Tissue-conserving cancer surgery is used increasingly in cancer treatment. It is a highly skilled procedure. One of the main challenges in this type of surgery is the detection of tumor margins which involves time-consuming tissue preparation. The goal of tissue-conserving cancer surgery is to remove as much of the tumour as possible while sparing healthy tissue.
Histopathology, which refers to the examination of a biopsy or surgical specimen by a pathologist, and is based on tissue sectioning and staining, has been the gold standard for cancer diagnosis for more than a century. However, when used during tissue-conserving surgery, this procedure is limited by time-consuming tissue preparation steps and the diagnostic variability inherent in subjective image interpretation.
…this technique is reliable and potentially fast enough to replace conventional methods that determine tumor clearance for basal cell carcinoma removed during Mohs micrographic surgery…
Spectroscopic Fingerprint
With funding from the United Kingdom’s National Institute for Health Research (NIHR), experts at The University of Nottingham in Nottingham, UK, in collaboration with Nottingham University Hospital National Health Service (NHS) Trust, Royal Holloway University, and the Centre of Evidence Based Dermatology (CEBD), have developed a highly accurate prototype tissue-conserving cancer surgery technique.
This new technique can produce a detailed “spectroscopic fingerprint,” of each tissue layer removed during surgery. The result is a detailed maps of the tissue rich in information at the molecular level. Scientists involved in the development of this concept explain that this new method has the potential to speed up and improve the diagnosis of cancer tissue during the operation as well as reduce unnecessary surgery.
The research has been published ahead of print in the September 3, 2013 issues of the prestigious journal Proceedings of the National Academy of Sciences(PNAS). The researchers, led by Ioan Notingher, PhD, an associate professor,at the Faculty of Science in the School of Physics and Astronomy, of the University of Nottingham, U.K., are now looking to build an optimized instrument that can be tested in the clinic.
Discussing the new technique, Notingher explained: ?By refining our prototype instrument to make it more user-friendly and even faster to use. Diagnosis of each tissue layer could be obtained in just a few minutes ? rather than hours. Such developments have the potential to revolutionize the surgical treatment of cancers. This technology will provide a fast and objective way for surgeons to make sure that all the cancer cells have been removed whilst at the same time preserving as much healthy tissue as possible.?
The challenges
Skin conserving surgery involves cutting away one thin layer of tissue after another and each layer after another is carefully examined to make sure that all the cancer has been removed. This lengthy process is stopped when only health tissue is left. Successful removal of all cancer cells is the key to achieving lower rates of the cancer returning but there is always a balance to be struck between making sure all the cancer is removed and preserving as much healthy tissue as possible in order to reduce scarring and disfigurement.
“It is important to recognize that what is visible on the skin?s surface may be just the tip of the iceberg,” noted dermatologic surgeon Christopher Zachary, M.D. chair of the UC Irvine Health School of Medicine‘s Department of Dermatology. Pointing to the real challenge of skin conserving technology, Zachary says: “[It’s important] determine the extent of the tumor.” Zachary says.
“A surgeon needs to know where the cancer starts and ends when looking at it during an operation. This helps him to understand when to stop cutting. Our technique can also diagnose the presence or absence of skin cancer in thick chunks of skin tissue, making it unnecessary to cut the tissue up further into thin slices,? Notingher explained. [This kind of] Surgery enables us to trace out the roots of the cancer, minimizing damage to the surrounding normal skin,” Zachary added.
Ongoing research
Scientific research in the field of skin conserving surgery started more than two decades ago. However, only now are scientists starting to publish the results of their work. The use of lasers and high-sensitivity light detection technologies allows faster and more sensitive imaging of tissues and discrimination of tumors.
Huge step forward
One particular technique, known as Mohs surgery, microscopically controlled surgery, is used for the treatment of difficult cases of a type of skin cancer called basal cell carcinoma (BCC).
