Cancer studies
Chapter 12 of the HBOT Manual
(If anyone has comments or documentation, studies, etc. that we can include here, please email us)

In Philadelphia, researchers at the University of Pennsylvania are laying the groundwork for a series of studies to determine how patients with head and neck tumors benefit from breathing pure oxygen before and after surgery.
The breathing treatment, called hyperbaric oxygen therapy (HBOT), is an unconventional method of treating cancer, though HBOT has been used for decades to treat other conditions such as heart problems, carbon monoxide poisoning, non-healing wounds such as severe burns, and scuba diving-related injuries. Breathing additional oxygen is believed to improve the body's ability to kill germs and heal. HBOT patients breathe pure oxygen, which is twice the atmospheric pressure and administered in either of two ways: The patient lies on a stretcher in a sealed, specially pressurized chamber, or inhales the oxygen from a mask or hood while sitting in a specialized chamber.
"Although scientists have known for years that hyperbaric oxygen can reverse tissue damage, there still are a lot of questions to be answered," said Stephen R. Thom, M.D., Ph.D., the center's principal investigator and a professor of emergency medicine at the University. "Our goals are to try to ascertain, under rigorous methods, the mechanisms of action, safety, and clinical efficacy of hyperbaric oxygen, and to develop and validate a model to say who benefits from this treatment."
The researchers at the new Specialized Center of Research in Hyperbaric Oxygen Therapy want to know "how much of an effect"--including on reversal of body tissue damage and on the growth and spread of tumors--HBOT has on people with head and neck tumors who have had radiation treatments, but need surgery again.
Dr. Thom said that previous studies have shown that HBOT can reverse tissue damage, but did not show by how much. A critical component of the clinical trial is that investigators will measure patient's blood vessels throughout the trial to determine if healthy tissue is growing back. The key question, Dr. Thom noted, is, "Do hyperbaric oxygen treatments have an effect on patient outcomes? We think they do, but the study will tell us for sure."

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NEW STRATEGY FOR ATTACKING BRAIN TUMORS.(News)

The Cincinnati Post (Cincinnati, OH); 6/18/2004; Wood, Roy

Byline: Roy Wood Post staff reporter

The concept of increasing atmospheric pressure to heal ailments dates to the 1600s.

Now, University of Cincinnati researchers and doctors at University Hospital are studying the use of hyperbaric chambers for treating brain tumor patients suffering potentially fatal side effects from brain radiation therapy.

"These patients don't have a whole lot of options," says Dr. Laurie Gesell, director of the Division of Hyperbaric Medicine in the UC's Department of Emergency Medicine, who's leading the study.

"They have a devastating disease, they have a brain tumor, which has significant morbidity associated with it," she said. "They then get treated aggressively to try to treat that horrific disease.

"They end up with a complication that can have just as much significant morbidity or mortality as the disease itself."

Gesell is working with University Hospital's new Brain Radionecrosis Center, the only facility in the country participating in the two-year, $450,000 study. It's funded by the National Cancer Institute, through the National Institutes of Health.

Gesell explains the problem this way.

When patients are diagnosed with brain tumors, typical treatment includes radiation therapy, chemotherapy or surgery.

That often leads to a usually treatable brain radiation injury.

Soft-tissue injury to the brain begins with swelling that sometimes disappears without treatment. So when it's first diagnosed, doctors might just watch it, Gesell says.

If patients start showing clinical symptoms they're put on steroids.

"If the steroids don't control the progressive injury pattern, the dose of the steroids will increase and increase and increase," Gesell says.

"But there are complications and side effects from the steroids, which can be just as devastating for individuals' health," she said.

"If the steroids don't work in controlling this disease, the only thing really left out there as a standard of care is to go in and surgically cut out that portion of the brain.

"But lots of brain tumors are in areas where you can't do surgery because they're too far down or in areas where it's too risky to do surgery."

Furthermore, the incidence seems to be increasing because of the aggressiveness with which doctors are trying to treat brain tumors, she says.

Although more study needs to be done to determine how many people develop side effects from brain radiation therapy, about 200,000 people a year in the United States are diagnosed with either primary or secondary brain tumors, says Gesell.

"Physicians have become more aggressive in treating these brain tumors in order to get better outcomes for their patients," Gesell says.

"That also means that the incidence of problems and complications from the radiation has also increased."

Knowing that hyperbaric oxygen treatment is the standard of care for conditions such as carbon monoxide poisoning, hard-to-heal wounds, crush injuries, decompression sickness and a host of other conditions, doctors at University began using hyperbaric treatments on the patients with the conciliation -- known as brain radionecrosis -- about six years ago.

The treatment involves placing the patient in a pressure chamber and having the patient breathe pure oxygen at a pressure similar to being under 33 to 66 feet of seawater, Gesell says. Each treatment lasts 1 1/2 hours.

Treatments are repeated every day for one to three months.

Preliminary results are promising, Gesell says. In many patients damaged tissues have been healed completely.

In about 86 percent of cases, doctors were able to stabilize or decrease the steroids dosage. In some cases, patients even were able to stop taking steroids.

MRIs showed that the disease had stabilized or improved in 78 percent of patients, Gesell says.

Armed with the results, doctors applied for the funding for the current study.

Doctors believe the pure oxygen at increased pressure causes new blood vessels to grow in injured tissue, but no one is sure exactly how, says Gesell.

Gesell and her team of researchers at UC and the Neuroscience Institute set up the Brain Radionecrosis Center to study not only how well hyperbaric oxygen therapy works, but also the mechanism that enables it to work.

Her collaborators in the research are Christopher Lindsell of the Institute for Health Policy and Health Services Research at UC; Dr. Ronald Warnick, a neurosurgeon with the Mayfield Clinic and the Neuroscience Institute and professor of neurosurgery at UC; and Dr. John Breneman, a neuroradiologist with institute and professor of radiation oncology and neurosurgery at UC.

