Peutz-Jeghers Research Articles

Clinical Efficacy of 755 nm Laser Treatment of Lip Mucosal Pigmentation in Children with Peutz–Jeghers Syndrome

Peutz–Jeghers syndrome (PJS) is a rare genetic disorder characterized by multiple gastrointestinal polyps and mucocutaneous pigmentation. Abnormal pigmentation typically develops in infancy or childhood. As PJS‐related facial pigmentation can lead to psychological burden due to its effects on esthetics, treatment is required. Herein, we report on the efficacy and safety of treatment of lip mucosal pigmentation using a Q‐switched 755 nm Alexandrite Laser in children with PJS, aged 2–12 years of age. A topical anesthetic was used prior to the application of laser therapy. A treatment efficacy of 100% was achieved with one to three treatments, with an excellent outcome achieved in five cases (62.5%) and a good outcome in three (37.5%). Recurrent pigmentation was observed in one case over the 6‐month follow‐up period. There were no adverse effects, such as scarring or hyperpigmentation or hypopigmentation. The treatment did cause pain, apprehension, and crying in some children, requiring special attention. Although our sample size is small, our findings do provide support of the high efficacy and safety of the Q‐switched 755 nm Alexandrite Laser for the treatment of lip mucosal pigmentation in children with PJS. Further studies are required to confirm these findings.

Cancer risk and mortality in patients with solitary Peutz-Jeghers polyps.

Cancer risk and mortality in patients with solitary Peutz-Jeghers polyps.

An overview of pigmented lesions of the oral cavity

It might be difficult to diagnose pigmented lesions of the mouth and perioral regions. Although several lesions may be correctly identified on the basis of clinical findings alone and while epidemiology may be helpful in guiding the clinician, the histological examination is typically necessary for the final diagnosis. Oral hyperpigmentation may present exogenously/ endogenously; pathologically/physiologically. The differential diagnosis depends on factors like medication usage, familial history in addition to the position, spread, and length as well as hue and pattern variations. Physiological pigmentation, melanotic macule, melanocytic nevus, smoker's melanosis, oral melanoacanthoma, pigmentation caused by foreign matter or medicines, Peutz-Jeghers syndrome, Addison's disease, and oral melanoma are examples of dark or black pigmented discolorations that can be unifocal, multifocal, or dispersed macular lesions.

A novel missense mutation of the STK11 gene in a Chinese family with Peutz-Jeghers syndrome

BackgroundPeutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited disease caused by mutations in the Serine-Threonine Kinase 11 (STK11) gene. This study aimed to diagnose a Chinese pedigree with PJS and to expand the spectrum of STK11 variants.MethodsWe performed an inductive analysis of clinical features, gastrointestinal endoscopy, radiologic imaging, and pathological findings in a Chinese family with PJS. Whole-exome sequencing (WES), Sanger sequencing, and STK11 protein 3D structure prediction were performed for establishing a molecular diagnosis.ResultsThe proband, her mother, and grandfather presented with pigmentation spots on lips, oral mucosa, and fingers. Her mother and grandfather also had pigmentation spots on face and feet, while her brother had pigmentation spots only on the lower lip. On endoscopy, polyps were discovered in the proband, her mother, and grandfather. A novel heterozygous mutation (c.521A > C) in exon 4 of STK11 was identified in all four patients, leading to a change from histidine to proline in amino acid 174. The variable site p.H174 was highly conserved in different species on multiple sequence alignment analysis.ConclusionsWe diagnosed a Chinese pedigree with PJS based on clinical features, gastrointestinal endoscopy, and genetic testing results. Our results expanded the spectrum of STK11 variants, which will be helpful for genetic counseling.

Strong Hereditary Predispositions to Colorectal Cancer

Cancer is one of the most common causes of death worldwide. A strong predisposition to cancer is generally only observed in colorectal cancer (5% of cases) and breast cancer (2% of cases). Colorectal cancer is the most common cancer with a strong genetic predisposition, but it includes dozens of various syndromes. This group includes familial adenomatous polyposis, attenuated familial adenomatous polyposis, MUTYH-associated polyposis, NTHL1-associated polyposis, Peutz-Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, Lynch syndrome, and Muir-Torre syndrome. The common symptom of all these diseases is a very high risk of colorectal cancer, but depending on the condition, their course is different in terms of age and range of cancer occurrence. The rate of cancer development is determined by its conditioning genes, too. Hereditary predispositions to cancer of the intestine are a group of symptoms of heterogeneous diseases, and their proper diagnosis is crucial for the appropriate management of patients and their successful treatment. Mutations of specific genes cause strong colorectal cancer predispositions. Identifying mutations of predisposing genes will support proper diagnosis and application of appropriate screening programs to avoid malignant neoplasm.

