Polyposis Conditions Research Articles

Pediatric Cancer Screening in Hereditary Gastrointestinal Cancer Risk Syndromes: An Update from the AACR Childhood Cancer Predisposition Working Group.

Gastrointestinal (GI) polyposis and cancer in pediatric patients is frequently due to an underlying hereditary cancer risk syndrome requiring ongoing cancer screening. Identification of at-risk patients through family history, clinical features of a syndrome, or symptom onset ensures appropriate cancer risk assessment and management in childhood and beyond. In this 2024 perspective, we outline updates to the hereditary GI cancer screening guidelines first published by the American Association of Cancer Research Pediatric Cancer Predisposition Workshop in 2017. These guidelines consider existing recommendations by pediatric and adult gastroenterology consortia to ensure alignment with gastroenterology practices in managing polyposis conditions. We specifically address the recommendations for pediatric screening in familial adenomatous polyposis, Peutz-Jeghers syndrome, and juvenile polyposis syndrome. Further, we emphasize the importance of multidisciplinary care and partnership with gastroenterology, as it is crucial in management of children and families with these conditions.

Differential Diagnoses and Management Approaches for Gastric Polyposis

Multiple gastric polyps are observed in various polyposis syndromes and conditions associated with polypoid lesion development in the stomach. Polyposis syndromes often occur concurrently with specific malignant tumors and can manifest at any point in an individual’s lifespan, thus explaining the diversity in surveillance methods. Furthermore, genetic counseling and surveillance are essential not only for the patients themselves but also for their blood relatives. Therefore, the accurate diagnosis and appropriate surveillance of multiple gastric polyps are crucial for improving patient outcomes. This review aims to provide essential information on such lesions along with representative endoscopic images of familial adenomatous polyposis, Peutz-Jeghers syndrome, Cowden syndrome, Cronkhite-Canada syndrome, juvenile polyposis syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, neuroendocrine tumors in autoimmune gastritis, proton pump inhibitor-related gastric mucosal changes, and multiple submucosal heterotopic glands. We wish for this review to serve as a valuable resource for endoscopists seeking to deepen their comprehension of gastric polyposis.

Merged testing for colorectal cancer syndromes and re-evaluation of genetic variants improve diagnostic yield: Results from a nationwide prospective cohort.

Approximately 5% of patients with colorectal cancer (CRC) have a Mendelian predisposition for the disease. Identification of the disease‐causing genetic variant enables carrier testing and tailored cancer prevention within affected families. To determine the panorama and genetic variation of Mendelian CRC syndromes among referrals at the cancer genetics clinics in Sweden, 850 patients clinically selected for CRC genetic investigation were included in a prospective study that tested for all major hereditary polyposis and nonpolyposis CRC conditions. Genetically defined syndromes were diagnosed in 11% of the patients. Lynch syndrome was predominant (n = 73) followed by familial adenomatous polyposis (n = 12) and MUTYH‐associated polyposis (n = 8); the latter of which two patients presented with CRC before polyposis was evident. One patient with a history of adolescent‐onset CRC and polyposis had biallelic disease‐causing variants diagnostic for constitutional mismatch repair deficiency syndrome. Post‐study review of detected variants of unknown clinical significance (n = 129) resulted in the reclassification of variants as likely benign (n = 59) or as diagnostic for Lynch syndrome (n = 2). Our results reveal the panorama of Mendelian CRC syndromes at the cancer genetics clinics in Sweden and show that unified testing for polyposis and nonpolyposis CRC conditions as well as regular reexamination of sequence data improve the diagnostic yield.

Meaningful relationships as a driving force in the experience of parents of a child living with polyposis conditions

ABSTRACT While much research has been conducted on the experiences of individuals with inflammatory bowel diseases, there remains a dearth of research conducted on those affected by polyposis conditions. As a result, little is known about the lived experiences of those with polyposis conditions, especially in the cases of parents of pediatric patients with these conditions. Using a hermeneutical phenomenological qualitative research approach, this study sought to explore the lived experiences of parents of children with polyposis conditions, with specific attention paid to the processes in which parents engage in order to adapt to their realities. In total, three major themes were revealed from the experiences of seven participants. Parents discussed the importance of building collaborative relationships with family physicians, building reassuring relationships with other parents, and building educative relationships with their child. These findings demonstrate the need for family-centered care practices by physicians, and role of relevant relationships as a driving force in helping parents in the management of their child’s illness.

