Sandbox:Hamid

Jump to navigation Jump to search


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Hamid Qazi, MD, BSc [2]

Overview

Historical Perspective

===Discovery===[1][2]

  • Peutz-Jeghers syndrome was first discovered by Dr. Connor, a British, in 1895 in identical twin sisters.
  • The association between gastrointestinal polyposis with distinctive pigmentation of the skin and Peutz-Jeghers syndrome was made in 1921 by Dr. Johannes Peutz of Holland.
  • In 1949, Dr. Harold Jeghers of United States was the first to discover the association between combination of intestinal polyposis and skin pigmentation, and the development of Peutz-Jeghers syndrome.
  • In 1954, A. Bruwer used the eponym Peutz-Jeghers syndrome
  • In 1998, serine/threonine-protein kinase 11 alias LKB1 (STK11/LKB1) gene mutations were first implicated in the pathogenesis of Peutz-Jeghers syndrome.

Classification

  • There is no established system for the classification of [disease name].

OR

  • [Disease name] may be classified according to [classification method] into [number] subtypes/groups:
    • [Group1]
    • [Group2]
    • [Group3]
    • [Group4]

OR

  • [Disease name] may be classified into [large number > 6] subtypes based on:
    • [Classification method 1]
    • [Classification method 2]
    • [Classification method 3]
  • [Disease name] may be classified into several subtypes based on:
    • [Classification method 1]
    • [Classification method 2]
    • [Classification method 3]

OR

  • Based on the duration of symptoms, [disease name] may be classified as either acute or chronic.

OR

  • If the staging system involves specific and characteristic findings and features:
  • According to the [staging system + reference], there are [number] stages of [malignancy name] based on the [finding1], [finding2], and [finding3]. Each stage is assigned a [letter/number1] and a [letter/number2] that designate the [feature1] and [feature2].

OR

  • The staging of [malignancy name] is based on the [staging system].

OR

  • There is no established system for the staging of [malignancy name].

Pathophysiology

Pathogenesis

  • It is thought that Peutz-Jeghers syndrome is the result of deletion or partial deletion of STK11 (LBK1) gene, located on chromosome 19p13.3.
  • STK11 protein plays an important role in second messenger signal transduction and is found to regulate cellular proliferation, controls cell polarity, and responds to low energy states.
  • In Mammalian studies, STK11 is shown in the inhibition of AMP-activated protein kinase (AMPK), and signals downstream to inhibit the mammalian target of rapamycin (mTOR).
    • The mTOR pathway is dysregulated in Peutz-Jeghers syndrome.

Pathology

  • Peutz-Jeghers syndrome associated polyps have a unique smooth muscle core that arborizes throughout the polyp.
    • These polyps can only be differentiated from other polyp types by histopathology.
    • insert image

Causes

  • Peutz-Jeghers syndrome is caused by STK11 gene mutation
  • Variable penetrance

Epidemiology and Demographics

Prevalence

  • The prevalence of Peutz-Jeghers syndrome is estimated to be 1 in 8300 to 250000
  • Most likely prevalence is 1 in 100000

Age

  • Peutz-Jeghers syndrome affects individuals between the ages of 10 to 30 years; average age of diagnosis is 23 years for males and 26 years for females.

Gender

  • Males and females are equally affected.

Risk Factors

  • There are no established risk factors for Peutz-Jeghers syndrome.

Screening

  • According to the American College of Gastroenterology (ACG) and the National Comprehensive Cancer Network (NCCN), screening for Peutz-Jeghers syndrome by physical exam, complete blood work for iron deficiency anemia, and endoscopy are recommended every year among patients with Peutz-Jeghers Syndrome.

Natural History, Complications, and Prognosis

Natural History

  • The symptoms of Peutz-Jeghers syndrome usually develop in the first decade of life, and start with symptoms such as hyperpigmentation, abdominal pain, and rectal bleeding.
  • If left untreated, patients with Peutz-Jeghers syndrome may progress to develop colon cancer, breast cancer, and gastrointestinal cancers.
  • Extraintestinal manifestation include pancreatic, lung, breast, uterine, ovarian and testicular malignancies.

Complications

  • Common complications of Peutz-Jeghers syndrome include:
    • Intussusception
    • Gastric outlet obstruction
    • Extraintestinal polyps

Prognosis

  • Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.
  • Depending on the extent of the [tumor/disease progression/etc.] at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as poor/good/excellent.
  • The presence of [characteristic of disease] is associated with a particularly [good/poor] prognosis among patients with [disease/malignancy].
  • [Subtype of disease/malignancy] is associated with the most favorable prognosis.
  • The prognosis varies with the [characteristic] of tumor; [subtype of disease/malignancy] have the most favorable prognosis.

References

  1. Kopacova, Marcela; Tacheci, Ilja; Rejchrt, Stanislav; Bures, Jan (2009). "Peutz-Jeghers syndrome: Diagnostic and therapeuticapproach". World Journal of Gastroenterology. 15 (43): 5397. doi:10.3748/wjg.15.5397. ISSN 1007-9327.
  2. Giardiello, F; Trimbath, J (2006). "Peutz-Jeghers Syndrome and Management Recommendations". Clinical Gastroenterology and Hepatology. 4 (4): 408–415. doi:10.1016/j.cgh.2005.11.005. ISSN 1542-3565.