Small intestine cancer
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Qurrat-ul-ain Abid, M.D.[2], Parminder Dhingra, M.D. [3]
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Small intestine cancer Microchapters |
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Small intestine cancer On the Web |
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Risk calculators and risk factors for Small intestine cancer |
Synonyms and keywords:
Overview
Historical Perspective
Despite of
Classification
Intestinal cancers can be classified into:[1]
- Benign tumors
- Malignant tumors
- Extra-intestinal tumors.
| Tumors | Types |
|---|---|
| Benign Tumors | 1- Leiomyoma
2-Lipoma 3-Hamartoma 4-Desmoid tumors |
| Malignant Tumors | 1-Adenocarcinoma
2-Leiomyosarcoma 3-Carcinoid tumors 4-Neuroendocrine tumors 5-Lymphomas |
| Extra- Intestinal Tumors | Metastasis to small intestine is mostly through:
1-Contagious spread (uncommon, mostly route of spread for Melanoma) 2-Peritoneal spread |
Pathophysiology
- Pathophysiology of the small intestinal cancers is not much studied domain, as it is a rare condition.
- Studies are being conducted to evaluate association with environmental risk factors. [2]
Associations:
- Cancer of small intestine can arise sporadically or they are associated with genetic diseases.
- The pathophysiology of small intestinal cancers depend on the histological subtype.
- Duodenal tumors are more common than the tumors of jejunum and illeum.[3] Adenomas arise more proximally, in the duodenum and lymphomas arise in jejunum and ileum.[4] Some of the associations of intestinal cancers are:[1]
- Familial Adenomatous Polyposis Coli
- Peutz-Jeghers syndrome
- Chronic intestinal inflammatory disorders e.g., Crohn's disease
- Celiac sprue
Adenocarcinoma:
- Adenocarcinoma of the smalls intestine originate locally or can be associated with malignant tumors of other sites.
- Rarely people with Peutz-Jeghers syndrome can develop malignant changes in polyps present in the small intestine.
- Primary adenocarcinoma consists of 40% of cases of malignant tumors of small intestine and it is the most common histologic type. [5]
- Adenocarcinomas can be polypoid, infiltrating, or as annular constricting lesions is small intestine. polyps and adenomas of small intestine are considered precursor lesions of adenocarcinoma.[6]
Neuroendocrine tumors:
- Small Intestinal neuroendocrine tumors (SI-NETs) are the most common gastrointestinal neuroendocrine tumors.[7]
- They are diverse neoplasms emerging from the endocrine cells of the intestinal mucosa.[8]
- These tumors originate from enterochromaffin (EC) cells and secrete serotonin.[9]
- The oncofetal protein IMP3 is a marker that plays a role in the growth of neuroendocrine cells and its expression is associated with prognostic value in neuroendocrine tumors.[8]
Carcinoid tumors:
- Carcinoid tumors are the second most common cancer of the small intestine.
- It is a slow growing tumor of small intestine arising as a subset of neuroendocrine cells.
- Carcinoid tumors of the smalls intestine are mostly associated with malignant tumors of the other sites. [5]
Non-Hodgkin Lymphoma:
- After stomach, small intestine is the most common extra-nodal site of presentation of non-Hodgkin lymphomas and it represents 4% to 20% of all the non-Hodgkin lymphomas.
- Some of the association of non-Hodgkin lymphomas are :[10]
- Helicobacter pylori infection
- Immunosuppression after solid-organ transplantation
- Celiac disease
- Inflammatory bowel disease
- Human immunodeficiency virus (HIV)
- Small intestinal lymphomas are of low-grade histology and arise from mucosal-associated lymphoid tissues (MALT) present in ileum and jejunum.Sometimies distinct clinicopathologic entities arise from these mucosal-associated lymphoid tissues (MALT), such as immunoproliferative small intestinal disease, primary intestinal T-cell lymphoma and multiple lymphomatous polyposis.[10]
Small intestinal stromal tumors (GISTs):
- Gastrointestinal stromal tumors (GISTs) are the most common benign tumors of the gastrointestinal (GI) tract.
- GISTs typically develop in older age. Stromal tumors are most common in the stomach, 60–70% of the stromal tumors, followed by small intestine which makes 20–25% of all the stromal tumors of GI tract, colon and rectum makes 5% and esophagus is less than 5%. GISTs are mostly benign tumors and rarely can be malignant.
