Management Conference

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Management Conference

• A WOMAN WITH
• EPIGASTRIC PAIN,
• VOMITING
• Raika Jamali M.D.
• Gastroenterologist and hepatologist
• Tehran University of Medical Sciences

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• 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.

3

• 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.

4

• 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.

5

• The epigastric pain persisted and did not respond
  to PPI so endoscopy performed
• GERD grade A Hiatal hernia pan gastritis
  mild duodenitis
• PPI continued

6

• 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.

7

• After 3 laparatomies the patient referred to
  gastroentrologist for evaluation of persistent
  epigastric pain, vomiting and weight loss in
  85.6.25.

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• OB negative
• AST26
• ALT36
• ALP612

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• UGI endoscopy Duodenitis
• Colonoscopy normal
• Sonography Multiple hypoechoic lesions in liver.
  Enlargment of pacreatic head.
• CT scan recommended.

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• What is the next diagnostic step ?
• Small intestine follow through for evaluation of
  partial obstructoin and GI blood loss?

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• Endoscopy was performed

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•                                                
                                            
                                                    
                                           
  Endoscopy
  Report
• EsophagusCrico-pharyngeus ,  upper third
  and  middle third were normal. Medium-sized
  Hiatal hernia was found. There was a  esophagitis
  in  lower third. ____________________________Sto
  machFundus,  body,  incisura,  antrum
  and  pre-pyloric area were normal.
  ____________________________DuodenumBulb 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. ____________________________

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• The pathology report was
• Poorly differentiated adenocarcinoma

24
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.

25
Distribution

• Deudenum(55)
• Jejunum (18)
• Ileum (13)
• Not specified in terms of location (14)

26
Histology

• Adenocarcinoma from mucosal glands(35-50)
• Carcinoid from argantaffin cells(20-40)
• Lymphoma (14)
• Leiomyosarcoma from smooth muscle
• Neurofibroma from neurons
• Angiosarcoma from endothelial cells
• GIST from mesenchymal cells

27
Adenocarcinomahistologic 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.

28
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 1.71 .
• Bile acids synergic effect of bile acids and
  germ line APC mutation to foster the high
  predilection of duodenal polyps and
  adenocarcinoma in FAP.

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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 Peutz-Jeghers syndrome (PJS).

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Pathogenesis and Risk Factors of Small Bowel
Adenocarcinoma A Colorectal Cancer Sibling?

• Thierry Delaunoit, M.D.
• The American Journal of GastroenterologyVolume
  100 Issue 3 Page 703 - March 2005

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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 .

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• 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 45 than at pH
• 68.

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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 )

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• 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

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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

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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 follow-through examination
  for diagnosing jejunal and ileal neoplasms. It is
  a relatively simple and rapid (lt 1 h)
  investigation .

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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.

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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 5070 of the mucosa of the bowel
  examined is not seen properly.

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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.

40
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
110(17)2585-7.

• Clinical analysis of primary small intestinal
  disease A report of 309 cases

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• 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.

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• What is the best management ?
• Chemotherapy
• Palliative surgery
• combination

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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.

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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
  SurgeryVolume 71 Issue 7 Page 428 - July 2001

45
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 lt 2 cm beyond serosaor
  non-peritonealized perimusculartissue (mesentery
  or retroperitoneum)
• T4 Perforates visceral peritoneumor invades
  adjacent structure gt 2 cm

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• N0 No regional nodes
• N1 Lymph node metastases
• Mx Metastases not evaluated
• M0 No metastases
• M1 Distant metastases

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AJCC staging system

• Stage 0 Tis N0 M0
• Stage 1 T1or2 N0 M0
• Stage 2 T3or4 N0 M0
• Stage 3 Any T N1 M0
• Stage 4 AnyT AnyN M1

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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.

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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.

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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 .

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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 long-term
  results of this therapy remain unknown.

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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.

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• 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 (Plt 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.

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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.

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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 12 cm.

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• 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.

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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.

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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.

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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.

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• Combination treatment (median survival 23.6
  months) with surgery appeared to affect survival
  better than single-modality therapy (median
  survival 15.917.2 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.

