Incidence Of Adenomas Research Articles

Correlation between Metabolite of Prostaglandin E2 and the incidence of colorectal adenomas.

Colorectal cancer is a common malignancy, and the incidence and mortality rates continue to rise. An important factor in the emergence of inflammation-induced colorectal carcinogenesis is elevated cyclooxygenase-2. Prostaglandin E2 (PGE2) over-production is frequently equated with cyclooxygenase-2 gene over-expression. PGE2 can be assessed by measuring the level of prostaglandin's main metabolite, PGE-M, in urine. Colorectal adenoma is a precancerous lesion that can lead to colorectal cancer. We conducted research to evaluate the association between urinary levels of the PGE-M and the risk of colorectal adenomas. In a western Chinese population, we identified 152 cases of adenoma and 152 controls patients without polyps. Adenoma cases were categorized into control, low-risk and high-risk groups. There was no significant change in PGE-M levels, between the control group and the low-risk adenoma group. In the high-risk group, the PGE-M levels were 23% higher than the control group. When compared to people with the lowest urine PGE-M levels (first quartile), people with greater urinary PGE-M levels had a higher chance of developing high-risk colorectal adenomas, with an adjusted odds ratio (95% CI) of 1.65 (0.76-3.57) in the fourth quartile group, (p= 0.013). We conclude urinary PGE-M is associated with the risk of developing high-risk adenomas. Urinary PGE-M level may be used as a non-invasive indicator for estimating cancer risk.

ВЛИЯНИЕ ПАНДЕМИИ COVID-19 НА ХИРУРГИЮ ЩИТОВИДНОЙ ЖЕЛЕЗЫ: РЕТРОСПЕКТИВНОЕ ИССЛЕДОВАНИЕ

Introduction. The COVID-19 pandemic has affected the pathomorphism of many diseases due to the pathophysiological impact of the infectious process and its drug therapy, and sometimes due to changes in the organization of medical care. During the pandemic, the number of patients with thyroid nodules has increased. Aim. To analyze the impact of the COVID-19 pandemic in Crimea on the surgical aspects of thyroid diseases. Material and methods. A study was made of the impact of the COVID-19 pandemic in Crimea on the surgical aspects of thyroid diseases. Statistical work was carried out with the data of the conclusions of cytological and pathomorphological diagnostics in 1244 patients during the period before, during and after the pandemic. A detailed analysis of cytology according to Bethesda was performed with the calculation of the percentage of conclusions of classes I-VI, morphological data of histological studies with a detailed assessment of malignant neoplasms. Results and discussion. After the start of the epidemic, at the preoperative stage of diagnosing thyroid nodules, an increase in the percentage of nodes with signs of cancer was noted compared to the period of 2019. During the pandemic, a reversible increase in the number of operations for toxic goiter and an irreversible increase in the proportion of malignant tumors were established; an increase in the incidence of B-cell adenomas; the prevalence after the pandemic of more differentiated forms of cancer with a low-risk prognosis, as well as tumors at earlier stages. Such dynamics is probably associated with a complex of factors: antigenic mimicry of the virus, its tropism for thyrocytes, stress and immunosuppression, paradoxically more timely seeking surgical care. Conclusion. The pandemic is characterized by an increase in the number of patients with primary manifestations of thyroid diseases, an increase in the number of toxic goiters and adenomas against the background of gland hyperfunction, a change in the incidence of papillary cancer - an increase in the number of patients, but the identification of prognostically more favorable forms.

Carcinogenicity and chronic toxicity of butyl methacrylate in rats and mice by a two-year inhalation study.

We conducted a two-year inhalation study of butyl methacrylate using F344/DuCrlCrlj rats and B6D2F1/Crl mice. Rats were exposed to 0, 30, 125 and 500 ppm (v/v) and mice were exposed to 0, 8, 30 and 125 ppm (v/v) using whole-body inhalation chambers. Non-neoplastic lesions developed in the nasal cavities of both rats and mice, but neoplastic lesions were not found. There was also a positive trend in the incidence of large granular lymphocytic (LGL) leukemia in the spleen of male rats. No changes were observed in female rats. Overall, there is some evidence of carcinogenicity in male rats, but there is no evidence of carcinogenicity in female rats. In male mice, there was a positive trend by Peto's test in the incidence of hepatocellular adenomas, and the incidence of hepatocellular adenomas and hepatocellular carcinomas combined was significantly increased compared to the controls by Fisher's exact test in the 30 ppm exposed male group. In female mice, the incidence of hemangiosarcoma in all organs combined showed a positive trend by Peto's test. Therefore, there is some evidence of carcinogenicity in male mice, and there is equivocal evidence of carcinogenicity in female mice.