- Instestinal stromal cell tumors should be differentiated from leiomyosarcomas and leiomyomas. They differ clinically and pathogenetically from leiomyosarcomas and leiomyomas. Leimyomas occur in the GI tract, commonly in the esophagus.
- One of the subset of intestinal stromal cell tumors is the GI autonomic nerve tumors (GANTs). Stromal tumors can be differentiated from other tumors of small intestine by their cell specific markers.
- GISTs express following stromal cell markers:[11]
- 70% of GISTs are positive for CD34
- 20–30% are positive for smooth muscle actin (SMA)
- 10% are positive for S100 protein
- <5% are positive for desmin
Etiology
- Some genetic syndromes are associated with small intestine cancers. Intestinal cancer caused by the genetic syndrome in the presence of a family history, are diagnosed at a younger age than sporadic tumors.
- Single nucleotide mutations, either on the same chromosome or on different chromosomes are considered to be associated with such cancer-associated genetic syndromes. Small intestinal cancers can be sporadic.[12]
- According to some studies done in Europe and United States, tobacco, alcohol and obesity are considered to play a role in the etiology of small intestine cancers.[13]
Epidemiology and Demographics
- Small intestinal cancer makes less than two percent of the gastrointestinal track cancers.[14]
- There incidence has increased recently particularly in African American males and it is unchanged for the females.[2]
- Age adjusted incidence rates were 1.2/100,000 inhabitants for men and 0.8/100,000 inhabitants for women shown by a study done in 2006.[15]
- According to a study done among 498,376 men and women in 2014, the age standardized incidence rates for small intestinal cancers were 5.5 and 4.8 per 100,000 person-years for men and women, respectively. For the histologic subtypes, the incidence rates per 100,000 person-years were 2.2 and 1.3 for adenocarcinomas, and 2.6 and 2.9 for carcinoids, for men and women, respectively.[16]
Risk Factors
- There are no established risk factors for small intestinal cancers.
- Crohn disease is considered to be the most important risk factor of small intestinal cancers.[3]
- Other associated risk factors are: [17]
Screening
- Currently there are no screening protocols and rarity of condition makes it a less suspected condition.[18]
Natural History, Complications, and Prognosis
- Clinical features and natural history of small intestinal tumors have not been clearly studied, as its a rare condition.[19]
- Adenocarcinoma of the duodenum is associated with low overall survival rate compared to the tumors located in Jejunum and ileum.[3]
Diagnosis
- Adenocarcinoma of the small intestine is usually diagnosed late and patients present with metastasis of lymph node or distant sites.
- Main stay of the treatment is surgery for these tumors. [20].
- Small intestinal cancers are not suspected clinically as their incidence is very low.
- Inaccessibility of endoscope to the small intestine can be the cause of their late diagnosis.
- Small intestinal tumors can be diagnosed using enteroscope.[18]
History and Symptoms
- The majority of patients with small Intestinal cancers are asymptomatic or have non-specific symptoms, which contributes to its late diagnosis, misdiagnoses and more investigations.[21]
- Symptoms are nonspecific and can include:
- Nausea and vomiting
- Abdominal pain
- Weight loss
- Abdominal mass
- Anemia
- Obstruction
- Jaundice
- Anorexia
- Melaena
- Small intestine contents are mostly fluid and symptoms related to obstruction appear very late, when tumor is at advance stage and are associated with very low five year survival rate.
- Due to the non-specific symptoms a very high level of suspicion is required.
Physical Examination
- Clinical features of small intestine tumors have not been clearly studied, as its a rare condition.[19]
Ultrasonography
- Ultrasonography can provide useful information in the diagnosis as small intestinal tumors have typical ultrasonographic features.
