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{{Carcinoid syndrome}}
{{Carcinoid syndrome}}
{{CMG}}{{AE}}{{PSD}}
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==Overview==
==Overview==
For symptomatic relief of carcinoid sydromes medical therapy many include: [[octreotide]], [[methysergide maleate]], and [[cyproheptadine]].
The predominant [[therapy]] for [[Carcinoid Syndrome|carcinoid syndrome]] is [[surgical resection]]. [[Supportive therapy]] for [[Carcinoid Syndrome|carcinoid syndrome]] includes [[somatostatin]] [[Analogue|analogs]][[Telotristat ethyl|,Telotristat]],[[interferons]], and [[radionuclides]].


==Medical Therapy==
==Medical Therapy==
Standard treatments for patients with gastrointestinal (GI) carcinoid tumors include the following:
[[Standard treatment|Standard treatments]] for [[patients]] with [[Gastrointestinal tract|gastrointestinal]] [[carcinoid tumors]] include the following:<ref>Treatment Option Overview for GI Carcinoid Tumors
. 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>
*[[Somatostatin]] [[analogue]]
* [[Telotristat ethyl|Telotristat]]
*[[Interferons]]
*Treatment of [[hepatic]] [[metastases]]
*[[Radionuclides]]
*Management of [[Carcinoid Disease|carcinoid]]-related [[fibrosis]]
*[[Surgery]]


*Surgery
===Somatostatin Analogs===
*Somatostatin analogs
* [[Somatostatin|Somatostatin analogs]] includes [[octreotide]] and [[Lanreotide acetate|lanreotide]].
*Interferons
* [[Somatostatin]] acts by binding to [[Somatostatin receptor|somatostatin receptors]] expressed on the majority of [[carcinoid tumors]].
*Treatment of hepatic metastases
* [[Flushing]] and [[Diarrheal|diarrhea]] are significantly improved in over 80 percent of [[patients]] with the [[Carcinoid Syndrome|carcinoid syndrome]] with [[somatostatin]] [[therapy]].<ref name="pmid27214300">{{cite journal |vauthors=Vinik AI, Wolin EM, Liyanage N, Gomez-Panzani E, Fisher GA |title=EVALUATION OF LANREOTIDE DEPOT/AUTOGEL EFFICACY AND SAFETY AS A CARCINOID SYNDROME TREATMENT (ELECT): A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL |journal=Endocr Pract |volume=22 |issue=9 |pages=1068–80 |date=September 2016 |pmid=27214300 |doi=10.4158/EP151172.OR |url=}}</ref>
*Radionuclides
*[[Experimentally|Experimentally,]] [[somatostatin]] has been shown to have a [[cytostatic]] effect on [[Tumor cell|tumor cells]]. This effect involves [[hyperphosphorylation]] of the [[retinoblastoma]] [[gene]] product and [[G1]] [[cell cycle]] arrest.<ref name="pmid11095353">{{cite journal |vauthors=Ducreux M, Ruszniewski P, Chayvialle JA, Blumberg J, Cloarec D, Michel H, Raymond JM, Dupas JL, Gouerou H, Jian R, Genestin E, Hammel P, Rougier P |title=The antitumoral effect of the long-acting somatostatin analog lanreotide in neuroendocrine tumors |journal=Am. J. Gastroenterol. |volume=95 |issue=11 |pages=3276–81 |date=November 2000 |pmid=11095353 |doi=10.1111/j.1572-0241.2000.03210.x |url=}}</ref>
*Management of carcinoid-related fibrosis
*[[Lanreotide]], a long-acting [[somatostatin]] [[Analogue|analog]] administered every 10 to 14 days, has an efficacy similar to that of [[octreotide]] and an agreeable formulation for [[patient]] use. The effects of [[Lanreotide acetate|lanreotide]] on [[Symptoms|symptom]] relief are comparable to those of [[octreotide]], with 75% to 80% of patients reporting decreased [[diarrhea]] and [[flushing]]. However, there appears to be little improvement in [[Tumor cell|tumor]] responses over shorter-acting [[octreotide]].
*Depot [[formulation]]<nowiki/>s include long-acting repeatable (LAR) [[octreotide]] and a slow-release depot preparation of [[lanreotide]].
*The typical [[duration]] of treatment with [[somatostatin]] analogs is approximately 12 months because of the development of [[tachyphylaxis]].
[[Adverse effects]] of [[somatostatin]] analog administration include:
*[[Nausea]]
*[[Cramping]]
*[[Loose stools]]
*[[Steatorrhea]]
*[[Cardiac]] [[Conduction System|conduction abnormalities]] and [[arrhythmia]]<nowiki/>s
*[[Endocrine|Endocrine disturbances]] (e.g., [[hypothyroidism]], [[hypoglycemia]], or [[hyperglycemia]]
*[[Gastric]] [[atony]]


