Day: 03/02/2011

Postoperative Chemoradiotherapy for Extrahepatic Bile Duct Cancer

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To evaluate the effect of postoperative concurrent chemoradiotherapy using three-dimensional conformal radiotherapy and to identify the prognostic factors that influence survival in patients with extrahepatic bile duct cancer.

Methods and Materials

We retrospectively analyzed the data from 101 patients with extrahepatic bile duct cancer who had undergone postoperative concurrent chemoradiotherapy using three-dimensional conformal radiotherapy. Of the 101 patients, 52 (51%) had undergone complete resection (R0 resection) and 49 (49%) had microscopic or macroscopic residual tumors (R1 or R2 resection). The median radiation dose was 50 Gy. Also, 85 patients (84%) underwent concurrent chemotherapy with 5-fluorouracil.

Results

The median follow-up period was 47 months for the surviving patients. The 5-year overall survival rate was 34% for all patients. A comparison between patients with R0 and R1 resection indicated no significant difference in the 5-year overall survival (44% vs. 33%, p = .2779), progression-free survival (35% vs. 22%, p = .3107), or locoregional progression-free survival (75% vs. 63%, p = .2784) rates. An analysis of the first failure site in the 89 patients with R0 or R1 resection indicated isolated locoregional recurrence in 7 patients. Elevated postoperative carbohydrate antigen 19-9 level was an independent prognostic factor for overall survival (p = .001) and progression-free survival (p = .033). A total of 3 patients developed Grade 3 or greater late toxicity.

Conclusion

Adjuvant concurrent chemoradiotherapy using three-dimensional conformal radiotherapy appears to improve locoregional control and survival in extrahepatic bile duct cancer patients with R1 resection. The postoperative carbohydrate antigen 19-9 level might be a useful prognostic marker to select patients for more intensified adjuvant therapy.

source: IJROBP

Targeted gene editing enters clinic

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Patients with HIV first to receive experimental gene therapy.


A gene-therapy method that specifically disrupts a single gene may have had its first success in the clinic, potentially boosting immune-cell counts in a small number of patients with HIV. The results, presented on 28 February at the Conference on Retroviruses and Opportunistic Infections in Boston, Massachusetts, mark an important therapeutic test for enzymes known as zinc finger nucleases — small proteins that can be designed to bind to and edit specific DNA sequences by virtue of their zinc-bearing structures.

“If they did this several times in a given patient, you could establish a high percentage of resistant cells.”


The study, a phase I safety trial, tested a zinc finger enzyme developed by Sangamo BioSciences in Richmond, California. It included six men with HIV who were already taking the standard regimen of antiretroviral drugs. The drugs had kept the virus at bay, but their immune-cell counts remained abnormally low. Researchers removed a sample of CD4+ T cells, the type of immune cells affected by HIV, from each man and used Sangamo’s enzyme to disrupt the CCR5 gene, which encodes a protein that HIV uses to enter CD4+ cells. The engineered cells were then infused back into the patients. Immune-cell counts subsequently rose for five of the six patients who received the therapy.

“It’s very exciting,” says John Rossi, a molecular biologist at the City of Hope’s Beckman Research Institute in Duarte, California. “If they did this several times in a given patient, you could establish a high percentage of resistant cells.”

The inspiration for targeting the CCR5 gene comes from the small percentage of people who, thanks to a natural mutation in the gene, are resistant to most types of HIV infection. At the meeting on Monday, Jacob Lalezari of Quest Clinical Research in San Francisco, California, reported that the engineered cells migrated throughout the body and thrived in the gut mucosa — a key reservoir of HIV. No serious side effects were seen.

The zinc finger nuclease technique is promising for the treatment of many diseases beyond HIV, says Patrick Aubourg, who studies gene therapy at France’s national biomedical agency INSERM in Paris. The method could replace the more common technique of inserting modified genes into the genome, in which researchers have less control over the gene in question. But he cautions that the technique still has a relatively low efficiency and might have off-target effects.

