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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 -
The American Journal of Gastroenterology Feb 2015This guideline presents recommendations for the management of patients with hereditary gastrointestinal cancer syndromes. The initial assessment is the collection of a... (Review)
Review
This guideline presents recommendations for the management of patients with hereditary gastrointestinal cancer syndromes. The initial assessment is the collection of a family history of cancers and premalignant gastrointestinal conditions and should provide enough information to develop a preliminary determination of the risk of a familial predisposition to cancer. Age at diagnosis and lineage (maternal and/or paternal) should be documented for all diagnoses, especially in first- and second-degree relatives. When indicated, genetic testing for a germline mutation should be done on the most informative candidate(s) identified through the family history evaluation and/or tumor analysis to confirm a diagnosis and allow for predictive testing of at-risk relatives. Genetic testing should be conducted in the context of pre- and post-test genetic counseling to ensure the patient's informed decision making. Patients who meet clinical criteria for a syndrome as well as those with identified pathogenic germline mutations should receive appropriate surveillance measures in order to minimize their overall risk of developing syndrome-specific cancers. This guideline specifically discusses genetic testing and management of Lynch syndrome, familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (AFAP), MUTYH-associated polyposis (MAP), Peutz-Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, serrated (hyperplastic) polyposis syndrome, hereditary pancreatic cancer, and hereditary gastric cancer.
Topics: Adenomatous Polyposis Coli; Colorectal Neoplasms, Hereditary Nonpolyposis; Disease Management; Gastrointestinal Neoplasms; Genetic Testing; Hamartoma Syndrome, Multiple; Humans; Intestinal Polyposis; Neoplastic Syndromes, Hereditary; Peutz-Jeghers Syndrome
PubMed: 25645574
DOI: 10.1038/ajg.2014.435 -
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 -
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 -
Pathology Jan 2018Colorectal cancer (CRC) accounts for over 8% of all deaths annually worldwide. Between 2 and 5% of all CRCs occur due to inherited syndromes, including Lynch syndrome,... (Review)
Review
Colorectal cancer (CRC) accounts for over 8% of all deaths annually worldwide. Between 2 and 5% of all CRCs occur due to inherited syndromes, including Lynch syndrome, familial adenomatous polyposis, MUTYH-associated polyposis, Peutz-Jeghers syndrome, juvenile polyposis and Cowden/PTEN hamartoma syndrome. In addition, serrated polyposis is a clinically defined condition characterised by multiple colorectal serrated polyps and an increased risk of CRC but the genetics are not known. In most hereditary CRC syndromes, polyps undergo carcinogenesis, but the exact route to carcinoma seems to differ between the conditions. Discovery of the key germline mutations in these syndromes has been instrumental to our understanding of the underlying molecular mechanisms of colorectal carcinogenesis. This review summarises the genetic and pathological alterations in hereditary CRC syndromes.
Topics: Adenomatous Polyposis Coli; Colonic Neoplasms; Colorectal Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis; Germ-Line Mutation; Humans; Intestinal Polyposis; Neoplastic Syndromes, Hereditary; Peutz-Jeghers Syndrome
PubMed: 29169633
DOI: 10.1016/j.pathol.2017.09.004 -
JAMA Dermatology Nov 2022
Topics: Humans; Peutz-Jeghers Syndrome; Female; Child, Preschool
PubMed: 36197686
DOI: 10.1001/jamadermatol.2022.3979 -
Autopsy & Case Reports 2022
PubMed: 35642203
DOI: 10.4322/acr.2021.384 -
The New England Journal of Medicine Jan 2019
Topics: Abdominal Pain; Humans; Intestinal Polyps; Intussusception; Jejunal Diseases; Male; Middle Aged; Peutz-Jeghers Syndrome; Tomography, X-Ray Computed
PubMed: 30699321
DOI: 10.1056/NEJMicm1806623 -
The American Journal of Surgical... Aug 2021We describe 22 examples of a novel, usually paratubal, adnexal tumor associated with Peutz-Jeghers syndrome in nearly 50% of cases that harbored STK11 alterations in all...
A Distinctive Adnexal (Usually Paratubal) Neoplasm Often Associated With Peutz-Jeghers Syndrome and Characterized by STK11 Alterations (STK11 Adnexal Tumor): A Report of 22 Cases.
We describe 22 examples of a novel, usually paratubal, adnexal tumor associated with Peutz-Jeghers syndrome in nearly 50% of cases that harbored STK11 alterations in all tested (n=21). The patients ranged from 17 to 66 years (median=39 y) and the tumors from 4.5 to 25.5 cm (median=11 cm). Most (n=18) were paratubal, with metastases noted in 11/22 (50%) and recurrences in 12/15 (80%). Morphologically, they were characterized by interanastomosing cords and trabeculae of predominantly epithelioid cells, set in a variably prominent myxoid to focally edematous stroma, that often merged to form tubular, cystic, cribriform, and microacinar formations, reminiscent of salivary gland-type tumors. The tumor cells were uniformly atypical, often with prominent nucleoli and a variable mitotic index (median=9/10 HPFs). The tumors were usually positive to a variable extent for epithelial (CAM5.2, AE1/AE3, cytokeratin 7), sex cord (calretinin, inhibin, WT1), and mesothelial (calretinin, D2-40) markers, as well as hormone receptors. PAX8, SF1, and GATA-3 were rarely positive, while claudin-4, FOXL2, and TTF-1 were consistently negative. All sequenced tumors (n=21) harbored alterations in STK11, often with a loss of heterozygosity event. There were no other recurrently mutated genes. Recurrent copy number alterations included loss of 1p and 11q, and gain of 1q, 15q, and 15p. Despite an extensive morphologic, immunohistochemical, and molecular evaluation, we are unable to determine with certainty the histogenesis of this unique tumor. Wolffian, sex cord stromal, epithelial, and mesothelial origins were considered. We propose the term STK11 adnexal tumor to describe this novel entity and emphasize the importance of genetic counseling in these patients as a significant number of neoplasms occur in association with Peutz-Jeghers syndrome.
Topics: AMP-Activated Protein Kinase Kinases; Adolescent; Adult; Aged; Female; Humans; Middle Aged; Mutation; Ovarian Neoplasms; Peutz-Jeghers Syndrome; Protein Serine-Threonine Kinases; Sex Cord-Gonadal Stromal Tumors; Young Adult
PubMed: 33534223
DOI: 10.1097/PAS.0000000000001677