Surveillance Outcomes in Patients With a Family History ofColorectal Cancer in Both Parents.

A family history of colorectal cancer (CRC) in a first-degree relative is a well-established risk factor for CRC. When individuals have 2 parents with CRC, the impact on risk is uncertain, and there are no established guidelines for surveillance. We sought to define the surveillance practices and outcomes in individuals with a family history of CRC in both parents. We identified probands with a family history of CRC in both parents from our Hereditary Gastrointestinal Cancer Database. Charts were retrospectively reviewed for colonoscopy surveillance patterns and incidence of adenomas and CRC. Sixty-six patients met the inclusion criteria. Forty-two patients (64%) had genetic testing, and no pathogenic germline mutations were identified. During a mean surveillance period of 144 ± 82.2 months and a mean surveillance interval of 33.4 ± 16.6 months, a total of 3.2 ± 8.9 adenomas were found per patient. These were small (median 6.5 mm), and 96% exhibited only low-grade dysplasia. Six patients (9%) were diagnosed with CRC at a mean age of 61.5 ± 11.3 years, corresponding to an incidence rate of 14 cases/10,000 person-years. Patients with CRC were older at first colonoscopy than those without cancer (59 vs 46 years, P= .03), and half of these cases were diagnosed at this first colonoscopy. Among patients with a family history of CRC in both parents, cases of CRC were seen primarily in those who significantly delayed their first colonoscopy. Initiation of colonoscopy at age 40 should be recommended to individuals with CRC in both parents, consistent with recommendations for those with 1 first-degree relative with CRC.

Clear evidence of the carcinogenic potential of anthracene: A 2-year feeding study in rats and mice.

Anthracene is an environmental pollutant and its adverse effects on human health have long been a concern due to its persistence and bioaccumulation properties. However, there is insufficient evidence for its chronic toxicity, especially carcinogenicity, in either humans or experimental animals. In this study, its carcinogenicity and chronic toxicity were investigated in compliance with the OECD test guideline 451 (OECD TG 451) and Good Laboratory Practice Standards. Fifty male and 50 female F344 rats and 50 female BDF1 mice were administrated 0, 8000, 20000, or 50000 ppm anthracene in the diet for 104 weeks, and 50 male BDF1 mice were fed diets containing anthracene at 0, 3200, 8000, or 20000 ppm. Anthracene treatment had no adverse effect on either the survival rate or general condition of the rats or mice during the study period. Body weights were lower or tended to be lower in the anthracene-treated groups than in the control groups. Increased incidence of hepatocellular carcinoma and hepatocellular adenoma was observed in male rats and female mice. Renal cell carcinoma and renal cell adenoma, fibroadenoma in the mammary gland, and uterine endometrial stromal sarcoma were increased in female rats. Transitional cell carcinoma and transitional cell papilloma in the urinary bladder were also increased in male and female rats. In addition, several different pre-neoplastic lesions were increased in the anthracene-treated male and female rats and female mice. These results provide clear evidence that oral administration of anthracene for 104 weeks has a carcinogenic effect in male and female rats and female mice.

