Hi again tmml-ga. Thanks for the clarification. As Pafalafa
mentioned, the rarity of small bowel tumors has meant that very few
clinical trials have been performed looking at them specifically. The
few studies that have been done are discussed in the eMedicine article
cited by Pafalafa:
http://www.emedicine.com/MED/topic2651.htm
There is, as you suggest, a feeling that treatments that are effective
for colon cancers might be effective for small bowel tumors. Any
clinical trials that are currently underway (or about to start) can be
found at this site:
http://www.clinicaltrials.gov
An appropriate search would be to click on "List by Condition" then
"By Disease Heading" then "Cancers and other Neoplasms."
You can further limit this search by searching for "Pennsylvania."
This will show you clinical trials that are studying intestinal
cancers in that are accepting patients in Pennsylvania. All of the
studies currently listed are focusing on colorectal cancer, but night
consider inclusion of your uncle, depending on the inclusion and
exclusion criteria of their particular study. As a shortcut, you can
find the search results here (Click the "Download" link):
http://ez-files.net/download.php?file=c3b8b8ca5ea61d26d7795d70124bd89c
_____________
A brief review article was recently published on small bowel tumors in
patients with Crohn's disease. You can find the full text (free)
here:
Kronberger IE, Graziadei IW, Vogel W. Small bowel adenocarcinoma in
Crohn?s disease: A case report and review of literature. World J
Gastroenterol 2006; 12(8): 1317-1320.
http://www.wjgnet.com/1007-9327/12/1317.asp
PDF format:
http://www.wjgnet.com/downpdf.asp?url=/1007-9327/12/1317
Unfortunately, this article has little to say about therapy.
_____________
Here is another article, not available freely online, that describes
the therapies and treatment outcomes at one Austrian institution over
30 years:
Ojha A. Zacherl J. Scheuba C. Jakesz R. Wenzl E. Primary small bowel
malignancies: single-center results of three decades. [Journal
Article] Journal of Clinical Gastroenterology. 30(3):289-93, 2000 Apr.
You can request a reprint from Dr. Zacherl at this address:
johannes.zacherl@akh-wien.ac.at
The main therapy in the patients in the above study was surgery:
"Surgical resection was the main therapy modality (n = 57). Jejunal or
ileal segment resection (n = 39), including the mesentery with all
involved segmental vascular trunks, reached free resection margins of
at least 5 cm. Primary end-to-end anastomosis was carried out in all
patients. Small bowel segment resection was extended by transversum
resection in two, appendectomy in two, colotomy and polypectomy in
one, splenectomy in one, omentectomy in one, cholecystectomy in one,
liver resection in one, gastrotomy in one, and ovariectomy in two
cases. Furthermore, six patients underwent right hemicolectomy and one
patient, ileocecal resection. Eleven patients underwent partial
pancreaticoduodenectomy and regional lymphadenectomy for malignancies
located in the duodenum. In four cases the Whipple procedure was
extended by splenectomy (n = 1), gastrectomy and splenectomy (n = 1),
transverse colon resection (n = 1), and ileocecal resection (n = 1).
Five patients underwent explorative laparotomy without resection,
including transversotomy and sample excision in one patient,
cholecystectomy in another, and resection of liver metastasis in a
third. In two cases, bypass anastomosis was required."
"Of all patients, 34 underwent palliative surgery (R1-resection with
microscopic tumor residuum, R2-resection with macroscopic tumor
residuum, or no resection) and 30 underwent radical resection (R0). In
ten cases, surgery was performed under emergency circumstances-eight
due to intestinal obstruction and two due to tumor perforation."
_____________
Another review article, with a broader overview, can be found here:
Hutchins RR. Bani Hani A. Kojodjojo P. Ho R. Snooks SJ. Adenocarcinoma
of the small bowel. [Review] [103 refs] [Journal Article. Review] ANZ
Journal of Surgery. 71(7):428-37, 2001 Jul.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11450920&query_hl=23&itool=pubmed_docsum
This article is also unavailable for free online. You can request a
reprint from Dr. Hutchins here:
rob@rhutchins.fsnet.co.uk
As this article again states, surgery is the primary mode of treatment:
"The mainstay of treatment of small bowel cancer is surgical
resection. This may be curative or palliative and the type of
procedure depends on the site of origin of the tumour. "
The above article also gives one of the few discussions of
chemotherapy and radiation therapy in the treatment of these tumors.