APC-associated polyposis conditions

APC-associated polyposis conditions

Pediatric Colonoscopic Polypectomy Technique.

Colonoscopy with polypectomy is frequently performed in pediatric patients based on symptoms, with the majority of polyps identified being benign juvenile pedunculated polyps with a vascular stalk. This is in distinction to adults where polypectomy is often performed as part of a colon cancer screening and prevention strategy and a higher fraction of polyps are sessile and or dysplastic. In adults, polypectomy techniques emphasize a need for deeper resection to ensure complete resection of adenomas or potential carcinoma in situ. Adenomatous polyps can occur in the pediatric age group and may be associated with an underlying polyposis, hereditary or chronic inflammatory conditions. Polypectomy techniques include use of cold biopsy forceps for very small polyps, cold snare polypectomy for small sessile polyps and hot snare polypectomy for the majority of polyps in the pediatric age group. Adjuvant techniques include epinephrine volume reduction, saline-assisted polypectomy and hemostatic techniques including injection, clip application and loop application to prevent or treat post-polypectomy bleeding. Electrosurgical principles guide the settings and type of current utilized during hot snare polypectomy. Polypectomy utilizing thermal techniques is associated with a higher risk of complications compared with diagnostic colonoscopy.

Pathogenic APC Variants in Latvian Familial Adenomatous Polyposis Patients.

Background and objectives: Familial adenomatous polyposis is one of the APC-associated polyposis conditions described as genetically predetermined colorectal polyposis syndrome with a variety of symptoms. The purpose of this study was to determine sequence variants of the APC gene in patients with familial adenomatous polyposis (FAP) phenotype and positive or negative family history. Materials and Methods: Eight families with defined criteria of adenomatous polyposis underwent molecular genetic testing. Coding regions and flanking intron regions of the APC gene were analyzed by Sanger sequencing. Results: Eight allelic variants of the APC gene coding sequence were detected. All allelic variants of the APC gene were predicted to be pathogenic based on criteria according to the “Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology” (2015), four of them c.1586_1587insAT, c.2336delT, c.3066_3067insGA, and c.4303_4304insC, were considered novel. Conclusions: The timely molecular genetic analysis of APC germline variants and standardized interpretation of the pathogenicity of novel allelic variants has a high impact on choice for treatment, cancer prevention, and family genetic counseling.

Management of Juvenile Polyposis Syndrome in Children and Adolescents: A Position Paper From the ESPGHAN Polyposis Working Group.

The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Polyposis Working Group developed recommendations to assist clinicians and health care providers with appropriate management of patients with juvenile polyposis. This is the first juvenile polyposis Position Paper published by ESPGHAN with invited experts. Many of the published studies were descriptive and/or retrospective in nature, consequently after incorporating a modified version of the GRADE system many of the recommendations are based on expert opinion. This ESPGHAN Position Paper provides a guide for diagnosis, assessment, and management of juvenile polyposis syndrome in children and adolescents, and will be helpful in the appropriate management and timing of procedures in children and adolescents. The formation of international collaboration and consortia is proposed to monitor patients prospectively to advance our understanding of juvenile polyposis conditions.

A Successful Steroid-Sparing Approach in Cronkhite-Canada Syndrome.

ABSTRACTCronkhite-Canada Syndrome (CCS) is a rare, sporadic polyposis condition. The literature on CCS consists mostly of case reports. Although disease presentation has been well-described, there is no consensus on the management of CCS. We present a severe case of CCS that demonstrated clinical and endoscopic response to corticosteroids. This response was maintained with azathioprine. This case provides additional experience on a therapeutic strategy to induce and maintain a durable corticosteroid-free remission.

