Extraovarian Fibroma with Minor Sex Cord Elements-a Rare Tumour at Rare Site.

Sex cord stromal tumour (SCST) of ovary account for 5-8% of all ovarian malignancies. These include fibroma, thecoma, fibro-thecoma, Leydig cell tumour, granulosa cell tumour, and Sertoli cell tumour. Although considered primary ovarian malignancy, SCST has been described in extraovarian location also. Extraovarian SCST is a rare occurrence, and so far, only 25 cases have been reported in literature and only one amongst them was extraovarian fibroma with minor sex cord element. Considering the rarity, diagnosis and proper treatment remain the real challenge in these tumours. To the best of our knowledge, this is the second case of extraovarian fibroma with minor sex cord element to be reported. Herein, we report a case of 41-year-old lady who presented with large abdomino-pelvic mass which was considered ovarian tumour; however, intraoperatively both ovaries and uterus were found to be normal, and the mass was actually arising from sigmoid mesocolon.

Dysgerminoma with Syncytiotrophoblastic Giant Cells Associated with a Concurrent Ectopic Pregnancy.

Background: Dysgerminomas constitute around 1-2% of all germ cell tumours. It is very very rare to have dysgerminoma with concurrent pregnancy with an incidence of 0.2-1 per 100,000 pregnancies. It is extremely difficult to conceive with no assisted reproductive interventions and carry it till completion with no complications in a concurrent dysgerminoma. Dysgerminoma has a characteristic specific histomorphology and is easy to diagnose. However, occasionally, syncytiotrophoblastic differentiation can be seen in dysgerminoma although it is a rare histopathological finding. Also, the raised serum B-HCG levels due to the syncytiotrophoblast giant cells seen can lead to a diagnostic dilemma. Clinical presentation: Here we report a case of a 27-year-old 8-week pregnant female who came to the hospital with chief complaints of left-sided abdominal pain and a lump abdomen. Clinical and radiological examination revealed a left ovarian tumour of malignant aetiology with the presence of right ectopic pregnancy. A staging laparotomy with left salpingoophorectomy was performed and sent for histopathological examination. It was reported as dysgerminoma with syncytiotrophoblastic giant cells. The right fallopian tube showed products of conception. Finally, she was planned for adjuvant chemotherapy and serial B-HCG levels. Summary: This case is reported not only just for its rare histopathological finding but also for the diagnostic dilemma it causes both to the surgeon as well as the pathologist. There are various factors which can act as prognosticators such as early suspicion of a tumor, radiological findings, surgery, histopathological examination, and oncology team.

Sternal Reconstruction with a Custom-Made 3D-Printed Titanium Neo-sternum Prosthesis After Resection for Primary Malignant Sternal Tumour.

Primary sternal tumours are rare. Most of them are malignant in nature. When localized, cure can be achieved by radical resection. However, it leaves a large bony defect in front of the heart that makes reconstruction a challenge. In this report, we describe our experience of sternal reconstruction using a custom-made 3D-printed titanium neo-sternum after en-bloc resection of sternal body and anterior ends of bilateral second to fifth ribs for chondrosarcoma.

Leveraging diverse cellular stress patterns for predicting clinical outcomes and therapeutic responses in patients with multiple myeloma.

Tumour microenvironment harbours diverse stress factors that affect the progression of multiple myeloma (MM), and the survival of MM cells heavily relies on crucial stress pathways. However, the impact of cellular stress on clinical prognosis of MM patients remains largely unknown. This study aimed to provide a cell stress-related model for survival and treatment prediction in MM. We incorporated five cell stress patterns including heat, oxidative, hypoxic, genotoxic, and endoplasmic reticulum stresses, to develop a comprehensive cellular stress index (CSI). Then we systematically analysed the effects of CSI on survival outcomes, clinical characteristics, immune microenvironment, and treatment sensitivity in MM. Molecular subtypes were identified using consensus clustering analysis based on CSI gene profiles. Moreover, a prognostic nomogram incorporating CSI was constructed and validated to aid in personalised risk stratification. After screening from five stress models, a CSI signature containing nine genes was established by Cox regression analyses and validated in three independent datasets. High CSI was significantly correlated with cell division pathways and poor clinical prognosis. Two distinct MM subtypes were identified through unsupervised clustering, showing significant differences in prognostic outcomes. The nomogram that combined CSI with clinical features exhibited good predictive performances in both training and validation cohorts. Meanwhile, CSI was closely associated with immune cell infiltration level and immune checkpoint gene expression. Therapeutically, patients with high CSI were more sensitive to bortezomib and antimitotic agents, while their response to immunotherapy was less favourable. Furthermore, in vitro experiments using cell lines and clinical samples verified the expression and function of key genes from CSI. The CSI signature could be a clinically applicable indicator of disease evaluation, demonstrating potential in predicting prognosis and guiding therapy for patients with MM.

