Colorectal Cancer in Patients Up to Age to 25 Years

In a nationwide retrospective cohort from The Netherlands (pop. ~17 million), a recent study (RM de Voer et al. Clin Gastroenterol Hepatol 2021; 19: 1642-1651. Full Text: Clinical, Pathology, Genetic, and Molecular Features of Colorectal Tumors in Adolescents and Adults 25 Years or Younger) characterizes the clinical and genetic features of colorectal cancer (CRC) in individuals <26 years of age (aka AYA group) from 2000-2017.

Key findings:

  • There were 139 patients in the AYA group identified: 9 (ages 10-15), 26 (ages 16-20), and 104 (ages 21-25)
  • Overall, the AYA group represents 0.1% of all CRC cases. However, AYA cases were much more likely to be at an advanced stage at diagnosis (66% at stage 3 or 4 compared with 46% of adults with CRC in The Netherlands).
  • Negative predictors for outcomes included age <16 yrs, signet ring cell carcinoma histology, and advanced stage at diagnosis.
  • Genetic tumor risk syndromes were identified in 39% and IBD was noted in 8.4% of the AYA group. The genetic risk is underestimated as the authors did not test for all CRC-predisposing genes. Lynch syndrome was the most common genetic disorder (identified in 22 patients) followed by familial adenomatous polyposis (identified in 5 patients)

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Sugary Diet and Colonic Adenomas

H-K Joh et al. Gastroenterol 2021; 161: 128-142. Full text: Simple Sugar and Sugar-Sweetened Beverage Intake During Adolescence and Risk of Colorectal Cancer Precursors

Methods: We prospectively investigated the association of adolescent simple sugar (fructose, glucose, added sugar, total sugar) and sugar-sweetened beverage (SSB) intake with CRC precursor risk in 33,106 participants of the Nurses’ Health Study II who provided adolescent dietary information in 1998 and subsequently underwent lower gastrointestinal endoscopy between 1999 and 2015.

Key Findings:

  • High sugar and SSB intake during adolescence was positively associated with risk of adenoma, but not serrated lesions.
  • Per each increment of 5% of calories from total fructose intake, multivariable ORs were 1.17 (95% CI, 1.05–1.31) for total and 1.30 (95% CI, 1.06–1.60) for high-risk adenoma

Full text (editorial, pg 27): JK Lee et al: Sugary Truth of Early-Onset Colorectal Neoplasia—Not So Sweet After All

Key points:

  • “In the United States, SSB [sugar-sweetened beverage] consumption has increased by nearly 5-fold over time, from 10.8 gallons per person in 1950 to 49.3 gallons per person in 2000.8 In adolescents, SSB consumption has more than doubled since the 1960s and comprises the largest source of simple sugar and calories in their diets”
  • “Recent studies, including several from the Nurses’ Health Study, have identified lifestyle factors from early adulthood, including Western diet,13,14 alcohol,15 tobacco,16 sedentary television viewing,11 diabetes,17 and obesity12 as risk factors for early-onset CRC or adenoma. Other studies report no association between sugar, fruit juice, and SSB consumption during adulthood and risk of CRC in older adults”

My take (borrowed from editorial): “Increasing fructose and SSB consumption, particularly among adolescents and young adults, is troublesome because substantial evidence links consumption to various health outcomes, including obesity, type 2 diabetes, cardiovascular disease, some cancers, all-cause mortality, and now early-onset high-risk adenoma…. clinicians should continue to support public health policies discouraging or reducing consumption of simple sugars and SSBs in adolescents, for whom exposure might have lifelong consequences.”

Anti-TNF Therapy and Lower Rates of Colon Cancer & Financial Hardship Due to IBD

M Aklkhayyat et al. Inflamm Bowel Dis 2021; 27: 1052-1060. Lower Rates of Colorectal Cancer in Patients With Inflammatory Bowel Disease Using Anti-TNF Therapy

Using a selected sample from a database with >62 million patients, this retrospective cohort study determined the rates of colorectal cancer among patients with IBD. Key finding:

Among the IBD cohort, patients treated with anti-TNF agents were less likely to develop CRC; patients with Crohn’s disease: odds ratio, 0.69; 95% confidence interval, 0.66-0.73; P < 0.0001 vs patients with ulcerative colitis: odds ratio, 0.78; 95% confidence interval, 0.73-0.83; P < 0.0001.

My take: This study found an association between anti-TNF therapy and a reduced risk of CRC in patients with IBD.