The initial study, known as a pilot trial, will involve only 30 patients, but researchers have already been receiving calls from all over the nation, Gesell says.

If the treatment proves to be as effective as preliminary findings indicate, the team expects to expand its study into a multi-center trial involving a large number of patients.

That ultimately could lead to the establishment of hyperbaric oxygen therapy as the main treatment for patients with brain radionecrosis.

CAPTION(S):

Photo (2)

MELVIN GRIER/The Post

The hyperbaric treatment area at the University Hospital.

MELVIN GRIER/The Post

Joshua Inham, an RN, checks a patient receiving hyberbaric oxygen therapy at University Hospital's hyperbaric treatment center.

COPYRIGHT 2004 The Cincinnati Post. All rights reserved. Reproduced with the permission of the Dialog Corporation by Gale Group.
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Some more info that was sent to me:
At 07:40 PM 01/21/2001 -0500, you wrote:
>Michael, can you tell me where to find these studies on the web?
>Robert
OK, here it is:
I have changed HBO to HDO.  I hope the tables transpose properly on email:

Active neoplastic disease is considered by many to be a relative contraindication - and, in fact, was listed as such by the Undersea and Hyperbaric Medical Society for nearly two decades. The concern centers
around: 1) does HDO2 enhance tumor cell replication?, 2) does HDO2 enhance the induction of carcinogenesis?, and 3) does HDO2 increase the incidence or degree of metastatic disease? A recent UHMS survey of hyperbaric physician consultants found that most respondents felt strongly that the available
literature failed to demonstrate a carcinogenic effect for HDO2. Nevertheless, 28-46% (depending on circumstances) felt that the potential carcinogenic effects of HDO2 belong in the informed consent, and 45%
believed they would be at legal risk if a tumor recurred/grew after HDO2 therapy. Ten percent of respondents felt that HDO2 was potentially carcinogenic.
Marx studied oral cancer in the hamster check pouch after application of 1,2-9, 10 dimetyl Beuzanthrocene (DMBA) and the effect of HDO2.1 DMBA was applied three times per week to both the control (no HDO2) and experimental group (HDO2 at 2.4 ATA qd). Animals were studied for 22 weeks and, surprisingly, HDO2 actually suppressed dysplasia and delayed the emergence of carcinoma from the dysplasia by one month. Growth rates of tumors were 'equal in both groups.
In a model of colon cancer Williams and colleagues exposed rats -to 1,2 Dimethylhydrozine over 20 weeks.2 Again, the control group received no HDO2 and the experimental group received I 00 HDO2 exposures (2. 6 ATA x 90 min. qd). There was no significant difference in cancer size or its distribution, suggesting HDO2 has no effect on the enhancement or inhibition of colon tumors in this model.

TABLE I

(Control)                         (HDO2) p Value

Mean # of tumors       2.9 3.0 >0.1
Mean Tumor Density   0.15 0.15 1.0
Tumors in proximal     1/3 30% 30% >0.1
Tumors in middle        1/3 35% 30% >0.1
Tumors in Distat         1/3 35% 40% >0.1

Williams RB et al 1991

Feldmeier has recently reviewed the literature for published reports or studies related to a possible cancer causing or growth enhancing effect by HDO2.3 He found 24 such references: 12 clinical reports,  11 animal studies, and one that reported both on animal study and a clinical report. (Tables 2-5)

TABLE 2
ANIMAL STUDIES SUGGESTING CANCER PROMOTING EFFECTS OF HDO2

AUTHOR YEAR COMMENT

Shewell &    1980 88% mets w/HDO2
Thompson         60% mets w/Air
McMillian   1989 DBA tumors in hamsters
   HDO2-3.56/animal (10.8mm2) Air-9.6/animal             (3.5mm2)

TABLE 3
CLINICAL REPORTS SUGGESTING CANCER PROMOTING EFFECTS OF HDO2

AUTHOR YEAR COMMENT

Johnson      1966 25 Radiosensitized pts. w/advanced cervical cancer
                 increased mets rate
Cade, et al. 1967 40 Radiosensitized pts. w/ bladder cancer increased
Eltorai,et al 1987 3 cases of increased urothelial tumor growth                                                          w/adjunt. HDO2

TABLE 4
ANIMAL STUDIES SHOWING NO CANCER PROMOTING EFFECTS OF HDO2*
*Feldmeier UHN4 1994;21:4

Author          Year     Comment

MoCredie      1966 C3 HBA mouse mammary tumor
Suit, et al     1966 Strong A and BDF mouse mammary tumor
Decosse       1966 Mouse Melanoma
Johnson       1967 Mouse Melanoma and Leukemia
Dettmer, et al       1968 Rat Carcinosarcoma
Evans           1969 Mouse Skin Cancer
Feder           1968 Mouse Rhabdomyosarcoma
Johnson       1971 Mouse Lymphoblastic Leukemia
Marx            1988 SCCA in hamsters
Headley       1991 SCCA in nude mice

TABLE 5
CLINICAL REPORTS SHOWING NO CANCER PROMOTING EFFECTS OF HDO2
Feldmeier, et al. UHM 1994;21(4)

Author           Year     Comment

Van Denbrenk etal   1967    85 Pts. w/ Head/Neck CA
Johnson, etal          1974    64 Pts. w/ Cervical CA
Henk, et al     1977    276 Pts. w/ Head/Neck CA
Henk, et al     1977    104 Pts. w/ Head/Neck CA
Bennett, et al 1977    213 Pts. w/Cervical CA
Perrins, et al   1978    236 Pts. w/Bladder CA
Watson, et al 1978    320 Pts. W/Cervical CA
Dische           1979          1500 Pts. W/ Head/Neck, Bronchus, or Cervical CA
Brady, et al    1981    65 Pts. W/ Cervical CA
Marx & Johnson             1988    2000 ORN Pts. W/ Head/Neck CA

Feldmeier points out that many of these studies occurred prior to our current understanding of cancer causation and progression and thus no definitive conclusions can be drawn. He does, however, contend that the literature to date fails to make a convincing case for a cancer-causing or growth enhancing effect of HDO2.

