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Introduction
to the FAQ
(answers to frequently asked questions)
This section consists of our
version of "answers" to very general pre-selected questions
about pancreatic cancer. This task is not easy, as there are
controversies in virtually every aspect of its related diagnosis
and treatment. Also, information regarding such treatment is
in a constant state of flux, with the results of new studies
often challenging assumptions or pushing our understandings just
a little further along. Additionally, general guidelines frequently
do not apply to individual circumstances. Each person's situation
is unique. If a cookbook-approach could work well in these circumstances,
doctors would not be needed. And make no mistake about it, in
our view, a strong bond with a compassionate and knowledgeable
physician-specialist is mandatory.
Our brief answers are attempts
to give a sense of overview to these very complicated subjects.
There are whole books dedicated to many of these individual subjects,
so our answers are (at best) summaries. Because they are designed
as summaries, it is possible that whole areas of controversy
are inadvertently (or intentionally) ignored or not given proper
weight. So be careful when reading these answers--all of the
information given here needs to be checked out with your own
doctor. And do not base any action or lack of action on these
answers, they are meant for educational purposes only! Please
read the disclaimer to this site.
We hope that these answers give
a balanced sense of some of the underlying issues about pancreas
cancer so that patients can bring more to the table when speaking
with members of their own health care team. These answers are
generally about conventional approaches, and are primarily based
on standard written bibliographic references. The main sources
that we used for these purposes are listed below.
In addition, some of the answers
contain hypertext links to other Internet sites. In supplying
these links, we are not necessarily vouching for the accuracy
of the information contained on these other linked sites. We
are rather trying to round out the information a bit AND to give
visitors a sense of what other related information exists on
the Internet (and how and where other sites might be found for
further self-directed research on the part of visitors).
These answers were generally
written with adenocarcinoma of the pancreas in mind, as this
is the most frequently occurring malignant tumor of the pancreas.
But there is one answer which briefly addresses various other
types of pancreatic cancer, and another answer which specifically
addresses neuroendocrine (islet-cell) tumors. Please send any
notice of mistakes, corrections or suggested additions (including
other recommended questions) to us at webmaster@pancreatica.org.
Bibliography
Cancer, principles & practice
of oncology; Seventh Edition. Edited by DeVita, Hellman and
Rosenberg. Lippincott, Williams & Wilkins; Philadelphia,
Pennsylvania; 2004.
The Chemotherapy Handbook; Fifth Edition. Fisher, Knobf and Durivage.
Mosby; St. Louis, Missouri; 1997.
The Complete Cancer Survival Guide. Teely and Bashe. Doubleday;
New York, New York; 2000.
The M.D. Anderson Surgical Oncology Handbook; Fourth Edition.
Feig, Berger and Furman. Lippincott, Williams and Wilkins; Philadelphia,
Pennsylvania; 2006.
The Pancreas. Edited by Beger, et al. Blackwell Science Ltd;
England; 1998.
Pancreatic Cancer. Edited by
Von Hoff, Evans and Hruban. Jones and Bartletts; Maine; 2005.
Pancreatic Cancer; M.D. Anderson Solid Tumor Oncology Series.
Edited by Evans, Pisters and Abbruzzese; Springer-Verlag; New
York; 2002
Pancreatic Cancer, pathogenesis, diagnosis and treatment.
Edited by Reber. Humana Press; Totowa, New Jersey; 1998.
Pancreatic Disease. Edited by Johnson and Imrie. Springer-Verlag;
Great Britain; 2004.
1. What is
Pancreatic Cancer?
The Pancreas
The pancreas is a small,
spongy organ which lies just under the curvature of the stomach
and deep within the abdomen. The function of the pancreas is
a complicated, but one could say that it primarily does two things.
It produces enzymes which are useful for the digestion of food
AND it secretes hormones which, among other things, help maintain
and regulate body sugar levels.
The pancreatic enzymes are produced
in cells which are called acinar cells; this part of the pancreas
is called the EXOCRINE part of the pancreas. The clumps of acinar
cells are found gathered throughout the pancreas; these cells
release salts and enzymes into small tributaries which collect
and transport this pancreatic fluid. These small rivlets eventually
coalesce into the pancreatic duct. This sixteenth-of-an inch
wide duct runs from left-to-right along the length of the pancreas,
eventually (usually) joining up with the bile duct and emptying
its combined digestive contents into the first part of the small
bowel (called the duodenum).
 Additionally, the pancreas has an ENDOCRINE
or hormonal function. For example, inside of specialized groupings
of cells called the Islets of Langerhans, the pancreas produces
hormones which are secreted directly into the blood stream. These
hormones have numerous effects, and will be addressed in a simplistic
fashion here. Insulin (produced by so-called beta cells) has
effects, among which it lowers the level of glucose in the blood.
Glucagon (produced by alpha cells) tends to increase the level
of blood sugar. Other hormones, as well as various peptides,
are produced by the endocrine pancreas--including also somatostatin,
a hormone which inhibits the secretion of insulin.
A site which has detailed information
about the matters as discussed in this answer is the NCI Booklet "What You Need To Know About
Cancer of the Pancreas".
Pancreatic Cancer
Malignant cancer is a
tumor (or growth) in which an aggregation of individual cells
begin to grow in a rapid, uncontrolled and abnormal manner; and
which may spread by aggressive local extension or by the seeding
of other organs through blood vessel channels or via the lymphatic
system. There also exist benign tumors which tend to be (but
are not always) less serious, which tend to grow more slowly
and orderly, and which tend not to spread by colonizing into
other parts of the body (this process known as metastasis). Cancer
can arise from virtually any kind of cell in the body.
In up to 95% of cases, pancreatic
cancer arises from the exocrine portion of the organ. The least
common exocrine cancer comes from acinar cells. Most of the exocrine
tumors (~90%) are from ductal cells--those which line the pancreatic
ducts. These tumors are classified as carcinomas, a word that
refers to tumors arising from a lining cell. Further, under the
microscope, the appearance and arrangement of these carcinoma
cells can appear as duct-like (or "adeno") giving the
term adenocarcinoma to this most common form of pancreatic cancer.
About three-quarters of exocrine
tumors of the pancreas arise in the head and neck of the pancreas
(the anatomic parts through which the pancreatic duct runs just
before it meets the duodenum). Some of these carcinomas arise
in the body of the organ, and less than ten percent arise in
the tail of the pancreas (the tapering smaller "left"
area, closest to the spleen).
It is now understood that cancer
is caused by the mutations of a gene which confer increased abnormal
growth potential to cells. Genes in which this potential is directly
conferred are called oncogenes. Other kinds of genes whose role
includes that of preventing this phenomenon from happening are
called tumor-suppressor genes. And finally there is a third kind
of gene, called DNA-repair genes, the loss of function through
mutation which may allow both activated oncogenes and thwarted
tumor-suppressor genes to lead to cancer. It is generally believed
that more than one mutation, modifying more than one regulatory
pathway, is necessary for cancer to occur.
An oncogene called K-ras
is found to be altered in up to 95% of ductal adenocarcinomas
of the pancreas. Common known tumor-suppressor genes which are
inactivated by mutation in this kind of pancreatic cancer are
the p53 and p16 genes. For example, p53 is inactivated in about
70% of adenocarcinoms of the pancreas. Still other genetic mutations
have been found. This area of inquiry is currently a source of
a great deal of interest and research, with an eye toward finding
effective treatment or earlier diagnosis.
It has been approximated that
about 30% of the changes which initiate cancer of the pancreas
are caused by smoking; and that about 10% are secondary to hereditary
genetic predisposition. There appears to be a mild correlation
between the onset of diabetes and pancreatic cancer, but it is
not entirely clear if this is fully a cause or perhaps an effect
of the cancer. There does not appear to be a strong correlation
between the onset of pancreatic adenocarcinoma and the drinking
of alcohol or of coffee (though these have been issues of some
controversy).
Metastasis and endocrine tumors
are two topics which are addressed in more detail in later questions.
