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BMJ Open Gastroenterology Jan 2024Colorectal cancer (CRC) has a significant role in cancer-related mortality. Colonoscopy, combined with adenoma removal, has proven effective in reducing CRC incidence.... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Colorectal cancer (CRC) has a significant role in cancer-related mortality. Colonoscopy, combined with adenoma removal, has proven effective in reducing CRC incidence. However, suboptimal colonoscopy quality often leads to missed polyps. The impact of artificial intelligence (AI) on adenoma and polyp detection rate (ADR, PDR) is yet to be established.
DESIGN
We conducted a randomised controlled trial at Sahlgrenska University Hospital in Sweden. Patients underwent colonoscopy with or without the assistance of AI (AI-C or conventional colonoscopy (CC)). Examinations were performed with two different AI systems, that is, Fujifilm CADEye and Medtronic GI Genius. The primary outcome was ADR.
RESULTS
Among 286 patients, 240 underwent analysis (average age: 66 years). The ADR was 42% for all patients, and no significant difference emerged between AI-C and CC groups (41% vs 43%). The overall PDR was 61%, with a trend towards higher PDR in the AI-C group. Subgroup analysis revealed higher detection rates for sessile serrated lesions (SSL) with AI assistance (AI-C 22%, CC 11%, p=0.004). No difference was noticed in the detection of polyps or adenomas per colonoscopy. Examinations were most often performed by experienced endoscopists, 78% (n=86 AI-C, 100 CC).
CONCLUSION
Amidst the ongoing AI integration, ADR did not improve with AI. Particularly noteworthy is the enhanced detection rates for SSL by AI assistance, especially since they pose a risk for postcolonoscopy CRC. The integration of AI into standard colonoscopy practice warrants further investigation and the development of improved software might be necessary before enforcing its mandatory implementation.
TRIAL REGISTRATION NUMBER
NCT05178095.
Topics: Humans; Aged; Artificial Intelligence; Prospective Studies; Early Detection of Cancer; Colonoscopy; Adenoma
PubMed: 38290758
DOI: 10.1136/bmjgast-2023-001247 -
Frontiers in Endocrinology 2023Somatotropinomas are the main cause of acromegaly. Surgery is the primary and most efficient method of treatment. The study aimed to compare the radicality of... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Somatotropinomas are the main cause of acromegaly. Surgery is the primary and most efficient method of treatment. The study aimed to compare the radicality of small-sized and medium (<30 mm) somatotropinoma removal and the incidence of postoperative complications in patients with acromegaly when using microscopic and endoscopic techniques.
METHODS
In this randomized controlled trial, a total of 83 patients with acromegaly underwent transspheroidal endoscopy or microscopic surgery. Somatotropinoma was the cause of acromegaly in all cases. Patients were randomly divided into two comparison groups depending on the applied surgical technique. Group 1 (n = 40) consisted of patients who underwent adenomectomy with transnasal transsphenoidal access by a microscope. Group 2 (n = 43) included patients who underwent the same surgical procedure with an endoscope. The following indicators were assessed: radicality of tumor removal, treatment effectiveness, postoperative complications, and remission rate.
RESULTS
The study has shown that removal of somatotropinoma in patients with acromegaly using endoscopic technique increases the radicality of tumor removal in comparison with microscopic technique. Total removal of somatotropinoma was successful in 88.4% of cases when using the endoscopic technique. Secondly, the segmentation of patients according to their tumor characteristics poses challenges, primarily owing to the rarity of acromegaly as a disease. The difference between groups was not statistically significant (p=1.02). There were no statistically significant differences in basal GH level and IGF-1 level between groups (p=0.546 and p=0.784, respectively).
DISCUSSION
Endonasal transsphenoidal endoscopic adenomectomy is proven efficacy, a less traumatic degree, and higher somatotropinoma removal radicality. Both surgical methods lead to disease remission.
Topics: Humans; Acromegaly; Endoscopy; Adenoma; Growth Hormone-Secreting Pituitary Adenoma; Postoperative Complications; Pituitary Neoplasms
PubMed: 37766690
DOI: 10.3389/fendo.2023.1128345 -
Population Health Management Aug 2023The Centers for Medicare & Medicaid Services (CMS) recommend covering blood-based tests meeting proposed minimum performance thresholds for colorectal cancer (CRC)...
