Effectiveness of combined first-line medical treatment in acromegaly with prolactin cosecretion.

OBJECTIVE: The aim of this study is to compare the response to first-line medical treatment in treatment-naive acromegaly patients with pure growth hormone (GH)-secreting pituitary adenoma (GH-PA) and those with GH and prolactin cosecreting PA (GH&PRL-PA). DESIGN: This is a retrospective multicentric study of acromegaly patients followed from 2003 to 2023 in 33 tertiary Spanish hospitals with at least 6 months of first-line medical treatment. METHODS: Baseline characteristics, first-line medical treatment strategies, and outcomes were analyzed. We employed a multiple logistic regression full model to estimate the impact of some baseline characteristics on disease control after each treatment modality. RESULTS: Of the 144 patients included, 72.9% had a GH-PA, and 27.1% had a GH&PRL-PA. Patients with GH&PRL-PA were younger (43.9 ± 15.0 vs 51.9 ± 12.7 years, P < .01) and harboring more frequently macroadenomas (89.7% vs 72.1%, P = .03). First-generation somatostatin receptor ligand (fgSRL) as monotherapy was given to 106 (73.6%) and a combination treatment with fgSRL and cabergoline in the remaining 38 (26.4%). Patients with GH&PRL-PA received more frequently a combination therapy (56.4% vs 15.2%, P < .01). After 6 months of treatment, in the group of patients under fgSRL as monotherapy, those patients with GH&PRL-PA had worse control compared to GH-PAs (29.4% vs 55.1%, P = .04). However, these differences in the rate of disease control between both groups disappeared when both received combination treatment with fgSRL and cabergoline. CONCLUSION: In GH&PRL-PA, the biochemical control achieved with fgSRL as monotherapy is substantially worse than in patients harboring GH-PA, supporting the inclusion of cabergoline as first-line medical treatment in combination with fgSRLs in these subgroups of patients.

Gut microbiota and serum metabolite signatures along the colorectal adenoma-carcinoma sequence: Implications for early detection and intervention.

AIM: Our study focuses on the microbial and metabolomic profile changes during the adenoma stage, as adenomas can be considered potential precursors to colorectal cancer through the adenoma-carcinoma sequence. Identifying possible intervention targets at this stage may aid in preventing the progression of colorectal adenoma (CRA) to malignant lesions. Furthermore, we evaluate the efficacy of combined microbial and metabolite biomarkers in detecting CRA. METHODS: Fecal metagenomic and serum metabolomic analyses were performed for the discovery of alterations of gut microbiome and metabolites in CRA patients (n = 26), Colorectal cancer (CRC) patients (n = 19), Familial Adenomatous Polyposis (FAP) patients (n = 10), and healthy controls (n = 20). Finally, analyzing the associations between gut microbes and metabolites was performed by a Receiver Operating Characteristic (ROC) curve. RESULTS: Our analysis present that CRA patients differ significantly in gut microflora and serum metabolites compared with healthy controls, especially for Lachnospiraceae and Parasutterella. Its main metabolite, butyric acid, concentrations were raised in CRA patients compared with the healthy controls, indicating its role as a promoter of colorectal tumorigenesis. α-Linolenic acid and lysophosphatidylcholine represented the other healthy metabolite for CRA. Combining five microbial and five metabolite biomarkers, we differentiated CRA from CRC with an Area Under the Curve (AUC) of 0.85 out of this performance vastly superior to the specificity recorded by traditional markers CEA and CA199 in such differentiation of these conditions. CONCLUSIONS: The study underlines significant microbial and metabolic alterations in CRA with a novel insight into screening and early intervention of its tumorigenesis.

Radiofrequency Ablation of Parathyroid Adenoma: Results of a Retrospective Analysis of 60 Patients.