Related blog posts:

NH Nguyen et al. Inflamm Bowel Dis 1068-1078. National Estimates of Financial Hardship From Medical Bills and Cost-related Medication Nonadherence in Patients With Inflammatory Bowel Diseases in the United States

Using the National Health Interview survey (2015), the authors identified individuals with self-reported IBD and assessed national estimates of financial toxicity. Key findings:

  • 23% reported financial hardships due to medical bills, 16% of patients reported cost-related medication nonadherence, and 31% reported cost-reducing behaviors
  • Approximately 62% of patients reported personal and/or health-related financial distress, and 10% of patients deemed health care unaffordable
  • Inflammatory bowel disease was associated with 1.6 to 2.6 times higher odds of financial toxicity across domains compared with patients without IBD

My take: In addition to the physical and emotional toll of having IBD, there is also significant financial hardships for many.

Colorectal Cancer: Rare in Pediatrics

A recent retrospective single-center in Turkey study (2013-2018) reports 5 cases of colorectal cancer (CRC).

E Polat et al. JPGN Reports; 2021 – Volume 2 – Issue 1 – p e039 Full text: Colorectal Carcinoma in Childhood

Key points:

  • Patients were between 12-16 yrs of age and presented with bloody stools and weight loss
  • “CRC in childhood is very rare, usually diagnosed at an advanced stage and often has poor prognosis. CRC in children are mostly sporadic, roughly 10% of cases may have a predisposing condition…familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, Gardner syndrome, Turcot syndrome, Peutz-Jeghers syndrome, juvenile polyposis of colon, and ulcerative colitis.”

45 Years –The New Recommendation for Colorectal Cancer Screening

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Surprising Genetic Mutations in Polyposis Study

A recent cross-sectional study (PP Stanich et al. Clin Gastroenterol Hepatol 2019; 17: 2008-15, editorial 1942-44) identified a high frequency of genetic mutations among adults with at least 10 colonic polyps (cumulative burden of either adenomatous or hamartomatous).

This study had 3789 subjects who underwent multigene panel testing (MGPT) from 2012-16.

  • All subjects had at least 14 CRC-associated genes tested: APC, BMPR1A, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, SMAD4, STK11, TP53
  • A subset had 3 more newly recognized polyposis genes: GREM1, POLD1, and POLE

Key findings:

  • A mutation in at least 1 gene was found in 13.7%
  • In those with fewer than 20 cumulative adenomas, 7.6% had a disease-associated genetic mutation with the majority (5.3%) being nonpolyposis CRC genes
  • Younger patients, 18-29, were more likely to have mutations in any gene.  For example, among patients with 10-19 polyps, these younger patients had a mutation in one of these genes in 27.8%; this is more than double the rate in any other age group.
  • Hamartomatous polyps, regardless of number, had a very high yield with genetic testing: 40% with 10-19 polyps and 72% with 20-99 polyps.

Limitations:

  • There is a referral bias in that the population was derived from a testing laboratory (Ambry)
  • In clinical practice, genetic testing frequently results in variants of unknown significance

My take: This study shows that genetic mutations are fairly frequent in patients with cumulative polyp burden of 10 or more, especially in younger age groups.  The surprising finding is the high frequency of nonpolyposis CRC genes.  Thus, in patients with adenomatous polyposis, testing beyond APC and MUTYH may be needed.

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Atlanta Botanical Garden

#NASPGHAN19 Postgraduate Course (Part 1)

Here are some selected slides and notes from this year’s NASPGHAN’s postrgraduate course.  My notes from these lectures may contain errors in omission or transcription.

Link to the full NASPGHAN PG Syllabus 2019

8:00 – 9:00 Module 1 – Endoscopy

11  David Brumbaugh, MD, Children’s Hospital Colorado  Management of foreign bodies

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22 Petar Mamula, MD, Children’s Hospital of Philadelphia Advanced endoscopic techniques for gastrointestinal bleeding

This talk had some terrific videos (not available in syllabus) and useful practical points.  For example, with cautery, the speaker recommended not just quickly taping the lesion, count for several seconds when applying.  For hemospray, the speaker considers this technically much easier but is using this mainly as a backup option.

Here are two screenshots (not from lecture) which provide information from manufacturer on Hemospray use (link to PDF on Hemospray Manufacturer’s PDF on Hemospray)

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36 Srinadh Komanduri, MD, Northwestern Medicine  Cancer screening top to bottom

Some of the key points:

  • IBD and colorectal cancer (CRC) screening 8-10 years after disease onset
  • ~10% of CRC in general population occurs between 20-49 years
  • Chromoendoscopy results in higher detection rates of dysplasia

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Disclaimer: NASPGHAN/gutsandgrowth assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. The discussion, views, and recommendations as to medical procedures, choice of drugs and drug dosages herein are the sole responsibility of the authors. Because of rapid advances in the medical sciences, the Society cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. Some of the slides reproduced in this syllabus contain animation in the power point version. This cannot be seen in the printed version.

