Efficacy and safety of Shenbai Granules for recurrent colorectal adenoma: A multicenter randomized controlled trial.

BACKGROUND: Colorectal adenoma is benign glandular tumor of colon, the precursor of colorectal cancer. But no pharmaceutical medication is currently available to treat and prevent adenomas. PURPOSE: To evaluate efficacy of Shenbai Granules, an herbal medicine formula, in reducing the recurrence of adenomas. STUDY DESIGN: This multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted by eight hospitals in China. METHODS: Patients who had received complete polypectomy and were diagnosed with adenomas within the recent 6 months were randomly assigned (1:1) to receive either Shenbai granules or placebo twice a day for 6 months. An annual colonoscopy was performed during the 2-year follow-up period. The primary outcome was the proportion of patients with at least one adenoma detected in the modified intention-to-treat (mITT) population during follow-up for 2 years. The secondary outcomes were the proportion of patients with sessile serrated lesions and other specified polypoid lesions. The data were analyzed using logistic regression. RESULTS: Among 400 randomized patients, 336 were included in the mITT population. We found significant differences between treatment and placebo groups in the proportion of patients with at least one recurrent adenoma (42.5 % vs. 58.6 %; OR, 0.47; 95 % CI, 0.29-0.74; p = 0.001) and sessile serrated lesion (1.8 % vs. 8.3 %; OR, 0.20; 95 % CI, 0.06-0.72; p = 0.01). There was no significant difference in the proportion of patients developing polypoid lesions (70.7 % vs. 77.5 %; OR, 1.43; 95 % CI, 0.88-2.34; p = 0.15) or high-risk adenomas (9.0 % vs. 13.6 %; OR, 0.63; 95 % CI, 0.32-1.25; p = 0.18). CONCLUSION: Shenbai Granules significantly reduced the recurrence of adenomas, indicating that they could be an effective option for adenomas. Future studies should investigate its effects in larger patient populations and explore its mechanism of action to provide more comprehensive evidence for the use of Shenbai Granules in adenoma treatment.

Randomized Trial of Patient Outreach Approaches to De-implement Outdated Colonoscopy Surveillance Intervals.

BACKGROUND AND AIMS: Guidelines now recommend patients with low-risk adenomas receive colonoscopy surveillance in 7-10 years and those with the previously recommended 5-year interval be re-evaluated. We tested 3 outreach approaches for transitioning patients to the 10-year interval recommendation. METHODS: This was a 3-arm pragmatic randomized trial comparing telephone, secure messaging, and mailed letter outreach. The setting was Kaiser Permanente Northern California, a large integrated healthcare system. Participants were patients 54-70 years of age with 1-2 small (<10 mm) tubular adenomas at baseline colonoscopy, due for 5-year surveillance in 2022, without high-risk conditions, and with access to all 3 outreach modalities. Patients were randomly assigned to the outreach arm (telephone [n = 200], secure message [n = 203], and mailed letter [n = 201]) stratified by age, sex, and race/ethnicity. Outreach in each arm was performed by trained medical assistants (unblinded) communicating in English with 1 reminder attempt at 2-4 weeks. Participants could change their assigned interval to 10 years or continue their planned 5-year interval. RESULTS: Sixty-day response rates were higher for telephone (64.5%) and secure messaging outreach (51.7%) vs mailed letter (31.3%). Also, more patients adopted the 10-year surveillance interval in the telephone (37.0%) and secure messaging arms (32.0%) compared with mailed letter (18.9%) and rate differences were significant for telephone (18.1%; 97.5% confidence interval: 8.3%-27.9%) and secure message outreach (13.1%; 97.5% confidence interval: 3.5%-22.7%) vs mailed letter outreach. CONCLUSIONS: Telephone and secure messaging were more effective than mailed letter outreach for de-implementing outdated colonoscopy surveillance recommendations among individuals with a history of low-risk adenomas in an integrated healthcare setting. (ClinicalTrials.gov, Number: NCT05389397).

Primary aldosteronism without hypertension:A case report and review of the literature / Hyperaldostéronisme primaire sans hypertension artérielle : à propos d'un cas et revue de la littérature

We describe the case of a patient who presented with hyperaldosteronism without arterial hypertension. She had been referred for consultation for persistent severe hypokalaemia despite oral KCl supplementation. The absence of hypertension had been proven by repeated clinical measurements and by ABPM. Hyperaldosteronism had been demonstrated by hormonal assays and catheterization of the adrenal veins. Abdominal CT revealed a left adrenal adenoma. Finally, the anatomopathological examination of the surgical specimen confirmed the adenoma. After the intervention, serum potassium normalized. The clinical case is completed by a review of the literature of hyperaldosteronisms without arterial hypertension.

