Download Epigastric pain and weight loss

Management Conference
A WOMAN WITH
EPIGASTRIC PAIN,
VOMITING
Raika Jamali M.D.
Gastroenterologist and hepatologist
Tehran University of Medical Sciences
• A 62 year old woman with epigastric
pain, post prandial vomiting and
weight loss from 2 months ago.
• The epigastric pain is constant with
episodes of colicky pain after meals
followed by vomiting.
• No radiation and no response to PPI
is reported for epigastric pain.
• Weight loss is about 8 Kg in the past
2 months.
• There was a history of cholecystectomy and
choledochodeudenostomy due to cholecystitis
and cholelithiasis In 83.12.27.
• The patient had epigastric pain from one year
before surgery which was aggravated in the
past 2 months before admission in 83.12.27.
• Epigastric pain aggravated by eating but no
vomiting was reported.
• The patient had an episode of acute
abdominal pain in 84.2.30 that lead to
laparotomy for evaluation of acute
abdomen.
• The surgical report was:
Serosanginous fluid in abdomen & pelvic.
Adhesions from previous surgery and
edematous pancreas but no mass was
seen in the pancreas.
• The patient discharged with the diagnosis
of pancreatitis.
• The epigastric pain persisted and
did not respond to PPI so
endoscopy performed :
• GERD grade A + Hiatal hernia +
pan gastritis + mild duodenitis
• PPI continued
• There was an episode of colicky
abdominal pain which resulted in third
laparotomy for evaluation of acute
abdomen (85.2.29).
• The surgical diagnosis was
pancreatitis.
• After 3 laparatomies the patient
referred to gastroentrologist for
evaluation of persistent epigastric
pain, vomiting and weight loss in
85.6.25.
•
•
•
•
OB = negative
AST=26
ALT=36
ALP=612*
• UGI endoscopy: Duodenitis
• Colonoscopy: normal
• Sonography: Multiple hypoechoic
lesions in liver. Enlargment of
pacreatic head.
CT scan recommended.
What is the next diagnostic step ?
Small intestine follow through for evaluation
of partial obstructoin and GI blood loss?
Endoscopy was performed
Endoscopy Report:
Esophagus:
Crico-pharyngeus , upper third and middle third were
normal. Medium-sized Hiatal hernia was found. There was
a esophagitis in lower third.
____________________________
Stomach:
Fundus, body, incisura, antrum and pre-pyloric area
were normal.
____________________________
Duodenum:
Bulb was normal. There was choledocoduodenostomy.
Also there was a mass lesion at begining of D3 with partial
obstruction . The scope was not passed through the mass.
____________________________
The pathology report was:
Poorly differentiated adenocarcinoma
Prevalence of small bowel
tumor
• 1.1 - 2.4 % of GI malignancies
• Approximately 2/3 small intestine
tumors are malignant.
• Adenocarcinoma is the most common
small bowel malignancy with
incidence of 3.9 cases per year.
• Mean age at the time of diagnosis is
between 50-60 years.
Distribution
•
•
•
•
Deudenum(55%)
Jejunum (18%)
Ileum (13%)
Not specified in terms of location
(14%)
Histology:
• Adenocarcinoma from mucosal
glands(35-50%)
• Carcinoid from argantaffin cells(2040%)
• Lymphoma (14%)
• Leiomyosarcoma from smooth muscle
• Neurofibroma from neurons
• Angiosarcoma from endothelial cells
• GIST from mesenchymal cells
Adenocarcinoma
histologic classification
• Approximately 50% of tumours will be
moderately differentiated while
• 15% will be well differentiated,
• 33.9% will be poorly differentiated
and 1.5% will be anaplastic.
Adenocarcinoma
• Risk factors:
• diets high in protein & animal fat.
• Two fold increase in consumers of meat
once a week.
• Smoked foods eaten one to three per month
with odds ratio of 1.7:1 .
• Bile acids: synergic effect of bile acids and
germ line APC mutation to foster the high
predilection of duodenal polyps and
adenocarcinoma in FAP.
Clinical Risk Factors
• SBAs are reported to occur more
frequently in patients with a history of CD,
celiac disease,
• and hereditary gastrointestinal cancers
syndrome such as familial adenomatous
polyposis (FAP), HNPCC, and PeutzJeghers syndrome (PJS).
Pathogenesis and Risk Factors
of Small Bowel
Adenocarcinoma: A Colorectal
Cancer Sibling?
• Thierry Delaunoit, M.D.
