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 offsp...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.展开更多
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 manif...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.展开更多
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 conside...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.展开更多
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.T...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.展开更多
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 ...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.展开更多
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 ...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.展开更多
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 trea...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.展开更多
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 complicatio...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.展开更多
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 treatme...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.展开更多
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 c...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.展开更多
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 associa...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.展开更多
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 ...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.展开更多
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 autosoma...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.展开更多
We report a case of 30-year-old woman with Peutz- Jeghers syndrome (PJS). Because of small intestinal obstruction, she received the small intestinal polypectomy in 2001, and the pathological diagnosis was Peutz-Jegher...We report a case of 30-year-old woman with Peutz- Jeghers syndrome (PJS). Because of small intestinal obstruction, she received the small intestinal polypectomy in 2001, and the pathological diagnosis was Peutz-Jeghers polyp canceration (mucinous adenocarcinoma, infiltrating full-thickness of the intestine). The patient did not feel uncomfortable after 6 mo of chemotherapy and other management. We kept a follow-up study on her and found that she suffered from cervical cancer in 2007, with a pathological diagnosis of cervical adenosquamous carcinoma.The patient presented with typical features of PJS, but without a family history. The PJS accompanied with both small intestinal and cervical malignancies has not been reported so far in the world.展开更多
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 responsibl...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展开更多
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 c...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.展开更多
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 ...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.展开更多
Peutz-Jeghers syndrome(PJS)is an inherited,autosomal dominant disorder distinguished by hamartomatous polyps in the gastrointestinal tract and pigmented mucocutaneous lesions.Prevalence of PJS is estimated from 1 in 8...Peutz-Jeghers syndrome(PJS)is an inherited,autosomal dominant disorder distinguished by hamartomatous polyps in the gastrointestinal tract and pigmented mucocutaneous lesions.Prevalence of PJS is estimated from 1 in 8300 to 1 in 280 000 individuals.PJS predisposes sufferers to various malignancies(gastrointestinal,pancreatic,lung,breast,uterine,ovarian and testicular tumors).Bleeding,obstruction and intussusception are common complications in patients with PJS.Double balloon enteroscopy(DBE)allows examination and treatment of the small bowel.Polypectomy using DBE may obviate the need for repeated urgent operations and small bowel resection that leads to short bowel syndrome.Prophylaxis and polypectomy of the entire small bowel is the gold standard in PJS patients.Intraoperative enteroscopy(IOE)was the only possibility for endoscopic treatment of patients with PJS before the DBE era.Both DBE and IOE facilitate exploration and treatment of the small intestine. DBE is less invasive and more convenient for the pa- tient.Both procedures are generally safe and useful. An overall recommendation for PJS patients includes not only gastrointestinal multiple polyp resolution,but also regular lifelong cancer screening(colonoscopy, upper endoscopy,computed tomography,magnetic resonance imaging or ultrasound of the pancreas, chest X-ray,mammography and pelvic examinationwith ultrasound in women,and testicular examination in men).Although the incidence of PJS is low,it is important for clinicians to recognize these disorders to prevent morbidity and mortality in these patients,and to perform presymptomatic testing in the first-degree relatives of PJS patients.展开更多
Peutz-Jeghers syndrome(PJS) ,a rare autosomal dominant inherited disorder,is characterized by hamartomatous gastrointestinal polyps and mucocutaneous pigmentation.Patients with this syndrome have a predisposition to a...Peutz-Jeghers syndrome(PJS) ,a rare autosomal dominant inherited disorder,is characterized by hamartomatous gastrointestinal polyps and mucocutaneous pigmentation.Patients with this syndrome have a predisposition to a variety of cancers in multiple organs.Mutations in the serine/threonine kinase 11(STK11) gene have been identified as a major cause of PJS.Here we present the clinical and molecular findings of two unrelated Thai individuals with PJS.Mutation analysis by Polymerase Chain Reaction-sequencing of the entire coding region of STK11 revealed two potentially pathogenic mutations.One harbored a single nucleotide deletion(c.182delG) in exon 1 resulting in a frameshift leading to premature termination at codon 63(p.Gly61AlafsX63) .The other carried an in-frame 9-base-pair(bp) deletion in exon 7,c.907_915del9(p.Ile303_Gln305del) .Both deletions were de novo and have never been previously described.This study has expanded the genotypic spectrum of the STK11 gene.展开更多
Peutz-Jeghers syndrome (PJS), also known as hereditary intestinal polyposis syndrome, is an autosomal dominant genetic disease characterized by the development of benign hamartomatous polyps in the gastrointestinal tr...Peutz-Jeghers syndrome (PJS), also known as hereditary intestinal polyposis syndrome, is an autosomal dominant genetic disease characterized by the development of benign hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on the lips and oral mucosa. Here, we reported 5 cases of PJS and our experience about its diagnosis and treatment.展开更多
基金Supported by the Natural Science Foundation of Hunan Province,China,No.2023JJ30422.
文摘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.
