Difference between revisions of "Colon"

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(→‎Spirochetes: +amebiasis)
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==Spirochetes==
==Spirochetes==
===General===
*Very rare cause of diarrhea.
*Very rare cause of diarrhea.
*Caused by ''Serpulina pilosicoli'' and ''Brachyspira aalborgi''.<ref name=pmid14718105>{{cite journal |author=Amat Villegas I, Borobio Aguilar E, Beloqui Perez R, de Llano Varela P, Oquiñena Legaz S, Martínez-Peñuela Virseda JM |title=[Colonic spirochetes: an infrequent cause of adult diarrhea] |language=Spanish; Castilian |journal=Gastroenterol Hepatol |volume=27 |issue=1 |pages=21–3 |year=2004 |month=January |pmid=14718105 |doi= |url=}}</ref>
*Caused by ''Serpulina pilosicoli'' and ''Brachyspira aalborgi''.<ref name=pmid14718105>{{cite journal |author=Amat Villegas I, Borobio Aguilar E, Beloqui Perez R, de Llano Varela P, Oquiñena Legaz S, Martínez-Peñuela Virseda JM |title=[Colonic spirochetes: an infrequent cause of adult diarrhea] |language=Spanish; Castilian |journal=Gastroenterol Hepatol |volume=27 |issue=1 |pages=21–3 |year=2004 |month=January |pmid=14718105 |doi= |url=}}</ref>
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Special stain:  
Special stain:  
*Silver stains highlight 'em (e.g. Warthin-Starry stain).
*Silver stains highlight 'em (e.g. Warthin-Starry stain).
==Amebiasis==
===General===
*Infection with ''Entamoeba histolytica''.<ref>URL: [http://www.health.state.ny.us/diseases/communicable/amebiasis/fact_sheet.htm http://www.health.state.ny.us/diseases/communicable/amebiasis/fact_sheet.htm]. Accessed on: 17 June 2010.</ref>
May cause:<ref name=pmid20303955>{{Cite journal  | last1 = Mortimer | first1 = L. | last2 = Chadee | first2 = K. | title = The immunopathogenesis of Entamoeba histolytica. | journal = Exp Parasitol | volume =  | issue =  | pages =  | month = Mar | year = 2010 | doi = 10.1016/j.exppara.2010.03.005 | PMID = 20303955 }}</ref>
*Dysentery (diarrhea containing mucus and/or blood in the feces).
*Colitis.
*Liver abscess.
May mimic colon cancer.<ref name=pmid19332922>{{Cite journal  | last1 = Fernandes | first1 = H. | last2 = D'Souza | first2 = CR. | last3 = Swethadri | first3 = GK. | last4 = Naik | first4 = CN. | title = Ameboma of the colon with amebic liver abscess mimicking metastatic colon cancer. | journal = Indian J Pathol Microbiol | volume = 52 | issue = 2 | pages = 228-30 | month =  | year =  | doi =  | PMID = 19332922 | url=http://www.ijpmonline.org/article.asp?issn=0377-4929;year=2009;volume=52;issue=2;spage=228;epage=230;aulast=Fernandes }}</ref>
===Microscopy===
Features:
*Round/Ovoid eosinophilic bodies ~ 40-60 micrometers in maximal dimension.
*Found in bowel lumen.
*Ingest RBCs.
Image:
*[http://commons.wikimedia.org/wiki/File:Amoebic_dysentery_in_colon_biopsy_%281%29.jpg Amebiasis (WC)].


==Polyps==
==Polyps==

Revision as of 00:44, 18 June 2010

The colon and rectum smell like poo... 'cause that's where poo comes from. It commonly comes to pathologists because there is a suspicion of cancer or a known history of inflammatory bowel disease (IBD).

Common clinical problems

Obstruction

Top three (in adults):[1]

  • Neoplasia,
  • Volvulus (cecal, sigmoid),
  • Diverticular disease + stricture formation.

