Precision Neuroendocrine Cancer Treatment Options Are One Call Away
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Early, Late-Stage, and Metastatic Neuroendocrine Cancer Treatment
Options
A neuroendocrine cancer diagnosis does not mean your options are limited because you have a rare disease. At
Envita Medical Centers, a world-class integrative center for Precision Oncology, we overcome the standard
treatment challenges of this uncommon type of cancer, which is in
the United States.
In our clinical practice of over 25 years, we have been able to help complicated, late-stage, and refractory to care
cancer patients with our proprietary precision-targeted treatment options, aimed at tackling the core of their unique
neuroendocrine cancer. Envita’s suite of innovative new treatments, including CIPI™ (Chemo Immuno Precision
Injections)
and GTFC™ (Genetically Targeted Fractionated Chemotherapy), go beyond standard treatments like chemotherapy,
radiation,
embolization, and Peptide Receptor Radionuclide Therapy (PRRT), to help even those with unresectable and advanced
neuroendocrine tumors.
Disclaimer: Individual results will vary. Envita makes no guarantees for outcomes. Each patient case is unique. Please
consult your doctor before making any changes to your medical treatment. Not every patient is a candidate for care or
achieves these results. Treatments used in this case may not all be FDA approved for the treatment of this condition.
Susan’s cancer started in the pelvic region, but Neuroendocrine neoplasms (NENs)- including Neuroendocrine
Tumors
(NETs)
and Neuroendocrine Carcinomas (NECs), may manifest in any part of the body. Depending on the cancerous cells’
degree
of
differentiation from the healthy cells, they are either known as NETs, which are well-differentiated, or NECs,
which
are
poorly differentiated. NENs’ incidence is common in the lungs, gastrointestinal tract, or the pancreas, and the
symptoms
of cancer vary depending on the site, size, stage, type, and grade of tumor.
This article deals with all aspects of Neuroendocrine Cancer, including:
How Envita Overcomes Challenges of Standard Treatment Options
Diagnosis and treatment of patients with this relatively rare form of cancer can be challenging due to its wide
variety
of symptoms, and in several cases, this lack of timely intervention causes disease progression. Medical
studies on the prognosis of neuroendocrine carcinomas of the colon, rectum, and anal canal show poor results [2]
when following
conventional care, but with our personalized precision oncology treatment options, patients may have a better chance
of
progression-free survival and a holistic recovery.
Envita’s precision oncology program not only takes into account extensive genomics, but it also includes an
advanced
immune system evaluation to custom-build protocols for each patient, which is especially crucial in treating
rare
cancers, like neuroendocrine carcinomas.
Our powerful combinations of leading-edge conventional treatments along with research-based natural therapies
may be
beneficial, even when resection is not an option for patients.
Envita’s expert team has been able to help improve outcomes, by precision-targeting each patient’s specific
cancer
expressions, instead of using the one-size-fits-all standard NCCN (National Comprehensive Cancer Network)
guidelines,
followed in major hospitals and cancer centers across the country.
Disclaimer: Individual results will vary. Envita makes no guarantees for outcomes. Each patient case is unique. Please
consult your doctor before making any changes to your medical treatment. Not every patient is a candidate for care or
achieves these results. Treatments used in this case may not all be FDA approved for the treatment of this condition.
Envita Medical Centers Medical Team
Physicians with MD, MD(h), and NMD medical
licenses, including certified oncologists, and certified interventional radiologists,
striving to provide the latest cancer innovations
22
Pharmacists specializing in integrative agents
7
Nurses trained in precision treatment delivery
40+
The NCCN guidelines dictate care regimens based on certain criteria, such as, primary site, tumor functionality,
somatostatin receptor status, and mitotic count for grade and degree of differentiation, which determines whether the
tumors are poorly differentiated neuroendocrine carcinomas or well-differentiated neuroendocrine tumors. However, in
our
clinical opinion, these criteria may not be enough to strike out the disease and the unique set of causes responsible
for its growth and spread in each individual patient. To overcome this challenge, Envita, being a truly integrative
clinic, breaks away from the one-size-fits-all NCCN guidelines and offers personalized precision oncology treatments
to
all its patients.
