Pathological Society

Colorectal cancer (CRC) remains one of the leading causes of cancer-related deaths worldwide, largely due to late-stage diagnosis and limited efficacy of current therapies. 5-Fluorouracil (5-FU) is the standard chemotherapeutic agent used in CRC treatment; however, its effectiveness is often hampered by resistance, toxicity, and suboptimal outcomes in advanced-stage tumors. Recent evidence suggests that gut microbiota-derived short-chain fatty acids (SCFAs) exert anticancer effects and may hold promise as therapeutic adjuvants. In this study, we investigated the potential of a physiologically relevant mixture of SCFAs to enhance the efficacy of 5-FU against CRC. Using a combination of 2D monolayer cultures, 3D models, and the in vivo chicken chorioallantoic membrane (CAM) assay, we demonstrated that SCFAs positively affect the antitumor effects of low-dose 5-FU. SCFAs contributed to the inhibition of CRC cell growth, proliferation, survival, and migration, with an overall increase of the anti-tumour effects observed across the different models. The combined treatment led to a significant reduction in tumour size in the CAM assay, contributing for an improvement of the effects of 5-FU alone. To our knowledge, this is the first report showing that physiologically relevant SCFA combinations can be harnessed to improve the therapeutic index of 5-FU in CRC, in a context-dependent manner. These findings support the development of microbiota-targeted co-adjuvant strategies to optimize CRC chemotherapy, reduce treatment toxicity, and improve patient outcomes, which is important given the clinical interest in microbiome-chemotherapy interactions.

Animal farming is associated with exposure to organic dust containing allergens, endotoxins, and alive microbial organisms. Microbial Volatile Organic Compounds (MVOCs) produced mainly by fungi and bacteria pollute the air and accumulate particularly in confined animal buildings, posing serious health hazards to workers, including veterinarians. The exposure can lead to rhinitis, chronic bronchitis, asthma, and chronic obstructive pulmonary disease (COPD). In a range of cross-sectional studies, wheeze and asthma were associated with exposure to swine, dairy cattle, horse, and sheep, but also to more specific exposures like manure. Occupational asthma has been reported in agricultural workers, including veterinarians. We report two cases of veterinarians who developed asthma in relation to prolonged and intense contact with sheep. No specific allergens could be found, MVOCs were considered as the causative agents.

Abstract Lipomas are benign mesenchymal neoplasms composed of mature adipose tissue, most frequently found in subcutaneous regions. We report a case of a pure intra-thyroid lipoma. A 55-year-old Moroccan woman presented with a longstanding cervical mass. Clinical examination revealed a goitre, and thyroid function tests showed a euthyroid profile. Cervical ultrasound revealed a large right lobar thyroid nodule and a 6 mm left-sided nodule classified as EU-TIRADS 3, with no suspicious features. The patient underwent a total thyroidectomy after discussion of management options; the patient preferred definitive surgical management. Histopathological examination demonstrated a follicular adenoma occupying the entire right lobe, while the left lobe contained a 6 mm, well-circumscribed, encapsulated lipomatous lesion composed entirely of mature adipocytes, with no associated thyroid tissue. Only histopathological images are available for inclusion. This case highlights the rarity of pure intra-thyroid lipoma and emphasizes the role of careful histopathological assessment in distinguishing fat-containing thyroid lesions.