Here is an excerpt:
"The rarity of small bowel tumours and the variety of treatments
offered contributes to the lack of evidence for benefit from
chemoradiotherapy in this disease. Only one study has looked at
preoperative treatment.90Thirty-one cases including both pancreatic
and duodenal tumours were offered radiotherapy (1.8Gy per day up to
50.4Gy) combined with two cycles of chemotherapy (5-fluorouracil
(5-FU) in two courses and one dose of mitomycin C). All four cases of
duodenal cancer were then resected and the patients are alive at 12,
23, 35 and 90 months. All four patients demonstrated pathological
evidence of complete response.
In the National Cancer Data Base series only 8.2% of patients
underwent radiotherapy treatment for localized disease, increasing to
15.6% for regional involvement and 11.5% for distant metastases.
Chemotherapy was offered to 14.2% of those with local disease, 35.4%
with regional disease and 36.9% with distant metastases. Because of
the small numbers of patients involved and the potential for selection
bias little can be made of the survival figures, but there was better
survival for surgery alone (median survival 47.8months) compared with
surgery and chemotherapy. Combination treatment (median survival
23.6months) with surgery appeared to affect survival better than
single-modality therapy (median survival: 15.9?17.2months).[6]
Most chemotherapy regimes have consisted of 5-FU alone or combinations
of 5-FU and multiple other drugs including
doxorubicin, cisplatin, lomustine (CCNU), carmustine (BCNU), mitomycin
C and cyclophosphamide. Adjuvant regimes have
been reported on a case report basis only. One death occurred from
sepsis in a report by Haq etal.,[91]and another patient survived to 18
months before recurrence.[92] Jigyasu reported a series of 14 patients
with 21 single- and multiple-agent regimes.[93] There were nine
patients with stable disease, two had minimal responses and one
patient had partial response.
The Royal Marsden experience showed that protracted venous infusion of
5-FU has activity in primary adenocarcinoma of the
small bowel.94 In this study treatment was with either mitomycin C or
epirubicin and cisplatin. Treatment was well-tolerated
with only two grade 3 toxicities (plantar?palmar erythema) both
responding to dose reduction. All treatment was palliative with
a 37% partial or complete response rate in eight patients as assessed
by CT scanning. Isolated reports have described very good responses to
5-FU therapy or combination 5-FU and methotrexate. One report has
described the complete disappearance of small bowel metastases with
5-FU therapy.[95] Another study of 73 cases, however, demonstrated no
survival benefit with adjuvant therapy.[4]
No recommendations can be made at present on whether or not adjuvant
therapy should be offered or whether palliative
therapy has an effect on survival. Randomized trials probably
including new agents are necessary. The role of radiotherapy is as
yet undefined. Small bowel cancers are thought to be relatively
radioresistant [96] but there may be a place for pursuing its role in
prevention of local recurrence either postoperatively or as an
intraoperative therapy."
To summarize the above... The survival numbers in these studies are
not likely to be very accurate (i.e., predictive) because of the small
numbers of patients. Combination chemotherapy seemed to help as
opposed to single agent chemotherapy. The best combination was 5-FU
combined with other drugs, including the CCNU regimen, BCNU regimen,
mitomycin C, and cyclophosphamide. 5-FU alone has been shown to have
some effect in these cancers, but was better with mitomycin C or
epirubicin plus cisplatin. Methotrexate has also been used with 5-FU.
The chemotherapy was generally well tolerated.
