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HEATED CHEMO SERVES A CULTURAL PURPOSE

August 29, 2011 - The New York Times

The Annals of Extreme Surgery

By BARRON H. LERNER

THE heat is on again in the world of cancer treatment, both literally and figuratively.

More and more doctors are now using an extremely aggressive procedure to treat certain colorectal and ovarian cancers called Hipec, in which patients first undergo surgery to remove any visible cancer, then have heated chemotherapy pumped into the abdominal cavity for 90 minutes to kill any remaining cells.

Although it has given some patients hope, there is almost no evidence that the treatment is more effective than traditional chemotherapy — besides one small trial in the Netherlands over a decade ago that did show a benefit, but in which 8 percent of the participants died from the procedure itself.

We shouldn’t be surprised by the sudden emergence of this therapy. Heated chemotherapy is the latest in a long list of very toxic treatments used by well-meaning cancer doctors who have confused doing more for patients with doing what is best for them.

History tells us that this “more is better” dictum is rarely true.

Aggressive cancer therapy started in the late 19th century with the radical mastectomy, which involved the removal of the breast, along with the chest muscle below it and nearby lymph nodes, and was championed by William S. Halsted, a surgeon at Johns Hopkins.

In the following decades, Dr. Halsted’s methods became more and more popular, particularly after World War II, when surgeons who had performed heroic operations on European battlefields returned to America optimistic about what could be achieved in cancer surgery. In an attempt to eradicate all potentially dangerous cells without the assistance of chemotherapy — which was not yet in wide use — surgeons began removing even parts of the sternum and rib cage of certain breast cancer patients in something called a super-radical mastectomy.

If the cancer had spread into the arms, surgeons at times removed entire shoulders (forequarter amputations). If the cancer was in the legs, part of the pelvis was removed with the leg (hindquarter amputations). The most aggressive operation of all was probably the pelvic exenteration, devised by the New York gynecologist Alexander Brunschwig. For cancers that had spread throughout a woman’s pelvis, he removed not only her gynecological organs but also her bladder and rectum.

The goal of these operations was straightforward: to remove as many cancer cells as possible, which would theoretically prolong the survival of patients and possibly even cure them. The problem was that none of these procedures had been formally tested in controlled clinical trials. By the 1960s, it had become clear that they were of little or no benefit, while causing dying cancer patients disfigurement and suffering.

Why such enthusiasm for aggressive surgery? The explanation can be gleaned from the language surgeons used to justify their operations. Military metaphors were ubiquitous. In 1946, Cushman Haagensen warned his colleagues against “surgical cowardice” in the face of the “formidable enemy” that was cancer. Jerome A. Urban, the father of the super-radical mastectomy, was fond of saying “lesser surgery is done by lesser surgeons.”

It was not only surgeons who made these assumptions. In the late 1980s, oncologists began treating metastatic breast cancer patients with a highly toxic and expensive regimen of so-called very-high-dose chemotherapy, followed by bone marrow transplants. Once again, early data proved misleading. Women who received this treatment turned out to live no longer than those getting standard chemotherapy, and many died from either the high doses or the side effects of the transplants.

Cancer patients and their families, desperate for anything that might work after exhausting all other treatment options, are also part of the problem. But the history of cancer treatment provides a crucial cautionary tale for both those seeking out and those providing heated chemotherapy today. Doing more for cancer patients has often served a cultural as opposed to a scientific purpose, reflecting more the desire to defeat the cancer enemy than to take care of sick patients. Hospitals should offer heated chemotherapy — and insurance companies should pay for it — only after controlled trials have proved its effectiveness.

In the meantime, we should remember not to conflate our efforts with our achievements.

Barron H. Lerner, a professor of medicine and public health at Columbia, is the author of “The Breast Cancer Wars: Hope, Fear and the Pursuit of a Cure in Twentieth-Century America” and the forthcoming “One for the Road: Drunk Driving Since 1900.”

 

 

VITAMIN D AND COLON CANCER

Confirmation that vitamin D acts as a protective agent against the advance of colon cancer

A study conducted by VHIO researchers confirms that a lack of vitamin D increases the aggressiveness of colon cancer

The indication that vitamin D and its derivatives have a protective effect against various types of cancer is not new. In the field of colon cancer, numerous experimental and epidemiological studies show that vitamin D3 (or cholecalciferol) and some of its derivatives inhibit the growth of cancerous cells. Researchers at the Vall d'Hebron Institute of Oncology (VHIO), in collaboration with the Alberto Sols Institute of Biomedical Research (CSIC-UAB), have confirmed the pivotal role of vitamin D, specifically its receptor (VDR), in slowing down the action of a key protein in the carcinogenic transformation process of colon cancer cells. These results are being published in the journal PLoS One.

