Peutz-Jeghers syndrome: management for recurrent intussusceptions.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by hamartomatous gastrointestinal polyps along with the characteristic mucocutaneous freckling. Multiple surgeries for recurrent intussusception in these children may lead to short bowel syndrome. Here we present our experience of management in such patients. METHODS: From January 2015 to December 2023, we reviewed children of PJS, presented with recurrent intussusceptions. Data were collected regarding presentation, management, and follow-up with attention on management dilemma. Diagnosis of PJS was based on criteria laid by World Health Organization (WHO). RESULTS: A total of nine patients were presented with age ranging from 4 to 17 years (median 9 years). A total of eighteen laparotomies were performed (7 outside, 11 at our centre). Among 11 laparotomies done at our centre, resection and anastomosis of bowel was done 3 times while 8 times enterotomy and polypectomy was done after reduction of intussusception. Upper and lower gastrointestinal endoscopy (UGIE & LGIE) was done in all cases while intraoperative enteroscopy (IOE) performed when required. Follow-up ranged from 2 months to 7 years. CONCLUSION: Children with PJS have a high risk of multiple laparotomies due to polyps' complications. Considering the diffuse involvement of the gut, early decision of surgery and extensive bowel resection should not be done. Conservative treatment must be tried under close observation whenever there is surgical dilemma. The treatment should be directed in the form of limited resection or polypectomy after reduction of intussusception.

[Early Duodenal Cancer Resected by Using Laparoscopic and Endoscopic Assistance Surgery in a Patient with Peutz-Jeghers Syndrome].

A 28-year-old female with a history of treatment for small intestinal polyps and characteristic pigmentation of her lip was clinically diagnosed with Peutz-Jeghers syndrome(PJS). Her sister had the pathogenic variant of STK11 upon genetic testing. A 20-mm polyp was identified in the second part the patient's duodenum on routine gastrointestinal surveillance, and biopsy revealed a well-differentiated adenocarcinoma. Laparoscopic partial duodenectomy with endoscopy was planned. After confirming the location of the tumor and Kocherization using a laparoscope, the polyp was resected via submucosal dissection under direct visualization with a small incision. The polyp was diagnosed as well-differentiated adenocarcinoma in situ and was resected without remnants. PJS is characterized by a high incidence of malignant tumors, and lifelong surveillance for gastrointestinal and extra-gastrointestinal tumors is necessary. The incidence of duodenal cancer is not high among patients with PJS. However, surgery for advanced cancer is highly invasive. It is desirable to detect the tumors at an early stage so that they can be resected via a less invasive treatment method such as endoscopic resection or laparoscopic surgery with an endoscope.

Peutz-Jeghers syndrome with polyps in the stomach, duodenum, and small and large intestine: a case report.

BACKGROUND: Peutz-Jeghers syndrome is a rare hereditary condition characterized by gastrointestinal polyps and pigmented oral lesions. The case contributes to a deeper understanding of Peutz-Jeghers syndrome and underscores the significance of interdisciplinary collaboration for accurate diagnosis and tailored therapeutic strategies. CASE DESCRIPTION: We present a case of a 15-year-old Afghan female patient with multiple polyps throughout the gastrointestinal tract and mucocutaneous pigmentation. Despite previous medical visits and colonoscopies, her symptoms persisted. A multidisciplinary team discussed the case and recommended further investigations and interventions. A polypectomy was performed, confirming the presence of hamartomatous polyps. The patient was diagnosed with Peutz-Jeghers syndrome, but during the course of treatment she went through complications and was managed surgically as well. CONCLUSION: Timely polyp removal and lifelong surveillance are crucial in managing Peutz-Jeghers syndrome. Further research and genetic analysis are needed to improve understanding and management of this rare disorder.

Contrast-enhanced ultrasound of polyp malignant transformation with multiple metastases in a patient with Peutz-Jeghers syndrome.

Multi-systemic metastasis in patients with Peutz-Jeghers syndrome (PJS) is very rare, and there are nearly no relevant imaging reports, especially in contrast-enhanced ultrasound (CEUS). We present here a 40-year-old male patient who underwent several partial small bowel resections and endoscopic polypectomy for intestinal polyps. After reviewing the patient's clinical diagnosis and treatment process, CEUS with sulfur hexafluoride microbubbles (SonoVue, Bracco, Milan, Italy) in the liver and gastrointestinal tract was performed. We imaged multiple abnormal masses with sonographic features consistent with malignancies. Combined with other imaging examinations and 18 gauge core-needle puncture biopsy of liver masses, multiple metastases outside the gastrointestinal tract were considered. This case report suggests CEUS may be an easy, effective, and supplementary method for evaluating PJS patients with suspected multi-systemic malignant lesions including the gastrointestinal tract.

