Publications by authors named "Wey L Leong"

16 Publications

  • Page 1 of 1

Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma.

Clin Cancer Res 2018 11 31;24(22):5685-5696. Epub 2018 Jul 31.

The Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.

Regulatory T (Treg) cells expressing the transcription factor FOXP3 are essential for the maintenance of immunologic self-tolerance but play a detrimental role in most cancers due to their ability to suppress antitumor immunity. The phenotype of human circulating Treg cells has been extensively studied, but less is known about tumor-infiltrating Treg cells. We studied the phenotype and function of tumor-infiltrating Treg cells in ovarian cancer and melanoma to identify potential Treg cell-associated molecules that can be targeted by tumor immunotherapies. The phenotype of intratumoral and circulating Treg cells was analyzed by multicolor flow cytometry, mass cytometry, RNA-seq, and functional assays. Treg cells isolated from ovarian tumors displayed a distinct cell surface phenotype with increased expression of a number of receptors associated with TCR engagement, including PD-1, 4-1BB, and ICOS. Higher PD-1 and 4-1BB expression was associated with increased responsiveness to further TCR stimulation and increased suppressive capacity, respectively. Transcriptomic and mass cytometry analyses revealed the presence of Treg cell subpopulations and further supported a highly activated state specifically in ovarian tumors. In comparison, Treg cells infiltrating melanomas displayed lower FOXP3, PD-1, 4-1BB, and ICOS expression and were less potent suppressors of CD8 T-cell proliferation. The highly activated phenotype of ovarian tumor-infiltrating Treg cells may be a key component of an immunosuppressive tumor microenvironment. Receptors that are expressed by tumor-infiltrating Treg cells could be exploited for the design of novel combination tumor immunotherapies. .
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http://dx.doi.org/10.1158/1078-0432.CCR-18-0554DOI Listing
November 2018

Mapping genomic and transcriptomic alterations spatially in epithelial cells adjacent to human breast carcinoma.

Nat Commun 2017 11 1;8(1):1245. Epub 2017 Nov 1.

Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, M5G 2M9.

Almost all genomic studies of breast cancer have focused on well-established tumours because it is technically challenging to study the earliest mutational events occurring in human breast epithelial cells. To address this we created a unique dataset of epithelial samples ductoscopically obtained from ducts leading to breast carcinomas and matched samples from ducts on the opposite side of the nipple. Here, we demonstrate that perturbations in mRNA abundance, with increasing proximity to tumour, cannot be explained by copy number aberrations. Rather, we find a possibility of field cancerization surrounding the primary tumour by constructing a classifier that evaluates where epithelial samples were obtained relative to a tumour (cross-validated micro-averaged AUC = 0.74). We implement a spectral co-clustering algorithm to define biclusters. Relating to over-represented bicluster pathways, we further validate two genes with tissue microarrays and in vitro experiments. We highlight evidence suggesting that bicluster perturbation occurs early in tumour development.
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http://dx.doi.org/10.1038/s41467-017-01357-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5665998PMC
November 2017

Changes in insulin receptor signaling underlie neoadjuvant metformin administration in breast cancer: a prospective window of opportunity neoadjuvant study.

Breast Cancer Res 2015 Mar 3;17:32. Epub 2015 Mar 3.

Introduction: The antidiabetic drug metformin exhibits potential anticancer properties that are believed to involve both direct (insulin-independent) and indirect (insulin-dependent) actions. Direct effects are linked to activation of AMP-activated protein kinase (AMPK) and an inhibition of mammalian target of rapamycin mTOR signaling, and indirect effects are mediated by reductions in circulating insulin, leading to reduced insulin receptor (IR)-mediated signaling. However, the in vivo impact of metformin on cancer cell signaling and the factors governing sensitivity in patients remain unknown.

Methods: We conducted a neoadjuvant, single-arm, "window of opportunity" trial to examine the clinical and biological effects of metformin on patients with breast cancer. Women with untreated breast cancer who did not have diabetes were given 500 mg of metformin three times daily for ≥2 weeks after diagnostic biopsy until surgery. Fasting blood and tumor samples were collected at diagnosis and surgery. Blood glucose and insulin were assayed to assess the physiologic effects of metformin, and immunohistochemical analysis of tumors was used to characterize cellular markers before and after treatment.