Hereditary breast cancer: syndromes, tumour pathology and molecular testing.

Hereditary factors account for a significant proportion of breast cancer risk. Approximately 20% of hereditary breast cancers are attributable to pathogenic variants in the highly penetrant BRCA1 and BRCA2 genes. A proportion of the genetic risk is also explained by pathogenic variants in other breast cancer susceptibility genes, including ATM, CHEK2, PALB2, RAD51C, RAD51D and BARD1, as well as genes associated with breast cancer predisposition syndromes - TP53 (Li-Fraumeni syndrome), PTEN (Cowden syndrome), CDH1 (hereditary diffuse gastric cancer), STK11 (Peutz-Jeghers syndrome) and NF1 (neurofibromatosis type 1). Polygenic risk, the cumulative risk from carrying multiple low-penetrance breast cancer susceptibility alleles, is also a well-recognised contributor to risk. This review provides an overview of the established breast cancer susceptibility genes as well as breast cancer predisposition syndromes, highlights distinct genotype-phenotype correlations associated with germline mutation status and discusses molecular testing and therapeutic implications in the context of hereditary breast cancer.

Endoscopic treatment of intussusception due to small intestine polyps in patients with Peutz-Jeghers Syndrome.

Background and study aims Intussusception caused by intestinal polyps in patients with Peutz-Jeghers syndrome usually requires laparotomy. Patients following successful endoscopic reduction using double-balloon endoscopy (DBE) have been reported. The aim of this study was to evaluate the feasibility of endoscopic treatment of intussusception. Patients and methods We retrospectively reviewed patients who underwent DBE for intussusception due to small intestine polyps in patients with Peutz-Jeghers syndrome from January 2004 to June 2020. Results Twenty-seven (antegrade 22, retrograde 5) DBEs were performed in 19 patients with 25 sites of intussusception identified during the study period. If the intussusception remained once the endoscope reached the site, endoscopic reduction of the intussusception was performed as needed (15 sites). Ultimately, endoscopic resections (8 sites) or ischemic polypectomies (16 sites) of the polyp causing the intussusception were completed at 24 sites. Only one site could not be treated endoscopically and was treated surgically. The final per-site and per-patient success rates of endoscopic treatment were 96 % (24/25) and 95 % (18/19) respectively. Two patients developed mild acute pancreatitis and one patient developed intussusception after the procedures, both of which were treated non-operatively. Conclusions Endoscopic treatment of intussusception is feasible to avoid laparotomy in patients with Peutz-Jeghers syndrome.

Intraoperative endoscopy-assisted tumor debulking in pediatric peutz-jeghers syndrome with early onset massive polyp burden phenotype

Peutz-Jeghers Syndrome is an autosomal dominant disorder linked to abnormalities in STK11, and is associated with mucocutaneous pigmentation, sex cord tumors, and gastrointestinal polyps. While it is extremely rare in children under the age of 2, several cases of profound disease have been documented in this population. Here, we detail a case of Peutz-Jeghers Syndrome presenting initially as intussusception, where massive polyp burden nearly occluded the duodenum of a 15-month-old patient and required multimodal operative intervention. Further, we posit that race-based implicit bias may contribute to delays in care and the identification of patients at risk for rare diseases, particularly with atypical presentation, such as the child highlighted in this case. • Varying genetic anomalies may yield more aggressive expression of Peutz-Jeghers Syndrome. • Variance in phenotypic aggression may require alternative screening models. • Social determinants of health and disparities should be considered in screening guidelines.

Clinical Features and Management of Small Bowel Masses Detected During Device-Assisted Enteroscopy: A Multi-Center Experience.