How to do a laparoscopic-assisted endoscopic 'clean sweep' for small bowel polyp clearance in Peutz Jeghers syndrome.

We demonstrate the technical details of laparoscopic-assisted endoscopic 'clean sweep' for small bowel polyp clearance in Peutz Jeghers Syndrome. A 'clean sweep' reduces the risk for future recurrences but was previously performed with an open technique. A minimally invasive approach is safe, reduces bowel trauma and has good postoperative outcomes.

Cellular and molecular characteristics of stromal Lkb1 deficiency-induced gastrointestinal polyposis based on single-cell RNA sequencing.

Liver kinase B1 (Lkb1), encoded by serine/threonine kinase (Stk11), is a serine/threonine kinase and tumor suppressor that is strongly implicated in Peutz-Jeghers syndrome (PJS). Numerous studies have shown that mesenchymal-specific Lkb1 is sufficient for the development of PJS-like polyps in mice. However, the cellular origin and components of these Lkb1-associated polyps and underlying mechanisms remain elusive. In this study, we generated tamoxifen-inducible Lkb1flox/flox;Myh11-Cre/ERT2 and Lkb1flox/flox;PDGFRα-Cre/ERT2 mice, performed single-cell RNA sequencing (scRNA-seq) and imaging-based lineage tracing, and aimed to investigate the cellular complexity of gastrointestinal polyps associated with PJS. We found that Lkb1flox/+;Myh11-Cre/ERT2 mice developed gastrointestinal polyps starting at 9 months after tamoxifen treatment. scRNA-seq revealed aberrant stem cell-like characteristics of epithelial cells from polyp tissues of Lkb1flox/+;Myh11-Cre/ERT2 mice. The Lkb1-associated polyps were further characterized by a branching smooth muscle core, abundant extracellular matrix deposition, and high immune cell infiltration. In addition, the Spp1-Cd44 or Spp1-Itga8/Itgb1 axes were identified as important interactions among epithelial, mesenchymal, and immune compartments in Lkb1-associated polyps. These characteristics of gastrointestinal polyps were also demonstrated in another mouse model, tamoxifen-inducible Lkb1flox/flox;PDGFRα-Cre/ERT2 mice, which developed obvious gastrointestinal polyps as early as 2-3 months after tamoxifen treatment. Our findings further confirm the critical role of mesenchymal Lkb1/Stk11 in gastrointestinal polyposis and provide novel insight into the cellular complexity of Lkb1-associated polyp biology. © 2024 The Pathological Society of Great Britain and Ireland.

Gentle Giant? Giant Gastric Solitary Peutz-Jeghers Polyp.

Solitary hamartomatous polyps with identical pathological features of the typical hamartomas of the Peutz-Jegher syndrome are extremely rare. These solitary lesions lack the associated intestinal polyposis, classic mucocutaneous pigmentation, and family history typifying the Peutz-Jegher syndrome. We describe the case of a 31-year-old woman with a giant solitary gastric hamartoma endoscopically diagnosed and laparoscopically resected.

Changes of gut microbiota and short chain fatty acids in patients with Peutz-Jeghers syndrome.

Peutz-Jeghers Syndromeis a rare autosomal dominant genetic disease characterized by gastrointestinal hamartomatous polyps and skin and mucous membrane pigmentation. The pathogenesis of PJS remains unclear; however, it may be associated with mutations in the STK11 gene, and there is currently no effective treatment available. The gut microbiota plays an important role in maintaining intestinal homeostasis in the human body, and an increasing number of studies have reported a relationship between gut microbiota and human health and disease. However, relatively few studies have been conducted on the gut microbiota characteristics of patients with PJS. In this study, we analyzed the characteristics of the gut microbiota of 79 patients with PJS using 16 S sequencing and measured the levels of short-chain fatty acids in the intestines. The results showed dysbiosis in the gut microbiota of patients with PJS, and decreased synthesis of short-chain fatty acids. Bacteroides was positively correlated with maximum polyp length, while Agathobacter was negatively correlated with age of onset. In addition, acetic acid, propionic acid, and butyric acid were positively correlated with the age of onset but negatively correlated with the number of polyps. Furthermore, the butyric acid level was negatively correlated with the frequency of endoscopic surgeries. In contrast, we compared the gut microbiota of STK11-positive and STK11-negative patients with PJS for the first time, but 16 S sequencing analysis revealed no significant differences. Finally, we established a random forest prediction model based on the gut microbiota characteristics of patients to provide a basis for the targeted diagnosis and treatment of PJS in the future.

[A man with brown discolorations]. / Een man met bruine vlekjes.