Results: Levels of IR expression decreased significantly in tumors (P = 0.04), as did the phosphorylation status of protein kinase B (PKB)/Akt (S473), extracellular signal-regulated kinase 1/2 (ERK1/2, T202/Y204), AMPK (T172) and acetyl coenzyme A carboxylase (S79) (P = 0.0001, P < 0.0001, P < 0.005 and P = 0.02, respectively). All tumors expressed organic cation transporter 1, with 90% (35 of 39) exhibiting an Allred score of 5 or higher.

Conclusions: Reduced PKB/Akt and ERK1/2 phosphorylation, coupled with decreased insulin and IR levels, suggest insulin-dependent effects are important in the clinical setting. These results are consistent with beneficial anticancer effects of metformin and highlight key factors involved in sensitivity, which could be used to identify patients with breast cancer who may be responsive to metformin-based therapies.

Trial Registration: ClinicalTrials.gov identifier: NCT00897884. Registered 8 May 2009.
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http://dx.doi.org/10.1186/s13058-015-0540-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381495PMC
March 2015

B7-H4 expression by nonhematopoietic cells in the tumor microenvironment promotes antitumor immunity.

Cancer Immunol Res 2015 Feb 19;3(2):184-95. Epub 2014 Dec 19.

Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, Toronto, Ontario, Canada. Department of Immunology, University of Toronto, Toronto, Ontario, Canada. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.

The B7 family plays a critical role in both positive and negative regulation of immune responses by engaging a variety of receptors on lymphocytes. Importantly, blocking coinhibitory molecules using antibodies specific for CTLA-4 and PD-1 enhances tumor immunity in a subset of patients. Therefore, it is critical to understand the role of different B7 family members since they may be suitable therapeutic targets. B7-H4 is another member that inhibits T-cell function, and it is also upregulated on a variety of tumors and has been proposed to promote tumor growth. Here, we investigate the role of B7-H4 in tumor development and show that B7-H4 expression inhibits tumor growth in two mouse models. Furthermore, we show that B7-H4 expression is required for antitumor immune responses in a mouse model of mammary tumorigenesis. We found that the expression levels of B7-H4 correlate with MHC class I expression in both mouse and human samples. We show that IFNγ upregulates B7-H4 expression on mouse embryo fibroblasts and that the upregulation of B7-H4 on tumors is dependent on T cells. Notably, patients with breast cancer with increased B7-H4 expression show a prolonged time to recurrence. These studies demonstrate a positive role for B7-H4 in promoting antitumor immunity.
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http://dx.doi.org/10.1158/2326-6066.CIR-14-0113DOI Listing
February 2015

Validation of the prognostic gene portfolio, ClinicoMolecular Triad Classification, using an independent prospective breast cancer cohort and external patient populations.

Breast Cancer Res 2014 Jul 4;16(4):R71. Epub 2014 Jul 4.

Introduction: Using genome-wide expression profiles of a prospective training cohort of breast cancer patients, ClinicoMolecular Triad Classification (CMTC) was recently developed to classify breast cancers into three clinically relevant groups to aid treatment decisions. CMTC was found to be both prognostic and predictive in a large external breast cancer cohort in that study. This study serves to validate the reproducibility of CMTC and its prognostic value using independent patient cohorts.

Methods: An independent internal cohort (n = 284) and a new external cohort (n = 2,181) were used to validate the association of CMTC between clinicopathological factors, 12 known gene signatures, two molecular subtype classifiers, and 19 oncogenic signalling pathway activities, and to reproduce the abilities of CMTC to predict clinical outcomes of breast cancer. In addition, we also updated the outcome data of the original training cohort (n = 147).

Results: The original training cohort reached a statistically significant difference (p < 0.05) in disease-free survivals between the three CMTC groups after an additional two years of follow-up (median = 55 months). The prognostic value of the triad classification was reproduced in the second independent internal cohort and the new external validation cohort. CMTC achieved even higher prognostic significance when all available patients were analyzed (n = 4,851). Oncogenic pathways Myc, E2F1, Ras and β-catenin were again implicated in the high-risk groups.