Standard NCCN guidelines allow precision oncology treatments only as a follow-up to failed first-line treatments, but
this delay may lead to devastating consequences in a life-threatening disease like cancer. However, Envita’s team is
not
limited by these restrictions which is why we utilize personalized precision oncology treatments to target cancerous
cells from all possible angles.
At Envita, every patient gets access to Personalized Precision
Oncology, right at the gate!
Even the handful of patients who receive standard precision oncology care do not get the benefits of Envita’s
detailed
and personalized precision oncology neuroendocrine cancer program. At Envita, we analyze many more parameters than
those
in standard precision oncology, to customize a treatment protocol aimed at each patient’s holistic recovery.
Envita Precision Algorithm vs. Standard Oncology Precision Testing
Envita Medical Centers
Standard Oncology Precision Testing
RNA Transcriptome Genes
Envita Medical Centers:20,000+
Standard Oncology:Unchecked
SNV/CNV Genes
Envita Medical Centers:452
Standard Oncology:309
Rearrangements/Fusion Genes
Envita Medical Centers:51
Standard Oncology:27
Microsatellite Instability (MSI)
Envita Medical Centers:Checked
Standard Oncology:Checked
Tumor Mutation Burden (TMB)
Envita Medical Centers:Checked
Standard Oncology:Checked
BRCA 1/2
Envita Medical Centers:Checked
Standard Oncology:Checked
Immunohistochemistry
Envita Medical Centers:Checked
Standard Oncology:Unchecked
Chemosensitivity
Envita Medical Centers:Checked
Standard Oncology:Unchecked
Concurrent Liquid Biopsy
Envita Medical Centers:Checked
Standard Oncology:Unchecked
Exosomal miRNA Analysis
Envita Medical Centers:Checked
Standard Oncology:Unchecked
Circulating Tumor Cells Enumeration
Envita Medical Centers:Checked
Standard Oncology:Unchecked
Pharmacogenomics
Envita Medical Centers:Checked
Standard Oncology:Unchecked
Individualized Therapy Recommendation
Envita Medical Centers:Checked
Standard Oncology:Unchecked
Carcinogenic Exposure - Root Causes
Envita Medical Centers:Checked
Standard Oncology:Unchecked
Inflammation Markers
Envita Medical Centers:Checked
Standard Oncology:Unchecked
Metabolic Target Drivers
Envita Medical Centers:Checked
Standard Oncology:Unchecked
*Individual results may vary. Envita
makes no guarantees for outcomes.
Personalized Precision Oncology to Improve Overall Survival
Personalizing precision oncology treatments is crucial to improve overall survival, as cancer is a disease of genetic
mutations and not of tissues or organs, and genetics vary from person to person. With varied genetics, cell mutations
may lead to different cancer expressions, which explains why people with the same cancer type, stage, grade, and site
may not respond similarly to the same treatment.
For instance, not everyone with the same site, stage, grade, and type of neuroendocrine cancer has the exact
same
cancer
biomarkers, pointing to the need for personalizing precision oncology. Biomarkers refer to the proteins, genes,
and
other molecules which affect your unique endocrine cancer’s growth and
spread to surrounding lymph nodes, liver, or other distant regions of the body. Patients with neuroendocrine
carcinomas
are prone to experiencing liver metastases or metastatic disease in other organs of the digestive system, as
NETs
commonly develop in and around the gastrointestinal tract.
A medical review on “Unmet Needs in
High-Grade
Gastroenteropancreatic Neuroendocrine
Neoplasms (WHO G3) highlights how biomarkers for prognosis and treatment have to be developed and
analyzing
genetic molecular markers will
be important [3]. However, at Envita, we have already developed proprietary tests for identifying many more
biomarkers
than standard tests, and we also utilize innovative technology for advanced analysis of genetic molecular
markers.
Incorporating such novel aspects into our program has led to the development of a suite of unique new treatments
for
all
stages and types of neuroendocrine cancer patients.
Envita’s New Treatments for all Stages and Types of Neuroendocrine Cancers
Envita’s new treatments are designed on the N of 1
model, which enables our team of integrative physicians to customize treatment based on patient-specific
biomarkers, with the goal of aggressively attacking their cancer, while reducing chances of side effects.
We personalize care at every level of our four-step precision oncology treatment approach to customize a unique
medical
blueprint for every patient. Building a patient-specific treatment plan enables us to target all the unique cancer
expressions of each patient’s specific neuroendocrine cancer, which aims to improve quality of life, increase
longevity,
and reduce toxicity.