Nous décrivons le cas d'une patiente qui s'est présentée avec un hyperaldostéronisme sans hypertension artérielle. Elle a été adressée en consultation pour une hypokaliémie sévère persistante malgré une supplémentation orale en chlorure de potassium (KCl). L'absence d'hypertension a été prouvée par des mesures cliniques répétées et par mesure ambulatoire de la pression artérielle (MAPA). L'hyperaldostéronisme a été mis en évidence par des dosages hormonaux et un cathétérisme des veines surrénales. Le scanner abdominal a révélé un adénome surrénalien gauche. Enfin, l'examen anatomopathologique de la pièce opératoire a confirmé l'adénome. Après l'intervention, le potassium sérique s'est normalisé. Le cas clinique est complété par une revue de la littérature des hyperaldostéronismes sans hypertension artérielle.

A hyperaldosteronism subtypes predictive model using ensemble learning.

This study aimed to develop a machine-learning algorithm to diagnose aldosterone-producing adenoma (APA) for predicting APA probabilities. A retrospective cross-sectional analysis of the Japan Rare/Intractable Adrenal Diseases Study dataset was performed using the nationwide PA registry in Japan comprised of 41 centers. Patients treated between January 2006 and December 2019 were included. Forty-six features at screening and 13 features at confirmatory test were used for model development to calculate APA probability. Seven machine-learning programs were combined to develop the ensemble-learning model (ELM), which was externally validated. The strongest predictive factors for APA were serum potassium (s-K) at first visit, s-K after medication, plasma aldosterone concentration, aldosterone-to-renin ratio, and potassium supplementation dose. The average performance of the screening model had an AUC of 0.899; the confirmatory test model had an AUC of 0.913. In the external validation, the AUC was 0.964 in the screening model using an APA probability of 0.17. The clinical findings at screening predicted the diagnosis of APA with high accuracy. This novel algorithm can support the PA practice in primary care settings and prevent potentially curable APA patients from falling outside the PA diagnostic flowchart.

Impact of Common Vitamin D-Binding Protein Isoforms on Supplemental Vitamin D3 and/or Calcium Effects on Colorectal Adenoma Recurrence Risk: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Variants in the vitamin D-binding protein (DBP) gene (GC) encode DBP isoforms that may affect vitamin D metabolism. However, whether these isoforms modify the effects of vitamin D3 and/or calcium supplementation on colorectal adenoma recurrence is unclear. We hypothesized that supplementation effects may be stronger among those with the DBP2 isoform (encoded by the rs4588*A allele), which is associated with vitamin D deficiency and modified the associations of circulating vitamin D with risk for colorectal neoplasms in observational studies. Objective: To estimate supplemental vitamin D3 and/or calcium effects on colorectal adenoma recurrence according to 3 common DBP isoforms (DBP1s, DBP1f, DBP2) encoded by 2 missense variants: rs7041 (NG_012837.3:g.57904T>G NP_001191235.1:p.Asp432Glu) and rs4588 (NG_012837.3:g.57915C>A NP_001191235.1:p.Thr436Lys). Design, Setting, and Participants: Secondary analysis of a randomized, double-blind, placebo-controlled clinical trial of 2259 participants with a recently diagnosed adenoma and no remaining polyps after complete colonoscopy in the US from July 1, 2004, to August 31, 2013. The current analyses were performed from August 12, 2019, to July 16, 2022. Interventions: Daily vitamin D3 (1000 IU), calcium (1200 mg), both, or placebo. Main Outcomes and Measures: One or more adenomas diagnosed during 3 to 5 years of follow-up. Treatment effects were estimated according to DBP isoform as risk ratios (RRs) and 95% CIs using Poisson regression analysis. Results: Of the 2259 participants randomized (mean [SD] age, 58 [6.8] years; 1033 [64%] men), 1604 non-Hispanic White participants (chosen to avoid population stratification bias) were included in the analysis. Among those with the DBP2 isoform (rs4588*AC or AA), the RRs (95% CI) for adenoma recurrence were 0.84 (0.72-1.00) with vitamin D3 relative to no vitamin D3, 0.83 (95% CI, 0.70-0.99) with calcium relative to no calcium, and 0.76 (95% CI, 0.59-0.98) with both agents relative to neither agent. Conversely, among those without DBP2 (rs4588*CC), the corresponding values were 1.08 (95% CI, 0.93-1.26; P = .03 for interaction) with vitamin D3 relative to no vitamin D3, 0.98 (95% CI, 0.84-1.14; P = .37 for interaction) with calcium relative to no calcium, and 1.09 (0.88-1.36; P = .03 for interaction) with both agents relative to neither agent. Among DBP2 homozygotes (rs4588*AA), the RR for adenoma recurrence was 0.57 (95% CI, 0.31-1.08) with both agents relative to neither agent. Conclusions and Relevance: The findings of this secondary analysis of a randomized clinical trial suggest that individuals with the DBP2 isoform-encoding rs4588*A allele may particularly benefit from vitamin D3 and/or calcium supplementation for colorectal adenoma prevention. Trial Registration: ClinicalTrials.gov Identifier: NCT00153816.

