|
|
Home | Site Map | Appointments | Second Opinions | Glossary | Links | Giving |
| Disease Information | At Johns Hopkins | What's New | Patient / Family Chat Room | FAQs | Advocacy |
Between January 1990 and July 1996 650 patients underwent a Whipple resection at The Johns Hopkins Hospital. Dr. Yeo followed these patients to determine the pathology, complications and outcomes. Most of the Whipple resections were performed for cancer of the pancreas (43%), however, Whipples were also performed for ampullary cancers (11%), distal common bile duct cancers (10%), duodenal cancers (4%), chronic pancreatitis (11%), neuroendocrine tumors (5%), periampullary adenomas (3%), cystadenocarcinomas (2%), cystadenomas (4%) and other conditions (7%). The median number of units of red cells transfused was 0 and the median operative time was 7 hours. During this period, 190 consecutive were performed without a mortality. The overall operative mortality rate for this group of 650 patients was only 1.4%. The most common complications included early delayed gastric emptying, pancreatic fistula, and wound infection. The median post-operative length of stay was 13 days.
In multivariate analysis the most powerful independent predictors favoring long term survival included a pathologic diagnosis of duodenal adenocarcinoma, tumor diameter less than 3 cm, negative resection margins, absence of lymph node metastases, well differentiated histology, and no reoperation. This single institution, high volume experience demonstrates that Whipple procedures can be performed safely for a variety of malignant and benign disorders of the pancreas. Overall survival is determined largely by the pathology within the resection specimen.
For specific questions about the Whipple procedures performed at Johns Hopkins, please contact Dr. Yeo at cyeo@gwgate1.jhmi.jhu.edu
Reference:
1. Yeo CJ, Cameron JL, Sohn TA, Lillemoe KD, Pitt HA, Talamini MA, Hruban
RH, Ord SE, Sauter PK, Coleman J, Zahurak ML, Growchow LB, Abrams RA. Six
hundred fifty consecutive pancreaticoduodenectomies in the 1900s.
Pathology, complications and outcomes. Annals of Surgery 226(3):248-260,
1997.
Most primary pancreatic cancers of the pancreas have mutations in the K-ras oncogene (1). In this study of over 100 liver nodules, the scientists found that when the primary pancreatic cancer had a K-ras mutation, the liver metastases also always had the same mutation. In contrast, the vast majority (94%) of benign bile duct proliferations did not harbor K-ras mutations.
These results suggest that K-ras mutations may be useful in distinguishing benign bile duct proliferations from metastases in the liver, and importantly, they demonstrate a potential clinical application of our improved knowledge of genetics of carcinoma of the pancreas. Other potential applications of tests for K-ras include blood or stool tests for rare pancreatic cancer cells and genetic tests as adjuncts to cytologic diagnoses (1,2).
References
Reference
Yeo CJ, Abrams RA, Grochow LB, Sohn TA, Ord SE, Hruban RH, Zahurak ML,
Dooley WC, Coleman J, Sauter PK, Pitt HA, Lillemoe KD, and Cameron JL.
Pancreaticoduodenectomy for pancreatic adenocarcinoma: Postoperative
adjuvant chemoradiation improves survival. Annals of Surgery
225(5):621-636, 1997.
In a
recent issue of the scientific journal, Cancer Research (June 1, 1997),
Drs. Chris Moskaluk, Ralph Hruban, and Scott Kern at Johns Hopkins seem to
have finally nailed the culprit. And it is indeed the common,
ordinary-looking duct lesion. They used a rare mutation in the p16 cell
cycle gene, found in infiltrating pancreas cancer, as a marker to
determine if any of the nearby duct lesions were related to the
infiltrating cancer. This mutation changed only one of the hundreds of
nucleotides (building blocks of DNA) in this gene, and could serve as a
genetic "fingerprint" for the origin of the cancer. Remarkably,
the same p16 mutation was found in the infiltrating pancreas cancer and in
a neighboring duct lesion. Another type of mutation, this time in the
K-ras gene, was also shared between the duct and the cancer. The proof
was now in: a rather unimpressive duct lesion had, over what was probably
the span of many years or decades, evolved into the cancer which finally
invaded through the duct wall to become an aggressive tumor. Evidence
from other patients was also identified to support this scenario. A
small proportion of duct lesions, about 20%, evolve to become more
aggressive-looking, as judged by the microscope. Previous work by the
Hopkins investigators and by researchers in Japan (Cancer Research 1994;
54:3568; Cancer Research 1993; 53:953) had indicated that mutations of the
K-ras gene, common in pancreatic cancers, also appeared more often in the
duct lesions with the most aggressive microscopic appearances. K-ras gene
mutations were found predominantly in the ducts having the features of
"dysplasia" and "papillary architecture". But a large
variety of pancreatic abnormalities harbor mutations of the K-ras gene,
and therefore they did not seem to be a very specific fingerprint for the
most aggressive lesions. The current work extends this type of analysis
by using a more specific marker, the p16 gene. Now that the origin of
pancreatic cancer is established, we can work harder to determine how
these lesions make the transition to cancer, and which individuals might
be at greatest risk for progression of their duct lesions.
