Adenoma Patients Research Articles

P13.16.A MACHINE LEARNING-BASED RADIOMIC MODEL USING MULTIPARAMETRIC MAGNETIC RESONANCE IMAGING FOR PREDICTION OF POSTOPERATIVE VISUAL RECOVERY OF PITUITARY ADENOMA PATIENTS

Abstract BACKGROUND Preoperative prediction of the visual outcome after pituitary adenoma surgery is crucial to clinical decision-making but remains challenging. We aimed to develop radiomic models based on multiparametric magnetic resonance imaging (MRI) to predict the postoperative visual outcome for pituitary adenoma patients using machine learning approaches. MATERIAL AND METHODS A cohort of 152 patients who underwent endoscopic endonasal transsphenoidal surgery of pituitary adenomas were retrospectively enrolled and divided into the recovery group and the non-recovery group based on the six-month postoperative visual examinations. Radiomic features of the optic chiasm were extracted from preoperative T1-weighted imaging (T1WI), T2-weighted imaging (T2WI) and contrast-enhanced T1-weighted imaging (T1CE), respectively. Predictive models were constructed by least absolute shrinkage and selection operator wrapped with support vector machine through the five-fold cross-validation in the development cohort, and then evaluated in the independent test cohort. Area under the receiver operating characteristic curve (AUC), accuracy, specificity and sensitivity were used to assess the predictive performance of models. RESULTS A total of four predictive models were established based on selected radiomic features from three sequences individually or in combinations. Three features from T1WI, two features from T2WI and nine features from T1CE were selected in the multiparametric radiomic model that represented the best performances among the four models, with AUC values of 0.851 (95% CI: 0.768 - 0.933) in the development cohort and 0.847 (95% CI: 0.722 - 0.971) in the independent test cohort. CONCLUSION Our proposed machine learning-based radiomic model using multiparametric MRI can be utilized to assist in predicting the postoperative visual recovery of pituitary adenoma patients in clinical practice.

Recovery of Third, Fourth, and Sixth Cranial Nerve Palsies in Pituitary Adenoma and Meningioma Patients.

This retrospective, observational cohort study aimed to determine recovery rate and recovery time of ocular motor nerve palsies (OMP) of third (CN III), fourth (CN IV), or sixth cranial nerves (CN VI)-and associated prognostic factors-in meningioma and pituitary adenoma (PA) patients. A total of 25 meningioma (28 eyes) and 33 PA patients (36 eyes), treated at the Leiden University Medical Center in the Netherlands from January 1, 1978 to January 31, 2021, were included. OMPs were evaluated according to a newly created recovery scale using on-clinical and orthoptic examinations, which were performed every 3-4 months until palsy recovery, or at 18 months follow-up. Recovery rates of CN III (meningioma 23.5% vs PA 92.3%), CN IV (meningioma 20% vs PA 100%), and CN VI (meningioma 60% vs PA 100%) palsies were observed at 18 months follow-up, with differences between the 2 tumor types being observed in the treated patients only. Median recovery time of all OMPs combined was significantly longer in meningioma patients (37.9 ± 14.3 months vs 3.3 ± 0.1 months; P < 0.001). No significant protective or risk factors for recovery rate or time were identified. OMP recovery rates in treated patients were more favorable in patients with PA compared with patients with meningiomas, independent of OMP cause. With these new insights in OMP recovery, more accurate prognoses and appropriate follow-up strategies can be determined for meningioma and PA patients with OMPs.

Associations of Adherence to the 2018 World Cancer Research Fund and the American Institute for Cancer Research Dietary Recommendations with Gut Microbiota and Inflammation Levels.