The most common sites of metastasis of pancreatic adenocarcinoma
are the liver, the peritoneum (the thin lining which contains
many structure in the abdominal cavity) and the lungs. Cancers
of the endocrine portion of the pancreas are less common than
exocrine cancer of the pancreas (about two to three thousand
cases are diagnosed each year in the U.S.). They are typically
referred to as neuroendocrine (or islet-cell) tumors. Although
they arise from the hormone producing area of the organ, neuroendocrine
tumors can be either functioning (demonstrating excess hormone
secretion which produces symptoms) or non-functioning. Endocrine
tumors have a different natural history than the exocrine tumors.
They tend to be slower growing and have a better prognosis. The
treatment of neuroendocrine tumors of the pancreas is distinct
from that of adenocarcinoma of the pancreas.
This above description of tumor
types is somewhat superficial as there really exist a number
of types of pancreatic cancer (many of these are very rare),
some of which have shared characteristics and which may be very
difficult to classify. The U.S. Armed Forces Institute of Pathology
histological classification of pancreatic cancer outlines several
kinds of malignant tumors of the exocrine pancreas (including
"miscellaneous carcinomas"), further offering a number
of sub-classifications of ductal adenocarcinoma alone and even
sub-classifications of acinar cell carcinoma. They identify other
forms of benign tumors and multiple "borderline" tumor
types, described as having uncertain malignant potential. From
this, one can perhaps get a better sense of the complexity of
the subject.
The Toll of Pancreatic Cancer
Each year more than 30,000
people in the United States are diagnosed with adenocarcinoma
of the pancreas and more than twice that in Europe. Most of these
people will have passed away by the end of the first year. The
incidence of pancreatic cancer increases with age; most people
are between the ages of 60 to 80 when they receive the diagnosis.
Men have tended to be over-represented, though in recent years
the gap between men and women has shrunk, possibly due to increased
cigarette smoking among women. In the U.S., pancreatic cancer
is 9th or 10th most commonly diagnosed cancer (depending on gender),
but the fourth leading cause of cancer death in men and women.
The median survival period from the time of diagnosis until demise
is arguably the worst of any of the cancers. The median survival
for untreated advanced cancer of the pancreas is about 3 ½
months; with good treatment this increases to about six months.
Perhaps in concluding, we might draw attention (in the midst
of delivering this difficult news) to an interesting paper about
one
man's struggle to not be the median.
2. What are
the Stages of Pancreatic Cancer?
On the surface this would seem
to be a fairly straight forward question, but as there exists
the controversy of competing nomenclatures, it is not as simple
as one might think. In fact, in the U. S., universal agreement
on a standardized staging system does not exist. The fundamental
problem is that the staging system for exocrine cancer of the
pancreas as put forth by, for example, the American Joint Committee
on Cancer ("AJCC") is felt to be somewhat impractical
by certain experts in the field. This classification rests on
knowing the status of the TNM (that is Tumor, lymph Nodes and
distal Metastasis).
Under this classification (roughly)
Stage I pancreatic cancer includes tumors which have not
spread into certain proscribed sensitive areas and which have
no involved regional nodes or distal metastasis. Stage II
includes tumors which have spread into the duodenum, bile duct,
or "peripancreatic" tissues AND which have no involved
regional nodes or distal metastasis. Stage III cancer
includes tumors which may have OR may not have spread
into these aforementioned areas and which have involved
regional nodes, but which show no evidence of distal metastasis.
Stage IVA includes tumors which have spread into the stomach,
spleen, large bowel OR the adjacent large vessels AND which have
involved regional nodes, but show no evidence of distal metastasis.
And Stage IVB includes pancreatic tumors of any kind with
node status of any kind AND with evidence of distal metastasis.
Leaving aside that fact that
this classification may not completely comport with similar nomenclature
by the International Union Against Cancer (Union Internationale
Contre le Cancer), in practice, though referred to, this
classification is rarely used in its pure form as the stages
do not fully match treatment options or even patient prognosis,
and very often the true lymph-node status cannot be fully determined
without surgery (which most people do not receive).
For doctors and patients then,
staging is based on sophisticated radiologic studies. And for
these cases, a clinical/radiographic staging classification for
pancreatic cancer has been proposed which attempts to more closely
follow prognosis and clinical decision making in regard to treatment.
This three stage classification (potentially resectable, locally
advanced and metastatic), is based on radiological findings,
and is not directly referent to the TNM status.
In this proposed classification,
potentially resectable pancreatic cancer is defined (roughly)
as that including no evidence of extra-pancreatic involvement
of the tumor, demonstration of fully patent superior mesenteric
/ portal veins and showing no evidence of encroachment ("encasment")
by the tumor on the arterial celiac axis or the superior mesenteric
artery. Locally advanced includes evidence of arterial
encroachment (celiac axis or superior mesenteric artery) or venous
occlusion (superior mesenteric / portal veins). And the metastatic
stage includes evidence of metastatic spread (typically to the
liver, peritoneum or lung).
There are other terms in use
and still other classifications. Of course, this makes for a
messy kind of communication, although in practice oncologists
seem to be able to speak with one another without apparent misunderstanding.
It is possible and even likely perhaps, over time, assuming the
great strides in the sophistication and power of radiographic
techniques continue to move forward, the future will further
free these classifications from their strictly surgical origins
and enable a more uniformly agreed upon staging nomenclature.
3. How is
Pancreatic Cancer Diagnosed?
Signs and Symptoms
Generally, the most common
symptoms of adenocarcinoma of the pancreas include loss-of-appetite,
weight loss, abdominal discomfort and nausea. As these are all
fairly non-specific symptoms, there is often delay in getting
to the final diagnosis. The most common physical sign of pancreatic
cancer is jaundice, with or without associated itching. Preceding
to a medical evaluation often requires a high index of suspicion
by the patient or by medical personnel.
Laboratory
Often lab results show
a high bibirubin (bile pigment found in the serum) and elevated
liver function enzymes. The CA 19-9 marker, a Lewis blood group-related
mucin, is frequently elevated in adenocarcinoma of the pancreas,
but its use in the screening for or diagnosis of the cancer is
presently not an accepted practice. High CA 19-9 results may
tend to be associated with (but do not always indicate) larger
sized tumors and with a decreased likelihood of surgical resectability.
The use of this marker is more universally accepted as a running
measure within a particular individual, to help reflect the stability
or the progression of the cancer.
Staging Studies
The main reason for the
staging of pancreatic cancer is to try to chart the best course
for treatment, especially to help decide whether a patient is
a candidate for surgical resection. There is a great deal of
flux and controversy in these areas; there are institutional
and even geographical variations in considered opinions as to
the correct approaches in regard to these staging techniques.
Also, there may be great variability in the experience level
of the operators and evaluators of a given procedure-thus (perhaps
rightfully) coloring the institution's approach at recommending
which studies are used. In the context of these understandings,
the following brief overview will try and point out some strengths
and weaknesses of certain of the current staging procedures.
Generally, in the U.S., the dynamic
spiral (or helical) CT scan with IV and oral contrast media enhancement
is considered to be the procedure of choice for the staging of
pancreatic cancer. With the latest equipment and with experienced
operators and evaluators, this approach can detect up to 90-95%
of pancreatic ductal adenocarcinomas. Tumors greater than ½
to one inch can usually be detected. These CTs can predict unresectability
about 90% of the time; but are less accurate at predicting surgical
resectabilty. Its strength in this regard is related to its ability
to demonstrate pancreatic extension involving local arteries.
This technique is less reliably able to show subtle local vein
involvement, to detect small liver metastasis or to pick up lymph
node involvement.
Transabdominal ultrasound is
a more popular procedure outside of the U.S. where operators
are more experienced and generally the patient-population may
be less obese -- a big problem in imaging structures through
the abdomen. In experienced hands, with a thin patient and with
good equipment, this ultrasound approach can often pick up smaller
tumors than are even found by the CT procedure.
