中国小肠镜诊治Peutz-Jeghers综合征的专家共识意见(2022年)

黑斑-息肉综合征(Peutz-Jeghers syndrome, PJS)是一种常染色体显性遗传疾病, 以皮肤黏膜色素沉着、胃肠道多发错构瘤性息肉和肿瘤易感性为主要特征。小肠是PJS息肉好发部位之一, 易伴发肠套叠、肠梗阻、消化道出血、癌变等并发症。随着小肠内镜技术的迅速发展, 小肠镜已经成为PJS诊治的关键技术, 在小肠息肉诊断及治疗中发挥重要作用。近年来, 随着对PJS临床实践和认识的不断深入, 我国消化内镜医师对PJS诊治有了较为丰富的经验积累。为进一步促进小肠镜技术在该领域的推广应用, 有必要制定中国小肠镜诊治PJS的专家共识意见。本共识基于循证依据及专家经验对PJS的流行病学、遗传特征、临床表现、诊断标准、内镜治疗、外科手术、息肉监测及随访等方面进行梳理, 以便于指导专科医师、内镜医师加强对PJS患者全生命周期的规范诊治和管理, 从而更好地发挥小肠镜在PJS患者小肠息肉诊治中的作用。     

中国小肠镜诊治Peutz‑Jeghers综合征的专家共识意见（2022年）

黑斑-息肉综合征（Peutz?Jeghers syndrome,PJS）是一种常染色体显性遗传疾病,以皮肤黏膜色素沉着、胃肠道多发错构瘤性息肉和肿瘤易感性为主要特征。小肠是PJS息肉好发部位之一,易伴发肠套叠、肠梗阻、消化道出血、癌变等并发症。随着小肠内镜技术的迅速发展,小肠镜已经成为PJS诊治的关键技术,在小肠息肉诊断及治疗中发挥重要作用。近年来,随着对PJS临床实践和认识的不断深入,我国消化内镜医师对PJS诊治有了较为丰富的经验积累。为进一步促进小肠镜技术在该领域的推广应用,有必要制定中国小肠镜诊治PJS的专家共识意见。本共识基于循证依据及专家经验对PJS的流行病学、遗传特征、临床表现、诊断标准、内镜治疗、外科手术、息肉监测及随访等方面进行梳理,以便于指导专科医师、内镜医师加强对PJS患者全生命周期的规范诊治和管理,从而更好地发挥小肠镜在PJS患者小肠息肉诊治中的作用。     

Peutz-Jeghers综合征的诊治进展和预防性治疗

Peutz-Jeghers综合征(Peutz-Jeghers syndrome,PJS)以皮肤黏膜色素斑、胃肠道错构瘤息肉和遗传性为临床特征.PJS胃肠道息肉可产生梗阻、出血、套叠、恶变等严重并发症,目前其临床治疗以手术和内镜治疗为主,其中双气囊电子小肠镜对于PJS胃肠道息肉的诊断和治疗具有重要的临床意义.随着转化医学...     

Peutz-Jeghers综合征1例报道并浅析

探讨Peutz-Jeghers综合征(Peutz-Jeghers syndrome,PJS)的临床特点及诊治方法。回顾性分析长安医院收治的1例PJS患者临床资料。患者临床表现以腹痛、便血为主。行胶囊内镜检查发现全胃肠道多发息肉、回盲部占位及簇状息肉。最终行剖腹探查手术切除部分肠段明确诊断。PJS患者患恶性肿瘤风险增加,目前内镜下息肉切除及手术治疗仍为主要治疗方法。     

1例黑斑息肉综合征的诊断及治疗

目的 总结黑斑息肉综合征（PJS）的有效诊断及治疗方法,为该病的临床诊治提供参考。方法 对1例PJS患者的临床资料进行回顾性分析。结果 该患者为16岁男性,因“腹痛伴黏液血便2 d”入院。患者有典型口唇及鼻周黑斑,以肠套叠为主要首诊症状,接受急诊剖腹探查术并切除病变段结肠,病理提示错构瘤性息肉,基因检测证实存在丝/苏氨酸蛋白激酶（STK11）突变,本例患者排除阳性家族史。结论 皮肤黏膜黑斑、胃肠道多发性息肉及家族遗传史可诊断为PJS,定期内镜监测胃肠道息肉状况有助于减少该类患者急腹症的发生及降低息肉癌变风险,内镜下息肉切除和（或）外科手术切除为其有效治疗方法。     

