Two missense STK11 gene variations impaired LKB1/adenosine monophosphate-activated protein kinase signaling in Peutz-Jeghers syndrome

BACKGROUND Peutz-Jeghers syndrome(PJS)is a rare hereditary neoplastic disorder mainly associated with serine/threonine kinase 11(STK11/LKB1)gene mutations.Preimplantation genetic testing can protect a patient’s offspring from mutated genes;however,some variations in this gene have been interpreted as variants of uncertain significance(VUS),which complicate reproductive decision-making in genetic counseling.AIM To identify the pathogenicity of two missense variants and provide clinical guidance.METHODS Whole exome gene sequencing and Sanger sequencing were performed on the peripheral blood of patients with PJS treated at the Reproductive and Genetic Hospital of Citic-Xiangya.Software was employed to predict the protein structure,conservation,and pathogenicity of the two missense variation sites in patients with PJS.Additionally,plasmids were constructed and transfected into HeLa cells to observe cell growth.The differences in signal pathway expression between the variant group and the wild-type group were compared using western blot and immunohistochemistry.Statistical analysis was performed using one-way analysis of variance.P<0.05 was considered statistically significant.RESULTS We identified two missense STK11 gene VUS[c.889A>G(p.Arg297Gly)and c.733C>T(p.Leu245Phe)]in 9 unrelated PJS families who were seeking reproductive assistance.The two missense VUS were located in the catalytic domain of serine/threonine kinase,which is a key structure of the liver kinase B1(LKB1)protein.In vitro experiments showed that the phosphorylation levels of adenosine monophosphate-activated protein kinase(AMPK)at Thr172 and LKB1 at Ser428 were significantly higher in transfected variation-type cells than in wild-type cells.In addition,the two missense STK11 variants promoted the proliferation of HeLa cells.Subsequent immunohistochemical analysis showed that phosphorylated-AMPK(Thr172)expression was significantly lower in gastric,colonic,and uterine polyps from PJS patients with missense variations than in non-PJS patients.Our findings indicate that these two missense STK11 variants are likely pathogenic and inactivate the STK11 gene,causing it to lose its function of regulating downstream phosphorylated-AMPK(Thr172),which may lead to the development of PJS.The identification of the pathogenic mutations in these two clinically characterized PJS patients has been helpful in guiding them toward the most appropriate mode of pregnancy assistance.CONCLUSION These two missense variants can be interpreted as likely pathogenic variants that mediated the onset of PJS in the two patients.These findings not only offer insights for clinical decision-making,but also serve as a foundation for further research and reanalysis of missense VUS in rare diseases.

Gynecological tumors in patients with Peutz-Jeghers syndrome (PJS)

Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by the development of hamartomatous polyposis in the gastrointestinal tract and melanin-pigmented macules on the skin mucosa. The responsible gene is a tumor suppressor, STK11/LKB1, on chromosome 19p13.3. PJS complicates with benign and malignant tumors in various organs. In gynecology, there has been a particular focus on complications of PJS with sex cord tumor with annular tubules (SCTAT) and minimal deviation adenocarcinoma (MDA), which are rare diseases. Approximately 36% of patients with SCTAT are complicated with PJS and these patients are characterized by multifocal, bilateral, small and benign lesions that develop into tumors with mucinous to serous ratios of 8:1. In addition, 10% of cases of MDA are complicated with PJS and mutation of STK11, the gene responsible for PJS, has a major effect on onset and prognosis. The disease concept of lobular endocervical glandular hyper-plasia (LEGH) has recently been proposed and LEGH is thought to be a potential premalignant lesion of MDA, however, the relationship between PJS and LEGH remains unclear. Several case reports of PJS patients complicated with gynecological tumors have been published and further studies are needed to determine the underlying

Clinical features,diagnosis,and treatment of Peutz-Jeghers syndrome:Experience with 566 Chinese cases

