An American man who suffered from AIDS appears to have been cured of the disease 20 months after receiving a targeted bone marrow transplant normally used to fight leukemia, his doctors said.

The middle school years can be tough. It’s a time of change and sometimes a little awkwardness. So imagine going through those years with a condition that causes your hands or arm pits to sweat so badly that you avoid social situations. It’s called hyperhidrosis, and doctors at Mayo Clinic say a minimally invasive outpatient surgery can stop the sweating.

Scientists at Sunnybrook Research Institute (SRI) are developing and commercializing a promising novel therapy for the treatment of prostate cancer that may offer patients a faster and more precise treatment than existing clinical alternatives, with fewer side effects.

The new treatment–magnetic resonance imaging (MRI)-guided transurethral ultrasound–uses heat from focused ultrasound to treat cancer in the prostate gland precisely while sparing the delicate noncancerous tissues around the prostate essential for healthy urinary, bowel and sexual function.

Sunnybrook researchers Dr. Michael Bronskill and Dr. Rajiv Chopra have licensed their innovation and formed Profound Medical Inc., which will develop the technology for clinical use.

Unlike surgical removal of the prostate, the treatment is minimally invasive and could be performed without a lengthy hospital stay. In preclinical studies, treatment takes less than 30 minutes. The therapy, on which clinicians at Sunnybrook will conduct preliminary testing in preparation for a clinical trial, could help limit the number of men living with the common, debilitating and often permanent side effects of surgery and radiation treatments currently used. More of these invasive therapies are being performed now because improved awareness among younger men has converged with better clinical detection tools.

Profound’s clinical development is targeted at treatment that reduces the high level of incontinence and impotence associated with current, invasive treatments. The therapy involves two different and naturally incompatible technologies, ultrasound and MRI, which Bronskill and Chopra spent 10 years making compatible. “You have to make an ultrasound heating applicator work inside a magnetic resonance imager, without the two technologies interfering with each other,” says Bronskill, who is a professor at the University of Toronto. “The prostate cancer site is a natural for this technology because it’s surrounded by structures you want to spare.” Dr. Laurence Klotz, chief of urology at Sunnybrook Health Sciences Centre, and a professor at the University of Toronto, says that a noninvasive therapy for early, localized prostate cancer could improve the quality of life of hundreds of thousands of men. “The key to effective noninvasive treatment is accurate imaging of the target organ and of the effects of the treatment on tissue. In that respect, MR-guided ultrasound has many potential advantages over transrectal ultrasound-guided focused ultrasound, now approved for use in Canada,” says Klotz.

The scientists’ creation of this clinically viable product was done in a setting committed to commercialization. “At SRI, we are dedicated not only to developing new and better therapies and technologies, but also to getting those discoveries to our patients,” says Dr. Michael Julius, vice-president of research at Sunnybrook. Profound Medical Inc. is the third imaging-technology company to be spun out of research at SRI in recent years. The other two are VisualSonics Inc. and Sentinelle Medical Inc.

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Tumors have a unique vulnerability that can be exploited to make them more sensitive to heat and radiation, researchers at Washington University School of Medicine in St. Louis report.

The Washington University radiation oncology researchers found that tumors have a built-in mechanism that protects them from heat (hyperthermia) damage and most likely decreases the benefit of hyperthermia and radiation as a combined therapy.

By interfering with that protection, the researchers have shown that tumor cells grown in culture can be made more sensitive to hyperthermia-enhanced radiation therapy.

Radiation therapy is a mainstay of cancer treatment but doesn’t always completely control tumors. For several years, raising tumor temperature has been investigated as a radiation therapy enhancer with few adverse side effects.

“Past research has shown that hyperthermia is one of the most potent ways to increase cell-killing by radiation,” says senior author Tej K. Pandita, Ph.D., associate professor of radiation oncology and of genetics and a researcher with the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital.

“But now we’ve found that heat also enhances the activity of an enzyme called telomerase in cancer cells,” he says. “Telomerase helps protect the cells from stress-induced damage and allows some of them to survive. We used compounds that inhibit telomerase and showed that cancer cells then become easier to destroy with hyperthermia and radiation used in combination.”

Telomerase repairs the ends of chromosomes by maintaining stability of specialized cellular structures called telomeres after cells divide. Without telomerase the number of cell divisions is limited. Telomerase is not active in most normal human cells but is active in most cancer cells, which rely on telomerase to continue to proliferate.

