Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_901_Библиотеки_им_академика_М_И_Перельмана
.pdf
118
Pancreatic Neuroendocrine Tumors
Pancreatic neuroendocrine tumors
Incidence Relatively uncommon
90% of symptomatic patients are caused by compressive effects of the tumor
Presentation
10% are characterized as functional because of hormone hypersecretion
Neuroendocrine tumors are graded based on Ki-67 proliferation, mitotic rates, and behavior
Staging
(angioinvasion or invasion of other organs)
Staging is based on the TNM grading system
Stage I: There is a small tumor in the pancreas and it has not spread elsewhere in the body (T1,
N0, M0)
Stage II: The tumor is larger and has not spread to the regional lymph nodes or elsewhere in the
body (T2 or T3, N0, M0)
Stage III: The tumor is any size and has spread to the regional lymph nodes (any T, N1, M0). Or,
the tumor has spread to the stomach, spleen, colon, or adrenal gland, or the wall of the celiac axis
or the superior mesenteric artery, but the cancer has not spread to the regional lymph nodes or
anywhere else (T4, N0, M0)
Stage IV: There is distant metastasis (any T, any N, M1)
GX: Grade cannot be evaluated
G1: Mitotic index is less than 2, or Ki-67 index is less than 3
G2: Mitotic index is between 2 and 20, or Ki-67 index is 3 to 20
G3: Mitotic index is more than 20, or Ki-67 index is more than 20
M. Krell et al.
Genetic syndromes associated with PNET
Syndrome Characteristics Management
Multiple
endocrine
neoplasia (MEN)
type 1
Von HippelLindau (VHD)
disease
Most frequent genetic syndrome associated with
PNET
Mutation of the MENIN tumor suppressor, on
chromosome 11q13
Autosomal dominant inheritance
Associated with parathyroid adenomas or
hyperplasia and pituitary adenomas
Most commonly associated with gastrinoma
Mutation in the VHD gene, on chromosome
3p25–26
Autosomal dominant inheritance
Characterized by renal cell carcinoma,
pheochromocytoma, and hemangioblastomas of the
brainstem and retina
PNET associated with genetic
syndromes may be difcult to manage
because tumors may be multifocal
Gastrinoma requires surgical resection
>2cm
Observation with close surveillance and
basal acid control may be appropriate
given their indolent course
4 Pancreas andSpleen
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Differentiation of solid pancreatic tumors based on imaging characteristics
PNET Adenocarcinoma
119
CT Hypoattenuating in early and late contrast phases enhancing
in the arterial phases because of hypervascularity
a
Axial CT urogram image with IV contrast incidentally
demonstrated a well-circumscribed, homogenous enhancing
pancreatic mass (arrow) which was later biopsy- proven to
be a pancreatic neuroendocrine tumor.
b
Hypovascular in the arterial phase
b
a
(A) Axial abdominal CT image with IV contrast
incidentally demonstrates a 4.3cm pancreatic head mass
(arrow). Subsequent (B) axial abdominal PET-CT with IV
Dotatate demonstrates intense uptake in the region of the
previously seen mass (arrow), consistent with pancreatic
neuroendocrine tumor
MRI Low signal intensity on T1-weighted images and high
signal intensity on T2-weighted images
Ring-like enhancement on early and late contrast images,
which may differentiate it from other pancreatic tumors
120
Nonfunctional pancreatic neuroendocrine tumors (PNETs)
Characteristics Most PNETs are found incidentally and are nonfunctional
M. Krell et al.
Symptoms
Laboratory
studies
Management
Follow-up
Abdominal pain, weight loss, and jaundice when tumors are large enough to cause compressive
symptoms—Usually at later stages
Pancreatic polypeptide and chromogranin A
Surgical resection is effective for management of localized PNETs
For tumors <2cm➔enucleation or observation
For tumors >2cm, close proximity to pancreatic duct, or if lymph nodes are involved➔formal
pancreatic resection
Octreotide is used for the treatment of locoregional and metastatic unresectable PNETs
Based on baseline size and observation of recent change. Dotatate PET/CT is highly sensitive
and may be used to evaluate for recurrence after resection or metastatic disease
Research
Reference Findings
Shah MH, Goldner WS, Halfdanarson TR, etal.
NCCN Guidelines Insights: Neuroendocrine and
Adrenal Tumors, Version 2.2018. J Natl Compr Canc
Netw. 2018;16(6):693–702.