This protein, known as beta-catenin, which is normally found in intestinal epithelial cells where it facilitates their cohesion, builds up in large quantities in other areas of the cells when the tumour transformation begins. As a result of these changes, the protein is retained in the cell nucleus, where it facilitate the carcinogenic process, and this is the point at which vitamin D intervenes, or rather, the vitamin D receptor (VDR). "Our study has confirmed the pivotal role of the VDR in controlling the anomalous signal that sparks off the growth and uncontrolled proliferation of colon cells which, in the final instance, ends up causing a tumour to emerge", says Héctor Palmer, the coordinator of this study and head of the VHIO's Stem Cells and Cancer laboratory. He continues, "The stimulation of this receptor suppresses the action of the beta-catenin protein, intercepting the series of events that change the intestinal cell into a malignant tumour cell".

The study was conducted on mice and human colon cancer cells. The mice were used as a model to replicate the initial phases of colon cancer. "These findings show that mice of this kind, which also lack the VDR and hence do not respond to vitamin D, present larger and more aggressive tumours than mice with the VDR", explains Dr. Palmer, and concludes: "The number of tumours is not influenced by the absence of VDR, which would indicate that this factor does not protect against the appearance of the tumour but does intervene in its growth phase, reducing its aggressiveness".

The researchers then analysed the effect of the VDR on human colon cancer cell cultures and observed that the concentration of the altered protein, beta-catenin, increased in cells without the VDR. These findings were repeated in the three types of colon cancer cells studied, and confirmed the results observed in the mice.

In two-thirds of advanced colon cancer tumours there was a lack of VDR in the cancer cells, and this circumstance leads us to believe that this loss may contribute to speeding up the growth of the tumour. The findings of this study confirm this supposition.

Vitamin D: essential in the initial phases of colon cancer

In light of these findings, chronic vitamin D deficiency represents a risk factor in the development of more aggressive colon tumours. Patients in the initial stages of colon cancer, the time when the VDR still has a substantial presence in the cells, could benefit from being treated with vitamin D3. However, this would not be useful in the advanced stages of the disease when the presence of the VDR is very much reduced.

The study data support the development of anti-tumour medicines based on the structure of vitamin D, although their use in patients will require further research in the next few years.

The body not only obtains vitamin D from food, especially milk and fish oils, but also manufactures it from exposure to sunlight. Prolonged exposure is not necessary; just 10 minutes in the sun every day when it is not at its peak is sufficient to stimulate its production. During the summer, when we are more likely to sunbathe, it is important to use the appropriate protective measures against sunburn to avoid future sun damage. Use high-factor solar protection products and do not expose the skin to the sun in the middle of the day to protect against skin cancers.

 

 

COLON PRE-CANCER CAN NOW BE DETECTED!

New high-speed 3-D imaging system holds potential for improved cancer screening

August 1st, 2011 in Cancer 

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This is a 3-D OCT volumetric data set from an excised human colon specimen. (A) En face view showing regular organization of normal colon. (B and C) Cross-sectional views along two different directions showing sub-surface features. Two cross-sections are shown as examples, however multiple cross-sectional views can be extracted from the 3-D OCT data. Scale bar: 500um. Credit: Massachusetts Institute of Technology

 

Researchers at the Massachusetts Institute of Technology (MIT) have developed a new imaging system that enables high-speed, three-dimensional (3-D) imaging of microscopic pre-cancerous changes in the esophagus or colon. The new system, described in the Optical Society's (OSA) open access journal Biomedical Optics Express, is based on an emerging technology called optical coherence tomography (OCT), which offers a way to see below the surface with 3-D, microscopic detail in ways that traditional screening methods can't.

Endoscopy is the method of choice for cancer screening of the colon or esophagus. In the procedure, a tiny camera attached to a long thin tube is snaked into the colon or down the throat, giving doctors a relatively non-invasive way to look for abnormalities. But standard endoscopy can only examine the surface of tissues, and thus may miss important changes occurring inside tissue that indicate cancer development.