PURPOSE: To present the effectiveness and safety of radiofrequency ablation (RFA) in parathyroid adenoma (PTA). MATERIALS AND METHODS: In this retrospective study, 60 patients with a single PTA were evaluated for changes in biochemical and ultrasonographic features up to 6 months after RFA of the lesion. Adenomas were ablated with an alternative technique so called "Nik jet dissection" which incorporates full hydrodissection and polar artery coagulation. Complications as well as the variations in biochemical data and nodule volumes were analyzed between baseline measurements and at each follow-up interval data (first day, 1, 3, and 6 months after ablation) were analyzed. RESULTS: A significant reduction in serum intact parathyroid hormone and calcium levels was observed 6 months after ablation, with a mean difference of - 83.4 ± 104.1 pg/mL, p < 0.001, and - 0.29 ± 0.22 mmol/L, p < 0.001, respectively. Serum phosphorus levels increased significantly with a mean difference of 0.09 ± 0.19 mmol/L, p = 0.040 at the end of the follow up. We observed a significant volume reduction rate of parathyroid adenomas with 89 ± 20.8 percent, p < 0.001. Also, 51% of adenomas disappeared at the end of the follow up. In this study, two cases of hematoma and one case of transient hoarseness (grade 1 of the CIRSE classification) were encountered. CONCLUSION: Our study showed that RFA with the alternative technique, called "Nik jet dissection" is a safe and effective modality in management of PTA. Therefore, we suggest expanding the indications for RFA in PTA management, especially when surgery is not feasible. LEVEL OF EVIDENCE: Level 3, Local non-random sample.

Differences in circulating lymphocyte subpopulations among patients with inflammatory polyps, colorectal adenomas and colorectal cancer.

BACKGROUND AND STUDY AIMS: Colorectal cancer (CRC) may develop from focal changes within benign or precancerous polyps. The immune system's failure to detect and eradicate tumor cells due to immune surveillance evasion, allows cancer to develop and spread. This study aims to analyze the differences in circulating lymphocyte subpopulations in patients with colorectal inflammatory polyps, colorectal adenomas and CRC. PATIENTS AND METHODS: We retrospectively reviewed patients from September 2016 to December 2019 at the Shaoxing Second Hospital. Using flow cytometry, the subset distribution and immunophenotype of T cells, CD4+ T cells, CD8+ T cells, B cells and NK cells were investigated in peripheral blood mononuclear cell samples. The counts of lymphocytes were determined by white blood cell counts. RESULTS: In total, 518 patients were included in this study. The counts of lymphocytes, T cells and NK cells in patients with inflammatory polyps, colorectal adenomas and CRC were lower than controls. The counts and percentages of CD8+ T cells in patients with inflammatory polyps, colorectal adenomas and CRC were lower than controls. The counts of CD4+ T cells were lower in patients with CRC than inflammatory polyps. The percentages of CD4+ T cells in patients with inflammatory polyps, colorectal adenomas and CRC were higher than controls, but lower in the CRC than inflammatory polyps, colorectal adenomas. The counts and percentages of B cells were lower in CRC patients than colorectal adenomas patients. In addition, the percentages of B cells were higher in patients with inflammatory polyps and colorectal adenomas than in controls. CONCLUSIONS: The decrease in counts of lymphocyte, T cells, CD8+ T cells and NK cells in patients may be related to the dysplasia of epithelial cells. Furthermore, the B cells and CD4+ T cells may be related to the malignant growth of the dysplastic epithelial cells.

Bilateral exploration in primary hyperparathyroidism: Double adenoma distribution and biochemical patterns over two decades.

BACKGROUND: We investigated if anatomic patterns of abnormal parathyroid glands have ch anged for primary hyperparathyroidism (pHPT) as atypical biochemical presentation (normohormonal and normocalcemic) has increased. METHODS: Retrospective review of patients with pHPT who underwent routine bilateral neck exploration. RESULTS: 2762 patients were included. The "late" cohort (2014-2020) exhibited lower preoperative calcium (10.8 vs 11.1 â€‹mg/dL; P â€‹= â€‹0.001) and PTH levels (101 vs. 146 â€‹pg/mL; P â€‹= â€‹0.001) compared to the "early" cohort (2000-2006). Patients with atypical biochemical profiles increased from 25.5% to 31.3% (P â€‹< â€‹0.001). The prevalence of single adenoma (SA) decreased (66.1% vs 58.9%, P â€‹= â€‹0.02) while the proportion of double adenoma (DA) increased (17.3% vs. 22.6%, P â€‹< â€‹0.01). Upper parathyroid adenoma(s) remained the most common finding for SA and DA in both time points. CONCLUSIONS: Despite changes in patient characteristics, single upper adenoma and bilateral double upper adenomas remain the most common findings for patients with pHPT.