BACKGROUND Peutz-Jeghers syndrome(PJS)is a clinically rare disease with pigmented spots on the lips and mucous membranes and extremities,scattered gastrointestinal polyps,and susceptibility to tumors as clinical manifestations.Effective preventive and curative methods are still lacking.Here we summarize our experience with 566 Chinese patients with PJS from a Chinese medical center with regard to the clinical features,diagnosis,and treatment.AIM To explore the clinical features,diagnosis,and treatment of PJS in a Chinese medical center.METHODS The diagnosis and treatment information of 566 cases of PJS admitted to the Air Force Medical Center from January 1994 to October 2022 was summarized.A clinical database was established covering age,gender,ethnicity,family history,age at first treatment,time and sequence of appearance of mucocutaneous pigmentation,polyp distribution,quantity,and diameter,frequency of hospitalization,fre-quency of surgical operations,etc.The clinical data was retrospectively analyzed using SPSS 26.0 software,with P<0.05 considered statistically significant.RESULTS Of all the patients included,55.3%were male and 44.7%were female.Median time to the appearance of mucocutaneous pigmentation was 2 years,and median time from the appearance of mucocutaneous pigmentation to the occurrence of abdominal symptoms was 10 years.The vast majority(92.2%)of patients underwent small bowel endoscopy and treatment,with 2.3%having serious complications.There was a statistically significant difference in the number of enteroscopies between patients with and without canceration(P=0.004,Z=-2.882);71.2%of patients underwent surgical operation,75.6%of patients underwent surgical operation before the age of 35 years,and there was a statistically significant difference in the frequency of surgical operations between patients with and without cancer(P=0.000,Z=-5.127).At 40 years of age,the cumulative risk of intussusception in PJS was approximately 72.0%,and at 50 years,the cumulative risk of intussusception in PJS was approximately 89.6%.At 50 years of age,the cumulative risk of cancer in PJS was approximately 49.3%,and at 60 years of age,the cumulative risk of cancer in PJS was approximately 71.7%.CONCLUSION The risk of intussusception and cancer of PJS polyps increases with age.PJS patients≥10 years old should undergo annual enteroscopy.Endoscopic treatment has a good safety profile and can reduce the occurrence of polyps intussusception and cancer.Surgery should be conducted to protect the gastrointestinal system by removing polyps.

Peutz-Jeghers syndrome without STK11 mutation may correlate with less severe clinical manifestations in Chinese patients

BACKGROUND Peutz-Jeghers syndrome(PJS) is an autosomal dominant genetic disease with skin mucosal pigment spots and gastrointestinal(GI) multiple hamartoma polyps as clinical characteristics. At present, it is considered that the germline mutation of STK11 gene is the genetic cause of PJS. However, not all PJS patients can be detected STK11 germline mutations. The specific clinical characteristics of these PJS patients without STK11 mutation is an interesting clinical question. Or, like wild type GI stromal tumor, whether these PJS without STK11 mutation are also called PJS is worth discussing. Therefore, we designed the study to understand the clinical characteristics of these PJS patients without STK11 mutation.AIM To investigates whether PJS patients with known STK11 mutations have a more severe spectrum of clinical phenotypes compared to those without.METHODS A total of 92 patients with PJS admitted to the Air Force Medical Center from 2010 to 2022 were randomly selected for study. Genomic DNA samples were extracted from peripheral blood samples, and pathogenic germline mutations of STK11 were detected by high-throughput next-generation gene sequencing. Clinicalpathologic manifestations of patients with and without STK11/LKB1 mutations were compared.RESULTS STK11 germline mutations were observed in 73 patients with PJS. Among 19 patients with no detectable STK11 mutations, six had no pathogenic germline mutations of other genes, while 13 had other genetic mutations. Compared with PJS patients with STK11 mutations, those without tended to be older at the age of initial treatment, age of first intussusception and age of initial surgery. They also had a lower number of total hospitalizations relating to intussusception or intestinal obstruction, and a lower load of small intestine polyps.CONCLUSION PJS patients without STK11 mutations might have less severe clinical-pathologic manifestations than those with.

