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Endocrine Regulations Jan 2023Hyperparathyroidism is a prevalent disease with parathyroid adenomas being the most common cause. Surgical excision remains the standard treatment for parathyroid...
Hyperparathyroidism is a prevalent disease with parathyroid adenomas being the most common cause. Surgical excision remains the standard treatment for parathyroid adenoma. Successful preoperative localization of the parathyroid adenoma could facilitate the decision regarding the extent of surgical exploration. The aim of the current study was to assess the correlation between the preoperative values of parathyroid hormone and ionized calcium with the adenoma weight and volume in patient with primary hyperparathyroidism caused by single-gland adenoma. We did this retrospective review for all patients who were diagnosed with primary hyperparathyroidism due to a solitary parathyroid adenoma in our general surgery department over 4 years. SPSS software was used to get the correlation coefficient between the peak preoperative levels of calcium and parathyroid hormone with the parathyroid adenoma weight and volume. Ninety-nine patients were included into the study. The average age at surgery was 62.65±12.00 years. The correlation coefficient between the adenoma volume and weight with the preoperative ionized calcium level was weakly positive (r=0.329, p<0.01) and (r=0.281, p=0.019), respectively, while the correlation with the preoperative parathyroid hormone level was stronger (r=0.708, p<0.01) and (r=0.650, p<0.01), respectively. The strong positive relationship between the preoperative parathyroid hormone and calcium levels with the parathyroid adenoma size and weight can help the surgeon to predict the volume of the involved gland and avoid an unnecessary dissection.
Topics: Humans; Middle Aged; Aged; Parathyroid Glands; Calcium; Parathyroid Neoplasms; Hyperparathyroidism, Primary; Parathyroid Hormone; Parathyroidectomy; Adenoma; Retrospective Studies
PubMed: 36753663
DOI: 10.2478/enr-2023-0002 -
The Korean Journal of Gastroenterology... Sep 2022Colonoscopic polypectomy is effective in decreasing the incidence and mortality of colorectal cancer (CRC). Premalignant polyps discovered during colonoscopy are... (Review)
Review
Colonoscopic polypectomy is effective in decreasing the incidence and mortality of colorectal cancer (CRC). Premalignant polyps discovered during colonoscopy are associated with the risk of metachronous advanced neoplasia. Postpolypectomy surveillance is the most important method for managing advanced metachronous neoplasia. A more efficient and evidence-based guideline for postpolypectomy surveillance is required because of the limited medical resources and concerns regarding colonoscopy complications. In these consensus guidelines, an analytic approach was used to address all reliable evidence to interpret the predictors of CRC or advanced neoplasia during surveillance colonoscopy. The key recommendations state that the high-risk findings for metachronous CRC following polypectomy are as follows: 1) adenoma ≥10 mm in size; 2) 3-5 (or more) adenomas; 3) tubulovillous or villous adenoma; 4) adenoma containing high-grade dysplasia; 5) traditional serrated adenoma; 6) sessile serrated lesion (SSL) containing any grade of dysplasia; 7) serrated polyp of at least 10 mm in size; and 8) 3-5 (or more) SSLs. More studies are needed to fully comprehend the patients who are most likely to benefit from surveillance colonoscopy and the ideal surveillance interval to prevent metachronous CRC.
Topics: Adenoma; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Humans; Republic of Korea; Risk Factors
PubMed: 36156035
DOI: 10.4166/kjg.2022.103 -
Reviews in Endocrine & Metabolic... Jun 2020Surgery of aggressive pituitary adenomas and pituitary carcinomas is part of the interdisciplinary management of these difficult to treat tumors. Invasion, giant size... (Review)
Review
Surgery of aggressive pituitary adenomas and pituitary carcinomas is part of the interdisciplinary management of these difficult to treat tumors. Invasion, giant size and unusual, asymmetric extent of these tumors frequently require modifications or extensions of the standard approaches for transsphenoidal and transcranial surgery. Frequently, only debulking procedures can be performed. In aggressive and hormone secreting adenomas, the remission rates achieved by surgery alone are relatively poor and adjuvant medical treatments or irradiation are needed. Safe resection of as much tumor as possible and symptomatic control is aimed at, rather than remission. Many procedures are required for rapid progression of lesions or recurrences, in order to extend the survival of the patients. Metastases of pituitary carcinomas within the cranial cavity or spine can be attacked. Since they can occur anywhere in the brain or spinal canal they require the entire battery of neurosurgical approaches. Unfortunately, in this group of pituitary tumors, the complication rates are higher than in primary operations of enclosed adenomas. The respective techniques with their facilities and limitations are reviewed in this article.