Two other ultrasound procedures
are of note. The endoscopic ultrasound (ultrasound through a
tube which is placed down the esophagus) can be very good at
finding small tumors in the pancreas. And laparoscopic ultrasound
(ultrasound through a small tube placed through the abdomen into
the region of the pancreas) is sensitive at finding liver and
peritoneal involvement, without having to resort to full surgery.
Pre-operative angiography (viewing
contrast dye placed in select arteries) is recommended by some
surgeons, although the introduction of spiral CT has provided
a competing option.
CT or ultrasound-guided percutaneous
biopsy (via needle) can retrieve a bit of pancreatic tumor tissue
for histologic (microscopic) viewing without requiring full surgery.
There exists some concern about the risk of inadvertent "seeding"
of the tumor into the peritoneum with this technique, but some
experts feel that the potential risks outweigh the potential
harm in selected cases.
Often an institution will have
a coordinated approach at diagnosis and staging toward pancreatic
cancer. For example, a spiral CT procedure might be done first.
If it appears that there is a tumor and that it might be resectable,
the next step might be a laparoscopy (for direct visualization)--with
perhaps a peritoneal wash (to check for malignant cells in the
peritoneum) and with or without a laparoscopic ultrasound exam.
If evidence of unresectability is found, a percutaneous biopsy
might be done, to fully establish the diagnosis and to help with
medical treatment planing. If no evidence of unresectability
is found, then a full abdominal surgery might typically ensue
to further evaluate the clinical status--and if finally so indicated
to proceed with the most appropriate surgical procedure.
4. What is
the surgical treatment of pancreatic cancer?
Surgery for adenocarcinoma of
the pancreas is only offered to patients whose tumor is localized
and meets other criteria (please note earlier FAQ answers). Only
about 15-20% of those individuals with pancreatic cancer will
be found to be eligible for surgery. In these cases, surgical
resection (removal) of the tumor from the pancreas (and resection
of select surrounding tissues) gives the best chance for a cure
and generally confers a better overall prognosis in contrast
to medical therapy. This is one reason why so much effort is
given in pre-operative testing to try to identify those patients
who may be good candidates for surgery. Another reason for such
care is to avoid the offering of unnecessary surgery to patients
who are already ill.
At surgery, the first job of
the surgeon is to assess the nature and extent of the cancer--to
verify if the patient is a true candidate for resection. If the
cancer has advanced further than the pre-operative testing has
indicated (which is not uncommon), then certain palliative surgical
measures as noted below (aimed at symptomatic relief) may be
offered, but the resection would typically not proceed.
The resection, known as the Whipple
operation / procedure (or pancreaticoduodenectomy), is typically
done for patients who have tumors which are located in the head
of the pancreas or which are located in regions adjacent to the
head of the pancreas. General information on this procedure exists
at the University of South Carolina website. And please note the extensive section
on the Whipple procedure at the Beth Israel website. There are a number of variations
of the Whipple procedure. The classic procedure, a modification
of the surgery described by A.O. Whipple and his colleagues in
1935, is a fairly extensive and somewhat complicated two-step
process whereby certain key structures in the surrounding vicinity
are removed (including that portion of the involved pancreas),
followed by a kind of surgical bypass-reconstruction, in effect
re-routing the digestive tube around the affected area. The Johns
Hopkins site has an illustrative site in this regard.
One of the fundamental questions
among researchers and surgeons relates to the necessary scope
and extent of the pancreaticoduodenectomy surgery. Which tissues
should be resected (and what are the optimal amounts to be taken)
in order to get the best chance of survival, as balanced against
quality-of-life issues. This topic is controversial and there
has been a see-sawing back and forth over time between advocates
of more radical procedures and those who advocate less radical
procedures.
If the pancreatic tumor is located
in the tail of the pancreas, usually that portion of the pancreas
will be removed along with the nearby spleen.
The Whipple surgery itself can
take several hours and is often grueling for the surgical team.
The region of the body where the pancreas lies is very busy and
complicated anatomically. Not only is the normal anatomy complex,
but individual anomalies are frequent among the various blood
vessels and ducts in the area. However, one of the great successes
in the treatment of cancer of the pancreas has been the improvement
in mortality related to the Whipple surgery. The mortality was
extremely high even a couple of decades back, but this has dramatically
improved. Now, operative mortality related to the Whipple procedure
is variously reported as 2-3%, but in some major U.S. institutions
the more recent operative mortality has been reported at less
than 1%.
Nevertheless, recovery can be
an ordeal for the patient. Serious complications following surgery
are still affect up to one-third of patients. These include the
development of fistulas (false channels), and leakage from the
site of the bowel reconnection. The judicious placement of surgical
drains may tend to reduce the incidence of these kinds of complications.The
survival of patients who received the Whipple procedure in one
study (from a very experienced Johns Hopkins team) were reported
out in 1995 as a 21% five-year survival rate, with a median survival
of 15.5 months.
If it is determined that the
cancer is too advanced to make surgical resection a viable option,
then certain palliative procedures may be offered. These are
typically targeted at the primary symptoms or causes of symptoms
in pancreatic cancer: pain, duodenal obstruction and jaundice
due to obstruction of the bile duct. Thus a nerve block of the
celiac nerve plexus may be done, and/or a gastrojejunostomy (stomach
bypass) and/or a bile duct bypass. Stents (inner wall supports)
may be used for certain of these procedures.
There are two principles that
need to be introduced at this time. Adjuvant therapy is a concept
that connotes the practice of giving medical and/or radio therapy
after surgery to help augment the effects of surgery.
And neoadjuvant is the term that describes the practice of giving
such therapy prior to surgery for potentially resectable
pancreatic cancer disease. For the past fifteen years, it has
been fairly common practice in the U.S. to give chemoradiation
(chemotherapy-typically the chemotherapy drug 5-FU-plus radiation)
as adjuvant treatment after the Whipple procedure. This practice
is based on the results of a 1985 landmark study which demonstrated
an almost double survival advantage for those who received such
therapy. This practice has recently been challenged (as offering
no statistical survival advantage), but a number of experts in
the field doubt the conclusions of this challenge and it is too
early to know if the challenge will hold up to long-term scrutiny.
The use of neoadjuvant therapy
is an area of research. According to some studies, chemoradiation
may push back the cancer enough to allow some patients (a minority)
with apparent unresectable adenocarcinoma of the pancreas who
otherwise might not be candidates--to be eligible for surgical
resection.
5. What is
the medical treatment of pancreatic cancer?
There are no universally agreed
upon firm guidelines for medical treatment for those patients
with adenocarcinoma of the pancreas who are not candidates for
surgery or who have a recurrence of the cancer after surgical
resection. In part, this is because there is no one great treatment
option-there are a number of treatment approaches which may be
more or less appropriate, given certain variables. Also, therapy
offerings are often tailored to patient circumstance and wishes--which
are highly individual.
In the discussion to follow,
very broad standard treatment practices are outlined. The discussion
does not touch upon general cancer therapy or the treatment of
some of the more common symptoms of pancreatic cancer. Keep in
mind while reviewing this information, as there is no single
exceptionally superior treatment, thoughtful and creative physician-guided
therapeutic regimens may be appropriate, and clinical trials
may offer options to (or even act to augment) standard practice.
Locally Advanced
Generally, in locally advanced unresectable adenocarcinoma of
the pancreas, chemotherapy plus radiation (in one form or another)
is often prescribed as standard therapy. As early as 1981, a
landmark report by the Gastrointestinal Tumor Study Group demonstrated
significant survival advantage to those patients with locally
unresectable adenocarcinoma of the pancreas who had received
both chemotherapy (5-FU) and radiation. This combination chemoradiation
gave better outcomes than either chemotherapy or radiation alone.
