The new era of prostate-specific membrane antigen-directed immunotherapies and beyond in advanced prostate cancer: a review.

The lack of success in prostate cancer from immune checkpoint inhibitors, which is likely multifactorial, has led to the development and investigation of a number of other novel immunotherapeutic techniques, including antibody-drug conjugates, T-cell redirected bispecific therapies, cancer vaccines and chimeric antigen receptor T-cell therapies. Prostate-specific membrane antigen (PSMA) is a tumour-associated antigen (TAA) that is highly expressed in metastatic prostate cancer and has been validated as an effective target for radionuclide treatment. But while PSMA has thus far been the 'front runner' target for these novel immunotherapeutic techniques, it may not be the ideal target for immunotherapy and there are other potential targetable TAAs that will require further exploration. This review will focus on these various PSMA-directed therapies, as well as other potential targets for immunotherapy beyond PSMA.

Genetics of testicular cancer: a review.

PURPOSE OF REVIEW: Testicular germ cell tumours (TGCTs) are the most common solid malignant cancer diagnosed in young males and the incidence is increasing. Understanding the genetic basis of this disease will help us to navigate the challenges of early detection, diagnosis, treatment, surveillance, and long-term outcomes for patients. RECENT FINDINGS: TGCTs are highly heritable. Current understanding of germline risk includes the identification of one moderate-penetrance predisposition gene, checkpoint kinase 2 ( CHEK2 ), and 78 low-to-moderate-risk single nucleotide polymorphisms identified in genome-wide-associated studies, which account for 44% of familial risk. Biomarker research in TGCTs has been challenging for multiple reasons: oncogenesis is complex, actionable mutations are uncommon, clonal evolution unpredictable and tumours can be histologically and molecularly heterogeneous. Three somatic mutations have thus far been identified by DNA exome sequencing, exclusively in seminomas: KIT, KRAS and NRAS . Several genetic markers appear to be associated with risk of TGCT and treatment resistance. TP53 mutations appear to be associated with platinum resistance. MicroRNA expression may be a useful biomarker of residual disease and relapse in future. SUMMARY: The biology of testicular germ cells tumours is complex, and further research is needed to fully explain the high heritability of these cancers, as well as the molecular signatures which may drive their biological behaviour.

Healthcare Professionals' Views of Working with Medical Interpreters in a Cancer Setting: an Exploratory Study.

Australia, like many other nations, continues to become more culturally and linguistically diverse. Medical interpreters play a key role in bridging the linguistic gap between healthcare professionals (HCPs) and patients. Little research exists from the HCP's perspective about working with interpreters. This study aimed to explore the views of HCPs regarding working with interpreters in a cancer setting. This exploratory study utilised a cross-sectional, qualitative design, involving focus groups and semi-structured interviews. HCPs from the Oncology and Palliative Care units were invited to participate and were asked about their experiences of working with interpreters in a cancer setting. Interviews were audio-recorded and transcribed. An inductive thematic analysis of qualitative data derived an understanding of attitudes and beliefs which may affect the way in which HCPs interact with interpreters and patients. Twenty-five participants were recruited. Five key themes emerged from the data: (1) communication practices and preferences, (2) training and supports, (3) alternative methods for translation, (4) challenges faced by HCPs and interpreters, and (5) limitations of translation. Communication with non-English-speaking patients using interpreters could be significantly improved with further training and support for both HCPs and interpreters, and a greater appreciation for the challenges each party faces.

Simple water-based tacrolimus enemas for refractory proctitis.

BACKGROUND AND AIMS: Rectal ulcerative colitis (UC) and Crohn's disease (CD) often do not respond to conventional therapies. Oral and suppository tacrolimus are effective but often poorly tolerated or are complex to formulate. Tacrolimus is topically active, water soluble, and has minimal systemic toxicity when administered rectally; we therefore tested a simple tap water-based enema formulation. METHODS: Tacrolimus powder from 1 mg capsules and tap water in a 60 mL syringe were delivered rectally. The primary end-point was endoscopic response (UC: MAYO score reduction by one point; CD: improvement in ulcer number and severity). Secondary end-points included endoscopic remission, clinical response, stool frequency, and rectal bleeding. RESULTS: Seventeen patients [12 UC, five CD, nine female, median age 31 years] with refractory rectal disease were treated. The majority of patients had failed immunosuppressive therapy [88% thiopurine; 71% biologic therapy]. Initial enemas included 1-4 mg tacrolimus daily and 1-3 mg tacrolimus maintenance three times a week for a median of 20 weeks (range 3-204). Concomitant thiopurine or biologic therapy continued. 94% tolerated therapy. Of 12 UC patients, eight (67%) achieved endoscopic remission, one further patient achieved endoscopic response, and median partial MAYO scores decreased (pre:4 vs. post:2; P = 0.010). Of five CD patients, three (60%) achieved endoscopic response, two (40%) endoscopic remission, and three (60%) clinical response. Stool frequency, rectal bleeding, and C-reactive protein levels improved. Strictures became endoscopically passable in all four affected patients. No major adverse events were reported, and four patients had disease flare. CONCLUSIONS: Tacrolimus enemas are easy to prepare, well tolerated, effective, and safe. They should be included in the treatment armamentarium for inflammatory bowel disease-related refractory proctitis.

