Using polygenic risk modification to improve breast cancer prevention: study protocol for the PRiMo multicentre randomised controlled trial.

INTRODUCTION: Established personal and familial risk factors contribute collectively to a woman's risk of breast or ovarian cancer. Existing clinical services offer genetic testing for pathogenic variants in high-risk genes to investigate these risks but recent information on the role of common genomic variants, in the form of a Polygenic Risk Score (PRS), has provided the potential to further personalise breast and ovarian cancer risk assessment. Data from cohort studies support the potential of an integrated risk assessment to improve targeted risk management but experience of this approach in clinical practice is limited. METHODS AND ANALYSIS: The polygenic risk modification trial is an Australian multicentre prospective randomised controlled trial of integrated risk assessment including personal and family risk factors with inclusion of breast and ovarian PRS vs standard care. The study will enrol women, unaffected by cancer, undergoing predictive testing at a familial cancer clinic for a pathogenic variant in a known breast cancer (BC) or ovarian cancer (OC) predisposition gene (BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51C, RAD51D). Array-based genotyping will be used to generate breast cancer (313 SNP) and ovarian cancer (36 SNP) PRS. A suite of materials has been developed for the trial including an online portal for patient consent and questionnaires, and a clinician education programme to train healthcare providers in the use of integrated risk assessment. Long-term follow-up will evaluate differences in the assessed risk and management advice, patient risk management intentions and adherence, patient-reported experience and outcomes, and the health service implications of personalised risk assessment. ETHICS AND DISSEMINATION: This study has been approved by the Human Research Ethics Committee of Peter MacCallum Cancer Centre and at all participating centres. Study findings will be disseminated via peer-reviewed publications and conference presentations, and directly to participants. TRIAL REGISTRATION NUMBER: ACTRN12621000009819.

Histopathological and Ultrastructural Study of a Canine Langerhans Cell Tumour (Canine Cutaneous Histiocytoma).

Canine cutaneous histiocytoma (CCH) represents a significant proportion of dog skin tumours, often manifesting as the most common neoplastic skin condition in young animals. Predominantly affecting dogs under four, these tumours appear primarily as solitary lesions that may regress spontaneously. This study, conducted over five years at the University of Trás-os-Montes e Alto Douro, involved a detailed histopathological and ultrastructural examination of 93 CCH cases. Histologically, these tumours showed distinct patterns of lymphoid infiltration, which contributed to their classification into four groups based on the inflammatory response and histological architecture. Most tumours displayed signs of epidermal invasion and frequent mitotic figures, with necrosis present in over half of the cases. Ultrastructurally, the neoplastic cells were characterised by pleomorphism, abundant organelles, and adherens-type junctions. This study offers significant insights into the pathophysiology and morphological characteristics of CCH, underscoring the importance of detailed histological and ultrastructural analysis in accurately diagnosing and understanding this common canine tumour.

Reduction of head and neck cancer risk following smoking cessation: a systematic review and meta-analysis.

OBJECTIVE: Head and neck (HN) cancer comprises the neoplasms originating from the oral cavity, pharynx and larynx. We aimed at reviewing the available literature on the effect of smoking cessation on HN cancer risk. METHOD: We conducted a systematic search in Medline, PubMed and Embase to June 2022. We abstracted or calculated relative risks (RR) and 95% CIs of HN cancer after cessation of tobacco smoking (both former smoking status and duration of quitting) and combined them using random effects meta-analyses. Papers included were case-control or cohort studies available in the English language. Studies investigating smoking cessation after cancer diagnosis, case reports, intervention studies or animal studies were excluded. Quality and susceptibility to bias of each included study were evaluated using the Newcastle-Ottawa Scale. Publication bias was assessed using funnel plot and Egger's test. RESULTS: A total of 65 studies were included in the review, including 5 cohort and 60 case-control studies. The RR of HN cancer for former smokers compared with current smokers was 0.40 (95% CI 0.35 to 0.46). In an analysis by cancer site, the RR of oral cancer was 0.44 (95% CI 0.35 to 0.55), that of pharyngeal cancer 0.44 (95% CI 0.32 to 0.60) and that of laryngeal cancer 0.38 (95% CI 0.29 to 0.50). The dose-response meta-analysis was based on 37 studies. The RR per 10-year increase in smoking cessation was 0.47 (95% CI 0.43 to 0.52). CONCLUSIONS: The risk of HN cancer declines within the first 5 years of quitting smoking. Quitting smoking is an essential element of HN cancer prevention. TRIAL REGISTRATION NUMBER: The protocol has been deposited in the PROSPERO repository (CRD42022338262).