• The American Journal of
Gastroenterology
Volume 100 Issue 3 Page 703 - March
2005
Why Are Duodenal SBAs more
Frequent
• Bile acids seem to promote the development of
intestinal cancer in animals studies .
• High fat and low fiber diets are often associated
with bile acid excess, as well as increased risk of
SBAs .
•
• Distribution of proximal SI neoplasms in patients
with FAP is also suggestive of a role played by
bile acids in adenoma and adenocarcinoma
development, since patients with FAP have been
shown to have relatively higher total and
unconjugated bile acids concentrations compared
to the general population .
• The capability of bile acids to produce DNA
adducts in FAP patients seems pH dependent.
• Scates and colleagues studied the role of an
acid environment on the development of DNA
adducts in patients with FAP and compared
those results to a control group.
• Bile acid from FAP patients produced higher
levels of DNA adducts at pH 4–5 than at pH
6–8.
Clinical features
• No specific sign or symptom
• Cramping periumbilical pain, vomiting and
distention ( GI obstruction)
• Constant pain, ( back pain suggest spread
to retroperitoneum, bleeding into the
tumor, invasion of ganglia, ischemia and
serosal involvement )
• GI bleeding is the second most frequent
sign ( massive GIB with sarcoma)
• Weight loss
• Intestinal perforation ( frequent with
lymphoma and sarcoma)
• Jaundice and pancreatitis ( periampulary
tumor)
• Cachexia, ascites, hepatomegaly
Diagnosis
• UGI Endoscopy
• Small bowel follow through
• Enteroclysis ( small bowel enema): with
greater accuracy
• Ct scan: for detecting extramural disease
• Small bowel enteroscopy: in cases with GIB
• Intra operative enteroscopy
• Video capsule enteroscopy: in cases with
GIB
Barium studies
• The most sensitive investigation for
assessing mucosal and intraluminal
abnormalities beyond the ligament of
Treitz is a barium contrast study .
• Enteroclysis has been suggested as a
more useful investigation than a followthrough examination for diagnosing jejunal
and ileal neoplasms. It is a relatively
simple and rapid (< 1 h) investigation .
CT scan
• Extra-mucosal spread, lymphadenopathy and
distant metastases can all be detected .
• Neoplastic disease is suspected when small
bowel thickness exceeds 1.5 cm (normal: 4
mm).
• The accuracy of CT in detecting small bowel
tumours is approximately 47%.
• There is a high sensitivity but low specificity
for the detection of lymphadenopathy.
Push enteroscopy
• Push enteroscopy as an alternative is not
practical in most cases. It takes up to 8 h
to perform, may not visualize the entire
small bowel and up to 50–70% of the
mucosa of the bowel examined is not seen
properly.
MRI
• Magnetic resonance (MR) enteroclysis is a
single investigation with no irradiation of
the patient.
• It separately enhances the small bowel
wall and lumen as well as giving images of
the mesentery, surrounding structures and
rest of the abdominal cavity.
Clinical analysis of primary small
intestinal disease: A report of
309 cases
Zhan J, et al. Gastrointestinal Division of Internal
Medicine, Second Hospital, Sun Yat-Sen University,
Guangzhou 510120, Guangdong Province, China.
World J Gastroenterol. 2004 Sep 1;10(17):2585-7.
•
•
•
•
•
The major clinical symptoms included
abdominal pain (71%),
abdominal mass (14%),
vomiting (10%),
melena (10%),
and fever (9%).
• Duodenum was the most common part
involved in small intestine.
• Double-contrast enteroclysis was still the
simplest and the most available examination
method in diagnosis of primary small
intestinal disease.
What is the best management ?
• Chemotherapy
• Palliative surgery
• combination
Treatment
• In the first or second portion of duodenum
usually are treated by
pancreaticoduodenectomy.
• Segmental resection is sufficient for
patients with tumors arising from the third
and forth portion of duodenum.
• Even with large tumors and positive lymph
nodes, surgeons resect the lesion for
symptomatic relief.
