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Current Opinion in Gastroenterology May 2021Peutz-Jeghers syndrome is a rare, autosomal dominant, hereditary polyposis syndrome defined by gastrointestinal hamartomas and mucocutaneous pigmentations, caused by a... (Review)
Review
PURPOSE OF REVIEW
Peutz-Jeghers syndrome is a rare, autosomal dominant, hereditary polyposis syndrome defined by gastrointestinal hamartomas and mucocutaneous pigmentations, caused by a germline mutation in the serine/ threonine kinase 11 or liver kinase B1 (STK11/LKB1) genes. Hamartomatous polyps located throughout the gastrointestinal tract can be complicated by bleeding and small bowel intussusception, potentially leading to the need for emergency surgery. Individuals suffering from Peutz-Jeghers syndrome have an increased lifetime risk of various forms of cancer (gastrointestinal, pancreatic, lung, breast, uterine, ovarian and testicular). Surveillance should lead to the prevention of complications and thus a reduction in mortality and morbidity of patients.
RECENT FINDINGS
A combined approach based on wireless capsule endoscopy, magnetic resonance enterography and device-assisted enteroscopy is effective in reduction of the polyp burden and thus decreasing the risk of bleeding and intussusception. Current guidelines for screening and surveillance are mostly based on expert opinion rather than evidence.
SUMMARY
Peutz-Jeghers syndrome is an emerging disease that significantly affects the quality of life enjoyed by patients. Despite of all the progress in improved early diagnostics, options for advanced endoscopic therapy and elaborate surveillance, acute and chronic complications decrease the life expectancy of patients suffering from Peutz-Jeghers syndrome.
Topics: Capsule Endoscopy; Humans; Intestinal Polyps; Intestine, Small; Peutz-Jeghers Syndrome; Quality of Life
PubMed: 33591027
DOI: 10.1097/MOG.0000000000000718 -
Digestion 2023Peutz-Jeghers syndrome (PJS) is a rare disease characterized by the presence of hamartomatous polyposis throughout the gastrointestinal tract, except for the esophagus,... (Review)
Review
BACKGROUND
Peutz-Jeghers syndrome (PJS) is a rare disease characterized by the presence of hamartomatous polyposis throughout the gastrointestinal tract, except for the esophagus, along with characteristic mucocutaneous pigmentation. It is caused by germline pathogenic variants of the STK11 gene, which exhibit an autosomal dominant mode of inheritance. Some patients with PJS develop gastrointestinal lesions in childhood and require continuous medical care until adulthood and sometimes have serious complications that significantly reduce their quality of life. Hamartomatous polyps in the small bowel may cause bleeding, intestinal obstruction, and intussusception. Novel diagnostic and therapeutic endoscopic procedures such as small-bowel capsule endoscopy and balloon-assisted enteroscopy have been developed in recent years.
SUMMARY
Under these circumstances, there is growing concern about the management of PJS in Japan, and there are no practice guidelines available. To address this situation, the guideline committee was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labour and Welfare with specialists from multiple academic societies. The present clinical guidelines explain the principles in the diagnosis and management of PJS together with four clinical questions and corresponding recommendations based on a careful review of the evidence and involved incorporating the concept of the Grading of Recommendations Assessment, Development and Evaluation system.
KEY MESSAGES
Herein, we present the English version of the clinical practice guidelines of PJS to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with PJS.
Topics: Adolescent; Humans; Adult; Child; Peutz-Jeghers Syndrome; Quality of Life; Intestinal Polyps; Intestine, Small; Capsule Endoscopy
PubMed: 37054692
DOI: 10.1159/000529799 -
Southern Medical Journal Mar 2021The incidence of esophageal cancer (EC) is on the rise. With the distinct subtypes of adenocarcinoma and squamous cell carcinoma comes specific risk factors, and as a... (Review)
Review
The incidence of esophageal cancer (EC) is on the rise. With the distinct subtypes of adenocarcinoma and squamous cell carcinoma comes specific risk factors, and as a result, people of certain regions of the world can be more prone to a subtype. For example, squamous cell carcinoma of the esophagus has the highest incidence in eastern Africa and eastern Asia, with smoking being a major risk factor, whereas adenocarcinoma is more prevalent in North America and western Europe, with gastroesophageal reflux disease being a leading risk factor. With that being said, adenocarcinoma and squamous cell carcinoma have similar and unfortunately poor survival rates, partly because EC is prone to early metastasis given that the esophagus does not have a serosa, as well as the superficial nature of its lymphatics compared with the rest of the gastrointestinal tract. This makes early detection of the utmost importance, and certain patients have been shown to have the benefit of screening/surveillance endoscopies, including those with Barrett's esophagus, lye-induced/caustic strictures, tylosis, and Peutz-Jeghers syndrome. Until treatments significantly improve, identifying EC at the earliest stage will have the best success for patient outcomes, and further elucidation of its pathogenesis and risk factors may lead to identifying other high-risk groups that should be screened.
Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Early Detection of Cancer; Esophageal Neoplasms; Gastroesophageal Reflux; Global Health; Humans; Incidence; Risk Factors; Smoking; Survival Rate
PubMed: 33655310
DOI: 10.14423/SMJ.0000000000001226 -
Journal of Clinical Medicine Jan 2021The scientific data to guide the management of Peutz-Jeghers syndrome (PJS) are sparse. The available evidence has been reviewed and discussed by diverse medical... (Review)
Review
The scientific data to guide the management of Peutz-Jeghers syndrome (PJS) are sparse. The available evidence has been reviewed and discussed by diverse medical specialists in the field of PJS to update the previous guideline from 2010 and formulate a revised practical guideline for colleagues managing PJS patients. Methods: Literature searches were performed using MEDLINE, Embase, and Cochrane. Evidence levels and recommendation strengths were assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). A Delphi process was followed, with consensus being reached when ≥80% of the voting guideline committee members agreed. Recommendations and statements: The only recent guidelines available were for gastrointestinal and pancreatic management. These were reviewed and endorsed after confirming that no more recent relevant papers had been published. Literature searches were performed for additional questions and yielded a variable number of relevant papers depending on the subject addressed. Additional recommendations and statements were formulated. Conclusions: A decade on, the evidence base for recommendations remains poor, and collaborative studies are required to provide better data about this rare condition. Within these restrictions, multisystem, clinical management recommendations for PJS have been formulated.
PubMed: 33513864
DOI: 10.3390/jcm10030473 -
Best Practice & Research. Clinical... 2022There are three major hereditable syndromes that affect primarily the stomach: hereditary diffuse gastric cancer (HDGC), gastric adenocarcinoma and proximal polyposis of... (Review)
Review
There are three major hereditable syndromes that affect primarily the stomach: hereditary diffuse gastric cancer (HDGC), gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) and familial intestinal gastric cancer (FIGC). HDGC is caused by germline mutations in CDH1 gene that occur in 10-40% of HDGC families and, in a minority of cases, by mutations in CTNNA1 gene. GAPPS is caused by germline mutations in the promoter 1B of APC gene, and the genetic cause of FIGC is not fully elucidated. Gastric cancer can also be observed as part of other inherited cancer disorders, namely in familial adenomatous polyposis, MUTYH-associated polyposis, Peutz-Jeghers syndrome, juvenile polyposis syndrome, Lynch syndrome, Li-Fraumeni syndrome, Cowden syndrome, and hereditary breast and ovarian cancer syndrome. In this article, the state of the art of familial gastric cancer regarding the clinical, molecular and pathology features is reviewed, as well as the practical aspects for a correct diagnosis and clinical management.
Topics: Adenocarcinoma; Adenomatous Polyposis Coli; Adenomatous Polyposis Coli Protein; Adenomatous Polyps; Antigens, CD; Cadherins; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Neoplastic Syndromes, Hereditary; Promoter Regions, Genetic; Stomach Neoplasms; alpha Catenin
PubMed: 35988963
DOI: 10.1016/j.bpg.2022.101800 -
International Journal of Molecular... Jan 2023Colorectal cancer is one of the most common tumors, and genetic predisposition is one of the key risk factors in the development of this malignancy. Lynch syndrome and... (Review)
Review
Colorectal cancer is one of the most common tumors, and genetic predisposition is one of the key risk factors in the development of this malignancy. Lynch syndrome and familial adenomatous polyposis are the best-known genetic diseases associated with hereditary colorectal cancer. However, some other genetic disorders confer an increased risk of colorectal cancer, such as Li-Fraumeni syndrome ( gene), -associated polyposis ( gene), Peutz-Jeghers syndrome ( gene), Cowden syndrome ( gene), and juvenile polyposis syndrome ( and genes). Moreover, the recent advances in molecular techniques, in particular Next-Generation Sequencing, have led to the identification of many new genes involved in the predisposition to colorectal cancers, such as , , , , , , and . In this review, we summarized the past and more recent findings in the field of cancer predisposition genes, with insights into the role of the encoded proteins and into the associated genetic disorders. Furthermore, we discussed the possible clinical utility of genetic testing in terms of prevention protocols and therapeutic approaches.