IBD Briefs August 2019

A Levine et al. Gastroenterol 2019; 157: 440-50.  This study found that a Crohn’s Disease Exclusion Diet plus partial enteral nutrition induced sustained remission in a 12-week prospective randomized controlled trial with 74 children.  At week 12, “76% of 37 children given CDED plus PEN were in corticosteroid-free remission compared with 14 (45.1%) of 31 children given” EEN followed by PEN.  The associated editorial on pages 295-6 provides a useful diagram of various dietary therapy components for a large number of diets that have been given for IBD.  The editorial recommends:

“For now, simple dietetic recommendations such as consuming a well-balanced diet prepared largely from fresh ingredients and thereby avoidance of emulsifiers and additives and processed foods are appropriate for all patients.  In select patients,…a trial of dietary therapy alone with a diet such as CDED could be attempted for a short period of time, with close follow-up, and with agreement with the patient that failure to fully respond is an indication to escalate therapy.”  More dietary trials are ongoing.

Related blog posts:

NJ Samadder et al Clin Gastroenterol Hepatol 2019; 17: 1807-13. In this cohort from Utah 1996-2011 with 9505 individuals with IBD, 101 developed colorectal cancer.  Standardized incidence ratio (SIR) for CRC in patients with Crohn’s disease was 3.4, in ulcerative colitis 5.2, in patients with primary sclerosing cholangitis 14.8.  A family history of CRC increased the risk of CRC in patients with IBD to 7.9 compared to general population.  Family hx/o CRC increased the SIR by about double the CRC risk in IBD patients without a family hx/o CRC.

CR Ballengee et al. Clin Gastroenterol Hepatol 2019; 17: 1799-1806. In this study with 161 subjects from the RISK cohort, the authors found that elevated CLO3A1 levels in subjects with CD was associated with the development of stricturing disease but was not elevated in those with strictures at presentation and in those who did not develop  strictures.

AL Lightner et al IBD 2019; 25: 1152-68.  Short- and Long-term Outcomes After Ileal Pouch Anal Anastomosis in Pediatric Patients: A Systematic Review.  This review included 42 papers.

  • Rates of superficial surgical site infection, pelvic sepsis, and small bowel obstruction at <30 days were 10%, 11%, and 14% respectively.
  • Rates of pouchitis, stricture, chronic fistula, incontinence and pouch failure were 30%, 17%, 12%, 20% and 8% respectively with followup between 37-109 months.
  • Mean 24-hour stool frequency was 5.

MC Choy et al IBD 2019; 25: 1169-86.  Systematic review and meta-analysis: Optimal salvage therapy in acute severe ulcerative colitis.  Among 41 cohorts (n=2158 cases) with infliximab salvage, overall colectomy-free survival was 69.8% at 12 months.  The authors could not identify an advantage of dose-intensification in outcomes, though this was used more often in patients with increased disease severity, “which may have confounded the results.”

Hood River, OR

Five Ways to Lower the Risk of Colon Cancer

A recent study (PR Carr, et al. Gastroenterol 2018; 155: 1805-15) used an ongoing population-based case-control DACHS study (in Germany since 2003) to determine the effects of lifestyle factors on the risk of colorectal cancer (CRC).

Among 4092 patients with CRC and 3032 control patients without CRC, the investigators examined five factors:

  • Smoking – For smoking, one point was given for being a nonsmoker or a former smoker with <30 pack years.
  • Alcohol consumption –  For alcohol, a point was garnered if consumption was moderate according to AICR recommendations.
  • Diet –  Diet quality was assessed based on WCRF/AICR recommendations (supplement table 1 [https://doi.org/10.1053/j.gastro.2018.08.044]). 1 point was given with highest diet scores.
  • Physical activity – A point was given with favorable physical activity which was based on moderate-intensity aerobic exercise for at least 150 minutes per week or 75 minutes of vigorous activity.
  • Body fatness – Those with a BMI between 18.5 and 25 which was considered a healthy weight were awarded a point.

 Key findings:

Compared to patients with 0 or 1 healthy lifestyle factor:

  • Participants with 2 points had odds ratio of 0.85
  • Participants with 3 points had odds ratio of 0.62
  • Participants with 4 points had odds ratio of 0.53
  • Participants with 5 points had odds ratio of 0.33

My take (borrowed from authors): Overall, 45% of CRC cases could be attributed to these lifestyle factors.  This occurred despite the patient’s genetic profile

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