Management of NET
Management of lymph nodes is controversial for
nonfunctional PNETs between 1 and 2cm, because the
risk of nodal metastases is low but measurable (reported
7–26%). Lymph node resection should be considered in
these patients
Case Management
• Nonfunctioning tumors < 2cm
• Insulinoma <2cm
• Nonfunctional PNET >2cm
• Functional PNET (somatostatinoma, VIPoma, glucagonoma)
• Tumors with lymph node involvement
Enucleation
Formal pancreatic resection
4 Pancreas andSpleen
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
DM, gallstones,
steatorrhea, and
hypochlorhydria (due
High-volume secretory
diarrhea (3–5L)
Hypokalemia (from
to decreased
gallbladder emptying)
Very rare
Most are malignant
Metastatic on
diarrhea), achlorhydria, and
metabolic acidosis
Most are malignant
Metastatic on presentation: >
presentation: 90%
Head of pancreas
70%
10% extrapancreatic
(retroperitoneal, thorax)
Fasting serum
somatostatin >10pg/
mL
Overnight fasting VIP level
of 225 to 2000pg/mL
121
Dermatitis, DM, DVT,
weight loss, and
necrolytic migratory
erythema (due to
hypoaminoaciduria),
glossitis
50% multiple
75% spontaneous and 25% MEN-1
Insulinoma Gastrinoma Glucagonoma VIPoma Somatostatinoma
hypoglycemia when fasting,
serum glucose <50mL/dL,
and relief of symptoms after
glucose administration
Most are malignant
-present with metastasis
Distal pancreas Tail of pancreas
50% malignant
Metastatic on presentation: 50%
MC islet cell tumor
Fasting glucagon
level>500pg/mL
of pancreas, and hepatoduodenal
ligament)
Fasting serum gastrin>1000pg/mL
and gastric pH <2 (off PPI for
(I/G)>0.4➔insulinoma
stimulation test (gastrinoma➔gas-
trin >200; Normal patient decreased
gastrin, Gastrinoma: Secretin
2weeks)
• Conrmatory test: Secretin
Fasting glucose <45–55mg/dL
• Insulin level>3 μU/mL
stimulates gastrin release)
• C-peptide >200pmol/L
Beta-hydroxybutyrate
<2.7mmol/L
• Screen negative for
• Inspection of gastrinoma triangle
sulfonylurea and meglitinide
• Absence of insulin antibodies
wall➔duodenotomy to inspect the
• Intraoperative U/S
• Octreotide scan
localizes 90%
• Intra-op U/S
duodenal wall
• Palpation of the duodenal
Functional PNET
Symptoms Whipple triad: Symptomatic
Characteristics 90% benign solitary adenoma
Location Anywhere in pancreas Gastrinoma triangle (duodenum, head
Diagnosis Fasting insulin/glucose
Localization • Pre-op selective angiography
122
Resection+cholecys-
tectomy
5-year survival: 30%
to 60%
5-year survival:
Approximately 70%
M. Krell et al.
Complete anatomic
resection
-distal pancreatec-
tomy+splenectomy
Enucleate if <2cm
Formal resection if >2cm
MEN1 syndrome must be ruled out
FU and streptozocin;
Insulinoma Gastrinoma Glucagonoma VIPoma Somatostatinoma
Formal resection if >2cm
• For metastatic disease➔5
octreotide
• Diazoxide for symptoms
5-year survival: 85%
10-year survival
stabilization; symptomatic
improvement
hypoglycemia in patients
• Somatostatin analogs: Tumor
with metastatic disease
• Everolimus➔for refractory
5-year survival with
metastatic disease: 60%
Nonaggressive forms: May be 90%
Aggressive forms: May be 30%
hyperglycemia on successful
benign disease
resection of insulinoma
• Normal life expectancy in
Functional PNET
Treatment Enucleate if <2cm
Survival Possible short-lived
4 Pancreas andSpleen
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Pancreatic Adenocarcinoma
Pancreatic adenocarcinoma
Epidemiology Men are affected slightly more than women with a 1.3:1 ratio
African Americans have a slightly higher risk of developing pancreatic cancer
Risk factors Environmental risk factors: Smoking (risk of developing cancer is a linear association with
pack-years smoked); chronic pancreatitis and obesity
Hereditary risk factors: Genetic syndromes account for 20% of hereditary pancreatic cancer (cystic
brosis, Peutz-Jeghers syndrome, BRCA2 gene mutation, lynch syndrome, familial adenomatous
polyposis, li-Fraumeni, CDKN2A, and familial pancreatitis)
Familial pancreatic cancer (no identiable syndrome) accounts for the other 80% of hereditary
pancreatic cancer
Pathogenesis KRAS Oncogene
Activated in >95% of pancreatic adenocarcinoma
CDKN2A, P53, and DPC4 Tumor suppressor genes
Presentation Weight loss, new-onset diabetes, abdominal pain
Presentation Lesion location
Painless jaundice Periampullary lesions
123
Tumor
markers
Diagnostic
imaging
Pain, weight loss Lesions in body and tail
CA 19–9 Most sensitive for pancreatic adenocarcinoma
Used for pretreatment evaluation
Used for surveillance
CT Should be performed as “pancreas protocol” with multiple
contrast phases and thin cuts through pancreas.
