AimsLupus nephritis (LN) is common in systemic lupus erythematosus (SLE) and is associated with adverse renal outcomes and premature mortality. There is limited data examining LN outcomes in Aotearoa New Zealand and none examining outcomes since mycophenolate mofetil (MMF) became subsidised for use in class III/IV LN induction. We describe a cohort of adults with biopsy-confirmed LN over an 18-year period in two regions of Aotearoa New Zealand, including LN characteristics, treatment, and outcomes.MethodsCases were identified from laboratory databases and relevant data extracted from patient records. Response was defined per Kidney Disease, Improving Global Outcomes (KDIGO) with overall renal response (ORR) defined as at least partial response (PR). Outcomes among patients with class III/IV LN were explored by induction treatment and timing of MMF restrictions.ResultsOne hundred cases were identified, including 74 with class III/IV LN. Most (85/100) were women, living in urban areas (78%), with ethnicities including Māori (25%), Pacific (13%) and NZ European (38%). The median age at LN diagnosis was 38 years (range 18-74) and the median time between SLE diagnosis and renal biopsy was 2 years. In the MMF-restricted period, MMF was used for induction in class III/IV LN in 43% (12/28) of cases, and in 72% (33/46) of cases in the MMF-unrestricted period (p = .01). In the MMF-unrestricted period, use of high dose cyclophosphamide stopped (18% to 0%), complete response (CR) rates doubled (14% to 33%, p = .08) whereas rates of ORR did not show statistically significant change (39% to 50%, p = .37). At last-observed follow up (mean 7 years from biopsy) 26/74 (36% cases) had poor outcomes with no renal response.ConclusionIn this LN cohort in Aotearoa New Zealand, half of people with LN class III/IV do not achieve early renal response and over one-third have poor outcomes over less than a decade of follow up. Subsidy of MMF substantively increased its use and patients in this time period had better rates of good LN outcomes. These data suggest considerable unmet need for effective treatments for LN and that funding of effective medicine for LN increases their use and improves LN outcomes.

Introduction: Health informatics (HI) is the study and practice of technology used to improve the quality and efficiency of healthcare. Formal HI teaching lacks visibility in most Australasian medical schools. In this study, medical students collected data from their peers and recent graduates on the teaching and learning of HI to inform development of a needs-based integrated HI curriculum. Methods: This mixed-methods case study of our medical degree program used clinically relevant vignettes to explore student confidence and opinions on HI. Current HI learning was benchmarked against recommendations. Recent graduates from University of Otago Medical School participated in an online survey (n = 26), and five focus group interviews of final-year medical students (n = 17) were carried out by a peer student. Results: More than half of the participants surveyed felt confident in most HI topics, though many were less confident in telemedicine, evaluating electronic resources for patient use, data communication and data storage. Most students recalled learning some HI principles and agreed these should be integrated within their degree. Students highlighted that HI curriculum development should consider students’ self-identity as digital natives and the need for clinically situated, relevant and authentic learning to avoid tensions between theoretical HI concepts and clinical environments. Conclusion: Medical students are critical consumers of potential HI curriculum content and expressed clear preferences for clinically relevant and up-to-date HI content. Key challenges in developing an HI curriculum will be ensuring a student-centered, authentic, contemporary and future-focused curriculum, with relevance demonstrated to digital native students.

Incidence of endometrial cancer (EC) is rising in the developed world. The current standard of care, hysterectomy, is often infeasible for younger patients and those with high body mass index. There are limited non-surgical treatment options and a lack of biologically relevant research models to investigate novel alternatives to surgery for EC. The aim of the present study was to develop a long-term, patient-derived explant (PDE) model of early-stage EC and demonstrate its use for investigating predictive biomarkers for a current non-surgical treatment option, the levonorgestrel intra-uterine system (LNG-IUS). Fresh tumour specimens were obtained from patients with early-stage endometrioid EC. Tumours were cut into explants, cultured on media-soaked gelatin sponges for up to 21 days and treated with LNG. Formalin-fixed, paraffin embedded (FFPE) blocks were generated for each explant after 21 days in culture. Tumour architecture and integrity were assessed by haematoxylin and eosin (H&E) and immunohistochemistry (IHC). IHC was additionally performed for the expression of five candidate biomarkers of LNG resistance. The developed ex vivo PDE model is capable of culturing explants from early-stage EC tumours long-term (21 Days). This model can complement existing models and may serve as a tool to validate results obtained in higher-throughput in vitro studies. Our study provides the foundation to validate the extent to which EC PDEs reflect patient response in future research.