Bleeding

Mnemonic CHAND:[2]

  • Colitis (radiation, infectious, ischemic, IBD (UC >CD), iatrogenic (anticoagulants)),
  • Hemorrhoids,
  • Angiodysplasia,
  • Neoplastic,
  • Diverticular disease.

Infectious colitis with bleeding - causes:

  • Enterohemorrhagic Escherichia coli (EHEC) -- commonly 0157:H7,
  • Campylobacter jejuni,
  • Clostridium difficile,
  • Shigella.

Infectious colitis in the immunosuppressed:

  • Cytomegalovirus (CMV).[3]
    • May afflict patients with IBD and lead to colectomy... as IBD patients are put on immunosuppression.
    • Organ transplant recipients.
    • HIV/AIDS.

Inflammatory bowel disease (IBD)

Exists in two main flavours:

  • Crohn's disease (CD).
  • Ulcerative colitis (UC).

Clinical

  • It is important to differentiate UC and CD as the management is different.
  • UC patients get pouches... CD patients do not.

Epidemiology:

  • NOD2/CARD15 variants are assoc. with stricturing CD, early need for surgery and recurrence.[4]

Microscopic

Features helpful for the diagnosis of IBD - as based on a study:[5]

  • Basal, i.e. crypt base, plasmacytosis with severe chronic inflammation,
  • Crypt architectural abnormalities, and
  • Distal Paneth cell metaplasia.
    • Paneth cells should not be in the left colon[6] - if you see 'em think of IBD and other long-standing injurious processes.
    • Some claim that (friendly right colonic) paneth cells and paneth cell metaplasia look quite different and can be distinguished.[7]

Notes:

  1. Microscopic features can be remembered by mnemonic CPP: Crypts (abnormal), Plasmacytosis, Paneth cells where they don't belong.
  2. If you see architectural distortion (e.g. crypt branching) in the left colon, look for Paneth cells.
  3. The hepatic flexure is considered the divider for normal paneth cells and abnormal paneth cells, i.e. paneth cells proximal to the hepatic flexure are normal; paneth cells distal to the hepatic flexure are abnormal.[8]

Crohn's disease vs. ulcerative colitis

UC features:[9]

  • Mucosal involvement --sometimes submucosa.
  • No skip lesions.
  • Colon/rectum only.
    • UC may have 'ileal backwash' -- mild ileal inflammation due to backwash of inflammatory soup from colon.
  • "No granulomas".
    • Superficial granulomas in the mucosa are non-specific, especially if they are beside an inflammed crypt, i.e. they may be present in UC.[10][11]
      • Deep granulomas are specific for Crohn's disease.

Example of a superficial granuloma that is non-specific, i.e. this could be UC or CD:

Ulcerative colitis

General

  • Often abbreviated as UC.

Epidemiology

Gross

  • Conventionally considered to be contiguous, i.e. no "skip lesions", with rectal involvement being most severe.
  • Dependent on the study one reads... rectal sparing may be seen in 15% of UC patients.[14]

Microscopic

  • Lack of granulomas.
  • No full wall-thickness inflammation.

Crohn's disease

General

  • Often abbreviated as CD.

Gross

Microscopic

Features:[5]

  • Segmental crypt architectural abnormalities,
  • Mucin depletion,
  • Mucin preservation at the active sites, and
  • Focal chronic inflammation without crypt atrophy.

Bowel ischemia

Radiologic correlate

  • Bowel wall thickening.

Gross

Features:[15]

  • Luminal part (mucosa & submucosa) affected.
  • Splenic flexture of colon commonly affected (vascular watershed).

Note:

  • May have pseudomembranes (classically assoc. with C. difficle colitis), i.e. mimics an infectious process.
  • DDx for pseudomembranes:[16]
    • C. difficle induced pseudomembranous colitis,
    • Ischemic colitis,
    • Volvulus,
    • Necrotizing infections,
    • ... anything that causes severe mucosal injury.

