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| __NOTOC__ | | __NOTOC__ |
| {{Appendix cancer}} | | {{Appendix cancer}} |
| {{CMG}} {{AE}} {{MV}} {{Faizan}} | | {{CMG}}; {{AE}} {{Soroush}} |
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| {{SK}} Tumors of the appendix; Appendiceal cancer; Cancer of the appendix; Neoplasms of the appendix
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| ==Overview== | | ==Overview== |
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| '''Appendix cancer''' is a rare malignancy of the vermiform appendix. The most common type of appendix cancer is carcinoid tumor. Appendix cancers often present with peritoneal seeding, resulting in [[peritoneal carcinomatosis]] or [[pseudomyxoma peritonei]].<ref name="pmid22302267">{{cite journal |vauthors=Turaga KK, Pappas SG, Gamblin T |title=Importance of histologic subtype in the staging of appendiceal tumors |journal=Ann. Surg. Oncol. |volume=19 |issue=5 |pages=1379–85 |year=2012 |pmid=22302267 |doi=10.1245/s10434-012-2238-1 |url=}}</ref> Appendix cancer may be classified according to WHO classification into 4 groups:
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| epithelial tumors, non-epithelial tumors, secondary tumors, and hyperplastic (metaplastic) polyp. Common causes of appendix cancer may include hereditary syndromes (eg. [[familial adenomatous polyposis]], [[Hereditary nonpolyposis colorectal cancer|hereditary non-polyposis colorectal cancer]]) and chronic inflammatory diseases (eg. [[ulcerative colitis]], [[Crohn's disease]]). Appendiceal neoplasms account for approximately 0.4% of gastrointestinal tumors. The estimated prevalence of appendix cancer is approximately 0.12 cases per 100,000 individuals in the United States. On gross pathology, well-demarcated mass, between 1-5 cm, gray or yellowish color are characteristic findings of appendix cancer. Early clinical features include periodical unspecific [[abdominal pain]], [[bloating]], and [[nausea]]. Enhanced CT is the imaging modality of choice for appendix cancer. On CT scan, appendix cancer is characterized by the following findings: soft tissue thickening, wall irregularity, presence of pseudomyxoma peritonei, calcification, and internal septations. Surgery is the mainstay of therapy for appendix cancer. Right [[hemicolectomy]] in conjunction with [[chemotherapy]] is the most common approach to the treatment of appendix cancer. The prognosis of appendix cancer will depend on tumor histology. However, the overall 5-survival rate of patients with appendix cancer is approximately 51%.<ref name="pmid16973770">{{cite journal |vauthors=Hoeffel C, Crema MD, Belkacem A, Azizi L, Lewin M, Arrivé L, Tubiana JM |title=Multi-detector row CT: spectrum of diseases involving the ileocecal area |journal=Radiographics |volume=26 |issue=5 |pages=1373–90 |year=2006 |pmid=16973770 |doi=10.1148/rg.265045191 |url=}}</ref> Once diagnosed and successfully treated, patients with appendix cancer are followed-up every 3, 12 months. Follow-up testing for appendix cancer include physical examination, medical history, imaging studies, chromogranin testing, and laboratory studies (eg. tumoral biomarkers).
