TOPICS IN ONCOLOGY
Selections from the University of California, San Francisco, School of Medicine’s Postgraduate Course in General
Surgery, March 17-19, 2005
| AMPULLARY CANCER —Lygia Stewart, MD, Associate Professor of General Surgery, University of California, San
Francisco, School of Medicine
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| Presentation: may present as ampullary adenoma; symptoms include pancreatitis, jaundice, and bleeding; most patients
have prominent ampulla
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| Endoscopic biopsy: incorrect in 60% of cases; study—7% of 300 ampullary endoscopic biopsies were carcinoma, and
69% agreed with pathology (83% agreed with pathology if 2 biopsies performed); sensitivity 77% with forceps; with full
papillectomy, 86% of tumors identified
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| Diagnosis: adenoma with dysplasia or any atypia should be treated as malignant lesion; resection indicated if patient good
surgical candidate
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| Removal of benign adenoma: endoscopic snare excision—may leave adenomatous tissue behind; surgical
ampullectomy—full-thickness resection of ampulla and duodenal wall; can get bile duct and surrounding surgical margins
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| Recurrence of adenoma: Mayo Clinic study—in 52 benign adenomas locally excised, recurrence rate 33%; 4 cases recurred
with cancer; German study—in 32 benign adenomas, recurrence 22%; 5 recurred with cancer; all had high-grade
dysplasia
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| Clinical algorithm: if endoscopic biopsy reveals malignancy and patient good surgical candidate, perform Whipple procedure;
if dysplasia and atypia present, consider Whipple procedure; if endoscopic ultrasonography (EUS) shows evidence
of invasion, perform Whipple procedure; if adenoma benign, consider local resection with frozen sections; if patient bad
surgical candidate, consider local resection
|
| Surgical treatment: for local resection, 5-yr survival 38% to 51%; factors predictive of survival—surgical margins;
lymph node status; lymphatic invasion; tumor grade; evidence of perineural invasion; intraoperative blood transfusion;
pancreatic invasion
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| Familial adenomatous polyposis (FAP): high risk for ampullary cancer; ampullary cancer leading cause of death in FAP
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| PERITONEAL CARCINOMATOSIS —Robert S. Warren, MD, Professor of General Surgery, University of California,
San Francisco, School of Medicine
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| Presenting symptoms: cramp and abdominal pain; anorexia and weight loss; bowel obstruction; ascites; infection
|
| Evolution of Carcinomatosis of the Peritoneum (EVOCAPE) study: prospective observational study of 370 patients
who underwent surgery for carcinomatosis within peritoneal cavity from nongynecologic sources; after surgical debulking,
patients with stage I disease had all tumors removed, patients with stage II disease had tumors <2.5 mm, patients
with stage III disease had tumors >2.5 mm, and patients with stage IV disease had tumors >2 cm; results—median survival
similar across groups (<1 yr), but slightly longer for patients with less disease after surgery; morbidity lower than
mortality (16% vs 21%), indicating most complications fatal
|
| Treatment options: surgical debulking not favored by speaker; systemic chemotherapy not effective; total abdominal radiation
and photodynamic therapy ineffective; bypass, diversion, or no operation preferred for palliative care; LeVeen shunt
helpful for patients with less bulky tumor and extensive ascites
|
| Intraperitoneal chemohyperthermia (IPCH): combines operative resection with intensive regional treatment for diseases
with propensity to progress in peritoneal cavity, eg, ovarian and gastrointestinal cancers and mesothelioma; delivers chemotherapy
and hyperthermia to all serosal surfaces, which has direct lethal effects on tumor and enhances chemotherapy toxicity;
favorable carcinomatosis features—surface malignancy; small tumors (2 to 3 mm); single-site disease;
disadvantages—pain; uneven distribution within peritoneal cavity, particularly with postoperative regional chemotherapy;
poor penetration into tumors >5 mm; limitations—difficult to differentiate effects of debulking procedure from effects of
chemotherapy
|
| Histology: pseudomyxoma peritonei—most common term used for mucinous tumors; divided into disseminated peritoneal
adenomucinosis (low-grade neoplasm, typically appendiceal) and peritoneal mucinous carcinomatosis (can be appendiceal
but typically gastrointestinal [GI] tract [small and large bowel]); median survival for patients with adenomucinosis phenotype
(>10 yr) much better than for patients with mucinous carcinomatosis
|
| Surgery for appendiceal carcinomas: Sugarbaker et al—174 patients had incomplete cytoreductive surgery for peritoneal
carcinomatosis from appendiceal malignancy; median survival 22 mo; patients who received intraperitoneal chemotherapy
had improved survival (median survival >3 yr)
|
| Intraperitoneal chemotherapy technique: involves exploratory laparotomy, lysis of adhesions, tumor debulking, insertion