Histology of pseudomembranes:[17]

  • Loss of surf. epithelium,
  • PMNs in lamina propria,
  • +/- capillary fibrin thrombi.

NB: Pseudomembranes arise from the crypts.

Image:

Angiodysplasia

General

  • Causes (lower) GI haemorrhage.
  • Generally, not a problem pathologists see.

Location

  • Cecum.

Epidemiology

  • Older people.

Etiology

  • Thought to be caused by the higher wall tension of cecum (due to larger diameter) and result from (intermittent) venous occulsion/focal dilation of vessels.[18]

Melanosis coli

  • AKA Pseudomelanosis coli.[19]
  • Not melanin as the name suggests; it is actually lipofuscin (in macrophages).[20]
  • Endoscopist may see brown pigmentation of mucosa and suspect the diagnosis.

Epidemiology

  • Classically associated with anthracene containing laxative (e.g. Senokot) use and herbal remedies.[20]

Features

  • Brown pigmentation of the mucosa.
  • Typically more prominent in the cecum and proximal colon.[20]

DDx of brown pigment:

  • Lipofuscin - comes with age (can be demonstrated with a Kluver-Barrera stain[21]).
    • Melanosis coli.
  • Old haemorrhage, i.e. hemosiderin-laden macrophages (may be demonstrated with Prussian blue stain[22]).
  • Melanin (from melanocytes) - rare in colon (may be demonstrated with a Fontana-Masson stain[23] -- though not so useful in the GI tract).
  • Foriegn material (e.g. tattoo pigment) - not seen in GI tract.

Images:

Microscopic colitis

General

Definition:

  • As the name suggests, they are microscopic, i.e. endoscopic examination is normal.

Presentation:

  • Chronic diarrhea, non-bloody.[24]

Microscopic colitis - types

  • Lymphocytic colitis (LC).
  • Collagenous colitis (CC).

Some believe that LC and CC are different time points in the same process-- but this is unproven.[24]

Epidemiology

  • Age: a disease of adults - usually 50s.
  • Sex:
    • LC males ~= females,[24]
    • CC females:males = 20:1.[24]
  • Drugs are associated with LC and CC.
    • NSAIDs - posulated association/weak association,
    • SSRIs (used primarily for depression) - moderate association, dependent on specific drug.
  • Associated with autoimmune disorders - celiac disease, diabetes mellitus, thyroid disorders and arthritis.[25]
  • No increased risk of colorectal carcinoma.[25]

Treatment

  • Sometimes just follow-up.
  • Steroids - budesonide -- short-term treatment.[25]

Characteristics

Lymphocytic colitis

  • Lots of intraepithelial lymphocytes (>=20/100 lymphocytes/surface epithelial cells[25]) and
  • lymphocytes in the lamina propria.
  • NEGATIVES:[26]
    • No PMNs.
    • No crypt distortion.

Collagenous colitis

  • Intraepithelial lymphocytes, and
  • lymphocytes in the lamina propria.
  • Collagenous material in the lamina propria (pink on H&E) -- key feature.
    • Can be demonstrated with a trichrome stain -- collagen = green on trichrome.
    • Subepithelial collagen needs to be >= 10 micrometres thick for Dx.[25]
      • 8 micrometres is the diameter of a RBC.
      • The normal thickness of the subepithelial collagen is 3 micrometres.[25]
    • Thickening "follows the crypts from the surface" - useful for differentiating from tangential sections of the basement membrane.[27]
    • Collagen may envelope capillaries - useful to discern from basement membrane.[28]
  • NEGATIVES[26]
    • No PMNs.
    • No crypt distortion.

Notes: CC is typically more prominent in the proximal colon - may reflect concentration gradient of offending causitive agents.[25]

Spirochetes

General

  • Very rare cause of diarrhea.
  • Caused by Serpulina pilosicoli and Brachyspira aalborgi.[29]
  • Tx: metronidazole.[30]

Histology

  • Hyperchromatic fuzz on luminal aspect of epithelial cells; at brush border.

