GI & Hepatology News is the official newspaper of the AGA Institute and provides the gastroenterologist with timely and relevant news and commentary about clinical developments and about the impact of health-care policy. The newspaper is led by an internationally renowned board of editors.GI & Hepatology News is published monthly and mailed to all U.S. members and available to all members online.
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Bilateral Foot Necrosis Caused by Hepatitis C Virus–Induced Mixed Type II Cryoglobulinemia
Alejandro Velasco, Sameer Islam, Kenneth Nugent
Article Outline
References
Copyright
A 52-year-old woman was admitted for increasing severe pain in her feet during the previous month. Her symptoms began 2 years earlier when she noticed skin discoloration and occasional blisters in her feet that became worse before admission. Her medical history included dyslipidemia and hepatitis C virus (HCV) infection incompletely treated 4 years earlier. On physical examination, she had livedo reticularis (Figure A) with purple skin discoloration and blisters on the dorsum of the feet. In addition, severe distal necrosis of the toes with diminished pedal pulses was seen (Figure B). Significant laboratory results included positive serum mixed cryoglobulin type II titer, elevated rheumatoid factor (127 IU/mL), low C3 and C4 levels, and an HCV RNA viral load of 153,000 IU/mL.
Skin biopsy of lower extremities confirmed leukocytoclastic vasculitis (Figure C). An arterial ultrasound of lower extremities showed mild-to-moderate plaques bilaterally with no significant stenosis. Angiographic studies showed aneurysms in the abdominal aorta and right common femoral artery. Clinical and laboratory findings were attributed to mixed cryoglobulinemia. The patient underwent bilateral amputation of lower extremities and treatment with pulse steroids.
Cryoglobulinemia can be detected in 36%–55% of patients infected with HCV, but only 3% develop vasculitic manifestations.1, 2 The most common clinical manifestations are cutaneous vasculitis, arthritis, peripheral neuropathy, and glomerulonephritis.2 Cutaneous vasculitis in mixed type II cryoglobulinemia is characterized by an orthostatic purpura in lower extremities caused by venous stasis and a nonspecific leukocytoclastic vasculitis with infiltration of skin, vessel walls, and microvascular thrombosis3; typically the presentation is not livedo or skin necrosis.4 The bilateral nature of the necrosis with insignificant arterial stenosis in this patient suggests diffuse systemic medium and small vessel disease. Endothelial dysfunction, atherosclerotic plaques, and vascular infiltration by immunocomplexes could cause this rapid presentation of bilateral foot necrosis.
The virologic response to antiviral therapy in HCV patients is not affected by the concurrent presentation of mixed cryoglobulinemia, and small studies show an improvement of cutaneous symptoms.3, 5, 6 Symptomatic response can be as high as 80% in patients receiving antiviral therapy, even when not associated with serologic response.7 However, the clinical remission is mostly limited to mild-to-moderate disease activity, and it is doubtful if it will improve symptoms in cases like ours with severe manifestations.
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Incidence of amoebic liver abscess had decreased in the USA
A study in September's issue of Liver International investigates the incidence, temporal trends and mortality with amoebic liver abscess in the USA.
Amoebic liver abscess may be associated with significant morbidity and mortality, but nationwide American data is unavailable.
Dr Stephen Congly and colleagues from Canada described amoebic liver abscess epidemiology and outcomes in USA from a population-based perspective.
Patients hospitalized with amoebic liver abscess between 1993 and 2007 were identified using the Nationwide Inpatient Sample. Patient characteristics, interventions and outcomes including mortality were determined.
The annual incidence was 1.4 per million population
Liver International
The annual incidence of amoebic liver abscess and temporal trends were determined using the negative binomial regression models.
Between 1993 and 2007, 848 hospitalizations for amoebic liver abscess, corresponding to ∼4100 hospitalizations nationwide, were identified.
The team found that the annual incidence was 1.4 per million population with a 2% average annual decline during this study.
The research team observed that most patients were hospitalized in western and southern states, and 48% were Hispanic.
The team found that males had the highest incidence rates.
The researchers noted that percutaneous and surgical drainage was required in 48% and 7% of patients, respectively.