There have been a wide range
of studies involving the delivery mode, method and amount of
radiation to the tumor area. These have included such approaches
as external beam radiotherapy, intraoperative radiotherapy and
the seeding of the tumor area with radioactive pellets or with
radioactive colloidal solution (brachytherapy). 5-FU (sometimes
with in combination with drugs which enhance its effect) has
been perhaps the standard chemotherapy agent in many chemoradiation
regimens, but the drug-agents mitomycin-C and cisplatin (a platinum-containing
compound) are among the stable of chemotherapy agents which have
also been utilized. Also, a number of studies have begun looking
at gemcitabine as an effective radiosensitizer for combination
with radiation therapy in chemoradiation for locally advanced
unresectable adenocarcinoma of the pancreas.
According to some studies, chemoradiation
may push back the cancer enough to allow some patients (a minority)
with apparent locally unresectable adenocarcinoma of the pancreas
who otherwise might not be candidates--to be eligible for surgical
resection.
The median survival duration
from diagnosis with chemotherapy in unresectable locally advanced
adenocarcinoma of the pancreas has been reported as 6-12 months.
Advanced
As the pancreatic cancer
becomes widespread, although there may be creative modalities
by way of exception, the advantages of radiation are diminished.
Thus, standard medical therapy for advanced adenocarcinoma of
the pancreas typically involves chemotherapy-type agents alone.
The chemotherapy agent 5-FU (fluorouracil)
which has been in use against cancer for about 40 years, acts
in several ways, but principally as a thymidylate synthase inhibitor,
interrupting the action of an enzyme which is a critical factor
in the synthesis of pyrimidine-which is important in DNA replication.
The underlying principle in many standard chemotherapy agents
has to do with interfering with the normal progression of the
cell cycle. As cancer consists of uncontrolled cell growth, one
if its weaknesses is inherent genetic instability. If an agent
hurts the ability of the cell to progress through its normal
cycle eventually to replicate itself, although this will tend
to hurt all the cells in the body, its effect will be selectively
severe on unstable and rapidly growing cells-the cancer itself.
Gemcitabine is a more recently
approved chemotherapy drug which tends to offer a slightly increased
median survival duration (and increased one year survival rates)
as compared to 5-FU, and also appears confer substantially improved
quality-of-life measures over treatment with 5-FU and over no
treatment. Additionally, Tarceva has been approved in the U.S.
for the treatment of pancreatic cancer. More information including
data about side effects, gemcitabine, flourouracil and other
cancer chemotherapy drugs is found at CancerSource.
There appear to be interesting
and potentially promising combinations of two or more conventional
chemotherapy agents in the same treatment regime which are in
practice and under study, including combinations involving more
conventional chemotherapy agents paired with some of the newer
experimental agents.
Additionally, there is a wide
range of single-mode approaches currently in clinical trials
against pancreatic cancer (please note the FAQ on clinical trials).
These include some of the newer experimental therapies which
are aimed more at molecular targets and at interrupting genetic
signaling pathways, newer chemotherapy agents and even vaccines
against pancreatic cancer.
In summary, in advanced adenocarcinoma
of the pancreas, chemotherapy is better than no therapy. And
gemcitabine, depending on circumstances, may confer advantages
that 5-FU does not. Creative, intelligently-crafted and individualized
treatment regimens as tailored by compassionate oncologists involving
single agents or even combination therapy may be appropriate.
And finally, clinical trials remain an option.
6. What are
emerging therapies in regard to the treatment of pancreatic cancer?
The difficulty in discussing
this topic is not because there are too few, but rather as there
are so many creative experimental clinical trials which are occurring
with newer agents and combinations against pancreatic cancer.
However, it is important to note that many agents in that past
have looked promising, only to show no advantage by the end of
phase III clinical trials. These are experimental therapies,
and can be highly risky.
In listing some of the categories
and individual agents below, this is in no way meant or to be
considered as an endorsement of that category of drug or mode-of-action
(or of a particular drug agent). These examples are given for
education and discussion purposes only. The categories are representative
of some of these newer agents and this listing is not meant to
be exhaustive.
As a better understanding is
gained of the activity of the cell at the molecular level, more
targeted approaches are being implemented to try and interrupt
certain functions that are thought to play a role in cancer formation
or of cancer support.
Some of these areas of interest
include new combinations with accepted chemotherapy agents such
as putting gemcitabine or 5-FU together with some of the newer
agents (or with each other).
More recently discovered classes
of chemotherapy drugs are in development such as those which
inhibit topoisomerase, an enzyme which helps in cell replication.
Also, platinum-containing compounds are in use and under study
(often in combination with other agents) including such agents
as cisplatin, carboplatin and oxaliplatin.
Trying to inhibiting angiogenesis
(the tumor's ability to selectively redirect vascular nutrient
channels to itself) has been another area of research. Agents
such as Erbitux (and many other kinds of anti-angiogenesis compounds)
have been under study against all solid tumors including cancer
of the pancreas.
The inhibition of certain of
the matrix metalloproteinase family of enzymes which have been
found to be over-expressed in pancreatic cancer, has been explored,
although the recent results of such drugs have been somewhat
disappointing.
Several agents which are directed
at inhibiting the signaling pathways which proceed from the ras
oncogene have been studied. One group of these drugs is known
as the farnesyl protein transferase inhibitors. Several of these
have been under study.
More genetically directed approaches
including anti-sense therapy and viral vectors which deliver
specifically designed genetic material to tumor cells have been
studied in clinical trials against pancreatic cancer.
There are a few vaccine trials
against pancreatic cancer. These are all in early stages, but
include one which marshals cellular factors in the body to enhance
a boosted immune response against the tumor. And the clinical
trials of anti-pancreatic cancer vaccines also include others
which are directed more at certain antigens which tend to be
over-expressed in all (or in select) pancreatic tumors-such antigens
(or targets) as CEA, MUC-1, COX-2 and the ras pathway.
Also, there are a number of studies
which are looking at more surgical oriented issues, especially
at adjuvant and neoadjuvant augmentation.
7. What are
alternative or complementary treatments of pancreatic cancer?
Although we understand the possible
benefits of some alternative therapies, this website is not strongly
oriented this way. On an anecdotal basis only, we have heard
of positive experiences that patients have had with the treatment
of symptoms related to pancreatic cancer (and chemotherapy) involving
such approaches as visualization therapy, prayer, acupuncture,
green tea and Chinese herbs. We are not adverse to alternative
treatment modalities in which the downside risks are minimal
(or better yet, nonexistent) and which do not appear likely to
interfere with other more conventional medical therapies. Playing
the role of a scold is no fun, and it is not our aim to deprive
anyone of hope. In fact, we strongly believe that faith and hope
are the two most powerful allies that one can have.
The overriding concern of this
website is the ancient admonition to physicians, "first
do no harm." This site is oriented to the scientific method
and to scientifically-based clinical trials. If you have to take
risks, our thought is at least do it under medical and scientific
guidance. Nonetheless, we know that there are a large number
of people who will not subscribe to this approach. To those people
we would say, "be careful."
With that warning, we note that
there are sometimes clinic trials against pancreatic cancer involving
unconventional alternative therapies. There are a number of researchers
who are in support of these trials. Some perhaps because they
think they will succeed. Others, who strongly feel that applying
the scientific method to these kinds of treatments, will finally
expose them as fraudulent. Only time will tell what the outcome
will be. Our advice: "be careful."
There are many sites on the Internet
about alternative therapy. In our attempt to suggest tempering
faith and hope with rationality and care, we offer two links
to a site that deals with treatments that are adjudged by them
to involve quackery. Along with these links, we reiterate: "be
careful."
Quackwatch 1 | Quackwatch 2
8. What about
neuroendocrine (islet cell tumors)?
Neuroendocrine tumors of the
pancreas (islet cell tumors) are much less common than tumors
arising from the exocrine pancreas. Reports often indicate that
there are about two to three thousand cases diagnosed in the
U.S. each year - although autopsy indicates that there may be
a higher incidence of these islet cell tumors than are diagnosed.
About 75% of these tumors are
"functioning." That is they are found to be producing
symptoms related to one or more of the hormone peptides that
they secrete. About one quarter of islet cell tumors do not produce
symptoms related to hormone secretion and thus are termed non-functioning.