Clinical Characteristics and Management of Cosecreting Thyroid Stimulating Hormone or Prolactin Pituitary Growth Hormone Adenomas: A Case-Control Study.

OBJECTIVE: Cosecreting thyroid stimulating hormone (TSH) or prolactin (PRL) in patients with pituitary growth hormone (GH) adenomas has been rarely reported. Our study aimed to elucidate their clinical characteristics. METHODS: We retrospectively collected data of 22 cases of cosecreting GH and TSH pituitary adenomas [(GH+TSH)oma] and 10 cases of cosecreting GH and PRL pituitary adenomas [(GH+PRL)oma] from Beijing Tiantan Hospital, Capital Medical University between January 2009 and January 2023. The clinical manifestation, preoperative hormone levels, imaging features, pathologic characteristics, and biochemical remission rates were compared among 335 patients with solo-secreting GH adenomas (GHoma) and 49 patients with solo-secreting TSH adenoma (TSHoma). Patients with (GH+TSH)oma and (GH+PRL)oma were grouped according to biochemical remission to explore the risk factors leading to biochemical nonremission. RESULTS: Cosecreting pituitary GH adenomas had various clinical manifestations and a larger tumor volume and were more likely to invade the cavernous sinus bilaterally and compress the optic chiasm. GH and TSH levels were lower in (GH+TSH)oma than in GHoma or TSHoma. Solo part remission was observed both in (GH+TSH)oma and (GH+PRL)oma. Cavernous sinus invasion was an independent risk factor for biochemical nonremission in patients with (GH+TSH)oma and (GH+PRL)oma. CONCLUSIONS: The clinical manifestation of (GH+TSH)oma and (GH+PRL)oma may be atypical. When screening for pituitary adenomas, a comprehensive evaluation of all pituitary target gland hormones is needed. Cosecreting pituitary GH adenomas are more aggressive and surgery is often unable to completely remove the tumor, requiring pharmacologic or radiological treatment if necessary. Clinicians should give high priority to biochemical remission, although solo part remission may occur.

Caloric restriction as a possible pitfall for persistent acromegaly follow-up - case report.

BACKGROUND: Acromegaly diagnosis is established when plasma levels of IGF-1 are increased and the Oral Glucose Tolerance Test (OGTT) with 75gr of glucose can't suppress Growth Hormone (GH) levels. These two parameters are also useful during follow-up, after surgical/radiologic therapy and/or during medical therapy. CASE PRESENTATION: A 29-year-old woman was diagnosed with acromegaly after a severe headache. Previous amenorrhea and facial and acral changes were noticed. A pituitary macroadenoma was found, biochemical evaluation was in agreement with the suspected acromegaly and a transsphenoidal adenectomy was performed. As the disease recurred, a surgical reintervention and radiosurgery (Gamma Knife, 22 Gy) were necessary. No normalization of IGF-1 was achieved during three years after radiosurgery. Surprisingly, then, and although clinical features seemed getting worse, IGF-1 levels became consistently controlled to 0.3-0.8 times the upper limit of the reference range. Questioned, the patient referred that she was following an intermittent fasting dietary plan. However, based on the dietary questionnaire, she was found to be under severe caloric restriction. First OGTT (under caloric restriction) showed absence of GH suppression and an IGF-1 value of 234 ng/dL (Reference Range 76-286 ng/mL). A second OGTT, one month after an eucaloric diet was instituted, showed an increased IGF-1 of 294 ng/dL, maintaining an unsuppressed, yet less elevated, GH. CONCLUSIONS: GHRH/GH/IGF-1 axis controls somatic growth. Regulation is complex, and nutrition status and feeding pattern have a recognized role. Like systemic inflammation or chronic liver disease, fasting and malnutrition decrease the expression of hepatic GH receptors, with consequent reduction of IGF-1 levels, through resistance to GH. This clinical report shows that caloric restriction may represent a pitfall in acromegaly follow-up.

[Acromegaly screening in patients with hyperprolactinemia and pituitary adenoma].