Symptomatic therapy
===Telotristat===
Symptomatic relief may be provided by any of the following medical therapies:
* [[Telotristat ethyl|Telotristat]] is an [[oral]] [[inhibitor]] o[[Tryptophan hydroxylase|f tryptophan hydroxylase]] which [[catalyzes]] the conversion of l-[[tryptophan]] into [[serotonin]]..<ref name="pmid29503551">{{cite journal |vauthors=Chan DL, Singh S |title=Developments in the treatment of carcinoid syndrome - impact of telotristat |journal=Ther Clin Risk Manag |volume=14 |issue= |pages=323–329 |date=2018 |pmid=29503551 |pmc=5824756 |doi=10.2147/TCRM.S126143 |url=}}</ref>
*[[Octreotide]] (somatostatin analogue- neutralizes [[serotonin]] and decreases urinary 5-HIAA)
* [[Tryptophan hydroxylase]] is an [[Aromatic amino acids|aromatic amino acid]] [[hydroxylase]] and is the rate-limiting [[enzyme]] in [[serotonin]] [[synthesis]].
*[[Methysergide maleate]] (antiserotonin agent but not used because of serious side effect of retroperitoneal fibrosis)
* [[Somatostatin|Somatostatin analogs]] (SSAs) are the mainstay of treatment, but are unable to ameliorate [[symptoms]] in all [[patients]] due to [[dose]]-limiting [[side effects]] and [[tachyphylaxis]].
*[[Cyproheptadine]] ([[antihistamine]])
* [[Telotristat ethyl|Telotristat]] represents a significant advance in the treatment of [[Carcinoid Syndrome|carcinoid syndrome]] [[Diarrheal|diarrhea]] in [[patients]] who have inadequate control on long-acting [[somatostatin]] [[Analogue|analogues]] and should be considered for [[patients]] with >4 [[bowel]] motions per day on [[somatostatin]] [[Analogue|analogues.]]


===Interferons===


*The most [[Research|researched]] [[interferon]] in the treatment of [[carcinoid disease]] is [[interferon-alpha]].
*[[Interferon-alpha]] (IFNα) is a [[cytokine]] that mediates [[Anti-viral drug|anti-viral,]] anti-proliferative and anti-[[tumour]] activities.


*Side-effects includes
#[[Flu]]-like [[symptoms]]
#[[Chronic (medical)|Chronic]] [[fatigue]]
#[[Depression (clinical)|Depression]]
#[[Anemia]]
#[[Neutropenia]].


===Somatostatin Analogs===
===Treatment of Hepatic Metastases===
The management of [[hepatic]] [[metastases]] may include:
*[[Surgical resection]]
*[[Hepatic artery]] [[embolization]] especially when complemented by the addition of regional [[chemotherapy]] (trans-[[arterial]] [[chemoembolization]] or [[TACE]])<ref name="pmid16508629">{{cite journal |vauthors=Strosberg JR, Choi J, Cantor AB, Kvols LK |title=Selective hepatic artery embolization for treatment of patients with metastatic carcinoid and pancreatic endocrine tumors |journal=Cancer Control |volume=13 |issue=1 |pages=72–8 |date=January 2006 |pmid=16508629 |doi=10.1177/107327480601300110 |url=}}</ref>
*[[Cryoablation]] and [[Radiofrequency ablation]] ([[RFA]])
*[[liver transplantation]]<ref name="Blonski2005">{{cite journal|last1=Blonski|first1=Wojciech C|title=Liver transplantation for metastatic neuroendocrine tumor: A case report and review of the literature|journal=World Journal of Gastroenterology|volume=11|issue=48|year=2005|pages=7676|issn=1007-9327|doi=10.3748/wjg.v11.i48.7676}}</ref>