A review of the most recent literature involving HDO2 and Head and Neck cancer in irradiated patients not only indicates that there is no evidence of cancer growth enhancement but rather shows a reduced incidence of cancer recurrence. While HDO2 should not currently be considered as an anti-neoplastic agent, the preponderance of data suggests that cancer, past or present, should not be a contraindication to the use of HDO2 in appropriately referred patients.

REFERENCES

I.Marx RE: Radiation Injury to tissue. In: Hyperbaric Medicine Practice.
Kindwall EP (Ed). Best Publishing Company. Flagstaff (AZ) 1994. Chapter 23,
498-503

2.Williams RB, et al.: Effect of hypetbaric oxygen on induced colon cancer in rats. Proceedings of the 25th Annual Meeting of the Association for Academic Surgery. 1991

3.Feldmeier JJ, et al.: Does hyperbaric oxygen have a cancer-causing or promoting effect? A review of the pertinent literature. Undersea and Hyperbaric Medicine 1994;2(4):467-475

4.Granstrom G: Tumor recurrence and development of new head and neck cancers after HDO2-treatment a prospective clinical study. Proceedings: Int. Joint Meeting on Hyperbaric and Underwater Medicine 1996, Milan:47-60

DOES HBO REDUCE CANCER RECURRENCE
IN IRRADIATED PATIENTS?
The National Cancer Institute issued a consensus statement in 1990 stating that osteoradionecrosis can be prevented but when present is best managed by hyperbaric oxygen (HBO) alone, or with surgery.1 Late radiation tissue injury is a progressive, obliterative endarteritis which results in a hypoxic, hypovascular, hypocellular tissue bed.2 These changes make healing after surgical procedures difficult or impossible. This has led to the development of the "Marx Protocol", which induces neovascularization and healing in these damaged tissues and has been proven clincally effective and cost-effective.
Marx previously reported the 5 year recurrence rate of squamous cell carcinoma in 405 patients followed from 1985-1991.2 Of these patients, 245 received HBO under a protocol for reconstructive surgery, or for mandibular osteoradionecrosis. All were staged using the Joint Commission of Cancer Staging TNM classification system.
TABLE 1
FIVE YEAR CANCER RECURRENCE RATES
Stage Non-HBO    Recurred   HBO Recurred
I   296 (21%)     36   6 (16%)
II 58 (24%) 94 17 (18%)
III 50       6 (32%)     92        19 (21%)
IV       23       9 (38%)     23         6 (28%)
The results reveal a reduced incidence of recurrence in every stage of squamous cell carcinoma in those who have been exposed to HBO.(Table 1) These differences, though statistically significant, were small, and Marx was quick to point out that while HBO may have a chemoprotective effect, it is also possible that the greater radiation dose was applied to those who required HBO and thus one would anticipate better tumor control.
A recent prospective study followed 46 cancer patients for 3 years who were exposed to a minimum of 30 hours of HBO.3 This study population was compared to a study-group matched for tumor type, age, sex, stage and year of treatment.
TABLE 2
CANCER RECURRENCE RATES
CONTROLS HBO GROUP
Tumor type # Recur. Rate # Recurr. Rate
Gingiva     10 2 10 1
Maxilla 7 3 7 0
Floor of mouth    7 2 7   0
Salivary gland     7 3 7   3
Tonsil 5 1 5   0
Oral tongue 4 1 4   0
Ear cana    3 0 3   0
Thyroid      2 0 2 0
Eye   2 0 2 0
Nose 1 0 1   0
Epipharynx 1 0 1   0

Totals 49     12 (24.5%)   49               4 (8.2%)

Review of this data (Table 2) shows a reduced incidence of cancer recurrence in the HBO group when compared to a matched control group.
Of note is the fact that the matched control group was not statistically different from a larger control group consisting of all 1175 cancer patients treated by the ENT Division of the author's institution, between 1988 and 1992.
Additional review of data indicated that within the HBO-treated group of patients, there were fewer than expected recurrences of maxillary carcinomas, gingival carcinoma, floor of the mouth carcinomas and tongue carcinomas. Only in the recurrence rate of adenoidcystic carcinomas of the salivary glands was there a comparable number between the HBO and non-HBO treated groups.
The preponderance of available literature now suggests that HBO is not cancer causing or cancer promoting.4 Work by both Marx and Granstrom has provided another provocative conflict that requires further clinical research - namely: can HBO be considered chemoprotective against cancer recurrence. Time (and research) will tell.
REFERENCES
1.National Cancer Institute: Monograph 1990: No. 9 Consensus Development Conference on Oral Complications of Cancer Therapies: Diagnosis, Prevention and Treatment. US Dept. HHS. National Institute of Health, Washington, D.C.
2.Marx RE:. Radiation Injury to Tissue. In: Hyperbaric Medicine Practice. Kindwall EP, Ed.. Best Publishing Co., Flagstaff (AZ) 1994;23:500-503.
3.Granstrom G: Tumor recurrence and development of new head and neck cancers after HBO treatment, a prospective clinical study. Proceedings: Int. Joint Meeting of Hyperbaric and Underwater Medicine. 1996, Milan:47-60
4.Feldmeier JJ, et al.: Does hyperbaric oxygen have a cancer causing or promoting effect? A review of the pertinent literature. Undersea and Hyperbaric Medicine 1994;21(4):467-475