Peutz-Jeghers综合征的研究进展

Peutz-Jeghers综合征（PIS）是一种常染色体显性遗传性疾病,伴有黏膜色素沉着和胃肠道错构瘤性息肉。PJS息肉可发生于整个胃肠道,但多发生于小肠。目前多认为PJS由位于染色体19p13.3的STKll基因突变所致。本文就PJS的致病基因、病理特征、临床诊治等方面的研究进展作一综述。     

黑斑息肉综合征6例临床分析

黑斑息肉综合征（PJS）是一种少见的家族性显性遗传病,以皮肤黏膜黑色素沉着、胃肠道多发性息肉和家族性遗传史为特征。1995年9月-2008年1月,我们收治6例PJS患者,现结合相关文献对其临床资料进行回顾性分析。     

Peutz-Jeghers综合征研究进展

Peutz-Jeghers综合征(Peutz-Jeghers syndrome,PJS)是一种以皮肤黏膜色素沉着、胃肠道多发息肉、家族遗传性为主要特征的常染色体显性遗传病,丝氨酸-苏氨酸激酶11/肝激酶B1(STK11/LKB1)基因突变被认为与该病的发生密切相关。PJS患者罹患肿瘤的风险较常人更高。目前针对PJS胃肠道息肉的治疗主要包括内镜及手术治疗。本文就近年来PJS的研究进展作一概述。     

Peutz-Jeghers综合征息肉的内镜下治疗及其病理特征分析

Peutz-Jeghers综合征(Peutz-Jeghers syndrome,PJS)是一种较少见的常染色体显性遗传病,本征具有皮肤、黏膜特定部位色素斑和胃肠道多发性息肉等特征性的临床表现.由于增加的癌症风险及众多的胃肠道并发症,本征受到越来越多的关注.但消化道肿瘤的发生是否由于错构瘤性息肉的癌变或伴发的腺瘤进展而来仍未明确,息肉的内镜下治疗风险及其特征亦需评估.本研究回顾性分析我院近10年来诊治的41例PJS患者资料,将对上述问题进一步探讨.     

Peutz-Jeghers综合征发病机制及临床诊治研究进展

Peutz-Jeghers综合征(peutz-jeghers syndrome, PJS)是一种常染色体显性遗传疾病,目前已被证实的致病基因为STK11.该病的特征性表现为皮肤黏膜色素斑、消化道多发错构瘤性息肉及肿瘤易感性.基于目前研究报道, STK11胚系突变可能通过干扰正常的细胞凋亡、细胞分裂G1期阻滞、细胞极化及细胞间质水平的细胞增殖抑制等导致了PJS消化道息肉及恶性肿瘤的发生.治疗消化道息肉及息肉相关并发症是干预该病的主要手段.近年来,气囊辅助小肠镜治疗PJS小肠息肉经验不断积累、安全性得到了充分认可,使得大部分患者避免了外科开腹手术,这对改善了患者生活质量及远期预后有重要意义.另外,针对PJS随年龄增长消化道息肉生长特点及显著增加消化道及非消化道恶性肿瘤风险,我们按照年龄阶段进行有差别有针对的随访策略.     

Laparoscopic restorative proctocolectomy with ileal pouch-anal anastomosis for Peutz-Jeghers syndrome with synchronous rectal cancer

We report on a patient diagnosed with PeutzJeghers syndrome(PJS) with synchronous rectal cancer who was treated with laparoscopic restorative proctocolectomy with ileal pouch-anal anastomosis(IPAA). PJS is an autosomal dominant syndrome characterized by multiple hamartomatous polyps in the gastrointestinal tract, mucocutaneous pigmentation, and increased risks of gastrointestinal and nongastrointestinal cancer. This report presents a patient with a 20-year history of intermittent bloody stool, mucocutaneous pigmentation and a family history of PJS, which together led to a diagnosis of PJS. Moreover, colonoscopy and biopsy revealed the presence of multiple serried giant pedunculated polyps and rectal adenocarcinoma. Currently, few options exist for the therapeutic management of PJS with synchronous rectal cancer. For this case, we adopted an unconventional surgical strategy and ultimately performed laparoscopic restorative proctocolectomy with IPAA. This procedure is widely considered to be the first-line treatment option for patients with ulcerative colitis or familial adenomatous polyposis. However, there are no previous reports of treating PJS patients with laparoscopic IPAA. Since the operation, the patient has experienced no further episodes of gastrointestinal bleeding and has demonstrated satisfactory bowel control. Laparoscopic restorative proctocolectomy with IPAA may be a safe and effective treatment for patients with PJS with synchronous rectal cancer.     

