Over 150 People Per Hour are Diagnosed With Cancer in the U.S.
This year, about 156 people every hour will learn they have cancer, and by
the end of 2004 scientists predict 563,700 people will have died from cancer in
the United States, according to a report from the American Cancer Society.
Evidence from the report shows that obesity and little exercise can cause as
many as one-third of the United States’ cancer cases.
Evidence also shows that lung cancer is down but is still increasing in
women, and African American men have a 40 percent higher chance of dying from
all cancers than white men. Further, African-American women have a lower
incidence of breast cancer but a higher death rate from the disease.
There are many reasons for such disparities, according to one of the study’s
authors, such as a limited access to health care due to poverty.
However, the report reveals that death rates have declined slightly and
five-year survival improved significantly for children, from 56 percent in the
mid-1970s to 78 percent in the 1990s. Additionally, certain steps have been made
to prevent cancer, such as anti-smoking campaigns.
.As far back as 5,000 B.C., Egyptian doctors treated tumors with heat. The Greeks
recognized the value of heat in some medical treatments; indeed, the word
hyperthermia comes from the Greek HYPER ("to raise") and THERME ("to heat").
Even the most ancient texts of the Law of Moses mention hot springs (Genesis
36:24) to therapeutically elevate body temperature.
For many years, scientists have recognized that cancer cells are more
sensitive to heat than normal cells, and that at high temperatures cancer cells
break down. This helps explain why, after the Renaissance, there were reports of
spontaneous tumor regressions in patients with smallpox, influenza, tuberculosis
and malaria, where the common factor was an infectious fever of about 104º. In
the late 19th and early 20th centuries, there were scattered reports of similar
successes.
Yet, it was not until dedicated medical scientist , like Valley Cancer
Institute's: Haim I. Bicher, M.D., a pioneer in the field,
had worked for decades to provide a cohesive body of clinical research and
testing, that hyperthermia was given legal status as an approved medical
procedure, in 1984.
For years, though the principles of tumor heating were widely understood,
the technology to direct the heat in a concentrated area lagged behind the
theory.
In modern day hyperthermia, controlling heating placement is done using
fine sensors and directional applicators, (many designed by Dr. Bicher), that
are now standard in hyperthermic medical treatment worldwide. Using microwaves
and computers with these devices, cancerous tumors are heated from 107º - 113º.
This breaks down the tumor without harming the surrounding tissues, with no
lasting side-effects.
Since 1984, hyperthermic oncology, using concentrated heat to destroy
cancerous tissue, has been regarded as standard and beneficial treatment,
specifically recommended for locally recurrent tumors, and for primary cancer,
where other treatment methods have a poor history of success
Hyperthermia can be used by itself, and results in impressive shrinkage and even
complete eradication (10-15%) of tumors. However, these results usually don’t
last, and the tumors regrow. (In some animal experiments, cures were effected by
hyperthermia. For example, in an animal experiment on transplanted mammary
carcinoma, radiation alone produced no cures, heat alone produced 22% cures, and
combined modality produced 77% cures.)
Hyperthermia is also an immune system enhancer, and very effective in providing
pain relief, controlling bleeding, and useful in other conditions such as
prostatic hypertrophy and psoriasis
Combination Chemotherapy With or Without Whole-Body
Hyperthermia in Treating Patients With
Recurrent Ovarian Epithelial, Fallopian Tube, or Peritoneal
Cancer
Sponsored by
Ludwig Maximillian Universitaet Women's Hospital
Purpose
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from
dividing so they stop growing or die. Hyperthermia therapy kills tumor cells by heating them to
several degrees above body temperature. Combining hyperthermia with
chemotherapy may kill more tumor cells. It is not yet known if chemotherapy is
more effective with or without whole-body hyperthermia therapy
in treating
gynecologic cancer.
PURPOSE: Randomized phase II/III trial to compare the effectiveness of
chemotherapy with or without whole-body hyperthermia in treating patients who have recurrent ovarian epithelial,
fallopian tube, or peritoneal cancer.
Condition
Treatment or Intervention
Phase
Fallopian Tube Cancer peritoneal cavity
cancer recurrent ovarian epithelial cancer
Study Type: Interventional Study Design: Treatment
Official Title: Phase II/III Randomized Study of Carboplatin
and Ifosfamide With or Without Whole Body Hyperthermia in Patients With
Recurrent Ovarian Epithelial, Fallopian Tube, or Extraovarian Peritoneal Cancer
Further Study Details:
OBJECTIVES:
Compare the time to progressive disease in patients with
recurrent ovarian epithelial, fallopian tube, or extraovarian peritoneal cancer
treated with carboplatin and ifosfamide with or without whole body hyperthermia.
Compare the response rate, duration of response, and survival time of
patients treated with these regimens.
Compare the effect on the presence of disseminated tumor cells in bone marrow in patients treated with
these regimens.
Compare the toxicity of these regimens in these patients.
Assess quality of life of patients treated with these regimens.
OUTLINE: This is a phase II safety and efficacy study followed by a phase III
randomized, open-label, multicenter study.
Phase II: Patients receive ifosfamide IV over 1 hour and carboplatin IV over
20 minutes on day 1. Patients also undergo whole body hyperthermia for at least
1 hour on day 1. Treatment repeats every 28 days for 6 courses in the absence of disease
progression or unacceptable toxicity.
Patients are stratified according to disease-free interval (6-12 months vs
more than 12 months), measurable disease (bidimensionally measurable vs
measurable by other clinical means), and disease recurrence (first recurrence vs
second or greater recurrence). Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive ifosfamide, carboplatin, and whole body hyperthermia as in phase II.
Arm II: Patients receive ifosfamide and carboplatin as in arm I.
In both arms,
treatment repeats every 28 days for 6 courses in the absence of disease
progression or unacceptable toxicity. Quality of life is assessed before each
course, 4 weeks after the last course, and then every 3 months for 2 years.