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| ==Historical Perspective== | | ==Historical Perspective== |
| *Appendix cancer was first described by Gagne, a French Physician, in 1969.<ref name="pmid5378353">{{cite journal |vauthors=Gagné F, Fortin P, Dufour V, Delage C |title=[Tumors of the appendix associating histologic features of carcinoid and adenocarcinoma] |language=French |journal=Ann Anat Pathol (Paris) |volume=14 |issue=4 |pages=393–406 |year=1969 |pmid=5378353 |doi= |url=}}</ref>
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| ==Classification== | | ==Classification== |
| *Appendix cancer may be classified according to WHO classification into 4 groups:<ref name="WHO">Chapter 5: Tumours of the Appendix - IARC. https://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb2/bb2-chap5.pdf Accessed on April 6, 2016</ref>
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| :*Epithelial tumors
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| :*Non-epithelial tumors
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| :*Secondary tumors
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| :*Hyperplastic (metaplastic) polyp
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| *The table below summarizes the different types of appendix cancer according to the WHO classification.<ref name="WHO">Chapter 5: Tumours of the Appendix - IARC. https://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb2/bb2-chap5.pdf Accessed on April 6, 2016</ref>
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| {| style="border: 5px; font-size: 90%; margin: 5px; width: 300px" align="center"
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| ! colspan="2" style="padding: 5px 5px; background: #4479BA; font-weight: bold; text-align:center;" |{{fontcolor|#FFF|'''WHO histological classification<br>Tumors of the appendix <br><SMALL> Adapted from WHO/IARC<ref name="WHO"> Chapter 5: Tumours of the Appendix - IARC. https://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb2/bb2-chap5.pdf Accessed on April 6, 2016</ref> </SMALL>'''}}
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| | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" | Epithelial tumors
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| *'''Adenoma'''
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| :*Tubular
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| :*Villous
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| :*Tubulovillous
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| :*Serrated
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| *'''Carcinoma'''
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| :*Adenocarcinoma
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| :*Mucinous adenocarcinoma
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| :*Signet-ring cell carcinoma
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| :*Small cell carcinoma
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| :*Undifferentiated carcinoma
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| *'''Carcinoid (well differentiated endocrine neoplasm)'''
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| *'''Tubular carcinoid'''
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| *'''Goblet cell carcinoid (mucinous carcinoid)'''
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| *'''Mixed carcinoid-adenocarcinoma'''
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| *'''Others'''
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| | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" | Non-epithelial tumors
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| *Neuroma
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| *Lipoma
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| *Leiomyoma
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| *Gastrointestinal stromal tumor
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| *Leiomyosarcoma
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| *Kaposi sarcoma
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| *Others
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| |-
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| | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" | Secondary tumors
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| *Metastasis (eg. Primary of urogenital tract, breast, lung)
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| |-
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| | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" | Hyperplastic polyp
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| |}
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| ==Pathophysiology== | | ==Pathophysiology== |
| *The pathogenesis of appendix cancer is characterized by an initial [[Dysplasia|epithelial dysplasia]], followed by the formation of cystic structures and angiolymphatic invasion. Subsequently, in the advanced stages of appendix cancer, tumor cells detach from the primary tumor mass and gain access to the peritoneal cavity.<ref name="pmid22084738">{{cite journal |vauthors=Ruoff C, Hanna L, Zhi W, Shahzad G, Gotlieb V, Saif MW |title=Cancers of the appendix: review of the literatures |journal=ISRN Oncol |volume=2011 |issue= |pages=728579 |year=2011 |pmid=22084738 |pmc=3200132 |doi=10.5402/2011/728579 |url=}}</ref>
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| *The KRAS gene mutation has been associated with the development of appendix cancer.
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| *On gross pathology, findings of appendix cancer, include:<ref name="pmid22084738">{{cite journal |vauthors=Ruoff C, Hanna L, Zhi W, Shahzad G, Gotlieb V, Saif MW |title=Cancers of the appendix: review of the literatures |journal=ISRN Oncol |volume=2011 |issue= |pages=728579 |year=2011 |pmid=22084738 |pmc=3200132 |doi=10.5402/2011/728579 |url=}}</ref>
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| :*Well-demarcated mass
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| :*Average size between 1 and 5 cm
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| :*Gray or yellowish color
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| :*Deformed appendix
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| *The image below demonstrates gross pathology of appendix cancer.
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| <gallery>image:800px-Appendiceal_carcinoid_1.JPG | Gross pathology appendix cancer</gallery>
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| *On microscopic histopathological analysis findings will depend on the subtype of appendicular cancer.