Step 1
Genomic Identification to Probe Root Causes of Neuroendocrine Cancer
Knowing the origin of your cancer is essential to treat it at its core, and a detailed genomic
identification helps to probe each patient’s specific mutations causing their cancer. NETs represent a spectrum
of tumors with a
diverse range of molecular abnormalities that share a common origin, which are neuroendocrine cells.
In certain patients, the disease could be the result of inherited genetic mutations, as a family history of cancer is
considered a significant risk factor for all
NETs [5]. In
other instances, a long-term history of diabetes could be triggering mutations causing certain cases of GI NET
as well as prolonged exposure to sunlight may initiate mutations leading to Merkel Cell Carcinoma.
At Envita, irrespective of your stage, type, or site of neuroendocrine cancer, we trace patient-specific
irregularities
down to the cellular and molecular level for establishing better treatment mechanisms. Medical studies show how genome-wide screening of different
types of NETs is likely to generate new insights into the tumor biology [6],
which is what we are doing here at Envita to precision-target the core of every patient’s specific cancer.
Step 2
Immuno Targeting to Limit Disease Progression
While attacking each patient’s specific neuroendocrine cancer biomarkers, it is critical to strengthen their immune
system because it plays a crucial role in limiting cancer progression. A robust immune system can kill thousands of
cancerous and precancerous cells in a day, but this ability gets impacted when you have a weak immune system. At
Envita,
we understand that cancer compromises the immune system of patients, which is why we identify immuno targets and
include
personalized immunotherapy for treating all stages, types, and grades of neuroendocrine cancers. Scientific studies prove how combining immunotherapy with
chemotherapy can be beneficial for treating certain types of neuroendocrine
cancers [7].
Ultra Analytes Liquid Biopsy
Ultra Analytes Liquid Biopsy is deployed to identify targeted immunotherapy options to help get your
immune system working properly again.
Learn more
about
Immunotherapy
Our Ultra Analytes Liquid Biopsy analyses the Circulating Tumor Cells (CTCs) in a patient’s blood sample to establish
immuno and chemo targets, allowing us to proactively treat early signs of metastasis. CTCs break away from a growing
tumor and enter the patient’s blood stream, spreading the cancer to different parts of the body.
A detailed examination of these CTCs enables us to track and treat the cancer in its micro-metastatic form, even
before
they manifest symptoms of spread. A
liquid biopsy fulfills the criteria for real-time disease management and avoids the negative invasive
implications and single
time-point limitations of tissue biopsy [8].
We not only manage your disease in real time, but we also harness your immune system’s innate ability to find and
kill
the cancer, via immunotherapy. According to a 2020 study on "Novel immunotherapy strategies for treatment
of neuroendocrine neoplasms," immunotherapy has been unexplored in NENs until recently [9].
However, Envita’s expert team of researchers have been pushing the boundaries of science to innovate and discover
advanced immunotherapies which are allowing patients to respond to care where they had not before. We go beyond the
typical immunotherapy drugs, such as, PD-1 inhibitors, mTOR inhibitors, and interferons, to build next level immuno
reactivation treatment plans, customized for each of our neuroendocrine cancer patients.
Step 3
Personalized Drug Design to Potentiate Treatment Regimens
At Envita, we use a powerful combination of FDA (Food and Drug Administration) approved drugs, repurposed
drugs, and
custom-compounded adjuvants to not only kill the cancerous cells, but also boost the immune system. Several
studies,
like the NETTER 1 trial show how
combination of two types of drugs can be more effective than high doses of a single anti-cancer agent [10],
which is why we have been utilizing our advanced technology to
design
various combination therapies suitable for each individual neuroendocrine cancer patient.
Our personalized drug design helps to potentiate treatment
regimens as the anti-cancer drugs available on the market may not always be effective
against all the treatment targets identified through our extensive tests. To overcome this limitation, we
custom-compound adjuvants at our in-house
pharmacy. These custom-compounded adjuvants fill up the gap in treatment by impacting the biomarkers, for which
there are no
compatible medicines on the market.