Patients are followed at 4 weeks and then every 3 months for 2 years.
PROJECTED ACCRUAL: A total of 15 patients will be accrued for phase II of
this study. A total of 226 patients (113 per treatment arm) will be accrued for
phase III of this study within 2 years.
Eligibility
Ages Eligible for Study: 18 Years - 65 Years, Genders Eligible for
Study: Both
Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed ovarian epithelial, fallopian tube, or extraovarian
peritoneal cancer
Recurrent disease (any FIGO stage)
Not amenable to curative surgery or radiotherapy alone
Failed prior primary platinum-based therapy at least 6 months after therapy
discontinuation
Measurable lesion by CT scan, MRI, chest x-ray, or sonography
Physical examination allowed for documenting lymph node and skin metastases
Physical gynecological examination allowed for well-defined palpable tumor
lesions
Increase in CA
125 without any measurable tumor is not acceptable as indication of recurrence
No CNS metastases
No tumor of borderline malignancy
PATIENT CHARACTERISTICS: Age
18 to 65
Performance status
ECOG 0-2
Life expectancy
At least 24 weeks
Hematopoietic
Neutrophil count at least 1,500/mm3
Platelet count at least 100,000/mm3
Hepatic
Not specified
Renal
Creatinine clearance at least 60 mL/min
No chronic or acute renal failure
Cardiovascular
Cardiovascular function sufficient for hyperthermia treatment by
stress-ECG
No cardiomyopathy with impaired ventricular function
No New York Heart Association class III or IV heart disease
No cardiac arrhythmias influencing LVEF and requiring medication
No myocardial infarction or angina pectoris within the past 6 months
No uncontrolled arterial hypertension
Pulmonary
Pulmonary function sufficient for hyperthermia treatment by pulmonary function tests
Other
No untreated endocrinological disease (e.g., hyperthyroidism or diabetes
mellitus)
No other primary malignancy except carcinoma in situ of the cervix or
adequately treated basal cell skin cancer
No contraindication against hyperthermia treatment (e.g., photodermatosis, history of malignant
hyperthermia, or
claustrophobia)
No hypersensitivity to carboplatin, ifosfamide, or any other study
medication
Not pregnant or nursing
PRIOR CONCURRENT THERAPY: Biologic therapy
Not specified
Chemotherapy
See Disease Characteristics
No concurrent cytotoxic or other antineoplastic therapy
Endocrine therapy
Concurrent hormone replacement therapy allowed
Concurrent steroid antiemetics allowed
Radiotherapy
See Disease Characteristics
At least 1 year since prior radiotherapy (tumoricidal dose) of the pelvis
Concurrent palliative local radiotherapy for painful (nonprogressive)
existing lesion is allowed if other measurable sites are present
No concurrent radiotherapy to a second existing lesion
Surgery
See Disease Characteristics
Other
No prior form of hyperthermic therapy
At least 3 weeks since other medications as part of another clinical study
At least 3 weeks since prior investigational agents
Investigation Units of the European Malignant Hyperthermia Group Since the first meeting in 1983
the group has met regularly. At present, twenty laboratories in twelve European
countries are performing in vitro contracture tests using the protocol of the
EMHG.
Austria: Prof. H. Gilly Klinik
für Anästhesie und allgemeine Intensivmedizin der Universität
Wien Spitalgasse 23 A-1090 Wien Tel: ++43 222 404 00 25 19 Fax: ++43
222 404 00 45 19 E-Mail: Hermann.Gilly@akh-wien.ac.at
Dr. Werner W. Lingnau Univ. Klinik für Anaesthesie und Allgemeine
Intensivmedizin Anichstrasse 35 A-6020 Innsbruck Tel: ++43
512/504-2465 Fax: ++43 512 /504-4556 E-Mail:
werner.lingnau@uibk.ac.at
Belgium: Dr. L. Heytens Department of
Intensive Care Universitair Ziekenhuis Antwerpen Wilrijkstraat
10 B-2650 Edegem Tel: ++32 03 829 11 11 ext. 1635 Fax: ++32 3 828 48
82 E-Mail:
Denmark: Dr. H. Ørding The Danish Malignant
Hyperthermia
Register Department of Anaesthesia Herlev University Hospital DK-2730
Herlev Tel: ++45 44 53 53 00 ext. 3571 Fax: ++45 44 53 53 32 E-Mail:
ording@inet.uni-c.dk
England: Prof. F.R. Ellis MH Investigation
Unit Clinical Sciences Building St. James's University
Hospital GB-Leeds LS9 7TF Tel: ++44 0113 206 5274 Fax: ++44 0113 206
4140 E-Mail: anapmh@stjames.leeds.ac.uk
France: Prof. P. Stieglitz Département
d'Anesthésie Réanimation 1 CHU de Grenoble BP 217 X F-38043 Grenoble
Cedex 9 Tel: ++33 76 76 54 26 Fax: ++33 76 76 51 83 E-Mail:
Prof. R. Krivosic-Horber Département d'Anesthésie Réanimation Hopital
B Centre Hospitalier Régional Universitaire Bd. du Proffesseur J.
Leclercq F-59037 Lille Tel: ++33 20 44 62 70 Fax: ++33 20 65 02
57 E-Mail: rkrivosic@aol.com
Dr. G. Kozak Ribbens C.R.M.B.M. Faculté de Médecine la Timone 27 Bd.
Jean Moulin F-13005 Marseille Tel: ++33 91 25 50 90 Fax: ++33 91 25 65
39 E-Mail:
Dr. Y. Nivoche Département d'Anesthésie Hopital Robert Debré 48 Bd.