Abstract Background and aims Intestinal fibrosis is present but under studied in Ulcerative colitis (UC), while Endoplasmic Reticulum stress proteins have been found associated with fibrosis in Crohn Disease. Our scientific aim is to better understand the impact and role of epithelium in intestinal fibrosis. Methods We have developed a model of apical-out organoids deriving from Ulcerative colitis patients intestinal stem cells, which present a pro-fibrogenic phenotype in response to transient Endoplasmic reticulum stress (ERS) induction[1]. These induce by paracrine action a fibroblast to myofiboblast transition (FMT). Deciphering the paracrine mediators and the molecular changes arising in such organoids compared to non-induced one not inducing FMT, will be evaluated by multi-Omic differential studies: secretomics, transcriptomics and proteomics. Afterwards, FMT assays will be used to confirm therapeutics targets using antibody blocking strategy as in (Vieujean et al, JCC 2021)[2]. IBD tissues, plasma, likely stool, will be used to confirm candidate markers association with fibrosis features[3]. Our pro-fibrogenic organoid model will be treated with 5ASA or corticoids, or other drugs with epithelial action, to assess any beneficial effect for mitigating the pro-fibrogenic phenotype observed and probably involved in IBD intestinal fibrosis development. Anticipated impact We expect to increase our knowledge on epithelial cell response to ERS involvement, in relation to fibrosis development. This model not generating any inflammatory response while inducing paracrine FMT, might explain partly why intestinal fibrosis development does not require inflammation and may progress even if inflammation is controlled in IBD. Currently, no evidence points cytokine trigger in our model, but only ERS response factors, as eAGR2. The multi-omic differential analyses comparing samples from organoids with and without induced pro-fibrogenic phenotype should highlight fibrogenic paracrine factors promoting FMT, and point epithelial changes as potential therapeutic target(s) or biomarker(s), detectable in biopsy, plasma or stools. Tests on treatment acting on epithelium might alleviate ERS and/or ERS response, and might unveil potential process and pathways involved in fibrosis progression and independent of inflammation and immune component.

Objective: To compare the expression of CyP-A, NF-κB, PARP-1, and apoptotic index in Non-Severe Preeclampsia (NS-PE) and Normal Pregnancy (NP) and explore their roles in inflammation during preeclampsia.Methods: Conducted in Depok, Indonesia, the cross-sectional study involved 28 participants divided into NS-PE and NP groups based on ISSHP criteria. NP was defined as uncomplicated pregnancies at 38–40 weeks gestation. Placental weight was measured, and ELISA was used to assess biomolecule levels. Data were analyzed using T-tests or Mann-Whitney tests.Result: Maternal gestational age, body mass index, and leukocyte levels were significantly higher in NS-PE. The apoptotic index, measured by TUNEL assay, was also significantly elevated in NS-PE (41.56 ±24.87) compared to NP (23.96 ±18.79; p = 0.044). While CyP-A, PARP-1, and NF-κB levels were higher in NS-PE eventhough they were not statistically significant. Immunohistochemistry confirmed an overall increase in these molecules, supporting their clinical relevance.Conclusion: Despite the lack of statistical significance, increased inflammation and apoptosis in NS-PE may contribute to placental dysfunction and adverse pregnancy outcomes.Key words: Apoptosis; inflammation; preeclampsia Non-Severe Preeclampsia dan Inflamasi Subklinis: Studi CyP-A, NF-κB, PARP-1, dan Apoptosis Plasenta pada ManusiaAbstrakTujuan: Penelitian ini bertujuan untuk mengetahui perbedaan ekspresi CyP-A, NF-κB, PARP-1, dan indeks apoptosis antara preeklamsia non-severe (NS-PE) dan kehamilan normal (NP), serta perannya dalam proses inflamasi pada preeklamsia.Metode: Metode penelitian yang digunakan dalam penelitian ini adalah cross-sectional. Penelitian ini dilakukan di Depok, Indonesia, dengan 28 partisipan yang dikelompokkan menjadi NS-PE dan NP berdasarkan kriteria ISSHP. Berat plasenta diukur dan kadar biomolekul dianalisis menggunakan ELISA. Uji T dan alternatif Mann-Whitney digunakan untuk analisis statistik.Hasil: Hasil penelitian menunjukkan bahwa usia kehamilan, indeks massa tubuh (IMT), dan kadar leukosit secara signifikan lebih tinggi pada NS-PE. Indeks apoptosis (TUNEL) juga lebih tinggi secara signifikan pada NS-PE (41,56 ±24,87) dibandingkan NP (23,96 ±18,79; p = 0,044). Kadar CyP-A, PARP-1, dan NF-κB lebih tinggi pada NS-PE meskipun tidak signifikan secara statistik, pemeriksaan IHK mengonfirmasi relevansi klinis peningkatan pada keseluruhan biomolekul tersebut.Kesimpulan: Meskipun signifikansi statistik rendah, peningkatan peradangan dan apoptosis pada NS-PE dapat menyebabkan disfungsi plasenta dan dampak buruk pada kehamilan.Kata kunci: Apoptosis; inflamasi; preeklamsia.