CT scan
- CT can help in differenting the small intestinal cancers. Different tumors have different appearance on CT:[25]
- In Peutz-Jeghers Syndrome, non-neoplastic lesions may resemble small intestinal neoplasm on CT.
| Tumors | Findings on CT |
|---|---|
| Adenocarcinmoa | Ulcerative lesions, nodular lesions and annular lesions |
| Carcinoid tumors | Poorly defined homogenous mass displacing intestinal loops
Calcification and desmoplastic reaction is a very specific finding of Carcinoid tumors on CT |
| Non-Hodgkin lymphoma | Bulky mass on CT
Lymphoma is associated with significant dilation of the lumen of intestine |
| Gastrointestinal stromal tumors(GISTs) | Intraluminal, subserosal or submucosal homogeneous masses with sharply defined borders
Calcifications |
| Lipoma | Intraluminal homogeneous mass, well-circumscribed and with some fat attenuation |
| Malignant metastasized tumors | Intraperitoneal seedings extending locally
Metastasized tumors give appearance of multiple small nodular masses in intestinal serosa, mesentery and omentum. |
MRI
- Primary and secondary small bowel neoplasms are rare and present with non-specific symptoms. MRI is an other modality to diagnose and stage small intestinal cancers. [26]
Enteroscopy
- X-ray, CT, MRI, and PET-CT are the foremost examination modalities for small intestinal tumors. However, with the advancement of radiology, a series of new diagnostic techniques have been developed, such as electronic enteroscopy, multi-slice spiral CT enteroclysis and capsule endoscopy. [27]
- On enteroscopy, gastrointestinal stromal tumor present as a nodule with enlarged mucosal folds or as a mass with abnormal surface vessels.
- Carcinoid tumors present with submucosal nodule or bulge, which can be associated with an ulcer.
- Lymphomas present with variable degrees of nodular mucosa and occasional ulcerations and strictures [28]
Biopsy
- MRI, CT and Ultrasound are reliable screening and diagnostic techniques for the identification and staging of small intestinal tumors but diagnosis of cancer can only be confirmed by the histopathology analysis. [29]
Treatment
- The treatment of small intestine cancer is clinically challenging due to its delayed diagnosis. [30]
Medical Treatment
- Treatment modality for the curative purpose of small intestinal cancer is surgery and chemotherapy. Medical therapy has no established role.
Surgical Treatment
- Primary treatment for cancer of the small intestine is curative surgical resection.[19]
- For non-metastatic disease curative surgery gives good results, when done in a tertiary care center.[3]
- Adenocarcinoma of duodenum has a comparitive low 5-year disease free survival rate after surgery.[3]
- Although surgical resection of small intestinal cancer plays an important role in the treatment, 5 yr survival rate is low even after surgery.[31]
Radiotherapy
- Radiotherapy is used as an adjunct therapy in the treatment of intestinal cancer.
Chemotherapy
- The role of adjuvant chemotherapy for small intestinal cancer is not established yet.[32]
- When resection is not possible, palliative surgery and chemotherapy are other options.[19]
Prevention
- There are no established preventive measures to prohibit developing small intestinal cancers. However, limiting tobacco and alcohol use, moderate healthy diet consumption and treatment of gastroenteritis and other intestinal pathology with increased risk of carcinomatos changes in polyps, can decrease the incidence of small intestinal cancers.
- People with genetic predisposition can undergo screening for early diagnosis.
Primary Prevention
- There are no established measures for the primary prevention of small intestinal cancers.
Secondary Prevention
- There are no established measures for the secondary prevention of small intestinal cancers.
References
- ↑ 1.0 1.1 Gill SS, Heuman DM, Mihas AA (October 2001). "Small intestinal neoplasms". J. Clin. Gastroenterol. 33 (4): 267–82. PMID 11588539.
- ↑ 2.0 2.1 Severson RK, Schenk M, Gurney JG, Weiss LK, Demers RY (February 1996). "Increasing incidence of adenocarcinomas and carcinoid tumors of the small intestine in adults". Cancer Epidemiol. Biomarkers Prev. 5 (2): 81–4. PMID 8850266.
- ↑ 3.0 3.1 3.2 3.3 3.4 Dabaja BS, Suki D, Pro B, Bonnen M, Ajani J (August 2004). "Adenocarcinoma of the small bowel: presentation, prognostic factors, and outcome of 217 patients". Cancer. 101 (3): 518–26. doi:10.1002/cncr.20404. PMID 15274064.
- ↑ Chow JS, Chen CC, Ahsan H, Neugut AI (August 1996). "A population-based study of the incidence of malignant small bowel tumours: SEER, 1973-1990". Int J Epidemiol. 25 (4): 722–8. PMID 8921448.