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Discussing patient histories is an essential part of communication and we have more science to support oxygen therapy than any other intervention in medicine. Why increasingthe inspired partial pressure a small amount over what is routinely used should be regarded as snake oil is beyond me and shows the fundamental ignorance of our profession. It is NOT quackery. There is no evidence that cancer is activated by HBO indeed the first post WW 2 use of HBO was as an adjunct to radiotherapy in which high tissue tensions increase the kill rate. There was a trial published from a London medical school about 5 years ago on  the value of HBOT in glottic cancer.
.
Best wishes
Philip James MD

Wolfson Hyperbaric Medicine Unit
University of Dundee
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Centers to research alternative medicine therapies for cancer -
               http://www.nccam.nih.gov 10/9/2000

               Recent national surveys reveal that the majority of cancer patients
               use some form of complementary or alternative medicine, such as
               herbs, vitamins, or meditation. In response to this, the National Center
               for Complementary and Alternative Medicine (NCCAM) plans to
               establish two specialized centers to conduct basic and clinical
               research on complementary and alternative medicine (CAM) therapies
               for cancer.

               "These approaches have not yet been proven effective. Moreover,
               some herbs may cause harmful interactions with other drugs used as
               standard treatment by cancer patients," said Stephen E. Straus, M.D.,
               NCCAM Director.

               Johns Hopkins University (Baltimore, MD) and the University of
               Pennsylvania (Philadelphia, PA) have received awards totaling some $8
               million each, over a five-year period for CAM research.

               The John Hopkins Center for Cancer Complementary Medicine is
               planning the following four research projects:

               Project 1 will examine anti-oxidant effects of herbs in cancer cells.
               Project 2 will use four established animal models that reflect different
               aspects of pain in cancer patients. Project 3 will investigate the
               safety and efficacy of PC-SPES, a popular mixture of Chinese herbal
               medications, in men with prostate cancer. Project 4 will examine the
               effects of prayer on disease recurrence, immune and neuroendocrine
               function in African American women with breast cancer.

               The University of Pennsylvania Specialized Center of Research in
               Hyperbaric Oxygen Therapy is proposing four projects designed to
               examine mechanisms of action, safety and clinical efficacy of
               hyperbaric oxygen therapy for the treatment of head and neck
               tumors:

               Project 1 will evaluate treatment outcomes for patients who have
               undergone laryngectomy. Project 2 will examine the effects of
               hyperbaric oxygen on growth of blood vessels and tumors. Project 3
               will characterize the effects of hyperbaric oxygen on cell adhesion and
               growth of metastatic tumor cells in the lung. Project 4 will test the
               effects of elevated oxygen pressures on cellular levels of nitric oxide.

               For more information, visit http://www.nccam.nih.gov.

               SOURCE: National Institutes of Health

               Edited by Kimberly Fryling Assistant Editor, Healthcare Group
               kfryling@vertical.net
                 
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Healing with Hyperbaric Oxygen Therapy

                                            Chronic wounds heal faster with Hyperbarics

Some people develop sores or wounds that just won't heal. This may be due to low oxygen in damaged tissues. HBOT restores the body's ability to heal the wound by increasing oxygen to the area.

HBOT Speeds Up The Healing Process in Smokers
People who smoke do not heal as well as non smokers. HBOT can help smokers undergoing some types of surgeries such as cosmetic surgery  heal more normally.

Burn Victims Improve With Hyperbaric Oxygen 
HBOT has been used for years to speed up healing in burn victims. It is also beneficial for patients with
smoke inhalation and carbon monoxide poisoning.

Diabetic Ulcers Heal Faster With Hyperbaric Oxygen
Diabetes is a disease that affects the small blood vessels in the tissues which results in wounds or ulcers that may last months to years. These wounds often develop from incidental injuries to the body and may become infected which can spread to the deeper tissues and the bones and may even require amputation. HBOT can help heal these wounds frequently without surgery.

Damaged Tissues from Cancer / Radiation Therapy Improve with Hyperbaric Oxygen
HBOT can restore tissues and cells damaged from chemotherapy and radiation treatments in cancer patients. Head, neck and other cancer treatments that damage the jaw bone may require HBOT to restore the tissues. Side effects of cancer therapy may cause damage to the bladder (hemorrhagic cystitis),
damage to the intestines (radiation enteritis) and other conditions that may be improved by HBOT. Breast cancer patients undergoing reconstruction may need HBOT to allow radiation damaged tissues to heal.

                                          British Medical Journal April 17, 1999
                                               Hyperbaric  Oxygen Therapy
(Letter to the Editor)
Author/s: Charlotte Coles

Combination with radiotherapy in cancer is of proved benefit but rarely used

EDITOR--Leach et al discuss various clinical applications of hyperbaric oxygen therapy.[1] They conclude that the use of hyperbaric oxygen should be evidence based, but their article omits an important and much researched clinical use--combined radiotherapy and hyperbaric oxygen in patients with cancer.

Hyperbaric oxygen was first used 50 years ago to increase cellular oxygen delivery and thus overcome hypoxia as a cause of tumour radioresistance. The Medical Research Council coordinated several large multicentre trials.  Significant benefit was found in both locoregional tumour control and
survival in head and neck cancer[2] and carcinoma of the uterine cervix.[3] A meta-analysis of combined hyperbaric oxygen and radiotherapy reviewed 19 trials in tumours at various sites with a total of
2488 patients.[4] Locoregional control with the combined modality was 62%, versus 53% with radiotherapy alone (P [is less than] 0.0001). Subgroup analysis showed that the greatest improvement in local control
and survival occurred in head and neck cancer.

This scientifically proved application of hyperbaric oxygen is now unused.
It was initially hoped that chemical radiosensitisers would substitute for hyperbaric oxygen and so simplify treatment, because animal studies had generated considerable optimism; clinical trials, however, showed only marginal therapeutic gain.

