| Chapter ? Clinical manifestations,diagnosis and treatment of patients with Peutz-Jeghers syndromeBackground and Objectives:Peutz-Jeghers syndrome(PJS)is an autosomal dominant inherited disorder clinically characterized by a triad of gastrointestinal hamartomatous polyps,mucocutaneous pigmentation and cancer predisposition.Germline mutation of the serine/threonine kinase 11(STK11)/liver kinase B1(LKB1)gene is considerd to be the main genetic cause of this disease.The characteristic hamartoma polyps of PJS patients can be distributed in the whole digestive tract except the esophagus and can grow repeatedly,often causing complications such as acute intestinal obstruction,intussusception,hematochezia and anemia.For the repeated and rapid growth of polyps in PJS patients,only regular endoscopic monitoring and timely treatment can be relied on at present.However,due to the rare nature of PJS,doctors and patients may have insufficient cognition and understanding of it thereby might miss the optimal intervention period,resulting in serious complications and subsequent emergency surgical operations.Research shows that nearly 70%of PJS patients have undergone at least one open surgical operation,and the main reasons for the operation are acute abdomen caused by acute intussusception or intestinal obstruction.Therefore,we believe that it is necessary to summarize the clinical manifestations,complications and diagnosis and treatment characteristics of PJS patients,so as to deepen the understanding of the disease and improve the corresponding diagnosis and treatment ability of clinical doctors,and to provide data support for the development of polyp monitoring programs for Chinese PJS patients.Methods:A total of 208 PJS patients admitted to Nanfang Hospital of Southern Medical University from December 2006 to July 2021 were included in a horizontal and longitudinal tracing of their pedigrees.A total of 412 PJS patients(including 86 deceased patients)were included.Clinical data and follow-up of all patients were collected and sorted out.The clinical manifestations,diagnosis and treatment of the surviving patients were retrospectively analyzed.Results:The clinical manifestations and management of 326 PJS patients were collected and analyzed.About 96%of PJS patients had perioral pigmentation,and the median age of lentigines onset is 1.5 years old,with no significant difference between genders and patients with or without PJS family history(Z=-1.118,P=0.263;Z=-0.727,P=0.467).The percentage of patients had experienced abdominal symptoms by age 10 years is 55.9%,and the median interval between the onset of lentigines and first abdominal symptoms was 7.5 years.Gastrointestinal polyps were mostly distributed in the small bowel and so did intussusceptions most frequently occur.The median age at first onset of intussusception was 16 years,and the cumulative risk of intussusception was 19.0%,55.0%,75.5%,and 86.4%at 10,20,30,40 years,respectively.The cumulative intussusception risk was significantly higher in sporadic cases than familial patients(P=0.004).Three hundred and twenty-two patients underwent an average of 5.3 endoscopies and 1.4 laparotomies per patient.Conclusions:The occurrence pigmentations in PJS patients is generally earlier than the on set of abdominal symptoms,and the occurrence of pigmentations should attracted attention from clinicians and PJS patients.Gastrointestinal polyps were mostly distributed in the small bowel and so did intussusceptions most frequently occur.Meanwhile,the cumulative risks for intussusceptions and laparotomy are highly elevated in PJS patients,therefore justifying the early and regular monitoring for polyps in the small bowel.Chapter ?:Cancer risk evaluation of patients with PJSBackground and Objectives:PJS patients have a significantly higher risk of cancer in different organs than regular people.Research shows that the lifetime cumulative risk of any cancer in PJS patients is up to 90%,mainly involving the digestive tract,while extra-digestive tract cancers mainly include breast cancer and female reproductive system cancers.In addition,PJS patients complicated with prostate cancer,bone cancer,leukemia,lymphoma,kidney cancer,etc.,have also been reported.At present,the focus of cancer prevention and treatment for PJS patients is to achieve early diagnosis and timely treatment as far as possible through targeted and regular monitoring and screening,so as to improve the prognosis of patients.In order to develop an effective and appropriate cancer screening and monitoring program,the spectrum and characteristics of cancer in Chinese PJS patients must be clarified first,and the risk of cancer in different organs should be assessed.Methods:Long-term prospective follow-up and retrospective analysis were performed on 412 patients with PJS,and their concomitant cancers were recorded and analyzed in detail,and the distribution characteristics of PJS cancers were summarized.Kaplan-meier analysis was used to calculate the cumulative risk of different cancers in PJS patients at different ages.The incidence of cancer at different sites in normal people of different genders and ages