Immunotherapy in combination with chemotherapy for Peutz-Jeghers syndrome with advanced cervical cancer:A case report

BACKGROUND Peutz-Jeghers syndrome(PJS)is a rare autosomal dominant disorder,and female patients may develop gynecologic tumours.The prognosis for such patients is poor and the specific pathogenesis remains uncertain.Therefore,there are currently no uniform treatment options.CASE SUMMARY Herein,we introduce the case of a 45-year-old female who was diagnosed with PJS for 45 years and cervical cancer for 3 years.Postoperative pathological examination showed metastases in the right external iliac lymph nodes.The patient was initially treated with a combination of doxorubicin and carboplatin chemotherapy and pelvic magnetic resonance showed that the metastases had grown.Subsequently,we performed whole exome sequencing in this patient and identified the relevant causative gene.In addition to the chemotherapy regimen,sindilizumab was administered and the patient was followed up.After 4 cycles of treatment,the metastases were substantially reduced and were not enlarged after six months of follow-up.This case report suggests that patients with PJS combined with cervical cancer may have a sustained response to immunecombination chemotherapy regimens.CONCLUSION Clinicians should be aware of the importance of immunotherapy in patients with PJS combined with advanced cervical cancer.

Clinical features, endoscopic polypectomy and STK11 gene mutation in a nine-month-old Peutz-Jeghers syndrome Chinese infant

AIM: To investigate multiple polyps in a Chinese PeutzJeghers syndrome(PJS) infant. METHODS: A nine-month-old PJS infant was admitted to our hospital for recurrent prolapsed rectal polyps for one month. The clinical characteristics, a colonoscopic image, the pathological characteristics of the polyps and X-ray images of the intestinal perforation were obtained. Serine threonine-protein kinase 11(STK11) gene analysis was also performed using a DNA sample from this infant.RESULTS: Here we describe the youngest known Chinese infant with PJS. Five polyps, including a giant polyp of approximately 4 cm × 2 cm in size, were removed from the infant's intestine. Laparotomy was performed to repair a perforation caused by pneumoperitoneum. The pathological results showed that this child had PJS. Molecular analysis of the STK11 gene further revealed a novel frameshift mutation(c.64_65het_del AT) in exon 1 in this PJS infant.CONCLUSION: The appropriate treatment method for multiple polyps in an infant must be carefully considered. Our results also show that the STK11 gene mutation is the primary cause of PJS.

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 smallbowel. 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 smallbowel 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.

Must Peutz-Jeghers syndrome patients have the LKB1/STK11 gene mutation?A case report and review of the literature

Peutz-Jeghers syndrome(PJS) is an autosomal dominant inherited disease, which is characterized by mucocutaneous pigmentation and multiple gastrointestinal hamartoma polyps. The germline mutation of LKB1/STK11 gene on chromosome 19 p13.3 is considered to be the hereditary cause of PJS. However, must a patient with PJS have the LKB1/STK11 gene mutation? We here report a case of a male patient who had typical manifestations of PJS and a definite family history, but did not have LKB1/STK11 gene mutation. By means of high-throughput sequencing technology, only mutations in APC gene(c.6662 T > C: p.Met2221 Thr) and MSH6 gene(c.3488 A > T: p.Glu1163 Val) were detected. The missense mutations in APC and MSH6 gene may lead to abnormalities in structure and function of their expression products, and may result in the occurrence of PJS. This study suggests that some other genetic disorders may cause PJS besides LKB1/STK11 gene mutation.

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.

Detection and analysis of common pathogenic germline mutations in Peutz-Jeghers syndrome

