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Sarcoma is a rare and complex disease comprising over 80 malignant subtypes that is frequently characterized by poor prognosis. Challenges in clinical management include uncertainties in diagnosis and disease classification, limited prognostic and predictive biomarkers, incompletely understood disease heterogeneity among and within subtypes, lack of effective treatment options, and limited progress in identifying new drug targets and novel therapeutics. Proteomics refers to the study of the entire complement of proteins expressed in specific cells or tissues. Advances in proteomics have included the development of quantitative mass spectrometry (MS)-based technologies which enable analysis of large numbers of proteins with relatively high throughput, enabling proteomics to be studied on a scale that has not previously been possible. Cellular function is determined by the levels of various proteins and their interactions, so proteomics offers the possibility of new insights into cancer biology. Sarcoma proteomics therefore has the potential to address some of the key current challenges described above, but it is still in its infancy. This review covers key quantitative proteomic sarcoma studies with findings that pertain to clinical utility. Proteomic methodologies that have been applied to human sarcoma research are briefly described, including recent advances in MS-based proteomic technology. We highlight studies that illustrate how proteomics may aid diagnosis and improve disease classification by distinguishing sarcoma histologies and identify distinct profiles within histological subtypes which may aid understanding of disease heterogeneity. We also review studies where proteomics has been applied to identify prognostic, predictive and therapeutic biomarkers. These studies traverse a range of histological subtypes including chordoma, Ewing sarcoma, gastrointestinal stromal tumors, leiomyosarcoma, liposarcoma, malignant peripheral nerve sheath tumors, myxofibrosarcoma, rhabdomyosarcoma, synovial sarcoma, osteosarcoma, and undifferentiated pleomorphic sarcoma. Critical questions and unmet needs in sarcoma which can potentially be addressed with proteomics are outlined. [ABSTRACT FROM AUTHOR]

An interdisciplinary team-taught course used a life-course approach to human development. Teaching strategies included elder reminiscence, life histories, and case studies. It is designed to prepare various health care professions for future roles on multidisciplinary team. (Contains 26 references.) (SK)

Background: Mesenchymal chondrosarcoma (MCS) is an ultra‐rare sarcoma that follows a more aggressive course than conventional chondrosarcoma. This study evaluates prognostic factors, treatments (surgery, chemotherapy, and radiation), and outcomes in an Australian setting. Methods: We collected demographics, clinicopathological variables, treatment characteristics, and survival status from patients with MCS registered on the national ACCORD sarcoma database. Outcomes include overall survival (OS) and progression‐free survival (PFS). Results: We identified 22 patients with MCS between 2001–2022. Median age was 28 (range 10–59) years, 19 (86%) had localised disease at diagnosis of whom 16 had surgery (84%), 11 received radiation (58%), and 10 chemotherapy (53%). Ten (52%) developed recurrence and/or metastases on follow‐up and three patients with initial metastatic disease received surgery, radiation, and chemotherapy. At a median follow‐up of 50.9 (range 0.4–210) months nine patients had died. The median OS was 104.1 months (95% CI 25.8–182.3). There was improved OS for patients with localised disease who had surgical resection of the primary (p = 0.003) and those with ECOG 0–1 compared to 2–3 (p = 0.023) on univariate analysis. Conclusions: This study demonstrates contemporary Australian treatment patterns of MCS. The role of chemotherapy for localised disease remains uncertain. Understanding treatment patterns and outcomes help support treatment decisions and design of trials for novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

