoICG was not cytotoxic to healthy pancreatic epithelial cells and did not induce chemotaxis or phagocytosis, it accumulated significantly within the pancreas in an orthotopic pancreatic ductal adenocarcinoma model, and demonstrated contrast-enhancement for pancreatic lesions relative to non-diseased portions of the pancreas. Fluorescence microscopy showed higher fluorescence intensity in pancreatic lesions and splenic metastases due to NanoICG compared to ICG alone. The in vivo safety profile of NanoICG, including, biochemical, hematological, and pathological analysis of NanoICG-treated healthy mice, indicates negligible toxicity. These results suggest that NanoICG is a promising contrast agent for intraoperative detection of pancreatic tumors.

[Incidence and survival of esophageal cancer with different histological types in Linzhou between 2003 and 2012].

Objective: To investigate the incidence and survival of esophageal cancer with different histological types and to understand the incidence trend and burden of esophageal cancer in Linzhou during 2003-2012. Methods: All incidence records of esophageal cancer and population reported were collected from Linzhou Cancer Registry during 2003-2012. Incidence rate was calculated using gender and histological types. Age standardized incidence rate was calculated according to world Segi's population and Chinese census data in 2000. Age standardized incidence rate by world population between 2003 and 2012 was analyzed with JoinPoint regression model and estimated annual percentage change (EAPC) was calculated. 5-year survival rate was calculated with Kaplan-Meier model. Results: There were 8 229 esophageal cancer cases in Linzhou during 2003-2012. The average annual incidence rate was 80.08/100 000 (8 229/10 276 481). Among all esophageal cancer cases, 7 019 (85.3%) were diagnosed as esophageal squamous cell carcinoma (ESCC). In Linzhou, the age standardized incidence rate by Chinese standard population and by world standard population was 80.92/100 000 and 81.85/100 000 in 2003, 67.97/100 000 and 68.63/100 000 in 2012. JoinPoint regression model showed that EAPC was-12.9% (95%CI:-16.4%--9.1%) for other and unspecified histological type between 2003 and 2012. The EAPC was-5.5% (95%CI:-9.2%--1.6%) for esophageal cancer between 2007 and 2012,-5.4% (95%CI:-7.0%--3.9%) for esophageal cancer in female between 2006 and 2012,-4.9% (95%CI:-9.5%--0.1%) for ESCC between 2007 and 2012. The 5-year prevalence of esophageal cancer was 215.49 per 100 000 (2 337/1 084 493), and 5 489 died within 5 years after incidence. 5-year survival rate of esophageal cancer was 34.6% (95%CI: 33.5%-35.6%). Conclusion: Esophageal cancer had a decreasing trend in Linzhou. The survival rate was increasing. But, esophageal cancer was still a major burden in Linzhou. The major histological type was ESCC. ESCC had a similar decreasing trend with esophageal cancer.

Gastric Cancer, Version 3.2016, NCCN Clinical Practice Guidelines in Oncology.

Gastric cancer is the fifth most frequently diagnosed cancer and the third leading cause of death from cancer in the world. Several advances have been made in the staging procedures, imaging techniques, and treatment approaches. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Gastric Cancer provide an evidence- and consensus-based treatment approach for the management of patients with gastric cancer. This manuscript discusses the recommendations outlined in the NCCN Guidelines for staging, assessment of HER2 overexpression, systemic therapy for locally advanced or metastatic disease, and best supportive care for the prevention and management of symptoms due to advanced disease.

Human papillomavirus type-18 prevalence in oesophageal cancer in the Chinese population: a meta-analysis.