Identifying prognostic predictors for postoperative pituitary neuroendocrine tumour recurrence: an integrated clinical, radiological, and immunohistochemistry assessment.

OBJECTIVE: Pituitary neuroendocrine tumours (PitNETs) are the second most common type of intracranial tumour. Several studies have explored the prognostic factors for PitNETs. However, prognostic factors for postoperative PitNET recurrence remain not fully understood. This study aimed to explore potential prognostic factors for PitNET recurrence, such as surrounding tissue invasion and the extent of surgical resection in patients with postoperative PitNETs. METHODS: We included 106 patients who underwent PitNET surgery between 2013 and 2018, dividing them into two groups: those with recurrence and those without recurrence. Tumours were classified based on demographics, neuroradiological, and immunohistological characteristics. Univariate and multivariate analyses were used to determine factors predicting recurrence. Kaplan-Meier plots and log-rank tests were used to analyse each independent factor based on the cumulative 5-year recurrence rate. RESULTS: During the 5-year follow-up period, 29.2% of the patients (n = 31) had disease recurrence. Univariate analysis showed that predictors of recurrence included cavernous and sphenoid sinus invasions, optic chiasm compression, larger tumour volume, giant adenoma >4 cm, and gross total resection (GTR). Multivariate analysis showed that lactotroph tumour type, sphenoid sinus invasion, and GTR were independent predictors. Kaplan-Meier analysis revealed significant differences in the 5-year recurrence rate among the three independent predictors, with significantly lower recurrence rate in patients with lactotroph tumours and GTR, and a significantly higher recurrence risk in patients with sphenoid sinus invasion. CONCLUSIONS: Lactotroph tumour type, sphenoid sinus invasion, and GTR are independent predictors of postoperative PitNET recurrence. This study provides insights into the factors affecting postoperative PitNET recurrence.

PitNETs are the second most common intracranial tumour typePrognostic factors for postoperative PitNET recurrence remain not fully understoodWe explored potential prognostic factors in patients with postoperative PitNETsProlactin secretion and GTR failure were independent recurrence predictorsProliferative factors did not correlate with recurrence.

Epidemiological trends and treatment abandonment of paediatric solid tumours in a nigerian tertiary hospital: a seven-year review (2016-2022).

BACKGROUND: Paediatric solid tumours, both benign and malignant, present significant health challenges, particularly in Sub-Saharan Africa where comprehensive data is limited. This study aims to elucidate the prevalence, distribution, and treatment outcomes of paediatric solid neoplasms in a tertiary hospital in South-East Nigeria over a seven-year period. METHODS: A retrospective cohort study was conducted at Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi, Nigeria. Clinical details and histological slides of confirmed cases from January 2016 to December 2022 were reviewed. Data extraction focused on socio-demographic variables and treatment outcomes, analysed using statistical methods. RESULTS: The study included 293 children diagnosed with solid tumours (58.1% malignant, 41.9% benign), with a female predominance (61.8%). The median age at diagnosis was 12 years. Fibroadenoma was the most common benign tumour (61.8% of benign cases), while non-Hodgkin lymphoma was the predominant malignant tumour (18.2% of malignant cases). Treatment abandonment rates differed significantly between benign (13.8%) and malignant (51.2%) tumours. Significant associations were found between treatment outcomes and factors such as gender (p = 0.0001 for benign tumours), age category (p = 0.0001 for benign tumours), and specific diagnoses (p = 0.0001 for both benign and malignant tumours). CONCLUSION: This study underscores the substantial burden of paediatric solid tumours in South-East Nigeria and highlights the critical need for improved treatment adherence strategies, particularly for malignant cases. The findings emphasize the importance of tailored interventions based on tumour type, age, and gender. These insights can inform future research, policy formulation, and healthcare strategies aimed at enhancing the management and outcomes of paediatric solid neoplasms in resource-limited settings.