PSAT213 Intrathyroidal Parathyroid Adenoma Diagnosed on Thyroseq v2

Abstract Background The incidence of intrathyroidal parathyroid adenoma varies from <1% to 6% and can be a diagnostic dilemma. Intrathyroidal parathyroid adenomas can have suspicious sonographic features that prompt fine needle aspiration (FNA) to evaluate for thyroid cancer. Differentiation between thyroid and parathyroid tissue on cytology can be difficult, and these lesions may be diagnosed as indeterminate thyroid nodules. Molecular testing is a useful adjunct that allows for identification of parathyroid adenomas in this setting. Clinical Case A 59-year-old female with osteopenia and a recent history of traumatic vertebral fracture presented for workup of asymptomatic hypercalcemia. Labs showed intact parathyroid hormone (iPTH) 168 pg/mL (reference 11-51 pg/mL), serum total calcium 12.2 mg/dL (reference range 8.6-10.4 mg/dL), albumin 4.7 g/dL (reference 4.1-5.3 g/dL), phosphorus 2.1 mg/dL (reference 2.3-4.4 mg/dL), creatinine 0.7 (reference 0.6-1.3 mg/dL), and 25-OH vitamin of 28 ng/mL (reference 20-50 ng/mL). Cervical ultrasound showed a 2.1 cm hypoechoic left thyroid nodule. Subsequent 99mTc-Sesatmibi scan showed increased tracer retention in the left posterior thyroid lobe. FNA of the left thyroid nodule was performed with cytology showing follicular lesion of undetermined significance (FLUS). Molecular testing with Thyroseq v2 showed parathyroid tissue consistent with intrathyroidal parathyroid adenoma. The patient underwent successful left thyroid lobectomy with removal of an intrathyroidal parathyroid gland, with subsequent decrease of iPTH to 44 pg/mL (reference 11-51 pg/mL) and total serum calcium to 9.5 mg/dL (reference 8.6-10.4 mg/dL). Surgical pathology confirmed parathyroid adenoma. Discussion Due to the ubiquity of thyroid FNAs to rule out malignancy, there has been a rise in the number of incidental parathyroid gland aspirations. Thyroid lesions with diagnosis of FLUS or oncocytic features are prone to misdiagnosis due to similarities in morphologic overlap and anatomic proximity. Molecular testing such as Thyroseq v2 routinely tests for PTH and can identify parathyroid tissue in lesions initially diagnosed as indeterminate thyroid nodules. Newer molecular test versions including ThyroSeq v3 similarly have high analytical accuracy in detecting thyroid cancer and parathyroid lesions. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Visceral Obesity Is a More Important Factor for Colorectal Adenomas than Skeletal Muscle or Body Fat.

Although the incidence of colorectal adenomas increases with obesity, the role of various body compositions is still unknown. We aimed to determine which body composition best reflects the risk of colorectal adenomas. Patients aged 50-75 years who underwent colonoscopy and a bioelectrical impedance analysis (BIA) for a health check-up from 2017 to 2019 were retrospectively enrolled. The skeletal muscle index (SMI), fat mass index (FMI), and visceral fat index (VFI) were obtained using BIA. The muscle-to-fat ratio (MFR) and the skeletal muscle mass to visceral fat area ratio (SVR) were calculated. Among 15,102 patients, 6605 (43.7%) had adenomas. SMI, FMI, MFR, VFI, and SVR were all associated with the risk of adenomas and high-risk adenomas in the age- and sex-adjusted model. When further adjusted for metabolic and lifestyle factors, VFI was the only factor significantly associated with the risk of colorectal adenomas and high-risk adenomas (adenomas: odds ratio (OR) 1.40, 95% confidence interval (CI) 1.22-1.61; high-risk adenomas: OR 1.47, 95% CI 1.16-1.87, for the highest quartile). Among the various body indices, VFI was the most important index associated with the development of colorectal adenoma. More attention should be paid to visceral fat when predicting the risk of colorectal adenomas.

The Emerging Role of Metformin in the Prevention and Treatment of Colorectal Cancer: A Game Changer for the Management of Colorectal Cancer.

Metformin is an old, inexpensive, and relatively safe anti-diabetic medication that can decrease the risk of several types of cancer in patients with diabetes. Recent meta-analyses have revealed that metformin markedly decreased the incidence of colorectal adenoma, advanced adenoma, and colorectal cancer (CRC) among patients with diabetes. Potential mechanisms by which metformin may decrease colorectal cancer risk include its effects on ameliorating intestinal inflammation and dysbiosis, suppressing major proliferative pathways, preventing DNA replication, accelerating tumor cells apoptosis, inhibiting intra-tumor angiogenesis and epithelial-mesenchymal transition (EMT), increasing tumor-infiltrating lymphocytes and CD68+ tumor-associated macrophages, and enhancing T cells cytotoxic activity. It is well-known that metformin can improve overall survival and CRC-specific survival among patients with diabetes and CRC. Interestingly, metformin decreases the incidence of colonic adenoma in patients with acromegaly and reduces the incidence of inflammatory bowel disease (IBD) among patients with diabetes, which can indirectly lower the risk of CRC. Results of phase II clinical trials have revealed that metformin can enhance the anti-cancer effects of chemotherapeutic agents, such as 5-Fluorouracil (5-FU) and irinotecan on refractory CRC. Furthermore, metformin decreases the risk of new polyps and adenomas in patients without diabetes. Regarding the results of previous preclinical and clinical studies, it is rational to assess the effect of metformin in normoglycemic patients with CRC and expand its clinical application for treating CRC or preventing it in a high-risk population.