Unveiling the functional roles of patient-derived tumour organoids in assessing the tumour microenvironment and immunotherapy.

Recent studies have established the pivotal roles of patient-derived tumour organoids (PDTOs), innovative three-dimensional (3D) culture systems, in various biological and medical applications. PDTOs, as promising tools, have been established and extensively used for drug screening, prediction of immune response and assessment of immunotherapeutic effectiveness in various cancer types, including glioma, ovarian cancer and so on. The overarching goal is to facilitate the translation of new therapeutic modalities to guide personalised immunotherapy. Notably, there has been a recent surge of interest in the co-culture of PDTOs with immune cells to investigate the dynamic interactions between tumour cells and immune microenvironment. A comprehensive and in-depth investigation is necessary to enhance our understanding of PDTOs as promising testing platforms for cancer immunotherapy. This review mainly focuses on the latest updates on the applications and challenges of PDTO-based methods in anti-cancer immune responses. We strive to provide a comprehensive understanding of the potential and prospects of PDTO-based technologies as next-generation strategies for advancing immunotherapy approaches.

Adrenal tumours in patients with pathogenic APC mutations: a retrospective study.

BACKGROUND: Adrenal tumours are associated with familial adenomatous polyposis (FAP). In the literature, most studies use the clinical definition of FAP (more than 100 adenomatous polyps found in endoscopic studies). However, not all patients that meet clinical criteria for FAP carry pathogenic mutations in the adenomatous polyposis coli (APC) gene, as there is genetic heterogeneity responsible for FAP with the polyposis sometimes explained by genetic and environmental factors other than pathogenic APC mutations. Reciprocally, not all the patients with pathogenic APC variants will fulfil the classic criteria of FAP. OBJECTIVE: This study aims to investigate the characteristics of adrenal tumours in patients with pathogenic or likely pathogenic APC variants and explore the hormonal function of these patients. METHOD: This is a retrospective cohort study. Patients with pathogenic or likely pathogenic APC variants were recruited and their radiological assessments were reviewed. Patient demographic data, APC variants, adrenal mass characteristics and hormonal testing results were collected. RESULT: The prevalence of adrenal mass was 26.7% (24/90) among patients with pathogenic or likely pathogenic APC variants. Using the classic definition, the prevalence was 32.4% (22/68). Four patients had adrenal hormone testing, two of which had Conn's syndrome and two had nonspecific subclinical results. CONCLUSION: In our cohort, the prevalence of adrenal tumours among patients with pathogenic and likely pathogenic APC mutations is at least twice to three times higher than the general population prevalence reported from international population-based studies. The hormonal functions of patients with pathogenic APC variants and adrenal tumours can be investigated with routine testing in further research.

Mantle cell lymphoma in the sphenoid sinus showing acute bilateral blindness.

A 57-year-old man was referred to our department with a mass in the sphenoid sinus. Surgical removal of the tumor was performed. However, a testicular mass was found that showed rapid growth. He had undergone inguinal orchiectomy. Five days after the urological surgery, he noticed visual disturbances and bilateral visual loss. Ophthalmological examination revealed total blindness, and magnetic resonance imaging revealed sphenoid mass growth. The patient underwent emergent removal of the tumor, and a diagnosis of malignant lymphoma was made. A final diagnosis of mantle cell lymphoma (MCL) in the testis and sphenoid sinus was made. After receiving treatment with intravenous corticosteroids and chemotherapy for lymphoma, his left vision completely recovered. Although his right vision was lost, he returned to normal social activities. This is the first report in the literature on MCL developing in the sphenoid sinus presenting with bilateral blindness and ipsilateral recovery.