Whether the World Cancer Research Fund and the American Institute for Cancer Research (WCRF/AICR) dietary recommendations affect the gut microbiota and inflammatory status remains unclear. We examined the association of dietary adherence scores to the WCRF/AICR with gut microbiota and inflammation in a cross-sectional setting. The WCRF/AICR diet adherence scores were calculated for 151 participants (adenoma 97, non-adenoma 54) from 7-day dietary records. The gut microbiota was analyzed by 16S rRNA gene sequencing of fecal samples. The levels of inflammatory biomarkers in both blood (i.e., IL-6, IL-8, IgA, IgM, and IgG) and fecal samples (i.e., FCP) were evaluated in 97 colorectal adenoma patients who had blood samples available. Multivariable linear regression analyses were conducted to examine the association of individual and total dietary adherence scores with gut microbiota and inflammatory biomarker levels. Participants with higher adherence had lower relative abundance of Proteobacteria (β = -0.041, 95%CI: -0.073, -0.009), Enterobacteriaceae (β = -0.035, 95%CI: -0.067, -0.003), and unidentified Enterobacteriaceae at the genus level (β = -0.029, 95%CI: -0.055, -0.003) compared to those with lower adherence. Plant-based food intake was positively correlated with increased abundance of Phascolarctobacterium (β = 0.013, 95%CI: 0.001, 0.026). Restricting fast food was linked to high abundance of Bacteroidaceae (β = 0.149, 95%CI: 0.040, 0.257) and Bacteroides (β = 0.149, 95%CI: 0.040, 0.257). Limiting sugary drinks was associated with reduced abundance of Lachnospiraceae (β = -0.155, 95%CI: -0.292, -0.018). Plant-based food intake (β = -0.251, 95%CI: -0.450, -0.052) and restriction of fast food (β = -0.226, 95%CI: -0.443, -0.008) were associated with reduced IGG levels in men. Alcohol restriction was linked to lower IL-6 (β = -7.095, 95%CI: -11.286, -2.903) and IL-8 (β = -7.965, 95%CI: -14.700, -1.230) levels in women, but with higher IL-6 (β = 0.918, 95%CI: 0.161, 1.675) levels in men. Our findings support the association of adherence to the WCRF/AICR diet with gut microbiota and inflammation. These results need to be validated in additional prospective or interventional studies.

Pituitary adenomas registry in Thailand

PurposePituitary adenomas are the most common sellar tumors, and may cause adverse outcomes in terms of morbidity and mortality if left untreated or if diagnosis is delayed. No data exists on the prevalence, characteristics, and prognosis of pituitary adenomas in Thailand. The systematic registration of clinical characteristics may improve patient care and prognosis for this disease in Thailand. MethodsThis was a retrospective study conducted in 11 academic referral centers. All patients diagnosed with pituitary adenomas during the 2011–––2014 period were enrolled in the study. The information was correlated with two national databases. ResultsA total of 1,283 pituitary adenoma patients were identified. The adenomas were: non-functioning 50.1%, prolactinoma 29.4%, acromegaly 14.7%, Cushing disease 3.8%, gonadotropin-producing tumor 1.0%, TSH-secreting tumor 0.6%. The mean age was 49.2±15.2 years. Sixty-three percent of patients were female. Most common complaint was visual impairment (27.7%). The average size of the tumor was 22.2±16.1 mm. Fifty-nine percent of patients underwent surgery. Median follow-up was 27.4 months (0–24 years). After treatment, 72.4% improved, and 10.4% were cured. Overall results of treatment in non-functioning adenoma, prolactinoma (medically treated), acromegaly, Cushing, TSH, gonadotropin producing adenoma were: improved/cured in 81/5.5, 86/5.7, 55.9/30, 54.2/31.2, 85.7/14.3, 69.2/15.4% respectively. ConclusionPituitary adenomas in academic centers in Thailand were found predominantly in female in the 4th decade of life. After treatment 72.4% of patients improved and 10% had full recovery. A health promotion system aimed to improve patient and physician recognition and physician expertise may improve the prognosis of these diseases.

Features of combined gut bacteria and fungi from a Chinese cohort of colorectal cancer, colorectal adenoma, and post-operative patients.

Colorectal cancer (CRC) accounts for the third highest morbidity burden among malignant tumors worldwide. Previous studies investigated gut microbiome changes that occur during colorectal adenomas (CRA) progression to overt CRC, thus highlighting the importance of the gut microbiome in carcinogenesis. However, few studies have examined gut microbiome characteristics across the entire spectrum, from CRC development to treatment. The study used 16S ribosomal ribonucleic acid and internal transcribed spacer amplicon sequencing to compare the composition of gut bacteria and fungi in a Chinese cohort of healthy controls (HC), CRC patients, CRA patients, and CRC postoperative patients (PP). Our analysis showed that beta diversity was significantly different among the four groups based on the gut bacterial and fungal data. A total of 51 species of bacteria and 8 species of fungi were identified in the HC, CRA, CRC, and PP groups. Correlation networks for both the gut bacteria and fungi in HC vs. CRA, HC vs. CRC, and HC vs. PP indicated some hub bacterial and fungal genera in each model, and the correlation between bacterial and fungal data indicated that a highly significant negative correlation exists among groups. Quantitative polymerase chain reaction (qPCR) analysis in a large cohort of HC, CRC, CRA, and PP patients demonstrated a significantly increasing trend of Fusobacterium nucleatum, Bifidobacterium bifidum, Candida albicans, and Saccharomyces cerevisiae in the feces of CRC patients than that of HC patients (p < 0.01). However, the abundance levels of CRA and PP were significantly lower in HC patients than those in CRC patients. Further studies are required to identify the functional consequences of the altered bacterial/fungal composition on metabolism and CRC tumorigenesis in the host.