Serurier F-75935 Paris Cedex 19 Tel: ++33 1 40 03 21 82 Fax: ++33 1 40
03 20 20 E-Mail: ynivoche.debre@invivo.edu.internet
Germany: Dr. F. Wappler University Hospital
Eppendorf Department of Anesthesiology (Chairman Prof. Dr. J. Schulte am
Esch) Martinistrasse 52 D-20251 Hamburg Tel: ++49 40 47 17 46
04 Fax: ++49 40 47 17 49 63 E-Mail: wappler@uke.uni-hamburg.de
Dr. I. Tzanova Klinik für Anästhesie Uniklinik
Mainz Langenbeckstrasse 1 D-55131 Mainz Tel: ++49 61 31 17 65
68 Fax: ++49 61 31 17 66 49 E-Mail:
Prof. F. Lehmann-Horn Institut für angewandte Physiologie der Universität
Ulm Albert-Einstein-Allee 11 D-89081 Ulm Tel: ++49 731 502 32
51 Fax: ++49 731 502 32 60 E-Mail:
frank.lehmann-horn@medizin.uni-ulm.de
Dr. E. Hartung Institut für Anästhesiologie der Universität
Würzburg Josef Schneider Strasse 2 D-97080 Würzburg Tel: ++49 931 201
33 59 Fax: ++49 931 201 34 44 E-Mail: hartungej@aol.com
Prof.Dr.med.habil. D. Olthoff Klinik und Poliklinik für Anästhesiologie
und Intensivtherapie der Universität zu Leipzig Liebigstraße
20a D-04103 Leipzig Tel: ++49 341 971 77 00 Fax: ++49 341 971 77
09 E-Mail: olthoff@server3.medizin.uni-leipzig.de
Iceland: Dr. Thorarinn
Olafson Department of Anaesthesia Landspitali IS-101 Reykjavik Tel:
++354 1 60 13 75 Fax: ++354 1 60 15 19 E-Mail: stefsig@rhi.hi.is
Ireland: Prof. J.J.A. Heffron Department of
Biochemistry University College EIR-Cork Tel: ++353 21 27 68 71 ext.
2208 Fax: ++353 21 27 40 34 E-Mail: stbi8006@ucc.ie
Dr. Mary Lehane Dept of Anaesthesia Cork University Hospital Wilton,
Cork Ireland Tel: ++35321546400 Fax:++35321546434 E-Mail:
johnj@indigo.ie
Italy: Dr. V.E. Tegazzin Department of
Anesthesiology Traumatic-Orthopedic Hospital Via Facciolati 71 I-35126
Padova Tel: ++39 49 821 65 22 Fax: ++39 49 821 66 36 E-Mail:
Teg1@ux1.unipd.it
Settore Biofarmacologico A.O. Cardarelli Via S. Giacomo dei Capri,
66 80131 Napoli Italy Tel:++39 81 2549524 Fax:++39 81
5608262 E-Mail: sifo@na.nettuno.it
Netherlands: Dr. Marc M.J. Snoeck Department
of Anaesthesia University Hospital Geert Grooteplein 10 NL-6525 GA
Nijmegen Tel: ++31 24 36 14 406 Fax: ++31 24 35 40 462 E-Mail:
MH_nl@anes.azn.nl
Norway: Dr. T.H. Fagerlund Department of
Anaesthesia Ullevål Sykehus N-0456 Oslo Tel: ++47 2 11 80 80 Fax:
++47 2 85 40 36 E-Mail:
Sweden: Dr. E. Ranklev Department of
Anaesthesia Lasarettet University Hospital S-221 85 Lund Tel: ++46 46
17 19 49 Fax: ++46 46 14 23 13 E-Mail: islander@algonet.se
Switzerland: Dr. A. Urwyler Departement
Anästhesie Universitätskliniken Kantonsspital CH-4031 Basel Tel:
++41 61 265 72 54 Fax: ++49 61 265 73 20 E-Mail:urwyler
Cytoreduction surgery with
intraperitoneal chemotherapy
Jun 2003 - Nationally renowned thought leaders discuss the optimal use of
therapeutics and drug sensitivity testing for the management of gynecologic
malignancies.
Jun 2002 - Questions regarding the best treatment for each stage and for
each individual patient with gynecologic cancers can best be answered by
reviewing the latest findings in the diagnosis, treatment, and prevention of
these diseases.
Apr 2003 - A discussion of recent developments in the treatment of ovarian
cancer, including approaches to improve first-line therapy as well as treatment
of recurrent and relapsed disease.
Mar 1999 - Assess the risk of lung cancer for women previously treated for
breast cancer who smoke. Cyclophosphamide and cisplatin compared with paclitaxel
and cisplatin in patients with stage III and stage IV ovarian cancer. When we
get there, we will be able to fine-tune treatment and decision-making for
individual patients, study new drugs in optimal circumstances, and improve the
outcomes for patients with all stages of breast cancer.
Sep 1999 - After numerous phase I/II trials of carboplatin and paclitaxel
combinations, three large randomized phase III trials were performed comparing
cisplatin-paclitaxel with carboplatin-paclitaxel. [5-7] All three trials
demonstrated equivalence with respect to median progression-free survival for
carboplatin-paclitaxel and cisplatin-paclitaxel. Cyclophosphamide and cisplatin
compared with paclitaxel and cisplatin in patients with stage III and stage IV
ovarian cancer.
Nov 2001 - The current treatment focus for ovarian cancer, the most lethal
gynecologic malignancy, is to minimize drug resistance by optimizing treatment
doses, schedules, and combinations, and properly integrating novel agents. Dr
Paul Vasey presents results of drug treatment trials that may help us better
understand this clinical challenge.
Nov 1999 - After this time, however, the incidence of second primary tumors
in p53-normal patients dropped precipitously, while patients with mutated p53 in
the primary tumor went on to have an increasing rate of development of secondary
malignancies. Dr. Hong next studied successfully treated head and neck cancer
patients given retinoic acid as an adjuvant to prevent second primary tumors
from occurring. Two presentations examined the role of primary radiation therapy
compared with surgery and with ...