The predominant hormone peptide being secreted gives the functioning
islet cell tumor its name. There are a surprising number of these
hormonal peptides that islet cell tumors have been found to secrete;
some are not even related to the pancreas. This array includes
insulin, gastrin, glucagon, somatostatin, neurotensin, pancreatic
polypeptide ("PP"), vasoactive intestinal peptide ("VIP"),
growth hormone releasing factor ("GRF"), ACTH and others.
Some of these are very rare.
Apart from producing no currently
discernible hormone peptide, non-functioning tumors may include
those which produce PP ("PPomas") or neurotensin ("neurotensinomas),
as these hormones usually produce no symptoms. The most common
functioning pancreatic endocrine tumors are insulinomas followed
by gastrinomas, glucagonomas and VIPomas, respectively. Typically,
the symptoms produced by the excess secretion of the predominant
hormone in a given functioning endocrine tumor, drives the eventual
diagnosis.
With the exception of insulinomas,
most of the islet cell tumors have fairly similar characteristics-belying
the apparent differences caused by the large range of symptom
effects related to the secretion of such different hormones.
Histologically (under the microscope) they tend to be quite similar.
It is not possible to ascertain malignancy from the histological
appearance; malignancy is seen primarily as a function of finding
additional metastatic sites. Except for insulinomas, very roughly
about 60% of islet cell tumors are malignant. This rate contrasts
with about 10% of insulinomas which are eventually found to be
malignant. The sites of metastasis of islet cell tumors most
commonly are the liver and the lymph nodes in the vicinity of
the pancreas.
Insulinomas are islet cell tumors
which secrete an excess of (predominantly) insulin. These tumors
will typically first present symptoms between the ages of 40
and 50, are more common among women and tend to be small, solitary
tumors located in the pancreas itself. The clinical features
of this tumor are related to the effects of insulin-and thus
primarily demonstrate symptoms related to hypoglycemia which
are relieved by food intake. Other general symptoms include episodic
sweating, tremor and rapid heart rate, as well as hunger, nausea,
weight gain, and sometimes even central nervous system symptoms
(including rarely, seizures).
Gastrinomas over-secrete the
hormone gastrin. The clinical effect of this circumstance is
what has come to be called the Zollinger-Ellison syndrome, a
triad of signs and symptoms including atypical peptic ulcer disease,
gastric hyperacidity and hyper-secretion, and an associated islet
cell pancreatic tumor. About 2% of patients with non-healing
peptic ulcers (after receiving an appropriate therapy regimen)
are found to have Z-E syndrome with its attendant tumor. Most
patients are male (~60%) and the average age at diagnosis is
about 60 years.
Patients with glucagonomas tend
to present with mild diabetes and a severe dermatitis. These
tumors are frequently fairly large by the time of diagnosis,
sometimes greater than two inches in diameter. Approximately
70% of these tumors are malignant. About 80% of VIPomas are located
in the pancreas itself-the rest elsewhere. Over-secretion of
this vasoactive intestinal peptide causes watery diarrhea, and
low serum potassium and chloride levels. Only about 200 cases
of this kind of tumor have been described in the medical literature;
the majority are malignant by the time of diagnosis.
Carcinoid cancer is the most
common of the neuroendocrine tumors, with one-and-a-half diagnosed
cases per 100,000 of population, although anatomy at autopsy
demonstrates about 400 times those that are diagnosed clinically.
The symptoms and signs of carcinoid tumors range widely, and
depend on the location and size of the tumor, on the presence
of metastases, and secretions. They can appear to the surgeon
as firm nodules bulging into the intestinal lumen (can originate
from pancreas, lungs, thymus, appendix, and ovaries, etc.), with
possible local expansion, and possible metastases to mesenteric
lymph nodes, liver, ovaries, peritoneum, testes, prostate, spleen
and other anatomic locations. Carcinoid tumors can secrete any
number of hormonal, growth and other factors. Symptoms related
to the tumor and its factors may be intermittent and vague, but
the most common presentation is periodic abdominal pain sometimes
accompanied by malignant carcinoid syndrome, characterized by
flushing of the face, severe diarrhea, and an asthma episode.
The initial evaluation of patients often includes measurement
of such factors as serotonin, 5-HT, catecholamines and histamine,
and especially urinary 5-HIAA levels. In general, survival rates
for patients with carcinoid cancers are related to the size of
the primary tumor - and the degree of metastasis.
The natural history of islet
cell and carcinoic tumors tends to be favorable as compared with
pancreatic adenocarcinoma. For example, the median survival duration
from the time of diagnosis for patients with non-functioning
metastatic islet cell tumors approaches five years. The diagnosis
of islet cell tumors is aided by the different abnormal biochemical
profiles that they may present, which often leads to radiographic
means to try and locate the tumor. It would be a mistake to generalize
too much about attempts to locate these tumors. But generally,
dynamic CT scans with radio-contrast dye, octreotide scintigraphy,
transabdominal ultrasound, and selective visceral angiography
are all methods employed to elicit radiographic information about
the cancer, depending on individual circumstance.
Although they arise from similar
cells, these different types of neuroendocrine cancers all behave
somewhat differently. The standard treatments tend to be tumor-type
specific, but some general observations can be made. Immediate
treatment of the symptomatic conditions created by the over-secretion
of the hormone(s) may be appropriate. (For example, the use of
H2-blockers, omeprazole and even octreotide in gastrinomas).
The treatment of choice for localized islet cell tumors is generally
curative surgery. The treatment of metastatic islet cell cancer
disease, depending on the tumor type, will often include chemotherapy
involving such agents as streptozocin, 5-FU, doxorubicin, dacarbazine
and octreotide. Recently, there have been published in the medical
literature promising studies of aggressive surgery benefiting
select cases of metastatic neuroendocrine tumors.
Apparently isolated liver metastases
have been treated with such creative approaches as hepatic artery
embolization. This may reduce the nutrient blood supply to the
metastatic liver tumor (which tend to be rather vascular), but
this approach remains controversial. It is difficult per the
limits of today's radiographic methods (and even via direct inspection
at surgery) to fully appreciate the presence of small tumors
in the liver-thus there well may be more metastases that have
been undetected. Currently, there are studies employing techniques
of radioimmunotherapy to selected patients with metastatic islet
cell cancer, wherein radioactive elements have been conjugated
together with specific compounds (sometimes hormonal elements)
which are chosen for their properties that tend to selectively
target islet cell tissue. These are very interesting early studies
which hold the virtue of biologic plausibility, but the final
results of the efficacy of this approach is not yet fully known.
Some percentage of islet cell
tumors may be a part of several well-defined hereditary syndromes
in which the tendency exists for the development of tumors in
various (typically multiple) endocrine glands in the body, and
which are known as the multiple endocrine neoplasia (or "MEN")
syndromes. There are at least three such syndromes as presently
defined.
Recent Neuroendocrine Research Results
Carcinoid
& Neuroendocrine Select Abstracts
Neuroendocrine and Carcinoid
Clinical Trials
Neuroendocrine
and Carcinoid Links
9. What about
clinical trials?
General
Clinical trials are,
ideally, a part of a system in which a series of scientifically-controlled
experiments shepherd a plausible agent, combination of agents
or procedure through a process whereby the efficacy of the agent
or procedure is established or not. In the U.S. this process
is overseen by the Food and Drug Administration ("FDA").
Until more recently, when fast-tracking
has became more possible, the process of taking a potential agent
from the biochemical stage through final FDA approval could take
as long as 15 years. This process begins long before human testing.
Generally, moving the process into human testing is predicated
on successful animal results. It is then that the three phases
of human testing begins. A phase I clinical trial with human
subjects seeks to answer questions about whether a drug-agent
is reasonably safe for use by humans, it also may seek to learn
something of the biokinetics of the drug and seeks to try and
establish what the maximum tolerated dose of the drug is. These
are the only real aims of a phase I clinical trial, although
researchers will, of course, be looking for subtle indications
that the drug may show future promise.