Vascular tissue - boon or bane? How pathogens usurp long-distance transport in plants and the defence mechanisms deployed to counteract them.

Evolutionary emergence of specialised vascular tissues has enabled plants to coordinate their growth and adjust to unfavourable external conditions. Whilst holding a pivotal role in long-distance transport, both xylem and phloem can be encroached on by various biotic factors for systemic invasion and hijacking of nutrients. Therefore, a complete understanding of the strategies deployed by plants against such pathogens to restrict their entry and establishment within plant tissues, is of key importance for the future development of disease-tolerant crops. In this review, we aim to describe how microorganisms exploit the plant vascular system as a route for gaining access and control of different host tissues and metabolic pathways. Highlighting several biological examples, we detail the wide range of host responses triggered to prevent or hinder vascular colonisation and effectively minimise damage upon biotic invasions.

Malignant Transformation of Plexiform Neurofibroma Due to Neglected Giant Soft Tissue Swelling of the Back: A Case Report.

Neurofibromatosis type 1 can be severe and associated with malignant transformation. Proper follow-up and monitoring are very important in preventing the malignant transformation of neurofibromatosis. We encountered a case of malignant transformation of plexiform neurofibroma into neurofibrosarcoma (also known as malignant peripheral nerve sheath tumor). She had been presenting with a large mass on her back for a few years, which was also associated with an ulcer. She underwent a wide-excision biopsy of her back, and the histopathology examination (HPE) came back with a malignant peripheral nerve sheath tumor. This case concludes that any patient with a known case of neurofibromatosis should undergo follow-up to detect any malignant transformation of the disease. Early detection of the malignant transformation of neurofibromatosis can help prevent the disease's progression. The main treatment is surgical resection; however, the risk of local recurrence is higher, especially in patients with neurofibromatosis type 1.

Minimally Invasive Plasma Device Management of Multiple Benign Skin Cancers Associated with Rare Genodermatoses-Case Series and Review of the Therapeutic Methods.

Background: Non-melanocytic benign skin tumours encompass a diverse group of lesions, classified based on their cellular origin, such as epidermal, vascular, fibrous, neural, muscle, and adnexal tumours. Though they often reveal solitary lesions, multiple skin tumours focus on genodermatoses. Each syndrome exhibits distinct clinical characteristics and potential complications, including cutaneous and extra-cutaneous malignancies, some of which are potentially life-threatening. Diagnosing genetic syndromes is complex and requires numerous histopathological and immunohistochemistry tests due to similarities between the adnexal tumours and basal cell carcinoma upon pathology. Methods: To illustrate the clinical practice, we conducted a retrospective case study that included eleven patients with genodermatoses referred to a tertiary dermatology clinic from September 2018 to April 2024. We have also conducted a research study on available treatment modalities in this setting. Results: Five patients with excellent aesthetic results were treated using a recently approved FDA plasma device. After searching SCOPUS and PubMed database records, we assessed 96 original articles to present current knowledge regarding the dermato-surgical approach. Conclusions: Multiple skin tumours, especially on the face, may significantly affect patients' quality of life and have psychological consequences. An appropriate treatment selection tailored to the patient's needs should be provided. There is no standardised treatment for multiple benign tumours in genodermatoses, and selected methods with varying efficacy are employed. We presented the utility of a new plasma device in these settings.