Other evidence based developments in radiotherapy have not been implemented.
Recent trials of altered radiotherapy fractionation have shown increased local control and survival in some tumours.[5] The head and neck hyperfractionation trial of the European Organisation for Research and
Treatment of Cancer showed a 19% absolute (47.5% relative) increase in local control and consequent increase in survival. In non-small cell lung cancer a 9% absolute improvement in survival was obtained with continuous hyperfractionated accelerated radiotherapy.

These strategies are largely neglected in the United Kingdom because of a lack of radiotherapy resources. The Faculty of Clinical Oncology's report on radiotherapy in 1992 7 shows large inequalities in service provision, with unacceptable delays before radiotherapy is started. To provide an acceptable minimum of four linear accelerators per million population, capital investment of 50[pounds sterling] million a year for five years is required, with commitment to the revenue cost of trained staff. This should be a stated target of the NHS modernisation fund.

Radiotherapy is the most important nonsurgical modality in the curative treatment of cancer, yet it is underused in the United Kingdom because of a lack of resources. At present, evidence based practice in radiotherapy is unachievable.

Charlotte Coles, Specialist registrar in clinical oncology
Michael Williams, Clinical director in oncology
Nell Burnet, Honorary consultant in oncology

Addenbrooke's Hospital, Oncology Centre, Cambridge CB2 2QQ
joncha7069@aol.com

[1] Leach RM, Rees PJ, Wilmshurst R ABC of oxygen. Hyperbaric oxygen
therapy. BMJ 1998;317:1140-3. (24 October.)

[2] Henk JM, Kunkler PB, Smith CW. Radiotherapy and hyperbaric oxygen in
head and neck cancer. Final report of  first controlled clinical trial.
Lancet 1977;ii: 101-3.

[3] Watson ER, Halnan RE, Dische S, Saunders MI, Cade IS, McEwen JB, et al.
Hyperbaric oxygen and radiotherapy: a Medical Research Council trial in
carcinoma of the cervix. Br J Radiol 1978;51:879-87.

[4] Horsman MR, Overgaard J. The oxygen effect. Basic clinical radiobiology.
2nd ed. London: Arnold, 1997.

[5] Benson RJ, Burner NG. Altered radiotherapy fractionation: an opportunity
not to be missed. Clin Oncol 1998;10:150-4.

Complication rates are much lower than authors suggest

EDITOR-
We would be interested to know where Leach et al obtained their figures for complication rates of hyperbaric oxygen therapy[1]; our practice and that of others suggest that they are pessimistic.

Our unit provides over 2700 treatments with hyperbaric oxygen in about 250 patients each year for a range of indications, including problem wounds, decompression illness, and carbon monoxide poisoning. According to Leach et al, we should expect two to five patients with severe central neurological
symptoms and 38 patients with symptomatic barotrauma or pulmonary symptoms each year. In fact, during 1997 one patient had an oxygen toxic fit, 18 had symptomatic barotrauma, and one had symptoms of severe pulmonary toxicity.

Over the past three years the incidence of central neurological toxicity has been 0.5% (three patients) and of symptomatic barotrauma 7% (49 patients).

We accept that many patients have minor measurable changes in respiratory function, but these are rarely symptomatic and not clinically important. A report of the international hyperbaric incident monitoring study running from the Royal Adelaide Hospital suggests figures of [is less than] 1% (seven patients) for neurological toxicity and [is less than] 10% (21 patients) for barotrauma overall.[2] Others have
produced comparable figures.[3 4] Patients are unlikely to develop decompression illness after hyperbaric oxygen therapy (as suggested by Leach et al) unless given air for prolonged periods. To our knowledge this has never been reported, although it is certainly a risk for staff breathing air.

Fire is the most common fatal complication. Over the past 20 years, with millions of compressions in clinical hyperbaric chambers, 52 deaths have been reported.[5] Almost all were preventable; 35 were in one country and due to inadequate precautions. In particular, 10 incidents resulting in 20 deaths occurred when banned substances (including lighted cigarettes) were taken into the chamber. Many treatment modalities and drugs could benefit from a safety record as good as that for modern hyperbaric medicine.

Safety figures are meaningless in the absence of therapeutic benefit, and evidence based admission and discharge criteria are essential for decision making. We strive to achieve evidence based practice but at present must rely on relatively low levels of evidence for many clinical decisions.

Barbara E Trytko Staff specialist, intensive care and hyperbaric medicine

Mike Bennett Director
Department of Diving and Hyperbaric Medicine, Prince of Wales Hospital,
Sydney, NSW 2031, Australia

Ref:
[1] Leach RM, Rees PJ, Wilmshurst R ABC of oxygen. Hyperbaric oxygen
therapy. BMJ 1998;317:1140-3. (24 October.)

[2] Pirone C, Bullock M, Williamson J. Report of 1996 data from the
international hyperbaric incident monitoring study (HIMS). Adelaide:
Australia Safety Foundation, Royal Adelaide Hospital, 1997.

[3] Clark JM. Oxygen toxicity. In: Bennett P, Elliott D, eds. The physiology
of medicine and diving. London: WB Saunders, 1993:121-69.

[4] Weslau W, Almeling M. Incidence of oxygen intoxication of the central
nervous system in hyperbaric oxygen therapy. In: Marroni A, Oriani G, Wattel
F, eds. Proceedings of the international joint meeting  of hyperbaric and
underwater medicine, Milan. Victoria: Graphica, 1996.

[5] Sheffield PJ, Desautels DA. Hyperbaric and hypobaric chamber fires: a 73
year analysis. Undersea and Hyperbaric Medicine 1997;24:153-64.



Authors' reply

EDITOR-
It was not our intention to neglect the value of hyperbaric oxygen therapy in the management of certain tumours. Our article acknowledges the advantages of hyperbaric over normobaric oxygen in promoting angiogenesis and wound healing in irradiated tissue. In particular, we reported the value of preoperative and postoperative hyperbaric oxygen in the prevention of soft tissue radionecrosis and osteonecrosis during treatment of local head and neck turnouts requiring local mandibular radiotherapy.