Ileoanal pouch

Proctocolectomy with an ileoanal pouch is the procedure of choice for a variety of underlying diseases, such as ulcerative colitis, classical familial adenomatous polyposis (FAP) and other polyposis syndromes or conditions with multiple synchronous cancers involving the rectum. Recently the indications for Crohn’s colitis and slow transit constipation are being revisited. Since the first description of the procedure in 1978 by Parks and Nicholls with an S‑pouch and the J‑pouch by Utsunomiya in 1983, the latter has become the overall recommended standard. Multiple procedural details are not described in the literature; however, these may contribute to important differences in functional outcome. The methodology varies with the recommended one, two and three-stage procedures and also in being performed conventionally or laparoscopically. Additionally, since the introduction of taTME for rectal cancer, a retake of the discussion regarding the most recommendable ileal pouch-anal anastomosis has evolved. In this article we describe our technical approach for a one-stage procedure of laparoscopic proctocolectomy. It has become our strategy of choice to defer from routine ileostomy and to perform the rectal resection as transanal laparoscopic total mesorectal excision (taTME). Additionally, perioperative management, outcome and the current literature are discussed. The report is illustrated with pictures of a 26-year-old female patient with FAP and profuse distal polyposis reaching the supra-anal level.

A Rare Case of Cronkhite-Canada Syndrome

Introduction: Cronkhite-Canada Syndrome (CCS) is a rare non-hereditary polyposis condition with unclear etiology. Estimated incidence is 1 case per million population. Symptoms include diarrhea, anorexia, and weight loss. Dermatologic changes are alopecia, onychodystrophy, and cutaneous hyperpigmentation. Classic endoscopic features include diffuse polyposis which spares the esophagus. Case: 71 yo M with irritable bowel syndrome, diabetes, atrial fibrillation on warfarin presented with abdominal pain, constipation and diarrhea. Gastroscopy and colonoscopy revealed inactive gastritis and two diminutive adenomatous polyps; no microscopic colitis. Over the course of five months diarrhea worsened, he developed dysgeusia and anorexia with a 25 lb weight loss. Exam: hair loss and dystrophic fingernails (Fig 1). Labs: low ferritin, hemoglobin, protein, and albumin. Stool guaic positive. Repeat EGD showed many antral polyps (Fig 2); histology: foveolar hyperplasia and chronic gastritis. Repeat colonoscopy showed many polyps throughout the colon (Fig 3) and terminal ileum; histology: chronic lamina propria inflammation and cystically dilated crypts and glands. Patient diagnosed with CCS. Weight improving on dietary supplements; symptoms are controlled with loperamide and simethicone. He declines steroids.FigureFigureFigureDiscussion: Hallmark features of CCS include diffuse polyps which are usually inflammatory, hyperplastic or juvenile but can be adenomatous. Histology is often non-specific and includes mixed inflammation, expanded lamina propia, cystic dilation of glands and crypts, and villous atrophy. Our patient had no signs of polyposis on recent EGD or nail changes on prior exams. Over 1 year, he developed non-specific symptoms that were unified by diffuse polyposis seen on repeat endoscopy. His disease onset is similar to the relatively acute onset described in the literature. Complications include malabsorption, gastrointestinal bleeding, small bowel obstruction, congestive heart failure, and sepsis. CCS has an increased risk of colon cancer. It is unclear if this relates to pre-existing polyps or is sporadic. Nutrition supplementation is crucial in therapy. Glucocorticoids are the most effective current therapy. Polyp sampling has been advocated for cancer prevention. It is important to be aware of this constellation of symptoms and to refer for endoscopic evaluation. Early diagnosis is key as this rare disease is progressive and confers significant mortality.

Hereditary Colorectal Polyposis and Cancer Syndromes: A Primer on Diagnosis and Management.

Colorectal cancer (CRC) is the fourth most common cancer amongst men and women. Between 3 and 6% of all CRCs are attributed to well-defined inherited syndromes, including Lynch syndrome, familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), and several hamartomatous polyposis conditions. Identification of these patients through family history and appropriate genetic testing can provide estimates of cancer risk that inform appropriate cancer screening, surveillance and/or preventative interventions. This narrative review examines the hereditary colorectal cancer and polyposis syndromes, their genetic basis, clinical management, and evidence supporting cancer screening.

