Sandbox:Hamid

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

Historical Perspective

===Discovery===

• 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.

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.

Overview

• The page name should be "[Disease name] diagnostic study of choice", with only the first letter of the title capitalized. Note that the page is called "Diagnostic study of choice."
• Goal:
  • To describe the most efficient/sensitive/specific test that is utilized for diagnosis of [disease name].
  • To describe the gold standard test for the diagnosis of [disease name].
  • To describe the diagnostic criteria, which may be based on clinical findings, physical exam signs, pathological findings, lab findings, findings on imaging, or even findings that exclude other diseases.
• As with all microchapter pages linking to the main page, at the top of the edit box put {{CMG}}, your name template, and the microchapter navigation template you created at the beginning.
• Remember to create links within WikiDoc by placing [[square brackets]] around key words which you want to link to other pages. Make sure you makes your links as specific as possible. For example, if a sentence contained the phrase anterior spinal artery syndrome, the link should be to anterior spinal artery syndrome not anterior or artery or syndrome. For more information on how to create links, click here.
• Remember to follow the same format and capitalization of letters as outlined in the template below.
• You should include the name of the disease in the first sentence of every subsection.

Diagnostic Study of Choice

Gold standard/Study of choice:

• [Name of the investigation] is the gold standard test for the diagnosis of [disease name].
• The following result of [gold standard test] is confirmatory of [disease name]:
  • Result 1
  • Result 2
• The [name of investigation] should be performed when:
  • The patient presented with symptoms/signs 1. 2, 3.
  • A positive [test] is detected in the patient.
• [Name of the investigation] is the gold standard test for the diagnosis of [disease name].
• The diagnostic study of choice for [disease name] is [name of investigation].
• There is no single diagnostic study of choice for the diagnosis of [disease name].
• There is no single diagnostic study of choice for the diagnosis of [disease name], but [disease name] can be diagnosed based on [name of the investigation 1] and [name of the investigation 2].
• [Disease name] is mainly diagnosed based on clinical presentation.
• Investigations:
  • Among patients who present with clinical signs of [disease name], the [investigation name] is the most specific test for the diagnosis.
  • Among patients who present with clinical signs of [disease name], the [investigation name] is the most sensitive test for diagnosis.
  • Among patients who present with clinical signs of [disease name], the [investigation name] is the most efficient test for diagnosis.

The comparison table for diagnostic studies of choice for [disease name]

	Sensitivity	Specificity
Test 1	✔	...%
Test 2	...%	✔

✔= The best test based on the feature

Diagnostic results

The following result of [investigation name] is confirmatory of [disease name]:

• Result 1
• Result 2

Sequence of Diagnostic Studies

The [name of investigation] should be performed when:

• The patient presented with symptoms/signs 1, 2, and 3 as the first step of diagnosis.
• A positive [test] is detected in the patient, to confirm the diagnosis.

Diagnostic Criteria

• Here you should describe the details of the diagnostic criteria.
• Always mention the name of the criteria/definition you are about to list (e.g. modified Duke criteria for diagnosis of endocarditis / 3rd universal definition of MI) and cite the primary source of where this criteria/definition is found.
• Although not necessary, it is recommended that you include the criteria in a table. Make sure you always cite the source of the content and whether the table has been adapted from another source.
• Be very clear as to the number of criteria (or threshold) that needs to be met out of the total number of criteria.
• Distinguish criteria based on their nature (e.g. clinical criteria / pathological criteria/ imaging criteria) before discussing them in details.
• To view an example (endocarditis diagnostic criteria), click here
• If relevant, add additional information that might help the reader distinguish various criteria or the evolution of criteria (e.g. original criteria vs. modified criteria).
• You may also add information about the sensitivity and specificity of the criteria, the pre-test probability, and other figures that may help the reader understand how valuable the criteria are clinically.
• [Disease name] is mainly diagnosed based on clinical presentation. There are no established criteria for the diagnosis of [disease name].
• There is no single diagnostic study of choice for [disease name], though [disease name] may be diagnosed based on [name of criteria] established by [...].

• The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].
• The diagnosis of [disease name] is based on the [criteria name] criteria, which includes [criterion 1], [criterion 2], and [criterion 3].

• [Disease name] may be diagnosed at any time if one or more of the following criteria are met:
  • Criteria 1
  • Criteria 2
  • Criteria 3

IF there are clear, established diagnostic criteria:

• The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].
• The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].
• The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].

IF there are no established diagnostic criteria: 

• There are no established criteria for the diagnosis of [disease name].

References

• References should be cited for the material that you have put on your page. Type in {{reflist|2}}.This will generate your references in small font, in two columns, with links to the original article and abstract.
• For information on how to add references into your page, click here.