Meanwhile, Rossi, who is himself embarking on an HIV study that will use Sangamo’s zinc finger nucleases, says that it is not yet clear whether the patients’ CD4+ cell count rose because of the CCR5 disruption or because the extracted cells were activated as part of the protocol for growing them outside the body. And because levels of HIV were already below the threshold of detection in these patients, it is too early to say what effect the therapy could have on patients that have more of the virus. Researchers do not yet know what fraction of a person’s CD4+ cells would need to be HIV-resistant to significantly rein in the virus’s spread and liberate patients from a lifetime of antiretroviral drugs.”It’s going to take a while to put all of those pieces together,” says Carl June, who studies T cells at the University of Pennsylvania in Philadelphia, and is an investigator on another HIV trial involving Sangamo’s nuclease. “But it’s at least conceivable now.”

source: nature

Fish Oil Counters Chemotherapy Weight Loss

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Fish Oil Helps Cancer Patients Maintain Weight During Chemotherapy, Study Finds

 

fish oil capsules

March 1, 2011 — Fish oil may counter weight loss in cancer patients undergoing chemotherapy, according to a new study published in the online edition of the journal Cancer.

In the study, researchers at the University of Alberta in Edmonton, Canada, enrolled 40 patients with non-small-cell lung cancer. They were all in the early stages of treatment. Sixteen of those patients took 2.2 grams of fish oil per day, while the remaining 24 received standard care. The study, which lasted about 10 weeks, ran until the patients completed their initial chemotherapy treatments.

The majority of patients in the study who supplemented their diet with fish oil, which is rich in omega-3 fatty acids, either maintained or gained weight. Weight loss is a common side effect of chemotherapy, as patients often lose their appetite. Chemotherapy can also affect a person’s sense of taste, dulling the flavor of foods and making them less appealing. Poor nutritional intake in turn can lead to fatigue, reduced quality of life, and worsening health.

Fish Oil Better Than Standard Care

Sixty-nine percent of the patients given fish oil maintained their weight. Some even gained weight. Less than a third of the patients in the other group kept their weight up. Instead, they lost an average of 2.3 kilograms (about 5 pounds) over the course of the study. Most of the patients taking fish oil also maintained muscle mass for the duration of the study, while the majority of those receiving standard care lost a significant amount of muscle mass.

Previous studies of fish oil’s role in weight maintenance focused on patients with advanced cancers, the study authors write. This study was unique in that it followed newly referred patients. Early intervention to prevent weight loss and related side effects may improve patients’ outcomes and their eligibility for a greater number of cancer treatments, study authors say. However, they say larger, randomized trials need to be conducted to verify their results.

“This holds great promise because currently there is no effective treatment for cancer-related malnutrition,” study co-author Vera Mazurak, PhD, says in a statement.

Cannabis Use Associated with Psychotic Symptoms in Young Adults

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Cannabis use is associated with the development of psychosis in young adults, according to a BMJ study.

Researchers followed some 1900 German participants, aged 14 to 24 at baseline, to assess their use of cannabis and incidence of psychotic experiences. When participants with prior cannabis use and previous psychotic experiences at baseline were excluded, those who started using cannabis during the first 3.5-year period of follow-up were nearly twice as likely to experience psychotic symptoms within the subsequent 5-year period, compared with those who didn’t use cannabis (odds ratio, 1.9). And continuing use in the 5-year period was, similarly, associated with a doubling in risk relative to nonusers.

Editorialists write, “The results cast doubt on the argument that uncontrolled confounding explains the association between cannabis and psychosis.”

Source:BMJ

 

Werner syndrome

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Werner syndrome (also called progeria) is a hereditary condition associated with premature aging and an increased risk of cancer and other diseases. Signs of Werner syndrome usually develop in the teenage years. A person with Werner syndrome does not have the usual growth spurt typical of a teenager and is shorter on average. Signs of aging, including gray hair and hair loss, may appear in the 20s. Cataracts, type 2 diabetes, and osteoporosis (decrease in bone mineral density) may develop in the 30s. One of the most significant health problems faced by people with Werner syndrome is the early development of atherosclerosis, commonly known as hardening of the arteries, which can lead to a heart attack.