Coles et al comment that combined radiotherapy and hyperbaric oxygen in the management of cancer, although of proved benefit, is not generally in common use. As they report, there are several reasons for this, not least of which are the cost and resource implications and the practical issues of delivering the two treatments simultaneously. They also suggest that available radiotherapy resources are unlikely to be directed towards the use of combined radiotherapy and hyperbaric oxygen in the near future. In our
brief article, which was for a non-specialist readership, we did not have enough space to give a detailed cost-benefit analysis or an explanation of why a proved treatment was not used. The lack of resources in radiotherapy and oncology is a problem currently affecting many specialties.

The complication rates for hyperbaric oxygen therapy that we quoted were derived from studies and review articles published during the past 25 years.  Complication rates in individual studies primarily depend on the definition of a severe complication, and this is likely to account for some of the variability between studies. Many of the early, small studies quote complication rates higher than those reported in our article.[1-4] Although recent complication rates are lower, the data from these early studies should not be dismissed. We hope that Trytko and Bennett will publish the data on their complication rates in peer reviewed form.

Finally, although the risk of decompression illness is small and likely to affect only staff breathing air, it still warrants mention in a list of risks of hyperbaric oxygen. Potential injuries to staff, as during the small
number of associated fires, should be included in a list of risks of the treatment.

Richard Leach Consultant physician

St Thomas's Hospital, London SE1 7EH v.snetkov@umds.ac.uk

Peter Wilmshurst Consultant cardiologist Royal Shrewsbury Hospital, Shrewsbury SY3 8XF

[1] Giebfried JW, Lawson W, Biller HF. Complications of hyperbaric oxygen in the treatment of head and neck disease. Otolaryngol Head Neck Surg  1986;94:508-12.

[2] Ellis ME, Mandal BK. Hyperbaric oxygen treatment: ten years' experience
of a regional infectious diseases unit. J Infect Dis 1983;6:17-28.

[3] Darke SG, King AM, Slack WK. Gas gangrene and related infection:
classification, clinical features and aetiology, management and mortality. A
report of 88 cases. Br J Surg 1977;64:104-12.

[4] Gabb G, Robin ED. Hyperbaric oxygen. A therapy in search of diseases.
Risk-benefit analysis in chest medicine. Chest 1987;92:1074-82.

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Early post-operative hyperbaric oxygen therapy  modifies neutrophile activation.
                                 
Department of Surgery, Kagoshima University School of Medicine


UI - 99357417 AU - Ueno S; Tanabe G; Kihara K; Aoki D; Arikawa K;  Dogomori H; Aikou T TI - Early post-operative hyperbaric oxygen therapy  modifies neutrophile activation. SO - Hepatogastroenterology 1999 May-Jun;46(27):1798-9 AD - First Department of Surgery, Kagoshima University School of Medicine, Japan.

BACKGROUND/AIMS:
To investigate the effect of acute hyperbaric oxygen  therapy (HBOT) on post-operative sinusoidal endothelial cell (SEC)  damage caused by activated neutrophils.

METHODOLOGY:
12 non-cirrhotic patients (Group H), who underwent elective > hepatectomy for liver cancer, were given 2 courses of HBOT: 2.0 atm with  inhalation of 100% oxygen, for 60 min, at 3 hours and 24 hours after  hepatectomy; they were then compared with the 12 patients (Group C) who  had been treated to maintain normal hemodynamic values.

RESULTS:
In  group H, peak levels of polymorphonuclear leukocyte elastase (PMNE) and thrombomodulin (TM) were clearly diminished and delayed compared to Group C.  All subjects in Group C showed more than a 10% increase in CD18  12 hours after surgery; however, in Group H, the elevation of CD18  expression was
clearly suppressed compared to Group C. No patient in Group H had post-operative hyperbilirubinemia or hepatic failure;  however, 3 had post-operative hyperbilirubinemia and 1 had > intraperitoneal infection in
Group C.

CONCLUSIONS:
Our results provide direct evidence that HBOT, especially  at 3 hours after hepatectomy, has favorable effects on the activation of  neutrophiles decreasing SEC injury.

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A study of the effect of Hyperbaric Oxygenation of Yoshida Sarcoma: Especially on its Influence on the Generation Time.
Osada, T. Nagoya J. Med. Sci. 31, 1968: 243-276.
“HBO at 3 ATA suppressed the mitosis of its cells and potentiated the mitosis suppression by alkylating agents and impairment of DNA synthesis; HBO has an additive effect to chemotherapeutic agents.”

Oxygen Poisoning and Tumor Growth.
Campbell, J.A. Br. J Expl. Path. 18; 1937: 191-197.
"Tumors in rodents were not altered.”

Hyperbaric Oxygen in Experimental Cancer in Mice.
Kluft, O., Boerema, I. Cl. Appl. of Hyperbaric Oxygen. Cited by McCredie, 1966.
“Growth of an allogenic tumor in the mouse was inhibited. Distant metastases were decreased.”

Effects of Hyperbaric Oxygen on Growth and Metastses of the C3HBA Tumor in the Mouse
McCredie, J.A., Inch, W.R., Kruuv, J., Watson, T.A. . Cancer, 19; 1966; 1537-1542.

”Found no effect on tumor growth nor on the incidence of lung metastases. "The results suggest that the clinical use of HBO is unlikely to increase the rate of cancer growth or the incidence of metastases."

The Effect of Hyperbaric Oxygen on Pulmonary Metastases in C#H Mice.
Feder, B.H., Stein, J.J., Smith, T.K., Schaeflein, J.W., Boutelle, J.L.,
Conroy, R.M. Radiology, 90:6, 1968: 1181-1184.
”HBO does not enhance the growth rate of distant metastases from C3H implanted tumor.”