Shear-Wave Elastography Gradient Analysis of Newly Diagnosed Breast Tumours: A Critical Analysis.

BACKGROUND: A better understanding of the peritumoral stroma changes due to tumour invasion using non-invasive diagnostic methods may improve the differentiation between benign and malignant breast lesions. This study aimed to assess the correlation between breast lesion differentiation and intra- and peritumoral shear-wave elastography (SWE) gradients. METHODS: A total of 135 patients with newly diagnosed breast lesions were included. Intratumoral, subsurface, and three consecutive peritumoral SWE value measurements (with three repetitions) were performed. Intratumoral, interface, and peritumoral gradients (Gradient 1 and Gradient 2) were calculated using averaged SWE values. Statistical analysis included descriptive statistics and an ordinary one-way ANOVA to compare overall and individual gradients among Breast Imaging-Reporting and Data System (BI-RADS) 2, 3, and 5 groups. RESULTS: Malignant tumours showed higher average SWE velocity values at the tumour centre (BI-RADS 2/3: 4.1 ± 1.8 m/s vs. BI-RADS 5: 4.9 ± 2.0 m/s, p = 0.04) and the first peritumoral area (BI-RADS 2/3: 3.4 ± 1.8 m/s vs. BI-RADS 5: 4.3 ± 1.8 m/s, p = 0.003). No significant difference was found between intratumoral gradients (0.03 ± 0.32 m/s vs. 0.0 ± 0.28 m/s; p > 0.999) or gradients across the tumour-tissue interface (-0.17 ± 0.18 m/s vs. -0.13 ± 0.35 m/s; p = 0.202). However, the first peritumoral gradient (-0.16 ± 0.24 m/s vs. -0.35 ± 0.31 m/s; p < 0.0001) and the second peritumoral gradient (-0.11 ± 0.18 m/s vs. -0.22 ± 0.28 m/s; p = 0.037) were significantly steeper in malignant tumours. The AUC was best for PTG1 (0.7358) and PTG2 (0.7039). A threshold value for peritumoral SWI PT1 above 3.76 m/s and for PTG1 below -0.238 m/s·mm-1 indicated malignancy in 90.6% of cases. CONCLUSIONS: Evaluating the peritumoral SWE gradient may improve the diagnostic pre-test probability, as malignant tumours showed a significantly steeper curve of the elasticity values in the peritumoral stroma compared to the linear regression with a relatively flat curve of benign lesions.

Comparative effect of different mindfulness-based intervention types and deliveries on depression in patients with breast cancer: a protocol for a systematic review and network meta-analysis.

INTRODUCTION: Breast cancer has become the most common cancer worldwide. Various types of mindfulness-based interventions (e.g., mindfulness-based cognitive therapy, mindfulness-based stress reduction) have been conducted in different delivery methods (including face to face and internet delivered) to help patients with breast cancer mitigate their depression. However, at present, there are no studies that compare the effectiveness of all these types and deliveries of mindfulness-based interventions. Therefore, this protocol aims to conduct a systematic review and network meta-analysis to assess the effectiveness of various types and deliveries of mindfulness-based interventions in mitigating depression in patients with breast cancer. METHODS: This protocol is according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The electronic databases, including PubMed, Web of Science, the Cochrane Library, Embase, Google Scholar, The China National Knowledge Infrastructure and OpenGrey, will be comprehensively retrieved for related randomised controlled trials (RCTs) from inception to December 2023. Two reviewers will independently assess the risk of bias using the Cochrane Risk of Bias Tool for Randomised Trials 2.0 (RoB 2.0). The network meta-analysis will be performed using the STATA V.16.0, and the assessment of heterogeneity, inconsistency, publication bias, evidence quality, subgroup analyses and sensitivity analyses will be conducted. ETHICS AND DISSEMINATION: This protocol does not require approval from an ethics committee as it is based on previous research findings. The results will be disseminated via peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42024495996.