Hereditary and common familial colorectal cancer: evidence for colorectal screening.

Colorectal cancer (CRC) is the fourth most common cancer among men and women. Between 3 and 6% of all CRCs are attributed to well-defined inherited syndromes, including Lynch syndrome, familial adenomatous polyposis, MUTYH-associated polyposis and several hamartomatous conditions. Up to 30% of CRC cases exhibit common familial risk, likely related to a combination of inherited factors and environment. Identification of these patients through family history and appropriate genetic testing can provide estimates of cancer risk that inform appropriate cancer screening, surveillance and/or preventative interventions. This article examines the colon cancer syndromes, their genetic basis, clinical management and evidence supporting colorectal screening. It also deals with the category of common (non-syndromic) familial risk including risk determination and screening guidelines.

A Novel APC Gene Mutation Associated With a Severe Phenotype in a Patient With Turcot Syndrome

Turcot syndrome is a rare inherited condition of colonic polyposis associated with central nervous system tumors. We report a patient with a novel adenomatous polyposis coli gene mutation leading to a severe phenotype including medulloblastoma, low-grade fibromyxoid sarcoma following cranial radiation, pilomatrixomas, colonic adenomas, and abdominal desmoid tumor following colectomy, all of which were successfully treated. Multiple tumors may be seen in patients with Turcot syndrome but the occurrence of sarcomas is rare. This case highlights the importance of close follow-up for patients with Turcot syndrome and the importance of a broad differential diagnosis in evaluating a condition in which multiple tumors are frequently seen.

Cronkhite-Canada Syndrome: A Case Report and Literature Review of Gastrointestinal Polyposis Syndrome

Cronkhite-Canada syndrome (CCS) is a rare, non-inherited polyposis syndrome, characterized by diffuse gastrointestinal (GI) hamartomatous polyposis with unique dermatologic changes including alopecia, skin hyperpigmentation, and nail dystrophy. Patients can typically present with diarrhea, weight loss, protein-losing enteropathy, and nutritional deficiency. However, it can demonstrate diverse other clinical features, usually with poor prognosis. Currently, there are no specific diagnostic criteria established yet. The etiology of CCS is still obscure, but an autoimmune process has been suggested. Here we present an 81-year-old Caucasian female who had clinical presentations, physical exam, imaging, endoscopy and pathology findings that were all consistent with the diagnosis of CCS. We also include a detailed literature review of the other gastrointestinal polyposis syndromes (hamartomatous, adenomatous, hyperplastic and inflammatory polyposis). A high index of suspicion and recognition of the characteristic clinical, endoscopic as well as histopathological findings of CCS, as well as different gastrointestinal polyposis conditions, can help clinicians with more timely and correct diagnosis.

MUTYH the base excision repair gene family member associated with colorectal cancer polyposis.

sporadic (70-75%), familial (20-25%) and hereditary (5-10%). hereditary colorectal cancer syndromes classified into two different subtypes: polyposis and non polyposis. Familial Adenomatous polyposis (FAP; OMIM #175100) is the most common polyposis syndrome, account for <1% of colorectal cancer incidence and characterized by germline mutations in the Adenomatous polyposis coli (APC, 5q21- q22; OMIM #175100). FAP is a dominant cancer predisposing syndrome which 20-25% cases are de novo. There is also another polyposis syndrome; MUTYH associated polyposis (MAP, OMIM 608456) which it is caused by mutation in human Mut Y homologue MUTYH (MUTYH; OMIM 604933) and it is associated with multiple (15-100) colonic adenomas. In this paper we discuss MUTYH mechanism as an important member of Base Excision Repair (BER) family and its important role in polyposis condition.

Proctocolectomy for persistent haematochezia in a patient with Cronkhite-Canada Syndrome.