REFERENCE
Pat Sauter, R.N. (410)-955-5718
In this week's issue of Science Magazine, (Science Vol 276:1268-1272,
1997) Lin Zhang, Wei Zhou, Victor E. Velculescu, Scott E. Kern, Ralph H.
Hruban, Stanley R.Hamilton, Bert Vogelstein and Kenneth W. Kinzler from
Johns Hopkins report the results of an analysis of a series of pancreas
cancers using a new technique called SAGE (serial analysis of gene
expression). SAGE is a powerful technique which can be used to identify
and quantify all of the genes expressed in a tissue. When the
investigators applied SAGE to pancreas cancer they were able to identify a
total of 404 transcripts (transcripts are pieces of RNA which code for
proteins which might be released into the blood of patients) that were
expressed at higher levels in pancreatic cancers as compared to normal.
The majority (268) of these transcripts were pancreas-specific; suggesting
that this technique could be used to identify new pancreas cancer specific
markers which could be used to develop screening tests for pancreas cancer
(see http://welchlink.welch.jhu.edu/~molgen-glhome.htm).
References:
V.E. Velculescu, L. Zhang, B. Vogelstein, K.W. Kinzler. Serial Analysis
of Gene Expression. Science 270:484-487, 1995.
By the late 1940s, the mutational theory was gathering
considerable excitement, even though the techniques to find mutations in
the tumors had
not yet been developed. One author in 1949 noted, "The recent work
on carcinogenesis and mutagenesis is of ... importance since the rational
control of a disease should be based upon its true biological nature"
(Yale J Biol Med 21:293, 1949). By the early 1950s, there were attempts
to
estimate the number of mutations needed. A number of investigators noted
that the sharp rise in cancer rates in the elderly could be matched to a
mathematical model where the age of a person, when multiplied by itself 4
to 6 times, seemed to match their expected cancer risk. This suggested
that
nearly half a dozen independent mutations, each with some small chance of
occurrence during any one year of life, were needed to form the common
cancers (Cancer 4:916, 1951 and Br J Cancer 7:68, 1953, and others). By
the late 1980s, there was some success in confirming these estimates, even
though the particular mutations and genes involved still were largely
unknown.
We now have made great strides in determining what the mutations are and
which genes they affect. In the latest issue of the scientific journal
Cancer Research (May 1, 1997), Dr. Ester Rozenblum and
colleagues report a
high-resolution picture of the genetic abnormalities of 40 pancreatic
cancers as determined in the Kern Laboratory at Johns Hopkins. Her study
probably represents the most precise and exhaustive description of the
prevalence of various mutations in a cancer type to date. She finds that
most of the cancers involve mutations in at least three to four different
genes. Many genes sustained mutations or loss of both of their normal
copies, and the number of gene abnormalities was therefore seen to be as
high as nine distinct mutations. Each mutation is thought to have aided
the
evolution of the expanding population of cells into its eventual invasive,
cancerous form.
Dr. Rozenblum also found that mutations of any one gene could co-exist
with mutations of any other gene she studied. For example, an inherited
mutation of the BRCA2 gene was clearly not adequate to cause the
pancreatic cancer of one patient. This particular tumor, in order to
become fully cancerous, had to develop eight additional mutations in key
genes. This is important information, especially for the BRCA2 gene
involved in inherited susceptibility to breast, pancreatic, and other
tumors (see the
What's New of December 2, 1996). It means
that the
important tumor-suppressive action of BRCA2 is distinct from the
suppressive action of the other genes previously
known to involve pancreatic cancer.
When combined with the discovery of the importance of the BRCA2 and DPC4
genes (see the What's New of
February and
July, 1996), the past fourteen months have
provided discoveries of two totally new avenues for understanding the
"true biological nature" of pancreatic cancer. Like the myriad
pixels in a digital picture, each mutated gene helps us to construct a
clearer picture of this cancer at ever-higher resolution.
