Clinical Guidelines for Diagnosis and Management of Peutz-Jeghers Syndrome in Children and Adults

Abstract

<b><i>Background:</i></b> 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. <b><i>Summary:</i></b> 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. <b><i>Key Messages:</i></b> 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.

Endoscopic Treatment of Colo-Colonic Intussusception in a Patient with Peutz-Jeghers Syndrome

“…The GeneReviews stated that prophylactic polypectomy of large polyps should be performed to decrease the sequelae of large polyps including bleeding, anemia, obstruction, and intussusception, and also to reduce the risk for cancer by the malignant transformation of PJS-type polyps [1]. Japanese guidelines also contain the same recommendations as GeneReviews [10]. Prophylactic polypectomy should Case Reports in Gastroenterology also be considered for colonic lesion according to this guideline, if appropriate follow-up was performed in our case, we believe that the onset of intussusception could have been prevented.…”

Major surgical conditions of childhood and their lifelong implications: comprehensive review

“…Late effects of cancer management in childhood therefore extend into adulthood. For patients with inherited polyposis disorders, such as Peutz–Jeghers syndrome, and family cancer predisposition syndromes, such as Li-Fraumeni syndrome, lifelong follow-up is also critical as multiple new tumours invariably occur in these vulnerable high-risk individuals 266 , 267 . Functional sequelae resulting from childhood cancer surgery are currently being investigated in an international multicentre collaborative study (FUSE (Functional Sequelae Assessment In Pediatric Surgical Oncology)) led by St Jude Children’s Research Hospital Memphis, USA, and the International Society of Paediatric Surgical Oncology.…”

Device-assisted enteroscopy and the need for surgery in Peutz-Jeghers syndrome: the long and winding road

“…Second, the size threshold for polyp removal is a matter for discussion: the majority of studies, as in the present paper from Elfeky et al, set the threshold for polyp removal at 10 mm [8], albeit in some other studies only those > 20 mm were resected [12]. Keeping in mind that avoidance of surgery in PJS patients is Device-assisted enteroscopy and the need for surgery in Peutz-Jeghers syndrome: the long and winding road the mainstay of surveillance protocols, DAE resection of polyps > 15 mm is strongly recommended by current guidelines [4], but even smaller polyps, which do not represent per se a clear indication for DAE, should be resected when encountered during the procedure because their future growth is expected [5].…”

“…Given the need for emergent surgery due to these complications, as seen in historical cohorts, enteroscopy-based preemptive approaches for resection of SB polyps have been promoted over the years, at first by means of intraoperative enteroscopy (IOE) 2 , push enteroscopy 3 and, more recently, device-assisted enteroscopy (DAE) 4 . DAE removal of SB polyps larger than 10 to 15 mm is currently recommended by scientific societies 1 4 5 .…”

“…Furthermore, although the overall results of the different studies are quite consistent in emphasizing the benefit of a DAE-based preemptive approach, there are still some important open unresolved issues, which are relevant when planning a structured and effective prevention program. First of all, current guidelines recommend the interval for SB surveillance based on phenotype 1 4 5 , whereas it is uncertain whether the strategy of removing most SB polyps by DAE might modify these surveillance intervals, especially when discrepancies (e.g., concerning polyp size, polyp location, histological examination) with other diagnostic procedures are also identified. Second, the size threshold for polyp removal is a matter for discussion: the majority of studies, as in the present paper from Elfeky et al, set the threshold for polyp removal at 10 mm 8 , albeit in some other studies only those > 20 mm were resected 12 .…”