Endoscopic findings after CT proven acute diverticulitis: a systematic review and meta-analysis.

BACKGROUND: Traditionally, international guidelines recommend patients with acute diverticulitis should be followed up with a colonoscopy 6-8 weeks after discharge. However, the need for an interval colonoscopy has been increasingly challenged in the setting of computed tomography (CT). Previous meta-analyses have included studies which combined suspected rather than imaging confirmed diverticulitis and often without correlation with endoscopic findings. This meta-analysis aims to investigate endoscopic findings of patients with CT confirmed diverticulitis. METHODS: An electronic search of Medline, PubMed, Cochrane Library, Embase, CINAHL, Web of Science, Scopus, Clinicaltrials.gov and WHO ICTRP was performed up to October 18, 2021. Studies which reported CT confirmed acute diverticulitis in adults and who underwent endoscopic follow-up with either a colonoscopy or flexible sigmoidoscopy were included. Studies were excluded if diverticulitis was diagnosed by clinical grounds alone, ultrasound, barium enema, or other non-CT forms of imaging. RESULTS: A total of 68 studies with 13 905 patients were included. Median age was 58 years and male to female ratio was 0.84. Cancer was detected in 2.0% and advanced adenoma in 3.8%. Complicated diverticulitis had 9.2 higher odds of cancer compared to uncomplicated diverticulitis (95% CI 4.42-19.08, P < 0.001). Adenomas were detected in 17%. Of those diagnosed with colorectal cancer, 85% were concordant with the site of the diverticulitis on CT while 15% were incidental findings. CONCLUSION: Routine colonoscopic follow up should be recommended in medically fit patients who have CT proven acute diverticulitis due to the higher than population prevalence of colorectal cancer and advanced adenomas.

[Guidelines for prevention and treatment of colorectal adenoma with integrated Chinese and western medicine].

The Guidelines for prevention and treatment of colorectal adenoma with integrated Chinese and western medicine are put forward by Nanjing University of Chinese Medicine and approved by China Association of Chinese Medicine. According to the formulation processes and methods of relevant clinical practice guidelines, the experts in clinical medicine and methodology were organized to discuss the key problems to be addressed in the clinical prevention and treatment of colorectal adenoma(CRA) and provided answers following the evidence-based medicine method, so as to provide guidance for clinical decision-making. CRA is the major precancerous disease of colorectal cancer. Although the prevention and treatment with integrated Chinese and western medicine have been applied to the clinical practice of CRA, there is still a lack of high-quality guidelines. Four basic questions, 15 clinical questions, and 10 outcome indicators were determined by literature research and Delphi questionnaire. The relevant randomized controlled trial(RCT) was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, and 2 clinical trial registries, and finally several RCTs meeting the inclusion criteria were included. The data extracted from the RCT was imported into RevMan 5.3 for evidence synthesis, and the evidence was evaluated based on the Grading of Recommendations, Assessment, Development, and Evaluations(GRADE). The final recommendations were formed by the nominal group method based on the evidence summary table. The guidelines involve the diagnosis, screening, treatment with integrated Chinese and western medicine, prevention, and follow-up of colorectal adenoma, providing options for the clinical prevention and treatment of CRA.

Association of Physician Adenoma Detection Rates With Postcolonoscopy Colorectal Cancer.