Some fraction of phase I clinical
trials will move on to the phase II-which seeks to answer the
question as to whether the drug has, in fact, an apparent effect
against the cancer in question. Many potential drug therapies
go no further than phase II--as they show no real effect against
tumor. Successful phase II candidates move on to phase III clinical
trials that seek to determine how the new therapy compares to
existing therapies. This is the real test of a potential new
drug. Phase III clinical trials are controlled experiments whereby
patients with similar characteristics are assigned to receive
either the existing therapy or to receive the new therapy. After
a time, the results of the arms of test are then compared. If
the new agent shows similar or improved results as compared to
existing therapy, (after another step or two) it is often approved
for release by the FDA. There is even a phase IV to this process
which has to do with after-approval monitoring of the new drug
for side-effects, etc. as it makes its way into wider use.
Participation
The decision to participate
in a clinical trial is a big one and should not be take lightly.
At its very heart a clinical trial is an experiment. Consequently,
clinical trials contain inherent risk-both active risks and passive
risks. An example of an active risk might be encountering an
unexpected side-effect of the drug. An example of a passive risk
might include following a particular clinical trial protocol
which may call for being off all standard therapy for 28 days
(which is not uncommon) before beginning the trial.
On the other hand, the prognosis
of certain stages of pancreatic cancer is not great. Some of
the emerging treatments may appear to hold more promise than
existing ones. Approaching the possibility of participating in
a clinical trial in a carefully reasoned, intelligent manner,
depending on circumstance, may be a smart personal decision.
There are many issues to consider.
Am I a good candidate for a clinical trial? What emerging drug
or combination of drugs looks to be promising? Is it really (realistically)
more promising than existing therapy? Which phase of clinical
trial am I comfortable participating in? Which institution is
hosting the trial? What is their reputation? What is their location
relative to mine? Which physicians will be involved? What support
do I have?
And there are other issues -
many of them. Probably more than you can come up with on your
own. This is when a strong bond with your personal physician
can be of great service to you. Be sure to ask for aid and guidance
from your physician (and other health professionals) in helping
sort through these kinds of complicated decisions.
We include here links which may
cover more information about clinical trials.
DUNN
| NCI 1
Pancreatica
offers the largest listing of clinical trials for pancreatic
cancer. Link to our clinical trials database.
10. How do I
find the best doctor for me?
On the surface, one would idealize
the perfect physician for oneself as a medical blend of Albert
Einstein and Mother Theresa. But the truth is more complex because
we are more complex. In fact, it is our contention in this brief
summary that it is virtually impossible to generalize about what
qualities that you should be looking for in a physician (of course
that won't keep us from trying).
The primary reason for this is
that each patient's circumstance is different. The range of variation
in patients' situations is extremely large. For example, issues
include the extent of disease, patient personality, desire-to-live,
financial circumstance, the possible existence of a primary caregiver
and the possible existence of a web of personal emotional support.
Personal qualities include depression, acceptance, resignation,
equanimity, spirituality, pugnacity, anger, a willingness to
fight, etc. These are not general qualities-they are highly individual.
Oncologist
The specialist who deals
with cancer is called an oncologist. Generally, an oncologist
has specialized in the medical field of Internal Medicine, and
has further become a sub-specialist in oncology. This training
is long and arduous, and thus tends to indicate an extraordinary
amount of dedication. And oncologists have chosen to work with
people who have cancer; this tends to show an orientation to
compassion. Often the oncologist is the leader or at least an
integral part of a team which clusters around an individual patient,
whose team members also may include a surgeon, a radiologist,
oncology nurses, social workers, nutritionists and others. For
the most part, we are addressing the assessment of oncologists
in this portion of the answer.
First, you may already have a
physician. And it may well be that this is the best person for
you to work with for a variety of reasons: you are presumably
already known, you may already have a sense of the character
of this oncologist, practical considerations may have led you
(in the context of the health-care system) to this person, they
may have come well recommended, there may be issues of convenience,
of location, etc. But apart from all this, here are some things
to consider in evaluating a physician.
 1. Congruity
Is the physician's overall orientation congruent with your deepest
wishes. For example, has the physician dismissed the idea of
making extraordinary efforts, when you stand ready and willing
to fight. Conversely, is the oncologist suggesting big efforts
(for example, having you enroll in clinical trials) when you
are more resigned to circumstance. Only you will know what your
real desires are, but they should generally comport with the
general orientation of your physician. Of course, this is one
time for direct communication. It may be that, even though each
of your individual personal orientations are not completely in
sync, this gulf can be bridged by honest and forthright communication.
2. Competence
It is difficult for patients to evaluate the competence of
their physicians. And there is not one good way to accomplish
this. Word of mouth can be useful; but it also can deceiving.
Our view is that though physician referral can be very useful,
even physicians are often not in the best stance to evaluate
the functioning competence of their fellow doctors. Sometimes
nurses are in a good position to see how physicians function:
how thorough is their hospital work, do they come in at 3 a.m.
when needed, etc. Certain institutions tend to attract great
physicians. These approaches can all give pieces to the puzzle,
but they each have their drawbacks. So to a great extent you
are on your own with this, using a variety of approaches to try
to come to an understanding.
One approach, again with potential
pitfalls, is to use aggregated data which exists about individual
physicians on the Internet. For example, though it is possible
to read too much into this data, the American Medical Association has physician
profiles about most practicing physicians in the U.S., including
their medical school and training institutions. The American Board of Medical Specialties provides
information about certified specialists (in the U.S.) These are
physicians who have generally undergone written specialty examinations
after meeting certain training requirements, and are thus "board
certified" in one or more specialties. And, with limitations,
some U.S. states
carry certain disciplinary information in regard to certain physicians.
3.
Compassion
Kindness and wisdom are invaluable qualities in a physician.
At difficult points, a strong bond with a compassionate and trusted
physician can make every difference.
Surgeon
One stands in awe of the surgeons who regularly perform the Whipple
procedure and other operations related to pancreatic cancer,
as these are among the most arduous of operations - requiring
great stamina and skill. Increasingly, the site of the performance
of these surgical procedures in regard to pancreatic cancer in
the U.S. has tended to move to major medical centers. And even
there, more and more of these procedures are increasingly being
done by fewer surgeons -- who may tend to specialize in these
kinds of oncology surgeries. This is not always true, and there
are accomplished surgeons in U.S. private practice who are renown
for their work in pancreatic cancer.
Each of the three "C's"
as listed above in regard as to what one might look for in an
oncologist also applies to surgeons: congruity, competence, and
compassion. In additional we would add a fourth "C"
for surgeons: Common. How commonly does the surgeon do this procedure.
All things being equal (which they rarely are), you would generally
be advised to work with a surgeon who performs these complicated
procedures, for example, twice a month -- rather than twice a
year. Of course, for any rule that one might make in areas like
this, one can certainly find exceptions.
Second Opinions
Finally, there is the
issue of second opinions. There are a number of instances where
second opinions are highly recommended. The microscopic histology
of many pancreatic tumors is complex. There can be as much art
as science in some of the diagnostic and therapeutic considerations
in pancreatic cancer. If there is any thought of seeking a second
opinion, do not hesitate to do so. Your physicians will (or should)
understand. There exist sites on the Internet about this topic.
We have selected a couple of representative links.
Cancer Second Opinions
The American Cancer Society
11. How do I
locate the best institution for me?
This is a companion to the previous
FAQ answer about finding the best physician "for me."
Again, there is no simple answer to this question. If you have
found a trusted oncologist at your local hospital, and are not
interested in making rather extraordinary efforts, then your
local hospital will probably be the best possible institution
for you. On the other hand, it is true that there exist exceptional
cancer referral institutions-and that exceptional physicians
and researchers tend to cluster to these research institutions.
It is also true that interesting clinical trials may be occurring
at one or another institution-this too may be a stimulus for
researching other institutions.
In a sense, this is a difficult
topic to discuss, as the range and even perhaps quality of the
treatment options which exist at some of these research-oriented
comprehensive cancer centers is often much more sophisticated
than that which can reasonable be expected from a community hospital.
