Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder, caused by germline variants in the serine/threonine kinase 11 (STK11) gene. However, mosaic variants in STK11 gene have been rarely described. A 25-year-old woman diagnosed with PJS due to multiple hamartomatous polyps in the gastrointestinal tract was referred to our clinic. In the molecular diagnosis, the patient was evaluated using the STK11 gene sequence analysis and multiplex ligation-dependent probe amplification (MLPA) method, which suggested no pathogenic variant to account for the clinical picture. Given that the clinical findings of the patient were consistent with those of PJS, the raw data from next-generation sequencing (NGS) were re-examined for mosaicism which led to the detection of a novel mosaic c.920 + 1G > T variant in STK11 gene with a rate of 23% (1860x). Deep read-level NGS was performed on buccal mucosa and polyp samples to determine mosaicism levels in other tissues. Variant frequencies were 29% (710x) and 31% (1301x), respectively. Mosaicism should be considered in cases with clear clinical diagnostic criteria, such as PJS, where the pathogenic variant cannot be detected by sequence analysis and MLPA methods. Identification of mosaicism in these patients is very important as it can have an impact on patient follow-up and genetic counseling for relatives.

Peutz-Jeghers syndrome is a rare, autosomal dominant polyposis syndrome. Presenting with a remarkable phenotype including development of characteristic gastrointestinal polyps, mucocutaneous pigmentations, and an increased risk of cancer, the syndrome has been subject to many studies concerning the natural course of disease. In most patients, pathogenic germline variants are detected in the STK11 gene including cases of mosaicism and structural variants. Yet, studies assessing the effect of surveillance, understanding of cancer development, as well as clinical studies evaluating chemoprevention are lacking. In addition, the impact of Peutz-Jeghers syndrome on mental health, education, and family planning are insufficiently addressed. In this progress report, we describe current knowledge, clinical phenotype, surveillance strategies, and future areas of research.

Familial adenomatous polyposis (FAP) is caused by pathogenic variants in the APC gene. FAP is usually categorized according to phenotype: classical FAP (CFAP) and attenuated FAP (AFAP); the latter is considered to have a milder disease course. We aimed to assess the risk of overall and specific cancers in patients with CFAP and AFAP compared with matched, nonexposed individuals.

All known Danish patients with FAP were classified as either CFAP or AFAP and assigned 4 matched, nonexposed individuals. The risk of overall and specific cancers, and mortality were analyzed.

The analysis included 311 patients with CFAP, 134 patients with AFAP, and 1,600 nonexposed individuals. The overall cancer risk was significantly higher for both patients with CFAP and AFAP than for nonexposed individuals, with hazard ratios (HRs) of 4.77 (95% confidence interval [CI], 3.61-6.32; P < 0.001) for CFAP and 3.22 (95% CI, 2.16-4.80; P < 0.001) for AFAP. No significant difference was observed when comparing CFAP and AFAP (HR = 1.48; 95% CI, 0.98-2.25; P = 0.0646). The HR of colonic cancer was 2.16 (95% CI, 0.99-7.72; P = 0.0522) and 2.72 (95% CI, 1.19-6.22; P = 0.0177 for CFAP and AFAP), respectively, compared with nonexposed and did not differ between patients with CFAP and AFAP (HR = 0.80; 95% CI, 0.32-2.00; P = 0.6278). Mortality was significantly higher in CFAP (HR = 2.96; 95% CI, 2.04-4.28; P < 0.001), but not in AFAP (HR = 1.40; 95% CI, 0.73-2.69; P = 0.311).

Nationwide data reveal differing risk profiles for specific cancers and mortality in AFAP and CFAP compared with nonexposed individuals. The cancer burden of AFAP necessitates consistent monitoring of these patients.

Peutz-Jeghers syndrome (PJS) is a rare hereditary disorder characterized by gastrointestinal hamartomatous polyps, due to mutation of the STK11/LKB1 gene located on chromosome 19p. The polyps are most commonly found in the small bowel followed by colon.

Our case series includes 4 patients, three being male and one female. Each of them either presented with abdominal pain and other associated symptoms. Oral cavity and lip melanin pigmentation were common. CT abdomen revealed multiple large jejunal, ileal, gastric and colon polyps. Cancer was found in one patient. Different surgical approaches were adopted. All recovered well.

PJS is an autosomal dominant disorder with an estimated incidence of 1:50,000 to 1:200,000 cases with a significant family history. Mostly found in small bowel followed by colon, it can also occur in a rare organ like gall bladder as evident in our case. PJS carries a substantial risk for gastrointestinal cancer. The treatment modality depends on the site of polyp, mode of presentation and availability of the expertise.

PJS is a common disease in our part which is usually observed in teen age groups male. They have a varied presentation, from intestinal obstruction (due to intussusception) to GI bleeding. Colonic malignancy at young age may be the first presentation of the disease. Observation of melanin pigmentations on lips helps diagnose the disease; and one should always look at this findings in a young patient with pain abdomen or in intestinal obstruction to confirm/exclude the disease.

Peutz-Jeghers syndrome (PJS) has brought significant physical, psychological and economic burdens on the patients and their families due to its early onset, diagnostic and therapeutic challenges and increased recurrence risk.

To explore the current research status and emerging hotspots of PJS.

Studies on PJS published during 1994-2023 were gathered based on Web of Science Core Collection. Additionally, a case of PJS-induced intestinal intussusception, successfully treated with endoscopic methods despite three laparotomies, was highlighted. Comprehensive bibliometric and visual analysis were conducted with VOSviewer, R and CiteSpace.

Altogether 1760 studies were identified, indicating a steady increase in the publication number. The United States had the highest influence, whereas the University of Helsinki emerged as the leading institution, and Aaltonen LA from the University of Helsinki was the most prolific author. Cancer Research, Oncogene and Endoscopy were the top three journals based on H-index. Keyword burst direction analysis revealed that "cancer risk", "management", "surveillance" and "familial pancreatic cancer" were the potential hotspots for investigation. Additionally, "early detection", "capsule endoscopy", "clinical management", "double-balloon endoscopy", "familial pancreatic cancer" and "molecular genetic basis" were identified as the key clusters of co-cited references. Endoscopic polypectomy remained effective on resolving intestinal intussusception in patients who underwent three previous laparotomies.

In the last three decades, global publications related to PJS show a steadily increasing trend in number. Endoscopic management is currently a research hotspot.

In this editorial, I commented on the paper by Lin et al, published in this issue of the World Journal of Gastrointestinal Oncology. The work aimed at analysing the clinicopathologic characteristics and prognosis of synchronous and metachronous cancers in patients with dual primary gastric and colorectal cancer (CRC). The authors concluded the necessity for regular surveillance for metachronous cancer during postoperative follow-up and reported the prognosis is influenced by the gastric cancer (GC) stage rather than the CRC stage. Although surveillance was recommended in the conclusion, the authors did not explore this area in their study and did not include tests used for such surveillance. This editorial focuses on the most characterized gastrointestinal cancer susceptibility syndromes concerning dual gastric and CRCs. These include hereditary diffuse GC, familial adenomatous polyposis, hereditary nonpolyposis colon cancer, Lynch syndrome, and three major hamartomatous polyposis syndromes associated with CRC and GC, namely Peutz-Jeghers syndrome, juvenile polyposis syndrome, and PTEN hamartoma syndrome. Careful assessment of these syndromes/conditions, including inheritance, risk of gastric and colorectal or other cancer development, genetic mutations and recommended genetic investigations, is crucial for optimum management of these patients.