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| *Common histopathological findings, may include:<ref name="pmid22084738">{{cite journal |vauthors=Ruoff C, Hanna L, Zhi W, Shahzad G, Gotlieb V, Saif MW |title=Cancers of the appendix: review of the literatures |journal=ISRN Oncol |volume=2011 |issue= |pages=728579 |year=2011 |pmid=22084738 |pmc=3200132 |doi=10.5402/2011/728579 |url=}}</ref>
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| :*Cystic structures
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| :*Angiolymphatic invasion
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| *The images below demonstrate different histopathological findings of appendix cancer.
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| <gallery>800px-Appendix_Carcinoid_Torsion_1X_PA.JPG | Appendiceal carcinoid<ref name=aaa>http://librepathology.org/wiki/index.php/Neuroendocrine_tumour_of_the_appendix</ref>
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| 800px-Appendix_Carcinoid_HP_14BR---.jpg | Appendiceal carcinoid<ref name=aaa>http://librepathology.org/wiki/index.php/Neuroendocrine_tumour_of_the_appendix</ref>
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| 800px-Appendix_Carcinoid_Necrosis_PA.JPG | Appendiceal carcinoid with necrosis<ref name =aaa>http://librepathology.org/wiki/index.php/Neuroendocrine_tumour_of_the_appendix</ref>
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| 800px-Appendix_Carcinoid_Synaptophysin_14BR---.jpg | Carcinoid synaptophysin<ref name=aaa>http://librepathology.org/wiki/index.php/Neuroendocrine_tumour_of_the_appendix</ref>
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| 800px-Appendix_Carcinoid_HP_CTR.jpg | Appendiceal tumor<ref name=aaa>http://librepathology.org/wiki/index.php/Neuroendocrine_tumour_of_the_appendix</ref>
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| </gallery>
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| ==Causes== | | ==Causes== |
| *Common causes of appendix cancer may include:<ref name="pmid22084738">{{cite journal |vauthors=Ruoff C, Hanna L, Zhi W, Shahzad G, Gotlieb V, Saif MW |title=Cancers of the appendix: review of the literatures |journal=ISRN Oncol |volume=2011 |issue= |pages=728579 |year=2011 |pmid=22084738 |pmc=3200132 |doi=10.5402/2011/728579 |url=}}</ref>
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| *Chronic inflammatory diseases, such as:
| | ==Differentiating Xyz from Other Diseases== |
| :*Ulcerative colitis
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| :*Crohn's disease
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| *Hereditary syndromes, such as:
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| :*Familial adenomatous polyposis
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| :*Hereditary non-polyposis colorectal cancer
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| ==Differentiating Appendix Cancer from Other Diseases== | |
| * Appendix cancer must be differentiated from other diseases that cause abdominal pain, nausea, vomiting such as:<ref name="pmid22084738">{{cite journal |vauthors=Ruoff C, Hanna L, Zhi W, Shahzad G, Gotlieb V, Saif MW |title=Cancers of the appendix: review of the literatures |journal=ISRN Oncol |volume=2011 |issue= |pages=728579 |year=2011 |pmid=22084738 |pmc=3200132 |doi=10.5402/2011/728579 |url=}}</ref>
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| :*[[Appendicitis]]
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| :*[[Typhlitis]]
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| :*I[[Ileitis|nfectious terminal ileitis]]
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| :*Ileocecal enteric duplication cyst
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| ==Epidemiology and Demographics== | | ==Epidemiology and Demographics== |
| * The estimated prevalence of appendix cancer is approximately 0.12 cases per 100,000 individuals in the United States.<ref name="pmid22302267">{{cite journal |vauthors=Turaga KK, Pappas SG, Gamblin T |title=Importance of histologic subtype in the staging of appendiceal tumors |journal=Ann. Surg. Oncol. |volume=19 |issue=5 |pages=1379–85 |year=2012 |pmid=22302267 |doi=10.1245/s10434-012-2238-1 |url=}}</ref>
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| * The estimated prevalence of adenocarcinoma of the appendix is 0.2 cases per 100,000 individuals worldwide.<ref name="pmid22302267">{{cite journal |vauthors=Turaga KK, Pappas SG, Gamblin T |title=Importance of histologic subtype in the staging of appendiceal tumors |journal=Ann. Surg. Oncol. |volume=19 |issue=5 |pages=1379–85 |year=2012 |pmid=22302267 |doi=10.1245/s10434-012-2238-1 |url=}}</ref>
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| *Appendiceal neoplasms account for approximately 0.4% of gastrointestinal tumors.
