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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_987_Библиотеки_им_академика_М_И_Перельмана.pdf
244
H. C. Stuart and J. L. Pasieka
• In the setting of locoregional disease Type 3G-NETs should be resected with a
total or subtotal gastrectomy and regional lymphadenectomy, similar to gastric
adenocarcinoma [6].
• The 5-year survival for type 3G-NETS is <35%, so options for systemic chemo-
therapy, targeted radionucleotide therapy, and radiofrequency ablation of metastatic disease should be discussed at a multidisciplinary tumor board [1, 2]
(Table27.1).
• Complications following surgical resection are usually related to the extent of
surgery and the type of gastric reconstruction. Retained gastric antrum, dumping
syndrome, and bile reux are all possibilities depending on the procedure.
Small Intestinal Neuroendocrine Tumors
• Small intestinal neuroendocrine tumors (SI-NETs) can develop in the duode-
num, jejunum, or ileum although >70% are found in the terminal ileum [7]. After
diagnosis and staging, surgery can be considered for denitive therapy in the
setting of locoregional disease or for palliation of symptoms in the setting of
metastatic or unresectable disease.
• For patients with locoregional disease a bowel resection and mesenteric lymph-
adenectomy should be performed to remove all palpable disease.
• Up to 40% of patients can have multifocal tumors in the small bowel so it is
essential to palpate the bowel from the ligament of Treitz to the ileocecal valve
[8]. If laparoscopic surgery is planned a mini laparotomy or hand port may be
considered to ensure there is no palpable disease left in situ [8].
• Cholecystectomy at the time of surgery should be considered as patients receiv-
ing long-term SSA appear to be at higher risk for biliary stone disease [9].
• SI-NET primary tumors are often small and difcult to detect on imaging [10].
Patients often present with a mesenteric mass representing lymph node metastases or liver metastases (Fig.27.2). SI-NETs secret bioactive amines and peptides
that induce brotic change around malignant mesenteric lymph nodes resulting
in the typical “spoke and wheel” pattern on CT scan from the desmoplastic reaction around these nodes (Fig.27.3). This change can cause tethering of the mesenteric blood vessels or adjacent bowel and can lead to ischemia, pain, and/or
bowel obstruction (Fig.27.4).
• Resectability of the primary tumor and lymph nodes is determined by the extent
of disease involvement of the mesenteric vessels. If the superior mesenteric
artery is involved close to the root of the mesentery this is often considered unresectable as it would require extensive bowel resection which prevents adequate
nutrient absorption [11] (Fig.27.5).
• Patients with low-grade SI-NETs and liver metastases can live for many years.
Cytoreductive liver surgery can be considered, especially if excess hormone
from a functional tumor is causing symptoms. There is retrospective evidence of
both biochemical and survival benet in patients who underwent resection of at
27 Surgery for Neuroendocrine Tumors of the Stomach, Small Intestine, Large…
Fig. 27.2 Liver metastases
from SI-NET.Extensive
liver metastases from a
small undetected ileal
primary (insert).
(Permission for these
intraoperative pictures was
given to Dr. JL Pasieka by
the patient for the purpose
of teaching)
ab
245
Fig. 27.3 (a, b) CT scan of small intestinal NETs. Classic desmoplastic reaction around the mesenteric lymph nodes from a SI-NET resulting in the classic “spoke and wheel” pattern (circle)
least 70% of liver metastases, although these series predate newer therapies
[1, 12–15].
• Survival benet following resection of the primary tumor and regional lymph
nodes in the setting of stage IV disease is debated in the literature [16, 17].
However, symptomatic relief and avoidance of future loco-regional complications are often considered as rational for surgery [12, 13, 18].
• If considered unresectable, alternative procedures can be considered such as
intestinal bypass or abdominal tumor debulking to alleviate mechanical obstruction. Thoughtful consideration should be given when performing palliative surgery to ensure the risk-to-benet ratio is favorable [11, 12].
• All patients with metastatic disease should all be reviewed in a multidisciplinary
setting as surgery is only one therapeutic option among several. Other options
include long-acting SSAs, peptide receptor radiotherapy, liver embolization, and
systemic chemotherapy or targeted agents.
246
Fig. 27.4 Small intestine NETs. Ischemic segment of small bowel resulting from the desmoplastic
lymph node metastases. Resection of this segment (insert) provided excellent palliation from ischemic pain. (Permission for these intraoperative pictures was given to Dr. JL Pasieka by the patient
for the purpose of teaching)
Fig. 27.5 Unresectable
SI-NET. MRI
demonstrating encasement
of the superior mesenteric
artery (arrow) by a large
mesenteric mass (circle) in
a patient with SI-NET of
the terminal ileum
H. C. Stuart and J. L. Pasieka
Carcinoid Syndrome andHeart Disease
• Approximately 20–30% of SI-NETs will develop carcinoid syndrome (CS) as a
result of bioactive amines produced by the tumor entering directly into the systemic circulation [1, 19]. This most commonly occurs in the presence of liver
metastases (Table27.3).