_____________
Here is another good review article on small bowel tumors, including
those in the context of Crohn's disease:
Dabaja BS. Suki D. Pro B. Bonnen M. Ajani J. Adenocarcinoma of the
small bowel: presentation, prognostic factors, and outcome of 217
patients. [Journal Article] Cancer. 101(3):518-26, 2004 Aug 1.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15274064&query_hl=25&itool=pubmed_docsum
This one is also not freely available. You can request a reprint from
Dr. Ajani at MD Anderson:
jajani@mdanderson.org
Here is what this article has to say about the 20 year experience in
treating these tumors at one of the major centers in the US:
"Surgery as a primary definitive therapy was performed in 146 patients
(67%). These surgeries included a Whipple procedure in 36 patients
(17%) and some type of resection, which varied by the surgeon, in 110
patients (51%). Only 1 of the 36 patients who underwent the Whipple
procedure died of postoperative complications on Day 29 after surgery.
Adjuvant chemotherapy was administered in only 59 of the 217 patients
(27%). Chemotherapy as a palliative treatment for locally advanced or
metastatic carcinoma not treated surgically was given to 48 patients
(22%). No treatment was offered to 23 patients (11%) (Table 7). The
primary tumor site was found to significantly influence the primary
modality of treatment offered and surgical resection was performed
more often in patients with distally located adenocarcinoma (i.e., the
jejunum and ileum) compared with patients with duodenal adenocarcinoma
(83% vs. 57%). Surgery was performed less often in patients age 60
years (n = 98 [73%]) versus patients age < 60 years (n = 48 [58%]; P =
0.02)."
The authors present their treatment statistics with respect to
treatment type and stage of disease in Table 7, which you can see
here:
http://img122.imageshack.us/img122/6307/tbl70ej.png
There are also figures showing survival vs. stage of disease, etc.
Overall survival with respect to treatment is given in Figure 5, which
you can see here:
http://img208.imageshack.us/img208/8772/fig57bv.png
They find that there may be a role for chemotherapy, given that
failure is usually due to distant disease recurrence:
"An early and accurate diagnosis is crucial to an acceptable outcome
in patients with SBA. This allows the surgeon to perform a curative
radical surgery, which, in our analysis, was the most important
prognostic factor. Distant disease recurrence remains the leading
cause of death, suggesting a role for adjuvant chemotherapy."
_____________
The National Cancer Institute has a good summary of the current status
of diagnosis and therapy of small bowel tumors here:
http://www.cancer.gov/cancertopics/pdq/treatment/smallintestine/healthprofessional/allpages/print
The Massachusetts General Hospital also has a good summary of
resources for patients with all types of GI tumors:
http://www.mgh.harvard.edu/cancer/crr/types/gi/info.asp
_____________
Drs. Alessandro Fichera and Fabrizio Michelassi summarize the current
thinking on the treatment of small bowel tumors in Chapter 79 of
Clinical Oncology:
"Treatment for advanced locoregional and distant disease includes both
medical and surgical modalities. In one published study, after
complete resection of all known disease a 73% actuarial 5-year
survival rate was obtained, compared to 29% in patients that were
deemed unresectable.[95] Therefore surgery should be indicated in
patients with resectable metastatic disease for potential cure or at
least meaningful palliation. Orthotopic liver transplantation (OLT)
has been used in the treatment of metastatic neuroendocrine tumors to
the liver. [96] [97] [98] [99] In a recent report all patients had
complete symptomatic response initially, but tumor recurrence was
noted in 6 of 11 cases at a median of 11 months, with a mortality rate
of 45%.[98] These discouraging results have limited the use of OLT
for metastatic carcinoid tumors.
The role of multimodality therapy, including alpha-2b interferon and
octreotide, for metastatic carcinoid remains limited.[100] [101] [102]
Interferon seems to provide symptomatic control in up to 70% of
patients with carcinoid syndrome [101] and to increase 5-year survival
rates to 71% in patients who continued treatment for 1 year compared
to 37% of those who stopped the treatment.[100] The addition of liver
chemoembolization has not been shown to have a significant effect on
survival in patients with metastatic disease to the liver[100] [101]
but may have a role in controlling or decreasing the symptoms
associated with carcinoid crisis. Octreotide has been effective in the
treatment of patients with carcinoid syndrome by improving diarrhea in
up to 83% of the patients and abolishing flushing and wheezing, but
has no effect on survival.[102] [103] [104] In consideration of the
slow growth rate of many carcinoid tumors, patients with distant
metastatic disease can also undergo resection for debulking and
palliation of symptoms.[95] [105] [106] [107] For those unfortunate
individuals with extensive unresectable disease, the indications for
surgical intervention are limited to the occurrence of obstruction,
perforation, and bleeding. Radiation therapy has not been proved to be
effective in either the adjuvant or palliative setting."