Conclusions: Both prospective internal cohorts and the independent external cohorts reproduced the triad classification of CMTC and its prognostic significance. CMTC is an independent prognostic predictor, and it outperformed 12 other known prognostic gene signatures, molecular subtype classifications, and all other standard prognostic clinicopathological factors. Our results support further development of CMTC portfolio into a guide for personalized breast cancer treatments.
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http://dx.doi.org/10.1186/bcr3686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226941PMC
July 2014

Lunatic fringe deficiency cooperates with the Met/Caveolin gene amplicon to induce basal-like breast cancer.

Cancer Cell 2012 May;21(5):626-41

Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, M5G 1L7, Canada.

Basal-like breast cancers (BLBC) express a luminal progenitor gene signature. Notch receptor signaling promotes luminal cell fate specification in the mammary gland, while suppressing stem cell self-renewal. Here we show that deletion of Lfng, a sugar transferase that prevents Notch activation by Jagged ligands, enhances stem/progenitor cell proliferation. Mammary-specific deletion of Lfng induces basal-like and claudin-low tumors with accumulation of Notch intracellular domain fragments, increased expression of proliferation-associated Notch targets, amplification of the Met/Caveolin locus, and elevated Met and Igf-1R signaling. Human BL breast tumors, commonly associated with JAGGED expression, elevated MET signaling, and CAVEOLIN accumulation, express low levels of LFNG. Thus, reduced LFNG expression facilitates JAG/NOTCH luminal progenitor signaling and cooperates with MET/CAVEOLIN basal-type signaling to promote BLBC.
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http://dx.doi.org/10.1016/j.ccr.2012.03.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3603366PMC
May 2012

Proteomic analyses reveal high expression of decorin and endoplasmin (HSP90B1) are associated with breast cancer metastasis and decreased survival.

PLoS One 2012 20;7(2):e30992. Epub 2012 Feb 20.

Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.

Background: Breast cancer is the most common malignancy among women worldwide in terms of incidence and mortality. About 10% of North American women will be diagnosed with breast cancer during their lifetime and 20% of those will die of the disease. Breast cancer is a heterogeneous disease and biomarkers able to correctly classify patients into prognostic groups are needed to better tailor treatment options and improve outcomes. One powerful method used for biomarker discovery is sample screening with mass spectrometry, as it allows direct comparison of protein expression between normal and pathological states. The purpose of this study was to use a systematic and objective method to identify biomarkers with possible prognostic value in breast cancer patients, particularly in identifying cases most likely to have lymph node metastasis and to validate their prognostic ability using breast cancer tissue microarrays.

Methods And Findings: Differential proteomic analyses were employed to identify candidate biomarkers in primary breast cancer patients. These analyses identified decorin (DCN) and endoplasmin (HSP90B1) which play important roles regulating the tumour microenvironment and in pathways related to tumorigenesis. This study indicates that high expression of Decorin is associated with lymph node metastasis (p<0.001), higher number of positive lymph nodes (p<0.0001) and worse overall survival (p = 0.01). High expression of HSP90B1 is associated with distant metastasis (p<0.0001) and decreased overall survival (p<0.0001) these patients also appear to benefit significantly from hormonal treatment.

Conclusions: Using quantitative proteomic profiling of primary breast cancers, two new promising prognostic and predictive markers were found to identify patients with worse survival. In addition HSP90B1 appears to identify a group of patients with distant metastasis with otherwise good prognostic features.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0030992PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282708PMC
June 2012

Clinical relevance of DNA microarray analyses using archival formalin-fixed paraffin-embedded breast cancer specimens.

BMC Cancer 2011 Jun 16;11:253:1-13. Epub 2011 Jun 16.

Ontario Cancer Institute and Campbell Family Institute for Breast Cancer Research, Princess Margaret Hospital, University Health Network, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada.

Background: The ability of gene profiling to predict treatment response and prognosis in breast cancers has been demonstrated in many studies using DNA microarray analyses on RNA from fresh frozen tumor specimens. In certain clinical and research situations, performing such analyses on archival formalin fixed paraffin-embedded (FFPE) surgical specimens would be advantageous as large libraries of such specimens with long-term follow-up data are widely available. However, FFPE tissue processing can cause fragmentation and chemical modifications of the RNA. A number of recent technical advances have been reported to overcome these issues. Our current study evaluates whether or not the technology is ready for clinical applications.