Suppression of Peutz-Jeghers polyposis by inhibition of cyclooxygenase-2

BACKGROUND & AIMS: Peutz-Jeghers syndrome (PJS) is typically manifested as severe gastrointestinal polyposis. Polyps in PJS patients and in Lkb1(+/-) mice that model PJS polyposis are frequently characterized by elevated cyclooxygenase-2 (COX-2). This study was designed to determine whether COX-2 inhibition would reduce tumor burden in Lkb1(+/-) mice or Peutz-Jeghers patients. METHODS: Genetic interactions between Cox-2 and Lkb1 in polyp formation were analyzed in mice with combined deficiencies in these genes. Pharmacologic inhibition of COX-2 was achieved by supplementing the diet of Lkb1(+/-) mice with 1500 ppm celecoxib between 3.5-10 and 6.5-10 months. In PJS patients, COX-2 was inhibited with a daily dose of 2 x 200 mg celecoxib for 6 months. RESULTS: Total polyp burden in Lkb1(+/-) mice was significantly reduced in a Cox-2(+/-) (53%) and in a Cox-2(-/-) (54%) background. Celecoxib treatment initiating before polyposis (3.5-10 months) led to a dramatic reduction in tumor burden (86%) and was associated with decreased vascularity of the polyps. Late treatment (6.5-10 months) also led to a significant reduction in large polyps. In a pilot clinical study, a subset of PJS patients (2/6) responded favorably to celecoxib with reduced gastric polyposis. CONCLUSIONS: These data establish a role for COX-2 in promoting Peutz-Jeghers polyposis and suggest that COX-2 chemoprevention may prove beneficial in the treatment of PJS.     

Peutz-Jeghers syndrome

Peutz-Jeghers syndrome (PJS) is an unusual polyposis syndrome that has enjoyed a rich and somewhat confusing history. Mucocutaneous pigmentation and diffuse gastrointestinal hamartomas are the hallmark features of this autosomal dominant inherited condition. Peutz-Jeghers syndrome is now also recognized as a cancer predisposition syndrome. In this review, we highlight the historical aspects of PJS polyposis with special emphasis on its extraintestinal manifestations, particularly genital tract tumors. A PJS management scheme for clinicians is included.     

Update on imaging of Peutz-Jeghers syndrome

Peutz-Jeghers syndrome (PJS) is a rare, autosomal dominant disease linked to a mutation of the STK 11 gene and is characterized by the development of benign hamartomatous polyps in the gastrointestinal tract in association with a hyperpigmentation on the lips and oral mucosa. Patients affected by PJS have an increased risk of developing gastrointestinal and extra-digestive cancer. Malignancy most commonly occurs in the small-bowel. Extra-intestinal malignancies are mostly breast cancer and gynecological tumors or, to a lesser extent, pancreatic cancer. These polyps are also at risk of acute gastrointestinal bleeding, intussusception and bowel obstruction. Recent guidelines recommend regular small-bowel surveillance to reduce these risks associated with PJS. Small-bowel surveillance allows for the detection of large polyps and the further referral of selected PJS patients for endoscopic enteroscopy or surgery. Video capsule endoscopy, double balloon pushed enteroscopy, multidetector computed tomography and magnetic resonance enteroclysis or enterography, all of which are relatively new techniques, have an important role in the management of patients suffering from PJS. This review illustrates the pathological, clinical and imaging features of small-bowel abnormalities as well as the role and performance of the most recent imaging modalities for the detection and follow-up of PJS patients.     

Hereditary colorectal cancer]