Nov 1999 - Dr. Kleinberg[1] from Johns Hopkins Oncology Center presented
long-term survival and local control outcome in 92 patients with esophageal
cancer (65 with adenocarcinoma and 27 with squamous cell carcinoma) who received
preoperative chemoradiation followed by surgical resection of esophageal cancer.
As expected, patients with a pathologic complete response had a better actuarial
survival rate of 73% at 4 years (median not reached), whereas the remainder of
the patients had 4-year actuarial ...
Jan 2002 - A 41-year-old female was diagnosed with stage IV colon cancer
with peritoneal seeding and metastases to the ovaries. Resection of the
transverse colon and left oophorectomy with intraoperative radiotherapy was
performed in 1998, and her postoperative CEA was 11.6. Chemotherapy of
intraperitoneal 5-FU and IV leucovorin followed surgery, and her CEA
dropped to 1.2.
Nov 2002 - Dr. Markman discusses open and settled issues in the
chemotherapeutic management of women with ovarian cancer at various stages of
the disease.
Mar 2001 - As part of a work-up for infertility, a 28-year-old woman
underwent a laparoscopy. Several papillary nodules were found on the pelvic
peritoneal surface, which were identified as papillary adenocarcinoma on biopsy.
During laparotomy, her ovaries appeared normal and some 20 nodules were found,
all of them on the pelvic peritoneal surfaces.
Mar 2002 - Describes the current treatment standards for ovarian cancer,
novel agents under investigation, and new methods to reduce toxicity and adverse
effects associated with ovarian cancer chemotherapy.
Mar 1999 - Enhanced clinician knowledge of pain syndromes, improved pain
assessment, and updated medical information can promote adequate management of
cancer pain.
Oct 2001 - We investigated the effect of surgery plus postoperative
(adjuvant) chemoradiotherapy on the survival of patients with resectable
adenocarcinoma of the stomach or gastroesophageal junction. Patients And Methods
Patients having histologic proof of localized carcinoma (either squamous cell
carcinoma or adenocarcinoma) of the esophagus or gastroesophageal junction
underwent full classification including endoscopic ultrasonography (EUS).
Background: The goals of this study were to assess the
...
Sep 2000 - PP is rare, but frequently misdiagnosed, and requires vigilance
from the clinician, gastroenterologist, or surgeon who conducts the initial
evaluation.
May 2003 - Drs. Edgardo Rivera and Robert Burger review the impact of
metastatic breast or ovarian cancer on quality of life and discuss strategies to
maximize efficacy while minimizing toxicity.
Nov 1999 - In this clinician´s practice, patients who have no
evidence of disease are followed with office visits and physical examination
every 6 months for 5 years; CA-125 levels or order imaging studies are not
routine unless required by protocol.
May 1999 - Two teams agree that carboplatin + paclitaxel is preferred over
cisplatin + paclitaxel for advanced ovarian cancer due to its more favorable
toxicity profile and ease of administration. However, 1 group concludes that
cisplatin-based regimens should be considered the standard chemotherapy
option in patients with high-risk ovarian cancer.
Aug 2001 - The only constant in lung cancer treatment is that patients
diagnosed with earlier-stage disease enjoy 5-year survival rates greater than
50%. Improvements in screening for lung cancer, the best method of detecting
early-stage cancers, as well as strategies to prevent lung cancer, were
discussed at the 2nd International Lung Cancer Congress in Kauai, Hawaii. Dr.
James Mulshine,[19] Head of the Intervention Section for Chemoprevention of Lung
Cancer at the National Cancer Institute in Bethesda...
May 1998 - These two trials demonstrate the clinical benefit of
anti-HER-2/neu antibody therapy in patients with metastatic breast cancer.
Long-term follow-up studies of early stage breast cancer patients treated
without adjuvant therapy have demonstrated that HER-2/neu overexpression by
tumors is associated with worse survival outcomes. Dr. F. A. Holmes of the M.D.
Anderson Cancer Center discussed the results of a related multi-center study
that compared 3-hour versus 96-hour paclitaxel infusion in
...
May 1999 - Shepherd F, Ramlau R, Mattson K, et al: Randomized study of
Taxotere (TAX) versus supportive care (BSC) in non-small cell lung cancer
(NSCLC) patients previously treated with platinum-based chemotherapy
[Abstract 1784]. Investigators from the Cleveland Clinic described a large
series of patients with clinically localized prostate cancer who were treated
with RP (1144 patients) or EBRT (1078 patients) and then randomized to receive
AD therapy or not. Improved survival in patients with locally
...
May 2000 - Discuss the results of clinical trials evaluating first- or
second-line treatment protocols for ovarian cancer. Among patients with at least
2 but not 3 prior regimens for metastatic breast cancer, and who had received
paclitaxel for advanced breast cancer, an objective response rate of 20% was
observed. Clinical course of breast cancer patients with complete pathologic
primary tumor and axillary node response to doxorubicin-based neoadjuvant
chemotherapy.
May 1998 - Because of cisplatin's toxicities, carboplatin will likely
continue to be the platinum compound of choice to use in combination with
paclitaxel as first-line therapy for ovarian cancer. Debate regarding the
benefit of IP therapy in this setting will likely
continue.
May 2000 - Based on a phase I study in which 8 of 14 patients with
relapsed/refractory SCLC responded, the Sarah Cannon Research Network[3] added
topotecan to the paclitaxel-carboplatin combination for treatment-naive
patients. Phase II trial of postoperative adjuvant cisplatin/etoposide (PE) in
patients with completely resected stage I - IIIA small cell lung cancer (SCLC):
the Japan Clinical Oncology Lung Cancer Study Group trial (JCOG9101). [15]
Patients with locally advanced NSCLC in this phase III
...
Jun 2003 - Maurie Markman, MD, and Paul A. Vasey, MD, review key
presentations from ASCO 2003 and offer insight into the latest research in the
treatment of gynecologic malignancies.