The development of long-acting and depot formulations of somatostatin analogs has been important in the amelioration of symptoms of carcinoid syndrome. The result has been a substantial improvement in quality of life with relatively mild adverse effects. Experimentally, somatostatin has been shown to have a cytostatic effect on tumor cells. This effect involves hyperphosphorylation of the retinoblastoma gene product and G1 cell cycle arrest, in addition to somatostatin receptor (SSTR) subtype 3 [sst(3)]-mediated (and to a lesser extent, SSTR subtype [sst(2)]-mediated) apoptosis. Somatostatin also appears to have some antiangiogenic properties. However, only a small number of patients treated with somatostatin analog therapy experience partial tumor regression.
===Radionuclides===
* The use of [[somatostatin]] [[analogue]] radiolabeled [[peptide]] therapy (PRRT) provides [[radiation]] directed to the [[cells]] that express [[somatostatin receptors]].<ref name="pmid26943056">{{cite journal |vauthors=Hörsch D, Ezziddin S, Haug A, Gratz KF, Dunkelmann S, Miederer M, Schreckenberger M, Krause BJ, Bengel FM, Bartenstein P, Biersack HJ, Pöpperl G, Baum RP |title=Effectiveness and side-effects of peptide receptor radionuclide therapy for neuroendocrine neoplasms in Germany: A multi-institutional registry study with prospective follow-up |journal=Eur. J. Cancer |volume=58 |issue= |pages=41–51 |date=May 2016 |pmid=26943056 |doi=10.1016/j.ejca.2016.01.009 |url=}}</ref>
* The four [[Radionuclides|radionuclide]] [[conjugates]] most commonly used in the treatment of [[carcinoid disease]] are:
**[[Metaiodobenzylguanidine|131I-MIBG (iodine-131-meta-iodobenzylguanidine)]]
**[[Indium|Indium-111]]
**[[Yttrium Y 90-DOTA-tyr3-octreotide|Yttrium-90]]
**[[Lutetium Lu 177 dotatate|Lutetium-177]]
* It is mandatory to quantify [[cells]] with [[somatostatin receptors]] using imaging prior to PRRT therapy.


Octreotide, a short-acting somatostatin analog and the first biotherapeutic agent used in the management of carcinoid tumors, exhibits beneficial effects that are limited to symptom relief, with about 70% of patients experiencing resolution of diarrhea or flushing.  
===Management of Carcinoid-Related Fibrosis===
*Currently, there is no effective [[Pharmacological|pharmacologic]] [[therapy]] for [[bowel obstruction]] and [[heart failure]] secondary to [[peritoneal]] [[Fibrosis|fibrosi]]<nowiki/>s and right-sided [[valvular]] [[fibrosis]] respectively.
*In the instance of [[bowel obstruction]], [[Surgery|surgical]] lysis of the [[adhesions]] often is technically demanding because of the cocoon-like effects of extensive [[fibrosis]] stimulated by the various [[Tumour|tumor]]-derived [[growth factors]].
*[[Valve replacement surgery|Valvular replacement]] usually is required to manage [[Carcinoid Disease|carcinoid heart diseas]]<nowiki/>e.<ref name="pmid15571597">{{cite journal |vauthors=Modlin IM, Shapiro MD, Kidd M |title=Carcinoid tumors and fibrosis: an association with no explanation |journal=Am. J. Gastroenterol. |volume=99 |issue=12 |pages=2466–78 |date=December 2004 |pmid=15571597 |doi=10.1111/j.1572-0241.2004.40507.x |url=}}</ref>


In the treatment of carcinoids, lanreotide, a long-acting somatostatin analog administered every 10 to 14 days, has an efficacy similar to that of octreotide and an agreeable formulation for patient use.[13] The effects of lanreotide on symptom relief are comparable to those of octreotide, with 75% to 80% of patients reporting decreased diarrhea and flushing; however, there appears to be little improvement in tumor responses over shorter-acting octreotide.
===Symptomatic Therapy===
*Nonspecific supportive care of [[patients]] is to avoid factors that induce [[flushing]] or [[Bronchospasm|bronchospastic]] episodes includes the following:


Depot formulations include long-acting repeatable (LAR) [[octreotide]] and a slow-release depot preparation of [[lanreotide]].
:*Ingestion of [[alcohol]], certain [[Cheese|cheeses]], [[capsaicin]]-containing foods and [[Nut (fruit)|nuts]]
:*[[Stress|Stressful]] situations
:*[[Physical activity]]
*[[Diarrhea]] may be treated with conventional [[anti-diarrheal]] agents such as [[loperamide]] or [[diphenoxylate]]
*Severe [[diarrhea]] may be treated with the [[5-HT receptor 2C|5-HT receptor subtype 2 antagonist]] [[cyproheptadine]], which is effective in as many as 50% of [[patients]] and may also help alleviate [[anorexia]] or [[cachexia]] in [[patients]] with a [[malignant carcinoid syndrome]].