Different types of pathogenic mutations may produce different clinical phenotypes,but a correlation between Peutz-Jeghers syndrome(PJS)genotype and clinical phenotype has not been found.Not all patients with PJS have detectable mutations of the STK11/LKB1 gene,what is the genetic basis of clinical phenotypic heterogeneity of PJS?Do PJS cases without STK11/LKB1 mutations have other pathogenic genes?Those are clinical problems that perplex doctors.AIM The aim was to investigate the specific gene mutation of PJS,and the correlation between the genotype and clinical phenotype of PJS.METHODS A total of 24 patients with PJS admitted to the Air Force Medical Center,PLA(formerly the Air Force General Hospital,PLA)from November 1994 to January 2020 were randomly selected for inclusion in the study.One hundred thirty-nine common hereditary tumor-related genes including STK11/LKB1 were screened and analyzed for pathogenic germline mutations by high-throughput nextgeneration sequencing(NGS).The mutation status of the genes and their relationship with clinical phenotypes of PJS were explored.RESULTS Twenty of the 24 PJS patients in this group(83.3%)had STK11/LKB1 gene mutations,90%of which were pathogenic mutations,and ten had new mutation sites.Pathogenic mutations in exon 7 of STK11/LKB1 gene were significantly lower than in other exons.Truncation mutations are more common in exons 1 and 4 of STK11/LKB1,and their pathogenicity was significantly higher than that of missense mutations.We also found SLX4 gene mutations in PJS patients.CONCLUSION PJS has a relatively complicated genetic background.Changes in the sites responsible for coding functional proteins in exon 1 and exon 4 of STK11/LKB1 may be one of the main causes of PJS.Mutation of the SLX4 gene may be a cause of genetic heterogeneity in PJS.

Mutation analysis of related genes in hamartoma polyp tissue of Peutz-Jeghers syndrome

BACKGROUND Peutz-Jeghers syndrome(PJS)is a rare disease with clinical manifestations of pigmented spots on the lips,mucous membranes and extremities,scattered gastrointestinal polyps,and susceptibility to tumors.The clinical heterogeneity of PJS is obvious,and the relationship between clinical phenotype and genotype is still unclear.AIM To investigate the mutation status of hereditary colorectal tumor-associated genes in hamartoma polyp tissue of PJS patients and discuss its relationship with the clinicopathological data of PJS.METHODS Twenty patients with PJS were randomly selected for this study and were treated in the Air Force Medical Center(former Air Force General Hospital)PLA between 2008 and 2017.Their hamartoma polyp tissues were used for APC,AXIN2,BMPR1A,EPCAM,MLH1,MLH3,MSH2,MSH6,MUTYH,PMS1,PMS2,PTEN,SMAD4,and LKB1/STK11 gene sequencing using next-generation sequencing technology.The correlations between the sequencing results and clinical pathological data of PJS were analyzed.RESULTS Fourteen types of LKB1/STK11 mutations were detected in 16 cases(80.0%),of which 8 new mutations were found(3 types of frameshift deletion mutations:c.243delG,c.363_364delGA,and c.722delC;2 types of frameshift insertions:c.144_145insGCAAG,and c.454_455insC;3 types of splice site mutations:c.464+1G>T,c.464+1G>A,and c.598-1G>A);9 cases(45.0%)were found to have 18 types of heterozygous mutations in the remaining 13 genes except LKB1/STK11.Of these,MSH2:c.792+1G>A,MSH6:c.3689C>G,c.4001+13C>CTTAC,PMS1:c.46C>t,and c.922G>A were new mutations.CONCLUSION The genetic mutations in hamartoma polyp tissue of PJS are complex and diverse.Moreover,other gene mutations in PJS hamartoma polyp tissue were observed,with the exception of LKB1/STK11 gene,especially the DNA mismatch repair gene(MMR).Colorectal hamartoma polyps with LKB1/STK11 mutations were larger in diameter than those with other gene mutations.

Peutz-Jeghers syndrome with mesenteric fibromatosis: A case report and review of literature