Methods: A modified RNA extraction method and a recent DNA microarray technique, cDNA-mediated annealing, selection, extension and ligation (DASL, Illumina Inc) were evaluated. The gene profiles generated from FFPE specimens were compared to those obtained from paired fresh fine needle aspiration biopsies (FNAB) of 25 breast cancers of different clinical subtypes (based on ER and Her2/neu status). Selected RNA levels were validated using RT-qPCR, and two public databases were used to demonstrate the prognostic significance of the gene profiles generated from FFPE specimens.

Results: Compared to FNAB, RNA isolated from FFPE samples was relatively more degraded, nonetheless, over 80% of the RNA samples were deemed suitable for subsequent DASL assay. Despite a higher noise level, a set of genes from FFPE specimens correlated very well with the gene profiles obtained from FNAB, and could differentiate breast cancer subtypes. Expression levels of these genes were validated using RT-qPCR. Finally, for the first time we correlated gene expression profiles from FFPE samples to survival using two independent microarray databases. Specifically, over-expression of ANLN and KIF2C, and under-expression of MAPT strongly correlated with poor outcomes in breast cancer patients.

Conclusion: We demonstrated that FFPE specimens retained important prognostic information that could be identified using a recent gene profiling technology. Our study supports the use of FFPE specimens for the development and refinement of prognostic gene signatures for breast cancer. Clinical applications of such prognostic gene profiles await future large-scale validation studies.
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http://dx.doi.org/10.1186/1471-2407-11-253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128009PMC
June 2011

Mammary ductoscopy in the evaluation and treatment of pathologic nipple discharge: a Canadian experience.

Can J Surg 2009 Dec;52(6):E245-8

Department of Surgical Oncology, Princess Margaret Hospital, Toronto, Ont.

Background: Mammary ductoscopy allows direct visualization of ductal epithelium using a fibreoptic microendoscope. As the first centre in Canada to apply ductoscopy to surgical practice, we report our experience with this technology.

Methods: Between 2004 and 2008, 65 women with pathologic nipple discharge underwent ductoscopy before surgical duct excision under general anesthetic. Prospective data collection included cannulation and complication rates, procedure length and lesion visualization rate compared with preoperative ductography, if performed. In addition, we classified the endoscopic appearance according to Makita and colleagues and correlated it with surgical pathology.

Results: It took longer than 6 months to overcome technical problems before the routine use of ductoscopy in the operating room. The ductoscope was easy to use: we achieved cannulation in 63 of 66 breast ducts (95%) and we visualized a lesion in 52 of 63 breast ducts (83%). The mean procedure length was 5.1 minutes, with no complications. Lesions seen on ductography were seen endoscopically 30 of 33 (91%) times. All 3 malignancies were seen: invasive carcinoma in 1 of 62 (1.6%) and in situ disease in 2 of 62 (3.2%) patients. Surgeons found ductoscopy helpful in defining the extent of duct excision. Except for the "polypoid solitary" class, which accurately predicted a papilloma (23/23), we found poor correlation between Makita and colleague's endoscopic classification and final pathology.

Conclusion: Ductoscopy is feasible, safe and practical. Our surgeons routinely use it to identify the location and extent of duct excision without ordering preoperative ductography. Identifying pathology based on the endoscopic appearance is unreliable unless the lesion is solitary and polypoid.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2792391PMC
December 2009

Feasibility study of autofluorescence mammary ductoscopy.

J Biomed Opt 2009 Jul-Aug;14(4):044036

Ontario Cancer Institute, University Health Network, 7-417 610 University Avenue, Toronto, M5G 2M9 Canada.

We report the technical feasibility of autofluorescence ductoscopy in the ex-vivo setting. The current imaging algorithm for visualizing tumor tissue against the normal tissue background, although developed and optimized for other organs, appears to provide discrimination between intraductal tumor and normal ductal tissue. Point fluoroscopy is also performed. Although the optical "geometry" for this is different, the findings are consistent with the imaging observations.
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http://dx.doi.org/10.1117/1.3210773DOI Listing
December 2009

Sentinel nodes in breast cancer: relevance of axillary level II nodes and optimal number of nodes that need to be removed.

Ann Surg Oncol 2008 Jun 7;15(6):1710-6. Epub 2008 Mar 7.

Department of Surgical Oncology, Princess Margaret Hospital, University Health Network and University of Toronto, Toronto, Ontario, Canada.

