The gene CDC73 (previously known as HRPT2) encodes the protein parafibromin. Biallelic mutation of CDC73 is strongly associated with malignancy in parathyroid tumors. Heterozygous germline mutations ...cause hyperparathyroidism jaw tumor syndrome,which is associated with a high life-time risk of parathyroid carcinoma. Therefore loss of parafibromin expression by immunohistochemistry may triage genetic testing for hyperparathyroidism jaw tumor syndrome and be associated with malignant behavior in atypical parathyroid tumors. We share our experience that parafibromin-negative parathyroid tumors show distinctive morphology. We searched our institutional database for parathyroid tumors demonstrating complete loss of nuclear expression of parafibromin with internal positive controls. Forty-three parafibromin-negative tumors from 40 (5.1%) of 789 patients undergoing immunohistochemistry were identified. Thirty-three (77%) were external consultation cases; the estimated incidence in unselected tumors was 0.19%. Sixteen (37.2%) fulfilled World Health Organization 2017 criteria for parathyroid carcinoma and 63% had serum calcium greater than 3mmol/L. One of 27 (3.7%) noninvasive but parafibromin-negative tumors subsequently metastasized. Parafibromin-negative patients were younger (mean, 36 vs. 63 y; P<0.001) and had larger tumors (mean, 3.04 vs. 0.62 g; P<0.001). Not all patients had full testing, but 26 patients had pathogenic CDC73 mutation/deletions confirmed in tumor (n=23) and/or germline (n=16). Parafibromin-negative tumors demonstrated distinctive morphology including extensive sheet-like rather than acinar growth, eosinophilic cytoplasm, nuclear enlargement with distinctive coarse chromatin, perinuclear cytoplasmic clearing, a prominent arborizing vasculature, and, frequently, a thick capsule. Microcystic change was found in 21 (48.8%). In conclusion, there are previously unrecognized morphologic clues to parafibromin loss/CDC73 mutation in parathyroid tumors which, given the association with malignancy and syndromic disease, are important to recognize.
To examine the relation of visual function to retinal nerve fiber layer (RNFL) thickness as a structural biomarker for axonal loss in multiple sclerosis (MS), and to compare RNFL thickness among MS ...eyes with a history of acute optic neuritis (MS ON eyes), MS eyes without an optic neuritis history (MS non-ON eyes), and disease-free control eyes.
Cross-sectional study.
Patients with MS (n = 90; 180 eyes) and disease-free controls (n = 36; 72 eyes).
Retinal never fiber layer thickness was measured using optical coherence tomography (OCT; fast RNFL thickness software protocol). Vision testing was performed for each eye and binocularly before OCT scanning using measures previously shown to capture dysfunction in MS patients: (1) low-contrast letter acuity (Sloan charts, 2.5% and 1.25% contrast levels at 2 m) and (2) contrast sensitivity (Pelli-Robson chart at 1 m). Visual acuity (retroilluminated Early Treatment Diabetic Retinopathy charts at 3.2 m) was also measured, and protocol refractions were performed.
Retinal nerve fiber layer thickness measured by OCT, and visual function test results.
Although median Snellen acuity equivalents were better than 20/20 in both groups, RNFL thickness was reduced significantly among eyes of MS patients (92 mum) versus controls (105 mum) (P<0.001) and particularly was reduced in MS ON eyes (85 mum; P<0.001; accounting for age and adjusting for within-patient intereye correlations). Lower visual function scores were associated with reduced average overall RNFL thickness in MS eyes; for every 1-line decrease in low-contrast letter acuity or contrast sensitivity score, the mean RNFL thickness decreased by 4 mum.
Scores for low-contrast letter acuity and contrast sensitivity correlate well with RNFL thickness as a structural biomarker, supporting validity for these visual function tests as secondary clinical outcome measures for MS trials. These results also suggest a role for ocular imaging techniques such as OCT in trials that examine neuroprotective and other disease-modifying therapies. Although eyes with a history of acute optic neuritis demonstrate the greatest reductions in RNFL thickness, MS non-ON eyes have less RNFL thickness than controls, suggesting the occurrence of chronic axonal loss separate from acute attacks in MS patients.
Purpose
Targeted axillary dissection (TAD) for the axillary staging of clinically node-positive (cN +) breast cancer patients converting to clinically node negative post neoadjuvant chemotherapy ...(NAC), has gained popularity due to its minimal false negative rate and low arm morbidity. The aim of this study is to shed more light on the variation in the clinical practice globally in terms of indications and perceived limitations of TAD.
Methods
A panel of expert breast surgeons constructed a structured questionnaire comprising of 18 questions and asked surgeons worldwide for their opinions and routine practice on TAD. The questionnaire was electronically distributed and answers were collected between May 1st and August 1st 2022.
Results
Responses included 137 entries from 36 countries. Of them, 73.7% consider TAD for cN + patients planned to receive NAC. Among them, the greatest number of respondents (45%) perform the procedure for tumours up to T3, whereas 27% regardless of T-stage. The majority (42%) perform TAD on patients with 1–3 positive nodes and only 30% consider TAD when matted nodes are present. HER2 positive and Triple Negative subtypes are more likely to undergo TAD than Luminal A and B (86%, 79.1%, 39.5%, and 62.8%, respectively). Maximum acceptable lymph node burden is median 3 nodes for any subtype with a tendency to accept more positive nodes for Triple Negative.
Conclusion
This study demonstrates the differences in current practice regarding TAD as well as the fact that the biology of the tumour heavily affects the method of axillary staging.