We use advanced phytotherapeutics, comprising plant extracts and herbs to custom-design adjuvants with enhanced
cytotoxicity for killing cancerous cells and debulking tumors, while helping to accelerate the healing process, for
each
individual patient. To potentially improve outcomes, we also adjust dosage of FDA approved and repurposed drugs, which
helps in enhancing benefits of the anti-cancer medications and reducing their side effects.
Step 4
Precision Deployment of New Treatments to Reduce Side Effects
Medical reviews indicate how managing certain
types of neuroendocrine tumors is often complex and may include a combination of surgery,
systemic treatments, and locoregional approaches [11]. To counter these treatment complexities, we have developed
several new minimally invasive treatments to not only avoid highly invasive surgeries but to also widen options for
patients with advanced and unresectable neuroendocrine cancers.
Depending on the site, size, grade, and type of tumor, our expert medical team determines a suitable precision
deployment mode to administer anticancer medications with the intent of targeting only the cancerous cells and
reducing
impact to the surrounding healthy cells. At Envita, targeted therapies are not just one of the many treatment options,
as all our patient-specific treatments are targeted to affect their unique neuroendocrine cancer.
Here are some of the innovative new treatments, which may be utilized by itself or in combination with other
therapies
to effectively treat each neuroendocrine cancer patient:
CIPI™ (Chemo Immuno Precision Injection)
CIPI™ (Chemo Immuno Precision Injections) is a revolutionary interventional radiology procedure for precision
tumor
chemoembolization. It is designed for deploying anti-cancer medications directly to difficult to reach tumors,
such as
hepatic, pulmonary, appendiceal, gastrointestinal, or pancreatic neuroendocrine tumors, which are common in
neuroendocrine carcinoma patients.
Through this proprietary technology we deliver personalized chemotherapy and immunotherapy adjunctive agents to kill
the
cancerous cells, seal the tumor’s blood supply, and deactivate it. The neo antigens released by the deactivated tumor,
triggers an immune system response to find and kill cancerous cells elsewhere in the body, reducing chances of a
potential metastases. CIPI™ has proved
exceptionally beneficial for many of our neuroendocrine carcinoma patients and helped them to progress in
their journey towards a long-term remission.
Envita's CIPI™ vs. Standard Surgery
Envita Medical Centers
Standard Surgery
Minimally invasive so it can be performed within 40-50 minutes, without the need for large surgical
incisions.
Envita's CIPI™:Checked
Standard Surgery:Unchecked
Can be performed multiple times, even at close intervals, because there is minimal risk of post-op
complications.
Envita's CIPI™:Checked
Standard Surgery:Unchecked
No need for general anesthesia, reducing the health risks that can result from being put into a
medically induced coma to perform an invasive surgery.
Envita's CIPI™:Checked
Standard Surgery:Unchecked
Faster recovery time as compared to traditional surgery, due to the minimally invasive administration.
Envita's CIPI™:Checked
Standard Surgery:Unchecked
Provides direct tumor targeting, which delivers patient-specific genomic agents into the tumor.
Envita's CIPI™:Checked
Standard Surgery:Unchecked
Causes a systemic immune response where the immune system is reactivated to find and attack other
metastatic cancer sites in the body.
Envita's CIPI™:Checked
Standard Surgery:Unchecked
Performed by highly trained medical professionals in an outpatient setting, so there is no need of
hospital stays for recovery.
Envita's CIPI™:Checked
Standard Surgery:Unchecked
*Individual results may vary. Envita
makes no guarantees for outcomes.
GTFC™ (Genetically Targeted Fractionated Chemotherapy) is our proprietary systemic therapy to deliver
precision-targeted
chemo medicines with the highest cytotoxicity for impacting each patient’s unique neuroendocrine carcinoma biomarkers.
This intravenous procedure increases the mechanism of action against each patient’s unique cancer expressions by using
a
greater number of targeted chemotherapy agents than standard untargeted chemotherapy. Though GTFC™ uses more chemo agents, their dosage is lower than standard maximum
therapeutic dosage chemotherapy, which is why many
of our patients do not experience common side effects, such as weakness and nausea.
This intravenous precision deployment mechanism of genetically typed chemo and immuno agents increases its
bioavailability, reducing the chances of impact on the healthy cells surrounding the cancerous cells. With the healthy
cells remaining intact, there are fewer chances of depressed immunity and resultant side effects. A healthy and
reactivated immune system is crucial to your holistic recovery because it is your first and last line of defense
against
neuroendocrine cancer relapse and metastasis.