Adenocarcinoma of the
small bowel
• REVIEW ARTICLE, Robert R. Hutchins, Ahmed
Bani Hani, Pipin Kojodjojo, Robyn Ho and
Steven J. Snooks
• Australian and New Zealand Journal of Surgery
Volume 71 Issue 7 Page 428 - July 2001
TNM Staging system
•
•
•
•
•
•
Tx : Primary tumour not evaluated
T0 : No pathological evidence of tumour
Tis: In situ cancer
T1 : Invades lamina propria or submucosa
T2 : Invades muscularis propria
T3 : Invades < 2 cm beyond serosa
or non-peritonealized perimuscular
tissue (mesentery or retroperitoneum)
• T4 : Perforates visceral peritoneum
or invades adjacent structure > 2 cm
• N0 : No regional nodes
• N1 : Lymph node metastases
• Mx : Metastases not evaluated
• M0 : No metastases
• M1 : Distant metastases
AJCC staging system
•
•
•
•
•
Stage 0
Stage 1
Stage 2
Stage 3
Stage 4
Tis
T1or2
T3or4
Any T
AnyT
N0
N0
N0
N1
AnyN
M0
M0
M0
M0
M1
Frequency of staging
•
•
•
•
•
Stage 0 is seen in 2.7% of patients,
stage I is seen in 12% of patients,
stage II is seen in 27% of patients,
stage III is seen in 26% of patients
stage IV is seen in 32.3% of patients.
Treatment
• The mainstay of treatment of small bowel
cancer is surgical resection.
• This may be curative or palliative and the
type of procedure depends on the site of
origin and stage of the tumor.
Curative surgery
• Jejunal and ileal tumours are resected en
bloc with draining regional lymph nodes in
a manner similar to colorectal tumours.
• The margin of tumor, is required to be at
least macroscopically and microscopically
clear .
Endoscopic resection
• Endoscopic resection of early duodenal
cancers and polypoid lesions up to 5 cm
has been reported in studies using the
submucosal saline infiltration technique.
• Although it is technically possible the longterm results of this therapy remain
unknown.
Curative resection
• Whether or not the pancreas-preserving
operation is an adequate cancer
procedure is still open to debate.
The site and stage of tumour determines
which operation is more appropriate.
• Segmental resection of duodenal cancers
preserving the pancreas is generally
carried out for distal duodenal tumours .
• Sohn et al. (n = 48 cases resected) found
a significant improvement in survival for
pancreaticoduodenectomy compared with
segmental resection (P< 0.005).
• In support of this poorer survival with the
pancreas-sparing operation, the Johns
Hopkins Institute reported only a 14%
disease-free survival in 11 cases treated
by this technique.
Palliative surgery
• Locally advanced tumours, or those with
distant metastases, may still be resected
for palliation and to avoid obstruction.
• Palliation may also include gastric or
enteric bypass procedures for
unresectable, obstructing lesions or
resection to relieve recurrent GI bleeding.
Endoscopic stent placement
• Endoscopic, fluoroscopic or combination
endofluoroscopic metal stent insertion can
be performed on an outpatient basis.
• Stents may be covered to prevent tumour
ingrowth and flared at the ends to
discourage migration.
• More than one stent may be placed to
overcome an obstruction by placing the
distal stent first and overlapping the stents
by 1–2 cm.
• Over 90 patients have had duodenal
and small bowel stents inserted with
an
• 89% rate of improvement in nutrition,
• 3% migration rate,
• 15% tumour ingrowth
• and 5% failure rate.
Gastrojejunostomy
• Laparoscopic and open gastrojejunostomy
have been compared in single centre
studies.
• laparoscopic cases had a significantly
shorter hospital stay and less blood loss in
the laparoscopic group.
Liver metastatectomy
• Two reports of liver resection for
metastases from small bowel cancer exist
,but unlike colorectal tumours where this is
now an established treatment with up to
40%, 5 years survival.
• little can be said to recommend this as a
treatment for metastatic small bowel
cancer.
Chemoradiation
• The rarity of small bowel tumours and the
variety of treatments offered contributes to
the lack of evidence for benefit from
chemoradiotherapy in this disease.
• Only one study has looked at
preoperative treatment. Thirty-one cases
were offered radiotherapy combined with
two cycles of chemotherapy.
• All four cases of duodenal cancer were
then resected and the patients are alive at
12, 23, 35 and 90 months.
• Combination treatment (median
survival 23.6 months) with surgery
appeared to affect survival better than
single-modality therapy (median
survival: 15.9–17.2 months).
• No recommendations can be made at
present on whether or not adjuvant
therapy should be offered or whether
palliative therapy has an effect on
survival. Randomized trials probably
including new agents are necessary.
Radiotherapy
• The role of radiotherapy is as yet
undefined. Small bowel cancers are
thought to be relatively radioresistant .
Prognosis
•
•
•
•
Resectability
Resection margin
Histological grade
Lymph node involvement
• Tumor limited to submucosa has a 5 year
survival rate of 100%
Poorly differentiated
adenocarcinoma with signet-ring
cells of the Vater's ampulla, without
jaundice but with disseminated
carcinomatosis
• Nabeshima S , Department of General Medicine,
Kyushu University Hospital, 3-1-1 Maidashi, Higashiku,
Fukuoka 812-8582, Japan
• Fukuoka Igaku Zasshi. 2003 Jul;94(7):235-40.