Bacillus Calmette-Guérin (BCG) treatment for non-muscle invasive bladder cancer (NMIBC) is an established immunotherapeutic, however, a significant portion of patients do not respond to treatment. Despite extensive research into the therapeutic mechanism of BCG, gaps remain in our understanding. This review specifically focuses on the epigenomic contributions in the immune microenvironment, in the context of BCG treatment for NMIBC. We also summarise the current understanding of NMIBC epigenetic characteristics, and discuss how future targeted strategies for BCG therapy should incorporate both epigenomic biomarkers in conjunction with genomic biomarkers.

Background: Learning anatomical pathology requires knowledge acquisition and visual pattern recognition for diagnostic assessment and reasoning, and clinical correlation. We are familiar with 20th century tools of learning: textbook reading, didactic lectures and apprenticeship. However, advances in the science of learning from cognitive psychology reveal many traditional teaching tools are ineffective. Also, 21st century trainees tell us textbook reading, note taking, and lectures are dull or difficult.

BackgroundCancer cell lines are invaluable model systems for biomedical research because they provide an almost unlimited supply of biological materials. However, there is considerable skepticism regarding the reproducibility of data derived from these in vitro models. Recent findingsChromosomal instability (CIN) is one of the primary issues associated with cell lines, which can cause genetic heterogeneity and unstable cell properties within a cell population. Many of these problems can be avoided with some precautions. Here we review the underlying causes of CIN, including merotelic attachment, telomere dysfunction, DNA damage response defects, mitotic checkpoint defects and cell cycle disturbances. ConclusionIn this review we summarize studies highlighting the consequences of CIN in various cell lines and provide suggestions on monitoring and controlling CIN during cell culture.

Purpose The aim of the study was to examine the validity evidence for the 19-item form of the MUSIC Model of Academic Motivation Inventory (College Student version) within health science schools in three different countries. The MUSIC Inventory includes five scales that assess the motivational climate by measuring students' perceptions related to five separate constructs: empowerment, usefulness, success, interest, and caring. Background The 26-item form of the MUSIC Inventory has been validated for use with undergraduate students and with students in professional schools, including students at a veterinary medicine school, a pharmacy school, and a medical school. A 19-item form of the MUSIC Inventory has also been validated for use with undergraduate students, but it has not yet been validated for use with medical school students. The purpose of this study was to provide validity evidence for the use of the 19-item form in heath science schools in three different countries to determine if this version is acceptable for use in different cultures. If validated, this shorter form of the MUSIC Inventory would provide more differentiation between the Interest and Usefulness scales and could reduce respondent fatigue. Methodology Cook et al's [1] practical guidelines were followed to implement Kane's [2] validity framework as a means to examine the evidence of validity through scoring inferences, generalization inferences, and extrapolation inferences. Students (n = 667) in health science schools within three countries were surveyed. Results The results produced evidence to support all five hypotheses related to scoring, generalization, and extrapolation inferences. Conclusions Scores from the 19-item form of the MUSIC Inventory are valid for use in health science courses within professional schools in different countries. Therefore, the MUSIC Inventory can be used in these schools to assess students' perceptions of the motivational climate.

Introduction: Genetics and genomics are of increasing importance in diagnosis and treatment of patients. We aimed to determine relevant genetics and genomics curricular content and learning objectives for contemporary New Zealand medical graduates. Methods: International and national undergraduate medical genetics curricula were identified and learning outcomes collated. Invited New Zealand subject experts (n = 58) contributed further learning objectives, with final pool of 73 learning objectives. A survey-based, two-round Delphi process was used to gain consensus on the level of learning for each learning objective. Learning outcomes with consensus for learning greater than “in some depth” or “in detail” were included in the proposed curriculum. Results: The response rate for the Delphi rounds were 41% (n = 24/58) and 29% (n = 17/58) for Rounds 1 and 2, respectively. Experts reached consensus on retaining 58/60 (97%) of proposed learning objectives that were to be learned to at least “some depth”. Learning objectives in interprofessional skills, pharmacogenetics, clinical reasoning and information management were retained but refined. Learning outcomes : taking an appropriate genetic history, understanding cultural tenets connected to whakapapa (genealogy), an understanding of DNA samples and genomic data being taonga (sacred), the application of genetic data to Māori and other Indigenous populations and the role of genetics in colonisation and racism and their impact on healthcare. Conclusions: Learning objectives for contemporary medical genetics curricula should consider including those focusing on Indigenous health. Findings highlight the necessity of timely re-evaluation of medical curricula.