What causes Werner syndrome?

Werner syndrome is a genetic condition. This means that the risk of Werner syndrome can be passed from generation to generation in a family. Mutations (alterations) in the WRN gene are known to cause Werner syndrome. Research is ongoing to learn more about Werner syndrome.

How is Werner syndrome inherited?

Normally, every cell has two copies of each gene: one inherited from the mother and one inherited from the father. Werner syndrome follows an autosomal recessive inheritance pattern, which means that a mutation must be present in both copies of the gene for a person to be affected. This means that both parents must pass on a gene mutation for a child to be affected. A person who has only one copy of the gene mutation is called a carrier. When both parents are carriers of a recessive gene mutation, there is a 25% chance that a child will inherit two mutations and be affected.

How common is Werner syndrome?

Werner syndrome is considered to be very rare. It is estimated that one in 200,000 people in the United States may have Werner syndrome. Werner syndrome is somewhat more common in Japan, where it is estimated that one in 30,000 people may have the condition.

How is Werner syndrome diagnosed?

Currently, the diagnosis of Werner syndrome is suspected if someone has several of the features that have been reported in people with this condition.

Common features of Werner syndrome (diagnosed after age 10):

  • Cataracts in both eyes (bilateral)
  • Skin changes associated with aging
  • Characteristic facial features, including wrinkling and loss of muscle tone
  • Short stature (height)
  • Early graying or thinning of the hair
  • Family history of Werner syndrome
  • Positive 24-hour urine hyaluronic acid test

Other features seen in Werner syndrome:

  • Type 2 diabetes
  • Decreased fertility
  • Osteoporosis
  • Cancer
  • Bone changes in the fingers and toes
  • Tissue changes
  • Early atherosclerosis (plaque build up in arteries)
  • Hoarse or high-pitched voice
  • Flat feet

Guidelines for the diagnosis of Werner syndrome have been proposed but may change over time as more is learned about this condition. Genetic testing for mutations in the WRN gene is available only as part of research studies (clinical trials). Mutations in the WRN gene are found in about 90% of people with Werner syndrome.

What are the estimated cancer risks associated with Werner syndrome?

The risk of cancer is increased in people who have Werner syndrome, but the specific risk of cancer is unknown. Types of cancers reported in people with Werner syndrome include thyroid cancer, melanoma, soft tissue sarcoma, and osteosarcoma (bone cancer).

What are the screening options for Werner syndrome?

Suggested screenings for people diagnosed with Werner syndrome include:

  • Yearly screening for type 2 diabetes
  • Yearly lipid profile (blood test)
  • Yearly eye examination to look for signs of cataracts
  • Yearly physical and dermatological (skin) examinations to screen for cancers associated with Werner syndrome

People with Werner syndrome should also avoid smoking, be physically active, and maintain a healthy weight to help decrease the risk of heart disease. Any chest pains (also known as angina) should be carefully evaluated by a doctor. Due to the risk of skin cancer, people with Werner syndrome should also limit sun exposure and use skin protection when outside.

Screening recommendations may change over time as new technologies are developed and more is learned about Werner syndrome. It is important to talk with your doctor about appropriate screening tests.

source: mayo clinic house call

Testing for Syphilis

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Reversing the sequence of screening tests has improved case identification but — in low-prevalence populations — has increased the likelihood of false-positive results.

The diagnosis of syphilis has never been straightforward. For the last several decades, the standard procedure has involved a nontreponemal (NT) screening assay followed by a confirmatory treponemal test (TT). The recent introduction of automated treponemal screening (ATS) tests has provided increased efficiency for high-volume laboratories; it has also led some laboratories to reverse the order of testing, such that an ATS assay is followed by a confirmatory NT assay. Two research groups have now investigated the effects of this reversal.