EUS Adjunct to establish tissue diagnosis and dene relationship to
vasculature.
MRCP Used to dene biliary anatomy; when paired with contrast-
enhanced MRI can also dene vascular anatomy
124
Pancreatic adenocarcinoma
Abutment is dened as <180° and encasement is >180°
Resectable Borderline resectable Unresectable
M. Krell et al.
Management
No radiographic evidence of
abutment or encasement of the
SMA, celiac artery, hepatic
artery. <50% narrowing of SMV
and/or portal vein
Surgical candidates Neoadjuvant Chemotherapy
Axial abdominal CT image with
IV contrast demonstrates a
slightly hypoattenuating mass
conned to the uncinated
process (star) of the pancreas
without any vascular invasion of
either the superior mesenteric
artery (solid arrow) or portal
vein (outlined arrow).
Abutment (<180° contact) of
the celiac axis or SMA, short
segment abutment without
extension to celiac artery or
hepatic artery bifurcation,
>50% narrowing of SMV and/
or portal vein, with distal and
proximal target available for
reconstruction
then re-assess
Axial abdominal CT image
with IV contrast demonstrates
a pancreatic head mass (star)
with <180-degree abutment of
the superior mesenteric artery
(arrow).
>180 abutment/encasement of
SMA, celiac artery, hepatic
artery, occlusion without
obvious option for
reconstruction of SMV/portal
vein
Neoadjuvant chemotherapy
Axial abdominal CT image with
IV contrast demonstrates a
pancreatic mass (star) encasing
the SMA (solid arrow) and
portal vein (outlined arrow).
Not shown is >180 abutment of
the celiac artery as well. Also
noted is inltration of the
duodenal-jejunal junction
(arrowhead)
Operative
treatment
Staging laparoscopy to reduce the frequency of nontherapeutic laparotomy for patients with
unsuspected metastatic disease
Tumor location Operative treatment
Head of pancreas Pancreaticoduodenectomy
Body or tail of pancreas Distal pancreatectomy and splenectomy
4 Pancreas andSpleen
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Pancreatic adenocarcinoma
125
Neoadjuvant
and adjuvant
therapy
Pancreatic cancer after resection Adjuvant chemotherapy (gemcitabine or uorouracil plus folinic
Metastatic pancreatic
cancer+good functional
status+normal bilirubin
Borderline resectable or locally
advanced
Follow-up Follow-up every 3–6months for 2years and then every 6–12months
On each follow-up obtain: CA 19–9, CT chest abdomen and pelvis
Case Treatment
acid) is associated with a survival benet
Chemotherapy FOLFIRINOX (leucovorin, uorouracil,
oxaliplatin, and irinotecan)
Neoadjuvant chemotherapy
Research
Reference Findings
Gilbert JW, Wolpin B, Clancy T, Wang J, Mamon H,
Shinagare AB, Jagannathan J, Rosenthal
M.Borderline resectable pancreatic cancer:
Conceptual evolution and current approach to
image-based classication. Ann Oncol.
2017;28(9):2067–76
Khorana AA, Mangu PB, Berlin J, etal. Potentially
curable pancreatic cancer: American Society of
Clinical Oncology clinical practice guideline update. J
Clin Oncol. 2017;35(20):2324–8
Borderline resectable pancreatic cancer is dened as
tumor abutment of <180° of the superior mesenteric
artery or celiac axis. Induction therapy may sterilize at
least the periphery of the tumor, thereby facilitating a
complete resection
Adjuvant chemoradiation is recommended in patients
with residual microscopic disease or node-positive
disease. These patients are known to benet from
adjuvant chemoradiation
Cameron JL, He J.Two thousand consecutive
pancreaticoduodenectomies. J Am Coll Surg.
2015;220(4):530–536.
Ripamonti CI, Santini D, Maranzano E, Berti M,
Roila F; ESMO Guidelines Working Group.
Management of cancer pain: ESMO clinical practice
guidelines. Ann Oncol. 2012;23(Suppl 7):vii139–154
Arcidiacono PG, Calori G, Carrara S, McNicol ED,
Testoni PA.Celiac plexus block for pancreatic cancer
pain in adults. Cochrane Database Syst Rev.