Topics: Adenoma; Carcinoma; Humans; Neoplasm Invasiveness; Pituitary Neoplasms
PubMed: 32500483
DOI: 10.1007/s11154-020-09563-8 -
Gastroenterology Jan 2021Mutations in the APC gene and other genes in the Wnt signaling pathway contribute to development of colorectal carcinomas. R-spondins (RSPOs) are secreted proteins that...
BACKGROUND & AIMS
Mutations in the APC gene and other genes in the Wnt signaling pathway contribute to development of colorectal carcinomas. R-spondins (RSPOs) are secreted proteins that amplify Wnt signaling in intestinal stem cells. Alterations in RSPO genes have been identified in human colorectal tumors. We studied the effects of RSPO1 overexpression in Apc mutant mice.
METHODS
An adeno associated viral vector encoding RSPO1-Fc fusion protein, or control vector, was injected into Apcmice. Their intestinal crypts were isolated and cultured as organoids. which were incubated with or without RSPO1-Fc and an inhibitor of transforming growth factor beta receptor (TGFBR). Livers were collected from mice and analyzed by immunohistochemistry. Organoids and adenomas were analyzed by quantitative reverse-transcription PCR, single cell RNA sequencing, and immunohistochemistry.
RESULTS
Intestines from Apc mice injected with the vector encoding RSPO1-Fc had significantly deeper crypts, longer villi, with increased EdU labeling, indicating increased proliferation of epithelial cells, in comparison to mice given control vector. AAV-RSPO1-Fc-transduced Apc mice also developed fewer and smaller intestinal tumors and had significantly longer survival times. Adenomas of Apc mice injected with the RSPO1-Fc vector showed a rapid increase in apoptosis and in the expression of Wnt target genes, followed by reduced expression of messenger RNAs and proteins regulated by the Wnt pathway, reduced cell proliferation, and less crypt branching than adenomas of mice given the control vector. Addition of RSPO1 reduced the number of adenoma organoids derived from Apc mice and suppressed expression of Wnt target genes but increased phosphorylation of SMAD2 and transcription of genes regulated by SMAD. Inhibition of TGFBR signaling in organoids stimulated with RSPO1-Fc restored organoid formation and expression of genes regulated by Wnt. The TGFBR inhibitor restored apoptosis in adenomas from Apc mice expressing RSPO1-Fc back to the same level as in the adenomas from mice given the control vector.
CONCLUSIONS
Expression of RSPO1 in Apc mice increases apoptosis and reduces proliferation and Wnt signaling in adenoma cells, resulting in development of fewer and smaller intestinal tumors and longer mouse survival. Addition of RSPO1 to organoids derived from adenomas inhibits their growth and promotes proliferation of intestinal stem cells that retain the APC protein; these effects are reversed by TGFB inhibitor. Strategies to increase the expression of RSPO1 might be developed for the treatment of intestinal adenomas.
Topics: Adenoma; Animals; Disease Models, Animal; Intestinal Neoplasms; Mice; Organoids; Thrombospondins; Transforming Growth Factor beta; Wnt Signaling Pathway
PubMed: 32941878
DOI: 10.1053/j.gastro.2020.09.011 -
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 -
Cancer Epidemiology, Biomarkers &... Sep 2023Individuals with adenomatous colorectal polyps undergo repeated colonoscopy surveillance to identify and remove metachronous adenomas. However, many patients with...
BACKGROUND
Individuals with adenomatous colorectal polyps undergo repeated colonoscopy surveillance to identify and remove metachronous adenomas. However, many patients with adenomas do not develop recurrent adenomas. Better methods to evaluate who benefits from increased surveillance are needed. We evaluated the use of altered EVL methylation as a potential biomarker for risk of recurrent adenomas.
METHODS
Patients with ≥1 colonoscopy had EVL methylation (mEVL) measured with an ultra-accurate methylation-specific droplet digital PCR assay on normal colon mucosa. The association between EVL methylation levels and adenoma or colorectal cancer was evaluated using three case/control definitions in three models: unadjusted (model 1), adjusting for baseline characteristics (model 2), and an adjusted model excluding patients with colorectal cancer at baseline (model 3).