OCT, which can examine tissue below the surface, is analogous to medical ultrasound imaging except that it uses light instead of sound waves to visualize structures in the body in real time, and with far higher resolution; OCT can visualize structures just a few millionths of a meter in size. Over the past two decades, OCT has become commonplace in ophthalmology, where it is being used to generate images of the retina and to help diagnose and monitor diseases like glaucoma, and has emerging applications in cardiology, where it's used to examine unstable plaques in blood vessels that can trigger heart attacks.

The new endoscopic OCT imaging system reported by OCT pioneer James G. Fujimoto of MIT and his colleagues, works at record speeds, capturing data at a rate of 980 frames (equivalent to 480,000 axial scans) per second—nearly 10 times faster than previous devices—while imaging microscopic features less than 8 millionths of a meter in size.

At such high speeds and super-fine resolution, the novel system promises to enable 3-D microscopic imaging of pre-cancerous changes in the esophagus or colon and the guidance of endoscopic therapies. Esophageal and colon cancer are diagnosed in more than 1.5 million people worldwide each year, according to the American Cancer Society.

"Ultrahigh-speed imaging is important because it enables the acquisition of large three-dimensional volumetric data sets with micron-scale resolution," says Fujimoto, a professor of electrical engineering and computer science and senior author of the paper.

"This new system represents a significant advance in real-time, 3-D endoscopic OCT imaging in that it offers the highest volumetric imaging speed in an endoscopic setting, while maintaining a small probe size and a low, safe drive voltage," says Xingde Li, associate professor at the Whitaker Biomedical Engineering Institute and Department of Biomedical Engineering at Johns Hopkins University, who is not affiliated with the research team.

In OCT imaging, microscopic-scale structural and pathological features are examined by directing a beam of light on a tissue and measuring the magnitude and echo time-delay of backscattered light. Because the amount of light that can be recaptured and analyzed decreases quickly with depth in tissue due to scattering, the technique can generally only be used to visualize sub-surface features to a depth of 1 to 2 millimeters. "However these depths are comparable to those sampled by pinch biopsies and unlike biopsy, information is available in real time," Fujimoto says. By using miniature fiber optic scanning catheters or probes, either on their own or in combination with standard endoscopes, colonoscopes, or laparoscopes, OCT imaging can be performed inside the body.

In collaboration with clinicians at the VA Boston Healthcare System and Harvard Medical School, the team is investigating endoscopic OCT as a method for guiding excisional biopsy—the removal of tissue for histological examination—to reduce false negative rates and improve diagnostic sensitivity.

"Excisional biopsy is one of the gold standards for the diagnosis of cancer, but is a sampling procedure. If the biopsy is taken in a normal region of tissue and misses the cancer, the biopsy result is negative although the patient still has cancer," notes Fujimoto, whose team is one of a number of research groups—including at Johns Hopkins University; the University of California, Irvine; Case Western University; and Massachusetts General Hospital—that are actively pursuing the development of smaller, faster endoscopic OCT systems.

Endoscopic OCT requires miniature optical catheters or probes—just a few millimeters in diameter—that can scan an optical beam in two dimensions to generate high-resolution 3-D data sets. Scanning the beam in one transverse direction generates an image in a cross-sectional plane, whereas scanning the beam in two directions generates a stack of cross-sectional images—that is, a 3-D (or volumetric), image.

"This device development is one of the major technical challenges in endoscopic OCT because probes must be small enough so that they can be introduced into the body, but still be able to scan an optical beam at high speeds," Fujimoto says. "Increasing imaging speeds has also been an important research objective because high-resolution volumetric imaging requires very large amounts of data in order to cover appreciable regions of tissue, so rapid image acquisition rates are a powerful advantage."

The optical catheter developed by the MIT researchers and their collaborators uses a piezoelectric transducer, a miniature device that bends in response to electrical current, allowing a laser-light emitting optical fiber to be rapidly scanned over the area to be imaged.

So far, the device—which must be further reduced in size, Fujimoto notes, before it can be deployed with the standard endoscopes now used—has only been used in animal models and in samples of human colons that had been removed during surgical procedures; further development and testing of the technology is needed before it can be tested in human patients. "The ultimate clinical utility of new devices must be established by large clinical studies, which assess the ability of the technology to improve diagnoses or therapy," he says. "This is a much more complex and lengthy task than the initial development of the technology itself."

More information: Biomedical Optics Express, Vol. 2, Issue 8, pp. 2438-2448 (2011) doi:10.1364/BOE.2.002438

Provided by Optical Society of America

 

"New high-speed 3-D imaging system holds potential for improved cancer screening." August 1st, 2011. http://medicalxpress.com/news/2011-08-high-speed-d-imaging-potential-cancer.html