Can ‘re-wilding’ at ‘earthquake disaster remains (shinsai ikō)’ introduce a new paradigm of memorializing the 2011 Great East Japan Earthquake and Tsunami? What sacrifices do conventional formulas of memorialization and heritagization demand of the 3.11 tsunami-affected residents and municipalities? This paper explores these questions by examining two atypical ‘earthquake disaster remains’ in Miyagi Prefecture: the former police box in Onagawa, and the concrete foundations of housing in Arahama. Brimming with vegetal desires for life, the two sites look viscerally chaotic and alarmingly unkempt, defying most people’s expectations. My analysis shows that conventional formulas of memorializing the sites of trauma require vigilance against weathering and decaying, lest changes in appearance threaten the authenticity of the sites. In this context, by foregrounding the earthquake disaster remains’ physical mutability through ecological entanglement, I argue, the two atypical sites under investigation distill the inherent contradictions and problematics that our ingrained practices of memorialization take for granted. Through re-wilding, what I call ‘partial forgetting by design’, will emerge as a possible intervention into imagining a life and future in the disaster-prone areas around the world in an era of planetary climate change.

Biopsy has limited value and is relatively effective only against cystic tumors for preoperative diagnosis of mediastinal cysts. Noninvasive clinical imaging is relevant here, taking into account the localization of the neoplasm and its relationship to neighboring structures. Non-tumor cysts of the thymus gland (CTG) are divided into monolocular (congenital, primary) and multilocular (acquired, secondary). A clinical case of a 45-year-old woman with a multilocular CTG diagnosed by computed tomography and videothoracoscopically removed is presented. The issues of diagnosis and differential diagnosis of multilocular CTG and their possible connection with COVID 19 are discussed.

To the Editor, The current grading system for prostate cancer (PCA) includes 5 Grade Groups (GG): GG1 (Gleason score ≤ 6); GG2 (Gleason score 3+4); GG3 (Gleason score 4+3); GG4 (Gleason score 4+4; or 3+5; or 5+3); GG5 (Gleason scores 4+5/5+4/5+5). The GG system is one of the most important predictors of outcome in PCA patients...

Critical illnesses imply vital organ dysfunctions with high risk of imminent death. Magnesium is a bioessential element with multiple physiological effects relevant for vital body functions. It stabilizes excitable membranes contributing to proper neuromuscular, cardiovascular and respiratory functions. Ionized Mg2+ (iMg2+) is free bioactive form of Mg2+ in body fluids. Magnesium disorders in critically ill patients are often overlooked. Chronic Mg2+ deficiency is a condition of growing incidence in the general population and a significant factor in overall morbidity and mortality in critical illness. Main goal of this study was to investigate the existing literature related to determination of iMg2+ in the critically ill and to raise awareness of the problem of chronic Mg2+ deficiency in these patients. Search was conducted across electronic PubMed library database from 1975 to November 2024 using keywords concerning iMg2+ and critical care patients, to identify studies investigating the measuring of blood concentration of iMg2+ fraction in patients with critical health conditions. Search was limited to English language. Selection criteria included only studies on human, and excluded studies on animal population. We identified 95 relevant studies. Reviewed papers show that abnormalities of Mg2+ levels are prevalent in critical illnesses. Their severity can impose vital threat. Disconcordance between total Mg2+ (tMg2+) and iMg2+ blood levels is frequently present in critical patients. Appropriate electrolyte analyzer assay is needed to promptly determine iMg2+ levels to assess Mg2+ status in critically ill patients, in order to help detect and correct Mg2+ imbalances and estimate the requirement for Mg2+ recompense in the case of deficiency, and thereby provide better outcome of the disease.