Globally, the prevalence of oesophageal cancer cases is particularly high in China. Since 1982, oncogenic human papillomavirus (HPV) has been hypothesized as a risk factor for oesophageal cancer, but no firm evidence of HPV infection in oesophageal cancer has been established to date. We aimed to conduct a meta-analysis to estimate the high-risk HPV-18 prevalence of oesophageal cancer in the Chinese population. Eligible studies published from 1 January 2005 to 12 July 2014 were retrieved via computer searches of English and Chinese literature databases (including Medline, EMBASE, Chinese National Knowledge Infrastructure and Wanfang Data Knowledge Service Platform). A random-effects model was used to calculate pooled prevalence and corresponding 95% confidence intervals (CIs). A total of 2556 oesophageal cancer cases from 19 studies were included in this meta-analysis. Overall, the pooled HPV-18 prevalence in oesophageal cancer cases was 4·1% (95% CI 2·7-5·5) in China, 6·1% (95% CI 2·9-9·3) in fresh or frozen biopsies and 4·0% (95% CI 2·3-5·8) in paraffin-embedded fixed biopsies, 8·2% (95% CI 4·6-11·7) by the E6/E7 region and 2·2% (95% CI 0·9-3·6) by the L1 region of the HPV gene. This meta-analysis indicated that China has a moderate HPV-18 prevalence of oesophageal cancer compared to cervical cancer, although there is variation between different variables. Further studies are needed to elucidate the role of HPV in oesophagus carcinogenesis with careful consideration of study design and laboratory detection method, providing more accurate assessment of HPV status in oesophageal cancer.

The value of APGA score, fibrosis index for diagnosing liver fibrosis in patients with chronic hepatitis B.

Background: Various non-invasive methods have been studied for assessing the fibrosis stage in patients with chronic hepatitis B. However, the performance of APGA, Fibrosis index in diagnosing liver fibrosis remains unclear globally and specifically in Vietnam. Methods: An analytical cross-sectional study was performed among 242 patients treated at Thong Nhat Hospital. Results: Both the APGA index and Fibrosis index showed good accuracy in diagnosing significant fibrosis (≥ F2), advanced liver fibro-sis (≥ F3), and cirrhosis (F4) with an area under the curve (AUROC) greater than 0.7. AUROC value of APGA index, Fibrosis index for diagnosing signifcant fibrosis (≥ F2) were 0.828, 0.767 respectively. AUROC value of APGA index, Fibrosis index for diagnosing advanced liver fibrosis (≥ F3) were 0.784, 0.755 respectively. AUROC value of APGA index, Fibrosis index for diagnosing cirrhosis (F4) were 0.736, 0.782 respectively. APGA index and the Fibrosis index were significantly positively correlated with the fibrosis stage (p < 0.001), with the APGA index showing the strongest correlation (r = 0.51, p < 0.001). Conclusions: The APGA values of 6.23, 7.88, and 8.99 can serve as cutoff points for the diagnosis of significant fibrosis (≥F2), advanced fibrosis (≥F3), and cirrhosis (F4) when combined with ARFI data.

Mucins as contrast agent targets for fluorescence-guided surgery of pancreatic cancer.

Pancreatic cancer is difficult to resect due to its unique challenges, often leading to incomplete tumor resections. Fluorescence-guided surgery (FGS), also known as intraoperative molecular imaging and optical surgical navigation, is an intraoperative tool that can aid surgeons in complete tumor resection through an increased ability to detect the tumor. To target the tumor, FGS contrast agents rely on biomarkers aberrantly expressed in malignant tissue compared to normal tissue. These biomarkers allow clinicians to identify the tumor and its stage before surgical resection and provide a contrast agent target for intraoperative imaging. Mucins, a family of glycoproteins, are upregulated in malignant tissue compared to normal tissue. Therefore, these proteins may serve as biomarkers for surgical resection. Intraoperative imaging of mucin expression in pancreatic cancer can potentially increase the number of complete resections. While some mucins have been studied for FGS, the potential ability to function as a biomarker target extends to the entire mucin family. Therefore, mucins are attractive proteins to investigate more broadly as FGS biomarkers. This review summarizes the biomarker traits of mucins and their potential use in FGS for pancreatic cancer.

Metastatic Giant Cell Tumor Causing Small Bowel Intussusception on 18 F-FDG PET/CT.

ABSTRACT: An 89-year-old man with a history of a malignant giant cell tumor of soft parts in the right thigh with recurrent/metastatic tumor in the right pelvis was found to have pulmonary nodules concerning for metastatic disease. Subsequent PET/CT unexpectedly demonstrated a right lower quadrant intussusception with a hypermetabolic mass serving as a lead point. Pathology of the resected mass causing the intussusception was compatible with a metastasis from the patient's malignant giant cell tumor of soft parts.