Special stain:

  • Silver stains highlight 'em (e.g. Warthin-Starry stain).

Amebiasis

General

  • Infection with Entamoeba histolytica.[31]

May cause:[32]

  • Dysentery (diarrhea containing mucus and/or blood in the feces).
  • Colitis.
  • Liver abscess.

May mimic colon cancer.[33]

Microscopy

Features:

  • Round/Ovoid eosinophilic bodies ~ 40-60 micrometers in maximal dimension.
  • Found in bowel lumen.
  • Ingest RBCs.

Image:

Polyps

Main article: Intestinal polyps

Polyps are the bread & butter of GI pathology. They are very common.

Main types:

  • Hyperplastic (most common)
  • Adenomatous (quite common, pre-malignant)
  • Hamartomatous (rare, weird & wonderful)
  • Inflammatory (associated with IBD)

Most common (images):

Colorectal Tumours

Epidemiology

Very common type of cancer.

Classification

Other tumours - many (incomplete list):[35]

  • Mucinous carcinoma.
  • Adenosquamous carcinoma.
  • Signet-ring carcinoma.
  • Squamous carcinoma.
  • Neuroendocrine neoplasms (carcinoid tumours).
  • Lipoma.
  • Leiomyoma.
  • GIST.
  • Angiosarcoma.
  • Lymphoma (Non-Hodgkin's lymphoma).

Grading

  • "adenocarcinoma in situ" and "high-grade dysplasia" is used interchangeably by many in the colon and rectum.
    • splitting hairs - adenocarcinoma in situ is invasion into the lamina propria, high-grade dysplasia does not have lamina propria invasion. Ergo, the difference (in my opinion) amounts to seeing a desmoplastic stroma (adenocarcinoma) or not seeing one (dysplasia).

Grading of tumours:

  • Tis - in situ (intramucosal),
  • T1 - into submucosa (through mucularis mucosae),
    • this is different than elsewhere,
  • T2 - into muscularis propria,
  • T3 - into fat beyond musclaris propria,
  • T4 - into something else.

Nodes:

  • N0 - no positive nodes,
  • N1 - 1-3 positive nodes,
  • N2 - 4+ positive nodes.

Staging of colorectal cancer

Simple version

Tumour/node grade for stage:[36]

  • Stage I - T1 or T2 N0 M0.
  • Stage II - T3 or T4 N0 M0.
  • Stage III - Tx N1 or N2 M0.
  • Stage IV - Tx Nx M1.

Complex version

Detailed tumour/node grade for stage:[37]

  • Stage I - T1 or T2.
  • Stage IIA - T3.
  • Stage IIB - T4.
  • Stage IIIA - T1 N1 or T2 N1.
  • Stage IIIB - T3 N1 or T4 N1.
  • Stage IIIC - Tx N2.
  • Stage IV - Tx Nx M1.

Surgery

Introduction to colorectal surgery:

  1. Colonic resection - remove a piece of large bowel.
  2. Total colectomy - leaves rectum and anus.[38]
  3. Subtotal colectomy - part of colon removed --or-- some of the rectum remains.
  4. right hemicolectomy - right colon + distal ileum.
  5. lower anterior resection (LAR) - proximal rectum +/- sigmoid (for proximal rectal malignancies).
  6. abdominoperineal resection (APR) - anus + rectum - results in a permanent stoma (for distal rectal malignancies).

Grossing

  • Lymph nodes - should get at least 12.[39]

Quirke method

  • Bowel is not opened.

Standard method

  • Bowel is prep'ed by opening it along the antimesenteric side.
  • Dimensions - length, circumference at both margins.
  • Radial margin/circumferential margin - should be painted.
    • Rectum starts/sigmoid ends @ place where serosa ends on the posterior aspect of the bowel.
      • The proximal, anterior aspect of the rectum has serosa, i.e. it is not painted.