• A 49-year-old man was hospitalized
because of a 2-month history of
purpura in his extremities and for
back pain.
• Laboratory findings showed alkaline
phosphatase to be greatly elevated,
and platelet counts and coagulation
factor showed that the patient had
disseminated intravascular
coagulation (DIC).
• Compression fractures of the
thoracic vertebrae were found on
radiological examination.
• The histological findings from
bone marrow showed metastasis
of adenocarcinoma with signetring cells, although the primary
site was unknown.
• To reduce tumor cells in number and
improve DIC, 11 cycles of 5Fluorouracil and leucovorin therapy
were done, and the patient survived
for 12 months.
• Autopsy showed a 0.8 cm diameter,
poorly differentiated adenocarcinoma
with the signet-ring cell type in the
lamina propria of the Vater's ampulla.
Many metastatic foci and micro tumor
emboli were found in the lung and in
bone marrow.
• This is a rare case of an
ampullary tumor of poorly
differentiated adenocarcinoma
with the signet-ring cell type,
without jaundice but with multiple
metastasis.
• 5-Fluorouracil and leucovorin
were effective for increasing
survival time and improving
quality of life.
Idiopathic acute recurrent
pancreatitis
• Michael J. Levy
• American Journal of Gastroenterology
Volume 96 Issue 9 Page 2540 September 2001
• In idiopathic acute recurrent pancreatitis,
ERCP, endoscopic ultrasound, or magnetic
resonance cholangiopancreatography typically
leads to a diagnosis of microlithiasis, sphincter
of Oddi dysfunction, or pancreas divisum. Less
commonly, hereditary pancreatitis, cystic
fibrosis, a choledochocele, annular pancreas,
pancreatobiliary tumors, or chronic pancreatitis
are diagnosed.
Primary adenocarcinoma of the
duodenum in the elderly:
Clinicopathological and
immunohistochemical study of
17 cases
• Tomio Arai, et al. Department of Pathology,
Tokyo Metropolitan Geriatric Hospital, Tokyo,
2Department of Pathology,
• Pathology International 1999; 49: 23–29
• Primary adenocarcinoma of the
duodenum, excluding that of ampulla of
Vater, is extremely rare, with an incidence
of only 0.35% of all gastrointestinal
carcinomas and 33–45% of all small
intestinal carcinomas.
• the incidence of duodenal carcinoma
detected at autopsy is between 0.019 and
0.5%.
• We reviewed 17 elderly patients (older
than 65 years) with primary
adenocarcinoma of the duodenum.
• True or doubtful carcinomas of the papilla
of Vater and cases of familial
adenomatous polyposis (FAP) were
excluded from the study.
•
•
•
•
•
•
Table 1
Summary of clinical and pathological findingsa
Age (yr)/
(Periods and
No.
Gender
Location
Gross feature
aliveg or cause of death)
1b
75/F
First
Polypoid
cancer
2b
76/F
First
Polypoid
lung cancer
3b
81/F
First
Polypoid
gastrointestinal
Follow-up
Size (mm)
Histologyd
Depthf
Metastasis
Symptoms or signs
15 � 15
Well
M
–
No symptom
2 weeks, lung
38 � 20
Well
M
–
Appetite loss
24 months,
12 � 7
Well
M
–
Appetite loss
3 days,
•
•
•
hemorrhage
4
83/M
cancer
5c
104/F
myocardial
First
Polypoid
17 � 10
Well
M
–
Anemia
?, Gastric
First
Polypoid
47 � 38
Well
M
–
No symptom
Acute
•
•
•
infarction
6
76/M
alive
7b
86/F
duodenal
First
Flat-elevated
55 � 40
Well
M
–
No symptom
60 months,
First
Vegetated and
30 � 15
Well
SI
Lymph nodes
Appetite loss
28 months,
20 � 20
Well
SS
Liver, lungs,
Virchow
•
•
ulcerative-invasive
8b
metastasis
cancer
69/M
First
Ulcerative-invasive
22 months, duodenal
•
•
•
•
•
•
lymph nodes
9
70/F
First
60 months, alive
10
72/F
First
Unknown
11
74/M
First
Unknown
12
80/M
First
24 months, alive
13b
84/F
First
discomfort 4 months, duodenal
Ulcerative-invasive
45 � 30
Welle
SI
–
Epigastralgia
Ulcerative-invasive
135 � 60
Well
SS
–
Appetite loss
Ulcerative-invasive
83 � 64
Poorly
SI
Lymph nodes
Dysphagia
Ulcerative-invasive
18 � 18
Welle
SI
–
Epigastralgia
Ulcerative-invasive
50 � 45
Well
SI
Lungs, bone,
Epigastric
•
lymph nodes
•
14
71/M
•
15b
66/M
Second
34 months, acute
Second
•
•
•
cancer
Polypoid
20 � 15
Flat-elevated with
cancer
Well
SM
–
No symptom
Unknown
30 � 25