Pre- and Postoperative Magnetic Resonance Imaging Comparative Studies of Pituitary Tissues Following Transsphenoidal Resection of Pituitary Macroadenomas.

Magnetic resonance imaging (MRI) has become the most important radiological procedure for diagnosing and following pituitary tumors. But previous MRI studies on pituitary adenomas are mainly focused on the posterior pituitary. Few research has been done on residual normal pituitary tissue before and after transsphenoidal surgery. This retrospective cohort study investigates the pre- and postoperative magnetic resonance imaging characteristics of normal pituitary tissues regarding transsphenoidal resection of pituitary macroadenomas. Pre- and postoperative magnetic resonance imaging scanning of 112 consecutive pituitary macroadenoma patients who underwent tumor resection via transsphenoidal approach was performed, and their medical records were studied. On preoperative MRI, 66 cases of pituitary stalks were identifiable, 9 of them were roughly in the middle, and 57 cases showed left or right deviation, with the angle between pituitary stalks and the sagittal plane was 5.32°-64.05° (average 21.65°). Among the 57 patients with preoperative pituitary stalk deviation, 55 of the pituitary stalk deviations improved in 1 week after surgery, and 30 cases were almost in the middle in 4-6 months after operation, with the other cases get better in varying degrees. The diameter of pituitary stalk was 1.08-3.89 mm (mean 2.36 mm) in pre-operation, and 1.29-3.43 mm (mean 2.30 mm) in 4-6 months after operation. The length of pituitary stalk was 1.41-11.74 mm (mean 6.12 mm) preoperatively, 3.61-11.63 mm (mean 6.93 mm) early postoperatively, and 5.37-17.57 mm (mean 8.83 mm) in 4-6 months after operation. Pituitary stalk was thickened or compressed on preoperative MR images, and gradually recovered to normal during postoperative period. It tended to be in the middle position and its length increased gradually until 4-6 months after operation. On preoperative MRI, 69 out of 112 patients showed residual pituitary tissues (RPT)(+) on enhanced MRI. RPT were likely located above the adenomas in somatotroph adenoma patients. Morphological restitution of postoperative normal pituitary tissues was better in lateral displacement than in superior or superolateral patterns on preoperative magnetic resonance imaging. Postoperative normal pituitary tissues usually subsided directly in superior displacement pattern on preoperative MRI, while were likely to be confined in the lateral side in lateral and superolateral displacement patients. Postoperative morphologic remodeling grade of RPT was positively correlated with the maximum diameter of pituitary adenoma (p = 0.000), but not with age. The larger the tumor diameter, the worse the pituitary morphological recovery after tumor resection. Relative locations of normal pituitary and adenoma tissues may be related to adenoma type and may affect postoperative reconstruction of residual normal pituitary tissues. These findings enable surgeons to distinguish pituitary tissue from residual or recurring tumor tissue on postoperative magnetic resonance imaging.

Association of cigarette smoking with risk of colorectal cancer subtypes classified by gut microbiota.

Both cigarette smoking and gut microbiota play important roles in colorectal carcinogenesis. We explored whether the association between smoking and colorectal cancer (CRC) risk varies by gut microbial enterotypes and how smoking-related enterotypes promote colorectal carcinogenesis. A case-control study was conducted. Fecal microbiota was determined by 16S rDNA sequencing. The cases with CRC or adenoma were subclassified by gut microbiota enterotypes. Multivariate analyses were used to test associations between smoking and the odds of colorectal neoplasm subtypes. Mann-Whitney U tests were used to find differential genera, genes, and pathways between the subtypes. Included in the study were 130 CRC patients (type I: n=77; type II: n=53), 120 adenoma patients (type I: n=66; type II: n=54), and 130 healthy participants. Smoking increased the odds for type II tumors significantly (all p for trend <0.05) but not for type I tumors. The associations of smoking with increased odds of colorectal neoplasm significantly differed by gut microbiota enterotypes (p<0.05 for heterogeneity). An increase in carcinogenic bacteria (genus Escherichia shigella) and a decrease in probiotics (family Lachnospiraceae and Ruminococcaceae) in type II tumors may drive disease progression by upregulating oncogenic signaling pathways and inflammatory/oxidative stress response pathways, as well as protein phospholipase D1/2, cytochrome C, and prostaglandin-endoperoxide synthase 2 expression. Smoking was associated with a higher odds of type II colorectal neoplasms but not type I tumors, supporting a potential role for the gut microbiota in mediating the association between smoking and colorectal neoplasms.