of cannula and temperature probes; fascia closed and catheters connected to perfusion circuit with roller pump and heat
exchanger; chemotherapy circulated and heated; abdomen perfused for 90 min under heat; abdomen reopened, chemotherapy
removed, and abdomen irrigated; Tenckhoff catheter inserted for postoperative chemotherapy
|
| Dutch study: 105 patients with colorectal cancer randomized to surgical debulking and systemic chemotherapy with or
without intraperitoneal chemotherapy at time of debulking; results—median survival for intraperitoneal chemotherapy
group almost twice that of standard group; for patients with residual tumors >2.5 mm, median survival 6 mo
|
| Multicenter study: retrospective study of 500 patients with colorectal cancer and carcinomatosis treated with debulking
and perioperative intraperitoneal chemotherapy; results—overall median survival 18 mo; 15% of patients survived 5 yr;
for patients with no macroscopic residual disease after treatment, median survival 2.5 yr; for patients with residual tumor
>2.5 mm, median survival 6 mo
|
| STOMACH CANCER —Kimberly S. Kirkwood, MD, Associate Professor of General Surgery, University of California,
San Francisco, School of Medicine
|
Case Presentation 1
| Presenting patient: 74-yr-old man with worsening band-like upper abdominal pain over past 6 mo and 15-lb weight loss;
one previous episode of hematemesis; Helicobacter pylori positive; 1.8-cm adenocarcinoma lesion in body of stomach
|
| Staging: computed tomography (CT) able to identify lesion on gastric body anterior wall; small calcific lesion found in distal
bile duct; abdominal pain likely due to chronic choledocholithiasis
|
| Treatment: patient underwent endoscopic retrograde cholangiopancreatography (ERCP) and stone extraction with relief of
abdominal pain; hemigastrectomy performed; extended lymphadenectomy—not necessary (adds morbidity in form of diarrhea
and bleeding); revised American Joint Commission on Cancer (AJCC) and Union International Contre le Cancer
(UICC) recommendations state 15 lymph nodes needed for accurate staging; frozen sections—proximal margin almost always
frozen; reduces likelihood of positive margins; splenectomy—indicated only for patients with splenic hilar involvement
or direct contiguous spread to spleen; jejunostomy—speaker recommends placing feeding jejunostomy tube; study
shows that patients malnourished preoperatively who undergo upper abdominal surgery appear to benefit from supplemental
enteral nutrition around time of surgery; malnourishment indicators—weight loss (>5% of body weight in 3 mo or >10%
in 6 mo); prealbumin and albumin levels (useful in ambulatory setting)
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| Additional patient information: low prealbumin; albumin 3.2 g/dL; T1, N0 (stage I) lesion identified (1.5 cm x 1.5 cm
carcinoma invading lamina propria); typical picture for elderly Asian man, including chronic gastritis on background and
intestinal metaplasia
|
| Helicobacter pylori: in several series, high prevalence of H pylori found in patients 3 yr after antrectomy or subtotal gastrectomy;
speaker has adopted policy of testing for H pylori when patients undergo screening endoscopy after subtotal
gastrectomy
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Case Presentation 2
| Patient information: 41-yr-old woman underwent hemigastrectomy with postoperative chemoradiation therapy at age 25
yr for stage III (T3, N2) signet-ring adenocarcinoma with involvement of 17 of 38 lymph nodes; presented in 2003 with
vomiting and abdominal pain
|
| Diagnostic evaluation: 2 cm x 3 cm nodular mass in posterior gastric remnant; no evidence of metastatic disease; remnant
cancer; patients ≥15 yr of age have increased risk for remnant cancer, regardless whether antrectomy performed for benign
or malignant disease; total gastrectomy performed with Roux-en-Y anastomosis; often hard to remove lymph nodes
in these patients due to scarring and obliteration of lymphatic channels; proximal and distal margins frozen, which were
negative; pT2, N0 signet-ring cancer remained
|
| Treatment: patient previously treated with 5-fluorouracil (5FU)-based therapy (doxorubicin, mitomycin) and external beam
radiation; oncologist elected to treat with 5FU/docetaxel (Taxotere) regimen; Willett study, 2002—5FU-based chemoradiation
shown to improve survival and to decrease locoregional recurrence
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Case Presentation 3
| Presenting patient: 49-yr-old man with history of dyspepsia and episode of coffee-grounds emesis; 35-lb weight loss in 6 mo
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| Diagnostic evaluation: patient had linitis plastica lesion (poorly differentiated adenocarcinoma); no metastasis but diffuse
thickening of stomach; patients with stage III disease most common; most cases involve palliative gastrectomy; remove lesion
unless it cannot be removed, abdomen full of tumor, or ascites present
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| Operative approach: biopsy of distant metastasis showed extensive perigastric nodal disease; stomach had serosal invasion;
begin by examining gastroesophageal (GE) junction (patient incurable if tumor encasing GE junction and involves
>3 cm of esophagus); if GE junction encased due to linitis lesion, no more action beneficial; feeding jejunostomy tube