Solitary rectal ulcer

General

  • Clinically may be suspected to a malignancy - biopsied routinuely.
  • Mucosal ulceration.
  • "Three-lies disease":[42]
  1. May not be solitary,
  2. May not be rectal -- can be in left colon,
  3. May not be ulcerating -- non-ulcerated lesions: polypoid and/or erythematous.

Note: Each of the words in solitary rectal ulcer is a lie.

Epidemiology

  • Typically younger patients - average age of presentation ~30 years in one study.[43]
  • Rare.

Clinical

  • Usually presents as BRBPR ~ 85% of cases.[43]
  • Abdominal pain present in approx. 1/3.[43]
    • May be very painful.

Histology

Features:[42]

  • Fibrosis of the lamina propria - should be obliterated.
  • Thickened muscularis mucosa - abnormally extends to the lumen.

Histologic DDx

  • Rectal prolapse. (?)

Treatment

  • Usually conservative, i.e. non-surgical.
  • Resection - may be done for fear of malignancy.

Rectal prolapse

Histopathology

Features:[44]

  • "Fibromuscular hyperplasia":
    • Fibrosis,
    • Muscularis mucosae is "too superficial".
  • Surface ulceration + inflammation (neutrophils).
  • +/-Serration of epithelium at the surface.
  • NEGATIVES:
    • No nuclear atypia.

Mucosal prolapse syndrome

  • Similar to rectal prolapse???

Weird stuff

Kayexalate (sodium polystyrene sulfonate):[45]

  • Used to treat hyperkalemia.
  • Purple blobs on H&E stain - look somewhat like calcium phosphate.
  • Can cause focal necrosis.

Image: Sodium polystyrene crystals - commons.wikimedia.org.

Chronic constipation

This is occasionally an indication for colectomy.

Causes:

  • Tumour.
  • Adhesions - due to previous surgery.
  • Neuropathy.
  • Congenital defect (Hirschsprung's disease).
  • Medications/substance use.
  • Idiopathic.

Work-up if no tumour is identified:[46]

  • Routine H&E.
  • Pan-actin.
  • Gomori trichrome.
  • CD117 - to look for the interstitial cell of Cajal.
  • HU - neuronal marker.[47]

Goblet cell carcinoid

Described in detail in the appendix article.
  • AKA crypt cell carcinoma.
  • Biphasic tumour; features of carcinoid tumour and adenocarcinoma.