Fecal Immunochemical Test (FIT) in Triage of Bleed-positive (Crab+) and Bleed-negative Colorectal Adenoma (Crab-) Patients in Colorectal Neoplasia Screening.

Fecal immunochemical tests (FITs) are sensitive and specific for detecting colorectal cancer (CRC), but their diagnostic accuracy (DA) in bleed-positive (CRAb+) and bleed-negative colorectal adenomas (CRAb-) has been rarely tested. A total of n=506 patients were included in the study, each collecting 3 consecutive stool samples for analysis. The stool samples were analyzed by the ColonView FIT (CV) and Hemoccult SENSA tests. A total of 484/5,090 (9.5%) patients returned all 3 samples and were subjected to final analysis. Hierarchical summary receiver operating characteristic (HSROC) analysis with different cut-offs for hemoglobin/haptoglobin (Hb and Hb/Hp) complex was performed to assess the DA of CV. In the HSROC analysis, the AUC values were as follows: i) bleed-positive adenoma patients by visual analysis mode (VA), AUC=0.566, ii) bleed-positive adenoma patients by automatic analysis mode (AA), AUC=0.546, iii) bleed-negative adenoma patients by VA, AUC=0.534 and iv) bleed-negative adenoma patients by AA, AUC=0.589: In roccomp analysis, there were significant differences in AUC values between iii) and iv) p=0.045. When stratified by the 'blood in stool' (as b+ or b- endpoint), the DA of the CV test is quite similar for CRAb+ and CRAb-. However, of the two modes (VA/AA) of the CV test, the AA reading gives a slightly higher DA both CRAb+ and CRAb-.

Predicting visual recovery in pituitary adenoma patients post-endoscopic endonasal transsphenoidal surgery: Harnessing delta-radiomics of the optic chiasm from MRI

ObjectivesTo investigate whether morphological changes after surgery and delta-radiomics of the optic chiasm obtained from routine MRI could help predict postoperative visual recovery of pituitary adenoma patients.MethodsA total of 130 pituitary adenoma patients were retrospectively enrolled and divided into the recovery group (n = 87) and non-recovery group (n = 43) according to visual outcome 1 year after endoscopic endonasal transsphenoidal surgery. Morphological parameters of the optic chiasm were measured preoperatively and postoperatively, including chiasmal thickness, deformed angle, and suprasellar extension. Delta-radiomics of the optic chiasm were calculated based on features extracted from preoperative and postoperative coronal T2-weighted images, followed by machine learning modeling using least absolute shrinkage and selection operator wrapped with support vector machine through fivefold cross-validation in the development set. The delta-radiomic model was independently evaluated in the test set, and compared with the combined model that incorporated delta-radiomics, significant clinical and morphological parameters.ResultsPostoperative morphological changes of the optic chiasm could not significantly be used as predictors for the visual outcome. In contrast, the delta-radiomics model represented good performances in predicting visual recovery, with an AUC of 0.821 in the development set and 0.811 in the independent test set. Moreover, the combined model that incorporated age and delta-radiomics features of the optic chiasm achieved the highest AUC of 0.841 and 0.840 in the development set and independent test set, respectively.ConclusionsOur proposed machine learning models based on delta-radiomics of the optic chiasm can be used to predict postoperative visual recovery of pituitary adenoma patients.Clinical relevance statementOur delta-radiomics-based models from MRI enable accurate visual recovery predictions in pituitary adenoma patients who underwent endoscopic endonasal transsphenoidal surgery, facilitating better clinical decision-making and ultimately improving patient outcomes.Key Points• Prediction of the postoperative visual outcome for pituitary adenoma patients is important but challenging.• Delta-radiomics of the optic chiasm after surgical decompression represented better prognostic performances compared with its morphological changes.• The proposed machine learning models can serve as novel approaches to predict visual recovery for pituitary adenoma patients in clinical practice.

Molecular characterization of colorectal adenoma and colorectal cancer via integrated genomic transcriptomic analysis.