BACKGROUND: Hyperprolactinemia accompanies growth hormone hypersecretion in approximately 25-39% of cases. There is a recommendation to determine the level of prolactin in clinical guidelines for diagnosis and treatment of acromegaly. However, there is no understanding of the necessity to investigate the IGF-1 level in patients with hyperprolactinemia and a pituitary adenoma. AIM: Determining the proportion of patients with hyperprolactinemia and pituitary adenoma, who were examined for IGF-1 levels, and identifying the proportion of patients with acromegaly among this cohort. MATERIALS AND METHODS: Between December 2019 and December 2022 a single-center observational single-stage single-sample uncontrolled study was conducted. At the first stage of the study, the proportion of patients with pituitary adenoma and hyperprolactinemia with studied IGF-1 levels was determined, according to medical records. At the second stage of the study, patients without known indicators of IGF-1 were determined. The concentration of growth hormone was studied during the oral glucose load in the case of increased IGF-1 levels. RESULTS: At the first stage, 105 patients were included in the study. The level of IGF-1 was determined in 41/105 (39%) cases. There were 22/41 (53.7%) cases in the subgroup with pituitary incidentalomas and 19/64 (29.7%) cases in the subgroup with hyperprolactinemia among them. At the second stage, the IGF-1 level was additionally determined in 53 patients with hyperprolactinemia and pituitary adenoma (total 94 patients). The level of IGF-1 was elevated in 11/94 patients, further acromegaly was confirmed in 3/94 patients (3.2%). CONCLUSION: In real clinical practice the level of IGF-1 is studied only in 39% of cases in patients with pituitary adenoma and hyperprolactinemia. The disease was detected in 3 cases (3.2%) out of 94 people with hyperprolactinemia and pituitary adenoma without clinical manifestations of acromegaly. We consider the study of IGF-1 levels justified as a screening for acromegaly in patients with hyperprolactinemia and pituitary adenoma.

AGA Clinical Practice Update on Approach to the Use of Noninvasive Colorectal Cancer Screening Options: Commentary.

The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update Commentary is to review the available evidence and provide expert advice regarding the approach to using noninvasive colorectal cancer (CRC) screening options, including evidence for their effectiveness, selection of individuals for whom these tests are appropriate, implications of a positive non-colonoscopy screening test, and opportunities to enhance the quality of noninvasive CRC screening programs. This Clinical Practice Update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology. This expert commentary reflects recently published studies in this field, as well as the experiences of the authors who are gastroenterologists with high-level expertise in CRC screening and prevention.

Circulating Sex Hormones and Risk of Colorectal Adenomas and Serrated Lesions in Men.

BACKGROUND: Sex hormones have been implicated in the etiology of colorectal neoplasia in women for over 40 years, but there has been very little investigation of the role of these hormones in men. METHODS: Using data from an adenoma chemoprevention trial, we conducted a secondary analysis to examine serum hormone levels [testosterone, androstenedione, DHEA sulfate (DHEAS), and sex hormone binding globulin (SHBG)] and risk of colorectal precursors in 925 men. Multivariable logistic regression models were fit to evaluate adjusted associations between hormone levels and risk of "low-risk" (single tubular adenoma < 1 cm) and "high-risk" lesions (advanced adenoma or sessile serrated adenoma or right-sided serrated polyp or >2 adenomas of any size). RESULTS: Overall, levels of free testosterone, total testosterone, androstenedione, DHEAS, or SHBG were not associated with either "low-risk" or "high-risk" early precursor lesions in the colorectum. CONCLUSIONS: These findings do not support the role of sex hormones in early colorectal neoplasia among men. IMPACT: This large prospective study address a missing gap in knowledge by providing information on the role of sex hormones in colorectal neoplasia in males.

Postoperative GH and Degree of Reduction in IGF-1 Predicts Postoperative Hormonal Remission in Acromegaly.

