Search Results for: BRCA e Adenoma del pancreas metastatico

We congratulate Djinbachian et al on their recent publication that addressed the utility of hybrid argon plasma coagulation (hAPC) to mitigate recurrence after endoscopic mucosal resection (EMR) of large non-pedunculated colorectal polyps (LNPCPs).1 In a 3-centre study, involving 391 patients (427 LNPCPs), they reported a lower residual or recurrent adenoma rate (RRA of 0.9%) with combined margin and base ablation, when compared with margin ablation alone (8.8%) or no ablation (23.4%). The insights presented in this paper open discussion on the potential enhancement of EMR outcomes. Our extensive 15-year research experience at Westmead Hospital, Sydney, aligns closely with this topic. The authors’ rationale behind base ablation is the need to treat polyp areas that might evade capture during a piecemeal resection. However, a systematic approach to LNPCP EMR may preclude its occurrence. This involves a systematic resection, starting from the lesion’s edge, ensuring a wide margin and…

Objective
Elucidating complex ecosystems and molecular features of gallbladder cancer (GBC) and benign gallbladder diseases is pivotal to proactive cancer prevention and optimal therapeutic intervention.

Design
We performed single-cell transcriptome analysis on 230 737 cells from 15 GBCs, 4 cholecystitis samples, 3 gallbladder polyps, 5 gallbladder adenomas and 16 adjacent normal tissues. Findings were validated through large-scale histological assays, digital spatial profiler multiplexed immunofluorescence (GeoMx), etc. Further molecular mechanism was demonstrated with in vitro and in vivo studies.

Results
The cell atlas unveiled an altered immune landscape across different pathological states of gallbladder diseases. GBC featured a more suppressive immune microenvironment with distinct T-cell proliferation patterns and macrophage attributions in different GBC subtypes. Notably, mutual exclusivity between stromal and immune cells was identified and remarkable stromal ecosystem (SC) heterogeneity during GBC progression was unveiled. Specifically, SC1 demonstrated active interaction between Fibro-iCAF and Endo-Tip cells, correlating with poor prognosis. Moreover, epithelium genetic variations within adenocarcinoma (AC) indicated an evolutionary similarity between adenoma and AC. Importantly, our study identified elevated olfactomedin 4 (OLFM4) in epithelial cells as a central player in GBC progression. OLFM4 was related to T-cell malfunction and tumour-associated macrophage infiltration, leading to a worse prognosis in GBC. Further investigations revealed that OLFM4 upregulated programmed death-ligand 1 (PD-L1) expression through the MAPK-AP1 axis, facilitating tumour cell immune evasion.

Conclusion
These findings offer a valuable resource for understanding the pathogenesis of gallbladder diseases and indicate OLFM4 as a potential biomarker and therapeutic target for GBC.

Studio identifica i pazienti a rischio di chirurgia inefficace

The pancreas is composed of endocrine and exocrine parts, and its interlacing structure indicates potential interaction between endocrine and exocrine cells. Although the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) has been well characterized, the role of pancreatic endocrine cells during carcinogenesis is relatively understudied.

Objective
Whether varying degrees of glycaemic control impact colonic neoplasm risk in patients with diabetes mellitus (DM) remains uncertain.

Design
Patients with newly diagnosed DM were retrieved from 2005 to 2013. Optimal glycaemic control at baseline was defined as mean haemoglobin A1c (HbA1c)

Clinical presentation A 65-year-old woman had a positive Faecal Immunochemical Test (FIT) on a bowel cancer screening programme. Her medical history included migraines and hypercholesterolaemia. She had no allergies; she took a statin daily. She worked as a teacher, smoked five cigarettes per day and drank one glass of wine per week. At colonoscopy, there was polyposis including a 20 mm caecal polyp extending into the appendiceal orifice (figure 1). This was removed with cold snare, followed by soft coagulation. Histology showed tubulovillous adenoma with low-grade dysplasia. A surveillance colonoscopy was performed 9 months later. Question What was found in the caecum at repeat colonoscopy (figure 2)? Answer Surveillance colonoscopy revealed an everted appendix entirely occupied by polyp (figure 2). This was initially presumed to be a recurrence of the previously removed adenoma and surgical resection was advised. At…

Most colorectal cancers (CRCs) develop via the adenoma-carcinoma sequence, a stepwise process characterized by mutations in healthy tissue that accumulate in the progression from adenomatous polyps to cancer. First coined the polyp-cancer sequence nearly a century ago, it is widely believed that the contemporary concept was first used by Jackman and Mayo in 1951. Even before more modern sequencing technology facilitated the elucidation of the underlying molecular mechanisms, it was well understood that this process is typically slow, generally taking approximately 10 years. This time frame is the empirical basis for most current colorectal cancer screening guidelines that endorse a 10-year interval after a colonoscopy with no abnormal findings.

Pancreatic ducts form an intricate network of tubules that secrete bicarbonate and drive acinar secretions into the duodenum. This network is formed by centroacinar cells, terminal, intercalated, intracalated ducts, and the main pancreatic duct. Ductal heterogeneity at the single-cell level has been poorly characterized; therefore, our understanding of the role of ductal cells in pancreas regeneration and exocrine pathogenesis has been hampered by the limited knowledge and unexplained diversity within the ductal network.