Idiopathic myointimal hyperplasia of the mesenteric veins: Case report and review of the literature.

In 1991, Genta and Haggitt described four patients with segmental ischemic colitis caused by idiopathic myointimal hyperplasia in the small mesenteric veins (IMHMV). There are now 33 published cases of IMHMV in the literature; however, this condition is still sufficiently rare that it poses a diagnostic challenge to pathologists and clinicians and is often clinically or histologically confused with inflammatory bowel disease (IBD) or ischemic colitis. IMHMV is characterized by intimal smooth muscle hyperplasia resulting in thickened small and medium-sized mesenteric veins (with arterial sparing). Clinically, it presents with symptoms that mimic IBD, such as bloody diarrhea, abdominal pain, and weight loss. Surgical resection appears to be curative. The present case describes a 63-year-old Vietnamese man with cardiovascular risk factors who was diagnosed with IMHMV after many months of severe symptoms. A review of the current literature follows the case report.

The Anorexia Nervosa Genetics Initiative (ANGI): Overview and methods.

BACKGROUND: Genetic factors contribute to anorexia nervosa (AN); and the first genome-wide significant locus has been identified. We describe methods and procedures for the Anorexia Nervosa Genetics Initiative (ANGI), an international collaboration designed to rapidly recruit 13,000 individuals with AN and ancestrally matched controls. We present sample characteristics and the utility of an online eating disorder diagnostic questionnaire suitable for large-scale genetic and population research. METHODS: ANGI recruited from the United States (US), Australia/New Zealand (ANZ), Sweden (SE), and Denmark (DK). Recruitment was via national registers (SE, DK); treatment centers (US, ANZ, SE, DK); and social and traditional media (US, ANZ, SE). All cases had a lifetime AN diagnosis based on DSM-IV or ICD-10 criteria (excluding amenorrhea). Recruited controls had no lifetime history of disordered eating behaviors. To assess the positive and negative predictive validity of the online eating disorder questionnaire (ED100K-v1), 109 women also completed the Structured Clinical Interview for DSM-IV (SCID), Module H. RESULTS: Blood samples and clinical information were collected from 13,363 individuals with lifetime AN and from controls. Online diagnostic phenotyping was effective and efficient; the validity of the questionnaire was acceptable. CONCLUSIONS: Our multi-pronged recruitment approach was highly effective for rapid recruitment and can be used as a model for efforts by other groups. High online presence of individuals with AN rendered the Internet/social media a remarkably effective recruitment tool in some countries. ANGI has substantially augmented Psychiatric Genomics Consortium AN sample collection. ANGI is a registered clinical trial: clinicaltrials.govNCT01916538; https://clinicaltrials.gov/ct2/show/NCT01916538?cond=Anorexia+Nervosa&draw=1&rank=3.

The Anorexia Nervosa Genetics Initiative: Study description and sample characteristics of the Australian and New Zealand arm.

OBJECTIVES: Anorexia nervosa is a severe psychiatric disorder with high mortality rates. While its aetiology is poorly understood, there is evidence of a significant genetic component. The Anorexia Nervosa Genetics Initiative is an international collaboration which aims to understand the genetic basis of the disorder. This paper describes the recruitment and characteristics of the Australasian Anorexia Nervosa Genetics Initiative sample, the largest sample of individuals with anorexia nervosa ever assembled across Australia and New Zealand. METHODS: Participants completed an online questionnaire based on the Structured Clinical Interview Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) eating disorders section. Participants who met specified case criteria for lifetime anorexia nervosa were requested to provide a DNA sample for genetic analysis. RESULTS: Overall, the study recruited 3414 Australians and 543 New Zealanders meeting the lifetime anorexia nervosa case criteria by using a variety of conventional and social media recruitment methods. At the time of questionnaire completion, 28% had a body mass index ⩽ 18.5 kg/m2. Fasting and exercise were the most commonly employed methods of weight control, and were associated with the youngest reported ages of onset. At the time of the study, 32% of participants meeting lifetime anorexia nervosa case criteria were under the care of a medical practitioner; those with current body mass index < 18.5 kg/m2 were more likely to be currently receiving medical care (56%) than those with current body mass index ⩾ 18.5 kg/m2 (23%). Professional treatment for eating disorders was most likely to have been received from general practitioners (45% of study participants), dietitians (42%) and outpatient programmes (42%). CONCLUSIONS: This study was effective in assembling the largest community sample of people with lifetime anorexia nervosa in Australia and New Zealand to date. The proportion of people with anorexia nervosa currently receiving medical care, and the most common sources of treatment accessed, indicates the importance of training for general practitioners and dietitians in treating anorexia nervosa.