Hereditary syndromes cause approximately 5 to 15% of overall colorectal cancer (CRC) cases. Hereditary CRC is conventionally divided into two major categories: hereditary non-polyposis colorectal cancer (HNPCC) and those related to polyposis syndromes including familial adenomatous polyposis (FAP), Peutz-Jegher syndrome (PJS), and juvenile polyposis (JP). The screening for the cancer and methods of treatment applied to patients with hereditary CRC are quite different from those applied to the general population. The genes responsible for these syndromes has recently identified, as a result, genetic testing has become the most important determining factor in clinical decisions. Germ-line mutation of the APC gene induces FAP, an autosomal dominant disorder, characterized by the development of hundreds to thousands of colonic adenomas. CRC appears in almost all affected individuals by the time they are 50 years of age. An affected individual should undergo colectomy by his/her late teens. Furthermore, according to the findings of genetic testing, at-risk family members also need endoscopic surveillance and surgery. Recently, a mutation on the MYH gene is increasingly being investigated in patients with multiple polyps, and autosomal recessive MYH polyposis is considered to be a new category of polyposis. More common than FAP, HNPCC is caused by germ-line mutations in DNA mismatch repair genes, mainly MLH1 and MSH2. Although there is no polyposis, polyps seem to be more villous and dysplastic and appear to grow rapidly into CRCs. The aggregate lifetime risk of CRC is about 80% for mutation carriers. The risk for other types of cancer, such as endometrial, ovarian, small bowel, and transitional cell cancer, is also increased. The Amsterdam criteria and Bethesda guidelines are the best-known tools for diagnosis and genetic testing, and colectomy followed by endoscopic follow-up is the standard treatment. PJS and JP are reported to be characterized by hamartomatous polyps throughout the GI tract and germ-line mutations in the STK11 gene (PJS) and the DPC4/BMPR1A gene (JP).     

Molecular insights into Peutz-Jeghers syndrome: two probands with a germline mutation of <Emphasis Type="Italic">LKB1</Emphasis>

LKB1 encodes a serine/threonine protein kinase that is defective in patients with Peutz-Jeghers syndrome (PJS), a hereditary disorder characterized by gastrointestinal hamartomatous polyposis and an increased risk of cancer development. Although a tentative molecular classification of PJS patients was recently made according to their LKB1 mutation status, it is difficult to clarify the genotype-phenotype relationship because of the rarity and genetic heterogeneity of this disease. Here we report on two probands with PJS whose intestinal hamartomatous polyposis was treated by laparoscopyassisted polypectomy. Direct sequencing analyses revealed a nonsense mutation at codon 240 in exon 5 in one patient, and a mutation at a splicing donor site in intron 5 in the other patient. No additional somatic mutations were detected in the resected hamartomas in either case. Immunohistochemical analysis revealed an elevated expression of cyclooxygenase-2, and almost complete loss of LKB1 expression in the polyps, suggesting that a biallelic inactivation of the LKB1 gene was responsible for the hamartoma formation. Methylation-specific polymerase chain reaction analysis revealed no hypermethylation of the LKB1 promoter. Mutation analysis is useful in making a precise diagnosis of PJS in candidate probands, and may in the near future provide valuable information for predicting cancer risk based on genotype-phenotype correlations.     

Mucosal prolapse in the pathogenesis of Peutz-Jeghers polyposis

Germline mutations in LKB1 cause the rare cancer prone disorder Peutz-Jeghers syndrome (PJS). Gastrointestinal hamartomatous polyps constitute the major phenotypic trait in PJS. Hamartomatous polyps arising in PJS patients are generally considered to lack premalignant potential although rare neoplastic changes in these polyps and an increased gastrointestinal cancer risk in PJS are well documented. These conflicting observations are resolved in the current hypothesis by providing a unifying explanation for these contrasting features of PJS polyposis. We postulate that a genetic predisposition to epithelial prolapse underlies the formation of the polyps associated with PJS. Conventional sporadic adenomas arising in PJS patients will similarly show mucosal prolapse and carry the associated histological features.     

A De Novo Mutation of <Emphasis Type="Italic">STK11</Emphasis> Gene in a Chinese Patient with Peutz–Jeghers Syndrome

Peutz–Jeghers syndrome (PJS) is an autosomal-dominant inherited disorder characterized by mucocutaneous pigmentation, hamartomatous polyposis of the gastrointestinal tract, and an increased risk for the development of both gastrointestinal and extraintestinal malignancies. Germline mutation of the STK11 gene, which encodes a serine-threonine kinase, is responsible for PJS. We collected blood samples from a Chinese PJS family consisting of a total of four individuals (one male and three females) including one PJS patient. The whole coding region of STK11 was amplified by polymerase chain reaction and products analyzed by direct sequencing. Molecular analysis of the STK11 gene in this case of PJS revealed a substitution of thymine 217 for adenine (C.217T > A) in exon 1, resulting in a change of codon 73 from cysteine to serine (C73S). The point mutation was not found in normal individuals in this PJS family or in 100 control individuals. The results presented here enlarge the spectrum of mutations of the STK11 gene by identifying a de novo mutation in a PJS patient and further support the hypothesis that STK11 mutations are disease-causing mutations for PJS.