• Excess serotonin can produce symptoms of carcinoid syndrome (Table 27.4),
and correlates with elevated 24 h urine 5-hydroxyindoleacetic acid
(5-HIAA) levels.
27 Surgery for Neuroendocrine Tumors of the Stomach, Small Intestine, Large…
247
Table 27.3
carcinoid syndrome
Table 27.4
Symptom Frequency
Flushing
Bright red ush to face/neck/upper torso
Type 1—Duration 1–5min
Type 2—Duration up to 1–2h residual facial telangiectasis
Type 3—Violet residual hue with exacerbation of the ushing
(Fig. 27.7)
Diarrhea Up to 80%
Carcinoid heart disease
Plaque-like deposits of brous tissue on endocardium and right-sided heart valves
Tricuspid and pulmonary regurgitation
Restrictive cardiomyopathy
Bronchospasm 10–20%
Pellagra (niacin deciency)
Dermatitis/diarrhea/dementia
Causes of
Features of carcinoid syndrome
Hepatic metastases
Peritoneal disease
Extensive retroperitoneal lymphadenopathy
Ovarian metastases
Signicant liver dysfunction
Carcinoid syndrome results from the release of bioactive amines
and peptides by SI-NETs directly into the systemic circulation.
This bypasses the deactivation of amines in the liver (rst-pass
metabolism) allowing for greater systemic effect
a
>90% of the cases
a
> 90%
40–50%
5%
• High levels of serum serotonin can cause brosis of the right-sided heart valves
so pre-operative cardiac echocardiography should be done on all patients as part
of their evaluation [20].
• It is important to document carcinoid syndrome pre-operatively as patients can
develop carcinoid crisis intra-operatively with tumor manipulation leading to
refractory hypotension and risk of cardiovascular collapse (Fig.27.6).
• Treatment with an SSA helps alleviate symptoms of CS and there is limited evi-
dence to suggest it may prevent intra-operative carcinoid crisis [1]. Should carcinoid crisis occur, resuscitation with uid and intravenous octreotide infusion is
recommended with low-level evidence [21].
248
ab
Fig. 27.6 Carcinoid crisis intraoperatively. Intraoperative picture of ushing seen during
manipulation of the liver. (a) corresponds to a drop in patient’s blood pressure that required
uid resuscitation and increasing the octreotide infusion. (b) 30min later once the blood
pressure returned to normal and the operative procedure continued. (Permission for use of
these photographs was given by the patient to Dr. JL Pasieka, for the purpose of teaching)
H. C. Stuart and J. L. Pasieka
Fig. 27.7 Type 3 facial
ushing of a patient with
carcinoid syndrome.
(Permission was given by
patient to Dr. JL Pasieka for
teaching purposes)
27 Surgery for Neuroendocrine Tumors of the Stomach, Small Intestine, Large…
249
Colon andAppendix
• Neuroendocrine tumors are the most common tumor of the appendix and are
often found incidentally on pathology following appendectomy for appendicitis.
• Tumors that are small with low-risk features can be treated denitively with
appendectomy (Table27.6).
• If higher risk features are present (Tables 27.5 and 27.6), a right hemicolectomy
should be performed for diagnostic and therapeutic purposes. Prior to colectomy,
staging with cross-sectional and functional imaging along with colonoscopy
should be performed to evaluate for additional lesions (Table27.6).
• Primary colon neuroendocrine tumors are rare (7% of all GI-NETs) [7] but are
often more aggressive with poor differentiation and higher grade. Patients should
have pre-operative cross-sectional imaging and complete colonoscopy for staging. Formal segmental colon resection with regional lymphadenectomy is recommended. Functional appendiceal and colonic NETs are rare therefore
biochemical work up can be guided by symptoms.