Background: In some patients, the radiocolloid used to perform sentinel lymph node biopsy (SLNB) for breast cancer appears in a number of lymph nodes and in different levels of the axilla. Most positive sentinel lymph node specimens (SLNSs) removed during SLNB are identified in level I of the axilla and within the first 4 SLNSs. Our objective was to verify the staging accuracy of harvesting only the first 4 SLNSs and to determine the relevance of SLNSs that reside in level II of the axilla.

Methods: A prospective database documenting the method of identification, radioisotope count, order of retrieval, and axillary level of SLNSs from 893 SLNBs was analyzed.

Results: A median of 2 SLNSs (range 1-9) were removed per patient. More than 4 SLNSs were found in 8.0%. All SLNSs harboring the largest nodal metastases were identified within the first 4 harvested. Twenty-one percent (184 of 870) of patients had level II SLNSs; 4.9% (9 of 184) were positive. When SLNSs were positive in both levels I and II, the nodal metastases were always of greater or equal size in the level I nodes. Only one patient (0.5%) had a positive level II SLNS macrometastasis (> 2 mm, pN1), with a negative level I SLNS, but it was the hottest node and was removed first.

Conclusions: Removal of more than the first 4 hottest SLNSs does not improve staging accuracy. Level II nodes can be ignored if a hotter level I SLNS is first identified.
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http://dx.doi.org/10.1245/s10434-008-9858-5DOI Listing
June 2008

Histological features of melanoma sentinel lymph node metastases associated with status of the completion lymphadenectomy and rate of subsequent relapse.

Ann Surg Oncol 2007 Feb 29;14(2):906-12. Epub 2006 Nov 29.

Division of General Surgery, University of Toronto, Toronto, ON, Canada.

Background: The current recommendation for patients with cutaneous melanoma and a positive sentinel lymph node (SLN) biopsy is a completion lymph node dissection (CLND). This study sought to define a population of SLN-positive patients, based on their histological pattern of SLN metastases, who may not require CLND.

Methods: All patients with SLN-positive cutaneous melanoma who underwent CLND between March 1999 and December 2004 at a single academic institution were enrolled. Metastatic deposits in the SLN were categorized by their histological zone of involvement (subcapsular, parenchymal and/or sinusoidal). Logistic regression was used to examine the effect of SLN zone, size of nodal metastases, and other histological factors on CLND positivity. Kaplan-Meier and Cox models were used to study disease recurrence.

Results: A total of 127 patients were included, and 15.8% had positive non-sentinel nodes. In adjusted analyses, the size of the largest tumor deposit in the SLN was the only factor associated with CLND status. No patients with a tumor deposit
Conclusion: Histologic features of tumor metastases in positive SLN may be useful in defining a population of patients who may be spared CLND and a group at high risk of recurrence.
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http://dx.doi.org/10.1245/s10434-006-9241-3DOI Listing
February 2007

Role of sentinel lymph node biopsy in ductal carcinoma-in-situ treated by mastectomy.

Ann Surg Oncol 2007 Feb 14;14(2):638-45. Epub 2006 Nov 14.

Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Background: Sentinel lymph node biopsy (SLNB) is a widely accepted alternative to axillary lymph node dissection in invasive breast cancer. Its role in ductal carcinoma-in-situ (DCIS) is unclear. The purpose of this study was to determine factors associated with the subsequent diagnosis of invasive disease and to determine the role of SLNB when performing a mastectomy for DCIS.

Methods: A retrospective study was conducted of all mastectomies performed on patients with a preoperative diagnosis of DCIS between 2000 and 2005 at a single tertiary-care institution.

Results: Ninety mastectomies for DCIS were included, 54 (60%) of which were performed with concurrent SLNB. Of 44 patients diagnosed preoperatively with DCIS by core biopsy only, 34 patients (63%) had a concurrent SLNB, while 10 patients (28%) were treated with mastectomy alone (P < .01). Overall, 30 patients (33%) had invasive disease, 22 of whom received concurrent SLNB. Seven SLNB patients (13%) had positive SLNs. On univariate analysis, multifocality (P = .03), multicentricity (P = .01), comedonecrosis (P = .01), and diagnosis by core biopsy (P < .001) were associated with invasive disease on pathology. On multivariate analysis, comedonecrosis (P = .04) and diagnosis by core biopsy (P < .01) were independent predictors for invasion. There was no statistically significant predictor for sentinel lymph node metastasis.