SMARCB1 (INI-1) deficient sinonasal carcinoma of the right maxillary sinus - A rare entity.

INTRODUCTION AND IMPORTANCE: SMARCB1 (INI-1) is a vital tumour suppressor gene on chromosome 22q11.2, preventing tumour development in the SWI/SNF complex. Mutations cause SMARCB1-deficient tumours with distinct features. Loss of INI-1 expression is seen in malignancies, including sinonasal carcinoma and atypical teratoid/rhabdoid tumours. Recently recognized as a separate entity, SMARCB1-deficient sinonasal carcinomas (SDSC) are rare, clinically aggressive, and mimic other malignancies, emphasizing their significant diagnosis due to poorer prognosis, particularly in the elderly. CASE PRESENTATION: A 66-year-old male presented with a 4-month-old right cheek swelling, diagnosed initially as a sinonasal neoplastic mass. The biopsy revealed sinonasal mucosal fragments infiltrated by a tumour with plasmacytoid morphology. Immunohistochemistry (IHC) of the tumour cells was positive for p63 and pan-cytokeratin and showed INI-1 loss. Subsequent subtotal maxillectomy was performed, and the patient received adjuvant chemotherapy and radiotherapy. At a thirteen-month follow-up, the patient achieved his daily activities with no signs of recurrence. CLINICAL DISCUSSION: The loss of protein expression in sinonasal cancer is predominantly attributed to the homozygous deletion of SMARCB1. SDSC, a profoundly invasive malignant carcinoma, tends to infiltrate sinuses and extend into the intracranial regions. The IHC findings of our case were in coherence with previous studies in SMARCB1. The prognosis is particularly unfavourable in males and advanced tumours. CONCLUSION: The tumour's microscopic and immunohistochemical characteristics indicated the SDSC. Due to its aggressive nature and high mortality rates, dealing with a paranasal mass, one should be suspicious of this tumour.

Hepatocellular Adenoma With Hepatocyte Nuclear Factor-1 Alpha (HNF-1α) Mutation: A Case Report.

Hepatocellular adenoma (HCA) is an uncommon benign liver tumor that exhibits a variety of subtypes, each distinguished by unique molecular alterations. This case report describes a 43-year-old man with a history of alcoholism who presented with stomach pain. Imaging revealed multiple hepatic lesions and sigmoid colon inflammation, while laboratory tests showed mild neutrophilic leukocytosis and elevated liver enzymes. Tumor markers were normal. A liver biopsy confirmed HCA with hepatocyte nuclear factor-1 alpha (HNF-1α) inactivation, characterized by negative immunostaining for glutamine synthetase, nuclear beta-catenin, serum amyloid A, C-reactive protein, and liver fatty acid-binding protein (L-FABP). This case is unique due to the patient's gender and the absence of typical risk factors such as abnormal hormone levels. HCAs in males, particularly with HNF-1α inactivation, are rare and pose diagnostic challenges. Comprehensive diagnostic approaches, including biopsy and immunohistochemical analysis, are crucial for accurate subtype identification. The potential for malignant transformation, particularly in male patients, underscores the need for vigilant monitoring and appropriate management. This case highlights the importance of considering HCA in differential diagnoses regardless of gender and typical risk factors, contributing valuable insights into the diverse presentations and risks associated with HCA, and emphasizing the need for awareness and further research to improve diagnosis and management of this rare condition.

Minimum Fascia-Tumour Distance for Differentiating Deep Lobe From Superficial Lobe Benign Parotid Tumours: A Retrospective Study and Meta-Analysis.