The Centers for Medicare & Medicaid Services (CMS) recommend covering blood-based tests meeting proposed minimum performance thresholds for colorectal cancer (CRC) screening. Outcomes were compared between currently available stool-based screening tests and a hypothetical blood-based test meeting CMS minimum thresholds. Using the Colorectal Cancer and Adenoma Incidence and Mortality Microsimulation Model (CRC-AIM), outcomes were simulated for average-risk individuals screened between ages 45 and 75 years with triennial multitarget stool DNA (mt-sDNA), annual fecal immunochemical test (FIT), and annual fecal occult blood test (FOBT). Per CMS guidance, blood-based CRC screening was modeled triennially, with 74% CRC sensitivity and 90% specificity. Although not specified by CMS, adenoma sensitivity was set between 10% and 20%. Published adenoma and CRC sensitivity and specificity were used for stool-based tests. Adherence was set at (1) 100%, (2) 30%-70%, in 10% increments, and (3) real-world rates for stool-based tests (mt-sDNA = 65.6%; FIT = 42.6%; FOBT = 34.4%). Assuming perfect adherence, a blood-based test produced ≥19 lower life-years gained (LYG) than stool-based strategies. At the best-case scenario for blood-based tests (100% adherence and 20% adenoma sensitivity), mt-sDNA at real-world adherence achieved more LYG (287.2 vs. 297.1, respectively) with 14% fewer colonoscopies. At 100% blood-based test adherence and real-world mt-sDNA and FIT adherence, the blood-based test would require advanced adenoma sensitivity of 30% to reach the LYG of mt-sDNA (297.1) and ∼15% sensitivity to reach the LYG of FIT (258.9). This model suggests that blood-based tests with CMS minimally acceptable CRC sensitivity and low advanced adenoma sensitivity will frequently yield inferior outcomes to stool-based testing across a wide range of adherence assumptions.
Topics: Aged; Humans; United States; Early Detection of Cancer; Medicare; Sensitivity and Specificity; Mass Screening; Colorectal Neoplasms; Adenoma
PubMed: 37466476
DOI: 10.1089/pop.2023.0037 -
Digestive Diseases and Sciences Aug 2023Streptococcus gallolyticus subspecies gallolyticus (SGG) and Fusobacterium (F.) nucleatum have been implicated in colorectal carcinogenesis. Here, the association of...
BACKGROUND
Streptococcus gallolyticus subspecies gallolyticus (SGG) and Fusobacterium (F.) nucleatum have been implicated in colorectal carcinogenesis. Here, the association of immune responses to bacterial exposure with advancing stages of colorectal neoplasia was assessed by multiplex serology.
METHODS
Immunoglobulin (Ig) A and G antibody responses to eleven proteins each of F. nucleatum and SGG were measured in plasma of controls (n = 100) and patients with colorectal cancer (CRC, n = 25), advanced adenoma (n = 82), or small polyps (n = 85). Multivariable logistic regression was used to evaluate the association of bacterial sero-positivity with colorectal neoplasia. In a cohort subset with matched data (n = 45), F. nucleatum sero-positivity was correlated with bacterial abundance in both neoplastic and matched normal tissue.
RESULTS
IgG sero-positivity to Fn1426 of F. nucleatum was associated with an increased CRC risk (OR = 4.84; 95% CI 1.46-16.0), while IgA sero-positivity to any SGG protein or specifically Gallo0272 and Gallo1675 alone was associated with increased advanced adenoma occurrence (OR = 2.02, 95% CI 1.10-3.71; OR = 2.67, 95% CI 1.10-6.46; and OR = 6.17, 95% CI 1.61-23.5, respectively). Only F. nucleatum abundance in the normal mucosa positively correlated with the IgA response to the Fn1426 antigen (Correlation coefficient (r) = 0.38, p < 0.01).
CONCLUSION
Antibody responses to SGG and F. nucleatum were associated with occurrence of colorectal adenomas and CRC, respectively. Further studies are needed to clarify the role these microbes or the immune response to their antigens may have in colorectal carcinogenesis stages.