A 58-year-old man presents with spontaneous brown discolorations of his mouth and hands. Our differential diagnosis included Peutz-Jeghers syndrome, Laugier-Hunziker syndrome or Addison's disease. There were no polyps in a previously performed colonoscopy and no other systemic symptoms. We made the diagnosis Laugier-Hunziker syndrome, a benign skin disorder that doesn't require treatment, confirmed by skin biopsy.

Máculas hiperpigmentadas y prolapso rectal, ¿qué debemos sospechar? / Hyperpigmented macules and rectal prolapse, what should we suspect?

El síndrome de Peutz-Jeghers (SPJ) es un síndrome autosómico dominante con una incidencia de 1 de cada 200 000 nacidos vivos. Las manifestaciones clínicas más frecuentes son las máculas hiperpigmentadas típicamente localizadas en la mucosa oral y la presencia de pólipos en el tracto gastrointestinal. A diferencia de la edad adulta, en Pediatría es excepcional el desarrollo de patología tumoral maligna. Sin embargo, en la edad pediátrica hay que tener un elevado índice de sospecha ante un paciente con diagnóstico de SPJ que presenta dolor abdominal compatible con una invaginación intestinal, ya que esta complicación es relativamente frecuente y precisa tratamiento quirúrgico urgente. Una vez realizado el diagnóstico de esta enfermedad, se deberán llevar a cabo controles periódicos mediante endoscopias a partir de los ocho años de edad (AU)

Peutz-Jeghers syndrome (PJS) is an autosomal dominant syndrome with an incidence of 1 in 200,000 live births. The most frequent clinical manifestations are hyperpigmented macules typically located on the oral mucosa and the presence of polyposis in the gastrointestinal tract.Unlike adulthood, in pediatrics the development of malignant tumor pathology is exceptional. However, in the pediatric age group, a high index of suspicion must be maintained when faced with a patient diagnosed with PJS who presents with abdominal pain compatible with intussusception, since this complication is relatively frequent and requires urgent surgical treatment. Once the diagnosis of this disease has been made, periodic controls should be carried out by means of endoscopies starting at eight years of age. (AU)

[Management of the Peutz-Jeghers Syndrome]. / Management des Peutz-Jeghers-Syndroms.

The current evidence to guide management of Peutz-Jeghers Syndrome (PJS) is sparse. Here we summarise the European guidelines that were published in 2021 by the EHTG (European Hereditary Tumour Group), extended with new evidence on some aspects of clinical management that have been generated since then. EHTG with this revised guideline has updated and extended their own previous expert opinion guideline from 2010. For this purpose, all published literature was systematically screened and the level of evidence determined by using the GRADE methodology (Grading of Recommendations Assessment. Development and Evaluation). This was followed by a Delphi process and the consensus for a statement was achieved if the voting committee reached ≥ 80% approval.The only other more recently published guidelines encountered only addressed the clinical management of gastrointestinal and pancreatic manifestations of PJS. These recommendations were reviewed and adopted, since no further relevant literature was identified in the systematic literature search. However, additional questions were identified and formulated into recommendations after following the described process. It may be stated that 10 years after the predecessor guideline, new evidence has been sparse. As with all rare diseases, a call for more collaborative studies must here be made in order to improve patient management by addressing open clinical questions and generating collaborative evidence with increased case numbers, both nationally and internationally. With the limited published evidence, these European guidelines are the most current reference for management of PJS patients.

Clinicopathologic comparison between sporadic and syndromic Peutz-Jeghers polyps.

Peutz-Jeghers polyps (PJPs) are hamartomatous polyps that may define patients with Peutz-Jeghers syndrome (PJS), a rare inherited polyposis syndrome with high cancer risk. However, the clinical significance of 1-2 sporadic PJPs (without other PJS stigmata) regarding malignant potential and identification of new PJS probands is still unclear. We identified 112 patients with 524 histologically confirmed PJPs and categorized them based on polyp number into syndromic (n = 38) if ≥3 PJPs or diagnosed PJS, solitary (1 PJP, n = 61), and intermediate (2 PJPs, n = 13). Clinicopathologic features, including presence of dysplasia in the polyp and development of neoplasia in the patient, were compared on a per-patient and per-polyp basis. Whereas patients with solitary and intermediate PJPs were not different from each other, patients with syndromic PJPs were, in multivariate analysis, younger (P = .001) and more likely to develop neoplasia (P = .02) over a 62.6-months median follow-up than patients with sporadic PJPs. On an individual polyp basis, syndromic PJPs were more likely, in multivariate analysis, to occur in the small intestine (P < .001), but less likely to harbor metaplasia (P = .03) or dysplasia (P = .001), than sporadic PJPs. Dysplasia and metaplasia were more likely in larger PJPs, by multivariate analysis (P = .007 and P < .001, respectively). These data suggest that strict criteria for PJS (including ≥3 PJPs), as currently used, stratify patients into distinct groups with significant differences in clinicopathologic parameters, particularly regarding risk of neoplasia. However, sporadic PJPs exhibit characteristics such as dysplasia and are thus important to recognize and diagnose but perhaps as heralding only a forme fruste PJS.