Purpose: Determine predictive factors for long-term remission of acromegaly after transsphenoidal resection of growth hormone (GH)-secreting pituitary adenomas. Methods: We identified 94 patients who had undergone transsphenoidal resection of GH-secreting pituitary adenomas for treatment of acromegaly at the USC Pituitary Center from 1999-2019 to determine the predictive value of postoperative endocrine lab values. Results: Patients underwent direct endoscopic endonasal (60%), microscopic transsphenoidal (38%), and extended endoscopic approaches (2%). The cohort was 63% female and 37% male, with average age of 48.9 years. Patients presented with acral enlargement (72, 77%), macroglossia (40, 43%), excessive sweating (39, 42%), prognathism (38, 40%) and frontal bossing (35, 37%). Seventy-five (80%) were macroadenomas and 19 (20%) were microadenomas. Cavernous sinus invasion was present in 45%. Available immunohistochemical data demonstrated GH staining in 88 (94%) and prolactin in 44 (47%). Available postoperative MRI demonstrated gross total resection in 63% of patients and subtotal resection in 37%. Most patients (66%) exhibited hormonal remission at 12 weeks postoperatively. Receiver operating characteristic (ROC) curves demonstrated postoperative day 1 (POD1) GH levels ≥1.55ng/mL predicted failure to remit from surgical resection alone (59% specificity, 75% sensitivity). A second ROC curve showed decrease in corrected insulin-like growth factor-1 (IGF-1) levels of at least 37% prognosticated biochemical control (90% sensitivity, 80% specificity). Conclusion: POD1 GH and short-term postoperative IGF-1 levels can be used to successfully predict immediate and long-term hormonal remission respectively. A POD1 GH cutoff can identify patients likely to require adjuvant therapy to emphasize clinical follow-up.

Bone Turnover Markers in Response to Ultrasound-Guided Microwave Ablation for Primary Hyperparathyroidism.

Objective: To assess the efficacy and safety of ultrasound-guided microwave ablation (MWA) in the treatment of primary hyperparathyroidism (PHPT), and to investigate whether MWA can improve the bone turnover and renal function. Methods: A total of 20 consecutive PHPT patients with 21 parathyroid lesions treated with MWA in our center from May 2019 to March 2021 were recruited in this study. Serum parathyroid hormone (PTH), calcium and phosphorus levels before MWA and at 20 minutes, 4 hours, 1 day, 3 months, 6 months and 12 months after MWA were measured. Bone turnover biomarkers, renal function and lesion volume with volume reduction rate (VRR) before MWA and at the last follow-up were compared. Any complication related with MWA was evaluated. The technical and clinical success rates of MWA in the treatment of PHPT were calculated. Clinical success was defined as normal serum PTH and calcium without PHPT-associated manifestations at more than 6 months after ablation. Technical success was defined as complete ablation indicated by immediate postoperative contrast-enhanced ultrasound. Results: The serum PTH, calcium and phosphorus levels at their respective follow-up time points dropped significantly after MWA (P <0.05). The volume of parathyroid lesions at the final examination was significantly reduced, compared with pre-ablation volume (P <0.001), with a median VRR reaching 89%. The technical and clinical success rates were 100% and 63.6%, respectively. Substantial changes of bone turnover biomarkers were observed before and after MWA (P <0.05), but the differences in renal function were not statistically significant. No major complications were reported in all cases. Pre-MWA serum PTH, lesion volume, maximum diameter of lesion and ablation time were significantly different between patients with successful and failed MWA. Conclusions: PHPT can be effectively and safely treated by ultrasound-guided MWA, as proven by drop in serum PTH and reduction in the volume of parathyroid adenomas. Besides, MWA can impede bone remodeling to suppress hyperparathyroidism in the condition of PHPT.

Syndrome of inappropriate secretion of thyroid-stimulating hormone in a subject with galactorrhea and menstrual disorder and undergoing infertility treatment: Case report.

RATIONALE: Syndrome of inappropriate secretion of thyroid-stimulating hormone (SITSH) is a rare cause of hyperthyroidism. Thyroid-stimulating hormone (TSH) levels are usually normal or high, and triiodothyronine (FT3) and free thyroxine (FT4) levels are usually high in subjects with SITSH. PATIENT CONCERN: A 37-year-old woman had experienced galactorrhea and menstrual disorder for a couple of years before. She had undergone infertility treatment in 1 year before, hyperthyroidism was detected and she was referred to our institution. DIAGNOSIS: She was suspected of having SITSH and was hospitalized at our institution for further examination. The data on admission were as follows: FT3, 4.62 pg/mL; FT4, 1.86 ng/dL; TSH, 2.55 µIU/mL. Although both FT3 and FT4 levels were high, TSH levels were not suppressed, which is compatible with SITSH. In addition, in brain contrast-enhanced magnetic resonance imaging, nodular lesions were observed in the pituitary gland with a diameter of approximately 10 mm. In the thyrotropin-releasing hormone load test, TSH did not increase at all, which was also compatible with TSH-secreting pituitary adenoma. In the octreotide load test, the TSH levels were suppressed. Based on these findings, we diagnosed this subject as SITSH. INTERVENTIONS: Hardy surgery was performed after the final diagnosis. In TSH staining of the resected pituitary adenoma, many TSH-producing cells were observed. These findings further confirmed the diagnosis of pituitary adenoma producing TSH. OUTCOMES: Approximately 2 months after the operation, TSH, FT3, and FT4 levels were normalized. Approximately 3 months after the operation, she became pregnant without any difficulty. LESSONS: We should consider the possibility of SITSH in subjects with galactorrhea, menstrual disorders, or infertility. In addition, we should recognize that it is very important to repeatedly examine thyroid function in subjects with galactorrhea, menstrual disorder, or infertility.

