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ABSTRACT: Bile duct injury is an uncommon but potentially serious complication in cholecystectomy. A recognized treatment for minor biliary injury is internal biliary decompression by endoscopic retrograde cholangiopancreatography (ERCP) and stent insertion. The aim of this study was to assess the effectiveness of ERCP in the management of minor biliary injuries.
A retrospective review of medical records at a tertiary referral centre identified 36 patients treated for postoperative minor biliary injuries between 2006 and 2010. Management involved establishing a controlled biliary fistula followed by ERCP to confirm the nature of the injury and decompress the bile duct with stent insertion.
Controlled biliary fistulae were established in all 36 patients. Resolution of the bile leak was achieved prior to ERCP in seven patients, and ERCP with stent insertion was successful in 27 of the remaining 29 patients. Resolution of the bile leak was achieved in all patients without further intervention. The median time to resolution after successful ERCP was 4 days. Two patients underwent ERCP complicated by mild pancreatitis. No other complications were seen.
This review confirms that postoperative minor biliary injuries can be managed by sepsis control and semi-urgent endoscopic biliary decompression.
HPB 10/2011; 13(10):699-705. · 1.60 Impact Factor
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Marie-Liesse Asselin-Labat,
Kate D Sutherland,
François Vaillant, David E Gyorki,
Di Wu,
Sheridan Holroyd,
Kelsey Breslin,
Teresa Ward,
Wei Shi,
Mary L Bath,
Siddhartha Deb,
Stephen B Fox,
Gordon K Smyth,
Geoffrey J Lindeman,
Jane E Visvader
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ABSTRACT: The transcription factor Gata-3 is a definitive marker of luminal breast cancers and a key regulator of mammary morphogenesis. Here we have explored a role for Gata-3 in tumor initiation and the underlying cellular mechanisms using a mouse model of "luminal-like" cancer. Loss of a single Gata-3 allele markedly accelerated tumor progression in mice carrying the mouse mammary tumor virus promoter-driven polyomavirus middle T antigen (MMTV-PyMT mice), while overexpression of Gata-3 curtailed tumorigenesis. Through the identification of two distinct luminal progenitor cells in the mammary gland, we demonstrate that Gata-3 haplo-insufficiency increases the tumor-initiating capacity of these progenitors but not the stem cell-enriched population. Overexpression of a conditional Gata-3 transgene in the PyMT model promoted cellular differentiation and led to reduced tumor-initiating capacity as well as diminished angiogenesis. Transcript profiling studies identified caspase-14 as a novel downstream target of Gata-3, in keeping with its roles in differentiation and tumorigenesis. A strong association was evident between GATA-3 and caspase-14 expression in preinvasive ductal carcinoma in situ samples, where GATA-3 also displayed prognostic significance. Overall, these studies identify GATA-3 as an important regulator of tumor initiation through its ability to promote the differentiation of committed luminal progenitor cells.
Molecular and cellular biology 09/2011; 31(22):4609-22. · 6.06 Impact Factor
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Journal of Clinical Oncology 02/2010; 28(9):e139; author reply e141-2. · 18.37 Impact Factor
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Elgene Lim,
François Vaillant,
Di Wu,
Natasha C Forrest,
Bhupinder Pal,
Adam H Hart,
Marie-Liesse Asselin-Labat, David E Gyorki,
Teresa Ward,
Audrey Partanen,
Frank Feleppa,
Lily I Huschtscha,
Heather J Thorne,
Stephen B Fox,
Max Yan,
Juliet D French,
Melissa A Brown,
Gordon K Smyth,
Jane E Visvader,
Geoffrey J Lindeman
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ABSTRACT: Basal-like breast cancers arising in women carrying mutations in the BRCA1 gene, encoding the tumor suppressor protein BRCA1, are thought to develop from the mammary stem cell. To explore early cellular changes that occur in BRCA1 mutation carriers, we have prospectively isolated distinct epithelial subpopulations from normal mammary tissue and preneoplastic specimens from individuals heterozygous for a BRCA1 mutation. We describe three epithelial subsets including basal stem/progenitor, luminal progenitor and mature luminal cells. Unexpectedly, we found that breast tissue from BRCA1 mutation carriers harbors an expanded luminal progenitor population that shows factor-independent growth in vitro. Moreover, gene expression profiling revealed that breast tissue heterozygous for a BRCA1 mutation and basal breast tumors were more similar to normal luminal progenitor cells than any other subset, including the stem cell-enriched population. The c-KIT tyrosine kinase receptor (encoded by KIT) emerged as a key marker of luminal progenitor cells and was more highly expressed in BRCA1-associated preneoplastic tissue and tumors. Our findings suggest that an aberrant luminal progenitor population is a target for transformation in BRCA1-associated basal tumors .