may be put in, depending on patient’s wishes; if GE junction clear (involves <3 cm of esophagus), examine posterior plane;
pancreatectomy dramatically increases morbidity; en-bloc splenectomy often safest thing to do if hilum involved with lymphadenopathy
or direct invasion by tumor; best technique involves starting on duodenal side, transect, lift up, and work up
to GE junction; important to recognize that once stomach lifted, gastric contents may flow into airway; aspiration most
underrecognized and lethal complication in total gastrectomy
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| Additional patient information: patient underwent total gastrectomy and frozen sections, which were negative; feeding jejunostomy
tube put in; stage III disease into serosa and extensive lymph node disease; after surgery, positive permanent
sections and proximal and distal margins
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| Considerations: study—surgeon’s macroscopic estimate of proximal margin compared to microscopic positive margins;
safest to estimate >6 cm for proximal margin; of patients who had negative frozen sections, 9% had positive permanent
sections; having microscopically positive margin does not increase risk for anastomotic leak; study—positive margins
worsen survival only for patients with earlier gastric cancer; if patient had >5 positive lymph nodes, survival and local recurrence
not worsened by having positive margin
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| GALLBLADDER CANCER —Carlos Corvera, MD, Assistant Professor of General Surgery, University of California, San
Francisco, School of Medicine
|
| Most common risk factor: chronic inflammation and presence of gallstones (98% of patients have gallstones); 0.3% to
3.0% of patients with gallstones develop gallbladder cancer
|
| Presentation: difficult to differentiate from biliary colic; presents with abdominal pain, jaundice, and weight loss
|
| Evaluation: symptoms include elevated bilirubin; jaundice poor prognostic indicator and predicts unresectability; plain x-
ray films of abdomen can reveal calcification and gallstones
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| Ultrasonography (US): inexpensive; easily obtained; can help distinguish patients who have benign disease processes; can
detect abnormalities in mucosa, define changes in polyps, and help locate mass in gallbladder; Doppler US can show encasement,
which indicates cancer unresectable; can provide information on liver invasion, level of obstruction, portal
venous involvement, and thrombosis of portal vein
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| Multiphasic CT: can assess patency of portal vein and define tumor mass; provides information on levels of obstruction, presence
of lobar atrophy, staging, presence of ascites, and carcinomatosis
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| Direct cholangiography: endoscopic retrograde and percutaneous transhepatic cholangiography can give information on
intraductal anatomy and strictures; stricture in main or mid bile duct without any contrast filling into cystic duct or gallbladder
highly suggestive of cancer; despite low staging value, can give diagnosis by bile cytology or brushings
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| Magnetic resonance cholangiopancreatography (MRCP): as effective as direct cholangiography but without bile contamination
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| Positron emission tomography (PET): study—of 31 patients found to have gallbladder cancer, stage and management of
6 patients changed due to information provided by PET
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| Staging system: AJCC system most widely accepted; T1—lesions confined to mucosa; T2—lesions extend into lamina
propria and muscular layer; T3—lesions extend beyond serosa and into liver ≤2 cm; T4—lesions extend into liver >2
cm; N0—no nodal metastasis; N1—pericystic nodes; N2—retropancreatic and celiac access nodes (unresectable)
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| Liver resection for gallbladder cancer: during exploration, perform Kocher maneuver and examine N2-level nodes, hepatic
artery, and celiac access; if resection appropriate, remove gallbladder and involved liver; perform segmental portal
resection if portal vein involved; if tumor in fundus, complete bile duct excision may not be necessary
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| Surgical options by stage: stage I tumors—simple cholecystectomy; if discovered intraoperatively, remove cystic node
and examine remaining lymph nodes; stage II tumors—survival rates of 50% to 70% being achieved with liver resection;
study showed patients treated with radical resection had 5-yr survival of 61%, compared to 19% for simple cholecystectomy;
stage III and IV tumors—strategy same as stage II; tumors tend to be more bulky and often require
extended resection; studies show patients with advanced T3 and T4 lesions have 5-yr survival of 50%
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Educational Objectives
| The goal of this program is to educate the listener about issues in oncology. After hearing and assimilating this program, the
clinician will be better able to:
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 | 1. Discuss the surgical treatment options for ampullary cancer.