Importance: Although colonoscopy is frequently performed in the United States, there is limited evidence to support threshold values for physician adenoma detection rate as a quality metric. Objective: To evaluate the association between physician adenoma detection rate values and risks of postcolonoscopy colorectal cancer and related deaths. Design, Setting, and Participants: Retrospective cohort study in 3 large integrated health care systems (Kaiser Permanente Northern California, Kaiser Permanente Southern California, and Kaiser Permanente Washington) with 43 endoscopy centers, 383 eligible physicians, and 735 396 patients aged 50 to 75 years who received a colonoscopy that did not detect cancer (negative colonoscopy) between January 2011 and June 2017, with patient follow-up through December 2017. Exposures: The adenoma detection rate of each patient's physician based on screening examinations in the calendar year prior to the patient's negative colonoscopy. Adenoma detection rate was defined as a continuous variable in statistical analyses and was also dichotomized as at or above vs below the median for descriptive analyses. Main Outcomes and Measures: The primary outcome (postcolonoscopy colorectal cancer) was tumor registry-verified colorectal adenocarcinoma diagnosed at least 6 months after any negative colonoscopy (all indications). The secondary outcomes included death from postcolonoscopy colorectal cancer. Results: Among 735 396 patients who had 852 624 negative colonoscopies, 440 352 (51.6%) were performed on female patients, median patient age was 61.4 years (IQR, 55.5-67.2 years), median follow-up per patient was 3.25 years (IQR, 1.56-5.01 years), and there were 619 postcolonoscopy colorectal cancers and 36 related deaths during more than 2.4 million person-years of follow-up. The patients of physicians with higher adenoma detection rates had significantly lower risks for postcolonoscopy colorectal cancer (hazard ratio [HR], 0.97 per 1% absolute adenoma detection rate increase [95% CI, 0.96-0.98]) and death from postcolonoscopy colorectal cancer (HR, 0.95 per 1% absolute adenoma detection rate increase [95% CI, 0.92-0.99]) across a broad range of adenoma detection rate values, with no interaction by sex (P value for interaction = .18). Compared with adenoma detection rates below the median of 28.3%, detection rates at or above the median were significantly associated with a lower risk of postcolonoscopy colorectal cancer (1.79 vs 3.10 cases per 10 000 person-years; absolute difference in 7-year risk, -12.2 per 10 000 negative colonoscopies [95% CI, -10.3 to -13.4]; HR, 0.61 [95% CI, 0.52-0.73]) and related deaths (0.05 vs 0.22 cases per 10 000 person-years; absolute difference in 7-year risk, -1.2 per 10 000 negative colonoscopies [95%, CI, -0.80 to -1.69]; HR, 0.26 [95% CI, 0.11-0.65]). Conclusions and Relevance: Within 3 large community-based settings, colonoscopies by physicians with higher adenoma detection rates were significantly associated with lower risks of postcolonoscopy colorectal cancer across a broad range of adenoma detection rate values. These findings may help inform recommended targets for colonoscopy quality measures.

Total Vitamin D Intake and Risks of Early-Onset Colorectal Cancer and Precursors.

BACKGROUND & AIMS: Vitamin D has been implicated in colorectal cancer (CRC) pathogenesis, but it remains unknown whether total vitamin D intake is associated with early-onset CRC and precursors diagnosed before age 50. METHODS: We prospectively examined the association between total vitamin D intake and risks of early-onset CRC and precursors among women enrolled in the Nurses' Health Study II. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for early-onset CRC were estimated with Cox proportional hazards model. Multivariable-adjusted odds ratios (ORs) and 95% CIs for early-onset conventional adenoma and serrated polyp were estimated with logistic regression model. RESULTS: We documented 111 incident cases of early-onset CRC during 1,250,560 person-years of follow-up (1991 to 2015). Higher total vitamin D intake was significantly associated with a reduced risk of early-onset CRC (HR for ≥450 IU/day vs <300 IU/day, 0.49; 95% CI, 0.26-0.93; P for trend = .01). The HR per 400 IU/day increase was 0.46 (95% CI, 0.26-0.83). The inverse association was significant and appeared more evident for dietary sources of vitamin D (HR per 400 IU/day increase, 0.34; 95% CI, 0.15-0.79) than supplemental vitamin D (HR per 400 IU/day increase, 0.77; 95% CI, 0.37-1.62). For CRC precursors, the ORs per 400 IU/day increase were 0.76 (95% CI, 0.65-0.88) for conventional adenoma (n = 1,439) and 0.85 (95% CI, 0.75-0.97) for serrated polyp (n = 1,878). CONCLUSIONS: In a cohort of younger women, higher total vitamin D intake was associated with decreased risks of early-onset CRC and precursors.

A germline c.1546dupC MEN1 mutation in an MEN1 family: A case report.