Colorectal adenoma can develop into colorectal cancer. Determining the risk of tumorigenesis in colorectal adenoma would be critical for avoiding the development of colorectal cancer; however, genomic features that could help predict the risk of tumorigenesis remain uncertain. In this work, DNA and RNA parallel capture sequencing data covering 519 genes from colorectal adenoma and colorectal cancer samples were collected. The somatic mutation profiles were obtained from DNA sequencing data, and the expression profiles were obtained from RNA sequencing data. Despite some similarities between the adenoma samples and the cancer samples, different mutation frequencies, co-occurrences, and mutually exclusive patterns were detected in the mutation profiles of patients with colorectal adenoma and colorectal cancer. Differentially expressed genes were also detected between the two patient groups using RNA sequencing. Finally, two random forest classification models were built, one based on mutation profiles and one based on expression profiles. The models distinguished adenoma and cancer samples with accuracy levels of 81.48% and 100.00%, respectively, showing the potential of the 519-gene panel for monitoring adenoma patients in clinical practice. This study revealed molecular characteristics and correlations between colorectal adenoma and colorectal cancer, and it demonstrated that the 519-gene panel may be used for early monitoring of the progression of colorectal adenoma to cancer.

Joint pain, physical function, and balance self-confidence in acromegaly versus nonfunctioning pituitary adenoma patients.

Patients with acromegaly (PWA) experience balance issues, despite achieving biochemical remission, that may significantly impair their quality of life. We sought to assess the prevalence of falls and balance self-confidence in PWA in comparison with a control group. Furthermore, we investigated the effect of joint pain and function as predictors for their balance self-confidence. Cross-sectional, case-controlled. Tertiary care centers. In this case-control study, we surveyed PWA (n = 94) and nonfunctioning pituitary adenoma (PNA; n = 82) with similar age, sex, and body mass index from two Canadian centers. None. Data were obtained on number of falls during the past 12 months, self-confidence to maintain balance, joint pain, joint surgery, pain medication usage, and upper and lower extremity musculoskeletal disability. While both PWA and PNA had a similarly high risk of falls, PWA had lower self-confidence to maintain balance (P < .01). Patients with acromegaly had higher joint pain scores and more functional impairment in upper extremity, hip, knee, and ankle joints (all P < .01). In both groups, age, sex, and ankle functional score were predictors of balance self-confidence. For PWA, hip functional score was also a predictor of balance self-confidence in contrast to knee and back pain scores being predictors for the PNA group. We confirmed an increased prevalence of falls in both groups with diminished balance confidence in PWA. This reduced balance self-confidence seems to be related to their increased hip functional impairment in comparison with PNA.

KCNJ5 mutation is a predictor for recovery of endothelial function after adrenalectomy in patients with aldosterone-producing adenoma.

The relationship of KCNJ5 mutation with vascular function and vascular structure in aldosterone-producing adenoma (APA) patients before and after adrenalectomy remains unclear. The purpose of this study was to evaluate the influence of KCNJ5 mutation on vascular function and vascular structure in APA and the effects of adrenalectomy on vascular function and vascular structure in APA patients with and those without KCNJ5 mutation. Flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation (NID), brachial artery intima-media thickness (IMT), and brachial-ankle pulse wave velocity (baPWV) were measured to assess vascular function and vascular structure in 46 APA patients with KCNJ5 mutation and 23 APA patients without KCNJ5 mutation and in 69 matched pairs of patients with essential hypertension (EHT). FMD, NID, brachial IMT and baPVW were evacuated before adrenalectomy and at 12 weeks after adrenalectomy in APA patients with KCNJ5 mutation and APA patients without KCNJ5 mutation. FMD and NID were significantly lower in APA patients than in patients with EHT. There was no significant difference in FMD or NID between patients with and those without KCNJ5 mutation. In APA patients with KCNJ5 mutation, FMD and NID after adrenalectomy were significantly higher than those before adrenalectomy. In APA patients without KCNJ5 mutation, only NID after adrenalectomy was significantly higher than that before adrenalectomy. Endothelial function in APA patients with KCNJ5 mutation was improved by adrenalectomy in the early postoperative period. KCNJ5 mutation is a predictor for early resolution of endothelial function by adrenalectomy. This study was approved by principal authorities and ethical issues in Japan (URL for Clinical Trial: http://www.umin.ac.jp/ctr/index.htm Registration Number for Clinical Trial: UMIN000003409).