While the exact number of people who develop or die from basal cell carcinoma is not completely known because statistics of basal cell skin cancers are not fully reported to cancer registries, this form of skin cancer is considered the most common cancer in humans with more than 60,000 new patients diagnosed each year in the United Kingdom alone. In the United States an estimated 3.5 million basal and squamous cell skin cancers are diagnosed each year, occurring in about 2.2 million Americans. Most of these cancers are basal cell cancers. Squamous cell cancers, an other frequently diagnosed skin cancer, occur less often. Around the world, these number have been increasing for many years. The incidence of basal cell carcinoma continues to increase each year because a longer living, aging population who have had a lot of sun exposure in the past. Better skin cancer detection is also involved in the increase.
“With Mohs surgery, a highly specialized surgical technique first developed in the 1930s by Frederic E. Mohs, M.D., a professor of surgery at the University of Wisconsin, each patient can be assured of the complete removal of all cancer cells while sparing surrounding tissue,” explained Zacharywho is certified by the American College of Mohs Surgery.As part of the procedure, the dermatologic surgeon carefully maps and color-codes the cancerous tissue before excising it. Tissue is then examined microscopically at the time of surgery. If the margins show evidence of more cancerous cells, more tissue is carefully excised and tested. The process is repeated until all margins are determined to be clear of cancerous cells.
Performed on an outpatient basis without the need for general anesthesia, Mohs surgery has the highest cure rate for BCC, close to 99% for new skin cancers and 95% for recurrent cancers. Unlike Mohs surgery, standard surgical excision technique requires that a specimen be sent to a pathologist for processing and review, which can take up to a week for results. In addition, standard excision only allows for examination of about 1% of the tumor?s margins. Because so small a percentage can be tested, residual tumor tissue may be overlooked. If more cancer cells are found in the subsequent pathology examination, a second surgery is required. However, Mohs surgery takes a lot of time because each new tissue layer has to be frozen and examined during the operation. Typically, this takes around 1-2 hours per layer. Depending on the extend of the cancer, an operation can take as long as five to seven hours in total. From a patient?s perspective, there
is a need to reduce the time involved by developing faster and objective ways of seeing whether the cancer has been completely removed during a shorter operation under a single local anesthetic.
A new approach
Notingher?s technique uses an integrated optical technique based on auto-fluorescence (natural fluorescence from the tissue) and Raman spectroscopy (a highly sensitive technique using lasers to identify the molecules in a tissue sample). ?Our technique does not rely on time consuming and laborious steps of tissue fixation, staining, labelling or sectioning. The beauty is that it can be automated and very objective. To make this new technique suitable for use in the middle of an operation such as Mohs surgery for BCC, we have combined tissue auto-fluorescence, which is quick and good at picking out all the cancer cells (but not at excluding normal tissue) as a first step, followed by Raman scattering, a rather slow but good at separating normal from cancer tissue. By combining these two methods into one technique high accuracy diagnosis of BCC can be obtained in only a few minutes.?
Hywel C. Williams, MSc, PhD, FRCP, one of the dermatologists involved in the project and Director of the Centre for Evidence Based Dermatology (CEBD) at The University of Nottingham, in Nottingham, U.K., noted ?I am now convinced that this technique is reliable and potentially fast enough to replace conventional methods that determine tumor clearance for basal cell carcinoma removed during Mohs micrographic surgery ? an advance that will increase the accessibility of Mohs to many more people across the world.?
The researchers conclude that their study demonstrates the potential of this technique to provide a rapid and objective intraoperative method to spare healthy tissue and reduce unnecessary surgery by determining whether tumor cells have been removed.
For more information:
[1]Kong K, Rowlands CJ, Varma S, Perkins W, Leach IH, Koloydenko AA, Williams HC, Notingher I. Diagnosis of tumors during tissue-conserving surgery with integrated autofluorescence and Raman scattering microscopy. Proc Natl Acad Sci U S A. 2013 Sep 3. [Epub ahead of print][Article][PubMed]
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