Effects of Breathing Gases Containing Oxygen and Carbon Dioxice at 1 and 3 Atmospheres Pressure on Blood Flow and Oxygenation of Tumors.
Kruuv, J., Inch, W.R., McCredie, J.A. Can. J. Physiol. Pharmacol., 45; 1967: 49-56.
”Oxygenation was often improved in the anoxic areas of the tumor in animals breathing O2 at 1 ATA and almost all those at 3 ATA”

Effecto of Duration of Breathing 95% Oxygen plus 5% Carbon Dioxide Before X-irradiation on Cure of C3H Mammary Tumor
Inch, W.R., McCredie, M.A., Sutherland, R.M. Cancer, 25:4; 1970; 926- 931.
“Increased X-Ray Therapy Cure Rate Combined with O2 inhalation.”

Hyperbaric Oxygen and Radiotherapy:
A medical research council trial in carcinoma of the cervix
Watson, E.R., Halnan, K.E., Dische, S., Sanders, M.I., Cade, I.S., McEwen,
J.B., Wiernik, G., Perrins, D.J., Sutherland, I. .
Br. J. Radiol., 51:611, 1978: 879-887.
“Favorable synergistic action of HBO and radiotherapy especially in cancer of the cervix and the head and neck but not the bladder.”

Carcinoma of cervix withy severe anaemia:
Treatment by radiotherapy without blood transfusion using hyperbaric oxygen.
Dische, S., Hewitt, H.B. Br. J. Radiol, 45:539, 1972: 848-850.
“Reported on the use of HBO and radiotherapy on recurrent cancer of the colon and rectum with symptomatic improvement in some cases.”

Does Hyperbaric Oxygenation provoke an Occult Carcinoma in Man?
Ward, et al. Cited by EItorai, I. et al Proceedings of the Eighth International Congress on Hyperbaric Medicine. 1987.
”HBOT was beneficial to cancers in certain cites when combined with radiation, viz.: larynx, salivary glands, tongue, palate, floor of mouth”

High-dose effects in the treatment of carcinoma of the bladder under air and Hyperbaric Oxygen Conditions.
Kirk, J., Wingate, G.W., Watson, E.R. Clin. Radiol. 27:2, 1976: 137-144.
“One third of patients with cancer of the bladder with radiotherapy under HBOT showed high dose effects.”

Radiotherapy and Hyperbaric Oxygen in head and neck cancer. Final report of first controlled clinical trial.
Henk, J.M., Kunkler, P.B., Smith, C.W. Lancet, 2:8028, 1977: 101-103.
“Survival and local recurrence-free rates significantly higher in head and neck cancer when given radiotherapy under HBO.”

Henk, J.M., Smith, C.W. Radiotherapy and Hyperbaric Oxygen in Head and Neck Cancer.
Interim report of 2nd clinical trial. Lancet, 2:8029, 1977: 104-105
Survival and local recurrence-free rates significantly higher in head and neck cancer when given radiotherapy under HBOT.

Does Hyperbaric Oxygenation Provoke an Occult Carcinoma in Man?
Eitorai, I. et al. Proceedings of the Eighth International Congress on Hyperbaric Medicine. 1987.
“HBOT plays some role in sensitizing certain tumors to radiotherapy.”

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Does Hyperbaric Oxygen enhance the effect of photodynamic therapy in patients with advanced esophageal carcinoma? A clinical pilot study.

Endoscopy 2000 Jan;32(1):42-8 (ISSN: 0013-726X)
Maier A; Anegg U; Tomaselli F; Rehak P; Sankin O; Fell B; Renner H; Pinter H; Smolle-Juttner FM; Friehs GB Department of Thoracic and Hyperbaric Surgery, University Medical School, Graz, Austria.

BACKGROUND AND STUDY AIMS:

Experimental studies have shown that the cytotoxicity of porphyrins and related substances is mediated mainly by singlet oxygen and that hypoxic cells are less affected by porphyrins and light. In a clinical pilot study we assessed the use of photodynamic therapy (PDT) under hyperbaric oxygen (HBOT), compared with PDT under normobaric conditions, in patients with advanced esophageal carcinoma.

PATIENTS AND METHODS:

After diagnostic work-up and staging, photosensitization in all patients was carried out using hematoporphyrine derivate (HpD) (2 mg/kg bodyweight 48 hours prior to PDT). We then applied light at 630 nm (KTP-Nd: YAG laser with DYE box) at dose of 300 J/cm, delivered by a fiber with a radial light-diffusing cylinder (length 1 cm), inserted through the biopsy channel of the endoscope. Of the patients, 14 (12 with stage III cancers, and two with stage IV cancers) were treated by PDT alone, and 17 patients (15 with stage III cancers, and two with stage IV cancers) received PDT under HBO at a level of 2 absolute atmospheric pressures (ATA). Transcutaneous PO2 levels of 500-750 mm Hg under HBO, compared with transcutaneous PO2 levels of 60-75 mm Hg under normobaric conditions, were measured.

RESULTS:

Improvements regarding dysphagia and stenosis diameter were obtained in both treatment arms with no significant differences (P = 0.36 and 0.14, respectively). The tumor length also decreased in both groups and showed a significant difference in favour of the PDT/ HBO group (P = 0.002). Kaplan-Meier statistics showed median overall survival for the PDT group and the PDT/HBO group as 7.0 and 12 months respectively. The 12-month survival rate was 28.6% for the PDT group and 41.2% for the PDT/HBO group. Logrank test showed a difference in survival in favor of the PDT/HBO group (P = 0.059). No major treatment-related complication occurred, and the 30-day mortality rate was 0%.

CONCLUSIONS:

Combined PDT/HBO represents a new approach in the treatment of esophageal cancer which, in this pilot study, appears to have enhanced the efficiency of PDT.