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. Contexte : La ductoscopie mammaire permet une visualisation directe de l'epithelium des canaux a l'aide d'un microendoscope a fibres optiques. En tant que premier centre au Canada a appliquer la ductoscopie a la pratique chirurgicale, nous faisons etat de l'experience que nous avons acquise avec cette technologie. Methodes : Entre 2004 et 2008, 65 femmes presentant un ecoulement pathologique au niveau du mamelon ont subi une ductoscopie avant une excision canalaire chirurgicale sous anesthesie generale. La collecte prospective des donnees a inclus les taux de canulation et de complications, la duree de l'intervention et le taux de visualisation des lesions, comparativement a la ductographie preoperatoire, le cas echeant. De plus, nous avons classifie l'aspect a l'endoscopie selon les criteres de Makita et coll. et nous avons etabli sa correlation avec la pathologie chirurgicale. Resultats : Il a fallu plus de six mois pour surmonter certains problemes techniques avant de pouvoir utiliser de routine la ductoscopie au bloc operatoire. Facile d'emploi, le ductoscope nous a permis d'effectuer avec succes la canulation de 63 canaux mammaires sur 66 (95%) et de visualiser une lesion dans 52 canaux mammaires sur 63 (83%). La duree moyenne de l'intervention a ete de 5,1 minutes, sans complications. Les lesions perceptibles a la ductographie s'observaient a l'endoscopie 30 fois sur 33 (91%). Les 3 neoplasies ont ete apercues : un carcinome envahissant dans 1 cas sur 62 (1,6%) et une maladie in situ dans 2 cas sur 62 (3,2%). Les chirurgiens ont trouve la ductoscopie utile pour determiner l'etendue de l'excision canalaire. A l'exception de la classe << solitaire et polypoide >> qui permettait de prevoir avec precision un papillome (23/23), nous avons observe une faible correlation entre la classification endoscopique de Makita et coll. et la pathologie finale. Conclusion : La ductoscopie est une intervention faisable, securitaire et pratique. Nos chirurgiens l'utilisent de routine pour localiser l'excision canalaire et en determiner l'ampleur, sans demander de ductographie preoperatoire. La reconnaissance de la pathologie a partir de l'aspect endoscopique est peu fiable, a moins que la lesion ne soit solitaire et polypoide., Pathologic nipple discharge is unilateral, persistent and spontaneous, and arises from a single duct. (1) Discharge of this type is responsible for up to 5% of consultations at breast clinics. [...]

Objective: To report treatment patterns and survival outcomes of patients with relapsed and refractory metastatic germ cell tumours (GCTs) treated with high‐dose chemotherapy (HDCT) and autologous stem‐cell transplantation in low‐volume specialized centres within the widely dispersed populations of Australia and New Zealand between 1999 and 2019. Patients and Methods: We conducted a retrospective analysis of 111 patients across 13 institutions. Patients were identified from the Australasian Bone Marrow Transplant Recipient Registry. We reviewed treatment regimens, survival outcomes, deliverability and toxicities. Primary endpoints included overall (OS) and progression‐free survival (PFS). Cox proportional hazards models were used to test the association of survival outcomes with patient and treatment factors. Results: The median (range) age was 30 (14–68) years and GCT histology was non‐seminomatous in 84% of patients. International Prognostic Factors Study Group (IPFSG) prognostic risk category was very low/low, intermediate, high and very high in 18%, 36%, 25% and 21% of patients, respectively. Salvage conventional‐dose chemotherapy (CDCT) was administered prior to HDCT in 59% of patients. Regimens included paclitaxel, ifosfamide, carboplatin and etoposide (50%), carboplatin and etoposide (CE; 28%), carboplatin, etoposide and ifosfamide (CEI; 6%), carboplatin, etoposide and cyclophosphamide (CEC; 5%), CEC‐paclitaxel (6%) and other (5%). With a median follow‐up of 4.4 years, the 1‐, 2‐ and 5‐year PFS rates were 62%, 57% and 52%, respectively, and OS rates were 73%, 65% and 61%, respectively. There were five treatment‐related deaths. Progression on treatment occurred in 17%. In a univariable analysis, worse International Germ Cell Cancer Collaborative Group (IGCCCG) and IPFSG prognostic groups were associated with inferior survival outcomes. An association of inferior survival was not found with the number of high‐dose cycles received nor when HDCT was delivered after salvage CDCT. Conclusion: This large dual‐national registry‐based study reinforces the efficacy and deliverability of HDCT for relapsed and refractory metastatic GCT in low‐volume specialized centres in Australia and New Zealand, with survival outcomes comparable to those found in international practice. [ABSTRACT FROM AUTHOR]