A case of superior mesenteric artery stenting for small intestinal ischaemia caused by superior mesenteric artery invasion of pancreatic cancer.

Superior mesenteric artery (SMA) invasion by a malignant tumour is a serious condition leading to intestinal ischaemia. Although SMA stenting has been reported to be useful for SMA dissection and stenosis caused by atherosclerotic plaque, SMA stenting for stenosis caused by malignant tumour invasion is rarely reported and uncertain. A 75-year-old woman presented intestinal ulcer and melena caused by SMA invasion of unresectable pancreatic cancer. The bare metal stent was implanted for the vessel stenosis, and a small intestinal ulcer was markedly improved after stenting. However, one and a half months after stenting the stent was occluded and a thrombectomy was performed. After thrombectomy, residual stenosis caused by tumour invasion was observed in the stent. The patient suddenly died 2 days after thrombectomy before additional covered stenting for residual stenosis. Stent implantation may be a treatment option for intestinal ischaemia caused by vessel invasion of malignant tumours. On the other hand, re-stenosis of the stent due to tumour ingrowth is a problem, and covered stenting is considered for long-term stent patency.

Exploring the impact of intra-tumoural heterogeneity on liquid biopsy cell-free DNA methylation and copy number in head and neck squamous cell carcinoma.

Liquid biopsy profiling is gaining increasing promise towards biomarker-led identification and disease stratification of tumours, particularly for tumours displaying significant intra-tumoural heterogeneity (ITH). For head and neck squamous cell carcinoma (HNSCC), which display high levels of genetic ITH, identification of epigenetic modifications and methylation signatures has shown multiple uses in stratification of HNSCC for prognosis, treatment, and HPV status. In this study, we investigated the potential of liquid biopsy methylomics and genomic copy number to profile HNSCC. We conducted multi-region sampling of tumour core, tumour margin and normal adjacent mucosa, as well as plasma cell-free DNA (cfDNA) across 9 HNSCC patients. Collectively, our work highlights the prevalence of methylomic ITH in HNSCC, and demonstrates the potential of cfDNA methylation as a tool for ITH assessment and serial sampling.

Deep Learning-Assisted interactive contouring of lung Cancer: Impact on contouring time and consistency.

BACKGROUND AND PURPOSE: To evaluate the impact of a deep learning (DL)-assisted interactive contouring tool on inter-observer variability and the time taken to complete tumour contouring. MATERIALS AND METHODS: Nine clinicians contoured the gross tumour volume (GTV) using the PET-CT scans of 10 non-small cell lung cancer (NSCLC) patients, either using DL-assisted or manual contouring tools. After contouring a case using one contouring method, the same case was contoured one week later using the other method. The contours and time taken were compared. RESULTS: Use of the DL-assisted tool led to a statistically significant decrease in active contouring time of 23 % relative to the standard manual segmentation method (p < 0.01). The mean observation time for all clinicians and cases made up nearly 60 % of interaction time for both contouring approaches. On average the time spent contouring per case was reduced from 22 min to 19 min when using the DL-assisted tool. Additionally, the DL-assisted tool reduced contour variability in the parts of tumour where clinicians tended to disagree the most, while the consensus contour was similar whichever of the two contouring approaches was used. CONCLUSIONS: A DL-assisted interactive contouring approach decreased active contouring time and local inter-observer variability when used to delineate lung cancer GTVs compared to a standard manual method. Integration of this tool into the clinical workflow could assist clinicians in contouring tasks and improve contouring efficiency.

STAT3 interactome predicts presence of proteins that regulates immune system in oral squamous cell carcinoma.