Small bowel mass lesions (SBMLs) are rare, span a range of different histologies and phenotypes, and our understanding of them is limited. Some lesions occur in patients with recognized polyposis syndromes and others arise sporadically. The current literature regarding SBMLs is limited to small retrospective studies, case reports, and small case series. This large multi-center study aims to understand the various clinical presentations, histologies and management options for SBMLs. After obtaining Institutional Review Board (IRB) approval, electronic records were used to identify all device-assisted enteroscopy (DAE) performed for luminal small bowel evaluation in adult patients at three US referral centers (Duke, LSU and UMass) from January 1, 2014, to October 1, 2020. We identified all patients within this cohort in whom a SBML was detected. Using a focused electronic medical record chart review, we collected patient, procedure, and lesion-related data and used descriptive statistics to explore relationships between these data and outcomes. A total of 218 patients (49 at Duke, 148 at LSU, and 21 at UMass) in this cohort had at least one SBML found on DAE. The most common presenting symptoms were iron-deficiency anemia/bleeding (73.3%) and abnormal imaging (33.6%). Thirty-five percent of patients had symptoms for more than a year prior to their diagnosis. Most patients (71.6%) underwent video capsule endoscopy (VCE) prior to DAE and 84% of these exams showed the lesion. The lesion was seen less frequently (48.9%) on computed tomography (CT) scan performed prior to DAE. The majority of lesions were found on antegrade (56%) or retrograde (29.8%) double-balloon enteroscopy (DBE). The most common lesion phenotypes were submucosal (41.3%) and pedunculated (33%) with a much smaller number being sessile (14.7%) or obstructing/invasive (11%). They were found equally as commonly in the jejunum (46.3%) and ileum (49.5%). Most lesions were 10 - 20 mm in size (47%) but 22.1% were larger than 20 mm. The most common histologies were neuroendocrine tumors (NETs, 20.6%) and hamartomas (20.6%). Primary adenocarcinoma of the small bowel was rare, constituting only 5% of lesions. The majority of polyps (78.4%) were sporadic, compared to 21.7% associated with a polyposis or hereditary cancer syndrome, most commonly Peutz-Jeghers syndrome (18.3%). After DAE, 37.6% were advised to undergo surgical resection and 48% were advised to undergo endoscopic surveillance or no further management because of benign histology or successful endoscopic resection. In this multi-center retrospective study we found that SBMLs are more likely to be sporadic than syndromic, medium in size and either pedunculated or submucosal. NETs and hamartomas predominated and symptoms, most commonly anemia, can be present for more than a year prior to diagnosis. Close to one half of lesions required either no further intervention or only endoscopic surveillance.

Proposal of a Risk Scoring System to Facilitate the Treatment of Enteroenteric Intussusception in Peutz-Jeghers Syndrome.

Enteroenteric intussusception in Peutz-Jeghers syndrome (EI-PJS) is traditionally treated by surgery. However, enteroscopic treatment is a minimally invasive approach worth attempting. We aimed to develop a risk scoring system to facilitate decision-making in the treatment of EI-PJS. This was a single-center case-control study, including 80 patients diagnosed with PJS and coexisting intussusception between January 2015 and January 2021 in Air Force Medical Center. We performed logistic regression analysis to identify independent risk factors and allocated different points to each subcategory of risk factors; the total score of individuals ranged from 0 to 9 points. Then, we constructed a risk stratification system based on the possibility of requiring surgery: 0-3 points for "low-risk," 4-6 points for "moderate-risk," and 7-9 points for "high-risk." Sixty-one patients (76.25%) were successfully treated with enteroscopy. Sixteen patients (20.0%) failed enteroscopic treatment and subsequently underwent surgery, and three patients (3.75%) received surgery directly. Abdominal pain, the diameter of the responsible polyp, and the length of intussusception were independent risk factors for predicting the possibility of requiring surgery. According to the risk scoring system, the incidence rates of surgery were 4.44% in the low-risk tier, 30.43% in the moderate-risk tier, and 83.33% in the high-risk tier. From low- to high-risk tiers, the trend of increasing risk was significant (p<0.001). We developed a risk scoring system based on abdominal pain, diameter of the responsible polyps, and length of intussusception. It can preoperatively stratify patients according to the risk of requiring surgery for EI-PJS to facilitate treatment decision-making.