See also

References

  1. ↑ http://www.emedicine.com/EMERG/topic65.htm
  2. ↑ TN 2007 G29.
  3. ↑ Golden MP, Hammer SM, Wanke CA, Albrecht MA (September 1994). "Cytomegalovirus vasculitis. Case reports and review of the literature". Medicine (Baltimore) 73 (5): 246–55. PMID 7934809.
  4. ↑ Alvarez-Lobos M, Arostegui JI, Sans M, et al. (November 2005). "Crohn's disease patients carrying Nod2/CARD15 gene variants have an increased and early need for first surgery due to stricturing disease and higher rate of surgical recurrence". Ann. Surg. 242 (5): 693–700. PMC 1409853. PMID 16244543. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1409853/.
  5. ↑ 5.0 5.1 Tanaka M, Riddell RH, Saito H, Soma Y, Hidaka H, Kudo H (January 1999). "Morphologic criteria applicable to biopsy specimens for effective distinction of inflammatory bowel disease from other forms of colitis and of Crohn's disease from ulcerative colitis". Scand. J. Gastroenterol. 34 (1): 55–67. PMID 10048734.
  6. ↑ Tanaka M, Saito H, Kusumi T, et al (December 2001). "Spatial distribution and histogenesis of colorectal Paneth cell metaplasia in idiopathic inflammatory bowel disease". J. Gastroenterol. Hepatol. 16 (12): 1353–9. PMID 11851832. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0815-9319&date=2001&volume=16&issue=12&spage=1353.
  7. ↑ Rubio CA, Nesi G (2003). "A simple method to demonstrate normal and metaplastic Paneth cells in tissue sections". In Vivo 17 (1): 67–71. PMID 12655793.
  8. ↑ STC. 14 December 2009.
  9. ↑ PBoD P.850.
  10. ↑ Shepherd, NA. (Aug 2002). "Granulomas in the diagnosis of intestinal Crohn's disease: a myth exploded?". Histopathology 41 (2): 166-8. PMID 12147095.
  11. ↑ Mahadeva, U.; Martin, JP.; Patel, NK.; Price, AB. (Jul 2002). "Granulomatous ulcerative colitis: a re-appraisal of the mucosal granuloma in the distinction of Crohn's disease from ulcerative colitis.". Histopathology 41 (1): 50-5. PMID 12121237.
  12. ↑ Beaugerie, L.; Sokol, H. (Aug 2009). "Appendicitis, not appendectomy, is protective against ulcerative colitis, both in the general population and first-degree relatives of patients with IBD.". Inflamm Bowel Dis. doi:10.1002/ibd.21064. PMID 19685454.
  13. ↑ 13.0 13.1 Timmer, A.; Obermeier, F. (2009). "Reduced risk of ulcerative colitis after appendicectomy.". BMJ 338: b225. PMID 19273505.
  14. ↑ Bernstein CN, Shanahan F, Anton PA, Weinstein WM (September 1995). "Patchiness of mucosal inflammation in treated ulcerative colitis: a prospective study". Gastrointest. Endosc. 42 (3): 232-7. PMID 7498688.
  15. ↑ PBoD P.852.
  16. ↑ PBoD P.837-8.
  17. ↑ PBoD P.837-8.
  18. ↑ PBoD P.854
  19. ↑ http://www.medicinenet.com/melanosis_coli/article.htm
  20. ↑ 20.0 20.1 20.2 Freeman HJ (July 2008). ""Melanosis" in the small and large intestine". World J. Gastroenterol. 14 (27): 4296-9. PMID 18666316. http://www.wjgnet.com/1007-9327/14/4296.asp.
  21. ↑ URL: http://education.vetmed.vt.edu/curriculum/VM8054/labs/Lab2/Examples/exkluvbarr.htm. Accessed on: 5 May 2010.
  22. ↑ URL: http://education.vetmed.vt.edu/curriculum/VM8054/labs/Lab2/Examples/exprussb.htm. Accessed on: 5 May 2010.
  23. ↑ URL: http://education.vetmed.vt.edu/curriculum/VM8054/labs/Lab2/Examples/exfontana.htm. Accessed on: 5 May 2010.
  24. ↑ 24.0 24.1 24.2 24.3 URL: http://emedicine.medscape.com/article/180664-overview. Accessed on: 31 May 2010.
  25. ↑ 25.0 25.1 25.2 25.3 25.4 25.5 25.6 Tysk C, Bohr J, Nyhlin N, Wickbom A, Eriksson S (December 2008). "Diagnosis and management of microscopic colitis". World J. Gastroenterol. 14 (48): 7280-8. PMID 19109861. http://www.wjgnet.com/1007-9327/14/7280.asp.