A. Fichera and F. Michelassi in Abeloff: Clinical Oncology, 3rd ed.,
Copyright © 2004 Churchill Livingstone, An Imprint of Elsevier .
Pages 1871-1873.
=================
In terms of alternative therapies, none have been studied in
sufficient detail in colon cancer or small bowel cancer. There are
some possibilities out there:
Probiotics:
"Lactobacillus and Bifidus species are the ?good? or beneficial
bacteria that live in the colon. By producing lactic acid and hydrogen
peroxide they inhibit the growth of ?bad? bacteria. Several studies
suggest that administration of bifidobacteria or lactobacilli alone
can alter colonic microflora populations to decrease early
preneoplastic lesions and tumors.[19] These probiotics are also being
studied for their potential in inhibiting an enzyme activated by fatty
foods that is thought to trigger malignant changes potentially leading
to colon cancer.
Probiotics may be beneficial in high-fat diets but further research is needed.
Dosage.
A supplement should contain at least 1 billion organisms and should be
taken on an empty stomach.
A product called Culturelle provides viable Lactobacillus GG. It may
be obtained on the producer?s Web site: www.culturelle.com. The usual
dose is 1 capsule daily (see Chapter 97 , Prescribing Probiotics).
Precautions.
Long-term use of these supplements needs further study. Probiotics may
best be used after proper evaluation of the intestinal flora of the
patient. Probiotics should be avoided in immune-compromised patients."
____________
Folic Acid
"Studies show an inverse relationship between the incidence of colon
cancer and dietary intake of folate. In the Nurses? Health Study in
nearly 90,000 nurses, women who took a daily multivitamin with 400 ?g
of folate over a 15-year period showed a 75% decrease in risk of colon
cancer.[17] It is thought that the folate exerts its protective effect
by reducing damage to DNA.
Dosage.
400 ?g of folic acid daily. This dose is found in most multivitamins.
Folate is also abundant in green leafy vegetables such as spinach,
kale, and chard. Other sources include legumes, especially lentils,
and broccoli, cabbage, and whole grains.
Precautions.
Elevated serum folate levels may be associated with altered sleep
patterns, irritability, vivid dreaming, lower seizure threshold,
nausea, flatulence, and zinc depletion."
____________
Calcium
"Most human studies show an inverse relationship between calcium
supplementation or high-calcium diets and the risk of colorectal
cancer or colorectal adenomas. One large study showed a decreased risk
of adenomatous polyps in people who took 1200 mg of supplemental
calcium.[18] It is thought that calcium may bind to bile acids and
fatty acids in the bowel lumen, thus decreasing proliferation of
colonic epithelial cells and tumor formation.
Dosage.
1200 mg of supplemental calcium a day. Calcium citrate has been found
to be best absorbed from the gastrointestinal tract, but most studies
have used calcium carbonate, which is generally cheaper. The citrate
form is best for patients older than 65 years of age.
Precautions.
Oral calcium can cause constipation and gastrointestinal irritation."
All of the above excerpts are from the following reference:
Rakel: Integrative Medicine, 1st ed., Copyright © 2003 Saunders,
An Imprint of Elsevier . Pages 551-553.
=================
In terms of the best physicians, there are multiple tertiary and
quaternary care centers throughout the US and Canada. Your uncle
happens to be in a large city near two large cancer centers (Fox Chase
and UPenn), so I will focus on this area, with a few other options as
well.