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| ===Age===
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| * The median age at diagnosis of patients with appendix cancer is 65 years.
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| * Appendix cancer is more commonly observed among patients aged 50 to 60 years old.<ref name="pmid22302267">{{cite journal |vauthors=Turaga KK, Pappas SG, Gamblin T |title=Importance of histologic subtype in the staging of appendiceal tumors |journal=Ann. Surg. Oncol. |volume=19 |issue=5 |pages=1379–85 |year=2012 |pmid=22302267 |doi=10.1245/s10434-012-2238-1 |url=}}</ref>
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| * Appendix cancer is more commonly observed among adults and elderly patients.<ref name="pmid22302267">{{cite journal |vauthors=Turaga KK, Pappas SG, Gamblin T |title=Importance of histologic subtype in the staging of appendiceal tumors |journal=Ann. Surg. Oncol. |volume=19 |issue=5 |pages=1379–85 |year=2012 |pmid=22302267 |doi=10.1245/s10434-012-2238-1 |url=}}</ref>
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| ===Gender===
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| *Males are more commonly affected with appendix cancer than females.<ref name="wiki">Appendix Cancer. Wikipedia. https://en.wikipedia.org/wiki/Appendix_cancer Accessed on April 7, 2016 </ref>
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| ===Race===
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| *There is no racial predilection for appendix cancer.
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| ==Risk Factors== | | ==Risk Factors== |
| *Common risk factors in the development of appendix cancer are family history of cancer, long-standing ulcerative colitis, and chronic [[Inflammatory bowel disease classification|inflammatory bowel diseases]].<ref name="pmid22302267">{{cite journal |vauthors=Turaga KK, Pappas SG, Gamblin T |title=Importance of histologic subtype in the staging of appendiceal tumors |journal=Ann. Surg. Oncol. |volume=19 |issue=5 |pages=1379–85 |year=2012 |pmid=22302267 |doi=10.1245/s10434-012-2238-1 |url=}}</ref>
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| == Natural History, Complications and Prognosis== | | ==Screening== |
| *The majority of patients with appendix cancer may be initially asymptomatic.
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| *Early clinical features include periodical unspecific abdominal pain, bloating, and nausea.
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| *If left untreated, the majority of patients with appendix cancer may progress to develop peritoneal carcinomatosis and metastases.<ref name="wiki">Appendix Cancer. Wikipedia. https://en.wikipedia.org/wiki/Appendix_cancer Accessed on April 7, 2016 </ref>
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| *Common complications of appendix cancer include [[perforation]], [[peritonitis]], and [[abscess]].
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| *Prognosis will depend on tumor histology. However, the overall 5 year survival rate of patients with appendix cancer is approximately 50%.<ref name="WHO">Chapter 5: Tumours of the Appendix - IARC. https://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb2/bb2-chap5.pdf Accessed on April 6, 2016</ref>
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| == Diagnosis == | | ==Natural History, Complications, and Prognosis== |
| ===Diagnostic Criteria===
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| *The diagnosis of appendix cancer is made with histopathological evaluation of the following diagnostic criteria:<ref name="pmid22302267">{{cite journal |vauthors=Turaga KK, Pappas SG, Gamblin T |title=Importance of histologic subtype in the staging of appendiceal tumors |journal=Ann. Surg. Oncol. |volume=19 |issue=5 |pages=1379–85 |year=2012 |pmid=22302267 |doi=10.1245/s10434-012-2238-1 |url=}}</ref>
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| :*Tumor confined to the appendix
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| :*Invasion to the [[muscularis mucosae]]
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| :*Presence of [[metastases]]
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| :*Spread to the [[peritoneal cavity]]
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| === Symptoms ===
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| *Symptoms of appendix cancer may include the following:<ref name="pmid24298858">{{cite journal |vauthors=Drake FT, Flum DR |title=Improvement in the diagnosis of appendicitis |journal=Adv Surg |volume=47 |issue= |pages=299–328 |year=2013 |pmid=24298858 |pmc=4214266 |doi= |url=}}</ref>
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| :*Chronic [[abdominal pain]]
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| ::*Periumbilical
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| ::*Right lower quadrant
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| :*[[Loss of appetite]]
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| :*[[Nausea]]
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| :*[[Vomiting]]
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| :*[[Diarrhea]]
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| :*[[Micturition]]
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| :*[[Tenesmus]]
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| :*[[Indigestion]]
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| :*[[Flatulence]]
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| :*Bowel irregularity
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| === Physical Examination === | | ==Diagnosis== |
| *Patients with appendix cancer may appear normal, pale or diaphoretic.