S206 Clinical Characteristics of Young Patients With Colonic Adenomas

Introduction: The incidence of colonic adenomas and colorectal cancer has been rising among young patients. Studies addressing the prevalence, risk factors, patient characteristics and appropriate surveillance intervals in young patients with adenomas are limited. In this study, we aim at describing the characteristics of young patients (< 50 years of age) with adenomatous polyps and characterizing those polyps. Methods: This was a retrospective chart review of the Department of Gastroenterology database to identify patients < 50 years of age who had polyp(s) on colonoscopy done between 2008 and 2021. Patient demographics, colonoscopy indication, and number, size, location, and pathology of polyps were documented. Timing and findings of follow-up colonoscopies were recorded. Patients with personal history of inflammatory bowel disease, personal or family history of colorectal cancer were excluded. Results: 877 patients were included in the study; mean age 42.4 ± 6.3 years, 62% males, mean BMI 27.7 ± 5.0. Colonoscopy indications were abdominal pain (26%), rectal bleeding (22%), change in bowel habits (17%), and evaluation of abnormal imaging/lab values. Of 877 patients, 610 (70%) had at least one adenoma: 571 (65%) tubular adenomas, 29 (3%) tubulovillous adenomas, 1 villous adenoma and 19 (2%) had sessile serrated adenomas. 267 (31%) patients had only hyperplastic polyps. Of patients with adenomas, 63 had a polyp > 10mm with mean polyp size 11 ± 9mm. 41% of patients had adenomas in the sigmoid, 34% in ascending, 27% in transverse, 24% in descending colon, and 22% in the rectum. Almost half (49%) of patients with adenomas were younger than 45 years and had similar demographic characteristics as patients between 45 and 50 years of age, but they had a larger mean polyp size (Table). Of the 610 patients with adenoma, 156 (26%) had a follow-up colonoscopy after a mean time of 2.9 ± 2.3 years, with 74 (47%) patients developing recurrent adenomas. 38 (6%) patients had a second follow-up after 2.1 ± 1.6 years and 15/38 had adenomas. Conclusion: Patients < 50 years of age with colonic adenomas were mostly males and overweight. Recurrence of adenomas was prevalent over the follow up of 3 years. For patients with GI complaints, colonoscopy should be considered in individuals with high-risk baseline characteristics. High rates of recurrent adenomas and larger polyp size in patients < 45 years of age may warrant more frequent surveillance than is done for patients > 45 years of age. Table 1. - Comparison of Demographics and Polyp Characteristics between Patients Younger than 45 Years of Age and Patients 45 to 50 Years of Age with Adenomatous Polyps Patients Younger than 45 Years of Age (N=299) Patients between 45 and 50 Years of Age (N=311) p-value Mean Age at Colonoscopy 38.27 (n=299) 47.45 (n=311) < 0.001 Males 58.6% (n=299) 63.0% (n=311) 0.256 BMI 26.77 (n=174) 28.20 (n=186) 0.886 Vitamin D Level 20.82 (n=161) 23.28 (n=186) 0.403 Smoking 50.0% (n=270) 51.6% (n=279) 0.705 Mean Size of Polyps 1.21 (n=109) 1.01 (n=97) < 0.001 High Risk Patients* 24.7% (n=299) 30.2% (n=311) 0.130 Follow Up Rate 24.7% (n=299) 26.1% (n=311) 0.713 BMI: Body Mass Index. N: Total number of patients. n: Total number of patients used to calculate a mean or a percentage.*High Risk patients are defined as having three or more adenomatous polyps and/or a villous component on pathology and/or a polyp size >1cm.

THE CLINICAL CORRELATION BETWEEN POLYCYSTIC OVARY SYNDROME (PCOS) AND PITUITARY ADENOMA

Hyperprolactinemia and polycystic ovary syndrome (PCOS) are on the list of the most frequent causes of female infertility. A pituitary adenoma is one of the most common brain tumors that cause infertility. In the neurosurgical field, pituitary adenoma with PCOS is not common. However, many neurosurgeons often experience these patients who are referred from obstetrics and gynecology (OBGY). Because most of the patients are young and reproductive women, neurosurgery alone is difficult to establish a treatment plan. In this study, we investigate the incidence of pituitary adenoma combined with PCOS, cut-off prolactin (PRL) level to detect pituitary adenoma and treatment strategy.

