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Biau D.J.,Hospital Cochin | Weiss K.R.,Shadyside Medical Center | Bhumbra R.S.,London Sarcoma Service | Davidson D.,University of Washington | And 6 more authors.
Clinical Orthopaedics and Related Research | Year: 2013

Background: Biopsies of musculoskeletal tumors lead to alterations in treatment in almost 20% of cases. Control charts are useful to ensure that a process is operating at a predetermined level of performance, although their use has not been demonstrated in assessing the adequacy of musculoskeletal biopsies. Questions/purposes: We therefore (1) assessed the incidence of and the reasons for inadequate musculoskeletal biopsies when following guidelines for performing the procedure; and (2) implemented a process control chart, the CUSUM test, to monitor the proportion of inadequate biopsies. Methods: We prospectively studied 116 incisional biopsies. The biopsy was performed according to 10 rules to (1) minimize contamination in the tissues surrounding the tumor; and (2) improve accuracy. A frozen section was systematically performed to confirm that a representative specimen was obtained. Procedures were considered inadequate if: (1) another biopsy was necessary; (2) the biopsy tract was not appropriately placed; and (3) the treatment provided based on the diagnosis from the biopsy was not appropriate. Results: Five (4.3%) of the 116 incisional biopsy procedures were considered failures. Three patients required a second repeat open biopsy and two were considered to receive inappropriate treatment. No alarm was raised by the control chart and the performance was deemed adequate over the monitoring period. Conclusions: The proportion of inadequate musculoskeletal open biopsies performed at a referral center was low. Using a statistical process control method to monitor the failures provided a continuous measure of the performance. © 2012 The Association of Bone and Joint Surgeons®.

Hoppo T.,Shadyside Medical Center | Badylak S.F.,University of Pittsburgh | Jobe B.A.,Shadyside Medical Center
World Journal of Surgery | Year: 2012

Background The optimal treatment strategy of esophageal high-grade dysplasia (HGD) and superficial adenocarcinoma remains controversial. Methods Here, we describe endoscopic, circumferential mucosal-submucosal en-bloc resection of the entire abnormal esophageal epithelium with extracellular matrix (ECM) placement to regenerate neoepithelium and minimize stricture. That procedure was then followed by a laparoscopic fundoplication as a novel esophageal-preserving approach to treat HGD and superficial adenocarcinoma in the face of chronic gastroesophageal reflux disease (GERD). Conclusions This approach could be an ideal option as an alternative to esophagectomy in selected patients. © Société Internationale de Chirurgie 2012.

Weiss K.R.,Mount Sinai Hospital | Weiss K.R.,Shadyside Medical Center | Bhumbra R.,Mount Sinai Hospital | Biau D.J.,Mount Sinai Hospital | And 9 more authors.
Journal of Bone and Joint Surgery - Series B | Year: 2011

Pathological fractures of the humerus are associated with pain, morbidity, loss of function and a diminished quality of life. We report our experience of stabilising these fractures using polymethylmethacrylate and non-locking plates. We undertook a retrospective review over 20 years of patients treated at a tertiary musculoskeletal oncology centre. Those who had undergone surgery for an impending or completed pathological humeral fracture with a diagnosis of metastatic disease or myeloma were identified from our database. There were 63 patients (43 men, 20 women) in the series with a mean age of 63 years (39 to 87). All had undergone intralesional curettage of the tumour followed by fixation with intramedullary polymethylmethacrylate and plating. Complications occurred in 14 patients (22.2%) and seven (11.1%) required re-operation. At the latest follow-up, 47 patients (74.6%) were deceased and 16 (25.4%) were living with a mean follow-up of 75 months (1 to 184). A total of 54 (86%) patients had no or mild pain and 50 (80%) required no or minimal assistance with activities of daily living. Of the 16 living patients none had pain and all could perform activities of daily living without assistance. Intralesional resection of the tumour, filling of the cavity with cement, and plate stabilisation of the pathological fracture gives immediate rigidity and allows an early return of function without the need for bony union. The patient's local disease burden is reduced, which may alleviate tumour-related pain and slow the progression of the disease. The cemented-plate technique provides a reliable option for the treatment of pathological fractures of the humerus. ©2011 British Editorial Society of Bone and Joint Surgery.

Dar J.A.,Shadyside Medical Center | Dar J.A.,King Saud University | Masoodi K.Z.,Shadyside Medical Center | Eisermann K.,Shadyside Medical Center | And 7 more authors.
Journal of Steroid Biochemistry and Molecular Biology | Year: 2014

Androgen-independent nuclear localization is required for androgen receptor (AR) transactivation in castration-resistant prostate cancer (CRPC) and should be a key step leading to castration resistance. However, mechanism(s) leading to androgen-independent AR nuclear localization are poorly understood. Since the N-terminal domain (NTD) of AR plays a role in transactivation under androgen-depleted conditions, we investigated the role of the NTD in AR nuclear localization in CRPC. Deletion mutagenesis was used to identify amino acid sequences in the NTD essential for its androgen-independent nuclear localization in C4-2, a widely used CRPC cell line. Deletion mutants of AR tagged with green fluorescent protein (GFP) at the 5′-end were generated and their signal distribution was investigated in C4-2 cells by fluorescent microscopy. Our results showed that the region of a.a. 294-556 was required for androgen-independent AR nuclear localization whereas a.a. 1-293 mediates Hsp90 regulation of AR nuclear localization in CRPC cells. Although the region of a.a. 294-556 does not contain a nuclear import signal, it was able to enhance DHT-induced import of the ligand binding domain (LBD). Also, transactivation of the NTD could be uncoupled from its modulation of AR nuclear localization in C4-2 cells. These observations suggest an important role of the NTD in AR intracellular trafficking and androgen-independent AR nuclear localization in CRPC cells. © 2014 Elsevier Ltd.

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