Splenic and PB immune recovery in neoadjuvant treated gastrointestinal cancer patients.

In recent years, immune therapy, notably immune checkpoint inhibitors (ICI), in conjunction with chemotherapy and surgery has demonstrated therapeutic activity for some tumor types. However, little is known about the optimal combination of immune therapy with standard of care therapies and approaches. In patients with gastrointestinal (GI) cancers, especially pancreatic ductal adenocarcinoma (PDAC), preoperative (neoadjuvant) chemotherapy has increased the number of patients who can undergo surgery and improved their responses. However, most chemotherapy is immunosuppressive, and few studies have examined the impact of neoadjuvant chemotherapy (NCT) on patient immunity and/or the optimal combination of chemotherapy with immune therapy. Furthermore, the majority of chemo/immunotherapy studies focused on immune regulation in cancer patients have focused on postoperative (adjuvant) chemotherapy and are limited to peripheral blood (PB) and occasionally tumor infiltrating lymphocytes (TILs); representing a minority of immune cells in the host. Our previous studies examined the phenotype and frequencies of myeloid and lymphoid cells in the PB and spleens of GI cancer patients, independent of chemotherapy regimen. These results led us to question the impact of NCT on host immunity. We report herein, unique studies examining the splenic and PB phenotypes, frequencies, and numbers of myeloid and lymphoid cell populations in NCT treated GI cancer patients, as compared to treatment naïve cancer patients and patients with benign GI tumors at surgery. Overall, we noted limited immunological differences in patients 6 weeks following NCT (at surgery), as compared to treatment naive patients, supporting rapid immune normalization. We observed that NCT patients had a lower myeloid derived suppressor cells (MDSCs) frequency in the spleen, but not the PB, as compared to treatment naive cancer patients and patients with benign GI tumors. Further, NCT patients had a higher splenic and PB frequency of CD4+ T-cells, and checkpoint protein expression, as compared to untreated, cancer patients and patients with benign GI tumors. Interestingly, in NCT treated cancer patients the frequency of mature (CD45RO+) CD4+ and CD8+ T-cells in the PB and spleens was higher than in treatment naive patients. These differences may also be associated, in part with patient stage, tumor grade, and/or NCT treatment regimen. In summary, the phenotypic profile of leukocytes at the time of surgery, approximately 6 weeks following NCT treatment in GI cancer patients, are similar to treatment naive GI cancer patients (i.e., patients who receive adjuvant therapy); suggesting that NCT may not limit the response to immune intervention and may improve tumor responses due to the lower splenic frequency of MDSCs and higher frequency of mature T-cells.

Axillary recurrence rate following negative sentinel node biopsy for invasive breast cancer: long-term follow-up.

OBJECTIVE: Sentinel lymph node (SLN) biopsy has replaced axillary lymph node dissection (ALND) as the definitive nodal staging procedure for breast cancer. SLN biopsy has been proven to cause less morbidity and be more cost effective than complete ALND. Short-term follow-up has shown that lymphatic mapping and SLN have a low false-negative rate, but there is limited data demonstrating long-term outcomes within a large consecutive series of patients. METHODS: Retrospective review of a prospective database of breast cancer patients at our institution was performed. The initial mapping of 1,530 patients with invasive breast cancer who demonstrated a negative sentinel node biopsy and no axillary dissection between January 1995 and June 2003 were collated and reviewed to achieve a long-term follow-up. These 1,530 patients were reviewed for follow-up time, local recurrences, distant metastases, and survival. RESULTS: 1,530 consecutively mapped invasive breast cancer patients had a negative SLN biopsy and no ALND. The mean invasive tumor size was 1.40 cm. Of 1,530 patients, 73% (1,121) underwent lumpectomy and 27% (409) underwent mastectomy. Mean follow-up was 4.92 years (range 0-12.0 years). There have been 4 (0.26%) patients presenting with local axillary recurrences, 54 (3.53%) patients presenting with local recurrences in the ipsilateral breast/chest wall, and 24 (1.57%) presenting with distant metastases. CONCLUSION: These data confirm that SLN biopsy is an effective and safe alternative to ALND for detection of nodal metastases in patients with invasive breast cancer and should be used as the standard tool for nodal staging.