Jun 2003 - This report from ASCO 2003 highlights new findings in ovarian
cancer research, particularly in treatment results based on cell type and in
salvage therapy.
Jun 2001 - The MILES (Multicenter Italian Lung Cancer Study) phase 3 trial:
gemcitabine+vinorelbine vs. vinorelbine and vs. gemcitabine in elderly advanced
NSCLC patients. Cisplatin/gemcitabine vs. cisplatin/gemcitabine/vinorelbine vs
sequential doublets of gemcitabine/vinorelbine followed by
ifosfamide/vinorelbine in advanced non-small cell lung cancer: results of a
Spanish Lung Cancer Group phase III trial (GEPC/98-02). Program and abstracts of
the 37th Annual Meeting of the American Society of ...
Jun 2001 - We evaluated the tolerability and toxicity attributed to
pegylated liposomal doxorubicin (PL-DOX) in women with recurrent or refractory
ovarian cancer, and reviewed procedures to prevent or treat toxicity induced by
the agent.
Jun 2000 - Journal Scan Surgery, June 2000 Albert B. Lowenfels, MD,
Contributing Editor Journal Scan is the clinician's guide to the latest clinical
research findings in the Annals of Surgery, Archives of Surgery, JAMA, The
Lancet, and The New England Journal of Medicine. This study suggests that
staging laparoscopy can prevent unnecessary surgery in about a third of patients
considered to be surgical candidates and focus appropriate treatment on patients
with pancreatic cancer who might benefit. ...
Dec 1998 - These CSFs, used to improve outcome in immunosuppressed cancer
patients, may also have an adjunctive role in the treatment of a variety of
infectious diseases.
Dec 2000 - Previous studies attempting to determine an increased risk of
second malignancies in patients with breast cancer treated with radiation
therapy have largely failed. Fowble and colleagues[15] at Fox Chase Cancer
Center reported on the increased risk of contralateral breast cancer in younger
patients and in those with a family history of breast cancer. Postoperative
radiotherapy in high-risk postmenopausal breast cancer patients given adjuvant
tamoxifen: Danish Breast Cancer Cooperative Group ...
Sep 2001 - Patients with recent (within 1 year) endometrial biopsy or large
uterine leiomyomas and patients medically unfit for operative hysteroscopy were
excluded. Adverse effects (abdominal pain, breast tenderness, acne, headache,
mood changes) were reported by 13 patients in the LNG IUD group and by 9
patients in the resection group. This study evaluated the diagnostic accuracy of
4 different diagnostic modalities (magnetic resonance imaging [MRI],
transvaginal sonography [TVS], hysterosonography [...
Feb 2001 - An otherwise healthy 59-year-old man with radiographically
resectable adenocarcinoma of the stomach was found to have minimal peritoneal
implants on laparoscopy.
New Treatment for Peritoneal Carcinomatosis
Laurie Barclay, MD
Jan. 13, 2003 — Hyperthermic chemotherapy with cytoreduction appears to
benefit patients with peritoneal carcinomatosis, according to the results of a
prospective trial published in the January issue of the Archives of
Surgery. This novel approach may improve survival and enhance quality of
life.
"As surgical techniques and perioperative care have improved, there has been
a greater trend towards more aggressive surgical treatment of solid tumors,"
lead author Perry Shen, MD, from Wake Forest University Baptist Medical Center,
says in a news release. "This trial and available data indicated that a
multimodality approach to treating patients with peritoneal carcinomatosis can
significantly alter the natural history of the disease, alleviate symptoms, and
even produce long-term survivors."
Between December 1991 and November 1997, 109 consecutive patients with
peritoneal carcinomatosis seen at a university surgical oncology service
underwent resection of gross disease followed by two-hour intraoperative
perfusion of 20 to 40 mg mitomycin C into the peritoneal cavity at a temperature
of 40.5 degrees C.
Overall, one-year survival was 61% and three-year survival was 33%. At median
follow-up of 52 months, median overall survival was 16 months. Based on
multivariate analysis, factors predicting longer survival were nonadenocarcinoma
histologic features (P = .001), the appendix as a primary site (P
= .003), lack of hepatic parenchymal metastases (P = .01), and complete
resection of all gross disease (P < .001). Three-year overall survival
was 68% for patients with an R1/0 resection compared with 21% for patients with
an incomplete resection of gross disease (P < .001).
Although the authors recommend confirmation of these results in prospective
randomized studies, they believe that in select patients this approach may
improve the uniformly poor prognosis of this disease.
In a follow-up study of 17 patients surviving more than three years after
cytoreductive surgery and intraperitoneal hyperthermic chemotherapy, more than
90% had minimal to no limitations of activity and functional assessments
comparable to the national norms for their respective age groups.
"Surgery combined with intraperitoneal hyperthermic chemotherapy is an
aggressive, multidisciplinary approach to treating a difficult cancer with few
meaningful therapeutic options," Dr. Shen says.
Arch Surg. 2003;138(1):26-33
Reviewed by Gary D. Vogin, MD
Pseudomyxoma Peritonei Manifesting as Intestinal
Obstruction
Arif Nawaz, MD, Ali Karakurum, MD, David
Weltman, MD, Ahmed Shehata, MD, Imtiaz Mohammed, MD,
Carylann Hadjiyane, MD, Crescens Pellecchia, MD, Nassau County
Medical Center, State University of New York at Stony Brook, East Meadow.
Pseudomyxoma peritonei is an appendiceal tumor with distinct
clinical and pathologic features. It frequently presents a problem in diagnosis
and management. We report a case of pseudomyxoma peritonei, which initially
appeared with intestinal obstruction. This is a rare initial manifestation in
patients who have not had multiple surgical procedures. We review the literature
and discuss the unique clinical features and misconceptions surrounding
pseudomyxoma peritonei.