2011;3:CD007519
Adjuvant chemotherapy decreases recurrence and
increases survival after pancreaticoduodenectomies for
pancreatic adenocarcinoma
Current management of pancreatic cancer pain follows
the World Health Organization 3-step ladder schema,
beginning with nonopioid analgesics such as
nonsteroidal anti-inammatory drugs, and eventually
progressing to opioid analgesics
For pancreatic cancer: A celiac plexus block is safe and
tremendously effective, with signicant advantages over
conventional opioid therapy for up to 6months,
including dramatic decreases in opioid use and attendant
side effects
126
M. Krell et al.
Surgical Approach
Distal pancreatectomy
Preoperative Perioperative vaccination for encapsulated bacteria prior to an operation that involves splenectomy
(given 2weeks prior to the procedure or 2weeks following the procedure)
Involves removal of the pancreas proximal to the pathology
A thorough diagnostic laparoscopy to exclude extrapancreatic disease
Key steps
Intraoperative
decision
making
Lesser sac is entered through division of the gastrocolic ligament
If the spleen is to be removed➔the short gastric vessels are divided
The splenocolic ligament is divided to allow caudal retraction of the transverse colon and splenic exure
Distal aspect of the pancreas is then mobilized from the posterior retropancreatic fat
Intra-op scenario Management
Cannot localize tumor Intra-op U/S to localize
Pancreatic tumor
invades PV or SMV
Unresectable tumor Abort resection+place metal markers for radiation
Indolent disease Splenic preservation
Splenic
Hemorrhage
Venous resection and reconstruction
• Kimura approach preserves splenic artery, vein, and short gastric vessels
• Warshaw approach preserves only short gastric arteries and resects the
splenic vessels away from the hilum
• Pack left upper quadrant
• Use hemostatic agents and argon beam coagulation
• Perform a splenectomy
Distal pancreatectomy with celiac artery resection (Appleby procedure)
Criteria for
Appleby
procedure
Criteria for Appleby procedure
1. Tumor must be located in the pancreatic neck or body without macroscopic extension into the
pancreatic head
2. Tumor invasion must be limited to celiac artery, CHA, or root of the splenic artery; with no
involvement of the root of the celiac artery from the aorta
3. No involvement of the GDA, proper hepatic artery, or SMA
4. No distant metastasis
Key steps Exploration of the peritoneum and the liver to identify metastases
Appleby procedure consists of distal pancreatectomy, splenectomy, lymphadenectomy, and en
bloc resection of the celiac artery and its branches
The common hepatic artery ligated, after conrming retrograde hepatic artery perfusion through the SMA
Pancreas is transected at the level of the neck
The splenic vein is transected at its conuence with the superior mesenteric vein. This allows for
the identication of SMA
SMA is used as a landmark and is followed cephalad until the celiac trunk is reached
The celiac artery is then transected at its origin from the aorta
Left
pancreatic
artery & vein
pancreaticoduodenal
4 Pancreas andSpleen
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Distal pancreatectomy with celiac artery resection (Appleby procedure)
Postoperative After an Appleby procedure, hepatic arterial perfusion occurs only by collateral circulation via
pancreaticoduodenal arcades supplied by the SMA➔risk of hepatic infarction
Stomach is supplied from SMA via pancreaticoduodenal artery (PDA) through gastroduodenal
artery (GDA) and right gastroepiploic artery (RGEA)➔risk of ischemic gastropathy
Abdominal
Hepatic
artery
proper
Gastroduodenal
Anterior & posterior
superior
artery
Anterior & posterior
inferior pancreaticoduodenal
artery
artery
Inferior
vena cava
Portal vein
aorta
Celiac
truck
Superior
masenteric
Splenic
artery
gastric artery
Spleen
Great
artery
127
Complications of distal pancreatectomy
Complications Characteristics Management
Pancreatic stula Tachycardia, fever, and high drain output
Fistulas are diagnosed using the international
study group on pancreatic stula (ISGPF)
denition of any measurable volume of uid
on or after postoperative day 3, with amylase
>3x serum amylase level
Fistulas are classied into three ISGPF groups
(A, B, and C) depending on the patient’s
clinical status
Splenic/portal vein
thrombosis
Symptomatic acute portal vein thrombosis
typically presents with abdominal pain
Most commonly develop at the distal
transection margin in up to one-third of
patients
Placement of an operative drain at the staple
line is recommended
Systemic anticoagulation
Recanalization without treatment can be
expected in 15% to 20% of patients; early
systemic anticoagulation results in
recanalization in 55% to 60% of patients
Thrombolysis➔if the disease is
progressive and signs of mesenteric
ischemia
Соседние файлы в папке Библиотека им академика М.И. Перельмана