Topics: Humans; Fusobacterium nucleatum; Streptococcus gallolyticus; Antibody Formation; Colorectal Neoplasms; Bacteria; Adenoma; Carcinogenesis; Fusobacterium Infections
PubMed: 37338617
DOI: 10.1007/s10620-023-08001-4 -
Endocrinology and Metabolism (Seoul,... Dec 2023Pituitary neuroendocrine tumors (PitNETs) are the third most frequently diagnosed intracranial tumors, with nonfunctioning PitNETs (nfPitNETs) accounting for 30% of all... (Review)
Review
Pituitary neuroendocrine tumors (PitNETs) are the third most frequently diagnosed intracranial tumors, with nonfunctioning PitNETs (nfPitNETs) accounting for 30% of all pituitary tumors and representing the most common type of macroPitNETs. NfPitNETs are usually benign tumors with no evidence of hormone oversecretion except for hyperprolactinemia secondary to pituitary stalk compression. Due to this, they do not typically present with clinical syndromes like acromegaly, Cushing's disease or hyperthyroidism and instead are identified incidentally on imaging or from symptoms of mass effects (headache, vision changes, apoplexy). With the lack of effective medical interventions, first-line treatment is transsphenoidal surgical resection, however, nfPitNETs often have supra- or parasellar extension, and total resection of the tumor is often not possible, resulting in residual tumor regrowth or reoccurrence. While functional PitNETs can be easily followed for recurrence using hormonal biomarkers, there is no similar parameter to predict recurrence in nfPitNETs, hence delaying early recognition and timely management. Therefore, there is a need to identify prognostic biomarkers that can be used for patient surveillance and as therapeutic targets. This review focuses on summarizing the current evidence on nfPitNETs, with a special focus on potential new biomarkers and therapeutics.
Topics: Humans; Pituitary Neoplasms; Neuroendocrine Tumors; Adenoma; Acromegaly; Biomarkers
PubMed: 37964483
DOI: 10.3803/EnM.2023.1838 -
Cell Death & Disease Nov 2023Mesothelioma is an aggressive cancer of the mesothelial layer associated with an extensive fibrotic response. The latter is in large part mediated by cancer-associated...
Mesothelioma is an aggressive cancer of the mesothelial layer associated with an extensive fibrotic response. The latter is in large part mediated by cancer-associated fibroblasts which mediate tumour progression and poor prognosis. However, understanding of the crosstalk between cancer cells and fibroblasts in this disease is mostly lacking. Here, using co-cultures of patient-derived mesothelioma cell lines and lung fibroblasts, we demonstrate that fibroblast activation is a self-propagated process producing a fibrotic extracellular matrix (ECM) and triggering drug resistance in mesothelioma cells. Following characterisation of mesothelioma cells/fibroblasts signalling crosstalk, we identify several FDA-approved targeted therapies as far more potent than standard-of-care Cisplatin/Pemetrexed in ECM-embedded co-culture spheroid models. In particular, the SRC family kinase inhibitor, Saracatinib, extends overall survival well beyond standard-of-care in a mesothelioma genetically-engineered mouse model. In short, we lay the foundation for the rational design of novel therapeutic strategies targeting mesothelioma/fibroblast communication for the treatment of mesothelioma patients.
Topics: Animals; Mice; Humans; Mesothelioma, Malignant; Mesothelioma; Fibroblasts; Cancer-Associated Fibroblasts; Lung
PubMed: 37938546
DOI: 10.1038/s41419-023-06240-x -
Endoscopy Dec 2023Texture and color enhancement imaging (TXI) was recently proposed as a substitute for standard high definition white-light imaging (WLI) to increase lesion detection... (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
BACKGROUND
Texture and color enhancement imaging (TXI) was recently proposed as a substitute for standard high definition white-light imaging (WLI) to increase lesion detection during colonoscopy. This international, multicenter randomized trial assessed the efficacy of TXI in detection of colorectal neoplasia.
METHODS
Consecutive patients aged ≥ 40 years undergoing screening, surveillance, or diagnostic colonoscopies at five centers (Italy, Germany, Japan) between September 2021 and May 2022 were enrolled. Patients were randomly assigned (1:1) to TXI or WLI. Primary outcome was adenoma detection rate (ADR). Secondary outcomes were adenomas per colonoscopy (APC) and withdrawal time. Relative risks (RRs) adjusted for age, sex, and colonoscopy indication were calculated.