Background: Current surgical treatment modalities for breast cancer include breast conserving surgery, mastectomy alone and mastectomy with breast reconstruction. There are recognized benefits of ...breast conservation and breast reconstruction over mastectomy but there are few studies assessing this area in Australia. The aim of the present study was to compare the various surgical strategies for breast cancer treatment in terms of quality of life, cosmesis and patient satisfaction.
Methods: A chart analysis was conducted of all patients who underwent Breast Cancer Reconstruction at the Royal Adelaide Hospital Breast Unit between 1990 and 2002. Patients were then traced and asked to take part in an interview. Mastectomy and breast conservation patients who attended outpatient clinic for follow up were also approached. All three groups were interviewed and self‐assessment quality of life questionnaires (Functional Assessment of Cancer Therapy−Breast, body image) were administered. The breast conservation and reconstruction groups also underwent assessment of satisfaction and cosmesis.
Results: A total of 78 mastectomy, 109 breast conservation and 123 breast reconstruction patients were interviewed. Quality of life assessment was similar between the three groups but the breast conservation and reconstruction patients’ body image scores were superior to the mastectomy group. Patient satisfaction was higher in the reconstruction group than the breast conservation group of patients, while cosmesis was similar.
Conclusion: While little difference was seen on quality of life assessment, body image is improved with the use of breast conservation and reconstruction. The high satisfaction and cosmesis scores in the breast reconstruction group are an indication of the superior results that can be achieved with breast reconstruction.
We report our experience about carotid artery stenting (CAS) in patients 80 years and older.
Out of 582 patients who underwent CAS at our institution from January 1999 to June 2010, 102 patients ...(group A) were 80 years or older. The clinical data of these patients were retrospectively reviewed, outcomes analyzed, and compared with those of younger patients who underwent CAS during the same period (group B).
Outcomes of group B were similar to those of group A, both at 30 days and at long term. Male gender, symptoms, and not using an embolic protection device were related to long-term complications in both groups. Occurrence of bradycardia/asystole during CAS was a risk factor for long-term myocardial infarction for group A only.
CAS can be safely performed in patients 80 years or older, with results that compare favorably to those of younger patients.
Background: Mastectomy is often recommended to women with early breast cancer who have large tumours or where the breast volume requiring resection to achieve adequate tumour clearance is too great ...to allow for a satisfactory cosmetic result after breast conservation surgery. The use of a latissimus dorsi muscular flap (latissimus dorsi miniflap (LDMF)) to replace the volume loss after major breast sector resection is an option where the tumour to breast volume ratio is large. The present study describes the technique and evaluates the experience of the LDMF at Royal Adelaide Hospital, Adelaide, Australia.
Methods: Between August 1997 and April 2002, 18 women aged 37–64 years underwent wide local excision for primary breast cancer with LDMF reconstruction. Tumour characteristics, breast specimen weight and postoperative sequelae were assessed. Quality of life measurements and objective assessments of aesthetic outcome were evaluated.
Results: Tumour diameter ranged from 13 to 80 mm (median 30 mm). Nine patients had multifocal or extensive intraductal component positive tumours. The weight of the resected specimens ranged from 75 to 395 g (median 130 g). There were no major postoperative complications, with a range of inpatient stay of 3–10 days. Seromas were aspirated in 14 patients but did not delay adjuvant treatment. Quality of Life results showed high patient satisfaction in all but one patient. A satisfactory cosmetic result was achieved in all but one patient who subsequently required mastectomy.
Conclusion: The LDMF procedure allows breast conservation to be achieved in women with large tumour to breast volume ratios, with satisfactory resection margins and good cosmetic and functional results. In the present experience standard oncological adjuvant treatment is not compromised.
Background: Breast reconstruction is an integral part of the surgical management of women with breast cancer. It is often performed by plastic surgeons but, in some centres, it is performed by ...breast surgeons trained in breast reconstruction and oncoplastic surgery. We evaluated the objective and subjective outcomes of reconstruction for breast cancer at the Royal Adelaide Hospital Breast Unit (Adelaide, Australia) between 1990 and June 2002.
Methods: A chart analysis was conducted of all patients who underwent breast cancer reconstruction at the Royal Adelaide Hospital Breast Unit with analysis of type of reconstruction and complications. Patients were interviewed and self‐assessment quality of life questionnaires (FACT‐B, body image), and overall satisfaction with reconstruction using an analogue scale were performed. Three observers carried out photographic analysis of the reconstructions. A comparison was then made between the different forms of reconstruction used.
Results: One hundred and ninety‐two patients underwent a total of 219 breast reconstructions during this period. The reconstructions included 18 latissimus dorsi mini flaps, 83 tissue expander/implants, 43 latissimus dorsi flaps and 75 TRAM flaps. There were no perioperative deaths. Significant systemic complications occurred in four patients (2%). Significant implant related complications occurred in four patients (3.2% of patients with implants). Total flap loss occurred in four patients (2.9% of flaps). One hundred and twenty‐three patients were able to be contacted and completed the questionnaires. Overall 77% of patients were highly satisfied with breast reconstruction and 82% scored a satisfactory result on photographic analysis. All four forms of reconstruction rated highly with respect to quality of life, body image, patient satisfaction and photographic assessment.
Conclusions: Breast reconstruction undertaken by breast surgeons trained in breast reconstruction and oncoplastic techniques has been performed with an acceptable rate of complications and a high level of patient satisfaction. Satisfaction with breast reconstruction was similar across the four methods of reconstruction used.
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