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Clinics in Colon and Rectal Surgery Nov 2023Peutz-Jeghers syndrome (PJS), also known as hereditary mucocutaneous pigmented gastrointestinal polyposis, is a clinically rare autosomal dominant genetic disease, which... (Review)
Review
Peutz-Jeghers syndrome (PJS), also known as hereditary mucocutaneous pigmented gastrointestinal polyposis, is a clinically rare autosomal dominant genetic disease, which falls into the category of hereditary colorectal cancer. There are ∼7,000 new cases of PJS in China every year, and 170,000 PJS patients may survive for a long time in society. PJS polyps are characterized by an early age of onset, difficult diagnosis and treatment, and easy recurrence. With repeated growth, polyps can lead to serious complications such as intestinal obstruction, intussusception, gastrointestinal bleeding, and cancerization, which cause serious clinical problems. Due to repeated hospitalization and endoscopic follow-up, PJS patients and their families suffer from great physical and mental pain and economic burden. With the in-depth understanding of PJS and the development and popularization of endoscopic techniques in the past decade, an integrated treatment modality based on endoscopy plus surgery has gradually become the preferred treatment in most hospitals, which greatly improves the quality of life of PJS patients. However, there is still a lack of effective drug prevention and cure means. In this paper, the current clinical treatment means for PJS polyps were summarized by literature review combined with the treatment experience of our medical center, with a focus on their clinical diagnosis, treatment, and cancer risk.
PubMed: 37795464
DOI: 10.1055/s-0043-1767704 -
BMC Microbiology Nov 2023Peutz-Jeghers Syndromeis a rare autosomal dominant genetic disease characterized by gastrointestinal hamartomatous polyps and skin and mucous membrane pigmentation. The...
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.
Topics: Humans; Peutz-Jeghers Syndrome; Gastrointestinal Microbiome; Germ-Line Mutation; Fatty Acids, Volatile; Butyrates
PubMed: 38036954
DOI: 10.1186/s12866-023-03132-0 -
Cureus Apr 2024A relatively rare inherited condition known as Peutz-Jeghers syndrome (PJS) causes mucocutaneous pigmentation and gastrointestinal hamartomatous polyps. These polyps are... (Review)
Review
A relatively rare inherited condition known as Peutz-Jeghers syndrome (PJS) causes mucocutaneous pigmentation and gastrointestinal hamartomatous polyps. These polyps are non-cancerous, but the presence of PJS significantly increases the chances of developing various types of cancers, such as colorectal, pancreatic, gastric, and breast cancer. The purpose of this review article is to give an abbreviated summary of what is currently known about this syndrome, covering its clinical symptoms, pathophysiology, genetics, and management. PJS also raises the risk of getting many malignancies, especially gastrointestinal and pelvic cancers. Symptoms of the gastrointestinal tract brought on by hamartomatous polyps are frequent and include stool blockage, bleeding, and stomach pain. The pigmentation commonly appears as prominent bluish-black macules and frequently affects the skin and mucous membranes. Small macules and large regions of lentiginous pigmentation are both possible. Numerous areas, including the perioral area, buccal mucosa, fingers, and lips, exhibit pigmentation. Bowel obstruction and intussusception risk can be decreased by early identification and routine surveillance of gastrointestinal polyps. The gene serine/threonine kinase 11 (STK11) controls several biological functions, including cell polarity, growth, and proliferation. Genetic counseling is recommended for the affected individuals and their families. This can help assess the risk of passing on the condition to future generations and provide information about available reproductive options. Regular surveillance is crucial for managing the syndrome and reducing the risk of cancer development. Other syndromes and extra-gastrointestinal characteristics, such as somatic tumor polyps outside the gastrointestinal tract, are also linked to this syndrome.