| | ===Diagnostic Study of Choice=== |
| *Abdominal examination may be remarkable for:<ref name="pmid24298858">{{cite journal |vauthors=Drake FT, Flum DR |title=Improvement in the diagnosis of appendicitis |journal=Adv Surg |volume=47 |issue= |pages=299–328 |year=2013 |pmid=24298858 |pmc=4214266 |doi= |url=}}</ref>
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| '''Palpation'''
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| *The abdominal wall is very sensitive to mild palpation
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| *[[Rebound tenderness]]
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| *[[Abdominal guarding]]
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| * [[Rovsing's sign]]
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| * [[Psoas sign]]
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| '''Rectal examination'''
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| *Tenderness in the [[rectovesical pouch]]
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| === Laboratory Findings === | | ===History and Symptoms=== |
| *Laboratory findings consistent with the diagnosis of appendix cancer, may include:<ref name="pmid3696178">{{cite journal |vauthors=Moertel CG, Weiland LH, Nagorney DM, Dockerty MB |title=Carcinoid tumor of the appendix: treatment and prognosis |journal=N. Engl. J. Med. |volume=317 |issue=27 |pages=1699–701 |year=1987 |pmid=3696178 |doi=10.1056/NEJM198712313172704 |url=}}</ref>
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| :* [[Leukocytosis]] and a shift to the left in the segmented [[neutrophils]].
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| :* Elevated serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA)
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| :* Elevated c-reactive protein (CRP)
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| :* Elevated plasma levels of Chromogranin A
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| ===Imaging Findings=== | | ===Physical Examination=== |
| *Enhanced CT is the imaging modality of choice for appendix cancer.
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| *On CT, appendix cancer is characterized by the following findings:<ref name="pmid16973770">{{cite journal |vauthors=Hoeffel C, Crema MD, Belkacem A, Azizi L, Lewin M, Arrivé L, Tubiana JM |title=Multi-detector row CT: spectrum of diseases involving the ileocecal area |journal=Radiographics |volume=26 |issue=5 |pages=1373–90 |year=2006 |pmid=16973770 |doi=10.1148/rg.265045191 |url=}}</ref>
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| :*Soft tissue thickening
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| :*Wall irregularity
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| :*Presence of pseudomyxoma peritonei
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| :*Calcification
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| :*Internal septations
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| :*Periappendiceal fat stranding and intraperitoneal free fluid is nonspecific.
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| *On abdominal MRI, appendix cancer is characterized by the following findings:
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| :*Nodular mass originating from the bowel wall
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| :*Regional uniform bowel wall thickening with moderate intense enhancement on postgadolinium T1-weighted fat-suppressed images.