BACKGROUND: This study was designed to evaluate the diagnostic efficacy of the minimum fascia-tumour distance (MFTD) in distinguishing deep-lobe benign parotid tumours from superficial-lobe tumours through both an original study and a meta-analysis. METHODS: In this study, we performed a retrospective analysis of data from 91 patients who had been diagnosed with benign parotid tumours. The MFTD values were sourced from preoperative ultrasound examinations. The locations of these tumours were confirmed through surgical findings. We assessed the diagnostic accuracy of MFTD by utilising receiver operating characteristic (ROC) curves. Additionally, we conducted a systematic review of the pertinent literature and performed a diagnostic meta-analysis to ascertain the overall diagnostic efficacy of MFTD in identifying benign parotid tumours. RESULTS: Patients with tumours in the deep lobe had a significantly greater MFTD than patients with tumours in the superficial lobe. Using a cutoff value of 3.50 mm for MFTD, we found an AUC of 0.93, a sensitivity of 81.8%, and a specificity of 98.8%. Our meta-analysis included seven studies covering a total of 1689 tumours. The pooled values for sensitivity, specificity, and diagnostic odds ratio (OR) of MFTD were 81.0%, 89.0%, and 32.2, respectively. The AUC of the summarised ROC curve of MFTD was 0.90. CONCLUSION: The MFTD demonstrated reliable diagnostic accuracy in identifying deep-lobe benign parotid tumours and may be incorporated into standard evaluations before parotidectomy.

Prognostic Heterogeneity Between Oral Tongue and Gingivobuccal Tumours Based on Lymph Node Ratio and Number of Positive Nodes: A Survival Analysis.

Introduction: Lymph node ratio (LNR) and number of pathological positive nodes (pN) have shown better prognostic prediction compared to laterality, size and number of nodes (single or multiple). This study evaluates the prognostic significance of LNR and the number of  pathological positive nodes in predicting the outcomes of node positive oral squamous cell carcinoma(OSCC). It attempts to assess the prognostic heterogeneity between oral tongue and gingivobuccal complex tumours based on the lymph node ratio and the number of pathological positive nodes. Materials and Methods: A retrospective chart review of 498 previously untreated OSCC patients from January 2014 to December 2017 at our tertiary cancer institute was done. Our analysis included 133 oral tongue and 79 gingivobuccal tumours with histopathologically proven lymph node metastasis. The impact of LNR and number of positive nodes on overall survival and disease free survival was studied. Results: Overall survival rate was found to vary significantly based on LNR (> 0.06) and number of positive nodes (> 2). Overall survival reduced significantly in GBC tumours when LNR was more than 0.06(63.37 vs 32.1, p 0.005) but the same trend was not seen with tongue cancers (55.61 vs 41.9, p 0.98). Both the groups shown no difference in DFS based on LNR. Overall survival reduced significantly in both the groups when >2o pathologically positive nodes were present but disease free survival did not vary significantly in both the groups. Conclusion: Lymph node ratio (> 0.06) and number of pathological positive nodes (> 2) provide a better prognostic stratification in node positive oral squamous cell carcinoma. Oral tongue and GBC tumours were found to have a differential impact on overall survival rate on the stratification based on LNR.

Clinical Characteristics of Macroprolactinomas and Response to Medical Therapy.

Introduction: The presentation of macroprolactinomas and response to treatment may vary according to age, sex and tumour characteristics. To analyse clinical phenotype, biochemical and radiological characteristics of macroprolactinomas presenting to a tertiary care centre. A retrospective observational study from January 2018 to December 2022. Methods: Thirty diagnosed cases (18 females, 12 males) of macroprolactinomas were included and followed up for one year. Results: The most common presentation was headache (73%), visual disturbances (50%), galactorrhoea (33.3%) and loss of libido (26.6%) along with menstrual cycle disturbances (94%), and infertility (55%) in females. Duration of symptoms (2.22 ± 2.87 vs 4.61 ± 3.4 years), tumour size (4.8 ± 2.09 vs 2.75 ± 1.24 cm) and prolactin levels (5153.5 ± 4755.3 vs 1803.5 ± 3785.5 ng/ml) were different significantly between males and females. Good response to medical therapy was observed in 84% of the treatment-naive patients. Conclusion: Macroprolactinomas in males present with shorter duration of symptoms, larger size, higher prolactin levels and more resistant tumours, emphasizing the need for early diagnosis and aggressive management. Medical therapy remains the treatment of choice irrespective of gender.