The CDC evaluated reverse-sequence screening in low- and high-prevalence populations (3 and 2 clinical sites, respectively). Among a total of 140,176 samples tested between 2006 and 2010, 4834 (3.4%) had a positive ATS result, with 2743 (56.7%) having a negative NT result. Of these 2743 samples, 866 (31.6%) had a negative confirmatory TT assay, suggesting that 17.9% of the positive ATS results were false positives. The percentage of samples with positive ATS results was higher at the high-prevalence clinical sites than at the low-prevalence ones; the percentage of samples with positive ATS results but negative NT results was higher at the low-prevalence sites.

In a retrospective, population-based study, Mishra and colleagues examined laboratory-based diagnoses of syphilis at the Public Health Laboratory of Toronto between 1998 and 2008. After the testing sequence was reversed, in August 2005, the monthly rate of confirmed positive results more than quadrupled, from 3.2 to 13.5 per 100,000 population. During the ATS-NT sequence period, 23,237 (2.2%) of 1,037,025 samples tested had a positive ATS result, with 69.6% of these having a negative NT result and 11.7% appearing — after confirmatory testing — to be falsely positive.

Comment: Together, these reports indicate that testing using the ATS-NT sequence identifies many individuals with syphilis who would have been missed using the traditional NT-TT sequence, but at the cost of additional false-positive results — not an insignificant concern, given the social ramifications of the diagnosis and the necessity to report positive results to public health authorities. The CDC continues to recommend the traditional testing sequence but notes that if the ATS-NT sequence is used, sera with ATS-NT discordant results should be further tested with Treponema pallidum particle agglutination. Patients with positive results on this last assay are considered to have past or present syphilis; those with negative results are unlikely to have syphilis.

— Richard T. Ellison III, MD

Published in Journal Watch Infectious Diseases March 2, 2011

 

Will Nanotechnology Influence Targeted Cancer Therapy?

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The rapid development of techniques that enable synthesis (and manipulation) of matter on the nanometer scale and the development of new nanomaterials will play a large role in disease diagnosis and treatment, specifically in targeted cancer therapy. Targeted nanocarriers are an intriguing means to selectively deliver high concentrations of cytotoxic agents or imaging labels directly to the cancer site. Often, solubility issues and an unfavorable biodistribution can result in a suboptimal response of novel agents even though they are very potent. New nanoparticulate formulations allow simultaneous imaging and therapy (“theranostics”), which can provide a realistic means for the clinical implementation of such otherwise suboptimal formulations. In this review, we did not attempt to provide a complete overview of the rapidly enlarging field of nanotechnology in cancer; rather, we presented properties specific to nanoparticles and examples of their uses, which show their importance for targeted cancer therapy.

source: seminars in radiation oncology

The Promise and Pitfalls of Positron Emission Tomography and Single-Photon Emission Computed Tomography Molecular Imaging–Guided Radiation Therapy

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External beam radiation therapy procedures have, until recently, been planned almost exclusively using anatomic imaging methods. Molecular imaging using hybrid positron emission tomography (PET)/computed tomography scanning or single-photon emission computed tomography (SPECT) imaging has provided new insights into the precise location of tumors (staging) and the extent and character of the biologically active tumor volume (BTV) and has provided differential response information during and after therapy. In addition to the commonly used radiotracer 18F-fluoro- 2-deoxyD-glucose (FDG), additional radiopharmaceuticals are being explored to image major physiological processes as well as tumor biological properties, such as hypoxia, proliferation, amino acid accumulation, apoptosis, and receptor expression, providing the potential to target or boost the radiation dose to a biologically relevant region within a tumor, such as the most hypoxic or most proliferative area. Imaging using SPECT agents has furthered the possibility of limiting dose to functional normal tissues. PET can also portray the distribution of particle therapy by displaying activated species in situ. With both PET and SPECT imaging, fundamental physical issues of limited spatial resolution relative to the biological process, partial volume effects for quantification of small volumes, image misregistration, motion, and edge delineation must be carefully considered and can differ by agent or the method applied. Molecular imaging–guided radiation therapy (MIGRT) is a rapidly evolving and promising area of investigation and clinical translation. As MIGRT evolves, evidence must continue to be gathered to support improved clinical outcomes using MIGRT versus purely anatomic approaches.

source: seminars in radiation onclogy