Envita's GTFC™ vs. Standard Chemotherapy
Envita Medical Centers
Standard Chemotherapy
Helps to improve chemotherapy delivery to the tumor using a "Trojan Horse" delivery mechanism.
Envita's GTFC™:Checked
Standard Chemotherapy:Unchecked
Uses genetic molecular profiling to understand all the facets of each patient's specific cancer.
Envita's GTFC™:Checked
Standard Chemotherapy:Unchecked
Uses targeted treatment to enhance the mechanism of cancer kill.
Envita's GTFC™:Checked
Standard Chemotherapy:Unchecked
Uses microdosed (fractionated) chemotherapies, reducing the chances of impacting healthy cells.
Envita's GTFC™:Checked
Standard Chemotherapy:Unchecked
Minimizes toxicity to normal cells, lowering the chance of side-effects related to administration.
Envita's GTFC™:Checked
Standard Chemotherapy:Unchecked
Uses patient-specific supportive immunotherapy to strengthen the immune system.
Envita's GTFC™:Checked
Standard Chemotherapy:Unchecked
Aims to reduce multidrug resistance by administering 10 - 20% of the medication delivered in maximum dose
chemo.
Envita's GTFC™:Checked
Standard Chemotherapy:Unchecked
Allows custom-compounded medications to be readministered in tandem to suit each patient's individual cancer
mutations.
Envita's GTFC™:Checked
Standard Chemotherapy:Unchecked
*Individual results may vary. Envita
makes no guarantees for outcomes.
Hormone therapy is used to check the release of excess hormones from neuroendocrine tumors often causing carcinoid
syndromes, like diarrhea and flushed skin, but at Envita we go beyond standard somatostatin analogs and other
medications to holistically treat our patients. Medical
studies indicate how the use of certain agents may improve symptoms of carcinoid syndrome[12], but we focus on
slowing down
tumor growth and deactivating them as well, while checking excess secretions from tumors. We enhance the efficacy of
these medicines by combining them with genetically typed immunotherapy agents and research-based phytotherapeutic
medications.
Tumor Ablation
Ablation is another way of destroying tumors by utilizing either excess heat or cold. We use different types of tumor
ablation techniques such as cryoablation, radiofrequency ablation, and microwave ablation to target each patient’s
unique NET depending on its size, site, type, and grade.
A customized image-guided metal probe is injected into the tumor to freeze or heat and destroy the cancerous cells
with
either cooling agents, or microwaves or high-energy radio waves. At Envita, we optimize the benefits of these
procedures
by utilizing the antigens from the deactivated tumors to train your immune system in identifying and killing cancer
cells elsewhere in the body, reducing chances of a potential metastasis.
Different Types of Neuroendocrine Cancers
Neuroendocrine cancers are divided into various types and sub-types based on their functionality and site of origin.
They are as follows:
Functionality
NENs begin in specialized neuroendocrine cells, with features of both hormone-producing endocrine cells and nerve
cells
Due to their origin in neuroendocrine cells, some neoplasms may be functional as the tumors produce excess
hormones,
while others are nonfunctional with no specific clinical symptoms in the early stages
NENs can be functional or non-functional, irrespective of their site of origin
Sites of Origin
The following NETs are called Neuroendocrine Carcinomas (NECs), if the tumors comprise poorly differentiated cells:
GI Tract NET used to be called carcinoid tumors: starts in the neuroendocrine cells of the GI tract
Lung NET also used to be called carcinoid tumors: starts in the neuroendocrine cells of the lungs
Gastroenteropancreatic Neuroendocrine Tumors (GEP NET) also known as carcinoid or islet cell tumors are
further subdivided into:
Foregut Tumors: starts in the neuroendocrine cells of esophagus, stomach, proximal duodenum, liver, and
pancreas
Midgut Tumors: distal duodenum ileum, jejunum, ascending colon, and proximal two thirds of transverse colon
Hindgut Tumors: distal third of transverse colon, descending colon, sigmoid colon, and rectum
Pancreatic NET (PNET), also known as islet cell tumors: starts in the neuroendocrine cells of the pancreas
Markel Cell Carcinoma: starts in the Markel cells (type of skin neuroendocrine cells) of the top layer of skin
Medullary Thyroid Cancer (MTC): starts in the thyroid gland
Pheochromocytoma: starts in the adrenal gland
Paraganglioma: starts outside of the adrenal glands
Symptoms of Neuroendocrine Cancer
Watch out for the following symptoms as any one or a combination of these symptoms could be manifestations of
neuroendocrine cancers:
Weight loss without trying
Exhaustion
Loss of appetite
Nausea
Lump or persistent pain in a specific part of the body
Our expert team comprising oncologists, interventional radiologists, researchers, and pharmacists, strives
relentlessly
to attack your unique neuroendocrine cancer from all possible angles. They undergo extensive training of over 1,500
hours in our personalized precision oncology approach to help you find the best possible treatment options for a
holistic recovery. If you or your loved ones have any questions regarding neuroendocrine cancer, please contact us at:
866-830-4576. May God bless you on your journey to healing.