Introduction
Pseudomyxoma peritonei is a rare but frequently
misdiagnosed condition. It has diverse and slightly confusing presentations,
including abdominal distention, ovarian tumors, or appendicitis-like syndromes.
In this article, we emphasize the unique pathophysiologic, clinical, and
management aspects of this disease entity.
Case Report
A 45-year-old black man was admitted with a 1-week history of
cramp-like lower abdominal pain and incessant vomiting. He had no history of
surgery or medical illnesses. He had used cocaine and alcohol in the past but
was currently taking no drugs. Physical examination showed a distended abdomen
with mild lower abdominal tenderness. Findings on the rectal examination were
normal. Laboratory data showed a white blood cell count of 20,600/dL, with
normal hemoglobin and hematocrit values. The patient was dehydrated with
hyponatremia and increased serum urea nitrogen concentration. Radiologic studies
(abdominal film and computed tomography [CT]) were suggestive of intestinal
obstruction (Figure).
Figure 1. Computed tomography without contrast medium showed (A)
multiple tubular, fluid-filled masses in pelvis; (B) calcification along wall of
mass (arrow); and (C) air bubbles within mass (arrow). (D) At 1-year follow-up,
cystic pelvic mass was seen (arrow).
The patient had exploratory laparotomy, and intraoperative findings consisted
of a large mass in the left lower quadrant adherent to the omentum and sigmoid
colon. After careful dissection, it was thought to be necrotic small bowel.
Since the mass appeared to be of small bowel origin, small bowel resection and
an ileostomy and mucus fistula were done. Pathology was consistent with
well-differentiated adenocarcinoma of appendiceal origin. The patient remained
asymptomatic for approximately 6 months, then had recurrent abdominal pain.
Workup revealed recurrence of the tumor (Figure). Chemotherapy was begun, and
the patient was doing well with some decrease in the bulk of the tumor 2 years
after the initial diagnosis.
Discussion
For years, the clinical syndrome of pseudomyxoma peritonei has
been enigmatic. The term pseudomyxoma peritonei was first used by
Werth[1] in 1884 to describe massive intraperitoneal accumulation of
gelatinous pseudomucin due to the perforation of ovarian pseudomucinous
cystomas. Based on recent studies reevaluating this condition, tumors previously
designated pseudomyxoma peritonei, can now be viewed as two pathologically and
prognostically distinct disease processes.[1-9]
Pseudomyxoma peritonei is a disease process characterized by copious
mucinous ascites and histologically bland peritoneal mucinous tumor. It is
attributable to a ruptured mucinous cystadenocarcinoma (appendiceal origin in
most cases). It has an indolent course but may recur over months to years.
Peritoneal mucinous carcinomatosis is a disease process characterized by
abundant peritoneal mucinous tumor, and its clinical appearance is similar to
that of pseudomyxoma peritonei. However, the peritoneal cells have architectural
and structural features of carcinoma. These cells are derived from the
gastrointestinal mucinous adenocarcinomas and are associated with a
significantly worse prognosis.[2]
In the past, pseudomyxoma peritonei was said to occur from a variety of
primary tumors.[3,4] This may be true, but in the vast majority of
cases, the patients have an appendiceal tumor giving rise to this clinical
entity.[4] Mucinous peritoneal carcinomatosis may arise from other
sites, such as the colon, gallbladder, pancreas, or stomach, but these tumors
usually have signet ring histology. They may show redistribution but do not
spare the small bowel and will implant and grow in the abdominal cavity in a
random fashion with extensive small bowel involvement, resulting in a much
poorer prognosis.
The redistribution phenomenon occurs in patients with pseudomyxoma peritonei
who have not had previous surgery.[2,4-8] Two physiologic principles
are involved. First, the mucinous tumors accumulate at the site of peritoneal
absorption (omentum and undersurface of the diaphragm). Second, gravity causes
the mucinous tumor cells to settle within the dependent portions of the abdomen
(pelvis, right retrohepatic space, left abdominal gutter, and ligament of
Treitz). The visceral peritoneal surfaces are usually spared, since they
relentlessly move during peristaltic activity.[4] For this unique
pattern of cancer dissemination to occur, several biologic requirements and
physiologic phenomena must be operating. Pseudomyxoma cells do not have
adherence molecules on their cell surface. This lack of "stickiness" means that
the tumor cell will not actively attach to an abdominal or pelvic surface. The
tumor will progress by the production of mucus, exfoliation of tumor cells, and
a redistribution of these cells around the abdomen according to the
aforementioned physiologic mechanisms. The "dissecting mucus" that is recognized
by the pathologist as part of the histologic picture of pseudomyxoma peritonei
should not be confused with invasive malignancy, which is not a part of this
syndrome.
Pseudomyxoma peritonei has multiple clinical manifestations that lead to
difficulties in definitive diagnosis and timely treatment. The usual clinical
features of this tumor are increasing abdominal girth (40%), bilateral or
unilateral ovarian tumors (20%), hernia sac tumors (20%), appendicitis-like
syndrome (10%), and infertility (10%).[4] Narrowing of the
gastrointestinal tract, but rarely complete obstruction, frequently occurs at
three well-defined anatomic sites -- the pyloric antrum, the ileocecal valve,
and the cul-de-sac of Douglas.[4] These are three portions of the
gastrointestinal tract that are attached to the retroperitoneum and are
relatively motionless. Intestinal obstruction is rarely an initial manifestation
of this disease and usually occurs when multiple previous surgeries have led to
small bowel entrapment.[5]
Our patient had intestinal obstruction and emergency surgery. The urgent
nature of this and other clinical manifestations such as appendicitis-like
syndrome may lead to unnecessary surgical procedures, resulting in poorer
outlook. Unwary clinicians may also mistake pseudomyxoma peritonei for multiple
abscesses or adenocarcinoma, and the patient may have repeated surgeries,
leading to intestinal obstruction and poor outcome. As mentioned earlier, this
disease is distinct from mucinous adenocarcinoma of the colon, gallbladder,
pancreas, or stomach in that, in the absence of repeated surgical procedures, it
spares the small bowel and has a much better prognosis.