RESULTS
We enrolled 747 patients (mean age 62.3 [SD 9.5] years, 50.2 % male). ADR was significantly higher with TXI (221/375, 58.9 %) vs. WLI (159/372, 42.7 %; adjusted RR 1.38 [95 %CI 1.20-1.59]). This was significant for ≤ 5 mm (RR 1.42 [1.16-1.73]) and 6-9 mm (RR 1.36 [1.01-1.83]) adenomas. A higher proportion of polypoid (151/375 [40.3 %] vs. 104/372 [28.0 %]; RR 1.43 [1.17-1.75]) and nonpolypoid (136/375 [36.3 %] vs. 102/372 [27.4 %]; RR 1.30 [1.05-1.61]) adenomas, and proximal (143/375 [38.1 %] vs. 111/372 [29.8 %]; RR 1.28 [1.05-1.57]) and distal (144/375 [38.4 %] vs. 98/372 [26.3 %]; RR 1.46 [1.18-1.80]) lesions were found with TXI. APC was higher with TXI (1.36 [SD 1.79] vs. 0.89 [SD 1.35]; incident rate ratio 1.53 [1.25-1.88]).
CONCLUSIONS
TXI increased ADR and APC among patients undergoing colonoscopy for various indications. TXI increased detection of polyps < 10 mm, both in the proximal and distal colon, and may help to improve colonoscopy quality indicators.
Topics: Humans; Male; Middle Aged; Female; Colorectal Neoplasms; Colonoscopy; Polyps; Adenoma; Colonic Polyps
PubMed: 37451283
DOI: 10.1055/a-2129-7254 -
Molecular Cancer Jul 2023Malignant Pleural Mesothelioma (MPM) is a dreadful disease escaping the classical genetic model of cancer evolution and characterized by wide heterogeneity and...
BACKGROUND
Malignant Pleural Mesothelioma (MPM) is a dreadful disease escaping the classical genetic model of cancer evolution and characterized by wide heterogeneity and transcriptional plasticity. Clinical evolution of MPM is marked by a progressive transdifferentiation that converts well differentiated epithelioid (E) cells into undifferentiated and pleomorphic sarcomatoid (S) phenotypes. Catching the way this transition takes place is necessary to understand how MPM develops and progresses and it is mandatory to improve patients' management and life expectancy. Bulk transcriptomic approaches, while providing a significant overview, failed to resolve the timing of this evolution and to identify the hierarchy of molecular events through which this transition takes place.
METHODS
We applied a spatially resolved, high-dimensional transcriptomic approach to study MPM morphological evolution. 139 regions across 8 biphasic MPMs (B-MPMs) were profiled using the GeoMx™Digital Spatial Profiler to reconstruct the positional context of transcriptional activities and the spatial topology of MPM cells interactions. Validation was conducted on an independent large cohort of 84 MPMs by targeted digital barcoding analysis.
RESULTS
Our results demonstrated the existence of a complex circular ecosystem in which, within a strong asbestos-driven inflammatory environment, MPM and immune cells affect each other to support S-transdifferentiation. We also showed that TGFB1 polarized M2-Tumor Associated Macrophages foster immune evasion and that TGFB1 expression correlates with reduced survival probability.
CONCLUSIONS
Besides providing crucial insights into the multidimensional interactions governing MPM clinical evolution, these results open new perspectives to improve the use of immunotherapy in this disease.
Topics: Humans; Mesothelioma, Malignant; Mesothelioma; Transcriptome; Ecosystem; Pleural Neoplasms; Lung Neoplasms; Prognosis; Biomarkers, Tumor; Immunotherapy
PubMed: 37460925
DOI: 10.1186/s12943-023-01816-9 -
Medicina (Kaunas, Lithuania) Nov 2023: Colorectal cancer (CRC) incidence is rapidly emerging among individuals <50 years, termed as early-onset colorectal cancer (EOCRC). This study aimed to probe...