Well
M
–
Unknown
granular surface
infarction
16
74/M
alive
17
74/M
alive
myocardial
Second
Flat-elevated
13 � 8
Well
M
–
No symptom
23 months,
Third
Flat-elevated
23 � 12
Well
M
–
No symptom
33 months,
Table 3 Ki-67-positive rates of primary
adenocarcinoma of the duodenum
Intramucosal area Invasive area
Gross feature
• Polypoid
35.6 (30.8) n = 6
• Flat-elevated
36.1 (16.2) n = 4
• Ulcerative invasive 36.1 (28.5) n = 7
27.0 n
–
32.7 (34.4) n = 5
Distant metastasis
• Positive
46.0 (32.0)* n = 4
38.4 (13.7) n = 2
• Negative
30.9 (33.1) n = 4
31.6 (30.8) n = 12
Table 2- Results of immunohistochemistry of p53 in
primary
duodenal cancer
Intramucosal cancer
• p53-Positive, diffuse
• p53-Positive, focal
• p53-Negative
2
5
2
Invasive cancer
5*
3
0
• The mean age of the patients in the
present study was higher than that of
previously reported series.
• The data of the present series indicate that
the peak age of patients with duodenal
adenocarcinoma is in the eighth decade,
while the published consensus places the
disease as appearing mostly in the fifth,
sixth or seventh decades.
The duodenum is divided into three
anatomical segments:
• (i) suprapapillary (from pylorus to the
ampulla of Vater)
• (ii) peripapillary (around the ampulla)
• (iii) infrapapillary (below the ampulla to
the duodenojejunal flexure).
• the incidence of peripapillary and
infrapapillary carcinomas of the duodenum
has been reported to vary widely: from 32
to 87% and from 2 to 56%, respectively.
• the data of the present series indicate that
suprapapillary carcinomas comprise
approximately 80% of duodenal
carcinomas.
• A recent study reported that the mean age of
patients with duodenal carcinoma of the first or
second duodenal portions was higher than that of
patients with cancer of the third or fourth portions.
• In the present study, the mean age of patients with
suprapapillary adenocarcinoma was 79.3 years
versus 71.3 years for patients with cancer in the
other portions. Moreover, all carcinomas in
patients older than 80 years occurred in the
suprapapillary portion.
• we conclude that a proximal shift of the primary
duodenal carcinomas may occur in elderly
patients.
• There are a few probable causes for a
proximal shift in the elderly; for example, a
slow flow time of chyme throughout the
duodenum, repeated ulceration in the
duodenal bulb, and cholelithiasis(?).
• Macroscopically, three types of lesion
have been described:
• ulcerative-invasive, polypoid and flatelevated (or sessile).2,4,12 In the present
study, most advanced cancers (88.9%)
exhibited an ulcerative-invasive
morphology.
• duodenal cancer of the polypoid type can
occur as intramucosal neoplasms even
though they may be relatively large.
• Close attention should therefore be paid
to accurate histological diagnosis, as this
type occasionally invades the duodenal
wall.
• Polypoid type tumors tend to occupy the
duodenal lumen, are often reddish and
friable, and bleed easily due to the
associated marked vascularization.
• Most flat-elevated type cancers are also
intramucosal. However, flat-elevated type
tumors may show microinvasion of the
lamina propria, as described earlier.
• There have also been a few reports
describing depressed type carcinomas of
the duodenum as well as in the large
intestine.
• Microscopically, well- or moderately
differentiated adenocarcinoma are the
most common. However, poorly
differentiated adenocarcinoma is often
observed in the infiltrating area of tumors
even though intramucosal areas are well
differentiated.
• The present study described p53 positivity
in approximately 40% of duodenal
adenocarcinomas, while previous reports
have estimated this figure at
approximately 20–30%.
• The mutational frequency of the p53 gene
in small intestinal carcinomas has been
reported as being lower than in colorectal
carcinomas.
• a poor prognosis for ulcerative-invasive
type carcinomas, whereas polypoid
carcinomas were associated with a
relatively good prognosis.
• The most important prognostic factors
include tumor stage and location.