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Annals of Agricultural and... Jun 2024Multiple endocrine neoplasia type 2B (MEN 2B) is a rare autosomal dominant hereditary cancer syndrome which is characterized by the appearance of medullary thyroid...
Multiple endocrine neoplasia type 2B (MEN 2B) is a rare autosomal dominant hereditary cancer syndrome which is characterized by the appearance of medullary thyroid carcinoma (MTC), pheochromocytoma, parathyroid adenomas, ganglioneuromas of the digestive tract, and musculoskeletal abnormalities. The case is presented of a 31-year-old male patient with numerous polyps in the colon described as ganglioneuromas which are ectodermal neoplasms emerging from a proliferation of ganglionic cells of the sympathetic nervous system. The results show elevated levels of normetanephrine, which is an endogenous catecholamine metabolite, and has high diagnostic sensitivity as well as specificity in pheochromocytoma detection. The patient underwent partial thyreoidectomy due to a nodular goiter. He was admitted to the Department of Gastroenterology to lead a diagnostic pathway towards MEN 2B.
Topics: Humans; Male; Adult; Multiple Endocrine Neoplasia Type 2b; Ganglioneuroma
PubMed: 38940117
DOI: 10.26444/aaem/171736 -
Respirology (Carlton, Vic.) Jun 2024
PubMed: 38932649
DOI: 10.1111/resp.14783 -
International Journal of Molecular... Jun 2024Triple-negative breast cancer (TNBC) patients are treated with traditional chemotherapy, such as the taxane class of drugs. One such drug, paclitaxel (PTX), can be...
Triple-negative breast cancer (TNBC) patients are treated with traditional chemotherapy, such as the taxane class of drugs. One such drug, paclitaxel (PTX), can be effective in treating TNBC; however, many tumors will develop drug resistance, which can lead to recurrence. In order to improve patient outcomes and survival, there lies a critical need to understand the mechanism behind drug resistance. Our lab made the novel observation that decreased expression of the Adenomatous Polyposis Coli (APC) tumor suppressor using shRNA caused PTX resistance in the human TNBC cell line MDA-MB-157. In cells lacking APC, induction of apoptosis by PTX was decreased, which was measured through cleaved caspase 3 and annexin/PI staining. The current study demonstrates that CRISPR-mediated APC knockout in two other TNBC lines, MDA-MB-231 and SUM159, leads to PTX resistance. In addition, the cellular consequences and molecular mechanisms behind APC-mediated PTX response have been investigated through analysis of the BCL-2 family of proteins. We found a significant increase in the tumor-initiating cell population and increased expression of the pro-survival family member Bcl-2, which is widely known for its oncogenic behavior. ABT-199 (Venetoclax), is a BH3 mimetic that specifically targets Bcl-2. ABT-199 has been used as a single or combination therapy in multiple hematologic malignancies and has shown promise in multiple subtypes of breast cancer. To address the hypothesis that APC-induced Bcl-2 increase is responsible for PTX resistance, we combined treatment of PTX and ABT-199. This combination treatment of CRISPR-mediated APC knockout MDA-MB-231 cells resulted in alterations in apoptosis, suggesting that Bcl-2 inhibition restores PTX sensitivity in APC knockout breast cancer cells. Our studies are the first to show that Bcl-2 functional inhibition restores PTX sensitivity in APC mutant breast cancer cells. These studies are critical to advance better treatment regimens in patients with TNBC.
Topics: Humans; Drug Resistance, Neoplasm; Cell Line, Tumor; Triple Negative Breast Neoplasms; Proto-Oncogene Proteins c-bcl-2; Apoptosis; Female; Adenomatous Polyposis Coli Protein; Gene Expression Regulation, Neoplastic; Sulfonamides; Paclitaxel; Up-Regulation; Taxoids; Bridged-Ring Compounds; Bridged Bicyclo Compounds, Heterocyclic
PubMed: 38928449
DOI: 10.3390/ijms25126745 -
International Forum of Allergy &... Jun 2024CRSwNP-specific mean total annual spending ranged from $5,837 (EDS-FLU) to $28,058 (dupilumab). Most CRSwNP patients receiving biologics had comorbid asthma and did not...
CRSwNP-specific mean total annual spending ranged from $5,837 (EDS-FLU) to $28,058 (dupilumab). Most CRSwNP patients receiving biologics had comorbid asthma and did not undergo sinus surgery. While biologics were covered by most Medicare Part D plans, only 37% of plans covered EDS-FLU.
PubMed: 38923795
DOI: 10.1002/alr.23362 -
Virchows Archiv : An International... Jun 2024Mixed adenoma-neuroendocrine tumor (MANET) comprises adenoma and well-differentiated neuroendocrine tumor (NET) components. Given the limited information on this due to...