In this study, Pandita’s research group found that moderately turning up the heat also turns up the activity of telomerase in tumor cells. The researchers found that if they inactivated telomerase and then increased the temperature of tumor cells, more cells were killed by ionizing radiation. Because nearly all cancers have telomerase, drugs that turn off its activity could be useful against many cancers.

The researchers tested three compounds, and one, GRN163L, more strongly inhibited telomerase than the others. Many groups are studying GRN163L as an anticancer therapeutic, and it recently received clearance by the U.S. Food and Drug Administration to enter human phase I/II clinical testing in chronic lymphocytic leukemia. In some preliminary studies, GRN163L has been shown to be additive when used in combination with existing cancer drugs or radiation.

Next, Pandita and colleagues will test the effect of GRN163L on tumors in mice to see if it will enhance the cell-killing effect of hyperthermia and radiation. They are also working to develop chemicals that have heat-like effects to bypass the need to supply a physical heat source to tissue.

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The investigators assessed health-related quality of life using questionnaires and estimated costs from the perspective of the National Health Service.

In their model, the base case starts at age 39 and continues through age 56. The investigators assumed “no clinical or cost differences between treatments after menopause.”

“The base-case results imply a cost saving and a small quality-adjusted life-year (QALY) gain per woman,” with a treatment strategy that starts with MRgFUS, Dr. Cairns and colleagues write.

“The cost per QALY gained is sensitive to cost of MRgFUS relative to other treatments, the age of the woman and the nonperfused volume relative to the total fibroids volume,” the investigators add.

In an accompanying editorial, Drs. I.T. Manyonda and M. Gorti of St. George’s Hospital, London point out that while MRgFUS “has already claimed a place in the armamentarium of treatment options for symptomatic fibroids,” the cost of the equipment will limit its availability for years to come.

A new type of bariatric surgery may eliminate the need for medication in patients with type 2 diabetes, according to a study reported here at the Society of American Gastrointestinal and Endoscopic Surgeons 2008 Annual Scientific Session and Postgraduate Course.

It has long been observed that very obese patients — those with a body mass index (BMI) of 35 kg/m2 or more — with type 2 diabetes have noticeably better control over the disease after undergoing bariatric surgery. This makes sense because the more weight a patient gains, the worse his or her glycemic control becomes. Therefore, surgeries performed to assist in weight reduction should and do lead to improved diabetes management.

Just as not all obese people have type 2 diabetes, many nonobese people do have the disease, and it can be inferred that perhaps something else is triggering this condition. Researchers have posited that perhaps something in the stomach that promotes type 2 diabetes (a relatively new type 2 diabetes drug [Byetta, Amylin Pharmaceuticals Inc and Eli Lilly & Co) works on the basis of this principle).

The study reported here looked at surgical treatment of nonobese (BMI, 21 – 29 kg/m2) patients with type 2 diabetes. A total of 69 patients (22 women and 47 men) were enrolled who had a history of type 2 diabetes mellitus for at least 3 years and had evidence of stable treatment with oral hypoglycemic agents or insulin for at least 12 months.

The Brazilian surgeons who carried out the study used a relatively new procedure involving laparoscopic ileal interposition associated to a diverted sleeve gastrectomy. This surgery involves connecting the ileum to the proximal intestine, which keeps digestive nutrients away from the bowel early in the digestive process. Thus, mostly undigested nutrients hit that part of the bowel relatively early, and various hormones are therefore secreted earlier than they would be without the surgery.

The researchers conclude that the new surgery appears to be effective in controlling type 2 diabetes and its complications in nonobese patients. After surgery, 65% of patients achieved a hemoglobin A1C test score below 6 without the aid of insulin or oral medications. The patients' fasting glucose levels decreased from a mean of 218 to 102 mg/dL, postprandial glucose levels decreased from 305 to 141 mg/dL, and insulin resistance decreased from 5.2 to 0.77.

Measures of comorbidities of diabetes also showed improvement. Hypertension was controlled in 91.3% of the patients, microalbuminuria was resolved in 85%, cholesterol levels were normalized in 95%, and hypertriglyceridemia was normalized in 92% of the patients.

Average patient follow-up was 21.7 months, but lead investigator Aureo L. de Paula, MD, director of gastrointestinal surgery at Hospital de Especialidades, Goiania, Brazil, recommended longer follow-up. There were no deaths, but postoperative complications occurred in 7.3% of patients. There also were reports of short-term dehydration, and in the first 6 months there were cases of external contamination of the ileal segment, which can lead to gastroenteritis and diarrhea.

Dr. de Paula told Medscape General Surgery that the procedure is designed to deal with "the pathophysiology of the disease, such as the defective early phase in saline secretion and the defective amplification of the insulin response by the hormone GIP."