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Radiotherapy

• The role of radiotherapy is as yet undefined.
  Small bowel cancers are thought to be relatively
  radioresistant .

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Prognosis

• Resectability
• Resection margin
• Histological grade
• Lymph node involvement
• Tumor limited to submucosa has a 5 year survival
  rate of 100

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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 Jul94(7)235-40.

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• 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).

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• Compression fractures of the thoracic vertebrae
  were found on radiological examination.
• The histological findings from bone marrow
  showed metastasis of adenocarcinoma with
  signet-ring cells, although the primary site was
  unknown.

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• To reduce tumor cells in number and improve DIC,
  11 cycles of 5-Fluorouracil 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.

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• 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.

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Idiopathic acute recurrent pancreatitis

• Michael J. Levy
• American Journal of GastroenterologyVolume 96
  Issue 9 Page 2540 - September 2001

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• 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.

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Primary adenocarcinoma of the duodenum in the
elderlyClinicopathological 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 2329

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• 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 3345 of all
  small intestinal carcinomas.
• the incidence of duodenal carcinoma detected at
  autopsy is between 0.019 and 0.5.

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• 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.

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• Table 1 Summary of clinical and pathological
  findingsa
• Age (yr)/ Follow-up (Periods and
• No. Gender Location Gross feature Size (mm)
  Histologyd Depthf Metastasis Symptoms or
  signs aliveg or cause of death)
• 1b 75/F First Polypoid 15 ? 15 Well M
  No symptom 2 weeks, lung cancer
• 2b 76/F First Polypoid 38 ? 20 Well M
  Appetite loss 24 months, lung cancer
• 3b 81/F First Polypoid 12 ? 7 Well M
  Appetite loss 3 days, gastrointestinal
• hemorrhage
• 4 83/M First Polypoid 17 ? 10 Well M
  Anemia ?, Gastric cancer
• 5c 104/F First Polypoid 47 ? 38 Well M
  No symptom Acute myocardial
• infarction
• 6 76/M First Flat-elevated 55 ? 40 Well M
  No symptom 60 months, alive
• 7b 86/F First Vegetated and 30 ? 15 Well SI
  Lymph nodes Appetite loss 28 months, duodenal
  
• ulcerative-invasive cancer
• 8b 69/M First Ulcerative-invasive 20 ? 20
  Well SS Liver, lungs, Virchow metastasis 22
  months, duodenal
• lymph nodes cancer
• 9 70/F First Ulcerative-invasive 45 ? 30
  Welle SI Epigastralgia 60 months, alive
• 10 72/F First Ulcerative-invasive 135 ? 60
  Well SS Appetite loss Unknown
• 11 74/M First Ulcerative-invasive 83 ? 64
  Poorly SI Lymph nodes Dysphagia Unknown

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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
  27.0 n
• Flat-elevated 36.1 (16.2) n 4
• Ulcerative invasive 36.1 (28.5) n 7 32.7
  (34.4) n 5
• Distant metastasis
• Positive 46.0 (32.0) n 4
  38.4 (13.7) n 2
• Negative 31.6 (30.8) n 12
  30.9 (33.1) n 4

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Table 2- Results of immunohistochemistry of p53
in primaryduodenal cancer

• Intramucosal cancer
  Invasive cancer
• p53-Positive, diffuse 2 5
• p53-Positive, focal 5 3
• p53-Negative 2 0
  

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• 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.

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• 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).

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• 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.

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• 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.

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• 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(?).

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• Macroscopically, three types of lesion have been
  described
• ulcerative-invasive, polypoid and flat-elevated
  (or sessile).2,4,12 In the present study, most
  advanced cancers (88.9) exhibited an
  ulcerative-invasive morphology.

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• 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.

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• 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.

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• 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.

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• The present study described p53 positivity in
  approximately 40 of duodenal adenocarcinomas,
  while previous reports have estimated this figure
  at approximately 2030.
• The mutational frequency of the p53 gene in
  small intestinal carcinomas has been reported as
  being lower than in colorectal carcinomas.

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• 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.