- ↑ 5.0 5.1 Barclay TH, Schapira DV (March 1983). "Malignant tumors of the small intestine". Cancer. 51 (5): 878–81. PMID 6821853.
- ↑ Levine JS, Ahnen DJ (December 2006). "Clinical practice. Adenomatous polyps of the colon". N. Engl. J. Med. 355 (24): 2551–7. doi:10.1056/NEJMcp063038. PMID 17167138.
- ↑ Modlin, Irvin M.; Champaneria, Manish C.; Chan, Anthony K.C.; Kidd, Mark (2007). "A Three-Decade Analysis of 3,911 Small Intestinal Neuroendocrine Tumors: The Rapid Pace of No Progress". The American Journal of Gastroenterology. 102 (7): 1464–1473. doi:10.1111/j.1572-0241.2007.01185.x. ISSN 0002-9270.
- ↑ 8.0 8.1 Massironi S, Del Gobbo A, Cavalcoli F, Fiori S, Conte D, Pellegrinelli A, Milione M, Ferrero S (November 2017). "IMP3 expression in small-intestine neuroendocrine neoplasms: a new predictor of recurrence". Endocrine. 58 (2): 360–367. doi:10.1007/s12020-017-1249-x. PMID 28210937.
- ↑ Sei Y, Feng J, Zhao X, Forbes J, Tang D, Nagashima K, Hanson J, Quezado MM, Hughes MS, Wank SA (July 2016). "Polyclonal Crypt Genesis and Development of Familial Small Intestinal Neuroendocrine Tumors". Gastroenterology. 151 (1): 140–51. doi:10.1053/j.gastro.2016.03.007. PMC 5578471. PMID 27003604.
- ↑ 10.0 10.1 Crump M, Gospodarowicz M, Shepherd FA (June 1999). "Lymphoma of the gastrointestinal tract". Semin. Oncol. 26 (3): 324–37. PMID 10375089.
- ↑ Schlotzhauer WS, Chortyk OT, Austin PR (1976). "Pyrolysis of chitin, a potential tobacco extender". J Agric Food Chem. 24 (1): 177–80. PMID 1432-2307 Check
|pmid=value (help). - ↑ Jass JR (December 2007). "Gastrointestinal polyposes: clinical, pathological and molecular features". Gastroenterol. Clin. North Am. 36 (4): 927–46, viii. doi:10.1016/j.gtc.2007.08.009. PMID 17996798.
- ↑ Boffetta P, Hazelton WD, Chen Y, Sinha R, Inoue M, Gao YT, Koh WP, Shu XO, Grant EJ, Tsuji I, Nishino Y, You SL, Yoo KY, Yuan JM, Kim J, Tsugane S, Yang G, Wang R, Xiang YB, Ozasa K, Nagai M, Kakizaki M, Chen CJ, Park SK, Shin A, Ahsan H, Qu CX, Lee JE, Thornquist M, Rolland B, Feng Z, Zheng W, Potter JD (July 2012). "Body mass, tobacco smoking, alcohol drinking and risk of cancer of the small intestine--a pooled analysis of over 500,000 subjects in the Asia Cohort Consortium". Ann. Oncol. 23 (7): 1894–8. doi:10.1093/annonc/mdr562. PMC 3493138. PMID 22147734.
- ↑ North JH, Pack MS (January 2000). "Malignant tumors of the small intestine: a review of 144 cases". Am Surg. 66 (1): 46–51. PMID 10651347.
- ↑ Lepage C, Bouvier AM, Manfredi S, Dancourt V, Faivre J (December 2006). "Incidence and management of primary malignant small bowel cancers: a well-defined French population study". Am. J. Gastroenterol. 101 (12): 2826–32. doi:10.1111/j.1572-0241.2006.00854.x. PMID 17026561.
- ↑ Miller RR, Menke JA, Hansen NB, Zwick DL, Bickers RG, Nowicki PT (August 1986). "The effect of naloxone on the hemodynamics of the newborn piglet with septic shock". Pediatr. Res. 20 (8): 707–10. doi:10.1203/00006450-198608000-00001. PMID 3737280.