Supernumerary Ectopic Mediastinal Parathyroid Adenoma Combined With Parathyroid Hyperplasia

Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by elevated parathyroid hormone levels. In most cases, the disease involves a single parathyroid adenoma, followed by parathyroid hyperplasia, but the incidence of ectopic parathyroid adenoma is rare. However, in cases where the parathyroid hormone level remains high even after parathyroid surgery, an ectopic parathyroid gland should be considered. Here in a case of a 60-year-old female who presented PHPT is reported. She had undergone a surgical removal of the parathyroid gland of suspected hyperplasia, but still represented persistent PHPT, postoperatively. Ectopic mediastinal parathyroid adenoma was identified by 99mTc-sestamibi parathyroid scan and surgical excision via a median sternotomy approach was performed. Thirty-eight months postoperatively, there was no evidence of recurrence. Preoperative localization assessment is critical for minimizing surgical failure in cases of PHPT.

Early gastric neoplasms are significant risk factor for colorectal adenoma: A prospective case-control study.

Although gastric cancer patients have a high incidence and risk of colorectal cancer, evidence is lacking regarding whether early gastric neoplasms (EGNs), such as gastric adenomas and early gastric cancer, are risk factors for colorectal adenoma. This study aimed to investigate the incidence of colorectal adenomas in patients with EGN.This prospective study was conducted between January 2015 and December 2016. Of the 307 patients who underwent gastric endoscopic submucosal dissection for EGN, 110 patients were enrolled in the EGN group, and 110 age- and sex-matched healthy persons from the screening population were included in the control group in a 1:1 ratio. Demographic factors and results of colonoscopy, including quality assessment, were collected, and analyzed.No significant differences in the quality of colonoscopy, including bowel preparation, cecal intubation rate, and withdrawal time between the 2 groups, were observed. The incidence of colorectal adenoma was significantly higher in the EGN group than in the control group (55.5% vs 26.4%, P = .001). Multivariate analysis confirmed that old age (odds ratio: 1.04, 95% confidence interval: 1.01–1.08, P = .005) and a history of EGN (odds ratio: 4.99, 95% confidence interval: 2.60–9.57, P = .001) were independent risk factors for colorectal adenoma.This is the first prospective study to reflect the quality indicator of colonoscopy and confirmed that old age and a history of EGN are significant risk factors for colorectal adenomas. Therefore, more stringent colonoscopy surveillance should be considered in elderly patients with EGN.

Generating novel pituitary datasets from open-source imaging data and deep volumetric segmentation.

The estimated incidence of pituitary adenomas in the general population is 10-30%, yet radiographic diagnosis remains a challenge. Diagnosis is complicated by the heterogeneity of radiographic features in both normal (e.g. complex anatomy, pregnancy) and pathologic states (e.g. primary endocrinopathy, hypophysitis). Clinical symptoms and laboratory testing are often equivocal, which can result in misdiagnosis or unnecessary specialist referrals. Computer vision models can aid in pituitary adenoma diagnosis; however, a major challenge to model development is the lack of dedicated pituitary imaging datasets. We hypothesized that deep volumetric segmentation models trained to extract the sellar and parasellar region from existing whole-brain MRI scans could be used to generate a novel dataset of pituitary imaging. Six open-source whole-brain MRI datasets, created for research purposes, were included for model development. Deep learning-based volumetric segmentation models were trained using 318 manually annotated MRI scans from a single open-source MRI dataset. Out-of-distribution volumetric segmentation performance was then tested on 418 MRIs from five held-out research datasets. On our annotated images, agreement between manual and model volumetric segmentations was high. Dice scores (a measure of overlap) ranged 0.76-0.82 for both in-distribution and out-of-distribution model testing. In total, 6,755 MRIs from six data sources were included in the final generated pituitary dataset. We present the first and largest dataset of pituitary imaging constructed using existing MRI data and deep volumetric segmentation models trained to identify sellar and parasellar anatomy. The model generalizes well across patient populations and MRI scanner types. We hope our pituitary dataset will be an integral part of future machine learning research on pituitary pathologies.