Cronkhite-Canada syndrome is an extremely rare condition of gastrointestinal polyposis in which the main presenting features are diarrhoea and dysgeusia. The polyps in this condition are characteristically distributed throughout the entire gastrointestinal tract except the oesophagus, and these patients exhibit unique ectodermal abnormalities. Herein, we report a 50-year-old male who had recurrent episodes of severe haematochezia from the polyps in the colon. Further examination and investigations revealed a diagnosis of Cronkhite-Canada syndrome. Proctocolectomy was carried out for medically refractory haematochezia and the patient is asymptomatic at present.

Genetic Testing by Cancer Site

Hereditary colonic polyposis conditions are all characterized by high rates of cancer, but they have diverse phenotypes, genetic heterogeneity, and assorted inheritance patterns. The most well known of these conditions include familial adenomatous polyposis, attenuated familial adenomatous polyposis, MUTYH (MutY human homolog)-associated polyposis, Peutz-Jeghers syndrome, juvenile polyposis syndrome, and Cowden syndrome. Early recognition of these conditions is not only vital for management in affected individuals, but also for prevention and early detection in at-risk relatives. Reviewed here are the genetic testing strategies for colonic polyposis, as well as an overview of characteristic features and management considerations for these syndromes.

Bowel cancer in a 17 year old: what could be the reason?

Inherited conditions predisposing to early onset bowel cancer include the autosomal dominant conditions of Lynch Syndrome, Familial Adenomatous Polyposis and PTEN Hamartoma Tumor Syndrome, as well as the autosomal recessive condition of MUTYH-Associated Polyposis. There is also an increased risk of early onset bowel cancer and other malignancies in individuals with biallelic mutations (homozygous or compound heterozygous) in the mismatch repair (MMR) genes. Screening recommendations are usually given to family members on the basis of the clinical diagnosis assisted by germline genetic testing for the proband and at-risk relatives. For an individual with very early onset bowel cancer, careful consideration of the pathology and wider attention to phenotypic features and/or their family history provide clues as to whether there may be an underlying genetic predisposition. These include: age at diagnosis; clinical examination; presence or absence of polyps; results of immunohistochemistry (IHC) for the MMR gene proteins +/- BRAF testing; tumour microsatellite instability (MSI) testing, and family history of bowel cancer or other syndrome related cancers. Sometimes, no clear conclusions can be reached about an underlying inherited mechanism, if any. We will present the case of BK, who was diagnosed with caecal cancer at the age of 17. A right hemi-colectomy demonstrated a moderately to poorly differentiated adenocarcinoma, with a 40% mucinous component and tumour infiltrating lymphocytes. No precursor lesion was identified, and no polyps were identified in the distal bowel or in the resected bowel. Three lymph nodes out of 32 were positive for adenocarcinoma. Staging was negative for distant metastatic disease. Adjuvant chemotherapy with FOLFOX was given. BK’s parents are second cousins. The only family history of cancer was a fifth-degree relative with bowel cancer. The results of genetic investigations will be presented, along with a reflection on the challenges for setting screening recommendations when two potentially at-risk relatives are severely intellectually delayed teenagers.

Phenotype/genotype in Gardner disease

Abstract Purpose Gardner syndrome is a variant of familial adenomatous polyposis and results in the manifestation of external and internal symptoms including gastrointestinal polyps, osteomas, tumors, epidermoid cysts and congenital hypertrophy of retinal pigment epithelium. Methods Three families of Gardner syndrome including 23 patients underwent complete check‐up to characterize ocular and general phenotype. Ophthalmologic manifestations are simple, non invasive reliable and very sensitive. The gene responsible for this disorder was localized on the long arm of the fifth chromosome. APC‐associated polyposis conditions are caused by mutations in the APC gene. A subset of individuals with clinical features of FAP will instead carry a mutation in the MUTYH gene. Results Of the 23 patients, 13 presented a bilateral congenital hypertrophy of retinal pigment epithelium. In these patients 6 had a positive coloscopic exploration. This inherited autosomal dominant disorder has a marked propensity to malignant transformation, so, it is important to detect affected patients early. Conclusion Currently, there are no specific screening recommendations for Gardner syndrome, but testing following general screening recommendations for extra‐colonic malignancies, genetic counseling, and endoscopy are encouraged.