OBJECTIVES: Signal transducer and activator of transcription 3 (STAT3) is one of the key proliferation mechanism-related proteins that helps in oral squamous cell carcinoma (OSCC) progression. Immune evasion by STAT3 is mediated by the JAK2/STAT3/PDL1 signaling axis. Based on previous findings, we hypothesized that STAT3-binding partners participate in the inhibition of anti-tumor activity in OSCC. METHODS: A 3D cancer-immune co-culture model was constructed using oral cancer cell lines SCC4, SCC9, SCC25, and CAL27 and normal oral cell line OKF6. The cells were co-cultured with natural killer (NK-92) and Jurkat cells. The target protein STAT3 was chosen based on SWATH data, and co-immunoprecipitation (Co-IP)-based proteomics was conducted. The Co-IP LC-MS/MS output was analyzed to determine the protein interaction network, gene ontology, pathway analysis, and protein cluster annotation. RESULTS: STAT3 in oral cancer cell lines interacts with the epidermal growth factor receptor (EGFR) and other proteins that participate in proliferation and immune mechanisms. Proteome analysis showed that some STAT3-binding proteins found in this study are known immune system regulators. CONCLUSION: Overall, STAT3 interactive proteins regulate the immune system in oral squamous cell carcinoma cells.

Exploiting the gut microbiome for brain tumour treatment.

Increasing evidence suggests that the gut microbiome plays a key role in a host of pathological conditions, including cancer. Indeed, the bidirectional communication that occurs between the gut and the brain, known as the 'gut-brain axis,' has recently been implicated in brain tumour pathology. Here, we focus on current research that supports a gut microbiome-brain tumour link with emphasis on high-grade gliomas, the most aggressive of all brain tumours, and the impact on the glioma tumour microenvironment. We discuss the potential use of gut-brain axis signals to improve responses to current and future therapeutic approaches. We highlight that the success of novel treatment strategies may rely on patient-specific microbiome profiles, and these should be considered for personalised treatment approaches.

Prognostic impact of the tumour microenvironment in intrahepatic cholangiocarcinoma: identification of a peritumoural fibro-immune interface.

The tumour microenvironment (TME) of intrahepatic cholangiocarcinoma (iCCA) is complex and plays a role in prognosis and resistance to treatments. We aimed to decipher the iCCA TME phenotype using multiplex sequential immunohistochemistry (MS-IHC) to investigate which cell types and their spatial location may affect its prognosis. This was a retrospective study of 109 iCCA resected samples. For all cases, we used an open-source software to analyse a panel of markers (αSMA, FAP, CD8, CD163) by MS-IHC for characterize the different TME cells and their location. RNA sequencing was performed to determine the main iCCA transcriptomic classes. The association of the TME composition with overall survival (OS) was assessed by univariate and multivariate analyses. A high proportion of activated fibroblasts (FAP +) was significantly associated with poor OS (HR = 2.33, 95%CI = 1.43-3.81, p = 0.001). CD8 T lymphocytes excluded from the epithelial compartment were significantly associated with worse OS (HR = 1.86, 95% CI = 1.07-3.22, p = 0.014). The combination of a high proportion of FAP + fibroblasts and CD8 T lymphocytes excluded from the epithelial compartment, observed in 21 cases (19%), was significantly associated with poor OS on univariate (HR = 2.49, 95% CI = 1.44-4.28, p = 0.001) and multivariate analyses (HR = 2.77, 95% CI = 1.56-4.92, p < 0.001). In these cases, CD8 T lymphocytes were predominantly located at the tumour/non-tumour interface (19/21, 90%), and an association with the transcriptomic inflammatory stroma class was observed (10/21, 48%). Our results confirm the TME prognostic role in iCCA, highlighting the impact in the process of spatial heterogeneity, especially cell colocalization of immune and fibroblastic cells creating a peritumoural fibro-immune interface.

Phenotypic and spatial heterogeneity of CD8+ tumour infiltrating lymphocytes.

CD8+ T cells are the workhorses executing adaptive anti-tumour response, and targets of various cancer immunotherapies. Latest advances have unearthed the sheer heterogeneity of CD8+ tumour infiltrating lymphocytes, and made it increasingly clear that the bulk of the endogenous and therapeutically induced tumour-suppressive momentum hinges on a particular selection of CD8+ T cells with advantageous attributes, namely the memory and stem-like exhausted subsets. A scrutiny of the contemporary perception of CD8+ T cells in cancer and the subgroups of interest along with the factors arbitrating their infiltration contextures, presented herein, may serve as the groundwork for future endeavours to probe further into the regulatory networks underlying their differentiation and migration, and optimise T cell-based immunotherapies accordingly.

Long-term TNF-alpha therapy for preserving beta cell function in new onset type 1 diabetes: a case report.