Introduction: Endosalpingiosis is the presence of tubal epithelium outside the fallopian tube. Usually presenting as gland-like lesions on peritonealised surfaces, papillary endosalpingiosis can mimic serous borderline tumour. Awareness of papillary endosalpingiosis and the diagnostic dilemma it provides, can prevent misdiagnosis. Case: A 44-year-old woman presented with two weeks left flank pain, and CA125 within normal limits. Radiologically, she had bilateral ovarian lesions (left- 70 mm cystic; right- 40 mm solid) and underwent a hysterectomy, bilateral salpingoophrectomy with omentectomy. Histopathology showed serous cystadenofibromas of both ovaries, with no atypia, stratification, or budding. There was a florid benign serous papillary proliferation on both ovarian surfaces, within paratubal tissue, surface of appendix, and mesoappendix. Psammoma bodies (salpingoliths) were present within fallopian tube lumina. Discussion: Papillary endosalpingiosis can be seen in isolation, or occasionally in conjunction with borderline tumours. While the exact aetiology is unknown, endosalpingiosis is thought to occur either from metaplastic change of the peritoneal mesothelial lining, or due to implantation of salpingoliths from the fallopian tube, secondary to chronic inflammation. Papillary endosalpingiosis can be mistaken for borderline or low grade serous carcinoma of the ovary, however low Ki67 and lack of a primary tumour would support a benign diagnosis. References 1. Cox HY, Alhatem A, Barlog L, et al. A rare mimic of malignancy: papillary endosalpingiosis. Int J Surg Pathol 2020; 28: 60–62. 2. Kurman RJ, Vang R, Junge J, et al. Papillary tubal hyperplasia: the putative precursor of ovarian atypical proliferative (borderline) serous tumors, noninvasive implants, and endosalpingiosis. Am J Surg Pathol 2011; 35: 1605–14.

The classification of malignant tumours is influenced by both immunohistochemical and molecular genetic findings. This is highlighted in the latest World Health Organization classification of renal neoplasia, which has a tumour category of 'tumours that are molecularly defined'. This implies that the defining molecular features are integral to tumourigenesis, which may not necessarily be the case. Renal oncocytoma is recognised as a benign tumour with variable morphology and immunoexpression. A variant of these tumours is hybrid oncocytic chromophobe tumour, which has features of both oncocytoma and chromophobe renal cell carcinoma and may, on rare occasions, show malignant behaviour. Recent reports have proposed two further entities with eosinophilic cytoplasm and varying nuclear pleomorphism, designated low grade oncocytic tumour (LOT) and eosinophilic vacuolated tumour (EVT), formally known as high grade oncocytic tumour (HOT). The diagnosis of these apparently benign tumours was made on the basis of morphological and immunohistochemical features. More recently it has been claimed that the mutations in the mTOR pathway are also a diagnostic feature and it is further suggested that these mutations are key to the pathogenesis of these tumours. As is seen in oncocytoma, immunohistochemical expression of tumours included in series of LOT and EVT is variable. The mutations in the mTOR pathway, where detected, were not constant, with any combination of mTOR, TSC1 and/or TSC2 being involved. A major issue is that in many of the studies full comparative genomic hybridisation results are not presented. In addition it is well recognised that mTOR mutations are seen in a variety of renal tumours. In view of these conflicting results, the rarity of these tumours and their apparent benign nature, raises questions as to why these tumours should be considered specific entities.

The MUSIC Inventory evaluates student’s academic motivation across five constructs. We aimed to examine its use in undergraduate medical pathology courses. Students from three pathology courses completed questions for three factors of the MUSIC Inventory plus one open-ended question. We conducted an exploratory analysis of the survey data. Results showed that the open-ended responses corresponded to differences in ratings on the MUSIC Inventory. Combining an open-ended question with the MUSIC Inventory identified differences in student motivation plus aspects of each course that could be improved. The MUSIC Inventory is an appropriate evaluation method for pathology teaching.