ASSOCIATION OF NATURAL KILLER CELLS ACTIVITY WITH THE INCIDENCE OF COLORECTAL NEOPLASIA AT SCREENING

Relevance: Increased natural killer cell (NK cells) activity reduces colorectal cancer (CRC) risk. Previously published studies examined the association of NK cells and CRC prevalence in individuals at high cancer risk.&#x0D; The study aimed to study the relationship between NK cell activity and the incidence of advanced adenomas (AA) and CRC in a population with average cancer risk.&#x0D; Methods: The activity of NK cells was assessed by enzyme immunoassay (ELISA) of blood in participants of average risk with a&#x0D; measurement range of 25-2500 pg/mL. The level of NK cells below 200 pg/mL was defined as pathological. The informativeness of&#x0D; the diagnostic test for determining NK cell activity was assessed using indicators such as sensitivity, specificity, negative and positive&#x0D; predictive value, and clinical utility index. The probability coefficient for the development of colorectal cancer was calculated using&#x0D; logistic regression.&#x0D; Results: NK cell activity was assessed in 354 persons of average risk (mean age – 59 years; 36% men). The diagnostic accuracy of&#x0D; NK cells determination for CRC and AA was 76% and 72%, respectively, and the negative predictive value was 96%. The NK cell test&#x0D; demonstrated a good negative clinical utility index for CRC and AA (0.66 and 0.74, respectively). Individuals with low NK cell levels were&#x0D; seven times more likely to be diagnosed with CRC (95% CI 2.3-20.3; p&lt;0.001). NK cell levels were higher in men compared to women&#x0D; (549 pg/mL vs 500 pg/mL) and lower in smokers (412 pg/mL versus 544 pg/mL), non-athletic participants (413 pg/mL versus 654 pg/mL),&#x0D; in people who abuse alcohol (389 pg/ml versus 476 pg/ml).&#x0D; Conclusion: Our study shows that a high level of NK cells can potentially exclude CRC and AA in individuals with average cancer risk

ASSOCIATION OF NATURAL KILLER CELLS ACTIVITY WITH THE INCIDENCE&#x0D; OF COLORECTAL NEOPLASIA AT SCREENING

Relevance: Increased natural killer cells (NK cells) activity is associated with reduced colorectal cancer (CRC) risk. Previously published&#x0D; studies examined the association of NK cells and CRC prevalence in individuals at high cancer risk.&#x0D; The purpose was to study the relationship between NK cell activity and the incidence of advanced adenomas (AA) and CRC in a population&#x0D; with average cancer risk.&#x0D; Methods: The activity of NK cells was assessed by enzyme immunoassay (ELISA) of blood in participants of average risk with a measurement&#x0D; range of 25-2500 pg/ml. The level of NK cells below 200 pg/ml was defined as pathological. The informativeness of the diagnostic test for determining NK cell activity was assessed using indicators such as sensitivity, specificity, negative and positive predictive value, and clinical utility index.&#x0D; The probability coefficient for the development of colorectal cancer was calculated using logistic regression.&#x0D; Results: The activity of NK cells was assessed in 354 persons of average risk (mean age 59 years; 36% of them men). The diagnostic accuracy&#x0D; of NK cells determination for CRC and AA was 76% and 72%, respectively, and the negative predictive value was 96%. The NK cell test demonstrated a good negative clinical utility index for CRC and AA (0.66 and 0.74, respectively). Individuals with low levels of NK cells were seven times&#x0D; more likely to be diagnosed with CRC (95% CI 2.3-20.3; p&lt;0.001). NK cell levels were higher in men compared to women (549 pg/mL vs 500 pg/&#x0D; mL) and lower in smokers (412 pg/mL versus 544 pg/mL), non-athletic participants (413 pg/mL versus 654 pg / ml), in people who abuse alcohol&#x0D; (389 pg/ml versus 476 pg/ml).&#x0D; Conclusion: Our study shows that a high level of NK cells can potentially exclude CRC and AA in individuals with average cancer risk

Pituitary Adenoma Incidence, Management Trends, and Long-term Outcomes: A 30-Year Population-Based Analysis