BACKGROUND: Type 1 diabetes mellitus (T1D) is an autoimmune disease caused by destruction of pancreatic islet beta-cells. There is significant residual beta-cell function, measured through circulating C-peptide, present at the time of T1D diagnosis but this subsequently decreases with time. Higher residual beta-cell function at diagnosis associates with better glycaemic control and less glucose variability, and later in the disease course with less hypoglycaemia, lower glucose variability and fewer microvascular complications. There is therefore value in preserving residual beta cell function in new onset T1D Immunotherapeutic agents can protect residual beta-cell function in type 1 diabetes. However, clinical trials of such agents, whilst demonstrating C-peptide preservation in short term studies, have yet to be taken forward into routine clinical care due to concerns around safety and long-term efficacy. Here we report the case of a gentleman with newly diagnosed T1D whose glycaemic control and insulin requirement improved whilst on a five year infusion programme of infliximab, a monoclonal antibody against TNF-alpha, for colitis. CASE PRESENTATION: A 52-year-old White Caucasian man was diagnosed with T1D in August 2018. Glucose was 25.6 mmol/L, HbA1c was 98mmol/mol and GAD antibodies were strongly positive. HbA1c marginally improved to 91mmol/mol following initiation of insulin detemir 5 units at night and 1:10 g of insulin aspart (November 2018). In June 2019, he developed rectal bleeding and abdominal pain. Following colonoscopy, he was diagnosed with "indeterminate colitis" and commenced on 6-weekly infusions of 400-450 mg infliximab. Thus far, he has received 32 doses and achieved colitis remission. Following infliximab initiation there was increased frequency of mild-moderate hypoglycaemia and he was gradually weaned off and discontinued detemir in June 2020. Since then, HbA1c improved from 57mmol/mol in August 2019 to 52mmol/mol in April 2022, remaining stable at 51mmol/mol. His most recent HbA1c is 54mmol/mol in February 2024. His c-peptide was 550pmol/L in October 2022 and 442pmol/L in February 2024, suggesting well-preserved beta-cell function almost 6 years post-diagnosis. CONCLUSIONS: Our patient's improvement in glycaemic control can be explained by immunomodulation and C peptide preservation from infliximab. With the growing focus on type 1 diabetes disease modulation and working towards an 'insulin free T1D', our findings strengthen the evidence base for the repurposing of and long-term treatment with anti-TNF-α agents to preserve beta-cell function in new onset T1D.

Connectivity defines the distinctive anatomy and function of the hand-knob area.

Control of the hand muscles during fine digit movements requires a high level of sensorimotor integration, which relies on a complex network of cortical and subcortical hubs. The components of this network have been extensively studied in human and non-human primates, but discrepancies in the findings obtained from different mapping approaches are difficult to interpret. In this study, we defined the cortical and connectional components of the hand motor network in the same cohort of 20 healthy adults and 3 neurosurgical patients. We used multimodal structural magnetic resonance imaging (including T1-weighted imaging and diffusion tractography), as well as functional magnetic resonance imaging and navigated transcranial magnetic stimulation (nTMS). The motor map obtained from nTMS compared favourably with the one obtained from functional magnetic resonance imaging, both of which overlapped well within the 'hand-knob' region of the precentral gyrus and in an adjacent region of the postcentral gyrus. nTMS stimulation of the precentral and postcentral gyri led to motor-evoked potentials in the hand muscles in all participants, with more responses recorded from precentral stimulations. We also observed that precentral stimulations tended to produce motor-evoked potentials with shorter latencies and higher amplitudes than postcentral stimulations. Tractography showed that the region of maximum overlap between terminations of precentral-postcentral U-shaped association fibres and somatosensory projection tracts colocalizes with the functional motor maps. The relationships between the functional maps, and between them and the tract terminations, were replicated in the patient cohort. Three main conclusions can be drawn from our study. First, the hand-knob region is a reliable anatomical landmark for the functional localization of fine digit movements. Second, its distinctive shape is determined by the convergence of highly myelinated long projection fibres and short U-fibres. Third, the unique role of the hand-knob area is explained by its direct action on the spinal motoneurons and the access to high-order somatosensory information for the online control of fine movements. This network is more developed in the hand region compared to other body parts of the homunculus motor strip, and it may represent an important target for enhancing motor learning during early development.