And, in saying this, we do not wish in any way to disparage the
remarkable efforts and comfort which are routinely given to patients
through the efforts of many under-appreciated professionals (and
non-professionals) at local community hospitals.
It is important to realize that
there are pros and cons related to moving beyond one's local
hospital, and for many many people with pancreatic cancer, the
disadvantages will truly be seen to outweigh the advantages.
Perhaps the biggest disadvantage is the distance/location problem.
The logistics alone can be a serious deterrent to seeking care
outside of one's local community.
There are Internet resources
which can help to perhaps gain a better sense of the geography
of this topic. For a fairly full list of community centers, the
Association of Community Cancer Centers has
a searchable database. Often the cancer centers and oncology
departments of the major teaching hospitals and medical schools
in a U.S. State offer advanced care options. Here is a site which
links to the medical schools in U.S. States and Canada.
The U.S. National Cancer Institute
though the National Institute of Health identifies a small number
of institutions in the U.S. as comprehensive cancer centers. Additionally,
though there is some duplication with NIH-designates, the members
of the National
Comprehensive Cancer Network are identified in this map of
the U.S.
The U.S. News and World Report
(a news magazine) periodically ranks what it sees, according
to its own criteria, as the best cancer institutions in the U.S.
Here are three links to cancer
institutions from around the world.
World 1
| World
2 | World
3
These approaches which rank cancer
centers have to be viewed with some caution and a little skepticism.
The best institution for you will be the one which is consistent
with your circumstance. And in many instances, it will turn out
to be your local hospital with your trusted oncologist together
with local resources.
12. What are
some of the main troubling symptoms and their treatment?
A. Selected symptoms related
to adenocarcinoma of the pancreas
1). Pain
The fear of pain is the leading concern of most patients with
advanced pancreatic cancer. Often a vague mid-abdominal pain
is one of the first symptoms of pancreatic cancer. There is no
fixed pattern, but often, over time, the pain of pancreatic cancer
may move or radiate more through the abdomen to the back area.
Inadequately treated pain can have profound negative effects
on the psychosocial and even physical well-being of patients,
and may subject patients to unnecessary anxiety and even depression.
On the positive side, there have never been more options for
good pain relief, and in the vast majority of patients excellent
pain control can be maintained by cooperative efforts with the
help of an enlightened health-care team.
Since the publication of the
World Health Organization's suggested three-step analgesic "ladder"
for pain control in 1986, pain is often classified as mild, moderate
or severe. Mild pain is generally treated with a non-opioid analgesic
agent (one which is not an opium-derived or opium-like narcotic)
such as a non-steroidal anti-inflammatory drug like ibuprofen
(Motrin). Moderate pain is treated with a "weak" opioid
such as codeine with or without a non-opioid analgesic and with
or without another adjuvant agent (such as an anti-anxiety drug).
And severe pain is treated with a strong opioid such as morphine
with or without a non-opioid analgesic and with or without another
adjuvant agent (such as an anti-anxiety drug).
Examples of strong opioids include
fentanyl (Actiq lozenges on a stick or duragesic transdermal
patches), hydromorphone (Dilaudid), oxymorphone, meperidine (Demerol),
methadone, and morphine. In addition to selecting the optimal
agent(s), there are routes of administration to be considered.
70-90% of pain can be controlled by oral opioids. Other routes,
for example, include those of injection (intravenous, subcutaneous
or intramuscular), skin patches, rectal suppositories and pump-delivered
(continuous or on-demand). The aim is to find an optimal agent(s)
to be given at the optimal dose and via the optimal route of
administration. The current concept among pain specialists is
that the cancer patient should have around-the-clock pain relief.
In addition, provisions are made to administer a fast-acting
agent should the occasion occur of any "break-through"
pain.
A specific palliative step in
pancreatic cancer may include a nerve block of the celiac nerve
plexus (located in the back/abdomen area where many patients
feel pain) via injection with alcohol or other agent. There are
other possible interventions including subarachnoid or epidural
blocks (both in the spinal space); and even further interventional
and surgical measures which are available.
Alternative or non-invasive methods
on the part of patients themselves exist, which may invoke mind-body
control, including those of acupuncture, massage, biofeedback,
relaxation, visualization techniques, hypnotherapy and others.
A thoughtful, integrated approach
toward pain will result in very good pain control for almost
all patients with pancreatic cancer. A couple of links to online
sources of information regarding cancer pain management are provided.
Pain
control 1 | Pain control 2 .
2). Gastrointestinal symptoms
As the pancreas is an integral part of the digestive system,
it would stand to reason that gastrointestinal symptoms would
figure prominently in pancreatic cancer.
Nausea
and vomiting may
be a problem in up to 40% of pancreatic cancer patients. The
cause of these symptoms are varied-and can range from, for example,
a reaction to chemotherapy or radiotherapy--to being a sign of
mechanical obstruction of the small bowel. Consequently, the
reason for the nausea and vomiting (sometimes referred to as
"emesis") needs to be sought out--and the underlying
cause dealt with appropriately. In addition, anti-emetic agents
may be prescribed. High-activity anti-emetic agents work as an
antagonists to type-3 serotonin receptors and include such drugs
as granisetron (Kytril) and ondansetron (Zofran). The anti-emetic
activity of metoclopramide (Reglan) is now thought to be as both
a serotonin and dopamine antagonist. Corticosteroids (such as
dexamethasone) are also potent anti-emetics and may be used selectively
in combination with serotonin antagonists to good effect. Older
agents with generally lower anti-emetic activity, including the
phenothiazines (such as phenergan or compazine), butyrophenones
(such as Haldol) and the cannabinoids (such as Marinol) and others
may have their place in selected circumstances. The actions of
each of these agents is somewhat different, and they each have
side-effects which must be considered.
Constipation is a frequent complication of opioid
therapy, and its prevention should begin at the onset of opioid
therapy. Other causes of constipation in pancreatic cancer patients
may include such elements as a low fiber diet, diminished fluid
intake, diminished physical activity and postural effects from
bed rest. More serious causes may include various metabolic abnormalities
and even bowel obstruction. The treatment is various, but should
include evaluating and correcting any underlying problems, insuring
adequate fluid intake, increasing physical activity if possible,
giving laxative drug therapy where appropriate and providing
enemas as needed. Laxatives include such agents, for example,
as lactulose, Senokot, colace and dulcolax.
Indigestion,
diarrhea and a change in bowel habits are not uncommon in pancreatic cancer. The causes
can range from the more mundane to the serious--and may, for
example, include laxative overuse, malabsorption, anxiety or
stress, infection, medication side-effect, radiation therapy,
the effect of the cancer itself, surgery, pancreatic enzyme deficiency
-- and can even represent a sign of bowel obstruction. The treatment
is individual, but should include evaluating and correcting any
underlying problems. Food and fluid regulation are likely required.
And anti-diarrheal medication may be indicated.
3). Nutrition and weight loss
Weight loss and muscle wasting (cachexia) are common and occur
in over 90% of patients with pancreatic cancer. These phenomena,
apart from physiological disadvantage which contribute to fatigue
and weakness, often have a pronounced deleterious effect on such
factors as a patient's sense of well-being. Contributors include
anorexia, nausea, other gastrointestinal symptoms, depression,
the side-effects of chemotherapy, surgery, new dietary constraints,
early satiety (sense of stomach fullness), medical procedures
and perhaps most importantly the metabolic effects of the cancer
itself. Some patients are unable to tolerate a diet which is
high in fat and protein, and in others the onset of diabetes
may occur.
These factors may have significant
consequences on patients and their caregivers as, in the midst
of these matters, a diet which is both palatable and effective
is implemented. The help of a nutritionist is useful, almost
mandatory. Adequate calories are required, including an adequate
balance of protein, fat and carbohydrates. Some nutritionists
recommend sources of omega-3 fatty acids. Vitamins and minerals
may need augmentation. Pancreatic enzymes may be prescribed.