Table 27.5
features of appendiceal
neuroendocrine tumors
Table 27.6 Treatment of appendiceal and rectal NETs based on size
Size of
primary Appendix
< 1cm Appendectomy 1% Conned to the
1–2cm Appendectomy
High-risk
Functional and cross-sectional
imaging to rule out metastatic
disease
Discussion at multidisciplinary NET
tumor board)
OR
Right hemicolectomy if high-risk
features found
(Table 27.5)
Poor differentiation
Grade>2 (Ki67>3%)
Positive margin following appendectomy
Size greater than 2cm
Invasion into the mesoappendix or serosa
Lymphovascular invasion
Positive lymph nodes
Goblet cell carcinoid or MINEN
Risk of
lymph
nodes Rectal
submucosa with no
lymph node involvement
➔ <5mm-EMR
➔ >5mm EMR or ESD
0–10% No muscularis propria
invasion
No perirectal lymph
nodes
➔ ESD or wide local
excision
Invasion, lymph node
involvement or high-risk
features
➔ should have low
anterior resection with
total mesorectal excision
Risk of
lymph
nodes
2%
10–15%
(continued)
250
Table 27.6 (continued)
Risk of
Size of
primary Appendix
> 2cm Diagnostic right hemicolectomy
OR
If G1 and completely excised,
consider functional and crosssectional imaging to rule out
metastatic disease (currently
controversial should be discussed at
multidisciplinary
NET tumor board)
EMR endoscopic mucosa resection, ESD endoscopic submucosa dissection
lymph
nodes Rectal
20–30%
H. C. Stuart and J. L. Pasieka
Low anterior resection
with total mesorectal
excision
OR
Abdominoperineal
resection
Risk of
lymph
nodes
60–80%
Rectum
• The incidence of rectal NETs has increased nine-fold over the last 3 decades and
they represent roughly 25% of GI-NETs [1, 3].
• Small tumors are often discovered incidentally on screening endoscopy.
Symptomatic patients more commonly present with rectal bleeding from large
invasive tumors [1].
• Management of rectal NETs is guided by the features predicting the risk of
lymph node metastases (Table27.6).
• Small (< 1cm) low-grade tumors (G1) can be treated with endoscopic or transanal excision and anatomical resection is rarely required. Guidelines recommend
sigmoidoscopy +/− pelvic MRI at 12months if the lesion was not completely
excised. Completely excised lesions <1cm require no ongoing surveillance [1].
• Local excision can be performed for lesions 1–2cm and these patients should be
followed with colonoscopy, EUS, and pelvic MRI at 1 year and yearly colonoscopy for 5years [1].
• Higher grade (G2, G3) tumors >2cm, with evidence of invasion into the submucosa and/or lymphovascular invasion, warrant staging with pelvic MRI and/or
endoscopic ultrasound (EUS) to assess regional lymph nodes and cross-sectional
imaging for distant disease.
• High-risk features or nodal involvement warrant a low anterior resection with total
mesorectal excision for removal of the primary tumor and lymph nodes (Table27.6).
These patients are followed with annual colonoscopy, EUS, and MRI.
• Rectal NETs are rarely functional so biochemical testing is not required unless
clinical symptoms suggest hormone excess.
Summary
• GI-NETs are rare, histologically distinct tumors, with unique site-specic traits.
• The majority have a slow indolent biological behavior.
• Surgery for this diverse group of GI-NET is dependent on the presenting stage,
the site of origin, and the presence or absence of a functional endocrinopathy.
27 Surgery for Neuroendocrine Tumors of the Stomach, Small Intestine, Large…
251
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Part V
Special Considerations
Chapter 28
Familial Endocrine Syndromes
TauqRajwani andJessicaE.Gosnell
Multiple Endocrine Neoplasia
Multiple Endocrine Neoplasia 1 (MEN1)
• MEN1 is an autosomal dominant syndrome that occurs as a result of mutations
in the tumor suppressor gene MENIN, located on chromosome 11q13. This syndrome most commonly manifests with primary hyperparathyroidism, tumors of
the pancreas and duodenum, and anterior pituitary tumors. Less commonly,
MEN1 can be associated with tumors of the adrenal glands, broncho-pulmonary
carcinoids, and other neuroendocrine tumors [1].
• Primary hyperparathyroidism is the most common endocrinopathy in patients
with MEN1. Approximately 95% of patients with MEN1 will develop primary
hyperparathyroidism.
• The disease tends to involve all four parathyroid glands. Treatment includes sub-
total parathyroidectomy or total parathyroidectomy with or without
autotransplantation.
• Following parathyroidectomy, it is estimated that 40–60% of patients will
develop recurrence within 10years [2]. The goals of treatment then are to
T. Rajwani
General and Endocrine Surgery, Sutter Medical Center, Sutter Capitol Pavilion,
Sacramento, CA, USA
e-mail: tauq.rajwani@ucsf.edu
J. E. Gosnell (*)
Department of Surgery, Endocrine Surgery Section, University California San Francisco,
San Francisco, CA, USA
e-mail: jessica.gosnell@ucsf.edu
Switzerland AG 2024
R. M. Gartland, J. A. Lee (eds.), Endocrine Surgery Clerkship, Contemporary
Surgical Clerkships, https://doi.org/10.1007/978-3-031-62091-1_28
255© The Author(s), under exclusive license to Springer Nature