Francesco Rubino, MD, chief of gastrointestinal metabolic surgery at Weill Cornell Presbyterian Hospital, New York City, strongly agreed that hormonal and other action in the stomach profoundly affects type 2 diabetes. After all, he told Medscape General Surgery, for almost 100 years, there have been reports of diabetes improvement after stomach surgery for ulcers and cancer, which are in some ways similar procedures to modern gastric bypass surgery. However, Dr. Rubino said he has serious reservations concerning the new procedure.

Dr. Rubino said he is interested in laparoscopic Ileal interposition associated to a diverted sleeve gastrectomy and is currently performing the procedure on animals himself. However, he told Medscape General Surgery, that he is concerned about the long-term effects of the surgery, which are, at present, unknown. In addition, the surgery is much more complicated to perform than gastric bypass, which is already known to be a safe and effective procedure that accomplishes much the same thing as the new procedure.

"I do think [the procedure] is an intriguing operation. Whether it is ready for clinical prime time as a primary application — that I don’t know,” Dr. Rubino said.

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A revolutionary cancer treatment using microscopic magnets to enable ‘armed’ human cells to target tumours has been developed by researchers funded by the Biotechnology and Biological Sciences Research Council (BBSRC). Research published online today in the journal, Gene Therapy, shows that inserting these nanomagnets into cells carrying genes to fight tumours, results in many more cells successfully reaching and invading malignant tumours.
Using human cells as delivery vehicles for anti-cancer gene therapy has long been an attractive approach for treating tumours, but these cells usually reach tumours in insufficient numbers to effectively attack them. Now, a new ‘magnetic targeting’ method has been developed to overcome this problem by Professor Claire Lewis at the University of Sheffield, Professor Jon Dobson at the University of Keele, and Professor Helen Byrne and Dr. Giles Richardson at the University of Nottingham.

The technique involves inserting nanomagnets into monocytes – a type of white blood cell used to carry gene therapy – and injecting the cells into the bloodstream. The researchers then placed a small magnet over the tumour to create a magnetic field and found that this attracted many more monocytes into the tumour.

The head of the laboratory in which the work was done, Professor Lewis, explains: “The use of nanoparticles to enhance the uptake of therapeutically armed cells by tumours could herald a new era in gene therapy – one in which delivery of the gene therapy vector to the diseased site is much more effective. This new technique could also be used to help deliver therapeutic genes in other diseases like arthritic joints or ischemic heart tissue.”

Professor Jon Dobson from the University of Keele, said: “Though the concept of magnetic targeting for drug and gene delivery has been around for decades, major technical hurdles have prevented its translation into a clinical therapy. By harnessing and enhancing the monocytes’ innate targeting abilities, this technique offers great potential to overcome some of these barriers and bring the technology closer to the clinic.”

Professor Nigel Brown, BBSRC Director of Science and Technology, said: “This exciting work could have huge implications in healthcare. Fundamental bioscience research may sometimes seem to have little relevance to everyday life, but understanding the basic workings of the human body and harnessing nanoscale technology has resulted in a process of great potential in tumour therapy.”

The team are now looking at how effective magnetic targeting is at delivering a variety of different cancer-fighting genes, including ones which could stop the spread of tumours to other parts of the body.

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The removal through endoscopy of tumours that affect only the superficial layers of the oesophagus can avoid complete extirpation of this part of the digestive tract. The technique, carried out at the University Hospital of Navarra for the last three years, was presented at the VI International Course on Therapeutic Endoscopy in the Digestive System, organized by the Digestive System Service at this hospital. Specifically, more than 90% of patients treated for this ailment at the University Hospital of Navarra have not needed the extirpation of the oesophagus.
400 specialists from ten different countries attended the course, focusing on the therapeutic possibilities of endoscopy in the digestive system. Treatment using digestive endoscopy, without having to carry out surgery, is increasing. These applications are less aggressive than surgical operations and are undertaken at out-patient clinics in about 99% of the cases, which usually enables the patient to go home after the walk-in/walk-out treatment, explained Doctor Miguel Ángel Muñoz Navas, Director of the Digestive System Service at the University Hospital of Navarra.

As is known, endoscopy is a technique carried out using a tube-like instrument which contains a light and a lens at its tip. The tube has, moreover, a duct for carrying other instruments with which, amongst other operations. biopsies, extirpation of polyps, injection of contrasting fluids, insertion of prostheses and clips, coagulation of bleedings, extraction of stones from the biliary or pancreatic zone and the draining of abscesses may be undertaken. There are also exists an ecoendoscope, which is one incorporating an ecograph at its end. While in a normal ecography the transducer of the ecograph is outside the body, ecoendoscopy provides better quality images of a lesion that is close to the digestive tract. From the digestive tract we can observe lesions in its vicinity and access them.