RATIONALE: Multiple endocrine neoplasia type 1 (MEN1) is a rare tumor syndrome with an autosomal dominant inheritance, and genetic testing for MEN1 gene is important for both affected individuals and their relatives. We present a 2-person family affected by a germline c.1546dupC MEN1 mutation, and one of them had a full-spectrum of MEN-related endocrine tumors. PATIENT CONCERNS: A female patient aged 32 years presented with jejunal ulcer perforation due to gastrinoma. DIAGNOSES: We conducted genetic analysis and extensive biochemical/radiological evaluation for detecting other endocrine tumors. Multiple pancreatic neuroendocrine tumors (NETs), prolactinoma and primary hyperparathyroidism were diagnosed, and a frame-shift mutation, NM_130799.1:c.1546dupC (p.Arg516Profs∗15), was detected. One daughter of the proband, aged 12 years, had the same mutation for MEN1. INTERVENTION: She underwent pancreatic surgery for pancreatic NETs and total parathyroidectomy for primary hyperparathyroidism. OUTCOMES: After pancreatic surgery, long-term symptoms of epigastric soreness, acid belching, sweating, and palpitation in fasting were improved. Hypercalcemia was improved after parathyroidectomy and she was supplemented with oral calcium and vitamin D. Her daughter showed normal biochemical surveillance until 15 years of age. LESSONS: We report 2 people in a family affected by MEN1 with the heterozygous germline c.1546dupC mutation, a variant that should be surveilled for early development of full-blown MEN1-associated endocrine tumors.

Development and validation of a risk prediction model for high-risk adenomas at the time of first screening colonoscopy among screening aged Canadians.

The aim of this study was to develop a risk prediction model for high risk adenomas (HRAs) detected at screening colonoscopy based on readily available participant information. The cohort consisted of 3035 participants aged 50 to 74 years with no history of cancer who underwent a primary screening colonoscopy at a centralized colon cancer screening centre between 2008 and 2016. A multivariable logistic regression model was created using CRC risk factors identified from prior research. Model covariates were collected from a baseline questionnaire and included participant demographics (age and sex), lifestyle parameters (body mass index, alcohol, smoking, and vitamin D supplement use) and medical history (family history of CRC and diabetes). Mean participant age was 58.8 years, and 54.7% were male. 249 participants with HRAs were identified (8.2%). An adjusted c-statistic of 0.67 was calculated, and a specificity and negative predictive value of 97.2% (95% CI: 96.5-97.8) and 92.5% (95% CI: 92.2-92.8) for the detection of HRAs, respectively, were achieved using 20% predicted probability as a high-risk threshold. However, only a sensitivity of 12.1% (95% CI: 8.3-16.8) was achieved. Our model has moderate predictive ability, with strengths in being able to rule out those with an absence of HRAs on screening colonoscopy. Maximizing screening efficiency through improved risk prediction can enhance resource allocation. Ultimately, this model has the potential to improve patient care by reducing unnecessary colonoscopies, limiting this invasive procedure to those most likely to have significant findings.

The anti-spasmodic effect of peppermint oil during colonoscopy: a systematic review and meta-analysis.

INTRODUCTION: Multiple pharmacological agents have been studied in literature with antispasmodic effect during colonoscopy. Peppermint oil, with its relaxing effect on colon has demonstrated varying results. We therefore conducted a systematic review and meta-analysis of the available literature to evaluate its role during colonoscopy. EVIDENCE ACQUISITION: Literature search of the following databases was undertaken: PubMed\Medline, Embase, Cochrane, Web of Science, and CINAHL. Outcomes that were evaluated included incidence of any spasticity, severe spasticity, and peristalsis during examination. Adenoma detection rate (ADR) was evaluated as a quality outcome metric. Risk ratios (RR), risk difference (RD) and mean difference (MD) were calculated using the DerSimonian-Laird method and random effects where applicable. EVIDENCE SYNTHESIS: Overall, six studies (with one abstract) were included in this review. Peppermint oil resulted in overall lower incidence for spasticity (RD: -0.39, P=0.02), severe spasticity (RD: -0.15, P=0.04), and peristalsis (-0.27, P≤0.001) during colonoscopy examination. An improved ADR (RR: 1.31, P=0.01) was also noted, however only two studies evaluated this effect. CONCLUSIONS: Peppermint oil resulted in relaxation of colon during colonoscopy with decrease incidence of spasticity, severe spasticity, peristalsis and improved ADR. These results are encouraging however results are limited due to significant heterogeneity found in the outcomes. Larger studies with standardized dosing are needed to evaluate this effect. Furthermore, studies evaluating additional colonoscopy outcomes such as polyp detection rate, advanced adenoma detection rate, and serrated adenoma detection rate are needed.