The typical duration of treatment with somatostatin analogs is approximately 12 months because of the development of tachyphylaxis (reported less frequently with long-acting formulations) and/or disease progression.[15-17] In the management of carcinoid crises, intravenous somatostatin analogs are effective; crises are usually precipitated by anesthesia, surgical interventions, or radiologic interventions.[18] Adverse effects of somatostatin analog administration include:[19,20]
*Treatment of s[[Skin rashes|kin rashes]], particularly in [[histamine]]-secreting [[Carcinoid tumors|gastric carcinoid tumors]] can be done with [[Histamine receptors|histamine 1 receptor]] blockade with [[fexofenadine]] and [[loratadine]]


[[Nausea]]
*[[Bronchospasm]] can be managed with [[theophylline]] or [[beta-2 adrenergic receptor]] [[agonists]] such as [[albuterol]].
[[Cramping]]
[[Loose stools]]
[[Steatorrhea]]
Cardiac conduction abnormalities and [[arrhythmias]]
Endocrine disturbances (e.g., [[hypothyroidism]], [[hypoglycemia]], or, more commonly, [[hyperglycemia]])
Gastric atony
 
===Chemotherapy===
[[Chemotherapy]] is of little benefit and is generally not indicated. [[Octreotide]] (a [[somatostatin]] analogue) may decrease the secretory activity of the carcinoid.


==References==
==References==
{{reflist|2}}
{{reflist|2}}


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Latest revision as of 22:22, 6 May 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Parminder Dhingra, M.D. [2] Anum Gull M.B.B.S.[3]

Overview

The predominant therapy for carcinoid syndrome is surgical resection. Supportive therapy for carcinoid syndrome includes somatostatin analogs,Telotristat,interferons, and radionuclides.

Medical Therapy

Standard treatments for patients with gastrointestinal carcinoid tumors include the following:[1]

Somatostatin Analogs

Adverse effects of somatostatin analog administration include:

Telotristat

Interferons

  • Side-effects includes
  1. Flu-like symptoms
  2. Chronic fatigue
  3. Depression
  4. Anemia
  5. Neutropenia.

Treatment of Hepatic Metastases

The management of hepatic metastases may include:

Radionuclides

Management of Carcinoid-Related Fibrosis

Symptomatic Therapy

References

  1. Treatment Option Overview for GI Carcinoid Tumors . NATIONAL CANCER INSTITUTE . http://www.cancer.gov/types/gi-carcinoid-tumors/hp/gi-carcinoid-treatment-pdq#link/_97_toc Accessed on September 22, 2015
  2. Vinik AI, Wolin EM, Liyanage N, Gomez-Panzani E, Fisher GA (September 2016). "EVALUATION OF LANREOTIDE DEPOT/AUTOGEL EFFICACY AND SAFETY AS A CARCINOID SYNDROME TREATMENT (ELECT): A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL". Endocr Pract. 22 (9): 1068–80. doi:10.4158/EP151172.OR. PMID 27214300.
  3. Ducreux M, Ruszniewski P, Chayvialle JA, Blumberg J, Cloarec D, Michel H, Raymond JM, Dupas JL, Gouerou H, Jian R, Genestin E, Hammel P, Rougier P (November 2000). "The antitumoral effect of the long-acting somatostatin analog lanreotide in neuroendocrine tumors". Am. J. Gastroenterol. 95 (11): 3276–81. doi:10.1111/j.1572-0241.2000.03210.x. PMID 11095353.
  4. Chan DL, Singh S (2018). "Developments in the treatment of carcinoid syndrome - impact of telotristat". Ther Clin Risk Manag. 14: 323–329. doi:10.2147/TCRM.S126143. PMC 5824756. PMID 29503551.
  5. Strosberg JR, Choi J, Cantor AB, Kvols LK (January 2006). "Selective hepatic artery embolization for treatment of patients with metastatic carcinoid and pancreatic endocrine tumors". Cancer Control. 13 (1): 72–8. doi:10.1177/107327480601300110. PMID 16508629.
  6. Blonski, Wojciech C (2005). "Liver transplantation for metastatic neuroendocrine tumor: A case report and review of the literature". World Journal of Gastroenterology. 11 (48): 7676. doi:10.3748/wjg.v11.i48.7676. ISSN 1007-9327.
  7. Hörsch D, Ezziddin S, Haug A, Gratz KF, Dunkelmann S, Miederer M, Schreckenberger M, Krause BJ, Bengel FM, Bartenstein P, Biersack HJ, Pöpperl G, Baum RP (May 2016). "Effectiveness and side-effects of peptide receptor radionuclide therapy for neuroendocrine neoplasms in Germany: A multi-institutional registry study with prospective follow-up". Eur. J. Cancer. 58: 41–51. doi:10.1016/j.ejca.2016.01.009. PMID 26943056.
  8. Modlin IM, Shapiro MD, Kidd M (December 2004). "Carcinoid tumors and fibrosis: an association with no explanation". Am. J. Gastroenterol. 99 (12): 2466–78. doi:10.1111/j.1572-0241.2004.40507.x. PMID 15571597.


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