Giant invasive pituitary adenomas: surgical approach selection paradigm and its influence on the outcome—case series

ObjectivePointing out our surgical strategy and experience in selection of surgical approaches in giant pituitary adenomas patients and its relation to surgical and clinical outcome.Methods31 patients with giant pituitary adenomas (maximum diameter ≥ 4 cm). We analyzed the preoperative clinical presentation, radiological criteria of the tumor, endocrinological profile, approach selected, extent of resection, clinical outcomes and complications.Results16 males (51.6%) and 15 females (48.4%). All the patients had a visual complaint (13 had mild impairment (41.9%), 18 had significant visual loss (58.1%). 20 were nonfunctioning (64.6%), 5 prolactin secreting (16%) and 6 growth hormone secreting (19.4%). Surgical approaches included: standard endoscopic endonasal approach in 7, extended approach in 4, transcranial (extended pterional approach) in 3. Staged endoscopic surgery in 5. Extended pterional approach followed endoscopic approach in 12. Gross total resection in 18 (58%) subtotal resection in 8 patients (25.8%) and partial resection in 5 patients (16.2%). The most common complications was tumor recurrence in 8, CSF leakage in 3, Permanent diabetes insipidus in 2, postoperative hydrocephalus in 1, transient 6th CN palsy in 3, and unfortunately only one patient died. 8 had complete Visual recovery, 9 were improved partially, and 11 remain unchanged. Only 3 showed further deterioration of vision.ConclusionsGiant invasive pituitary adenoma is still one of the challenging issues in decision making for selection of the appropriate management strategy. Advancement of the endoscopic surgical techniques made the transsphenoidal approach is the primary choice for management of giant pituitary adenoma. However, the door is still opened for transcranial approach as staged the procedure after endoscopic approach or sole approach for some selected cases.

Associations between Ileal Juice Bile Acids and Colorectal Advanced Adenoma.

There is an urgent need to identify biomarkers for advanced adenoma, an important precursor of colorectal cancer (CRC). We aimed to determine alterations in ileal juice bile acids associated with colorectal advanced adenoma. We quantified a comprehensive panel of primary and secondary bile acids and their conjugates using an ultraperformance liquid chromatography triple-quadrupole mass spectrometric assay in ileal juice collected at colonoscopy from 46 study subjects (i.e., 14 biopsy-confirmed advanced adenomas and 32 controls free of adenoma or cancer). Using analysis of covariance (ANCOVA), we examined the differences in bile acid concentrations by disease status, adjusting for age, sex, body mass index, smoking status and type 2 diabetes. The concentrations of hyodeoxycholic acid (HCA) species in ileal juice of the advanced adenoma patients (geometric mean = 4501.9 nM) were significantly higher than those of controls (geometric mean = 1292.3 nM, p = 0.001). The relative abundance of ursodeoxycholic acid (UDCA) in total bile acids was significantly reduced in cases than controls (0.73% in cases vs. 1.33% in controls; p = 0.046). No significant difference between cases and controls was observed for concentrations of total or specific primary bile acids (i.e., cholic acid (CA), chenodeoxycholic acid (CDCA) and their glycine- and taurine-conjugates) and total and specific major secondary bile acids (i.e., deoxycholic acid and lithocholic acid). Colorectal advanced adenoma was associated with altered bile acids in ileal juice. The HCA species may promote the development of colorectal advanced adenoma, whereas gut microbiota responsible for the conversion of CDCA to UDCA may protect against it. Our findings have important implications for the use of bile acids as biomarkers in early detection of colorectal cancer.

Racial and ethnic disparities in the presentation size and timing of pituitary adenomas resected via endoscopic endonasal approach.

In a single-center cohort of pituitary adenoma patients, non-White race independently predicted larger tumor size at initial presentation. Uninsured patients suffered a significantly higher rate of pituitary apoplexy at initial presentation. Geographically distant care appeared to present a greater barrier for non-White and Hispanic patients relative to their White and non-Hispanic counterparts.

Targeted metabolomics analysis of nucleosides and the identification of biomarkers for colorectal adenomas and colorectal cancer.