Primary Hyperparathyroidism Masquerading as Rickets.

Primary hyperparathyroidism (PHPT) is common among adults. However, its incidence is rare among children associated invariably with delay in diagnosis. In children, it is caused by hyperplasia, adenoma or related hereditary disorders. Herein, a 17-year male with PHPT presented with rare skeletal manifestations of genu valgum and bilateral epiphyseal displacement of femur. Investigations done three years ago reported hypocalcemia and vitamin-D deficiency. He was diagnosed with rickets and received plenty of calcium and vitamin D supplements. Due to lack of clinical improvement following the supplementation, re-evaluation revealed hypercalcemia, elevated vitamin D levels and elevated parathyroid hormone (PTH). A 99mTc-sestamibi scan reported increased uptake in the left inferior lobe of the thyroid gland. Surgical removal of the parathyroid gland was done and histopathology revealed parathyroid adenoma. Rickets in the setting of PHPT can masquerade as PHPT. In a patient with rickets, hypercalcemia at presentation or following the calcium and vitamin supplementations, should warn the physicians to rule out PHPT.

The compliance rate for the second diagnostic evaluation after a positive fecal occult blood test: A systematic review and meta-analysis.

Introduction: Only a minority of patients with a positive fecal occult blood test (FOBT) undergo a follow-up second diagnostic procedure, thus minimizing its contribution for colorectal cancer (CRC) prevention. We aimed to obtain a precise estimation of this problem and also assess the diagnostic yield of CRC and adenomas by colonoscopy in these patients. Methods: Literature searches were conducted for "compliance" OR "adherence" AND "fecal occult blood test" OR "fecal immunohistochemical test" AND "colonoscopy." Comprehensive meta-analysis software was used. Results: The search resulted in 42 studies (512,496 patients with positive FOBT), published through December 31, 2017. A funnel plot demonstrates a moderate publication bias. Compliance with any second procedure, colonoscopy, or combination of double-contrast barium enema with or without sigmoidoscopy in patients with a positive FOBT was 0.725 with 95% confidence interval (CI) 0.649-0.790 (p = 0.000), 0.804 with 95% CI 0.740-0.856 (p = 0.000) and 0.197 with 95% CI 0.096-0.361 (p = 0.000), respectively. The diagnostic yield for CRC, advanced adenoma and simple adenoma was 0.058 with 95% CI 0.050-0.068 (p = 0.000), 0.242 with 95% CI 0.188-0.306 (p = 0.000) and 0.147 with 95% CI 0.116-0.184 (p < 0.001), respectively. Discussion: Compliance with diagnostic evaluation after a positive FOBT is still suboptimal. Therefore, measures to increase compliance need to be taken given the increased risk of CRC in these patients.

No Evidence for Posttreatment Effects of Vitamin D and Calcium Supplementation on Risk of Colorectal Adenomas in a Randomized Trial.

Vitamin D and calcium supplementation are postulated to have chemopreventive effects against colorectal neoplasia, yet in our previously reported randomized trial, there was no overall efficacy of calcium and/or vitamin D3 against colorectal adenoma recurrence. It is possible vitamin D3 and calcium chemopreventive effects are not detectable until beyond the 3- to 5-year follow-up captured in that trial. Accordingly, we explored possible vitamin D and calcium effects on posttreatment (observational) adenoma occurrence. In this secondary analysis of the observational follow-up phase of the Vitamin D/Calcium Polyp Prevention Study, participants who completed the treatment phase were invited to be followed for one additional surveillance colonoscopy cycle. We evaluated adenoma occurrence risk at surveillance colonoscopy, with a mean of 55 ± 15 months after treatment follow-up, according to randomized treatment with vitamin D versus no vitamin D, calcium versus no calcium, and calcium plus vitamin D versus calcium alone. Secondary outcomes included advanced and multiple adenomas. Among the 1,121 participants with observational follow-up, the relative risk (95% confidence interval, CI) of any adenoma was 1.04 (0.93-1.17) for vitamin D versus no vitamin D; 0.95 (0.84-1.08) for calcium versus no calcium; 1.07 (0.91-1.25) for calcium plus vitamin D versus calcium; and 0.96 (0.81-1.15) for calcium plus vitamin D versus neither. Risks of advanced or multiple adenomas also did not differ by treatment. Our results do not support an association between supplemental calcium and/or vitamin D3 for 3 to 5 years and risk of recurrent colorectal adenoma at an average of 4.6 years after treatment.