ObjectiveTo perform a population-based study of pituitary adenoma epidemiology, including longitudinal trends in disease incidence, treatment patterns, and outcomes. Patients and MethodsIn this study of incident pituitary adenomas in Olmsted County, Minnesota, from January 1, 1989, through December 31, 2019, we identified 785 patients who underwent primary screening, 435 of whom were confirmed as harboring incident pituitary adenomas and were included. Primary outcomes of interest included demographic characteristics, presenting features, and disease outcomes (tumor control, biochemical control, and complications). ResultsAmong our 435 study patients, 438 unique pituitary adenomas were diagnosed at a median patient age of 39 years (interquartile range [IQR], 27 to 58 years). Adenomas were incidentally identified in 164 of the 438 tumors (37%). Common symptomatic presentations included hyperprolactinemia (188 of 438 [43%]) and visual field deficit (47 of 438 [11%]). Laboratory tests confirmed pituitary hormone hypersecretion in 238 of the 435 patients (55%), which was symptomatic in 222. The median tumor diameter was 8 mm (IQR, 5 to 17 mm). Primary management strategies were observation (156 of 438 tumors [36%]), medication (162 of 438 tumors [37%]), and transsphenoidal resection (120 of 438 tumors [27%]). Tumor and biochemical control were achieved in 398 (95%) and 216 (91%) secreting tumors, respectively. New posttreatment pituitary or visual deficits were noted in 43 (11%) and 8 (2%); apoplexy occurred in 28 (6%). Median clinical follow-up was 98 months (IQR, 47 to 189 months). Standardized incidence rates were 3.77 to 16.87 per 100,000 population, demonstrating linear expansion over time (R2=0.67). The mean overall standardized incidence rate was 10.1 per 100,000 population; final point prevalence was 175.1 per 100,000 population. ConclusionPituitary adenoma is a highly incident disease, with prolactin-secreting and incidental lesions representing the majority of tumors. Incidence rates and asymptomatic detection appear to be increasing over time. Presenting symptoms and treatment pathways are variable; however, most patients achieve favorable outcomes with observation or a single treatment modality.

Five- or 10-year colonoscopy for 1-2 non-advanced adenomatous polyps (FORTE) NRG-CC005 study: A randomized phase III non-inferiority trial comparing colorectal cancer incidence in participants with 1-2 non-advanced adenomas randomized to a 5- and 10-year surveillance colonoscopy exam schedule versus a 10-year surveillance colonoscopy exam schedule.

TPS3631 Background: Adenomatous polyps are the acknowledged precursors of colorectal cancer (CRC). Identification and removal of adenomas is the mechanism by which screening is effective in reducing CRC incidence and mortality. Patients with 1-2 non-advanced adenomas ( &lt; 1 cm with neither villous components nor high grade dysplasia) are recommended to return at a timing ranging from 5-10 yrs. However, evidence for the benefit, optimal timing, and recommended frequency of surveillance colonoscopy is not available. A randomized, clinical trial to demonstrate the difference in results between 5- or 10-yr surveillance for participants with non-advanced adenoma can guide clinical practice. Methods: NRG-CC005/FORTE is a prospective, randomized, non-blinded, Phase III, non-inferiority clinical trial comparing CRC incidence in participants randomized to recommendation for a 5- and 10-yr vs. a 10-yr only surveillance colonoscopy exam schedule. Other pre-defined exploratory endpoints include incidence of advanced adenomas, CRC mortality, and incidence of stage III-IV CRCs. Stratification factors include age, gender, and time from qualifying colonoscopy to randomization. Participants ≥50 and &lt; 70 yrs of age at the time of randomization with a first-time diagnosis of 1-2 non-advanced tubular adenomas from the qualifying colonoscopy within 4 yrs prior to randomization will be eligible. Participants with a clinical diagnosis of a significant genetic risk for CRC or with a family history of CRC diagnosed at ≤60 yrs in a first degree relative or in two first degree relatives diagnosed at any age are ineligible. Other ineligibility criteria include prior history of CRC or colorectal adenomas, a hyperplastic polyp measuring ≥1 cm or traditional serrated adenomas, or life expectancy &lt; 10 yrs due to comorbid conditions. Collection of blood, stool, and tissue samples is planned. Statistics: The primary endpoint for the trial is CRC incidence. The trial is focused on CRCs diagnosed between year 5 and year 10. By incorporating a window of +/- 1 yr to allow for somewhat earlier and later procedures, as typically occurs in clinical medicine, the primary endpoint will include incident cancers identified in years 4 through 11. A crude 4- to 11-yr incidence rate of 0.387% is assumed for the 5- and 10-yr schedule arm. The study is powered at 90% to detect a non-inferiority margin difference of 0.387% at alpha 5% in CRC incidence rate between two schedules. 9,500 participants are to be enrolled. Support: U10CA180868, -180822, UG1CA189867, U24CA196067 Clinical trial information: NCT05080673.