Dr. Neal J Meropol, MD
Director, Gastrointestinal Cancer Program
Director, Gastrointestinal Tumor Risk Assessment Program
Fox Chase Cancer Center
333 Cottman Avenue
Philadelphia, PA 19111-2497
1-888-FOX CHASE (1-888-369-2427)
Neal.Meropol@fccc.edu
Phone: 215-728-2450
http://www.fccc.edu/physician_directory/medical/meropol.html
An oncologist is the person who typically coordinates the care of
cancer patients as they receive surgery, chemotherapy, radiation
therapy, etc. Dr. Meropol is a national and international leader in
the field of GI cancer and would be an excellent place to start. You
can read some general information about the GI cancer program at Fox
Chase here:
http://www.fccc.edu/docs/sci_report/Meropol.pdf
____________
Dr. Louis M Weiner, MD
http://www.fccc.edu/physician_directory/medical/weiner.html
Dr. Weiner is the Chair of the Medical Oncology department at Fox
Chase and is interested in the use of immunotherapy in the treatment
of GI tumors.
You can read more about his research and that of the department here:
http://www.fccc.edu/docs/sci_report/Weiner.pdf
http://www.fccc.edu/docs/sci_report/ClinicalTrials.pdf
Both Dr. Weiner and Dr. Meropol are involved in clinical trials of
novel treatments for GI cancers.
____________
Dr. Nevena Damjanov, MD
Fox Chase Cancer Center
http://www.fccc.edu/physician_directory/medical/damjanov.html
Dr. Damjanov is a medical oncologist specializing in GI malignancies at Fox Chase.
____________
Dr. David S Weinberg, MD, MSc
Fox Chase Cancer Center
http://www.fccc.edu/physician_directory/medical/weinberg.html
Dr. Weinberg is the director of the GI Medical Oncology program at Fox
Chase and participates in multiple clinical trials of new therapies.
____________
Dr. Weijing Sun, MD
Hospital of the University of Pennsylvania
15 Penn Tower
3400 Spruce Street
Philadelphia, PA 19104
1-800-789-PENN (7366)
http://www.pennhealth.com/WagForm/MainPage.aspx?config=provider&P=PP&ID=9021
Dr. Sun specializes in the treatment of gastrointestinal tumors. He is
the Director of Upper GI and Pancreatic-biliary-hepatic Cancer Group
and the Associate Director of the GI Cancer Program.
____________
Dr. Jeffrey A. Drebin, MD, PhD, FACS
Chief of Gastrointestinal Surgery at UPenn
http://www.pennhealth.com/WagForm/MainPage.aspx?config=provider&P=PP&ID=9543
Hospital of the University of Pennsylvania
4 Silverstein Building
3400 Spruce Street
Philadelphia, PA 19104
1-800-789-PENN (7366)
____________
Dr. Anil K. Rustgi, MD
Dr. Rustgi is the Chair of the GI department at UPenn and specializes
in GI cancers.
http://www.uphs.upenn.edu/gastro/faculty/rustgi.html
Gastroenterology Division
600 CRB
University of Pennsylvania
415 Curie Boulevard
Philadelphia, PA 19104
Phone: (215) 898-0154
Fax: (215) 573-2024
anil2@mail.med.upenn.edu
____________
Here are some other top people outside of Philly:
Dr. Robert J. Mayer, MD
Dana-Farber Cancer Institute, Harvard Medical School
44 Binney Street
Dana 1602
Boston, MA 02115
USA
Office phone: (617) 632-3474
Fax: (617) 632-2260
Preferred contact method: office phone
Dr. Mayer heads the GI Cancer program at Dana Farber, one of the best
cancer centers in the world.
____________
Dr. David Paul Kelsen
Memorial Sloan-Kettering Cancer Center
http://www.mskcc.org/prg/prg/bios/120.cfm
Appointments for New Patients:
(646) 497-9053
Dr. Kelsen is the Chief of the MSKCC Gastrointestinal Oncology Service
and the Edward S. Gordon Chair in Medical Oncology.
=======================================================
I hope this information is helpful. Please feel free to request any
clarification prior to rating. My best wishes to your uncle in this
difficult struggle.
-welte-ga |