RESULTS
Between 2001 and 2020, 136 patients were included; 74 healthy patients and 62 patients with a history of colorectal cancer. Older age, never smoking, and baseline colorectal cancer were associated with higher levels of mEVL (P ≤ 0.05). Each log base 10 difference in mEVL was associated with an increased risk of adenoma(s) or cancer at/after baseline for model 1 [OR, 2.64; 95% confidence interval (CI), 1.09-6.36], and adenoma(s) or cancer after baseline for models 1 (OR, 2.01; 95% CI, 1.04-3.90) and model 2 (OR, 3.17; 95% CI, 1.30-7.72).
CONCLUSIONS
Our results suggest that EVL methylation level detected in the normal colon mucosa has the potential to be a biomarker for monitoring the risk for recurrent adenomas.
IMPACT
These findings support the potential utility of EVL methylation for improving the accuracy for assigning risk for recurrent colorectal adenomas and cancer.
Topics: Humans; Adenoma; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Intestinal Mucosa; Methylation
PubMed: 37294695
DOI: 10.1158/1055-9965.EPI-22-1020 -
Endoscopy Jun 2023Previous studies have reported the effectiveness of narrow-band imaging (NBI) and linked-color imaging (LCI) in improving the detection of colorectal neoplasms. There... (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
BACKGROUND
Previous studies have reported the effectiveness of narrow-band imaging (NBI) and linked-color imaging (LCI) in improving the detection of colorectal neoplasms. There has however been no direct comparison between LCI and NBI in the detection of colorectal sessile serrated lesions (SSLs). The present study aimed to compare the effectiveness of LCI and NBI in detecting colorectal SSLs.
METHODS
A prospective, parallel, randomized controlled trial was conducted. The participants were randomly assigned to the LCI or NBI arms. The primary end point was the SSL detection rate (SDR).
RESULTS
406 patients were involved; 204 in the LCI arm and 202 in the NBI arm. The total polyp detection rate, adenoma detection rate, and SDR were 54.2 %, 38.7 %, and 10.8%, respectively. The SDR was not significantly different between the LCI and NBI arms (12.3 % vs. 9.4 %; = 0.36). The differences in the detection rate and the per-patient number of polyps, adenomas, diminutive lesions, and flat lesions between LCI and NBI also were not statistically significant. Multivariate analysis showed that LCI and NBI were not independent factors associated with SDR, whereas Boston Bowel Preparation Scale score (odds ratio [OR] 1.35, 95 %CI 1.03-1.76; = 0.03), withdrawal time (OR 1.13, 95 %CI 1.00-1.26; = 0.04), and operator experience (OR 3.73, 95 %CI 1.67-8.32; = 0.001) were independent factors associated with SDR.
CONCLUSIONS
LCI and NBI are comparable for SSL detection, as well as for the detection of polyps and adenomas.
Topics: Humans; Colonic Polyps; Colonoscopy; Prospective Studies; Colorectal Neoplasms; Narrow Band Imaging; Adenoma
PubMed: 36482165
DOI: 10.1055/a-1995-2685 -
Alimentary Pharmacology & Therapeutics Apr 2022We previously reported a panel of novel faecal microbiome gene markers for diagnosis of colorectal adenoma and cancer.
BACKGROUND
We previously reported a panel of novel faecal microbiome gene markers for diagnosis of colorectal adenoma and cancer.
AIM
To evaluate whether these markers are useful in detecting adenoma recurrence after polypectomy.
METHODS
Subjects were enrolled in a polyp surveillance study from 2009 to 2019. Stool samples were collected before bowel preparation of index colonoscopy (baseline) and surveillance colonoscopy (follow-up). Fusobacterium nucleatum (Fn), Lachnoclostridium marker (m3), Clostridium hathewayi (Ch) and Bacteroides clarus were quantified in baseline and follow-up samples by quantitative polymerase chain reaction (qPCR) to correlate with adenoma recurrence. Recurrence was defined as new adenomas detected >6 months after polypectomy. Faecal immunochemical test (FIT) was performed for comparison.
RESULTS
A total of 161 baseline and 104 follow-up samples were analysed. Among patients with adenoma recurrence, Fn and m3 increased (both P < 0.05) while Ch were unchanged in follow-up versus baseline samples. Among patients without recurrence, Fn and m3 were unchanged while Ch decreased (P < 0.05) in follow-up versus baseline samples. Logistic regression that included changes of m3, Fn and Ch at follow-up compared with baseline achieved an area under receiver operating characteristic curve (AUROC) of 0.95 (95%CI: 0.84-0.99) with 90.0% sensitivity and 87.0% specificity for detecting recurrent adenoma. Combination of m3, Fn and Ch at follow-up sample achieved AUROC of 0.74 (95%CI: 0.65-0.82) with 81.3% sensitivity and 55.4% specificity for detecting recurrent adenoma. FIT showed limited sensitivity (8.3%) in detecting recurrent adenomas.