  26. ↑ 26.0 26.1 http://hopkins-gi.nts.jhu.edu/pages/latin/templates/index.cfm?pg=disease1&disease=29&organ=6&lang_id=1
  27. ↑ BEC 4 Mar 2009
  28. ↑ BEC 4 Mar 2009
  29. ↑ Amat Villegas I, Borobio Aguilar E, Beloqui Perez R, de Llano Varela P, Oquiñena Legaz S, Martínez-Peñuela Virseda JM (January 2004). "[Colonic spirochetes: an infrequent cause of adult diarrhea]" (in Spanish; Castilian). Gastroenterol Hepatol 27 (1): 21–3. PMID 14718105.
  30. ↑ Calderaro A, Bommezzadri S, Gorrini C, et al. (November 2007). "Infective colitis associated with human intestinal spirochetosis". J. Gastroenterol. Hepatol. 22 (11): 1772–9. doi:10.1111/j.1440-1746.2006.04606.x. PMID 17914949.
  31. ↑ URL: http://www.health.state.ny.us/diseases/communicable/amebiasis/fact_sheet.htm. Accessed on: 17 June 2010.
  32. ↑ Mortimer, L.; Chadee, K. (Mar 2010). "The immunopathogenesis of Entamoeba histolytica.". Exp Parasitol. doi:10.1016/j.exppara.2010.03.005. PMID 20303955.
  33. ↑ Fernandes, H.; D'Souza, CR.; Swethadri, GK.; Naik, CN.. "Ameboma of the colon with amebic liver abscess mimicking metastatic colon cancer.". Indian J Pathol Microbiol 52 (2): 228-30. PMID 19332922. http://www.ijpmonline.org/article.asp?issn=0377-4929;year=2009;volume=52;issue=2;spage=228;epage=230;aulast=Fernandes.
  34. ↑ PBoD P.864.
  35. ↑ WMSP P.198.
  36. ↑ TN 2006 GS27
  37. ↑ http://www.cancer.org/docroot/CRI/content/CRI_2_4_3X_How_is_colon_and_rectum_cancer_staged.asp
  38. ↑ http://www.allaboutbowelsurgery.com/shared/stoma_care/stoma_surgery/procedures/surgery_colon/subtotal.htm
  39. ↑ Bilimoria KY, Bentrem DJ, Stewart AK, et al. (September 2008). "Lymph node evaluation as a colon cancer quality measure: a national hospital report card". J. Natl. Cancer Inst. 100 (18): 1310–7. doi:10.1093/jnci/djn293. PMID 18780863. http://www.medscape.com/viewarticle/581463.
  40. ↑ West NP, Morris EJ, Rotimi O, Cairns A, Finan PJ, Quirke P (September 2008). "Pathology grading of colon cancer surgical resection and its association with survival: a retrospective observational study". Lancet Oncol. 9 (9): 857–65. doi:10.1016/S1470-2045(08)70181-5. PMID 18667357.
  41. ↑ West NP, Finan PJ, Anderin C, Lindholm J, Holm T, Quirke P (July 2008). "Evidence of the oncologic superiority of cylindrical abdominoperineal excision for low rectal cancer". J. Clin. Oncol. 26 (21): 3517–22. doi:10.1200/JCO.2007.14.5961. PMID 18541901.
  42. ↑ 42.0 42.1 Crespo Pérez L, Moreira Vicente V, Redondo Verge C, López San Román A, Milicua Salamero JM (November 2007). "["The three-lies disease": solitary rectal ulcer syndrome"] (in Spanish; Castilian). Rev Esp Enferm Dig 99 (11): 663–6. PMID 18271667. http://www.grupoaran.com/mrmUpdate/lecturaPDFfromXML.asp?IdArt=459864&TO=RVN&Eng=1.
  43. ↑ 43.0 43.1 43.2 Chong VH, Jalihal A (December 2006). "Solitary rectal ulcer syndrome: characteristics, outcomes and predictive profiles for persistent bleeding per rectum". Singapore Med J 47 (12): 1063–8. PMID 17139403. http://www.sma.org.sg/smj/4712/4712a7.pdf.
  44. ↑ NEED REF.
  45. ↑ Abraham SC, Bhagavan BS, Lee LA, Rashid A, Wu TT (May 2001). "Upper gastrointestinal tract injury in patients receiving kayexalate (sodium polystyrene sulfonate) in sorbitol: clinical, endoscopic, and histopathologic findings". Am. J. Surg. Pathol. 25 (5): 637-44. PMID 11342776. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0147-5185&volume=25&issue=5&spage=637.
  46. ↑ IAV. 15 December 2009.
  47. ↑ PMID 8586967.
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