Diagnosis of pseudomyxoma requires a high index of suspicion supplemented by
various radiologic studies, including CT, followed by pathologic
diagnosis.[10] Recently, some sonographic features of pseudomyxoma
have also been reported, thereby adding to the growing list of available
diagnostic modalities.[11] A case of pseudomyxoma peritonei with
abnormal radionuclide uptake has also been described,[12] though the
utility of this diagnostic modality has not been thoroughly evaluated.
The prognosis of pseudomyxoma peritonei has always been extremely guarded.
Sugarbaker[4] has shown that repeated surgeries result in a median
survival of approximately 2 years, with only a small percentage alive at 5
years. Patients who have repeated surgeries and extensive systemic chemotherapy
show some improvement in survival, but no long-term, disease-free survival is
expected.
The Washington Hospital Center has pursued a "cytoreductive approach" for
these patients.[4,9,13] This treatment approach involves an initial
series of well-defined peritonectomy procedures that strip all disease from the
parietal peritoneal surfaces and resect all visceral peritoneal involvement,
leaving the abdomen virtually free of disease. Additionally, perioperative
chemotherapy is used to kill any remaining cancer cells.
Sugarbaker[4] recommended that patients with grade I mucinous
adenocarcinoma be treated with extensive cytoreduction followed by
intraoperative and postoperative chemotherapy. Other
investigators[15] have reported on the success of a similar approach
in patients who are in poor general condition. Some centers have also tried
intraperitoneal chemotherapy through implantable port systems with varying
success.[14,15] If managed appropriately, these tumors have an
excellent 5-year survival rate exceeding 80%.
Conclusions
Pseudomyxoma peritonei is a distinct clinical entity with
unique clinical and pathologic features. It requires vigilance by the clinician,
gastroenterologist, or surgeon who evaluates the patient initially, since early
diagnosis is essential for the appropriate treatment of this disease. It may
rarely manifest as intestinal obstruction, and the patient may have emergency
surgery and small bowel resection, which lead to an adverse outcome. Success has
been reported with an approach combining cytoreductive surgery and chemotherapy.
If properly treated, patients with these tumors have a 5-year survival rate
exceeding 80%.
Ronnett BM, Shmookler BM, Sugarbaker PH, et al: Pseudomyxoma peritonei: new
concepts in diagnosis, origin, nomenclature and relationship to mucinous
borderline low malignant potential tumors of the ovary. Anat Pathol 1997;
2:197-226
Limber GK, King RE, Silverberg SG: Pseudomyxoma peritonei: a report of ten
cases. Ann Surg 1973; 178:587-593
Sugarbaker PH: Pseudomyxoma peritonei (Review). Cancer Treat Res 1996;
81:105-119
Nitecki SS, Wolf BG, Schlinkert, et al: The natural history of surgically
treated primary adenocarcinoma of the appendix. Ann Surg 1994; 29:51-57
Sugarbaker PH, Kern K, Lack E: Malignant pseudomyxoma peritonei of colonic
origin. natural history and presentation of a curative approach to treatment.
Dis Colon Rectum 1987; 30:772-779
Fann JI, Vierra M, Fisher D, et al: Pseudomyxoma peritonei. Surg Gynecol
Obstet 1993; 177:441-447
Sugarbaker PH: Pseudomyxoma peritonei: a cancer whose biology is
characterized by a redistribution phenomenon (Editorial). Ann Surg 1994;
219:109-111
Sugarbaker PH, Jablonski KA: Prognostic features of 51 colorectal and 30
appendiceal cancer patients with peritoneal carcinomatosis treated by
cytoreductive surgery and intraperitoneal chemotherapy. Ann Surg 1995;
221:124-132
Jacquer P, Jelenich J, Sugarbaker PH: Evaluation of computed tomography in
patients with peritoneal carcinomatosis. Cancer 1994; 72:1631-1636
Tsai CJ: Ultrasound features of disseminated adenomucosis (pseudomyxoma). Br
J Radiol 1998; 71:564-566
Chintapalli KN, Chopra S, Metter DF: Abnormal radionuclide uptake in
pseudomyxoma peritonei. Clin Nucl Med 1998; 23:90-92
Sugarbaker PH: Peritonectomy procedures. Ann Surg 1995; 221:29-42
Suzuki T, Umekita N, Inoue S, et al: Three cases of pseudomyxoma peritonei
treated with intraperitoneal inoculation of cisplatin through an implantable
system. Gan To Kagaku Ryoho 1998; 25:1449-1451
Ohta Y, Shima Y, Sasaki N, et al: Successful treatment of pseudomyxoma
peritonei using combination chemotherapy of intraperitoneal low-dose CDDP and
oral 5'DFUR administration. Gan To Kagaku Ryoho 1998; 25:929-932
Hyperthermia exerts its beneficial effect in several ways, according to the
current understanding.
Several studies have shown increased apoptosis in response to heat.
Hyperthermia damages the membranes, cytoskeleton, and nucleus functions of
malignant cells. It causes irreversible damage to cellular perspiration of these
cells.
Heat above 41 C also pushes cancer cells toward acidosis (decreased cellular
pH) which decreases the cells’ viability and transplantability.
Hyperthermia activates the immune system. One source says: "Heat has a well
known stimulatory effect on the immune system causing both increased production
of interferon alpha, and increased immune surveillance." Another source mentions
the release of lysosomes.
Tumors have a tortuous growth of vessels feeding them blood, and these
vessels are unable to dilate and dissipate heat as normal vessels do. So tumors
take longer to heat, but then concentrate the heat within themselves. Tumor
blood flow is increased by hyperthermia despite the fact that tumor-formed
vessels do not expand in response to heat. Normal vessels are incorporated into
the growing tumor mass and are able to dilate in response to heat, and to
channel more blood into the tumor.