Although length of stay, and hospital charges were substantial, in-hospital mortality was rare.
Females, patients 60 years or older, and those with 3 or more comorbidities, particularly malnutrition, had an increased risk of death.
Dr Congly's team concludes, "Amoebic liver abscess is rare and the incidence has decreased in USA."
"Young, Hispanic males in southwestern states are most frequently affected."
"Mortality caused by amoebic liver abscess is lower than what was reported previously."
Liver Int 2011: 31(8): 1191–119801 September 2011
Non-Invasive Markers for Hepatic Fibrosis *Full Text Available
Ancha Baranova, Priyanka Lal, Aybike Birerdinc, Zobair M YounossiBMC Gastroenterology 2011, 11:91 (17 August 2011)
'Hepatitis C has been accepted as not being a dirty word'
Sept 1
Educating inmates about hepatitis C is rewarding for Kim Mudd, Marie Hair, Jayne Dodd and Sharon Pyatt
Hepatitis C is curable. Yet, it is responsible for some 86,000 deaths in Europe and 9 million people are infected, according to the World Health Organization. Tackling this are four nurses at HMP Forest Bank in Greater Manchester who are testing, treating and educating prisoners.
Jayne Dodd, hepatitis specialist nurse for prisons in Greater Manchester, is responsible for assessing suitability for treatment as well as comprehensive care and monitoring of patients being treated. Marie Hair is the lead nurse and works with Kim Mudd, healthcare assistant, to screen and treat patients until they are discharged. Sharon Pyatt, primary care manager, accesses, facilitates and funds training for the nurses.
Recognised by WHO this year for a Best Practice Award, the team also received a Sodexo Services Star Award for continuous improvement in hepatitis C service. Since 2009, it has increased awareness and testing in the prison and throughout Greater Manchester
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HIV
Tackling the spread of HIV in the UK
Terrence Higgins Trust is launching ‘Tackling the Spread of HIV in the UK’, a plan to bring down HIV transmission and reduce the growing financial burden on the NHS at a time it can least afford it.
AIDS vaccine research
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Dr David Cook, who is the Executive Vice President of IAVI, the International AIDS Vaccine Initiative, visited Sydney last week. He talks about the latest research into AIDS vaccines. Read Transcript
Cancer
Cancer-stricken grandfather given just 12 months to live sees tumours killed in TWO DAYS after breakthrough treatment
By Jessica Satherley
Last updated at 12:51 PM on 1st September 2011
A cancer-stricken grandfather given just 12 months to live has undergone a breakthrough treatment which killed his tumours - in just two days.
Brian Brooks, 72, received the devastating prognosis after a random bowel screening test showed his colon and liver was riddled with cancer.
With nothing to lose, the father-of-two from Ely, Cambridgeshire, put himself forward for a trial therapy for liver cancer called Foxfire, spearheaded by Cancer Research UK's Bobby Moore Fund.
Great news: Brian Brooks (pictured with his wife Nicky) had his tumours killed in just two days by the new treatment
The radical treatment, called radioembolisation, places radioactive material inside blood vessels which deliver a dose of radiation directly into the liver.
Remarkably, his tumours were killed off after only two days of treatment - which meant doctors were then able to treat the cancer in his colon.
Experts now believe the breakthrough treatment could help treat thousands of cancer sufferers across Britain.
The Bobby Moore Fund was established by Stephanie Moore in 1993 in memory of her late husband Bobby. He was captain of the England team which won the World Cup and captained West Ham. He died from bowel cancer aged just 51.
Mr Brooks, of Ely, Cambridgeshire, is one of only 40 Britons to be treated in the Foxfire trial and one of the first to be given the all-clear.
He is now in remission - and describes his treatment as a ‘miracle’.
He said: ‘I was given a death sentence, it's a very difficult thing to get your head around.
'My family were devastated and one of the worst things for me was thinking I may not see my three year-old granddaughter grow up.
'But they never gave up hope and were tremendously supportive, that helped me through the treatment.
'To be told you have 12 months to live and then to have completely healed 12 months down the line, we believe is a miracle.