Surgical Management of Benign Neoplasms of the Small Intestine

Small intestinal benign tumours are uncommon clinical conditions that frequently go asymptomatic for the entirety of a patient's life. The small bowel contains only a tiny number of primary neoplasms, while making up most of the surface area and most of the length of the gastrointestinal (GI) tract. There are the following subtypes: Hyperplastic polyps, hamartomas, adenoma, stromal tumours, lipomas, hemangiomas, and patients who have Peutz-Jeghers syndrome. Clinically, speaking, benign small-bowel lesions are distinguished by the absence of distinguishing symptoms. Up to the proximal duodenum lesions can be diagnosed with enteroscopy. Push or double-balloon enteroscopy methods can be used to reach the GI tract beyond the ligament of Treitz. The sole method of treatment for those who have small bowel adenocarcinoma is surgery. The majority of research state that between 40 and 65 percent of patients lend themselves to curative resection. The utilisation of laparoscopic surgery (LS) for small intestine gastrointestinal stromal tumours (GISTs) has expanded with the introduction of LS. There is currently no evidence to suggest a statistically significant difference between LS and open surgery in terms of prognosis. This review aims to summarize evaluation and management of benign neoplasms of the small intestine.

Case report on Management and Complication of Peutz Jegher Syndrome

Introduction: Infrequent and characterized by mucocutaneous pigmentations, gastrointestinal polyposis, and an increased risk of malignancy, Peutz-Jeghers syndrome is an autosomal dominant genetic condition. The usual perioral macules and patches that are colored in the buccal mucosa are present in 90% of patients, and numerous but not continuously contiguous lesions, primarily in the gastrointestinal (G.I.) tract, with rarely more than 20 hamartomata's polyps, are the characteristics of Peutz-Jeghers syndrome (P.J.S.). Present complaints and Investigation:-Suddenly felt sick to my stomach and started to puke. Abdominal pain, Black stools, repeated vomiting, weight loss of 5 kg in 15 days, loss of appetite, and Intussusception were discovered during examinations in the upper small bowel. A thorough study of the gastrointestinal tract was conducted. Endoscopically, the enormous polyps of the stomach and duodenum were discovered and biopsied. Resulting of bleeding due to the G.I. polyps, she became anemic. There were polyps. Later removed endoscopically while being sedated, C.T.'s Abdomen and pelvis found multiple mildly enhanced polypoidal lesions notes attached to the pyloric part of stomach and duodenum proximal jejunal loops, similar lesions of Ascending colon, transverse colon, and advice colonoscopy. History: The patient was admitted in 2015 And Operated on 26/12/2015, the year Jejunoileal intussusception. The primary diagnosis, therapeutic intervention, and outcomes: After physical examination and investigation, Hamartomatous polyp (P-J Secondary Intussuseception ) Conclusions: The following primary complaints were the reason for the patient's hospital admission. Upon entry to the hospital, the patient's main complaint was that Peutz Jegher Syndrome was identified as the patient's condition once all investigations were complete. The patient now needs appropriate medical attention and quality nursing care.

Peutz Jeghers syndrome with multiple intussusceptions

Peutz Jegher’s syndrome is a rare autosomal dominant disorder characterized by the development of hamartomatous polyps and mucocutaneous melanin pigmentation. This case report shows the case of an adult Indian female with intestinal obstruction due to multiple intussusceptions that were caused by hamartomatous polyp of Peutz Jegher’s syndrome. A 32-year-old female presented to the surgical emergency with complaints of colicky abdominal pain, vomiting and melena and with a positive family history for Peutz Jegher’s syndrome. On abdominal examination, a mass was palpable in her right lumbar area and per rectal examination showed ballooning and blood staining. She was provisionally diagnosed with Peutz Jegher’s syndrome with intussusception and her ultrasound imaging of the abdomen also showed the features suggestive of intussusception. She underwent an emergency laparotomy with resection and anastomosis of the involved segment of the jejunum and limited right hemicolectomy. Intraoperative findings showed multiple intussusceptions in her both large and small bowels along with multiple polyps which was seen to be hamartomatous polyps in the histopathological studies. The postoperative period was uneventful and during the review she was healthy. Intussusception is the major complication of Peutz Jegher’s syndrome and it can be prevented with regular surveillance in known cases. Intussusception should be kept in mind as the first differential diagnosis when these patients present with acute abdomen. The investigation of choice that’s preferred is a cross sectional imaging of the gastrointestinal tract to confirm with the diagnosis. Periodic surveillance is essential in those patients with known history or those with the mutation of STK11 (LKB1) gene.