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| 2. Describe treatment options for peritoneal carcinomatosis.
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| 3. Review the empiric data supporting the use of intraperitoneal chemotherapy during surgery for peritoneal carcinomatosis.
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| 4. Diagnose stomach cancer.
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| 5. Evaluate gallbladder cancer.
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Discussed on This Program
Docetaxel [Taxotere]
Doxorubicin [Adriamycin PFS, Adriamycin RDF, Doxil, Rubex]
Fluorouracil (5-fluorouracil, 5-FU) [Adrucil, Carac, Efudex, Fluoroplex]
Mitomycin (mitomycin-C; MTC) [Mutamycin]
Suggested Reading
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in cirrhotic patients with severe portal hypertension. J Am Coll Surg 193(1):46, 2001; Baker JE: Erythropoietin mimics
ischemic preconditioning. Vascul Pharmacol 42(5-6):233, 2005; Farnsworth N et al: Child-Turcotte-Pugh versus
MELD score as a predictor of outcome after elective and emergent surgery in cirrhotic patients. Am J Surg 188(5):580,
2004; Friederich PW et al: Effect of recombinant activated factor VII on perioperative blood loss in patients undergoing
retropubic prostatectomy: a double-blind placebo-controlled randomised trial. Lancet 361(9353):201, 2003; Friederich
PW et al: The effect of the administration of recombinant activated factor VII (NovoSeven) on perioperative blood loss in
patients undergoing transabdominal retropubic prostatectomy: the PROSE study. Blood Coagul Fibrinolysis 11(Suppl
1):S129, 2000; Fuster J et al: Abdominal drainage after liver resection for hepatocellular carcinoma in cirrhotic patients: a
randomized controlled study. Hepatogastroenterology 51(56):536, 2004; Goodnough LT: Autologous blood donation.
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target? The role of erythropoietin. Hell J Cardiol 46(3):222, 2005; Kertai MD et al: The prognostic value of dobutamine
stress echocardiography in patients with abdominal aortic aneurysm and concomitant coronary artery disease. J
Cardiovasc Surg (Torino) 44(3):423, 2003; Maddox TM: Preoperative cardiovascular evaluation for noncardiac surgery.
Mt Sinai J Med 72(3):185, 2005; Mahdy AM, Webster NR: Perioperative systemic haemostatic agents. Br J Anaesth
93(6):842, 2004; Mangano DT et al: Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery.
Multicenter Study of Perioperative Ischemia Research Group. N Engl J Med 335(23):1713, 1996; Maull KI, Turnage B:
Trauma in the cirrhotic patient. South Med J 94(2):205, 2001; Merli M et al: Malnutrition is a risk factor in cirrhotic patients
undergoing surgery. Nutrition 18(11-12):978, 2002; O'Meara E et al: Anemia and heart failure. Curr Heart Fail
Rep 1(4):176, 2004; Poldermans D et al: Bisoprolol reduces cardiac death and myocardial infarction in high-risk patients
as long as 2 years after successful major vascular surgery. Eur Heart J 22(15):1353, 2001; Poldermans D et al: The effect
of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch
Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. N Engl J Med 341(24):1789,
1999; Pomier-Layrargues G et al: Transjugular intrahepatic portosystemic shunt (TIPS) versus endoscopic variceal ligation
in the prevention of variceal rebleeding in patients with cirrhosis: a randomised trial. Gut 48(3):390, 2001; Romney R
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of a multicenter prospective study. Gastroenterol Clin Biol 29(3):275, 2005; Silverberg DS et al: The importance of
anemia and its correction in the management of severe congestive heart failure. Eur J Heart Fail 4(6):681, 2002; Stasi R et
al: Management of cancer-related anemia with erythropoietic agents: doubts, certainties, and concerns. Oncologist
10(7):539, 2005; Wallace A et al: Prophylactic atenolol reduces postoperative myocardial ischemia. McSPI Research
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noncardiac surgery. Anesthesiology 101(2):284, 2004.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship
with the manufacturer or provider of any commercial product or service discussed. For this issue, the speakers reported
nothing to disclose.
Drs. Stewart, Warren, Kirkwood, and Corvera were recorded March 17-19, 2005, in San Francisco at the University
of California, San Francisco, School of Medicine’s Postgraduate Course in General Surgery. The Audio-Digest
Foundation thanks the speakers and the University of California, San Francisco, School of Medicine for their cooperation
in the production of this program.
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