in China during 1989-2015 was obtained from the National Cancer Center,and poisson regression was used to calculate the cancer risk of PJS patients relative to the normal population.At the same time,STK11 gene mutations of PJS patients were collected and detected,and the relationship between STK11 genotype and cancer occurrence was explored.Results:In all,113 cancers occurred in 109 patients,with the median age of first cancer diagnosis being 40 years.The cancer incidence in patients with family history was significantly higher than that in sporadic cases(?2=17.277,P<0.001),but no significant difference in cancer incidence was found between different genders.For the distribution of the 113 malignancies,gastrointestinal tract was the most affected organ,while gynecological cancers and breast cancers being the most common extra-gastrointestinal tract tumors.Gastrointestinal cancer was the most common type in male patients,but non-gastrointestinal cancers account for more distribution in female patients.The cumulative risk of developing any cancer was 94.2%at age 70,and the corresponding risk for gastrointestinal cancer was 78.8%,no significant difference was found between different genders and patients with or without family history of PJS(P>0.05).However,the cumulative risk for colorectal cancer is significantly higher in male patients than in female patients(P=0.04).interestingly,the cumulative risk for lung cancer at 70 years was even higher than that of colorectal cancer.Thirty-one STK11 germline mutations were detected in pedigrees associated with cancer,of which 7 were novel.The median age of first cancer diagnosis was significantly lower in patients with truncated mutations than in patients without truncated mutations(Z=-2.639,P=0.008).Conclusions:PJS patients carry a highly increased lifetime risk of cancer,and the median age of cancer diagnosis at all sites is rather young.Gastrointestinal tumors were more common in male patients with PJS,while extra-gastrointestinal tumors were more common in female patients,and thus female patients should pay more attention to the screening for breast cancer and gynecological cancer.Seven novel germline mutation on STK11 were detected in this study,thereby extended the mutant spectrum of STK11.Patients with truncating mutations were more commonly associated with cancer and had a younger diagnostic age,but this observation needed to be validated by more basic researches.Chapter ? Meta-analysis of cancer risk and characteristics of PJSBackground and Objectives:Due to the rarity of PJS,previous studies on PJS associated with cancer were mostly case reports,and the sample size of patients included in single-center cohort studies was small.Moreover,transnational multi-center studies could not exclude the racial heterogeneity of genetic diseases.The above deficiencies are the often cause of the inconsistencies among studies from different countries/regions.Therefore,this study intends to conduct a meta-analysis and integrated description of published literatures about PJS patients with cancer,in order to assess the risk and characteristics of PJS patients with cancer more accurately on the basis of a large sample,and attempt to analyze the differences of research results between different countries/regions.Methods:With "Peutz-Jeghers Syndrome" and "cancer" as search terms,all literatures that reported the occurrence of cancer in PJS patients were searched in authoritative database systems.Data related to cancer were extracted and high-quality studies were meta-analyzed using Stata software.Results:A total of 21 literatures on PJS complicated with cancer were included,and 945 cases of cancer occurred in 877 of 4286 PJS patients,with the average age at cancer diagnosis being 41 years old.Meta-analysis of single rate showed that the overall cancer incidence of PJS patients was 24.96%,and subgroup analysis found that the region/country of PJS patients was the main reason affecting the heterogeneity of various literatures.Meta-analysis of dichotomous variables showed that male PJS patient had a lower cancer incidence than female patients(OR=0.62,P=0.042),and the cancer incidence was higher in familial PJS patients than in sporadic cases.(OR=2.63,P=0.003).The incidence of digestive tumors in male PJS patients is higher than that of non-digestive tumors(OR=3.96,P<0.001)and it goes contrary for female patients(OR=0.53,P=0.002).In female PJS patients,the rate of incidence of breast cancer,gynecological system tumor and digestive system tumor is similar.The cumulative risk of any cancer in patients with PJS has been reported in the literature to be between 67%and 94.2%,and the cancer risk tends to rise steeper between the age period 40-60 years.The cumulative risk for gastrointestinal cancer was reported to be 55%-78.8%at 65-70 years old and rise sharply between 50-70 years old.Last but not least,the steeper rise for breast cancer between 50-60 years.Conclusions:PJS patients had a risk of developing cancer at different targeted organs,and the risk started to risk sharply since 40 years old,especially for patients with positive family history. |
PDF Full Text Request