Adequate fluid intake is important. The diabetes, if present,
will need to be controlled. High-calorie liquid dietary supplements
are often required. Intelligent experimentation with such measures
as more frequent, smaller food portions can be helpful. The National
Cancer Institute has provided access to an online guide entitled
Eating Hints for Cancer Patients.
The use of appetite stimulants
such as megestrol (Megace) and even (according to some experts)
corticosteroids (such as dexamethasone), as well as cannabinoids
may be helpful in selected patients.
4). Symptoms secondary to
bile duct obstruction
Because the tumor mass of ductal adenocarcinoma most commonly
arises from the head of the pancreas (and in areas adjacent to
the head of the pancreas) which are the sections where the bile
duct joins with the pancreatic duct, the normal flow of the bile
duct is often obstructed, thus disrupting the natural deposition
of the bile fluid (including its bile salts and pigments) into
the small bowel. This bile duct obstruction causes a back-up
of the bile pigment into areas where it shouldn't normally go---creating
the clinical symptoms of jaundice with its attendant yellowish
skin coloration and other associated changes, and which is often
accompanied by a loss of appetite (anorexia) and by the symptom
of unrelenting and often debilitating pruritis-itching of the
skin.
Additionally, the lack of bile
salts which are now unavailable for normal digestive and other
bowel processes, can result in complex physiological interactions
leading to liver and immune dysfunction. This interruption of
normal bile deposition may also disrupt the absorption of fat-soluble
vitamins and the conjugation of endotoxins, thus leading to possible
blood coagulation difficulties, malabsorption syndromes and even
kidney failure. Also, up to ten percent of so affected patients
may develop cholangitis (an inflammatory condition of the biliary
tree with often very serious consequences).
The treatment for this bile duct
obstruction is some form of biliary bypass procedure. The majority
of patients who receive such a procedure will experience relief
of anorexia and jaundice, and will tend to live longer--in a
more comfortable fashion. This bypass procedure is done via surgery
and/or with the application of stents (inner wall prosthetic
supports). The biliary stent prosthesis, in selected circumstances,
may be placed via endoscopic route, without the necessity of
resorting to full surgery. There are controversies in this area
of treatment which are not yet resolved, none of these treatment
options is without complication and it all is highly dependent
on the individual situation. But progress has been made and options
continue to improve, to the benefit of affected patients.
5). Ascites (increased abdominal
fluid)
In some pancreatic cancer patients, there can be a troubling
large collection of fluid in the abdominal cavity itself, which
increases abdominal girth. This is called ascites (pronounced:
as-site-ees), sometimes referred to as malignant ascites. The
true cause of this fluid build-up is not fully understood, and
may vary from person to person--but it is presumably often due
in part to factors related to the existence of lymphatic or peritoneal
metastases.
Some physicians will prescribe
diuretic medication which may work well in selected patients,
but which also can give mixed results. Additionally, another
approach is to offer patients with ascites an abdominal Tap (or
paracentesis), in which a special needle is inserted directly
into the abdominal cavity and the fluid is drawn off. There are
some risks to this procedure including the possible introduction
of infection into the abdomen, but generally this procedure is
surprising well-tolerated. Unfortunately--often--with progression
over time, this abdominal tap procedure may need to be increasingly
repeated. There do exist a number of very clever surgical shunting
procedures which in selected circumstances are occasionally employed,
whereby through changes made to anatomic "plumbing,"
the ascites fluid is internally re-routed back into the body's
own vascular system.
6). Fatigue
Fatigue can be a early symptom of pancreatic cancer, manifesting
even before diagnosis. Sooner or later, the majority of pancreatic
cancer patients indicate fatigue as a significant symptom for
themselves. Typically described as a loss of customary energy
levels and even as affecting mental processes, fatigue can be
so severe as to be debilitating.
The range of causes of fatigue
under these circumstances is very large and can include such
factors as the cancer itself, sleeplessness (possibly due to
pain or for other reasons), anemia, chemotherapy side-effect,
anxiety or depression, medication side-effect (including pain
medication), infection, electrolyte disturbance, and/or dehydration.
The treatment of fatigue is first
directed at trying to eliminate any correctable medical or psychological
underlying causes. This may include the adjustment of medications.
Attention should be given to those factors which help promote
adequate and restorative sleep. Short-term pharmaceutical aids
to sleep may be prescribed. Hypnotic drugs such as Ambien (zolpidem
tartrate) and Sonata (zaleplon) are sometimes used for these
purposes.
Underlying psychological matters
should be addressed. If possible, where appropriate, patients
are encouraged to remain physically active, but not to overstep
reasonable activity bounds. Some physicians will prescribe psychostimulant
drugs in selected instances. But generally, the primary approach
remains to take the symptom of fatigue seriously and to try,
where possible, to identify and remove specific underlying causes.
B. Selected symptoms related to chemotherapy
Information on the actions and
side-effects of commonly used cancer chemotherapy drugs can be
found at: CancerSource
Some of the more common side
effects of fluorouracil (5-FU) include: decreased white blood
cell and platelet counts, darkening of the skin and fingernail
beds (and brittle fingernails), dry skin, nausea and vomiting
(and diarrhea), hair loss, increased sensitivity to the sun and
sores in the mouth area. Some of the more common side effects
of gemcitabine include: decreased white blood cell and platelet
counts, nausea and vomiting, abnormal values of liver-function-tests
and fatigue.
The treatment of these and other
chemotherapy-related symptoms will not specifically be addressed
here. The U.S. National Cancer Institute offers access to an
online booklet which contains general information
on chemotherapy, and which further includes general suggestions
regarding basic care of the more common side-effects of chemotherapy.
13. Where can
I find support?
In the U.S. there exist in most
communities, often loosely clustered around community hospitals,
a number of resources for cancer patients including access to
local support groups, and often access to such assets as patient
resource centers and libraries. Also, medical personnel will
generally have insight regarding local groups. Books are freely
available in local libraries and in medical libraries. National
organizations exist such as the American Cancer Society and the
National Coalition for Cancer Survivorship. Local chapters of
national organizations may be available.
Online resources for information
and direction exist in a number of places on the Internet. The
National Cancer Institute has information at several related
web-sites. NCI 1 | NCI 2 | NCI 3
Information for caregivers are
included at such sites as: Oncolink | Cancer.gov
Online discussion groups exist
at: Hopkins
| ACOR
And finally, last but not least,
the Pancreatic
Action Network (PanCAN) which is a national advocacy group
devoted to the fight against pancreatic cancer and has local
chapters in selected locations.
14. How do
I approach certain financial and legal matters?
Financial and legal issues can
affect patients as well as their caregivers. The information
as offered below and through hypertext links are for educational
purposes only. Any financial or legal matters should be reviewed
by relevant professionals, including attorneys.
Financial
There are some common general
financial and related issues which affect cancer patients and
which are addressed in two National Cancer Institute sites.
NCI
1 | NCI 2
Information on U.S. social security
matters is found at: SSA
Health insurance overview including
information on the U.S. 1986 COBRA act which gives certain protections
regarding the retaining of term-limit rights to health insurance
is found at:
INFO
| U.S.
COBRA act of 1986
General information on how to
get medicines at lower cost (including for free) is found at:
DRUG | NEEDYMEDS
Airlines often offer surprisingly
inexpensive compassionate use rates. Certain major cancer referral
centers in the U.S will offer inexpensive air flight rates (to
and from their facilities) through linked booking services. In
addition, a number of services offer free or very inexpensive
private airfare to people in need. AIR 1 | AIR 2 | AIR 3 | AIR 4
Legal
General legal advocacy in medical
matters is found at: LINC
| ADVOCATE
More specific advocacy and information
about the Americans with Disabilities Act is found at: JANWEB.
15. Where can
I find more information on hospice and end of life issues?
There are a number of sites which
carry information on hospice care. The National Hospice and Palliative Care Organization,
in addition to other resources, has a geographically-based searchable
database of U.S. hospice programs. More hospice information is
found at Hospice
Net.
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