: Colorectal cancer (CRC) incidence is rapidly emerging among individuals <50 years, termed as early-onset colorectal cancer (EOCRC). This study aimed to probe variations in tumorigenic pathology and relevant manifestations (polyp and adenoma incidence) between suspected cases of EOCRC and late-onset CRC (LOCRC; ≥50 years of age). : Between September 2022 and February 2023, colonoscopy-based screening data from 1653 patients were included in this study. All eligible participants were divided into two groups, depending upon patient age, where Group 1 consisted of 1021 patients aged <50 years while Group 2 consisted of 632 patients aged ≥ 50 years. Polyp samples were collected when identified peri-procedurally and characterized according to World Health Organization criteria. : Polyp detection rate was 42% for the <50-year age group, while this was 76% for the ≥50-year age group. Additionally, the <50-year age group predominated in hyperplastic polyp manifestation, particularly within the rectum and sigmoid colon. In addition, the ≥50-year age group had increased prevalence of serrated polyps and differing adenoma manifestations. : This investigation served to highlight the importance of age stratification for CRC colonoscopy-based screening effectiveness, with particular reference to evaluations that are based on polyp localization within differing colon regions.
Topics: Humans; Middle Aged; Colonic Polyps; Early Detection of Cancer; Colonoscopy; Colorectal Neoplasms; Adenoma
PubMed: 38004066
DOI: 10.3390/medicina59112017 -
BMC Pediatrics Aug 2023Hepatocellular adenomas (HCAs) are rare benign tumors of the liver that occur predominantly in women taking oral contraceptives. In children, HCAs comprise < 5% of... (Review)
Review
BACKGROUND
Hepatocellular adenomas (HCAs) are rare benign tumors of the liver that occur predominantly in women taking oral contraceptives. In children, HCAs comprise < 5% of hepatic tumors. We report a case of HCAs in a 7-year-old girl with estrogen and glucose imbalance.
CASE PRESENTATION
A 7-year-old girl was presented to our hospital with bilateral breast enlargement for 2 months, polydipsia, polyuria, polyphagia, hyperglycemia, and significant weight gain. Computed tomography (CT) showed a 7.2 cm×6.9 cm×5.3 cm round-shaped mass in the left inner lobe of the liver, ovarian ultrasound showed multiple follicles in the ovaries bilaterally, and cranial magnetic resonance imaging (MRI) showed an enlarged superior pituitary. Hematological and biochemical results were as follows: fasting glucose was 19.7 mmol/L, estradiol was 122.9 pmol/L, follicle-stimulating hormone 10.81 IU/L, luteinizing hormone 10.99 IU/L, insulin-like growth factor 1,513 ng/mL, glutamine aminotransferase 86 U/L, and alkaline phosphatase 362 U/L. Thyroid functions, methemoglobin, fetal protein, carcinoembryonic antigen, and chorionic gonadotropin were normal. The patient had a complete surgical resection of the liver tumor, and the postoperative histopathological diagnosis was HCAs. After the surgery, insulin was injected and the glucose levels were stable. During the 36-month follow-up period, neither tumor recurrence nor significant abnormalities were detected using color Doppler ultrasound of the liver. The child's precocious puberty is currently under control.
CONCLUSIONS
HCAs are particularly rare in children with liver tumors, and risk factors for the development of HCAs in children include sex hormone imbalance, obesity, Fanconi anemia (FA), glycogen storage diseases (GSDs) type I, III, and IV, galactosemia, immunodeficiency, congenital portosystemic shunts (CPSS), cardiac hepatopathy status-post Fontan procedure, Hurler syndrome, familial adenomatous polyposis, germline HNF1A mutations, and maturity-onset diabetes of the young type 3. Most HCAs are detected during a physical examination without clinical symptoms, and some patients may present with symptoms such as abdominal pain, abdominal distension, and abdominal masse. Serum liver function tests can show increased alkaline phosphatase (ALP) and γ- glutamyl transferase (GT), whereas α-Fetoprofein (AFP) levels are normal. The definitive diagnosis relies mainly on histopathological examination. Because HCAs can rupture and bleed and become malignant. Early surgical treatment is recommended after detection.
Topics: Child; Humans; Female; Adenoma, Liver Cell; Alkaline Phosphatase; Neoplasm Recurrence, Local; Liver Neoplasms
PubMed: 37620840
DOI: 10.1186/s12887-023-04209-5