The morbidity and mortality of colorectal cancer (CRC) have been increasing in recent years, and early detection of CRC can improve the survival rate of patients. RNA methylation plays crucial roles in many biological processes and has been implicated in the initiation of various diseases, including cancer. Serum contains a variety of biomolecules and is an important clinical sample for biomarker discovery. In this study, we developed a targeted metabolomics method for the quantitative analysis of nucleosides in human serum samples by using liquid chromatography with tandem mass spectrometry (LC-MS/MS). We successfully quantified the concentrations of nucleosides in serum samples from 51 healthy controls, 37 patients with colorectal adenomas, and 55 patients with CRC. The results showed that the concentrations of N 6-methyladenosine (m6A), N 1-methyladenosine (m1A), and 3-methyluridine (m3U) were increased in patients with CRC, whereas the concentrations of N 2-methylguanosine (m2G), 2'-O-methyluridine (Um), and 2'-O-methylguanosine (Gm) were decreased in patients with CRC, compared with the healthy controls and patients with colorectal adenomas. Moreover, the levels of 2'-O-methyluridine and 2'-O-methylguanosine were lower in patients with colorectal adenomas than those in healthy controls. Interestingly, the levels of Um and Gm gradually decreased in the following order: healthy controls to colorectal adenoma patients to CRC patients. These results revealed that the aberrations of these nucleosides were tightly correlated to colorectal adenomas and CRC. In addition, the present work will stimulate future investigations about the regulatory roles of these nucleosides in the initiation and development of CRC.

Integrated analysis of colorectal neoplasia tissue and gut microbiome associated serum metabolites for diagnosis of early-stage CRC and advanced adenoma.

e15523 Background: Detection and excision of early-stage CRC or colorectal precancerous lesions (advanced adenoma) has been recognized as an effective way to reduce CRC induced mortality. Integrating signals from both tumoral tissues and microenvironment exhibit better accuracy for tumor detection, especially for early-stage tumors. Gut microbiome carried out profound effects on initiation and progression of colorectal cancer and adenoma, and our previous findings have also revealed that gut microbiome-associated serum metabolites exhibited potential for detecting colorectal neoplasia patients. Here, we carried out an integrated analysis of both early colorectal neoplasia tissues and related gut microbiome to define their combined effect on serum metabolome and develop diagnostic test for early-stage CRC and advanced adenoma. Methods: Integrated analysis of untargeted metabolomics of serum and tissue samples and metagenome sequencing of paired fecal samples were applied to define tissue metabolome and gut microbiome variations between normal and colorectal neoplasia patients. Selected metabolic biomarkers were quantified by targeted LC-MS detection, and a diagnostic model based on the integrated serum metabolite biomarkers was established and evaluated in an independent modeling cohort. Results: Consensus participants undergoing coloscopy were enrolled. The serum-fecal matched discovery cohort includes 120 individuals, ranging from normal, non-adenoma polyp individuals to adenoma and early-stage CRC patients, and among them, resected neoplastic tissue samples were also examined. Co-relation analysis was caried out to build associations of serum metabolome with either tissue metabolome or gut microbiome enriched in early neoplasia patients. More than 100 candidate metabolic biomarkers in serum were selected and transferred to targeted metabolomics detection in an independent modeling cohort including 696 individuals (265 normal individuals, 122 with hyperplastic polyps, 155 with low-risk colorectal adenoma were assigned to the negative group; and positive group includes 136 advanced colorectal adenoma and 18 early-stage CRC patients). After feature selection, an integrated diagnostic model was established to detect early CRC and advanced adenoma, yielded an area under the curve (AUC) of 0.89 in the training set and an AUC of 0.87 (66.7% sensitivity, 90.4% specificity) in the testing set. As for advanced adenoma, the model could also achieve an AUC of 0.84 in the testing set (59.7% sensitivity, 90.4% specificity), significantly higher than previously reported fecal based FIT-DNA test and blood based Septin 9 test. Conclusions: Integrating serum metabolic biomarkers associated with both tumor tissue and colorectal neoplasia related gut microbiota could effectively detect early colorectal cancer and advanced adenoma.

Endoscopic Transsphenoidal Surgery of Pituitary Adenomas: Preliminary Results of the Neurosurgery Service of Hospital Cristo Redentor

Abstract Objective The transsphenoidal surgery is a safe and effective technique to manage different skull base pathologies, such as pituitary adenomas. The purpose of the present study is to describe the initial experience with endoscopic transsphenoidal surgery in the treatment of pituitary adenoma patients at a tertiary hospital that is a reference in neurosurgery in Southern Brazil. Materials and Methods We retrospectively analyzed data from 60 patients with pituitary adenoma who underwent endoscopic transsphenoidal surgery between 2012 and 2019. Demographic characteristics, type of tumor, baseline hormonal changes, and clinical presentation were reported, as well as postoperative outcomes, tumor resection rate, and complications. Results The male/female ratio was of 0.53:1, and the mean age of the sample was of 54 (range: 26 to 79) years. In total, 34 patients (57%) presented the non-functioning adenoma subtype, and 26 (43%), the functioning adenoma subtype. In the non-functioning and functioning subtype groups, the average tumor diameter was of 32 mm and 18 mm, and the mean follow-up was of 27 months and 32 months respectively. Regarding visual symptoms, 79% of the patients showed improvement after surgery. Hormonal remission was achieved in 71% of the patients with prolactinoma, 85% of those with cushing, and 57% of patients with acromegaly. Overall, gross total resection (GTR) was achieved in 50% of patients but with a significantly lower rate among patients with tumors with parasellar growth (high grade on the Knosp classification). The most prevalent surgical complications observed were postoperative cerebrospinal fluid (CSF) leak and meningitis in 11% and 6% of the cases respectively. Conclusion We have shown that transsphenoidal endoscopic surgery can produce good results in the management of pituitary adenomas, with acceptable peri- and postoperative morbidity and mortality. Regardless of the technique used, the presence of large and giant pituitary adenomas with a high Knosp grade represents an enormous challenge for contemporary neurosurgery.