This SPORE is designed to develop areas of basic science with
potential impact on pancreatic and colorectal cancer and to move these
promising areas into clinical evaluation including clinical trials. The
SPORE is also designed to communicate important findings rapidly into the
research community to stimulate investigation, and to bring validated
transitional findings into the medical community where the research can
ultimately reduce the incidence and mortality of these common cancers.
A Genetic Fingerprint Proves the Origin of Pancreatic
Cancer
The best way to fight pancreatic cancer would be to detect it in its
earliest stages. But there has been some uncertainty as to what the
earliest form might look like. The pancreases of elderly persons often
have ducts with abnormal lining cells, but for years these lesions were
largely overlooked as trivial. In the vast majority of cases, the
microscopic appearance of these lesions does not readily suggest that they
might be worrisome. Indeed, one could calculate that if these ductal
lesions were the precursor of pancreatic cancer, then only about 1% of
them appear to progress to that stage. These small numbers, and the
rather benign microscopic appearance of most duct lesions, have raised
interesting questions about the true origin of pancreatic cancer.
July 1, 1997
Moskaluk CA, Hruban RH, Kern SE. p16 and K-ras gene mutations in the
intraductal precursors of human pancreatic adenocarcinomas. Cancer
Research 57:2140-2143, 1997.
PANCREAS CANCER VACCINE APPROVED FOR STUDY
Hopkins clinicians/scientists involved in pancreas cancer research are
pleased to announce that the FDA has just approved a new vaccine trial for
the treatment of pancreas cancer. We are now enrolling patients into
this pancreatic tumor vaccine study. Patients who have newly diagnosed
stage I, II, or III adenocarcinoma of the pancreas are eligible. Patients
must be able to undergo resection of their pancreatic tumor at The Johns
Hopkins Hospital. For more information, please contact one of the
following co-investigators:
June 10,
1997
This trial will use an allogeneic irradiated pancreas cancer vaccine
generated by ex vivo granulocyte-macrophage colony-stimulating
factor gene transfer. Such an approach has already proven "feasable,
safe and bioactive" in patients with renal cell carcinoma (see
Cancer Research vol 57, 1537-1546, 1997).
JoAnn Coleman, R.N. (410)-955-5718
Charles Yeo, M.D. (410)-955-7496
John Cameron, M.D. (410)-955-5166
Keith Lillemoe, M.D. (410)-955-7495
GENE EXPRESSION IN PANCREAS CANCER
The first step in developing a convenient screening test for a cancer is
to identify the proteins that the cancer makes. Once these proteins are
identified one can then test blood samples from patients with cancer to
see if these proteins are released into and detectable in the blood. For
example, prostate cancers make a "prostate specific antigen"
which is detectable in the blood and which forms the basis for the current
screening test for the detection of early prostate cancers.
May 28, 1997
L. Zhang, W. Zhou, V. E. Velculescu, S.E. Kern, R.H. Hruban, S.R.
Hamilton, B. Vogelstein, K.W. Kinzler. Gene Expression Profiles in Normal
and Cancer Cells. Science 276:1268-1272, 1997.
Hopkins Researchers Show A Genetic Picture of Pancreatic
Cancer
For centuries, physicians and the public have wondered about the nature of
cancer: What is it? How does it arise? Why do most cancers appear in the
later years of life? By the turn of the century, many authorities were
already convinced that a cancer represented a highly related aberrant
group of cells, the errant offspring of a single original cell of the
body. This cell presumably had, through uncontrolled growth and division,
given rise to many generations of progeny cells which eventually formed a
much larger and ever-proliferating lesion.
May 1, 1997
Johns Hopkins awarded Specialized Program of Research
Excellence (SPORE) in Gastrointestinal Cancer
The National Institutes of Health have awarded the Johns Hopkins Medical
Institutions a Specialized Program of Research Excellence (SPORE) in
gastrointestinal cancer. This 5 year award supports a highly interactive
multidisciplinary program of transitional research directed at reducing
the incidence of and mortality from pancreatic and colorectal cancer. The
SPORE includes 4 research programs involving 8 research projects which
build upon successful existing research programs. In addition, 4 core
laboratories are funded. The programs include:
February 12, 1997
Four cores will support these research programs. These include:
Finally, and importantly, the SPORE grant will support a
developmental research program headed by Bert Vogelstein, M.D. This
program will help fund pilot projects. The SPORE also provides funding
for a career development program which will allow for the development of
young investigators interested in cancer research.
2003 News
2002 News
2001 News
2000 News
1999 News
1998 News
1996 News