Nature medicine 09/2009; 15(8):907-13. · 27.14 Impact Factor
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ABSTRACT: Macrophages, derived from circulating monocytes, are located within virtually all adult tissues. There, these specialized cells adopt tissue-specific functions that are important for normal tissue homeostasis and response to physiological challenges. Increasing evidence suggests that macrophages play a role in the normal development of certain organs, such as the breast. Intriguingly, macrophages are often found in the stroma of breast tumours, where they may promote tumour growth and metastasis. In this review we discuss this emerging area of developmental and tumour biology.
ANZ Journal of Surgery 06/2008; 78(6):432-6. · 1.25 Impact Factor
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ABSTRACT: Desmoplastic melanoma (DM) is a rare variant characterized by the presence of fusiform melanocytes in a sclerotic stroma. Pathologic heterogeneity within DM may account for the controversy regarding the clinical presentation and prognosis of DM compared with conventional melanoma (CM).
We identified 131 patients with a diagnosis of DM seen between 1979 and 2002. Tumors were categorized as either pure DM (pDM; n = 92), if desmoplasia was prominent throughout the entire invasive tumor, or mixed DM (mDM; n = 39), if fibrosis was well developed in only parts of an otherwise non-DM. Differences in clinical behavior among pDM, mDM, and CM (n = 3976) were examined.
Seventy-three percent of patients with DM had tumors >2 mm in depth, compared with 31% of patients with CM (P < .001). Regional nodal metastasis was uncommon in patients who presented with clinically localized pDM (1%) compared with those with mDM (10%) or CM (6%) (P < .05, pDM vs. CM). Five-year melanoma-specific mortality was lower for patients who presented with pDM compared with mDM (11% vs. 31%; P < .01). Patients with pDM and CM had a similar melanoma-specific mortality despite a 3-fold difference in median tumor depth (3.6 vs. 1.2 mm, respectively).
DMs can be divided into two subtypes based on a histological quantification of desmoplasia. Tumors with prominent fibrosis (pure subtype) are unlikely to disseminate to regional lymph nodes and are associated with a favorable outcome when compared with those with mixed desmoplasia or CM.
Annals of Surgical Oncology 03/2005; 12(3):207-13. · 4.17 Impact Factor
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ABSTRACT: Interferon-alpha2b (IFNalpha2b) is the only form of systemic adjuvant therapy for stage III melanoma with documented survival benefit. Radiotherapy can also be utilized in the adjuvant setting in patients at high risk of nodal basin recurrence. As IFNalpha2b is associated with substantial toxicity, we sought to determine both the systemic and radiation-related toxicities in patients treated with combined adjuvant IFNalpha2b and regional adjuvant radiotherapy delivered in the setting of a single institution. Eighteen consecutive patients who commenced adjuvant IFNalpha2b between November 1997 and August 2002 were analysed retrospectively for toxicities associated with the combination of IFNalpha2b and adjuvant radiotherapy (40-50 Gy in 15-25 fractions) to nodal basins delivered during the maintenance phase of IFNalpha2b therapy (median dose during radiotherapy of 6.5 MU/m three times per week). Seven out of 18 patients who received concurrent radiotherapy and IFNalpha2b displayed grade 3 skin reactions. Severe radiation-induced toxicity was seen in three further patients, one who developed radiation pneumonitis, one who developed severe oral mucositis, and one who developed wound dehiscence that took 10 months to resolve. Non-radiation-related toxicity to IFNalpha2b therapy was typical for this dose and schedule. We conclude that concurrent use of adjuvant radiotherapy and IFNalpha2b may enhance radiation-induced toxicity. However, overall we found concurrent radiation and IFNalpha2b could be safely delivered with appropriate clinical monitoring.
Melanoma Research 07/2004; 14(3):223-30. · 2.19 Impact Factor
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ABSTRACT: Although desmoplastic melanoma (DM) often presents at a locally advanced stage, nodal metastases are rare. We describe our experience with lymphatic mapping and sentinel lymph node biopsy (SLNB) in patients with DM to characterize the biological behavior of these tumors.
Twenty-seven patients with cutaneous DM underwent wide excision and attempted SLNB between 1996 and 2001. All pathology was reviewed by a single dermatopathologist (KB). Clinical and histological features were recorded.
There were 20 male and 7 female patients. The median age was 64 years (range, 35-83 years). The head and neck was the most commonly involved anatomical region (n = 14). The median Breslow thickness was 2.2 mm. Twenty-four patients underwent successful SLNB. No patient had a positive sentinel node. At a median follow-up of 27 months, five patients recurred (four systemic and one local); all five had undergone successful SLNB. Two of these patients died of disease, two are alive with disease, and one remains alive and disease free. No patient experienced failure in a regional nodal basin.
DM is a biologically distinct form of melanoma, with a very low incidence of regional lymph node metastases, either at presentation or in long-term follow-up. This biology should be considered when designing rational treatment strategies for these patients.
Annals of Surgical Oncology 06/2003; 10(4):403-7. · 4.17 Impact Factor