Previous studies have shown that the percentage of high grade prostatic adenocarcinoma (Gleason patterns 4 and 5) in a biopsy correlates with outcome parameters. It has also been shown that the percentage Gleason pattern 4/5 tumour correlates with biochemical failure and overall survival. There are little data relating to the prognostic significance of quantifying the percentage of Gleason pattern 5 in isolation. We investigated the prognostic predictive value of quantifying the percentage of Gleason pattern 5 tumour in needle biopsies from a series of 196 cases of Gleason score 4+5=9 prostate adenocarcinoma from patients who had also undergone radical prostatectomy. Division of cases according to the percentage of Gleason pattern 5 present (based upon the core with the highest grade) and analysing these with tumour grouped as Gleason score 4+5 with <5% pattern 5 (GS 4+5 <5%), Gleason score 4+5 with 5-20% pattern 5 (GS 4+5 5-20%) and Gleason score 4+5 with 21-49% pattern 5 (GS 4+5 21-49%) showed no difference in outcome determined as time interval to prostate specific antigen biochemical failure. The results showed that each of the subgroups of GS 4+5 tumours had a significantly shorter biochemical recurrence-free survival than for a control group of 179 patients with Gleason score 4+3=7 (GS 4+3) cancer. Similar results were obtained when grading was based upon percentage of Gleason pattern 5 present in all the cores taken from the same patient (case-based grade). Adverse findings at radical prostatectomy showed each of the subgroups of GS 4+5 tumours to have a higher incidence of extraprostatic extension and seminal vesicle invasion than the GS 4+3 group of controls. Further, the differences in incidence between each of the subgroups were not significant for either extraprostatic extension or seminal vesicle invasion. These observations applied to both the highest core-based grade and the case-based grade. Our study has shown that any proportion of Gleason pattern 5 tumour in a needle biopsy is associated with a worse prognosis when compared to GS4+3 tumours and that these results are similar for grading that is core- or case-based.

Background: Aotearoa, New Zealand, has one of the fastest-rising rates of endometrial cancer (EC) worldwide, increasing particularly in younger Māori and Pasifika women. There is a move towards using molecular profiling to direct treatment for each EC subtype. Aim: This study aimed to explore the molecular profiling of primary EC tissue in Aotearoa. Methods: We used the PORTEC guidelines for the molecular subtyping of 90 patients’ samples into four categories: POLE-mutated, p53 abnormal, mismatch repair deficient (MMRd) and no specific molecular profile (NSMP). The CTNNB1 mutation and L1CAM expression were also included in the analysis. POLE and CTNNB1 mutations were analysed using targeted next-generation sequencing (NGS). Novel mutations were assessed using VarSome. MMRd, L1CAM and p53 abnormalities were analysed using immunohistochemistry. Results: In total, 15 samples were MMRd, 9 were p53 abnormal, 8 were POLE-mutated and the rest (56) were NSMP. Eleven samples had exon 3 CTNNB1 mutations and eleven novel POLE mutations were described. Conclusion: Surrogate markers for POLE mutations should be investigated. The validation of POLE variants and CTNNB1 mutations as part of an Aotearoa-based molecular panel is warranted.

Background Colorectal cancer is one of the leading causes of cancer-associated morbidity and mortality worldwide. The local anti-tumour immune response is particularly important for patients with stage II where the tumour-draining lymph nodes have not yet succumbed to tumour spread. The lymph nodes allow for the expansion and release of B cell compartments such as primary follicles and germinal centres. A variation in this anti-tumour immune response may influence the observed clinical heterogeneity in stage II patients. Aim The aim of this study was to explore tumour-draining lymph node histomorphological changes and tumour pathological risk factors including the immunomodulatory microRNA-21 (miR-21) in a small cohort of stage II CRC. Methods A total of 23 stage II colorectal cancer patients were included. Tumour and normal mucosa samples were analysed for miR-21 expression levels and B-cell compartments were quantified from Haematoxylin and Eosin slides of lymph nodes. These measures were compared to clinicopathological risk factors such as perforation, bowel obstruction, T4 stage and high-grade. Results We observed greater Follicle density in patients with a lower tumour T stage and higher germinal centre density in patients with higher pre-operative carcinoembryonic antigen levels. Trends were also detected between tumours with deficiency in mismatch repair proteins, lymphatic invasion and both the density and size of B-cell compartments. Lastly, elevated tumour miR-21 was associated with decreased Follicle and germinal centre size. Conclusion Variation in B-cell compartments of tumour-draining lymph nodes is associated with clinicopathological risk factors in stage II CRC patients.