Topics: Humans; Genetic Predisposition to Disease; Adenomatous Polyposis Coli; Neoplastic Syndromes, Hereditary; Colorectal Neoplasms, Hereditary Nonpolyposis; Genetic Testing; Colorectal Neoplasms
PubMed: 36768460
DOI: 10.3390/ijms24032137 -
JAMA Dermatology Nov 2022
Topics: Humans; Peutz-Jeghers Syndrome; Female; Child, Preschool
PubMed: 36197686
DOI: 10.1001/jamadermatol.2022.3979 -
Gastroenterology Jul 2020The purpose of this American Gastroenterological Association Institute Clinical Practice Update is to describe the indications for screening for pancreas cancer in... (Review)
Review
DESCRIPTION
The purpose of this American Gastroenterological Association Institute Clinical Practice Update is to describe the indications for screening for pancreas cancer in high-risk individuals.
METHODS
The evidence reviewed in this work is based on reports of pancreas cancer screening studies in high-risk individuals and expert opinion. BEST PRACTICE ADVICE 1: Pancreas cancer screening should be considered in patients determined to be at high risk, including first-degree relatives of patients with pancreas cancer with at least 2 affected genetically related relatives. BEST PRACTICE ADVICE 2: Pancreas cancer screening should be considered in patients with genetic syndromes associated with an increased risk of pancreas cancer, including all patients with Peutz-Jeghers syndrome, hereditary pancreatitis, patients with CDKN2A gene mutation, and patients with 1 or more first-degree relatives with pancreas cancer with Lynch syndrome, and mutations in BRCA1, BRCA2, PALB2, and ATM genes. BEST PRACTICE ADVICE 3: Genetic testing and counseling should be considered for familial pancreas cancer relatives who are eligible for surveillance. A positive germline mutation is associated with an increased risk of neoplastic progression and may also lead to screening for other relevant associated cancers. BEST PRACTICE ADVICE 4: Participation in a registry or referral to a pancreas Center of Excellence should be pursued when possible for high-risk patients undergoing pancreas cancer screening. BEST PRACTICE ADVICE 5: Clinicians should not screen average-risk individuals for pancreas cancer. BEST PRACTICE ADVICE 6: Pancreas cancer screening in high-risk individuals should begin at age 50 years, or 10 years younger than the initial age of familial onset. Screening should be initiated at age 40 years in CKDN2A and PRSS1 mutation carriers with hereditary pancreatitis and at age 35 years in the setting of Peutz-Jeghers syndrome. BEST PRACTICE ADVICE 7: Magnetic resonance imaging and endoscopic ultrasonography (EUS) should be used in combination as the preferred screening modalities in individuals undergoing pancreas cancer screening. BEST PRACTICE ADVICE 8: The target detectable pancreatic neoplasms are resectable stage I pancreatic ductal adenocarcinoma and high-risk precursor neoplasms, such as intraductal papillary mucinous neoplasms with high-grade dysplasia and some enlarged pancreatic intraepithelial neoplasias. BEST PRACTICE ADVICE 9: Screening intervals of 12 months should be considered when there are no concerning pancreas lesions, with shortened intervals and/or the performance of EUS in 6-12 months directed towards lesions determined to be low risk (by a multidisciplinary team). EUS evaluation should be performed within 3-6 months for indeterminate lesions and within 3 months for high-risk lesions, if surgical resection is not planned. New-onset diabetes in a high-risk individual should lead to additional diagnostic studies or change in surveillance interval. BEST PRACTICE ADVICE 10: Decisions regarding therapy directed towards abnormal findings detected during screening should be made by a dedicated multidisciplinary team together with the high-risk individual and their family. BEST PRACTICE ADVICE 11: Surgical resection should be performed at high-volume centers. BEST PRACTICE ADVICE 12: Clinicians should consider discontinuing pancreas cancer screening in high-risk individuals when they are more likely to die of non-pancreas cancer-related causes due to comorbidity and/or are not candidates for pancreas resection. BEST PRACTICE ADVICE 13: The limitations and potential risks of pancreas cancer screening should be discussed with patients before initiating a screening program.
Topics: Comorbidity; Decision Making, Shared; Early Detection of Cancer; Gastroenterology; Genetic Predisposition to Disease; Genetic Testing; Humans; Mass Screening; Medical History Taking; Neoplastic Syndromes, Hereditary; Pancreas; Pancreatectomy; Pancreatic Neoplasms; Practice Guidelines as Topic; Registries; Risk Assessment; Risk Factors; Societies, Medical; Time Factors; United States
PubMed: 32416142
DOI: 10.1053/j.gastro.2020.03.088