Leiomyosarcoma of the abdomen and retroperitoneum; a systematic review.

Background: Intraabdominal and retroperitoneal leiomyosarcomas are rare cancers, which cause significant morbidity and mortality. Symptoms, treatment and follow up differs from other cancers, and proper diagnosis and treatment of intraabdominal and retroperitoneal leiomyosarcomas is of utmost importance. We performed a systematic review to collect and summarize available evidence for diagnosis and treatment for these tumours. Methods: We performed a systematic literature search of Pubmed from the earliest entry possible, until January 2021. Our search phrase was (((((colon) OR (rectum)) OR (intestine)) OR (abdomen)) OR (retroperitoneum)) AND (leiomyosarcoma). All hits were evaluated by two of the authors. Results: Our predefined search identified 1983 hits, we selected 218 hits and retrieved full-text copies of these. 144 studies were included in the review. Discussion: This review summarizes the current knowledge and evidence on non-uterine abdominal and retroperitoneal leiomyosarcomas. The review has revealed a lack of high-quality evidence, and randomized clinical trials. There is a great need for more substantial and high-quality research in the area of leiomyosarcomas of the abdomen and retroperitoneum. Systematic Review Registration: PROSPERO, identifier, CRD42023480527.

Mapping the cited evidence of ductal carcinoma in situ from the 5th edition of the World Health Organisation classification of tumours of the breast.

AIMS: Ductal carcinoma in situ (DCIS) is recognised by the World Health Organisation (WHO) Classification of Tumours (WCT) as a non-invasive neoplastic epithelial proliferation confined to the mammary ducts and lobules. This report categorises the references cited in the DCIS chapter of the 5th edition of the WCT (Breast Tumours) according to prevailing evidence levels for evidence-based medicine and the Hierarchy of Evidence for Tumour Pathology (HETP), identifying potential gaps that can inform subsequent editions of the WCT for this tumour. METHODS AND RESULTS: We included all citations from the DCIS chapter of the WCT (Breast Tumours, 5th edition). Each citation was appraised according to its study design and evidence level. We developed our map of cited evidence, which is a graphical matrix of tumour type (column) and tumour descriptors (rows). Spheres were used to represent the evidence, with size and colour corresponding to their number and evidence level respectively. Thirty-six publications were retrieved. The cited literature in the DCIS chapter comprised mainly case series and were regarded as low-level. We found an unequal distribution of citations among tumour descriptors. 'Pathogenesis' and 'prognosis and prediction' contained the most references, while 'clinical features', 'aetiology' and 'diagnostic molecular pathology' had only a single citation each. 'Prognosis and prediction' had the greatest proportion of moderate- and high-levels of evidence. CONCLUSION: Our findings align with the disposition for observational studies inherent in the field of pathology. Our map is a springboard for future efforts in mapping all available evidence on DCIS, potentially augmenting the editorial process and future editions of WCTs.

SMARCB1/INI1-deficient undifferentiated tumour of the thorax: a case report and review of the literature.

The 5th WHO classification of thoracic tumours includes thoracic SMARCA4-deficient undifferentiated tumour (SMARCA4-UT) among the "other epithelial tumours of the lung" chapter. Herein, we present a case of undifferentiated thoracic neoplasm with retention of SMARCA4 expression, lack of NUT fusion protein and loss of SMARCB1/INI1 expression. After presenting the clinical and pathological features of the tumour, we carried out a review of the literature on the same topic. Albeit very rare, we believe this entity should be included in the heterogeneous group of undifferentiated neoplasms of the thorax.