A Fecal MicroRNA Signature by Small RNA Sequencing Accurately Distinguishes Colorectal Cancers: Results From a Multicenter Study

Fecal tests currently used for colorectal cancer (CRC) screening show limited accuracy in detecting early tumors or precancerous lesions. In this respect, we comprehensively evaluated stool microRNA (miRNA) profiles as biomarkers for noninvasive CRC diagnosis. A total of 1273 small RNA sequencing experiments were performed in multiple biospecimens. In a cross-sectional study, miRNA profiles were investigated in fecal samples from an Italian and a Czech cohort (155 CRCs, 87 adenomas, 96 other intestinal diseases, 141 colonoscopy-negative controls). A predictive miRNA signature for cancer detection was defined by a machine learning strategy and tested in additional fecal samples from 141 CRC patients and 80 healthy volunteers. miRNA profiles were compared with those of 132 tumors/adenomas paired with adjacent mucosa, 210 plasma extracellular vesicle samples, and 185 fecal immunochemical test leftover samples. Twenty-five miRNAs showed altered levels in the stool of CRC patients in both cohorts (adjusted P < .05). A 5-miRNA signature, including miR-149-3p, miR-607-5p, miR-1246, miR-4488, and miR-6777-5p, distinguished patients from control individuals (area under the curve [AUC], 0.86; 95% confidence interval [CI], 0.79-0.94) and was validated in an independent cohort (AUC, 0.96; 95% CI, 0.92-1.00). The signature classified control individuals from patients with low-/high-stage tumors and advanced adenomas (AUC, 0.82; 95% CI, 0.71-0.97). Tissue miRNA profiles mirrored those of stool samples, and fecal profiles of different gastrointestinal diseases highlighted miRNAs specifically dysregulated in CRC. miRNA profiles in fecal immunochemical test leftover samples showed good correlation with those of stool collected in preservative buffer, and their alterations could be detected in adenoma or CRC patients. Our comprehensive fecal miRNome analysis identified a signature accurately discriminating cancer aimed at improving noninvasive diagnosis and screening strategies.

Altered hemispheric asymmetry of attentional networks in patients with pituitary adenoma: an event-related potential study.

Emerging evidence has been reported of attentional dysfunction in pituitary adenoma patients. However, the effect of pituitary adenomas on lateralized attention network efficiency remained to be clear. Thus, the present study aimed to investigate the impairment of lateralized attention networks in patients with pituitary adenoma. Eighteen pituitary adenoma patients (PA group) and 20 healthy controls (HCs) were included in this study. Both behavioral results and event-related potentials (ERPs) were acquired while subjects performed the Lateralized Attention Network Test (LANT). Behavioral performances indicated the PA group had a slower reaction time and a similar error rate relative to the HCs group. Meanwhile, significantly increased executive control network efficiency suggested the dysfunction of inhibition control in PA patients. Regarding ERP results, there were no group differences in the alerting and orienting networks. The target-related P3 was significantly reduced in the PA group, suggesting an impairment of executive control function and attentional resources allocation. Moreover, the mean amplitude of P3 was significantly lateralized to the right hemisphere, and interacted with the visual field, exhibiting that the right hemisphere dominated the bilateral visual field, whereas the left hemisphere dominated the left visual field. In the specific high-conflict condition, the pattern of hemispheric asymmetry in the PA group was altered due to a mixed effect resulting from the compensatory recruitment of attentional resources in the left central parietal area and the destructive effects of hyperprolactinemia. These findings suggested that, in the lateralized condition, the decreased P3 in the right central parietal area and the diminished hemispheric asymmetry under high conflict load, may serve as the potential biomarkers of attentional dysfunction in patients with pituitary adenoma.