S1571 Device-Assisted Enteroscopy (DAE) in the Surveillance of Intestinal Polyposis in Peutz-Jeghers Syndrome

Introduction: Peutz-Jeghers Syndrome (PJS) is an autosomal dominant, genetic disorder characterized by the formation of hamartomatous polyps in the gastrointestinal tract. These polyps are a source of significant morbidity and mortality in this population due to associated complications of intestinal obstruction, bleeding, and malignant transformation. Surveillance of intestinal polyposis in patients with PJS has not been extensively studied, although centers which perform a significant volume of device-assisted enteroscopies (DAEs) encounter multiple cases each year. With the progressive adoption of DAE, examination of the deep small bowel for monitoring and prophylactic polypectomy has the potential to prevent complications of PJS and minimize the need for repeated laparotomy. Methods: After obtaining IRB approval, electronic health records were used to identify all DAEs performed on patients with PJS at 3 US referral centers (LSU, Duke, and UMass) between January 1, 2007 and January 1, 2020. Electronic medical records were reviewed to collect and analyze multiple data points. Primary endpoints included the complications associated with DAE performed for removal of intestinal hamartomas and the rate of laparotomy in PJS patients prior to and after index DAE. Secondary data points included patient characteristics, procedural details, and size/location/distribution of small bowel hamartomas. Results: Twenty-four patients met our inclusion criteria. Of these, 18 (75%) had previously undergone small bowel surgery for complications related to small bowel hamartomas. Between 2007 - 2020, a total of 46 DAEs were performed in these patients with an average of one surveillance exam every 2.5 years. A total of 131 polypectomies were performed during our study period with an observed complication rate of 1.5%, including one bowel perforation requiring surgery. Only one patient underwent surgery related to small bowel hamartomas following initial DAE surveillance exam over a total of 366 years of aggregated follow-up (Figure). Conclusion: Endoscopic management of small bowel polyps in patients with PJS using DAE is an effective strategy for prophylactic removal of hamartomas. DAE surveillance and endoscopic polypectomy is safe and may decrease the need for repeated laparotomy due to complications from intestinal hamartomas in patients with PJS.Figure 1.: Hamartomatous polyp in the ileum removed with saline injection-lift technique and hot snare polypectomy

S1583 Surveillance With Double Balloon Enteroscopy in Adult Patients With Peutz-Jeghers Syndrome: A Single Center Experience

Introduction: Peutz-Jeghers syndrome (PJS) is an inherited polyposis syndrome caused by mutation in the STK11 gene, and characterized by hamartomatous polyps throughout the gastrointestinal tract, most often in the small bowel (60-90%) and colon (50-64%). Presenting symptoms in PJS are often related to symptomatic polyps, including intestinal obstruction, abdominal pain, and bloody stools. For PJS patients, current recommendations support screening upper endoscopy, colonoscopy, and video capsule endoscopy at age 8-10, and if no polyps identified then again at age 18. Small bowel screening is recommended every 2-3 years. Deep enteroscopy, via antegrade or retrograde balloon enteroscopy, is often required for clearance of larger polyps visualized on video capsule endoscopy (VCE). The optimal follow-up strategy and modality of screening and surveillance of small bowel polyps is controversial. We aimed to evaluate if proactively performing deep enteroscopy vs serial VCE in adult PJS patients reduces risk of requiring subsequent surgical intervention. Methods: We retrospectively collected data from adult patients over 18 years of age with Peutz-Jeghers syndrome who underwent deep balloon enteroscopy for small bowel surveillance. Patients within this subset underwent proactive screening with antegrade double balloon enteroscopy performed approximately every one to 2 years. Data collected included number of prior small bowel surgeries before onset of and during deep enteroscopy surveillance, and complications. Results: Thirteen patients underwent deep enteroscopy from 2010 through 2021. Average number of prior small bowel surgeries was 1.9 (SD 1.4), average number of balloon enteroscopies during surveillance period 2.8 (SD 1.4), and average number of surgeries during balloon enteroscopy surveillance 0.46 (SD 0.66). There was a significant difference between number of surgeries before and during surveillance period (P=0.002). Conclusion: The initial standard screening modality for small bowel polyps and malignancy, VCE, can be complicated by increased risk of capsule retention given likelihood of prior surgery and possibility of obstructing polyps. Additionally, within the PJS cohort, there is a high yield for pathology which may ultimately require therapeutic deep enteroscopy anyhow. Our study, though small, does indicate that on a proactive balloon enteroscopy surveillance protocol there is a significantly lower risk of requiring small bowel surgery.