ANZ Journal of SurgeryEarly View IMAGES FOR SURGEONS Periappendicitis in children: What does it mean? Katie J. Hoeksema MBChB, DCH, Department of Paediatric Surgery, Wellington Children's Hospital, Wellington, New Zealand Contribution: Data curation, Writing - original draftSearch for more papers by this authorDiane N. Kenwright MBChB, FRCPA, Department of Pathology and Molecular Medicine, University of Otago, Wellington, New Zealand Contribution: Data curation, ​Investigation, MethodologySearch for more papers by this authorMark D. Stringer MS, FRACS, orcid.org/0000-0003-3024-7971 Department of Paediatric Surgery, Wellington Children's Hospital, Wellington, New Zealand Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand Contribution: Conceptualization, Supervision, Writing - review & editingSearch for more papers by this author Katie J. Hoeksema MBChB, DCH, Department of Paediatric Surgery, Wellington Children's Hospital, Wellington, New Zealand Contribution: Data curation, Writing - original draftSearch for more papers by this authorDiane N. Kenwright MBChB, FRCPA, Department of Pathology and Molecular Medicine, University of Otago, Wellington, New Zealand Contribution: Data curation, ​Investigation, MethodologySearch for more papers by this authorMark D. Stringer MS, FRACS, orcid.org/0000-0003-3024-7971 Department of Paediatric Surgery, Wellington Children's Hospital, Wellington, New Zealand Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand Contribution: Conceptualization, Supervision, Writing - review & editingSearch for more papers by this author First published: 20 August 2021 https://doi.org/10.1111/ans.17152Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Early ViewOnline Version of Record before inclusion in an issue RelatedInformation

ANZ Journal of SurgeryEarly View IMAGES FOR SURGEONS Ruptured foetal corpus luteal cyst: a rare cause of congenital ascites Hannah E. Bascand BSc, MBBS, Department of Paediatric Surgery, Wellington Hospital, Wellington, New Zealand Contribution: Writing - original draftSearch for more papers by this authorJay Marlow FRANZCOG, CMFM, Department of Maternal Fetal Medicine, Wellington Hospital, Wellington, New Zealand Contribution: Data curation, MethodologySearch for more papers by this authorDiane N. Kenwright MBChB, FRCPA, Department of Pathology and Molecular Medicine, The University of Otago, Wellington, New Zealand Contribution: Formal analysisSearch for more papers by this authorMark D. Stringer MS, FRACS, orcid.org/0000-0003-3024-7971 Department of Paediatric Surgery, Wellington Hospital, Wellington, New Zealand Department of Paediatrics and Child Health, The University of Otago, Wellington, New Zealand Contribution: Conceptualization, Methodology, Supervision, Writing - review & editingSearch for more papers by this author Hannah E. Bascand BSc, MBBS, Department of Paediatric Surgery, Wellington Hospital, Wellington, New Zealand Contribution: Writing - original draftSearch for more papers by this authorJay Marlow FRANZCOG, CMFM, Department of Maternal Fetal Medicine, Wellington Hospital, Wellington, New Zealand Contribution: Data curation, MethodologySearch for more papers by this authorDiane N. Kenwright MBChB, FRCPA, Department of Pathology and Molecular Medicine, The University of Otago, Wellington, New Zealand Contribution: Formal analysisSearch for more papers by this authorMark D. Stringer MS, FRACS, orcid.org/0000-0003-3024-7971 Department of Paediatric Surgery, Wellington Hospital, Wellington, New Zealand Department of Paediatrics and Child Health, The University of Otago, Wellington, New Zealand Contribution: Conceptualization, Methodology, Supervision, Writing - review & editingSearch for more papers by this author First published: 02 March 2021 https://doi.org/10.1111/ans.16703Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Early ViewOnline Version of Record before inclusion in an issue RelatedInformation