Maintenance proton pump inhibitor use and risk of colorectal cancer: a Swedish retrospective cohort study.

OBJECTIVES: We aimed to evaluate the risk of colorectal adenocarcinoma (CRA) associated with long-term use of proton pump inhibitors (PPIs) in a large nationwide cohort. DESIGN: Retrospective cohort study. SETTING: This research was conducted at the national level, encompassing the entire population of Sweden. PARTICIPANTS: This study utilised Swedish national registries to identify all adults who had ≥180 days of cumulative PPI use between July 2005 and December 2012, excluding participants who were followed up for less than 1 year. A total of 754 118 maintenance PPI users were included, with a maximum follow-up of 7.5 years. INTERVENTIONS: Maintenance PPI use (cumulative≥180 days), with a comparator of maintenance histamine-2 receptor antagonist (H2RA) use. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was the risk of CRA, presented as standardised incidence ratios (SIRs) with 95% confidence intervals (CIs). Subgroup analyses were performed to explore the impact of indications, tumour locations, tumour stages and the duration of follow-up. A multivariable Poisson regression model was fitted to estimate the incidence rate ratios (IRRs) and 95% CIs of PPI versus H2RA use. RESULTS: Maintenance PPI users exhibited a slightly elevated risk of CRA compared to the general population (SIR 1.10, 95% CI=1.06 to 1.13) for both men and women. Individuals aged 18-39 (SIR 2.79, 95% CI=1.62 to 4.47) and 40-49 (SIR 2.02, 95% CI=1.65 to 2.45) had significantly higher risks than the general population. Right-sided CRA showed a higher risk compared to the general population (SIR 1.26, 95% CI=1.20 to 1.32). There was no significant difference in the risk of CRA between maintenance PPI users and maintenance H2RA users (IRR 1.05, 95% CI=0.87 to 1.27, p<0.05). CONCLUSIONS: Maintenance PPI use may be associated with an increased risk of CRA, but a prolonged observation time is needed.

Comparing the antireflux effect of laparoscopic proximal gastrectomy with double-flap technique reconstruction versus laparoscopic total gastrectomy with Roux-en-Y reconstruction for proximal early gastric cancer: study protocol for a multicentre, prospective, open-label, randomised controlled trial.

INTRODUCTION: Laparoscopic proximal gastrectomy with double flap technique (LPG-DFT) reconstruction has been used for proximal early gastric cancer in recent years. However, its feasibility and safety remain uncertain, as only a few retrospective studies have contained postoperative complications and long-term survival data. LPG-DFT for proximal early gastric cancer is still in the early stages of research. Large-scale, prospective randomised controlled trials (RCTs) are necessary to assess the value of LPG-DFT for proximal early gastric cancer. METHODS AND ANALYSIS: This study is a multicentre, prospective, open-label, RCT that investigates the antireflux effect of LPG-DFT compared with laparoscopic total gastrectomy with Roux-en-Y (LTG-RY) reconstruction for proximal early gastric cancer. A total of 216 eligible patients will be randomly assigned to the LPG-DFT group or the LTG-RY group at a 1:1 ratio using a central, dynamic and stratified block randomisation method, if inclusion criteria are met. General and clinical data will be collected when the patient is enrolled in the study and keep pace with the patient at each stage of his medical and follow-up pathway. The primary endpoint is the proportion of patients with reflux esophagitis (Los Angeles Grade B or more) within 12 months postoperatively. The secondary endpoints included intraoperative outcomes, postoperative recovery, postoperative pain assessment, pathological outcomes, postoperative quality of life, postoperative nutrition status, morbidity and mortality rate, and oncological outcomes (3-year overall survival (OS), 3-year disease-free survival (DFS), 5-year DFS and 5-year OS). ETHICS AND DISSEMINATION: The protocol is approved by the Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University ethics committee (registration number: SYSKY-2022-276-02) on 28 September 2022.We will report the positive as well as negative findings in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05890339.