S3424 Imaging-Negative Double Jejunal Intussusception Diagnosed on Laparoscopy With Intraoperative Enteroscopy in a Patient With Peutz-Jeghers Syndrome

Introduction: Peutz-Jeghers syndrome (PJS) is a rare, autosomal dominant syndrome characterized by gastrointestinal polyposis, mucocutaneous pigmentation, and an increased risk of malignancy. Although generally benign, PJ-type polyps can be large and can act as lead points for intussusception. We describe the case of a 25-year-old female with PJS who presented with recurrent abdominal pain in the setting of negative cross-sectional imaging who was found to have a double intussusception on diagnostic laparoscopy with intraoperative enteroscopy. Case Description/Methods: The patient’s surgical history was notable for five reductions of small bowel intussusception related to PJ-type polyps since age 9. She initially presented with intermittent abdominal pain six months prior to this admission, at which time seventeen small bowel PJ-type polyps were resected via anterograde small bowel enteroscopy. Her pain persisted despite intervention, and magnetic resonance cholangiopancreatography (MRCP) and magnetic resonance enterography (MRE) four months prior to admission demonstrated two additional polyps in the terminal ileum which were resected via colonoscopy. The patient then presented with acutely worsening abdominal pain that she described as similar to her past episodes of intussusception. Although a computed tomography (CT) scan with IV contrast was unremarkable, there was high clinical suspicion for intussusception, so a multidisciplinary decision was made to proceed with diagnostic laparoscopy. Two jejunal intussusceptions related to large polyps were identified and reduced, and one large (25 mm) polyp was surgically resected (Figure A and B). On intraoperative enteroscopy via enterotomy, one smaller (15 mm) duodenal polyp and three large (20-25 mm) jejunal polyps were removed. The patient was discharged three days postoperatively with resolution of her pain. Discussion: Patients with PJS require multidisciplinary care given their significantly increased risk of both gastrointestinal and extraintestinal malignancy and complications such as intussusception. While CT is generally the preferred imaging study when evaluating for intussusception in adults, there is limited data on its sensitivity, with estimates ranging from 58-100%. Our case highlights two important points: first, although PJ-type polyps are generally benign, they may grow rapidly; and second, even if imaging is unremarkable, clinicians should still consider intussusception in patients with predisposing risk factors and a compatible clinical picture.Figure 1.: (A) Laparoscopic view of a small bowel intussusception (arrow) related to a Peutz-Jeghers-type polyp. (B) Endoscopic view of a large hamartomatous Peutz-Jeghers-type polyp.

S3467 Primary Duodenal Adenocarcinoma: A Rare Malignancy

Introduction: Primary duodenal adenocarcinoma (PDA) is extremely rare, representing 0.3 – 1% of all gastrointestinal malignancies. It poses a significant challenge to the physicians due to late non-specific symptoms that delays the diagnosis. Surgical resection is the only treatment option although PDA with distant or nodal metastasis have a very poor prognosis. Case Description/Methods: A 33-year-old male patient presented with epigastric abdominal pain, nausea, vomiting, lipase > 2000, elevated LFTs and hyperbilirubinemia, consistent with acute pancreatitis. CT abdomen and pelvis revealed an irregular mass in the second and third portion of the duodenum near ampulla, dilation of pancreatic and common bile duct along with multiple hepatic lesions, consistent with metastatic malignancy. EGD showed non bleeding duodenal ulcer along with enlarged lymph nodes in the peripancreatic region. Biopsy of the ulcer was suggestive of moderately differentiated invasive duodenal adenocarcinoma with background of high-grade dysplasia. Due to metastatic malignancy, patient was started on folinic acid, fluorouracil and oxaliplatin without undergoing surgery. Percutaneous biliary drain was placed with resolution of pancreatitis and hyperbilirubinemia. Patient also completed a course of antibiotics due to pseudomonas bacteremia and sepsis secondary to pancreatic phlegmon that was drained. Pain was management with fentanyl patch and oral opioids. Patient was later discharged home with outpatient follow up. Discussion: This case highlights the importance of primary duodenal adenocarcinoma (PDA) which is a very rare malignancy. Its etiology is unknown, however patients with familial adenomatosis polyposis, Peutz-Jeghers syndrome, Crohn’s and celiac disease are at higher risk. Due to non-specific symptoms including anorexia, postprandial fullness, nausea, vomiting, jaundice and abdominal pain, early diagnosis is a challenge for physicians. PDA is most commonly seen in second part of the duodenum with an incidence of 50 -70%. It can be diagnosed with the help of contrast imaging studies along with EGD and biopsy. Management is usually surgical resection with tumors of the second part of the duodenum, proximal and distal infiltrating tumors requiring pancreaticoduodenectomy to ensure radical resection. Lymphovascular invasion, lymph node metastasis and perineural invasion are features associated with poor prognosis and high mortality. For unresectable tumors, palliative surgery or endoscopic treatment is usually indicated.