Tumor masses tend to have hypoxic (oxygen deprived) cells within the inner
part of the tumor. These cells are resistant to radiation, but they are very
sensitive to heat. This is why hyperthermia is an ideal companion to radiation:
radiation kills the oxygenated outer cells, while hyperthermia acts on the inner
low-oxygen cells, oxygenating them and so making them more susceptible to
radiation damage. It is also thought that hyperthermia’s induced accumulation of
proteins inhibits the malignant cells from repairing the damage sustained.
One source puts it thus: "It can be hypothesized that hypoxic cells in the
center of a tumor are relatively radioresistant but thermosensitive, whereas
well-vascularized peripheral portions of the tumor are more sensitive to
irradiation. This supports the use of combined radiation and heat; hyperthermia
is especially effective against centrally located hypoxic cells, and irradiation
eliminates the tumor cells in the periphery of the tumor, where heat would be
less effective."
Hyperthermia is considered a modifier of radiation response. "Heat
selectively kills cells that are chronically hypoxic and nutritionally deficient
and have a low pH -- characteristics shared by tumor cells in comparison with
the better oxygenated and better nourished normal cells. Furthermore, heat
preferentially kills cells in the S phase of the proliferative cycle, which are
known to be resistant to irradiation." Another source notes that "marked
complementary synergism across the cell cycle was observed when heat and
radiation were combined."
As the research gains momentum, more reasons for the use of hyperthermia are
continuously being identified.
How does hyperthermia work?
Cancer
cells are different from normal cells in many ways, including their responses to
heat. In most cases, these differences make it possible for hyperthermia to kill
cancer cells without significantly harming normal tissue surrounding the tumor.
Hyperthermia damages the tumor’s blood vessel structure and causes other
changes in tumor cell function. These effects are enhanced in hypoxic
(oxygen-deprived), highly acidic environments. Tumors are often more hypoxic and
acidic than normal tissues, which may also partially explain why hyperthermia
can damage cancer cells while leaving healthy surrounding tissue largely
intact.
Although hyperthermia alone is damaging to tumors, it is most
effective when used in conjunction with radiation therapy and, to a more limited
extent, with chemotherapy. When used in combination with radiation therapy,
hyperthermia makes it more difficult for tumor cells to repair radiation-induced
damage. It also makes certain cells that are normally resistant to radiation
more sensitive to the therapy
HYPERTHERMIA
This is the process of heating a tumor approximately 10
degrees fahrenheit. It is generally done with a microwave type mechanism. This
in and of itself is capable of killing certain types of cancers. But that is not
where the great promise lies. It has been found that hyperthermia can magnify
the benefits of chemotherapy or radiation therapy several fold without much
downside risk. A critical matter is monitoring the exact temperature of the
tumor and the surrounding tissue. For this reason, it had previously been done
on lesions relatively near the surface. However, great advances are being made,
and it is being tried with many types of cancers. The moderate increase in
temperature is not damaging to ordinary cells and not dramatically uncomfortable
to the patient. In many applications, hyperthermia is considered experimental today with
tremendous potential.
-The Society was organized to provide a forum for members to discuss their
ideas on the use of hyperthermia and present their clinical experience at
meetings.
Valley Cancer Institute - Cancer Hyperthermia Holistic
Center http://www.vci.org
- Valley Cancer Institute researches and clinically uses Hyperthermia, natural
less toxic cancerocidal modality, to improve cancer treatment results while
decreasing side effects of conventional therapies
Intraperitoneal Chemotherapy for Mucinous Tumor of the
Appendix?
Question The
patient had a recent appendectomy with pathologic findings of mucinous tumor
with uncertain malignant potential by immunohistochemical investigation. The
computerized tomography scan, colonoscopy, and liver function tests are normal.
We are planning a right hemicolectomy. What is your opinion about
intraperitoneal chemotherapy in this case?
Markon Ilya, MD
Response from Lewis
Flint, MD Professor, Department of Surgery, University of South Florida
College of Medicine; Director, Regional Trauma Center, Tampa General Hospital;
Department of Surgery, Tampa General Hospital, Tampa, Florida.
The question, as posed, is straightforward. Mucinous tumors of
uncertain malignant potential are associated with a good prognosis as long as
the tumor is completely removed (usually with right hemicolectomy), there are no
lymph node or distant metastases (in which case the uncertainty of malignant
potential would be eliminated), and there are no signs of extension of the tumor
outside the appendix. Carr reported that these tumors behave as benign tumors
with prognosis determined by mucin found outside of the appendix and
extra-appendiceal epithelial cells.[1] Sugarbaker and Jablonski
reported a large experience with early postoperative intraperitoneal
chemotherapy done for patients with peritoneal carcinomatosis.[2]
They observed generally good results, especially in patients with tumors arising
from the appendix. However, they emphasized the significant morbidity and
mortality that accompanies this approach. Their results would strongly suggest
that there is no role for intraperitoneal chemotherapy unless peritoneal
carcinoma implants are documented. Even if peritoneal carcinomatosis is
documented, chemotherapy should probably be done as part of an investigational
effort.
Posted 06/27/2002
References
Carr NJ. Epithelial noncarcinoid tumors and tumor-like lesions of the
appendix. A clinicopathologic study of 184 patients with a multivariate analysis
of prognostic factors. Cancer. 1995;75:757-768.
Sugarbaker PH, Jablonski KA. Prognostic features of 51 colorectal and 130
appendiceal cancer patients with peritoneal carcinomatosis treated by
cytoreductive surgery and intraperitoneal chemotherapy. Ann Surg.
1995;221:124-133.
Purpose 
European Malignant Hyperthermia Group Since the first meeting in 1983
the group has met regularly. At present, twenty laboratories in twelve European
countries are performing in vitro contracture tests using the protocol of the
EMHG. 
