The ATP binding cassette transporter A1 (ABCA1) is involved in the regulation of lipid trafficking and export of cholesterol from cells to high density lipoprotein (HDL).
ABCA1 gene defects cause ...Tangier disease, an autosomal recessive disorder characterised by the absence of HDL-cholesterol in plasma, abnormal deposition of cholesteryl esters in the reticuloendothelial system, defective platelet dense and lysosomal granule release, and disordered cellular cholesterol efflux. We describe the case of a 62-year-old man with Tangier disease who presented with severe anaemia secondary to a spontaneous splenic haematoma. He underwent elective splenectomy without haemorrhage and his thrombocytopaenia resolved with a platelet count rising from 97 to 560
×
10
9/L. Macroscopically, the resected spleen was enlarged with evidence of splenic haematoma. Histologic analysis of sections of spleen revealed lipid histiocytosis consistent with the diagnosis of Tangier disease. DNA sequence analysis revealed the subject to be a homozygote for a novel
ABCA1 mutation c.4121C
>
T, which changes arginine 1270 to a stop codon (R1270X). In conclusion, we describe a case of Tangier disease in association with an unrecognised bleeding tendency, in a man homozygous for a novel
ABCA1 gene mutation, R1270X.
Acute cholecystitis is increasingly managed by laparoscopic cholecystectomy. Some reports have shown conversion and complication rates that are increased in comparison to elective laparoscopic ...cholecystectomy. This study reviews the combined experience of two hospitals where the intention was to perform early laparoscopic cholecystectomy for acute cholecystitis. A total of 152 cases of laparoscopic cholecystectomy for acute cholecystitis (evidence of acute inflammation clinically and pathologically) were identified. Conversion to open cholecystectomy was required in 14 cases (9%) in the total series. Laparoscopic cholecystectomy was performed within 2 days of admission in 76% (115 of 152) of patients. Conversion was significantly less likely in patients undergoing laparoscopic cholecystectomy within 2 days of admission (4 of 115) compared to those undergoing surgery beyond 2 days (10 of 37;
P <0.0001). Eleven patients (7%) had postoperative complications; however, there were no cases of injury to the biliary system and no perioperative deaths. This series shows that laparoscopic cholecystectomy can be performed safely in patients with acute cholecystitis and suggests that early laparoscopic cholecystectomy is preferable to delaying surgery. Although the conversion rate to open surgery is higher than for elective cholecystectomy, the majority of patients (91%) still derive the well-recognized benefits of laparoscopic cholecystectomy. Early laparoscopic cholecystectomy is an acceptable approach to acute cholecystitis for the experienced laparoscopic surgeon.
It is unclear whether breast cancer has a similar prognosis in males and females.
A 20-year retrospective study of all male breast cancer patients in our region was undertaken. We compared this ...series with a group of females matched for the major prognostic factors and an unmatched series of female patients treated over the same period.
Forty-one patients with invasive cancer and 2 with ductal carcinoma in situ were identified. One invasive cancer was treated with radiotherapy, 40 had surgery. Local recurrence occurred in 23% and axillary recurrence in 40% of cases. Male and female patients (n = 123) matched for the major prognostic factors showed a similar outcome for disease-free interval (P = 0.90) and survival (P = 0.27). However, both the above groups had a significantly worse outcome than the unmatched series of female patients with breast cancer.
When prognostic factors are allowed for, male and female breast cancer patients have a similar outcome. This suggests that such features should be taken into account when determining management for males with breast cancer just as they are in females.
Pre-treatment oestrogen receptor (ER) expression in breast cancer predicts for rate of response to endocrine therapy but not for the quality or duration of response (DofR). ER is known to be ...down-regulated by anti-oestrogens. This study has tested the hypothesis that the degree of down-regulation of ER and the ER-regulated marker bcl-2 are associated with the quality and duration of tamoxifen response. 80 patients with ER+ve breast cancer (H-score > 10) receiving primary tamoxifen (n = 51 Stage I-II elderly; n = 29 Stage III) underwent sequential tumour biopsies for immunocytochemical assessment of ER, bcl-2 and the proliferation marker MIB1. Median follow-up is 45 months. By 6-months on therapy three patients had attained complete response (CR), 27 partial response (PR); 44 static disease (SD) and six progression (PD) by UICC criteria. Greater decrease in ER and bcl-2 H-score from pre-treatment to 6 weeks (p = 0.035, p = 0.037) and ER and bcl-2 H-score from pre-treatment to 6 months (p = 0.058, p = 0.036) were significantly associated with better quality of response (CR/PR vs SD/PD). Greater 6-week and 6-month reduction in bcl-2 H-score (p = 0.041, p = 0.036) and 6-week reduction in MIB1 (p = 0.013) were significantly correlated with longer DofR. This study demonstrates that greater down-regulation of ER and the ER-regulated protein bcl-2 on primary tamoxifen are significantly associated with a better quality of response and bcl-2 and the proliferation marker MIB1 a longer duration of response in ER+ve breast cancer.