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| === Other Diagnostic Studies === | | ===Laboratory Findings=== |
| * Appendix cancer may also be diagnosed using the following diagnostic studies:<ref name="pmid3696178">{{cite journal |vauthors=Moertel CG, Weiland LH, Nagorney DM, Dockerty MB |title=Carcinoid tumor of the appendix: treatment and prognosis |journal=N. Engl. J. Med. |volume=317 |issue=27 |pages=1699–701 |year=1987 |pmid=3696178 |doi=10.1056/NEJM198712313172704 |url=}}</ref>
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| :*[[Somatostatin]] [[scintigraphy]] with 111-indium-octreotide
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| :*[[Bone]] [[scintigraphy]] with 99mTc-methylene diphosphonate (99mTcMDP)
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| :*[[Capsule endoscopy]]
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| :*[[Enteroscopy]]
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| :*[[Positron emission tomography]] (PET)
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| == Treatment == | | ===Electrocardiogram=== |
| === Medical Therapy === | |
| *The mainstay medical therapy for appendix cancer is supportive care.<ref name="wiki">Appendix Cancer. Wikipedia. https://en.wikipedia.org/wiki/Appendix_cancer Accessed on April 7, 2016 </ref>
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| *Supportive care for appendix cancer, may include:<ref name="pmid3696178">{{cite journal |vauthors=Moertel CG, Weiland LH, Nagorney DM, Dockerty MB |title=Carcinoid tumor of the appendix: treatment and prognosis |journal=N. Engl. J. Med. |volume=317 |issue=27 |pages=1699–701 |year=1987 |pmid=3696178 |doi=10.1056/NEJM198712313172704 |url=}}</ref><ref>Treatment Option Overview for GI Carcinoid Tumors
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| . NATIONAL CANCER INSTITUTE . http://www.cancer.gov/types/gi-carcinoid-tumors/hp/gi-carcinoid-treatment-pdq#link/_97_toc Accessed on September 22, 2015</ref>
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| :*[[Somatostatin]] analogs
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| ::*Octreotide or lanreotide.
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| :*Systemic chemotherapy or intraperitoneal chemotherapy
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| ::*Common chemotherapy regimen, include: cyclophosphamide, doxorubicin, vincristine, and prednisone.
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| :*[[Interferons]]
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| :*[[Loperamide]] or [[diphenoxylate]] (for diarrhea)
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| === Surgery === | | ===X-ray=== |
| *Surgery is the mainstay of therapy for appendix cancer.<ref name="pmid3696178">{{cite journal |vauthors=Moertel CG, Weiland LH, Nagorney DM, Dockerty MB |title=Carcinoid tumor of the appendix: treatment and prognosis |journal=N. Engl. J. Med. |volume=317 |issue=27 |pages=1699–701 |year=1987 |pmid=3696178 |doi=10.1056/NEJM198712313172704 |url=}}</ref>
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| *Right hemicolectomy in conjunction with chemotherapy is the most common approach to the treatment of appendix cancer.
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| === Prevention === | | ===Echocardiography and Ultrasound=== |
| *There are no primary preventive measures available for appendix cancer.
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| *Once diagnosed and successfully treated, patients with appendix cancer are followed-up every 3, 12 months.<ref name="wiki">Appendix Cancer. Wikipedia. https://en.wikipedia.org/wiki/Appendix_cancer Accessed on April 7, 2016 </ref>
| | ===CT scan=== |
| *Follow-up testing for appendix cancer includes physical examination, medical history, imaging studies, chromogranin testing, and laboratory studies (eg. tumoral biomarkers).<ref name="pmid3696178">{{cite journal |vauthors=Moertel CG, Weiland LH, Nagorney DM, Dockerty MB |title=Carcinoid tumor of the appendix: treatment and prognosis |journal=N. Engl. J. Med. |volume=317 |issue=27 |pages=1699–701 |year=1987 |pmid=3696178 |doi=10.1056/NEJM198712313172704 |url=}}</ref>
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| | ===MRI=== |
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| | ===Other Imaging Findings=== |
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| | ===Other Diagnostic Studies=== |
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| | ==Treatment== |
| | ===Medical Therapy=== |
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| | === Interventions === |
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| | ===Surgery=== |
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| | ===Primary Prevention=== |
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| | ===Secondary Prevention=== |
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| ==References== | | ==References== |
| {{Reflist|2}} | | {{reflist|2}} |
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