基金Supported by Beijing Capital Medical Development Research Fund,No.Shoufa2020-2-5122Outstanding Young Talents Program of Air Force Medical Center,PLA,No.22BJQN004Clinical Program of Air Force Medical University,No.Xiaoke2022-07.
文摘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.
基金Beijing Capital Medical Development Research Fund, No. Shoufa2020-2-5122Outstanding Young Talents Program of Air Force Medical Center, PLA, No. 22BJQN004Clinical Program of Air Force Medical University, No. Xiaoke2022-07
文摘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.
文摘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.
基金by Beijing Capital Medical Development Research Fund,No.Shoufa2020-2-5122。
文摘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.
文摘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.
基金Supported by the Beijing Health System of High Level Health Technical Personal Training Project,No.2013-3-067Beijing Municipal Science and Technology Commission,No.D171100006517003
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
基金Supported by Major Projects of Chinese PLA"13th Five-Year Plan"Logistics Research Subject,No.AKJ15J003
文摘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.
文摘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.
文摘We report a case of 30-year-old woman with Peutz- Jeghers syndrome (PJS). Because of small intestinal obstruction, she received the small intestinal polypectomy in 2001, and the pathological diagnosis was Peutz-Jeghers polyp canceration (mucinous adenocarcinoma, infiltrating full-thickness of the intestine). The patient did not feel uncomfortable after 6 mo of chemotherapy and other management. We kept a follow-up study on her and found that she suffered from cervical cancer in 2007, with a pathological diagnosis of cervical adenosquamous carcinoma.The patient presented with typical features of PJS, but without a family history. The PJS accompanied with both small intestinal and cervical malignancies has not been reported so far in the world.
文摘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
基金Supported by Major Projects of the Chinese PLA"Thirteenth Five-Year Plan"Logistics Research Subject,No.AKJ15J003No.AKJ15J001+1 种基金Incubation Project of Military Medical Science and Technology Youth Cultivation Program,No.17QNP023Beijing Capital Medical Development Research Fund,No.Shoufa2020-2-5122.
文摘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.
文摘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.
基金Supported by Research Project MZO 00179906 From theMinistry of Health,Czech Republic
文摘Peutz-Jeghers syndrome(PJS)is an inherited,autosomal dominant disorder distinguished by hamartomatous polyps in the gastrointestinal tract and pigmented mucocutaneous lesions.Prevalence of PJS is estimated from 1 in 8300 to 1 in 280 000 individuals.PJS predisposes sufferers to various malignancies(gastrointestinal,pancreatic,lung,breast,uterine,ovarian and testicular tumors).Bleeding,obstruction and intussusception are common complications in patients with PJS.Double balloon enteroscopy(DBE)allows examination and treatment of the small bowel.Polypectomy using DBE may obviate the need for repeated urgent operations and small bowel resection that leads to short bowel syndrome.Prophylaxis and polypectomy of the entire small bowel is the gold standard in PJS patients.Intraoperative enteroscopy(IOE)was the only possibility for endoscopic treatment of patients with PJS before the DBE era.Both DBE and IOE facilitate exploration and treatment of the small intestine. DBE is less invasive and more convenient for the pa- tient.Both procedures are generally safe and useful. An overall recommendation for PJS patients includes not only gastrointestinal multiple polyp resolution,but also regular lifelong cancer screening(colonoscopy, upper endoscopy,computed tomography,magnetic resonance imaging or ultrasound of the pancreas, chest X-ray,mammography and pelvic examinationwith ultrasound in women,and testicular examination in men).Although the incidence of PJS is low,it is important for clinicians to recognize these disorders to prevent morbidity and mortality in these patients,and to perform presymptomatic testing in the first-degree relatives of PJS patients.
基金Supported by Chulalongkorn University,National Science and Technology Development Agency,and the Thailand Research Fund
文摘Peutz-Jeghers syndrome(PJS) ,a rare autosomal dominant inherited disorder,is characterized by hamartomatous gastrointestinal polyps and mucocutaneous pigmentation.Patients with this syndrome have a predisposition to a variety of cancers in multiple organs.Mutations in the serine/threonine kinase 11(STK11) gene have been identified as a major cause of PJS.Here we present the clinical and molecular findings of two unrelated Thai individuals with PJS.Mutation analysis by Polymerase Chain Reaction-sequencing of the entire coding region of STK11 revealed two potentially pathogenic mutations.One harbored a single nucleotide deletion(c.182delG) in exon 1 resulting in a frameshift leading to premature termination at codon 63(p.Gly61AlafsX63) .The other carried an in-frame 9-base-pair(bp) deletion in exon 7,c.907_915del9(p.Ile303_Gln305del) .Both deletions were de novo and have never been previously described.This study has expanded the genotypic spectrum of the STK11 gene.
文摘Peutz-Jeghers syndrome (PJS), also known as hereditary intestinal polyposis syndrome, is an autosomal dominant genetic disease characterized by the development of benign hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on the lips and oral mucosa. Here, we reported 5 cases of PJS and our experience about its diagnosis and treatment.