- ↑ Sarosiek T, Stelmaszuk M (February 2018). "[Small intestine neoplasms]". Pol. Merkur. Lekarski (in Polish). 44 (260): 45–48. PMID 29498365.
- ↑ 18.0 18.1 Rossini FP, Risio M, Pennazio M (January 1999). "Small bowel tumors and polyposis syndromes". Gastrointest. Endosc. Clin. N. Am. 9 (1): 93–114. PMID 9834319.
- ↑ 19.0 19.1 19.2 19.3 Higashi D, Ishibashi Y, Tamura T, Nii K, Egawa Y, Koga M, Tomiyasu T, Harimura T, Tanaka R, Futatsuki R, Noda S, Futami K, Maekawa T, Takaki Y, Hirai F, Matsui T (August 2010). "Clinical features of and chemotherapy for cancer of the small intestine". Anticancer Res. 30 (8): 3193–7. PMID 20871040.
- ↑ Ogata Y, Yamaguchi K, Sasatomi T, Uchida S, Akagi Y, Shirouzu K (August 2010). "[Treatment and outcome in small bowel cancer]". Gan To Kagaku Ryoho (in Japanese). 37 (8): 1454–7. PMID 20716869.
- ↑ Williamson JM, Williamson RC (January 2014). "Small bowel tumors: pathology and management". J Med Assoc Thai. 97 (1): 126–37. PMID 24701741.
- ↑ Zollinger RM (June 1986). "Primary neoplasms of the small intestine". Am. J. Surg. 151 (6): 654–8. PMID 2424326.
- ↑ Wilson JM, Melvin DB, Gray GF, Thorbjarnarson B (August 1974). "Primary malignancies of the small bowel: a report of 96 cases and review of the literature". Ann. Surg. 180 (2): 175–9. PMC 1343634. PMID 4843046.
- ↑ Ouriel K, Adams JT (January 1984). "Adenocarcinoma of the small intestine". Am. J. Surg. 147 (1): 66–71. PMID 6691554.
- ↑ Buckley, J A; Fishman, E K (1998). "CT evaluation of small bowel neoplasms: spectrum of disease". RadioGraphics. 18 (2): 379–392. doi:10.1148/radiographics.18.2.9536485. ISSN 0271-5333.
- ↑ Anzidei M, Napoli A, Zini C, Kirchin MA, Catalano C, Passariello R (August 2011). "Malignant tumours of the small intestine: a review of histopathology, multidetector CT and MRI aspects". Br J Radiol. 84 (1004): 677–90. doi:10.1259/bjr/20673379. PMC 3473441. PMID 21586504.
- ↑ Zhao Z, Guan X, Chen Y, Wang X (January 2017). "[Progression of diagnosis and treatment in primary malignant small bowel tumor]". Zhonghua Wei Chang Wai Ke Za Zhi (in Chinese). 20 (1): 117–120. PMID 28105627.
- ↑ Bartel MJ, Stark ME, Lukens FJ (November 2014). "Clinical Review of Small-Bowel Endoscopic Imaging". Gastroenterol Hepatol (N Y). 10 (11): 718–726. PMC 5395713. PMID 28435408.
- ↑ Tanzer J, Lessard M, Guilhot F, Brizard A (1987). "[Rearrangement of the short arm of chromosome 12 in chronic myelomonocytic leukemias]". Nouv Rev Fr Hematol (in French). 29 (1): 65–8. PMID 3473441.
- ↑ Tang L, Huang LY, Cui J, Wu CR (June 2018). "Effect of Double-Balloon Enteroscopy on Diagnosis and Treatment of Small-Bowel Diseases". Chin. Med. J. 131 (11): 1321–1326. doi:10.4103/0366-6999.232802. PMC 5987504. PMID 29786046.
- ↑ Coco C, Rizzo G, Manno A, Mattana C, Verbo A (April 2010). "Surgical treatment of small bowel neoplasms". Eur Rev Med Pharmacol Sci. 14 (4): 327–33. PMID 20496543.
- ↑ Overman MJ, Kopetz S, Lin E, Abbruzzese JL, Wolff RA (May 2010). "Is there a role for adjuvant therapy in resected adenocarcinoma of the small intestine". Acta Oncol. 49 (4): 474–9. doi:10.3109/02841860903490051. PMID 20397775.