CIC‐rearranged sarcoma is a recently established, ultra‐rare, molecularly defined sarcoma subtype. We aimed to further characterise clinical features of CIC‐rearranged sarcomas and explore clinical management including systemic treatments and outcomes. Methods: A multi‐centre retrospective cohort study of patients diagnosed between 2014–2019. Results: Eighteen patients were identified. The median age was 27 years (range 13–56), 10 patients were male (56%), 11 patients (61%) had localised disease and 7 patients had advanced (metastatic or unresectable) disease at diagnosis. Of 11 patients with localised disease at diagnosis, median overall survival (OS) was 40.6 months and the 1‐, 2‐ and 5‐year OS estimates were 82%, 64% and 34% respectively. Nine patients (82%) underwent surgery (all had R0 resections), 8 (73%) patients received radiotherapy to the primary site (median dose 57Gy in 28 fractions), and 8 (73%) patients received chemotherapy (predominantly Ewing‐based regimens). Metastases developed in 55% with a median time to recurrence of 10.5 months. In patients with advanced disease at diagnosis, median OS was 12.6 months (95% CI 5.1–20.1), 1‐year OS was 57%. Median progression‐free survival was 5.8 months (95% CI 4.5–7.2). Durable systemic therapy responses occurred infrequently with a median duration of systemic treatment response of 2.1 months. One durable complete response of metastatic disease to VDC/IE chemotherapy was seen. Responses to pazopanib (n = 1) and pembrolizumab (n = 1) were not seen. Conclusion: In this series, CIC‐rearranged sarcomas affected young adults and had a high incidence of presenting with, or developing, metastatic disease. The prognosis overall was poor. In advanced disease, durable systemic therapy responses were infrequent. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most common paediatric and adolescent primary bone malignancy and is highly chemosensitive. Gastrointestinal metastases from osteosarcomas are rare. Bowel perforation secondary to chemotherapy is a potential serious complication reported in ovarian, colorectal and haematological malignancies. We report the first documented case of chemotherapy-mediated bowel perforation in an osteosarcoma patient with gastrointestinal metastases. A man in his 20s, with a history of resected osteosarcoma in remission, presented with abdominal pain. A computed tomography (CT) scan demonstrated a large calcified intrabdominal mass (15×13×9 cm) consistent with new peritoneal disease. After one cycle of palliative ifosfamide and etoposide chemotherapy, he developed a large bowel perforation and neutropenic sepsis consequently requiring resection of the perforated mass. Chemotherapy-induced bowel perforation is a rare but serious complication that should be considered in patients with osteosarcoma, and other chemosensitive malignancies, with intra-abdominal metastases. Recommencement of systemic therapies after bowel complications must be assessed cautiously on a case-bycase basis. [ABSTRACT FROM AUTHOR]

Antipsychotic medication use for nursing home residents with dementia poses major patient safety challenges. This article investigates health professionals' experiences with decision-making during changes under the National Partnership to Improve Dementia Care in Nursing Homes (National Partnership) and its companion state coalitions. These programs were introduced in 2012 to encourage reductions in antipsychotic use and increased use of nonpharmacological treatments for dementia. Interviews with 40 nursing home physicians and staff in seven states found that reducing antipsychotics is more time and resource-intensive than relying on medication, because it requires a person-centered approach. However, respondents supported reductions in antipsychotic use, and indicated that with sufficient staffing, effective communications, and training, they could create or implement individualized treatments. Their positive attitudes suggest that the National Partnership has been a catalyst in reducing antipsychotic medications, and their perspectives can inform further research, policy and practice in nursing homes toward achieving quality dementia care. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant therapy may increase the likelihood of complete (R0) resection for borderline resectable pancreatic cancer. The optimal approach is unknown and differs amongst treatment centres. Methods: We identified patients with biopsy-proven borderline resectable pancreatic adenocarcinoma who commenced neoadjuvant therapy between January 2012 and June 2019 at three centres in Sydney, Australia. Patterns of care and outcomes of varying approaches were examined. Results: Forty-eight patients were identified. Median age was 66 years (range: 41–84). Staging included endoscopic ultrasound in 98%, PET-CT scan in 77%, laparoscopy in 46%. Neoadjuvant regimens used were a combination of chemotherapy and chemo-radiation (58%), chemotherapy alone (13%) and chemoradiation alone (29%). Radiologic complete or partial response occurred in 33% and progression in 25%. Complete macroscopic surgical resection was achieved in 50%, and R0 resection in 38%. At median follow-up of 15 months, the 1-year and 2-year overall survival was 75% and 63% respectively, and the 1-year and 2-year progression-free survival was 50% and 29% respectively. Significant predictors of macroscopic resectability were radiologic response (p = 0.005) but not addition of radiotherapy to chemotherapy (OR 0.87, p = 0.81). Predictors of overall survival included baseline Ca19.9 level (p = 0.04) and a trend to the use of systemic chemotherapy (HR 0.51, p = 0.07), but not use of radiotherapy (HR 0.70, p = 0.47). Conclusion: There is high variability in staging and neoadjuvant approaches for borderline resectable pancreas cancer. Despite aggressive neoadjuvant therapies, R0 resection and prolonged survival are uncommon. The incremental benefit of neoadjuvant radiotherapy after neoadjuvant chemotherapy was not demonstrated in this observational study. [ABSTRACT FROM AUTHOR]