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Immune system blamed for cancer
The immune system may help to create tumors
Hyperbaric Oxygen Reduces Inflammation and restores circulation

Long-term over-activation of the immune system may be the single most Important cause of cancer, say experts. When the immune system goes into over-drive it leads to inflammation of the tissues.

Many scientists agree that this inflammation may play a role in the Development of cancer. An inflamed tissue is a melting pot of cancer-causing molecules.

Professor Angus Dalgleish However, a new report suggests that the Importance of this role may have previously been under-estimated.

The authors argue that long-standing over-activation of the immune system is the key event in the genesis of many forms of the disease.

The research could herald an entirely new approach to both preventing and treating cancer. Drug therapy.

It raises the prospect that some existing anti-inflammatory drugs - currently front-line treatments for conditions like arthritis and inflammatory bowel disease - could be used to keep cancer at bay.

According to conventional wisdom, cancer has a variety of causes.

But Dr Ken O'Byrne, of the University of Leicester, and Professor Angus Dalgleish of St George's Hospital in London argue that many of these factors work in the same way - by switching on the immune system for too long.

Dr O'Byrne said: "One of the biggest mysteries of cancer is why the body allows cells to build up cancerous mutations, when it has an immune system that ought to stop this from happening. "But we think that when the immune system overcooks, perhaps because of long-term exposure to an infection or carcinogenic chemical, it loses its ability to fight disease and instead may actually begin to nurture and protect young cancer cells.

"If we could calm the immune system down with certain anti-inflammatory drugs, we might be able to reduce the rates of many common cancers. Kicked into action"

This review makes a fascinating case for the link between exhausted immunity, chronic inflammation and cancer Dr Mary Berrington Tissues become inflamed when the immune system is kicked into action by injury, infection or an allergic reaction.

White blood cells and molecules involved in the immune response are produced to fight off infection and aid the healing process.

However, the same molecules that stimulate the regeneration of damaged tissues may also play a part in the birth of cancer and accelerate its growth and spread.

The researchers argue that continually switching on the immune system encourages cancer in a number of ways:

   * Immune cells that would normally kill developing cancer cells can be switched off.
   * Immunity for healthy cells can be spread to cancer cells too.
   * Blood vessel growth is stimulated, providing nutrition for cancer cells
   * Many immune system molecules are extremely chemically reactive, and may actually cause cancerous mutations by attacking DNA.

The researchers believe that nearly all carcinogens work by over-cooling the immune system. For instance, tobacco smoke can cause long-term inflammation.

They also believe that cancer might cause inflammation too, thus creating the conditions needed to boost the growth and spread of the disease.

Professor Dalgleish said: "An inflamed tissue is a melting pot of cancer-causing molecules, so what better way for a cancer cell to give itself a helping hand that by learning to copy those very same conditions?

"Of course this means that some anti-inflammatory pills might not only help in preventing cancer, but in treating the disease too."

Dr Mary Berrington, Science Information Manager for The Cancer Research Campaign, said: "This review makes a fascinating case for the link between exhausted immunity, chronic inflammation and cancer.

"It's essential that we look at all the evidence, although much of it at the moment is circumstantial."

The report is featured in the British Journal of Cancer.


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Improvement of tumor response by manipulation of tumor oxygenation during photodynamic therapy.

Photochem Photobiol 2002 Aug;76(2):197-203 (ISSN: 0031-8655)
Chen Q; Huang Z; Chen H; Shapiro H; Beckers J; Hetzel FW
Research and Development, HealthONE Alliance, Denver, CO, USA.

Photodynamic therapy (PDT) requires molecular oxygen during light irradiation to generate reactive oxygen species. Tumor hypoxia, either preexisting or induced by PDT, can severely hamper the effectiveness of PDT. Lowering the light irradiation dose rate or fractionating a light dose may improve cell kill of PDT-induced hypoxic cells but will have no effect on preexisting hypoxic cells. In this study hyperoxygenation technique was used during PDT to overcome hypoxia. C3H mice with transplanted mammary carcinoma tumors were injected with 12.5 mg/kg Photofrin and irradiated with 630 nm laser light 24 h later.

Tumor oxygenation was manipulated by subjecting the animals to 3 atp (atmospheric pressure) hyperbaric oxygen or normobaric oxygen during PDT light irradiation.

The results show a significant improvement in tumor response when PDT was delivered during hyperoxygenation. With hyperoxygenation up to 80% of treated tumors showed no regrowth after 60 days. In comparison, when animals breathed room air, only 20% of treated tumors did not regrow. To explore the effect of hyperoxygenation on tumor oxygenation, tumor partial oxygen pressure was measured with microelectrodes positioned in preexisting hypoxic regions before and during the PDT.

The results show that hyperoxygenation may oxygenate preexisting hypoxic cells and compensate for oxygen depletion induced by PDT light irradiation. In conclusion, hyperoxygenation may provide effective ways to improve PDT efficiency by oxygenating both preexisting and treatment-induced cell hypoxia.

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Successful treatment of radiation-induced brain necrosis by
Hyperbaric Oxygen Therapy

Neurol Sci 2003 May 15;209(1-2):115-7 (ISSN: 0022-510X)
Kohshi K; Imada H; Nomoto S; Yamaguchi R; Abe H; Yamamoto H
Department of Neurosurgery, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, 807-8555, Kitakyushu, Japan.

We describe a 68-year-old man who underwent Hyperbaric Oxygen (HBOT) therapy to manage radiation necrosis of the brain, which developed after two treatments with stereotactic radiosurgery (SRS) to the same lesion. The necrosis was subsequently treated with steroids alone for 2 months; however, he progressed clinically and radiographically. Improvement again was noted with the reinstitution of HBO therapy.

This case suggests that HBO therapy is an important therapeutic option in the treatment of brain radiation necrosis caused by SRS.