[Prepubertal gynecomastia at the debut of hereditary tumors predisposition syndrome (clinical case reports)].

Peutz-Jeghers Syndrome (Peutz-Jeghers Syndrome, PJS) refers to syndromes of hereditary tumor predisposition and is caused by pathological variants of the STK11 gene, leading to a defect in the synthesis of serine/threonine kinase 11 protein, which acts as a tumor suppressor.Clinical symptoms of the syndrome are combination of hamartomatous polyposis of the gastrointestinal tract and specific skin-mucosal hyperpigmentation. Also, this disease is characterized by a high risk of developing gastrointestinal and extra-intestinal tumors, including benign or malignant tumors of the reproductive system.One of the first signs of the disease in male patients may be prepubertal gynecomastia associated with large-cell calcifying Sertoli cells tumors expressing aromatase. In contrast to from pubertal gynecomastia, prepubertal is extremely rare, and it is often based on pathological causes. Early diagnosis of patients with pre-pubertal gynecomastia, including Peitz-Jaegers syndrome, defines the tactics of gynecomastia management and protocols for monitoring the development of other components of the disease in the future.This article describes two patients with pre-pubertal gynecomastia and Peitz-Jaegers syndrome with different molecular genetic defects: in one case associated with duplication of the STK11 gene site, in the other - with microdeletion of the short arm of chromosome 19 containing this gene.

CHRONIC ANEMIA CAUSED BY GIANT AND SOLITARY PEUTZ-JEGHERS HAMARTOMATOUS POLYP TREATED BY ENDOSCOPIC RESECTION.

•Giant and solitary polyps evolve with anemia. •EUS is an important tool for stage and manage this disease. •Endoscopic treatment is the best treatment choice. •Supplementary video available on this case report.

Updates in the diagnosis and management of non-ampullary small-bowel polyposis.

Advances in endoscopic instruments and techniques changed the strategy of diagnosis and management for non-ampullary small-bowel polyposis. In patients with Peutz-Jeghers syndrome, gastrointestinal surveillance using capsule endoscopy should commence no later than eight years old. Small bowel polyps >15 mm should be treated to prevent intussusception. Recently, endoscopic ischemic polypectomy and endoscopic reduction of intussusception were described. In patients with familial adenomatous polyposis, the first endoscopic screening using a lateral viewing and a longer endoscope to check the proximal jejunum should be performed around 25 years. Some experts recommend a first duodenal examination with a first colonoscopy (13 years). The surveillance intervals for duodenal polyposis should be adjusted individually. ESGE recommended the resection of every adenoma larger than 1 cm. Cold snare polypectomy has the potential to change the threshold of size for endoscopic resection. In patients with Juvenile polyposis syndrome, small bowel involvement seems infrequent and mostly located in the duodenal part. There is no indication for distal small bowel investigation.

Familial intestinal polyposis and device assisted enteroscopy: where do we stand?

INTRODUCTION: Hereditary polyposis syndromes are a group of inherited disorders associated with a high risk of developing colorectal cancer. The best known ones are familial adenomatous polyposis (FAP), Peutz-Jeghers (PJS), juvenile polyposis and Cowden syndromes, as well as conditions predisposing to cancer, such as Lynch syndrome. Some of them are characterized by an increased risk of small bowel polyps occurrence. AREAS COVERED: Literature search in PubMed was performed in November 2022 and a narrative review was carried out. Since performing small bowel polypectomy is important in such patients, device assisted enteroscopy (DAE) is the key for this procedure. A screening strategy for small bowel polyps is recommended only for PJS. Guidelines endorse either magnetic resonance imaging (MRI) or videocapsule endoscopy (VCE) every 1-3 years, according to the phenotype of the disease. Enteroscopy should be considered for therapeutic purpose in patients with a positive VCE or MRI. DAE has a central role in the resection of polyps larger than mm or causing symptoms of subocclusion or intussusception. Both single (SBE) and double balloon enteroscopy (DBE) are indicated and able to resect polyps up to 6-10 cm. American guidelines have restricted the indications to small bowel enteroscopy only to FAP patients with grade IV Spiegelman. EXPERT OPINION: Only some groups of patients (PJS, FAP with demonstrated small bowel polyp burden) may benefit from DAE.