Objectives
To assess the association of socioeconomic demographics with recommendation for and uptake of risk-reducing bilateral salpingo-oophorectomy (rrBSO) in patients with BRCA1 and BRCA2 (BRCA1/2) mutations.

Design
Retrospective cohort, semistructured qualitative interviews.

Setting and participants
BRCA1/2 mutation carriers at an urban, public hospital with a racially and socioeconomically diverse population.

Intervention
None.

Primary and secondary outcomes
The primary outcomes were rate of rrBSO recommendation and completion. Secondary outcomes were sociodemographic variables associated with rrBSO completion.

Results
The cohort included 167 patients with BRCA1/2 mutations of whom 39% identified as black (n=65), 35% white (n=59) and 19% Hispanic (n=32). Over 95% (n=159) received the recommendation for age-appropriate rrBSO, and 52% (n=87) underwent rrBSO. Women who completed rrBSO were older in univariable analysis (p=0.05), but not in multivariable analysis. Completion of rrBSO was associated with residence in zip codes with lower unemployment and documented recommendation for rrBSO (p

Objectives
Women who inherit a pathogenic BRCA1 or BRCA2 mutation are at substantially higher risk of developing breast and ovarian cancer than average. Several cancer risk management strategies exist to address this increased risk. Decisions about which strategies to choose are complex, personal and multifactorial for these women. Decision aids (DAs) are tools that assist patients in making health-related decisions. The aim of this scoping review was to map evidence relating to the development and testing of patient DAs for cancer unaffected BRCA mutation carriers.

Design
Scoping review conducted according to the Joanna Briggs Institute’s (JBI’s) scoping review methodological framework.

Data sources
MEDLINE, EMBASE, CINAHL, Web of Science. No restrictions applied for language or publication date. A manual search was also performed.

Eligibility criteria for selecting studies
Studies on DAs for cancer risk management designed for or applicable to women with a pathogenic BRCA1 or BRCA2 mutation who are unaffected by breast or ovarian cancer.

Data extraction and synthesis
Data were extracted using a form based on the JBI instrument for extracting details of studies’ characteristics and results. Data extraction was performed independently by two reviewers. Extracted data were tabulated.

Results
32 evidence sources relating to development or testing of 21 DAs were included. Four DAs were developed exclusively for cancer unaffected BRCA mutation carriers. Of these, two covered all guideline recommended risk management strategies for this population though only one of these was readily available publicly in its full version. All studies investigating DA effectiveness reported a positive effect of the DA under investigation on at least one of the outcomes evaluated, however only six DAs were tested in randomised controlled trials.

Conclusion
This scoping review has mapped the landscape of the literature relating to developing and testing, DAs applicable to cancer unaffected BRCA mutation carriers.

Objective
Currently, there is no cure for chronic pancreatitis (CP). Germline loss-of-function variants in SPINK1 (encoding trypsin inhibitor) are common in patients with CP and are associated with acute attacks and progression of the disease. This preclinical study was conducted to explore the potential of adeno-associated virus type 8 (AAV8)-mediated overexpression of human SPINK1 (hSPINK1) for pancreatitis therapy in mice.

Design
A capsid-optimised AAV8-mediated hSPINK1 expression vector (AAV8-hSPINK1) to target the pancreas was constructed. Mice were treated with AAV8-hSPINK1 by intraperitoneal injection. Pancreatic transduction efficiency and safety of AAV8-hSPINK1 were dynamically evaluated in infected mice. The effectiveness of AAV8-hSPINK1 on pancreatitis prevention and treatment was studied in three mouse models (caerulein-induced pancreatitis, pancreatic duct ligation and Spink1 c.194+2T >C mouse models).

Results
The constructed AAV8-hSPINK1 vector specifically and safely targeted the pancreas, had low organ tropism for the heart, lungs, spleen, liver and kidneys and had a high transduction efficiency (the optimal expression dose was 2×1011 vg/animal). The expression and efficacy of hSPINK1 peaked at 4 weeks after injection and remained at significant level for up to at least 8 weeks. In all three mouse models, a single dose of AAV8-hSPINK1 before disease onset significantly alleviated the severity of pancreatitis, reduced the progression of fibrosis, decreased the levels of apoptosis and autophagy in the pancreas and accelerated the pancreatitis recovery process.

Conclusion
One-time injection of AAV8-hSPINK1 safely targets the pancreas with high transduction efficiency and effectively ameliorates pancreatitis phenotypes in mice. This approach is promising for the prevention and treatment of CP.

Present in all eukaryotic cells, the integrated stress response (ISR) is a highly coordinated signaling network that controls cellular behavior, metabolism and survival in response to diverse stresses. The ISR is initiated when any one of four stress sensing kinases (PERK, GCN2, PKR, HRI) becomes activated to phosphorylate the protein translation initiation factor eIF2α, shifting gene expression toward a comprehensive rewiring of cellular machinery to promote adaptation. While the ISR has been shown to play an important role in the homeostasis of multiple tissues, evidence suggests that it is particularly crucial for the development and ongoing health of the pancreas.