The Automatically Analyzed (AA) ColonView (CV) Quick Test for Fecal Occult Blood Shows Higher Diagnostic Accuracy in Detection of Colorectal Adenoma than Visually Analyzed Tests.

BACKGROUND/AIM: The present study compared the accuracy of visually analyzed (VA) and automatically analyzed (AA) ColonView (CV) quick test; a new-generation fecal immunochemical test (FIT) for hemoglobin (Hb) and hemoglobin/haptoglobin (Hb/Hp) (Biohit Oyj, Helsinki, Finland) in subjects participating in colorectal neoplasia (CRN) detection in Brazil. A traditional guaiac-based fecal occult blood test (gFOBT) test (HemoccultSENSA) was used as a reference. PATIENTS AND METHODS: A cohort of 509 colonoscopy-referral patients were asked to collect three consecutive fecal samples, to be analyzed by both CV and SENSA. RESULTS: In ROC analysis for the AA reading, the optimal cut-off value for CV Hb was ≥8.0912 and that for CV Hb/Hp was ≥1.8983. With these cut-offs, the sensitivity (Se), specificity (Sp), and efficiency of CV AA in detecting colorectal adenoma (CRA) were: 64.2%/78.6%, 53.4%/35.3%, and 58.6%/56.5%, for Hb and Hb/Hp, respectively. In the HSROC analysis, the AUC values for i) VA and ii) AA modes were as follows: i) AUC=0.551 (95%CI=0.500-0.602), ii) AUC=0.606 (95%CI=0.550-0.662). The difference between these AUC values was statistically significant (p=0.0160). CONCLUSION: The present study confirms the previous results on the applicability of the ColonView quick test in CRN screening. Of the two optional reading modes, the AA reading showed significantly better diagnostic accuracy as compared to the VA reading (or SENSA), in detecting the CRA endpoint in colonoscopy-referral patients.

A Protective Role for Arachidonic Acid Metabolites against Advanced Colorectal Adenoma in a Phase III Trial of Selenium.

Oxylipins derived from arachidonic acid (ARA) have been implicated in the development of colorectal adenomas and colorectal cancer. The primary purpose of this work was to determine the relationship between plasma levels of oxylipins and colorectal adenoma characteristics at study entry, as well as with the development of a new adenoma during follow-up within a Phase III adenoma prevention clinical trial with selenium (Sel). Secondarily, we sought to determine whether the selenium intervention influenced plasma oxylipin levels. Four oxylipins were quantified in stored plasma samples from a subset of Sel study subjects (n = 256) at baseline and at 12-months. There were significantly lower odds of an advanced adenoma at baseline with higher prostaglandin E2 (PGE2), with an OR (95% CI) of 0.55 (0.33-0.92), and with 5-hydroxyeicosatetraenoic acid (5-HETE) ((0.53 (0.33-0.94)); and of a large adenoma with higher PGE2 ((0.52 (0.31-0.87)). In contrast, no associations were observed between any oxylipin and the development of a new adenoma during follow-up. Selenium supplementation was associated with a significantly smaller increase in 5-HETE after 12 months compared to the placebo, though no other results were statistically significant. The ARA-derived oxylipins may have a role in the progression of non-advanced adenoma to advanced, but not with the development of a new adenoma.

Glycosylated Hemoglobin as an Age-Specific Predictor and Risk Marker of Colorectal Adenomas in Non-Diabetic Adults.