Mixed adenoma-neuroendocrine tumor (MANET) comprises adenoma and well-differentiated neuroendocrine tumor (NET) components. Given the limited information on this due to its rarity, we aimed to clarify the clinicopathologic features and optimal management of gastric MANETs in a case series and literature review. Nine patients with gastric MANETs, including eight male and one female patient (mean age, 72 years), were identified from the institutional pathology archive. Endoscopically, the tumors appeared as flat elevated lesions with sizes ranging from 0.8 to 4.4 cm. One patient had familial adenomatous polyposis, and no patient had autoimmune gastritis. All MANETs developed in the gastric body mucosa exhibiting chronic metaplastic atrophic gastritis. The glandular components were intestinal-type low-grade adenoma, and focal high-grade dysplasia was also recognized in three cases. The NET component was in middle/deep lamina propria in six cases and confined to deep lamina propria in the remaining three cases. Minimal cytologic atypia was found in the NET component, with no recognizable mitosis and a Ki-67 labeling index of < 2%. The NET component mostly showed diffuse positivity for serotonin and CDX2, suggesting that it consists of enterochromaffin cells. Diffuse p53 immunostaining was observed only in the high-grade adenomatous component of one case. No recurrence was observed during the follow-up period of 2-94 months. Correct distinction between the NET and poorly differentiated carcinoma components is crucial to prevent overtreatment of gastric MANETs. Considering its indolent nature, endoscopic resection is the primary recommendation for gastric MANETs as well as for pure adenomas.
PubMed: 38922356
DOI: 10.1007/s00428-024-03851-3 -
JGH Open : An Open Access Journal of... Jun 2024Sessile-serrated lesions (SSLs) are challenging to detect due to their typically subtle appearance. The Workgroup serrAted polypS and Polyposis (WASP) classification was...
BACKGROUND/AIMS
Sessile-serrated lesions (SSLs) are challenging to detect due to their typically subtle appearance. The Workgroup serrAted polypS and Polyposis (WASP) classification was developed to diagnose SSLs endoscopically. This study aimed to evaluate the endoscopic characteristics of SSLs and the performance of the WASP classification in the Vietnamese population.
METHODS
This cross-sectional study was carried out on patients with lower gastrointestinal symptoms who underwent colonoscopy at a Vietnamese tertiary hospital. Univariate and multivariate analyses were performed to identify endoscopic features associated with SSLs. The performance of the WASP classification for diagnosing SSLs was assessed, and SSLs were diagnosed according to the 2019 World Health Organization (WHO) criteria.
RESULTS
There were 2489 patients, with a mean age of 52.1 ± 13.1 years and a female-to-male ratio of 1:1.1. A total of 121 specimens from 105 patients were diagnosed with SSLs. According to multivariate analysis, the endoscopic features significantly associated with SSLs were proximal location (odds ratio [OR]: 2.351; 95% confidence interval [CI]: 1.475-3.746), size >5 mm (OR: 2.447; 95% CI: 1.551-3.862), flat morphology (OR: 2.781; 95% CI: 1.533-5.044), irregular shape (OR: 4.516; 95% CI: 2.173-9.388), varicose microvascular vessels (OR: 5.030; 95% CI: 2.657-9.522), and dark spots inside the crypts (OR: 5.955; 95% CI: 3.291-10.776). The accuracy of the WASP classification for diagnosing SSLs was 94.0% (95% CI: 92.8%-95.0%).
CONCLUSION
Proximal location, size >5 mm, flat morphology, irregular shape, varicose microvascular vessels, and dark spots inside the crypts were significantly associated with SSLs. The WASP classification had high accuracy in the diagnosis of SSLs.
PubMed: 38919272
DOI: 10.1002/jgh3.13109 -
Endoscopy International Open Jun 2024There is limited consensus on the optimal method for measuring disease severity in familial adenomatous polyposis (FAP). We aimed to systematically review the operating... (Review)
Review
There is limited consensus on the optimal method for measuring disease severity in familial adenomatous polyposis (FAP). We aimed to systematically review the operating properties of existing endoscopic severity indices for FAP. We searched MEDLINE, EMBASE, and the Cochrane Library from inception to February 2023 to identify randomized controlled trials (RCTs) that utilized endoscopic outcomes or studies that evaluated the operating properties of endoscopic disease severity indices in FAP. A total of 134 studies were included. We evaluated scoring indices and component items of scoring indices, such as polyp count, polyp size, and histology. Partial validation was observed for polyp count and size. The most commonly reported scoring index was the Spigelman classification system, which was used for assessing the severity of duodenal involvement. A single study reported almost perfect interobserver and intra-observer agreement for this system. The InSIGHT polyposis staging system, which was used for assessing colorectal polyp burden, has been partially validated. It showed substantial interobserver reliability; however, the intra-observer reliability was not assessed. Novel criteria for high-risk gastric polyps have been developed and assessed for interobserver reliability. However, these criteria showed a poor level of agreement. Other scoring indices assessing the anal transition zone, duodenal, and colorectal polyps have not undergone validation. There are no fully validated endoscopic disease severity indices for FAP. Development and validation of a reliable and responsive endoscopic disease severity instrument will be informative for clinical care and RCTs of pharmacological therapies for FAP.