PubMed: 38800180
DOI: 10.7759/cureus.58887 -
Therapeutic Advances in Gastroenterology 2024Before the development of double-balloon enteroscopy (DBE), the standard management of small-bowel polyposis was surgical resection. This is an invasive procedure that... (Review)
Review
Before the development of double-balloon enteroscopy (DBE), the standard management of small-bowel polyposis was surgical resection. This is an invasive procedure that could lead to short bowel syndrome. In the 21st century, several new enteroscopy techniques were distributed worldwide, including DBE, single-balloon enteroscopy, spiral enteroscopy, and motorized spiral enteroscopy. These devices enable the diagnoses and endoscopic interventions in the entire small bowel, even in patients with a history of laparotomy. In patients with Peutz-Jeghers syndrome (PJS), endoscopic ischemic polypectomy with clips or a detachable snare is the preferred method for managing pedunculated polyps because it is less likely to cause adverse events than conventional polypectomy. Although polyps in patients with PJS always recur, repeat endoscopic resection can reduce the total number and mean size of polyps in the long-term clinical course. Endoscopic reduction of small-bowel intussusception caused by PJS polyps can be successfully performed using DBE without surgery. A transparent hood is useful for securing a visual field during the treatment of small-bowel polyps, and minimal water exchange method is recommended to facilitate deep insertion. Familial adenomatous polyposis (FAP) is a genetic disorder that increases the risk of developing colorectal cancer. Because jejunal and ileal polyps in patients with FAP have the potential to develop into cancer the adenoma-carcinoma sequence, periodical surveillance, and endoscopic resection are needed for them, not only polyps in the duodenum. In cases of multiple small-bowel polyps in patients with FAP, cold snare polypectomy without retrieval is an acceptable treatment option for polyps that are 10 mm or smaller in size. Additional good pieces of evidence are necessary to confirm these findings because this narrative review mostly includes retrospective observational studies from single center, case reports, and expert reviews.
PubMed: 38164364
DOI: 10.1177/17562848231218561 -
International Journal of Surgery Case... Aug 2023Peutz-Jeghers syndrome is an inherited disorder distinguished by hamartomatous polyps in the gastrointestinal tract and pigmented mucocutaneous lesions. Treatment of the...
INTRODUCTION
Peutz-Jeghers syndrome is an inherited disorder distinguished by hamartomatous polyps in the gastrointestinal tract and pigmented mucocutaneous lesions. Treatment of the polyps is never definitive, with most patients needing several laparotomies. For this reason, surgeons should be economical in terms of surgical resection to prevent a short bowel syndrome in the long run. In this paper, we report two observations of patients presented a Peutz Jeghers syndrome (PJS).
CASES PRESENTATION
Case report 1: A 32-year-old women, who was operated on for an intestinal perforation related to a Peutz-jeghers hamartoma of the small bowel and was later re operated on for colonic intussusception, Case report 2: A 15-year-old patient that has been operated on three times already for small bowel intussusception and later for duodenal obstruction.
CLINICAL DISCUSSION
In an attempt to reduce complications, the 2010 guidelines updated in 2021 by the European Hereditary Tumor group introduced obligatory monitoring by fibroscopy and colonoscopy associated with an entero-MRI or a videocapsule from the age of 8 years. Laparotomy is indicated when endoscopic treatment is impossible or in emergency setting. When surgery is indicated, intestinal resection should be reserved for rare cases in order to avoid short bowel syndrome. The association of an intraoperative endoscopic treatment is recommended by some authors.
CONCLUSION
Peutz Jeghers syndrome is a rare entity with a complicated surveillance. Adequate polyp mapping is necessary for adequate planning of the treatment. The need for multiple laparotomies makes a comprehensive approach to surgery mandatory to prevent short bowel syndrome.
PubMed: 37506527
DOI: 10.1016/j.ijscr.2023.108511 -
Gut Pathogens Apr 2024Peutz-Jeghers syndrome (PJS) is a rare genetic disorder characterized by the development of pigmented spots, gastrointestinal polyps and increased susceptibility to...
BACKGROUND
Peutz-Jeghers syndrome (PJS) is a rare genetic disorder characterized by the development of pigmented spots, gastrointestinal polyps and increased susceptibility to cancers. Currently, most studies have investigated intestinal microbiota through fecal microbiota, and there are few reports about mucosa-associated microbiota. It remains valuable to search for the key intestinal microbiota or abnormal metabolic pathways linked to PJS.
AIM
This study aimed to assess the structure and composition of mucosa-associated microbiota in patients with PJS and to explore the potential influence of intestinal microbiota disorders and metabolite changes on PJS.
METHODS
The bacterial composition was analyzed in 13 PJS patients and 12 controls using 16S rRNA gene sequencing (Illumina MiSeq) for bacteria. Differential analyses of the intestinal microbiota were performed from the phylum to species level. Liquid chromatography-tandem mass spectrometry (LC‒MS) was used to detect the differentially abundant metabolites of PJS patients and controls to identify different metabolites and metabolic biomarkers of small intestinal mucosa samples.