Extirpation of oesophageal tumours

As regards the technique for the extirpation of distal tumours of the oesophagus undertaken at the University Hospital of Navarra, Doctor Muñoz explained that this was effective when the carcinoma occurs at surface layers. “The oesophagus is made up of three layers: mucous, sub-mucous and muscular. When the tumour is located in the mucous, we can take it out completely in most cases and thus avoid extirpation of the oesophagus. Until recently patients with this ailment – although affecting only the primary layers – were recommended the total extirpation of the oesophagus, which involved surgery with a high morbidity risk and even death”.

In any case, according to the Director of the Digestive System Service at the University Hospital of Navarra, Doctor Miguel Ángel Muñoz Navas, sometimes a surgical operation is inevitable. “There are times when you have to operate but there are others when a solution with endoscopy can be tried. But, in this case, monitoring of the patient has to be undertaken. It could be the case that we extirpate a tumour with endoscopy and the anatomopathology shows up the fact that the cancer is more infiltrated than had been thought from the biopsies or the ecoendoscopy. In these cases a surgical operation is required. Our experience has shown that more than 90% of patients that we have treated with this technique have not needed subsequent surgery”.

Extirpation of oesophageal tumours using endoscopy is not a very widespread treatment, in part due to its complexity. Nevertheless, it is a real possibility – and scientifically recognised – avoiding the extirpation of the oesophagus. Moreover, the technique can be applied in a walk-in/walk- out manner.

Surgery through natural orifices

Amongst other advances within the sphere of therapeutic digestive endoscopy, on the course organised by the Digestive System Service at the University Hospital of Navarra, surgical operations have been carried out using natural orifices, known as NOTES (natural orifice transluminal endoscopic surgery). Access can be through the buccal cavity, the anus, the vagina and the urinary bladder, the most commonly used routes being oral and vaginal. With the same endoscopy we usually use we can get to the stomach, perforate it and enter the abdominal cavity in order to, for example, extirpate a vesicle or deal with other lesions. Currently in this type of surgery, endoscopy and laparoscopy are being combined.

Endoscopic treatment has also been used in obesity cases. For patients with morbid obesity who do not respond to dietetic treatment, it is common to have recourse to bariatric surgery. This can be aggressive and, from time to time, news stories appear about patients who have died as a consequence of such operations. Such mortality is due, in part, to the fact that these patients are in a bad state of health generally and may have other diseases associated with obesity. They are beginning to work with the possibility of reducing the size of the stomach via endoscopy and of short-circuiting the intestinal loops.

Another novel application presented at the course involves therapeutic endoscopy in the biliary and pancreatic ducts. Despite the small diameter of these ducts, a new technology enables them to be accessed in order to examine them directly and to apply therapeutic techniques.

The Digestive System Service at the University Hospital of Navarra has presented a technique for draining the vesicle directly into the stomach by means of ecoendoscopy; as the Director of the Service explains: when the vesicle is very inflamed it is not possible to carry out surgery and it is less aggressive to access the organ by perforating the stomach and draining the contents of the vesicle into the stomach.

In the session devoted to the diagnostic application of endoscopy, the possibilities of carrying out direct microscopy were considered. Although it does not substitute biopsy, this technique is a complement in deciding where to take samples or in being more certain that a lesion found during examination is a malignant tumour or not.

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The treatment of uterine fibroids with 3T MR-guided focused ultrasound (MRgFUS) is safe, non-invasive and effective, according to a recent study conducted by researchers at Weill Cornell Medical College in New York, NY.
“Approximately 25% of women in the United States have clinically symptomatic fibroids, and treatment has most commonly been surgical with hysterectomy or myomectomy. However, in the past decade, new options have been developed in radiology, includingnon-invasive MR-guided focused ultrasound (MRgFUS) and minimally invasive uterine artery embolization (UAE) to treat these patients,” said Elizabeth K. Arleo, MD, lead author of the study along with Robert J. Min, MD, MBA, chairman of radiology at Weill Cornell Medical College.

The study evaluated 20 patients who had symptomatic leiomyomas and were treated with 3T MRgFUS. These patients had a pelvic MRI and completed a symptom severity score (SSS) of the uterine fibroid symptom and health related quality of life prior to the procedure and at 6 and 12 months after the procedure.