References
[1] Yao JC, Hassan M, Phan A, et al. One hundred years after "carcinoid": epidemiology of and prognostic factors
for
neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26(18):3063-3072.
doi:10.1200/JCO.2007.15.4377
[2] Aytac E, Ozdemir Y, Ozuner G. Long term outcomes of neuroendocrine carcinomas (high-grade neuroendocrine
tumors) of the
colon, rectum, and anal canal. J Visc Surg. 2014;151(1):3-7. doi:10.1016/j.jviscsurg.2013.12.007
[3] Sorbye H, Baudin E, Borbath I, et al. Unmet Needs in High-Grade Gastroenteropancreatic Neuroendocrine
Neoplasms (WHO
G3). Neuroendocrinology. 2019;108(1):54-62. doi:10.1159/000493318
[4] Lillie EO, Patay B, Diamant J, Issell B, Topol EJ, Schork NJ. The n-of-1 clinical trial: the ultimate
strategy for
individualizing medicine?. Per Med. 2011;8(2):161-173. doi:10.2217/pme.11.7
[5] Hassan MM, Phan A, Li D, Dagohoy CG, Leary C, Yao JC. Risk factors associated with neuroendocrine tumors: A
U.S.-based
case-control study. Int J Cancer. 2008;123(4):867-873. doi:10.1002/ijc.23529
[6] Öberg K. The genetics of neuroendocrine tumors. Semin Oncol. 2013;40(1):37-44.
doi:10.1053/j.seminoncol.2012.11.005
[7] Horn L, Mansfield AS, Szczęsna A, et al. First-Line [removed due to editorial restrictions] plus Chemotherapy
in
Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018;379(23):2220-2229. doi:10.1056/NEJMoa1809064
[8] Modlin IM, Kidd M, Malczewska A, et al. The NETest: The Clinical Utility of Multigene Blood Analysis in the
Diagnosis
and Management of Neuroendocrine Tumors. Endocrinol Metab Clin North Am. 2018;47(3):485-504.
doi:10.1016/j.ecl.2018.05.002
[9] Al-Toubah T, Cives M, Strosberg J. Novel immunotherapy strategies for treatment of neuroendocrine neoplasms.
Transl
Gastroenterol Hepatol. 2020;5:54. Published 2020 Oct 5. doi:10.21037/tgh.2019.12.18
[10] Strosberg JR, Caplin ME, Kunz PL, et al. [removed due to editorial restrictions] plus long-acting [removed
due to
editorial restrictions] versus highdose long-acting [removed due to editorial restrictions] in patients with midgut
neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label,
randomised,
controlled, phase 3 trial [published correction appears in Lancet Oncol. 2022 Feb;23(2):e59]. Lancet Oncol.
2021;22(12):1752-1763. doi:10.1016/S1470-2045(21)00572-6
[11] Laskaratos FM, Caplin M. Treatment challenges in and outside a network setting: Gastrointestinal
neuroendocrine tumours.
Eur J Surg Oncol. 2019;45(1):52-59. doi:10.1016/j.ejso.2018.03.012
[12] Pavel M, Hörsch D, Caplin M, et al. [removed due to editorial restrictions] for carcinoid syndrome: a
single-arm,
multicenter trial. J Clin Endocrinol Metab. 2015;100(4):1511-1519. doi:10.1210/jc.2014-2247
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