BACKGROUND Peutz-Jeghers syndrome(PJS) and mesenteric fibromatosis(MF) are rare diseases,and PJS accompanying MF has not been previously reported. Here, we report a case of a 36-year-old man with both PJS and MF, who underwent total colectomy and MF surgical excision without regular follow-up. Two years later, he sought treatment for recurrent acute abdominal pain. Emergency computed tomography showed multiple soft tissue masses in the abdominal and pelvic cavity, and adhesions in the small bowel and peritoneum. Partial intestinal resection and excision of the recurrent MF were performed to relieve the symptoms.CASE SUMMARY A 36-year-old male patient underwent total colectomy for PJS with MF. No regular reexamination was performed after the operation. Two years later, due to intestinal obstruction caused by MF enveloping part of the small intestine and peritoneum, the patient came to our hospital for treatment. Extensive recurrence was observed in the abdomen and pelvic cavity. The MF had invaded the small intestine and could not be relieved intraoperatively. Finally, partial bowel resection, proximal stoma, and intravenous nutrition were performed to maintain life.CONCLUSION Regular detection is the primary way to prevent deterioration from PJS. Although MF is a benign tumor, it has characteristics of invasive growth and ready recurrence. Therefore, close follow-up of both the history of MF and gastrointestinal surgery are advisable. Early detection and early treatment are the main means of improving patient prognosis.

Malignant tumors associated with Peutz-Jeghers syndrome: Five cases from a single surgical unit

BACKGROUND Peutz-Jeghers syndrome(PJS) is an autosomal dominant inherited disease easily causing secondary malignant changes without effective treatments.AIM To assess the clinical characteristics, diagnosis, and treatment of malignant changes secondary to PJS.METHODS The clinical data of five patients with malignant changes secondary to PJS diagnosed and treated at Beijing Friendship Hospital from June 2014 to January 2017 were retrospectively analyzed;the follow-up ended in May 2018.RESULTS There were three male and two female patients with an average age of 43.6 years.Intestinal obstruction, intussusception, and abdominal pain were the first symptoms. Computed tomography and gastrointestinal imaging combined with endoscopy helped evaluate the depth of tumor infiltration and determine the need for radical resection. Three patients underwent surgery. Postoperative pathology confirmed adenocarcinoma, genetic test indicated STK11 mutation,and the patients received chemotherapy, including one who succumbed to tumor progression 6 months post-surgery. Other two patients underwent endoscopic resection, and postoperative pathology confirmed high grade intraepithelial neoplasia. The surviving patients had no recurrence by May 2018.CONCLUSION Endoscopy combined with computed tomography and gastrointestinal imaging is of great significance in the diagnosis and treatment of PJS, and pathological examination and gene detection are the gold standards for detecting malignant changes secondary to PJS. Some malignant polyps can be removed under endoscopy, and surgery is feasible when malignant polyps cannot be remove dunder an endoscope. For patients unable to achieve R0 resection, clinical symptoms should be relieved, and postoperative adjuvant chemotherapy could improve long-term prognosis. Meanwhile, close and regular surveillance should be conducted to prevent severe complications.

Double intussusception in a teenage child with Peutz-Jeghers syndrome:A case report

BACKGROUND Peutz-Jeghers syndrome(PJS)is a genetic disorder characterized by the development of gastrointestinal hamartomatous polyps and mucocutaneous melanin pigmentation.Patients with PJS are at risk of complications such as intussusception.Intussusception is a condition where one segment of the intestine invaginates into another,causing intestinal obstruction.We report a PJS patient who was diagnosed with double intussusception in a single setting.CASE SUMMARY A 16-year-old teenage male PJS patient presented with a history of colicky abdominal pain,vomiting,blood in stools,loss of appetite,and weight loss.On abdominal examination,a vague mass was palpable over the right upper quadrant.Contrast-enhanced computed tomography(CT)of the abdomen was performed and an intussusception involving the jejunum and rectosigmoid junction was observed.The patient subsequently underwent a laparotomy and intussusception involving the jejunum and another over the ileum was noted intra-operatively.Bowel resection and an endoscopic polypectomy were performed,followed by a primary anastomosis.The patient was discharged well and reviewed again one month later,and was noted to be well.CONCLUSION PJS patients have a high risk of intussusception and can be diagnosed accurately by endoscopic surveillance or radiologically with abdominal CT or magnetic resonance imaging.The mainstay of treatment is surgical intervention followed by endoscopic surveillance with periodic polypectomy.