Background: Diabetes is a risk factor for colorectal neoplasms. The association between the level of glycosylated hemoglobin (HbA1c) and the risk of colorectal adenomas (CRAs) in non-diabetic adults needs to be investigated. Methods: A cross-sectional study was performed on non-diabetic adults with normal HbA1c level who underwent colonoscopy between January 2010 and December 2016 during health check-ups in our hospital in China. The association between HbA1c level and CRAs was assessed by multiple logistic regression models stratified by age group (<40, ≥40 and <50, and ≥50 years old). The age group-specified thresholds for HbA1c on elevated risk of CRAs were estimated using the piecewise logistic regression. Results: Among the 2,764 subjects, 445 (16.1%) had CRA. The prevalence of CRA varied across the three age groups. A higher HbA1c level was found to be significantly associated with increased CRA risk in the 40-50 years group (odds ratio [OR]=1.70, 95% confidence interval [CI] 1.04-2.78, p=0.035) after adjusting for other related factors, while this association was borderline significant among the 50 years and older group (OR=1.57, 95% CI 0.97-2.54, p=0.067). Based on the piecewise logistic regression analysis results, the thresholds for HbA1c on elevated risk of CRA were 5.44% for the 40-50 years group and 4.81% for the 50 years and older group, respectively. Conclusions: Higher levels of HbA1c, even within the normal range, were associated with elevated CRA risk among non-diabetic adults. The threshold effects of HbA1c on the risk of CRA varied across different age groups, and early screening colonoscopy might be needed for individuals in their 40s and with HbA1c levels ≥5.44%.

Epithelial argininosuccinate synthetase is dispensable for intestinal regeneration and tumorigenesis.

The epithelial signaling pathways involved in damage and regeneration, and neoplastic transformation are known to be similar. We noted upregulation of argininosuccinate synthetase (ASS1) in hyperproliferative intestinal epithelium. Since ASS1 leads to de novo synthesis of arginine, an important amino acid for the growth of intestinal epithelial cells, its upregulation can contribute to epithelial proliferation necessary to be sustained during oncogenic transformation and regeneration. Here we investigated the function of ASS1 in the gut epithelium during tissue regeneration and tumorigenesis, using intestinal epithelial conditional Ass1 knockout mice and organoids, and tissue specimens from colorectal cancer patients. We demonstrate that ASS1 is strongly expressed in the regenerating and Apc-mutated intestinal epithelium. Furthermore, we observe an arrest in amino acid flux of the urea cycle, which leads to an accumulation of intracellular arginine. However, loss of epithelial Ass1 does not lead to a reduction in proliferation or increase in apoptosis in vivo, also in mice fed an arginine-free diet. Epithelial loss of Ass1 seems to be compensated by altered arginine metabolism in other cell types and the liver.

Machine-Learning Prediction of Postoperative Pituitary Hormonal Outcomes in Nonfunctioning Pituitary Adenomas: A Multicenter Study.

Objective: No accurate predictive models were identified for hormonal prognosis in non-functioning pituitary adenoma (NFPA). This study aimed to develop machine learning (ML) models to facilitate the prognostic assessment of pituitary hormonal outcomes after surgery. Methods: A total of 215 male patients with NFPA, who underwent surgery in four medical centers from 2015 to 2021, were retrospectively reviewed. The data were pooled after heterogeneity assessment, and they were randomly divided into training and testing sets (172:43). Six ML models and logistic regression models were developed using six anterior pituitary hormones. Results: Only thyroid-stimulating hormone (p < 0.001), follicle-stimulating hormone (p < 0.001), and prolactin (PRL; p < 0.001) decreased significantly following surgery, whereas growth hormone (GH) (p < 0.001) increased significantly. The postoperative GH (p = 0.07) levels were slightly higher in patients with gross total resection, but the PRL (p = 0.03) level was significantly lower than that in patients with subtotal resection. The optimal model achieved area-under-the-receiver-operating-characteristic-curve values of 0.82, 0.74, and 0.85 in predicting hormonal hypofunction, new deficiency, and hormonal recovery following surgery, respectively. According to feature importance analyses, the preoperative levels of the same type and other hormones were all important in predicting postoperative individual hormonal hypofunction. Conclusion: Fluctuation in anterior pituitary hormones varies with increases and decreases because of transsphenoidal surgery. The ML models could accurately predict postoperative pituitary outcomes based on preoperative anterior pituitary hormones in NFPA.