A Case of Pregnancy Complicated by Primary Hyperparathyroidism Due to a Parathyroid Adenoma.

BACKGROUND Primary hyperparathyroidism is most common in women during the menopause and its occurrence in pregnant women is rare. However, because neonatal mortality is associated with maternal hyperparathyroidism, early diagnosis is essential. This report describes the case of a late diagnosis of primary hyperparathyroidism in a 28-year-old pregnant woman and describes the effects on the mother and neonate. CASE REPORT During her second pregnancy, a 28-year-old woman presented with symptoms of general weakness, bone and joint pain, multiple fractures with bone deformity, muscle weakness, and gait disturbance. Due to the high risk of perinatal pathology, a cesarean section was performed. Several weeks later, she underwent thoracoscopic removal of an ectopic parathyroid gland located at the aortic arch. Hypocalcemia in the newborn infant required treatment with calcium and magnesium supplements. CONCLUSIONS This case demonstrates that primary hyperparathyroidism during pregnancy requires timely diagnosis and treatment to reduce potential maternal and fetal complications. Screening for primary hyperparathyroidism should be undertaken in pregnant women with any symptoms associated with hypercalcemia. Treatment should be individualized and includes conservative management, parathyroidectomy in the second trimester, or parathyroidectomy performed in the early postpartum period.

Receipt of Colonoscopy Following Diagnosis of Advanced Adenomas: An Analysis within Integrated Healthcare Delivery Systems.

BACKGROUND: To reduce colorectal cancer incidence and mortality, experts recommend surveillance colonoscopy 3 years after advanced adenoma removal. Little is known about adherence to that interval. METHODS: We describe patterns of and factors associated with subsequent colonoscopy among persons with ≥3 adenomas and/or ≥1 adenoma with villous/tubulovillous histology in four U.S. integrated healthcare delivery systems. We report Kaplan-Meier estimators of the cumulative percentage of patients undergoing colonoscopy 6 months to 3.5 years after an index colonoscopy with high-risk findings. Combining data from three healthcare systems, we used multivariable logistic regression with inverse probability of censoring weights to estimate ORs and 95% confidence intervals (CI) for associations between patient characteristics and receipt of subsequent colonoscopy. RESULTS: Among 6,909 persons with advanced adenomas, the percent receiving a subsequent colonoscopy 6 months to 3.5 years later ranged from 18.3% (95% CI: 11.7%-27.8%) to 59.5% (95% CI: 53.8%-65.2%) across healthcare systems. Differences remained significant in the multivariable model. Patients with ≥3 adenomas were more likely than those with 1 to 2 villous/tubulovillous adenomas to undergo subsequent colonoscopy. Subsequent colonoscopy was also more common for patients ages 60-74 and less common for patients ages 80 to 89 compared with those ages 50 to 54 years at their index colonoscopy. Sex, race/ethnicity, and comorbidity index score were generally not associated with subsequent colonoscopy receipt. CONCLUSIONS: Colonoscopy within the recommended interval following advanced adenoma was underutilized and varied by healthcare system, age, and number of adenomas. IMPACT: Strategies to improve adherence to surveillance colonoscopy following advanced adenomas are needed.

Calcium and vitamin D supplementation and increased risk of serrated polyps: results from a randomised clinical trial.

OBJECTIVE: Serrated lesions such as sessile serrated adenomas or polyps (SSA/Ps) are important colorectal cancer precursors, but aetiological factors for these lesions are largely unknown. We aimed to determine the effects of calcium and vitamin D supplementation on the incidence of serrated polyps (SPs) in general and hyperplastic polyps and SSA/Ps specifically. DESIGN: Participants with one or more adenoma at baseline were randomised to receive 1200 mg/day of elemental calcium, 1000 IU/day of vitamin D3, both or neither agent. Treatment continued for 3 or 5 years, when risk of polyps was determined from surveillance colonoscopy (treatment phase). Outcomes after treatment ceased were also assessed (observational phase). Adjusted risk ratios (aRRs) of SPs were determined via multivariable generalised linear models. RESULTS: SPs were diagnosed in 565 of 2058 (27.5%) participants during the treatment phase and 329/1108 (29.7%) during the observational phase. In total, 211 SSA/Ps were identified during follow-up. In the treatment phase, there was no effect of either calcium or vitamin D on incidence of SSA/Ps. However, during the later observational phase, we observed elevated risks of SSA/Ps associated with calcium alone and calcium+vitamin D treatment (aRR (95% CI): 2.65 (1.43 to 4.91) and 3.81 (1.25 to 11.64), respectively). CONCLUSION: In a large multicentre chemoprevention study, we found evidence that calcium and vitamin D supplementation increased the risk of SSA/Ps. This appeared to be a late effect: 6-10 years after supplementation began. These possible risks must be weighed against the benefits of calcium and vitamin D supplementation. : Trial registration NUMBER: NCT00153816; Results.

