Andrew M. Lowy

JR Howe

KY Bilimoria

MA Talamini

RD Kim

English

PubMed

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Beyond the Ivory Tower: Outcomes Following Surgery
for Ampullary Cancer
Andrew M. Lowy, MD
Department of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego,
3855 Health Sciences Drive, ML 0987, La Jolla, CA 92093-0987, USA
A frequently uttered wisecrack amongst academic
surgeons refers to those manuscripts in which the au-
thors outnumber the study subjects. While ampullary
carcinoma is rare, manuscripts on the subject do not
usually engender this kind of criticism. As Dr.
O’Connell and colleagues state in their manuscript,
published in the current issue of Annals of Surgical
Oncology: while uncommon, ampullary carcinoma
represents the second most common cause of periam-
pullary malignancy.1 They utilized the Surveillance
Epidemiology and EndResults (SEER) tumor registry
to analyze the outcomes of more than 3000 patients
who underwent surgical resection for ampullary car-
cinoma.As the authors state, this represents the largest
such analysis of outcomes for patients with this
uncommon malignancy. They conclude that, com-
pared to most series published in the last 15 years,
SEER data reveals a lower resection rate, a higher
overall mortality rate, and lower observed 5-year sur-
vival. These ﬁndings are not particularly enlightening
in and of themselves, but rather serve as a gentle re-
minder of the fragile truths we accept daily in the
practice of surgical oncology: that data derived from
small, retrospective single-institution studies are re-
plete with numerous biases. In the current study, the
authors reference reports from revered institutions
such as Johns Hopkins, Memorial Sloan–Kettering,
and Toronto General.2–4 It should not be surprising,
but rather expected, that patient outcomes from these
institutions might look different from those of a pop-
ulation treated in smaller centers, as is represented by
the SEER registry. To the authors’ credit, they do a
reasonably thorough job of discussing the biases that
contribute to at least some of these differences. The
ﬁrst striking difference reported by the authors refers
to differential rates of surgical resection. In the SEER
registry, 40% of patients with ampullary carcinoma
underwent resection as compared to 82% atMemorial
and 88% at Johns Hopkins. As noted in the manu-
script, there is likely a strong referral (selection) bias
wherein tertiary care centers specializing in complex
gastrointestinal and hepatobiliary surgery will see pa-
tients who have been prescreened as more likely to be
resectable. The more aggressive resection policies of
these groups also certainly contribute to the difference
in resectability rates. One important piece of data from
the O’Connell et al. paper is that more than 18% of
ampullary cancer patients with stage Ia disease did not
undergo surgical resection. While the explanation for
this cannot be discerned from the available data, this is
consistent with recent ﬁndings on the treatment of
pancreatic duct carcinoma and point to an area that
deserves further study.5 Differences in perioperative
mortality rates were also noted between single-insti-
tution studies (generally less than 5%) and the SEER
registry data (8%). Such differences have been the
subject of an extensive body of literature that generally
reveals perioperative mortality to be bound to
comorbid illness (not assessable by SEER), and sur-
geon and hospital volume in a relationship that is not
easily deﬁnable.
Finally, the 5-year survival for patients in the
current study was 36.8%, whereas survival rates from
single-institution studies ranged from 40% to 70%.
Interestingly, however, some of the larger studies,
including those from Johns Hopkins and Memorial
Sloan-Kettering revealed only a modest diﬀerence
Published online April 19, 2008.
Address correspondence and reprint requests to: Andrew M.
Lowy, MD; E-mail: alowy@ucsd.edu
Published by Springer Science+Business Media, LLC  2008 The Society of
Surgical Oncology, Inc.
Annals of Surgical Oncology 15(7):1813–1814
DOI: 10.1245/s10434-008-9918-x
1813
from the SEER data, with both revealing a 5-year
survival rate of 46%. This diﬀerence could easily be
explained by the lower perioperative mortality rate at
these centers, by a more favorable patient population
in terms of both stage and overall health status, and
perhaps by a more liberal use of adjuvant therapy.
The authors err however when they overreach to
conclude that their ‘‘data highlight the debate for
pancreaticoduodenectomy to be regionalized to high
volume centers’’. For the reasons stated previously
and acknowledged by the authors, diﬀerences in
outcomes between large registries and single-institu-
tion studies reﬂect numerous biases and not simply a
diﬀerential in the quality of health care. One bias the
authors fail to acknowledge is perhaps one of the
most potent of all: publication bias. That is, of
course, our very human tendency to publish results
only when they are favorable. Thus, it should always
be expected that unbiased registry data will reveal
outcomes that are inferior to those self-reported by
individuals and it is probably unrealistic to expect
these two to be concordant. The concept of region-
alization has been much debated, but remains
impractical given US geography and healthcare
ﬁnance. Rather than being an agent that drives
regionalization, the O’Connell et al. study and others
like it serve the important purpose of raising our
consciousness regarding what may be a more
accurate picture of the natural history of rare diseases
and the current patterns of care nationwide. They
serve the important functions of generating hypoth-
eses that warrant testing in the setting of multi-
institutional or cooperative group trials and by
pointing out where these robust datasets fail us,
thereby suggesting important data ﬁelds that should
be incorporated in future registry design. Finally,
when such studies reveal that potentially curable
patients are not receiving surgical care, they point to
potential areas for improvement in education and
process which can raise the level of cancer care across
the country, a very important contribution indeed.
REFERENCES
1. O’Connell JB, Maggard MA, Manunga Jr. J, et al. Survival
following resection of ampullary carcinoma: a national popu-
lation-based study. Ann Surg Onc 2008.
2. Talamini MA, Moesinger RC, Pitt HA, et al. Adenocarcinoma
of the ampulla of Vater. A 28-year experience. Ann Surg 1997;
225:590.
3. Howe JR, Klimstra DS, Moccia RD, et al. Factors predictive of
survival in ampullary carcinoma. Ann Surg 1998; 228:87–94.
4. Kim RD, Kundhal PS, McGilvray ID, et al. Predictors of failure
after pancreaticoduodenectomy for ampullary carcinoma. J Am
Coll Surg 2006; 202:112–9.
5. Bilimoria KY, Bentrem DJ, Ko CY, et al. National failure to
operate on early stage pancreatic cancer. Ann Surg 2007;
246:173–80.
EDITORIAL1814
Ann. Surg. Oncol. Vol. 15, No. 7, 2008


Beyond the Ivory Tower: Outcomes Following Surgery for Ampullary Cancer

Crossref

Adenocarcinoma of the ampulla of Vater. A 28-year experience. Ann Surg

Factors predictive of survival in ampullary carcinoma. Ann Surg

National failure to operate on early stage pancreatic cancer. Ann Surg

Predictors of failure after pancreaticoduodenectomy for ampullary carcinoma. JA m Coll Surg

Survival following resection of ampullary carcinoma: a national population-based study. Ann Surg Onc

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Beyond the Ivory Tower: Outcomes Following Surgery for Ampullary Cancer

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