Conclusions: Approximately one-third of patients with DCIS treated with mastectomy at our institution later had invasive disease, and factors associated with invasion have been identified. On the basis of our results, routine SLNB is recommended in this patient population.
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http://dx.doi.org/10.1245/s10434-006-9211-9DOI Listing
February 2007

Anti-Ri antibody opsoclonus-myoclonus syndrome and breast cancer: a case report and a review of the literature.

J Surg Oncol 2004 Sep;87(3):143-5

General Surgery and Surgical Oncology, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada.

Opsoclonus-myoclonus is a rare neurological paraneoplastic syndrome associated with breast cancer and the presence of anti-Ri antibody. We presented a case of a 79-year-old woman with this syndrome and a small invasive ductal carcinoma [pT1aN0(sn)M0], whose symptoms improved 3 months following her simple mastectomy without any adjuvant therapy. Based on the 15 previously reported cases in the literature, there is no uniform treatment option available, and the response to such treatments is mixed.
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http://dx.doi.org/10.1002/jso.20103DOI Listing
September 2004

Previous wide local excision of primary melanoma is not a contraindication for sentinel lymph node biopsy of the trunk and extremity.

J Surg Oncol 2003 Mar;82(3):143-6

Department of Surgical Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.

Background And Objectives: The role of sentinel lymph node biopsy (SLNB) in patients with a previous wide local excision (WLE) was examined with case-control methodology.

Methods: A total of 168 consecutive cases of SLNB were performed in patients with truncal and extremity melanoma with tumor thickness of > or = 1 mm between October 1997 and June 2000 and were followed prospectively. For comparison, 65 of the 103 SLNB patients referred to us after their WLE (cases) were matched by tumor thickness to 65 patients who had SLNB with concurrent WLE (controls). Radiocolloid (technetium-99m sulfur colloid) was used in all cases; in addition, vital blue dye (patent blue) was used in the control group. The two groups were followed for a median of 15.4 months.

Results: SLNs were identified in all patients with an average of 2.1 (cases) and 2.0 (controls) SLNs excised per patient (P = 0.77). Twenty one (32.3%) of those having SLNB after previous WLE (cases) and 23 (35.4%) of those with concurrent WLE and SLNB (controls) were found to have metastatic disease in the SLN. The only false-negative in this group was detected in clinical follow-up in a patient whose truncal WLE was previously closed with a rotation flap (case). There was no significant difference in relapse-free survival (P = 0.209) and overall survival (P = 0.692) between groups.

Conclusions: SLNB is feasible in patients with previous WLE for extremity and truncal melanoma. Similar rates of sentinel positivity are found when compared with those in whom their WLE was done concurrently.
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http://dx.doi.org/10.1002/jso.10205DOI Listing
March 2003

Regression of metastatic carcinoid tumors with octreotide therapy: two case reports and a review of the literature.

J Surg Oncol 2002 Mar;79(3):180-7

Division of Surgical Oncology, University of Calgary, Calgary, Alberta, Canada.

Background: The antiproliferative effect of the somatostatin analogue, octreotide, on metastatic carcinoid tumors is poorly understood. Partial tumor regression seen radiographically has been reported with the use of octreotide therapy for neuroendocrine tumors. Complete regression of carcinoid tumors is rarely reported.

Results: Two patients with metastatic midgut carcinoid tumors were treated with subcutaneous octreotide 300 microg/day for symptomatic control of their carcinoid syndrome before debulking palliative surgery. During the laporatomies, both patients were found to have complete macroscopic regression of the metastatic lesions that had been identified radiologically before surgery, including liver metastases in one patient and periportal and retrocaval lymph nodes in the other. After surgery, the patients were evaluated every 3 months, and had no detectable disease at 30 and 43 months, respectively. Thirty cases of partial tumor regression with octreotide administered with or without other treatment modalities have been reported in the literature. Most of the patients involved received other treatment modalities. Only one other case reported in the literature showed complete regression with octreotide monotherapy.

Conclusions: We report two cases of metastatic midgut carcinoid tumors that demonstrated a significant anti-proliferative response to octreotide monotherapy. Review of the literature failed to identify any specific prognostic factors with which the response to octreotide can be predicted. Possible mechanisms for this antiproliferative effect of octreotide on carcinoid tumors are discussed.
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http://dx.doi.org/10.1002/jso.10062DOI Listing
March 2002