Adult Intussusception in Patients with Peutz-Jeghers Syndrome: Case Series and Review of Literature

Background: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder characterized by gastrointestinal hamartomatous polyps and mucocutaneous pigmentations in the mouth, facial skin, hands & feet. Small bowel obstruction, intussusception, bleeding, intestinal and extra-intestinal malignancies are the major complications of PJS. The aim of this study is to analyze the clinical characteristics, preoperative diagnosis, and surgical management of PJS associated-intussusception in adults. Patients and Methods: This study included 5 cases with intussusception in PJS patients presented to Surgical Oncology Unit, General Surgery Department, Tanta University Hospital, Egypt and Hamad General Hospital, Hamad Medical Corporation, Qatar, between October 2011 and March 2016. Patients’ demographics were collected. After thorough clinical examination, abdominal X-ray, US, & CT scan were done. All the patients were submitted to midline laparotomy with resection anastomosis of the affected bowel segment. Results: The mean age was 28.4 years. Female: male ratio was 3:2. Abdominal pain was the most common presenting complaint with or without intestinal obstruction manifestations. Palpable abdominal mass was found in 3 patients (60%). Intussusception was proved pre-operatively in all the cases by abdominal ultrasound and CT scan. The intussusception was found in the jejunum in 3 patients, ileum in 1 patient, & in 1 patient, there was double intussusception (one jejunal & one ileo-cecal). Histopathological examination revealed the presence of typical Peutz-Jeghers hamartomatous polyp. No morbidity or mortality was reported at a mean follow-up period of 32 months. Conclusion: Family history, physical examination, abdominal ultrasound and CT scan were important in the diagnosis of acute intussusception caused by PJS. Surgical management of PJS associated intussusception is the recommended treatment to relieve patient’s symptoms and to avoid missing underlying malignancy. Patients with PJS should be followed up throughout their lives because of the increased risk of malignant changes.

A case of labial lentigines in Peutz-Jeghers syndrome treated using a Q-switched alexandrite laser

Peutz-Jeghers syndrome(PJS)is a polygenic autosomal dominant disease characterized by multiple gastrointestinal polyps and pigmentation of the mucosa and skin.While there are a few reports regarding successful treatment of intestinal polyps in PJS,there is little research regarding treatment of mucocutaneous melanosis.This study investigated the many advantages of using a Q-switched alexandrite laser to treat mucocutaneous melanosis.In this case,a 19-year-old male with PJS presented with labial lentigines and received two Q-switched alexandrite laser treatments in 2018.Subsequently,the efficacy of the treatment was evaluated.The result of the evaluation was that,after the two laser treatments,the labial lentigines were successfully removed,and there were no complications.

Peutz-Jeghers综合征的临床病理特点、诊断及鉴别诊断(附18例分析)

目的 总结Peutz-Jeghers综合征(PJs)的临床病理特点、诊断及鉴别诊断方法。方法 回顾性分析18例PJs患者的临床病理资料。结果 18例患者均查见多发消化道息肉,15例有不同程度的皮肤黏膜色素斑,5例有明确的家族史。18例均有诊断明确的PJ息肉,9例伴有假浸润,3例假浸润腺体形成黏液性囊肿;18例中有4例伴发腺瘤,3例伴发恶性肿瘤(2例为息肉恶变,1例合并甲状腺癌)。18例均符合PJs。PJ息肉中假浸润的腺体呈小叶状,无异型性及间质反应,P53、Ki67表达于小叶状腺体的周边,黏液囊肿内的上皮细胞无异型性,结合临床特点,可以与普通浸润性腺癌、黏液腺癌及其他类型的错构瘤性息肉病鉴别。结论 PJs以皮肤黏膜色素斑、多发胃肠道息肉和家族遗传为特点,PJ息肉典型的组织学特点是树枝状增生的平滑肌束,表面被覆黏膜组织形成小叶状结构;典型的组织学特点结合明确的临床特点(皮肤黏膜色素斑、家族史)即可作出PJs的诊断;典型的PJs临床、病理特点有助于和浸润性腺癌及其他类型的错构瘤性息肉病进行鉴别。

Hereditary polyposis syndromes remain a challenging disease entity:Old dilemmas and new insights