CONCLUSION
Our combinations of faecal microbiome gene markers can be potentially useful non-invasive tools for detecting adenoma recurrence.
Topics: Adenoma; Clostridiaceae; Colonoscopy; Colorectal Neoplasms; Humans; Microbiota; Neoplasm Recurrence, Local; Occult Blood
PubMed: 35224756
DOI: 10.1111/apt.16799 -
Familial Cancer Jan 2023Biallelic MSH3 germline variants are a rare cause of adenomatous polyposis as yet reported in two small families only. We describe the phenotype of a third family, the...
Biallelic MSH3 germline variants are a rare cause of adenomatous polyposis as yet reported in two small families only. We describe the phenotype of a third family, the largest thus far, with adenomatous polyposis related to compound heterozygous MSH3 pathogenic variants. The index patient was a 55-years old male diagnosed with rectal cancer and adenomatous polyposis (cumulatively 52 polyps), with a family history of colorectal polyposis with unknown cause. Next-generation sequencing and copy number variation analysis of a panel of genes associated with colorectal cancer and polyposis revealed compound heterozygous germline pathogenic variants in the MSH3 gene. Nine out of 11 siblings were genotyped. Three siblings carried the same compound heterozygous MSH3 variants. Colonoscopy screening showed predominantly right-sided adenomatous polyposis in all compound heterozygous siblings, with a cumulative number of adenomas ranging from 18 to 54 in an average of four colonoscopies, and age at first adenoma detection ranging from 46 to 59. Microsatellite analysis demonstrated alterations at selected tetranucleotide repeats (EMAST) in DNA retrieved from the rectal adenocarcinoma, colorectal adenomas as well as of normal colonic mucosa. Gastro-duodenoscopy did not reveal adenomas in any of the four patients. Extra-intestinal findings included a ductal adenocarcinoma in ectopic breast tissue in one female sibling at the age of 46, and liver cysts in three affected siblings. None of the three heterozygous or wild type siblings who previously underwent colonoscopy had adenomatous polyposis. We conclude that biallelic variants in MSH3 are a rare cause of attenuated adenomatous polyposis with an onset in middle age.
Topics: Male; Humans; Female; DNA Copy Number Variations; Adenomatous Polyposis Coli; Colorectal Neoplasms; Adenoma; Adenocarcinoma; MutS Homolog 3 Protein
PubMed: 35675019
DOI: 10.1007/s10689-022-00297-x -
International Journal of Molecular... May 2020Colorectal cancer (CRC) is a malignant disease with an incidence of over 1.8 million new cases per year worldwide. CRC outcome is closely related to the respective stage... (Review)
Review
Colorectal cancer (CRC) is a malignant disease with an incidence of over 1.8 million new cases per year worldwide. CRC outcome is closely related to the respective stage of CRC and is more favorable at less advanced stages. Detection of early colorectal adenomas is the key to survival. In spite of implemented screening programs showing efficiency in the detection of early precancerous lesions and CRC in asymptomatic patients, a significant number of patients are still diagnosed in advanced stages. Research on CRC accomplished during the last decade has improved our understanding of the etiology and development of colorectal adenomas and revealed weaknesses in the general approach to their detection and elimination. Recent studies seek to find a reliable non-invasive biomarker detectable even in the blood. New candidate biomarkers could be selected on the basis of so-called liquid biopsy, such as long non-coding RNA, microRNA, circulating cell-free DNA, circulating tumor cells, and inflammatory factors released from the adenoma into circulation. In this work, we focused on both genetic and epigenetic changes associated with the development of colorectal adenomas into colorectal carcinoma and we also discuss new possible biomarkers that are detectable even in adenomas prior to cancer development.
Topics: Adenoma; Animals; Biomarkers, Tumor; Cell Transformation, Neoplastic; Colorectal Neoplasms; Disease Susceptibility; Early Detection of Cancer; Gene Expression Regulation, Neoplastic; Genetic Variation; Humans
PubMed: 32380676
DOI: 10.3390/ijms21093260