JEJUNO-JEJUNAL INTUSSUSCEPTION IN A PATIENT WITH PEUTZ-JEGHERS SYNDROME: A CASE REPORT AND REVIEW

Peutz-Jeghers syndrome is an autosomal dominant genetic disorder associated with pigmented spots on the skin and mucous membrane especially around oral mucosa, lips, nasal alae, palm and soles, as well as hamartomatous polyps in the alimentary canal. Prevalence of Peutz-Jeghers syndrome is between 1 in 8300 and 1 in 280000 people. Here, we present a case of 18 years old lady who presented with complains of peri-umbilical pain and vomiting for 2 months. Physical examination revealed multiple pigmentations over lips, palms and soles. Ultrasonography was normal. On further evaluation using a contrast enhanced computerized tomographic scan of abdomen and pelvis, jejuno-jejunal intussusception was noted. She then underwent exploratory laparotomy along with resection and anastomosis of the involved jejunal segment. Biopsy specimen containing multiple pedunculated polyps was sent for histopathological examination which revealed hamartomatous polyp.

Peutz-Jeghers syndrome and sinonasal diseases: A case report and literature review.

Peutz-Jeghers syndrome is an unusual inherited intestinal polyposis syndrome associated with distinct mucocutaneous pigmentation. Peutz-Jeghers syndrome is known to show variable penetrance and clinical heterogeneity. It can involve various organs and lead to intestinal and extra-intestinal malignancies. Sinonasal inverted papilloma is a benign tumor originating from the nasal cavity and paranasal sinuses. It is characterized by high recurrence and malignant transformation; however, the exact pathogenesis and risk factors remain unclear. Recently, we encountered a case of sinonasal inverted papilloma in a patient with Peutz-Jeghers syndrome. Although we performed a molecular genetic study to evaluate the STK11/LKB1 mutation, we could not provide direct evidence of the association between sinonasal inverted papilloma and Peutz-Jeghers syndrome. Based on our experience, we here tried to introduce Peutz-Jeghers syndrome and the potential involvement of the upper airway tract based on previously reported cases.

356P Biallelic MUTYH germline inactivation in patients with colon polyposis and subjects with sporadic colorectal cancer

MUTYH-associated polyposis (MAP) is a rare recessive condition typically characterized by the presence of 10-100 colorectal polyps and the elevated risk of colorectal cancer (CRC). CRCs arising in biallelic carriers of MUTYH mutation often contain KRAS G12C substitution and frequently arise without concomitant polyposis. This study included 74 consecutive patients with colon polyposis and 3486 consecutive patients with CRC referred to the N.N. Petrov Institute of Oncology (St. Petersburg, Russia) for molecular testing. Normal DNA obtained from subjects with polyposis was analyzed by NGS using custom panel for hereditary cancer genes. CRC patients were screened for recurrent MUTYH pathogenic alleles p.Y179C, p.R245H and p.G396D. The status of the remaining allele in MUTYH-heterozygous CRC cases was analyzed by Sanger sequencing. Biallelic MUTYH mutations were identified in 8/74 (11%) patients with polyposis. MAP was the second most common hereditary polyposis syndrome after familial adenomatous polyposis (47/74, 64%), with Peutz-Jeghers syndrome being in the third place (3/74, 5%). MUTYH biallelic alterations were detected in 9/3486 (0.3%) consecutive CRC patients. Somatic KRAS G12C substitution was observed in 223/3486 (6%) CRCs. Germ-line MUTYH inactivation was identified in 7/223 (3%) KRAS G12C-positive CRCs vs. 2/3253 (0.06%) patients without this mutation (p < 0.00001). Germ-line MUTYH biallelic mutations are significant contributors to the incidence of polyposis, while their impact in CRC morbidity is moderate. However, MUTYH gene analysis is highly feasible in CRC patients whose tumor harbors KRAS G12C substitution.