According to the study, at 6 month follow-up, there was a decrease in SSS (ranging between 10-59%), treated fibroid volume, and total uterine volume. At 12 month follow-up, there was a persistent decrease in SSS (ranging between 15-62%), treated myoma volume, and total uterine volume.

“In contrast to having major abdominal surgery with possible removal of their uterus, a patient can have a safe and effective, totally noninvasive procedure in an outpatient setting without the risks of general anesthesia, no ionizing radiation and a much shorter recovery period,” said Dr. Arleo. “Patients have returned to work as early as one day after MRgFUS, instead of approximately three days after UAE or six weeks after a myomectomy or hysterectomy,” she said.

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Heart surgeons at Washington University School of Medicine in St. Louis report that by adding a simple 10-20 second step to an operative procedure they achieved a significant improvement in the outcome for the surgical treatment of atrial fibrillation (AF).
Reporting in the April issue of the Journal of Thoracic and Cardiovascular Surgery, the surgeons describe an enhancement to the Cox-Maze procedure, a surgical procedure that redirects wayward electrical impulses causing AF by creating precisely placed scars, or ablations, in the heart muscle. The Cox-Maze procedure is highly effective, offering the best long-term cure rate for persistent atrial fibrillation.

The surgeons added one ablation to the series of ablations typically made during the Cox-Maze procedure and that short step improved how well patients did after surgery. As a result, they recommend using this extra ablation in all patients undergoing the procedure.

“The single additional ablation creates what we call a box lesion,” explains Ralph J. Damiano Jr., M.D., the John Shoenberg Professor of Surgery at the School of Medicine. “The box lesion surrounds and electrically isolates the pulmonary veins and the posterior left atrial wall from the rest of the left atrium. Our study shows excellent success when using the box lesion, and we recommend it for any patient with long-standing atrial fibrillation.”

AF is the most common irregular heart rhythm and affects more than 2 million people in the United States. During atrial fibrillation, the upper chambers (atria) of the heart beat rapidly and quiver instead of contracting, drastically reducing the amount of blood they pump. AF can cause fatigue, shortness of breath, exercise intolerance, heart palpitations and stroke.

The area of the heart near the pulmonary veins is a common source of the irregular electrical impulses that can cause AF. Without the box lesion, in some patients this area could still support electrical signals that disrupt the regular contractions of the heart’s upper chambers.

Led by Damiano, also chief of cardiac surgery at the School of Medicine and a cardiac surgeon at Barnes-Jewish Hospital, the Washington University surgeons revolutionized AF treatment in 2002 by helping develop a radiofrequency clamp that creates the ablation lines needed to reroute electrical impulses in the heart. The clamp directs radiofrequency energy into the heart muscle and creates a full-thickness scar.

The radiofrequency clamp procedure is quicker and easier than the original “cut and sew” Cox-Maze procedure, which was developed by James Cox, M.D., at Washington University in 1987. The original procedure relied on a complex series of 10 incisions in the heart muscle, creating a “maze” to channel errant electrical impulses where they should go. In the newer version, called Cox-Maze IV, most of these incisions were replaced by radiofrequency ablations, reducing the operation from an average of 90 minutes to about 30 minutes.

The current study involved two groups of patients with AF. One group underwent radiofrequency ablation-assisted Cox-Maze IV procedures without a box lesion and the other with a box lesion. The box lesion group had a 48 percent lower occurrence of atrial flutter and fibrillation in the first weeks after surgery. These patients also had shorter hospital stays (nine days on average) than patients who had the standard Cox-Maze IV procedure (average stay of 11 days).

Three months after surgery, 95 percent of patients who had the box lesion had no signs of AF, while only 85 percent of the patients who had the standard Cox-Maze IV procedure were free from AF. By six and 12 months postsurgery, all of the patients in the box lesion group were free from AF compared to 90 percent of the other group, although that difference was not statistically significant.

“We also saw that the use of antiarrhythmic drugs was lower after three and six months in those who received a box lesion,” Damiano says. “These drugs can have serious side effects, and if patients can stop using them they often feel better. Overall, the use of the box lesion set was associated with shorter hospitalization, fewer medications and reduced recurrence of atrial fibrillation. We were very pleased with these results.”

Compared to those without atrial fibrillation, people with the disorder are five times more likely to suffer from stroke and have up to a two-fold higher risk of death. For some patients, medications can control the abnormal heart rhythms and the risk of clotting associated with atrial fibrillation, but unlike the Cox-Maze procedure, the drugs usually do not cure the disorder.

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