Multiple papillomas (MP) are subject to debate in terms of their clinical and pathological significance and management. To date the ideal management is still not well established. The Royal Perth ...Hospital Multidisciplinary Breast Service has prospectively accrued clinical and pathological data on over 9000 patients since 1994. The database was interrogated and all pathology reports retrospectively reviewed. A total of 23 cases with the diagnosis of MP were retrieved from the database between 1994 and 2004. Of these 23 cases, 13 (56.5%) were diagnosed by core biopsy, nine (39.1%) on excision biopsy, and one (4.4%) on a mastectomy specimen.
The average age of patients was 56.4 years (range 44–74 years). The average duration of follow up is 4.1 years (range 1–10 years). In our series a close association with malignancy was noted for MP, which was also associated with a spectrum of proliferative breast disease. Contemporary guidelines should be developed for this controversial condition. We recommend that all patients with MP, especially when associated with atypia, undergo wide excision of the lesion with clear margins of at least 10
mm and that these patients be monitored closely with annual imaging.
Aims: To assess the feasibility of a standardized multidisciplinary protocol for the management of locally advanced breast cancer (LABC). We also evaluated the accuracy of magnetic resonance imaging ...(MRI) and positron emission tomography (PET) in predicting the extent of residual disease.
Methods: Patients with LABC were offered preoperative chemotherapy of docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 (TAC), every 21 days for six cycles, until progression or intolerable toxicity. MRI and PET were performed at baseline and six cycles. Patients underwent a mastectomy or complete local excision, followed by radiotherapy. Trastuzumab and endocrine treatment were recommended where appropriate.
Results: Between April 2005 and October 2006, 51 patients were included from three institutions, and 50 received TAC (90% commenced within 35 days of diagnosis), with 44 patients completing six cycles (88%). Pathological complete response was seen in 10 patients (19.6%); all had invasive ductal carcinoma. No patient with invasive lobular carcinoma achieved pathological complete response. MRI was the most accurate method of assessing the extent of residual cancer. In total, 45 (88%) patients underwent surgery within the protocol‐specified time and 12 (23%) patients had breast conservation surgery. At a median follow‐up of 41.3 months, there were three local recurrences. Ten patients (19.6%) developed distant metastases, resulting in an 80% actuarial disease‐free survival.
Conclusion: This regimen of TAC is effective and well‐tolerated and is likely to result in improved outcomes since patients can receive optimal multimodality treatments.
The tissue expression of c-erbB-2 protein in breast cancer is a marker of poor prognosis in a number of studies. More recently it has also been suggested that c-erbB-2 expression may predict response ...to systemic therapy in patients with advanced breast cancer. The measurement of c-erbB-2 protein in the serum of breast cancer patients has now been reported, but the significance of this finding is not clear. In this study an ELISA assay was used to measure c-erbB-2 in the sera of 23 normal controls, 46 benign breast disease patients, and 119 breast cancer patients. Elevated serum c-erbB-2 protein levels were detected in 13% (3/23) of normal controls, 15% (7/46) of benign disease patients, 15% (7/46) of Stage I/II patients, 26% (9/35) of Stage III patients, and 21% (8/38) of Stage IV patients. The tissue expression of the c-erbB-2 protein showed no association with detection of the serum c-erbB-2 protein (p = 0.31). In the 67 Stage III and IV patients who had assessable disease the presence of the c-erbB-2 protein in the serum bore no relationship to response to hormonal therapy (p = 0.71). Serum detection of the c-erbB-2 protein in Stage I/II patients predicted for a worsening of both survival outcome (p = 0.002) and disease free interval (p = 0.002). A worse outcome was also seen for the Stage III patients (p = 0.04) and Stage IV patients, although the latter did not reach statistical significance (p = 0.27). This study found that the presence of c-erbB-2 in the serum of breast cancer patients was of prognostic significance for all stages of disease.
male breast cancer is uncommon and studies regarding the potential clinical relevance of the histopathological and immunohistochemical features are infrequently reported.
We investigated the ...biological characteristics of forty-one male patients with invasive breast cancer by assessing histopathological and multiple immunohistochemical features.
The majority were no special type (ductal) (37/41), lobular cancer was not seen. 73% were histological grade 3, 93% were positive for oestrogen receptor and 73% for progesterone receptor. The proportion of cancers positive for c-ebB-2 (45%), EGFR (20%), p53 (58%), MiB1 (40%), NCRC11 (78%), were similar to reports for female breast cancer. Nonsignificant associations between poor survival outcome and grade 3 tumours, and positive tissue staining for MiB1 and p53 were seen.
While there ar similarities in the biological features of breast cancer in males and females, some differences were identified. Male breast cancer is more likely to be grade 3 tumours and hormone receptor positive.