PubMed: 38904059
DOI: 10.1055/a-2330-8037 -
Expert Opinion on Biological Therapy Jun 2024Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent inflammatory condition with heterogenous underlying endotypes, the most common being type 2 mediated... (Review)
Review
INTRODUCTION
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent inflammatory condition with heterogenous underlying endotypes, the most common being type 2 mediated inflammation. Several biologics have been developed to target specific pro-inflammatory cytokines and their receptors with proven efficacy in both quantitative and qualitative outcomes in patients with severe uncontrolled disease. However, there is an ongoing debate on the role of biologics relative to conventional therapies for CRSwNP and their efficacy in patient subgroups with non-polyp type 2 disease.
AREAS COVERED
This review examines the evidence on the efficacy and safety of biologics in CRSwNP, recommendations for their use, and discusses the broader economic factors influencing their application in clinical practice.
EXPERT OPINION
Emerging real-life data demonstrating the variable efficacy of the available biologics for patients with CRSwNP, coupled with the high cost compared to conventional therapies such as surgery, renders biologics to be considered as an add-on therapy in the majority of cases. However, ongoing research into increasing biologic dose intervals and novel therapies targeting alternative pathways may offer a more cost-effective and sustainable option in future.
PubMed: 38900023
DOI: 10.1080/14712598.2024.2370397 -
World Journal of Gastroenterology Jun 2024The association between the intestinal microbiota and psychiatric disorders is becoming increasingly apparent. The gut microbiota contributes to colorectal...
BACKGROUND
The association between the intestinal microbiota and psychiatric disorders is becoming increasingly apparent. The gut microbiota contributes to colorectal carcinogenesis (CRC), as demonstrated with colibactin-producing (CoPEC).
AIM
To evaluate the association between CoPEC prevalence and anxiety- and depressive-like behaviors with both preclinical and clinical approaches.
METHODS
Patients followed after a CRC surgery and for whom the prevalence of CoPEC has been investigated underwent a psychiatric interview. Results were compared according to the CoPEC colonization. In parallel C57BL6/J wild type mice and mice with a CRC susceptibility were chronically infected with a CoPEC strain. Their behavior was assessed using the Elevated Plus Maze test, the Forced Swimming Test and the Behavior recognition system PhenoTyper.
RESULTS
In a limited cohort, all patients with CoPEC colonization presented with psychiatric disorders several years before cancer diagnosis, whereas only one patient (17%) without CoPEC did. This result was confirmed in C57BL6/J wild-type mice and in a CRC susceptibility mouse model (adenomatous polyposis coli). Mice exhibited a significant increase in anxiety- and depressive-like behaviors after chronic infection with a CoPEC strain.
CONCLUSION
This finding provides the first evidence that CoPEC infection can induce microbiota-gut-brain axis disturbances in addition to its procarcinogenic properties.
Topics: Animals; Mice, Inbred C57BL; Humans; Male; Polyketides; Depression; Gastrointestinal Microbiome; Anxiety; Mice; Female; Aged; Middle Aged; Escherichia coli Infections; Disease Models, Animal; Peptides; Escherichia coli; Colonic Neoplasms; Prevalence; Brain-Gut Axis
PubMed: 38899326
DOI: 10.3748/wjg.v30.i21.2817 -
Otolaryngology--head and Neck Surgery :... Jun 2024To evaluate the severity and prevalence of headache and facial pain/pressurere in the chronic rhinosinusitis (CRS) population. (Review)
Review
OBJECTIVE
To evaluate the severity and prevalence of headache and facial pain/pressurere in the chronic rhinosinusitis (CRS) population.
DATA SOURCES
CINAHL, PubMed, Scopus.
REVIEW METHODS
The literature was searched from inception through June 2023 for English language articles documenting "headache" or "facial pain/pressure" and "chronic rhinosinusitis." Data collected included Lund-MacKay computed tomography score, Lund-Kennedy endoscopy score, sinonasal outcome test, and visual analog scale. Meta-analyses were performed on continuous measures (mean), proportions (%), and regression.
RESULTS
A total of 69 studies were included with 8643 CRS patients and 703 control patients. The CRS group had a mean age of 44.1 (range: 16-82; 95% confidence interval [CI]: 40.3-48) and 86.1% [95% CI: 76.4-93.5] with nasal polyposis. The control group had a mean age of 39.2 (range: 17-88; 95% CI: 28.7-49.8). All CRS subgroups had significantly more severe headache and facial pain/pressure when compared to the control (P < .0001). Patients without polyps had significantly more severe facial pain/pressure and headache when compared to patients with polyps (P < .0001). Facial pain/pressure is a moderate problem or worse in 29.8% of polypoid patients versus 56.4% of nonpolypoid patients; Δ26.6% [95% CI: 0.7-50; P = .045].
CONCLUSIONS
Across all outcome metrics, CRS patients experience significantly more severe headache and facial pain/pressure when compared to a control population. Nonpolypoid patients experience significantly more severe facial pain/pressure and headache when compared to polypoid patients. The majority of nonpolypoid patients experience facial pain/pressure that is moderate in severity or worse.
PubMed: 38895867
DOI: 10.1002/ohn.855