RESULTS
High-throughput sequencing confirmed the special characteristics and biodiversity of the mucosa microflora in patients with PJS. They had lower bacterial biodiversity than controls. The abundance of intestinal mucosal microflora was significantly lower than that of fecal microflora. In addition, lipid metabolism, amino acid metabolism, carbohydrate metabolism, nucleotide metabolism and other pathways were significantly different from those of controls, which were associated with the development of the enteric nervous system, intestinal inflammation and development of tumors.
CONCLUSION
This is the first report on the mucosa-associated microbiota and metabolite profile of subjects with PJS, which may be meaningful to provide a structural basis for further research on intestinal microecology in PJS.
PubMed: 38678229
DOI: 10.1186/s13099-024-00617-9 -
The Journal of Biological Chemistry Jul 2023The tumor suppressor Liver Kinase B1 (LKB1) is a multifunctional serine/threonine protein kinase that regulates cell metabolism, polarity, and growth and is associated...
The tumor suppressor Liver Kinase B1 (LKB1) is a multifunctional serine/threonine protein kinase that regulates cell metabolism, polarity, and growth and is associated with Peutz-Jeghers Syndrome and cancer predisposition. The LKB1 gene comprises 10 exons and 9 introns. Three spliced LKB1 variants have been documented, and they reside mainly in the cytoplasm, although two possess a nuclear-localization sequence (NLS) and are able to shuttle into the nucleus. Here, we report the identification of a fourth and novel LKB1 isoform that is, interestingly, targeted to the mitochondria. We show that this mitochondria-localized LKB1 (mLKB1) is generated from alternative splicing in the 5' region of the transcript and translated from an alternative initiation codon encoded by a previously unknown exon 1b (131 bp) hidden within the long intron 1 of LKB1 gene. We found by replacing the N-terminal NLS of the canonical LKB1 isoform, the N-terminus of the alternatively spliced mLKB1 variant encodes a mitochondrial transit peptide that allows it to localize to the mitochondria. We further demonstrate that mLKB1 colocalizes histologically with mitochondria-resident ATP Synthase and NAD-dependent deacetylase sirtuin-3, mitochondrial (SIRT3) and that its expression is rapidly and transiently upregulated by oxidative stress. We conclude that this novel LKB1 isoform, mLKB1, plays a critical role in regulating mitochondrial metabolic activity and oxidative stress response.
Topics: AMP-Activated Protein Kinase Kinases; Mitochondria; Oxidative Stress; Protein Isoforms; Protein Serine-Threonine Kinases; Sirtuin 3; Mutation; Protein Sorting Signals; Protein Transport; Mitochondrial Proton-Translocating ATPases; Alternative Splicing; Codon, Initiator
PubMed: 37302555
DOI: 10.1016/j.jbc.2023.104906 -
Cancers Dec 2023Ovarian sex cord-stromal tumors (SCSTs) account for 8% of all primary ovarian neo-plasms. Accurate diagnosis is crucial since each subtype has a specific prognostic and... (Review)
Review
Ovarian sex cord-stromal tumors (SCSTs) account for 8% of all primary ovarian neo-plasms. Accurate diagnosis is crucial since each subtype has a specific prognostic and treatment. Apart from fibrosarcomas, stromal tumors are benign while sex cord tumors may recur, sometimes with a significant time to relapse. Although the diagnosis based on morphology is straightforward, in some cases the distinction between stromal tumors and sex cord tumors may be tricky. Indeed, the immunophenotype is usually nonspecific between stromal tumors and sex cord tumors. Therefore, molecular pathology plays an important role in the diagnosis of such entities, with pathognomonic or recurrent alterations, such as variants in adult granulosa cell tumors. In addition, these neoplasms may be associated with genetic syndromes, such as Peutz-Jeghers syndrome for sex cord tumors with annular tubules, and DICER1 syndrome for Sertoli-Leydig cell tumors (SLCTs), for which the pathologist may be in the front line of syndromic suspicion. Molecular pathology of SCST is also relevant for patient prognosis and management. For instance, the variant is associated with moderately to poorly differentiated SLCTS and a poorer prognosis. The present review summarizes the histomolecular criteria useful for the diagnosis of SCST, using recent molecular data from the literature.
PubMed: 38136408
DOI: 10.3390/cancers15245864