Efficacy and Acceptability of 1 Liter of Polyethylene Glycol with Ascorbic Acid vs. 2 Liters of Polyethylene Glycol Plus Mosapride and Sennoside for Colonoscopy Preparation.

BACKGROUND [color=black]Bowel preparation is an important factor for an optimal outcome of colonoscopy. Recently, polyethylene glycol (PEG) solution has been in common use for bowel cleansing for colonoscopy, but some patients are intolerant of PEG because of taste or volume. A low-volume PEG administered with ascorbic acid solution (PEG-Asc) was designed to improve tolerability, but the administration of this method is more complex than that with PEG alone. This study aimed to compare bowel cleansing efficacy, safety, and tolerability of 1 L PEG-Asc with a 2 L PEG preparation with use of sennosides and mosapride.[/color] MATERIAL AND METHODS [color=black]This was a prospective, single-center, non-inferiority trial that included 112 patients (PEG-Asc group, 68; PEG group, 44). The primary endpoint was the efficacy of colon cleansing assessed by endoscopists using a validated 4-point scale according to the Aronchick scale and was verified by a blinded investigator. Acceptability, tolerability, and adenoma detection rate (ADR) of these 2 regimens were secondary endpoints.[/color][color=black] [/color] RESULTS [color=black]We found no statistically significant differences between the groups in colon-cleansing efficacy or in the adenoma detection rate (ADR). Moreover, overall, patients significantly favored PEG-Asc over PEG, reflecting better acceptance of PEG-Asc. Additionally, more patients favored PEG-Asc over PEG for a hypothetical future colonoscopy. [/color] CONCLUSIONS [color=black]The alternate 1 L PEG-Asc regimen and standard 2 L PEG regimen were clinically equivalent with respect to cleansing efficacy, safety, and ADR, and more patients favored PEG-Asc than PEG. This alternate regimen may improve patient compliance and acceptance of surveillance colonoscopy.[/color].

Diagnosis and predictors of sessile serrated adenoma after educational training in a large, community-based, integrated healthcare setting.

BACKGROUND AND AIMS: Sessile serrated adenomas (SSAs) are precursors of 15% to 30% of colorectal cancers but are frequently underdiagnosed. We sought to measure the SSA detection rate (SDR) and predictors of SSA detection after educational training for community gastroenterologists and pathologists. METHODS: Colonoscopy and pathology data (2010-2014) from 3 medical centers at Kaiser Permanente Northern California were accessed electronically. Gastroenterologists and pathologists attended a training session on SSA diagnosis in 2012. Mean SDRs and patient-level predictors of SSA detection post-training (2013-2014) were investigated. RESULTS: Mean SDRs increased from .6% in 2010-2012 to 3.7% in 2013-2014. The increase in the detection of proximal SSAs was accompanied by a decrease in the detection of proximal hyperplastic polyps (HPs). Among 34,161 colonoscopies performed in 2013 to 2014, SDRs for screening, fecal immunochemical test positivity, surveillance, and diagnostic indication were 4.2%, 4.5%, 4.9%, and 3.0%, respectively. SSA detection was lower among Asians (adjusted odds ratio [aOR], .46; 95% confidence interval [CI], .31-.69) and Hispanics (aOR, .59; 95% CI, .36-.95) compared with non-Hispanic whites and higher among patients with synchronous conventional adenoma (aOR, 1.46; 95% CI, 1.15-1.86), HP (aOR, 1.74; 95% CI, 1.30-2.34), and current smokers (aOR, 1.78; 95% CI, 1.17-2.72). SDRs varied widely among experienced gastroenterologists, even after training (1.1%-8.1%). There was a moderately strong correlation between adenoma detection rate (ADR) and SDR for any SSA (r = .64, P = .0003) and for right-sided SSAs (r = .71, P < .0001). CONCLUSIONS: Educational training significantly increased the detection of SSA, but a wide variation in SDR remained across gastroenterologists. SSA detection was inversely associated with Asian and Hispanic race/ethnicity and positively associated with the presence of conventional adenoma, HP, and current smoking. There was a moderately strong correlation between ADR and SDR.