GLP-1R polymorphism (rs1042044) and expression are associated with the risk of papillary thyroid cancer among the Egyptian population

BackgroundGlucagon like peptide-1 receptor (GLP-1R) agonist usage has previously been linked to an elevated incidence of thyroid cell adenomas and carcinomas in animals. AimThe goal of this study was to determine if there was an association between GLP-1R gene polymorphism and expression with the risk of papillary thyroid carcinoma (PTC) and its clinical characteristics among the Egyptian population. Material and methodsA total of eighty PTC patients and eighty healthy controls were included in the study. Real-time polymerase chain reaction (real-time PCR) and immunohistochemistry were used to determine GLP-1R expression in tumor tissue. The polymorphisms rs1042044 and rs6923761 in the GLP-1R gene were determined using PCR -restriction fragment length polymorphism (PCR-RFLP). ResultsPTC patients exhibited considerably greater frequencies of rs1042044 AA genotypes and A allele than controls (OR (95% CI) = 4.5 (1.75–11.8), P < 0.001; OR (95% CI) = 2.032 (1.301–3.17), P < 0.001 respectively). GLP-1R mRNA and protein expressions were higher in tumor samples than normal thyroid tissues among PTC patients. In addition, high GLP-1R expressions were more common in rs1042044 AA genotype carriers than CC carriers (P < 0.001). GLP-1R mRNA expression showed 95 % sensitivity and 97% specificity for PTC diagnosis. Moreover, GLP-1R expression was closely associated with LN metastasis, tumor size, tumor stage, and multifocality in PTC patients. ConclusionThis research provides new evidence linking the GLP-1R genetic polymorphism and tissue expression to PTC risk and invasiveness among the Egyptian population.

Two-year intermittent exposure of a multiwalled carbon nanotube by intratracheal instillation induces lung tumors and pleural mesotheliomas in F344 rats

BackgroundA mounting number of studies have been documenting the carcinogenic potential of multiwalled carbon nanotubes (MWCNTs); however, only a few studies have evaluated the pulmonary carcinogenicity of MWCNTs in vivo. A 2-year inhalation study demonstrated that MWNT-7, a widely used MWCNT, was a pulmonary carcinogen in rats. In another 2-year study, rats administered MWNT-7 by intratracheal instillation at the beginning of the experimental period developed pleural mesotheliomas but not lung tumors. To obtain data more comparable with rats exposed to MWNT-7 by inhalation, we administered MWNT-7 to F344 rats by intratracheal instillation once every 4-weeks over the course of 2 years at 0, 0.125, and 0.5 mg/kg body weight, allowing lung burdens of MWNT-7 to increase over the entire experimental period, similar to the inhalation study.ResultsAbsolute and relative lung weights were significantly elevated in both MWNT-7-treated groups. Dose- and time-dependent toxic effects in the lung and pleura, such as inflammatory, fibrotic, and hyperplastic lesions, were found in both treated groups. The incidences of lung carcinomas, lung adenomas, and pleural mesotheliomas were significantly increased in the high-dose group compared with the control group. The pleural mesotheliomas developed mainly at the mediastinum. No MWNT-7-related neoplastic lesions were noted in the other organs. Cytological and biochemical parameters of the bronchoalveolar lavage fluid (BALF) were elevated in both treated groups. The lung burden of MWNT-7 was dose- and time-dependent, and at the terminal necropsy, the average value was 0.9 and 3.6 mg/lung in the low-dose and high-dose groups, respectively. The number of fibers in the pleural cavity was also dose- and time-dependent.ConclusionsRepeated administration of MWNT-7 by intratracheal instillation over the 2 years indicates that MWNT-7 is carcinogenic to both the lung and pleura of rats, which differs from the results of the 2 carcinogenicity tests by inhalation or intratracheal instillation.

Results from two-year rodent oral carcinogenicity studies of cizolirtine, a substance-P and calcitonin gene-related peptide release modulator

Cizolirtine is a substance-P and calcitonin gene-related peptide release modulator developed for the treatment of pain and urinary incontinence. To assess its carcinogenic potential, cizolirtine was administered by oral route once daily for up to 104 weeks to CD-1 mice at doses of 40, 90, or 200 mg/kg/day, and to Han Wistar rats at doses of 40, 90 or 200 mg/kg/day to males and 40, 110 or 160 mg/kg/day to females. There were treatment-related neoplastic findings both in mice and rats. In mice, administration of cizolirtine was associated to an increase in skin fibrosarcomas and sarcomas among high-dose males, considered secondary to increased aggression and specific to the animal model. In rats, there was an increased incidence of liver adenomas in males and females, and carcinomas in males, in association with an increased incidence of hepatocyte hypertrophy, vacuolation and clear cell foci, and considered related to sustained long-term enzyme induction resulting in increased liver metabolism and associated hypertrophic changes. The observed neoplastic findings in mouse skin and rat liver after life-time oral administration of cizolirtine are considered related to rodent-specific non-genotoxic mechanisms of questionable relevance to man.