To Elucidate the Effective Role of Small Molecule Regulated lncRNAs in the Tumour Microenvironment in Immunotherapy.

The tumour microenvironment is a complex ecosystem comprising tumour cells, and cancer stem cells, and support cells that facilitate cancer growth and escape from treatment. Cancer immunotherapy focuses on immunological pathways such as PD-1/PD-L1 and CTLA-4 to target cancer stem cells via immune cells. Small molecules, immune checkpoint inhibitors, are employed to impede tumour growth by targeting cellular mediators in the cell cycle and tumour microenvironment. Long non-coding RNAs (lncRNAs) affect the growth, development, motility, and differentiation of cancer cells by regulating gene expression and are therefore considered important biomarkers. Small molecules demonstrate their effects on gene expression and behaviour of cancer cells by inducing lncRNAs. This relationship between lncRNAs and small molecules is of great importance in terms of their impact on cancer and the tumour microenvironment. The evaluation of this communication in clinical trials is of critical importance for the development of therapeutic strategies. This review provides a detailed description of the role of lncRNAs and small molecules in the tumour microenvironment and their relationship with cancer stem cells. Thus, the potential of controlling lncRNAs and using anti-cancer small molecules in TME to improve the efficacy of cancer therapy was evaluated.

Challenging Nasal Pathologies: An Inverted Nasal Papilloma Case Series Illustrating Diagnostic Challenges and Management Strategies.

The sinonasal inverted papilloma is a benign tumor located in the sinuses lining the nasal cavity. It is a very rare tumor, representing approximately 4% of all sinonasal tumors. The incidence of sinonasal inverted papilloma is higher in males than females and is most commonly diagnosed in the 5th decade of life. Four separate cases of sinonasal pathology involving inverted papillomas are presented in this case series. The first clinical case presents a 68-year-old man with persistent nasal symptoms, who was found to have a sinonasal papilloma, which was successfully removed surgically. In the second case, a 61-year-old woman needed multiple procedures for a comprehensive surgical approach due to her inverted papilloma. Despite postoperative complications, the patient showed improvement at later follow-up appointments. In the third case, a 65-year-old man who had an inverted nasal papilloma previously needed surgery to remove and clear the tumor after developing acute sinusitis and rhinosinusitis symptoms. Last but not least, a 57-year-old male presented with nasal blockage and purulent discharge. Polyps were observed during the examination. The initial biopsy indicated the presence of chronic inflammatory polyps. However, during the operation, a first sample biopsy revealed an inflammatory polyp, but due to the appearance of the mass, the surgeon became suspicious and decided to take another biopsy. The second biopsy confirmed the presence of an inverted nasal papilloma. All things considered, these cases demonstrate clinical variability, difficulties in diagnosing, and effective management techniques related to inverted and sinonasal papillomas. The aim of this case series is to emphasize the importance of proper history taking, physical examination, and use of diagnostic tools to distinctly diagnose inverted nasal papilloma as its symptoms are similar to rhinosinusitis, especially chronic rhinosinusitis.

Oncoplastic breast surgery - a pictorial classification system for surgeons and radiation oncologists (OPSURGE).

INTRODUCTION: Changes to the tumour bed following oncoplastic breast surgery complicate the administration of adjuvant radiotherapy. Consensus guidelines have called for improved interdisciplinary communication to aid adjuvant boost radiotherapy. We propose a framework of tumour bed classification following oncoplastic surgery to enhance understanding and communication between the multidisciplinary breast cancer team and facilitate effective and more precise delivery of adjuvant boost radiotherapy. METHODS: A classification system was devised by grouping oncoplastic procedures based on skin incision, tissue mobilization, tumour bed distortion, seroma formation and flap reconstruction. The system is supplemented by a colour-coded pictorial guide to tumour bed rearrangement with common oncoplastic procedures. RESULTS: A 5-tier framework was developed. Representative images were produced to describe tumour bed alterations. CONCLUSION: The proposed framework (OPSURGE) improves the identification of the primary tumour bed after initial breast-conserving surgery, which is imperative to both the surgeon in planning re-excision and the radiation oncologist in planning boost radiotherapy.