In this editorial we present an overview and insights of the management of hereditary polyposis syndromes.The primary focus was on familial adenomatous polyposis,juvenile polyposis syndrome and Peutz-Jegher syndrome.Genetic testing has become increasingly available and is easier than ever to integrate into clinical practice.Furthermore,several genes have been added to the expanding list of genes associated with hereditary polyposis syndromes,allowing for precise diagnostics and tailored follow-up.Endoscopic evaluation of patients with hereditary polyposis syndromes is paramount in the surveillance strategies.Current endoscopic procedures include both diagnostic procedures and surveillance as well as therapeutic interventions.Recommendations for endoscopic procedures in the upper and lower gastrointestinal canal were described.Surgery is still a key component in the management of patients with hereditary polyposis syndromes.The increased cancer risk in these patients often render prophylactic procedures or intended curative procedures in the case of cancer development.Surgical interventions in the upper and lower gastrointestinal canal were described with relevant considerations.Development of chemopreventive medications is ongoing.Few drugs have been investigated,including nonsteroidal anti-inflammatory drugs.It has been demonstrated that cyclooxygenase-2 inhibitors may lower the number of polyps.Other medications are currently under investigation,but none have,to date,consistently been able to prevent development of disease.

注水小肠镜下黏膜切除术治疗Peutz-Jeghers综合征息肉的临床应用

目的探讨注水小肠镜下治疗Peutz-Jeghers综合征(PJS)肠道息肉的有效性及安全性。方法选取2021年4月至2022年10月空军特色医学中心由一名特定医师完成的小肠镜下治疗PJS息肉的患者为研究对象,将患者分为注水小肠镜组和普通注气小肠镜组,对两组患者年龄、性别、肠道息肉切除情况、术中术后并发症、住院天数及住院费用等进行比较。结果共84例PJS患者纳入分析,注水小肠镜组49例患者,普通注气小肠镜组35例患者。两组患者在年龄、性别、切除息肉情况、住院天数及住院费用方面均没有统计学差异。注水组小肠镜治疗术中及术后总并发症发生率明显低于注气组,差异有统计学意义(0%vs 20%,P=0.001)。结论注水法小肠镜可降低Peutz-Jeghers综合征肠道息肉治疗并发症的发生,值得临床应用及推广。

Effect of Accessory Pathway Conduction on PJ Interval in Wolff-Parkinson-White Syndrome

Objective To observe the effect of accessory pathway (AP) conduction on PJ interval in patients with Wolff-Parkinson-White syndrome. Methods 129 patients with a single manifestation of AP who underwent successful radiofrequency ablation (RFCA) were included. Patients were divided into 10 groups according to AP location. The PR intervals, QRS durations and the PJ intervals were measured using simultaneous 12-lead ECG before and after ablation. The PJ intervals before ablation were compared with that after ablation. The atrioventricular (AV) conduction time via atrioventricular node-His conduction system before ablation were compared with the PR intervals after ablation. The ventricular depolarization time via atrioventricular node-His conduction system before ablation were compared with the QRS durations after ablation. Delta waves were compared between each two groups. Results (1) The PJ intervals of right posterior (RP) group and right posteroseptal (RPS) group before ablation were shorter than that after ablation (RP group 226±18 ms vs 236±19 ms, P<0.01, RPS group 221±18 ms vs 238±31 ms, P<0.05, respectively). (2) There were no significant differences between the atrioventricular (AV) conduction time via atrioventricular node-His conduction system before ablation and the PR intervals after ablation. (3)The ventricular depolarization time via atrioventricular node-His conduction system of RP group and RPS group before ablation were shorter than the PR intervals after ablation(RP group 79±12 ms vs 87±9 ms, P=0.01; RPS group 70±13 ms vs 86±9 ms, P<0.05, respectively). (4)The delta waves of RP group and RPS group were longer than that of left posterior group and left posteroseptal group(P<0.05). Conclusion PJ interval is shortened by AP conduction which pre-excites the general last excited part of left ventricle. It is determined by AP location and the extent of preexcitation.