'Obviously there is always the risk that the cancer can come back but I am now in remission and that is something that the doctors did not believe was possible.'
His wife, Nicky, 67, said: 'It was completely random - Brian's name was picked and he underwent the trial alongside his chemotherapy.
'We've just had the results back and my doctors can't believe its success - they say they are astonished.
'If we hadn't been informed about this trial, Brian would not be here today.'
Brian, a retired boarding kennel owner from Ely, Cambridgeshire, went for a random bowel screening test at Addenbrooke's Hospital on September 6, 2010.
The scans showed a tumour in his colon and others in his liver - which doctors told him they were unable to operate on.
Brian and Nicky were forced to break the news to their son Iain, 45, daughter Joanne, 40, and grandson William, 3.
But they were given hope when Brian was accepted onto the Foxfire trial, to try radioembolisation therapy, which is only available on the NHS to patients treated the second time around.
Brian was given the treatment at Addenbrooke's Hospital in Cambridge and went for the first stage, when doctors plotted the blood flow over his liver, on November 17.
The following day he was given the second part of the treatment which involved a blast of nuclear spores into the blood cells which were feeding the tumour.
The grandfather-of-one was treated at Addenbrooke's Hospital in Cambridge
Four months later Brian was told the tumours in his liver had completely disappeared and he could now undergo chemotherapy to shrink the tumour in his colon.
He began 11 sessions of traditional chemotherapy to shrink the tumour in his colon, which doctors removed seven weeks ago.
Brian added: 'I remember seeing the results of my scan and reading 'Complete resolution of all liver tumours' - it was incredible.
'My family and I are so grateful to the Bobby Moore Fund, Cancer UK and of cause the wonderful doctors at Addenbrookes.'
Radioembolisation is a combination of radiation therapy and a procedure called embolisation to treat cancer of the liver.
Unlike traditional radiotherapy, which is directed at the tumour from outside the body, this delivers a high dose of radiation from inside the diseased area of the body.
Tiny resin beads called microspheres are placed inside the blood vessels that feed a tumour to block the supply of blood to the cancer cells.
Once these radioactive microspheres become lodged at the tumour site they deliver a high dose of radiation with minimal damage to healthy cells.
The trial co-ordinated by Oxford University was launched in February 2010 and 40 patients have so far enrolled.
Worldwide 800 patients have been treated, half receiving chemotherapy and radioembolisation and the other 400 given chemotherapy alone.
Kate Law, Cancer Research UK's director of clinical trials said: 'Without clinical trials like Foxfire, we wouldn't be able to improve techniques for cancer that are hard to treat.
'It's a promising trial and we look forward to following its progress and seeing the results.'
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UPDATE 1-Delcath says colorectal cancer treatment not effective
Thu Sep 1, 2011 7:22am EDT
* Says will continue to study the efficacy
* Says will start a new mid-stage in 2012 second half (Follows alerts)
Sept 1 (Reuters) - Delcath Systems Inc said its experimental cancer treatment failed to show any efficacy in patients with colorectal cancer in a mid-stage trial.
The company said its chemosaturation system, which was using melphalan for the treatment, did not prove to be efficacious as the patients had been heavily pre-treated with numerous other chemotherapies.
The fresh results come more than a week after the same treatment showed strong efficacy in treating primary liver cancer patients.
Delcath said it would also initiate a new mid-stage single-arm study in the second half of 2012.
"We will continue to study the efficacy of our chemosaturation system in this patient population that currently has few treatment options," Chief Executive Eamonn Hobbs said.
Sixteen patients with very late stage colorectal cancer, which had spread to the liver, were recruited into this arm of the trial, the company said.
The study included four patient cohorts -- hepatobiliary cancer, metastatic cancer of neuroendocrine, ocular or cutaneous melanoma, and colorectal cancer.
Delcath said the safety profile of the chemosaturation system was consistent with a previous late-stage melanoma trial.
Shares of the New York-based company closed at $4.14 on Wednesday on Nasdaq.
(Reporting by Kavyanjali Kaushik in Bangalore; Editing by Saumyadeb Chakrabarty)
Researchers report new understanding of role of telomeres in tumor growth
Study published in The American Journal of Pathology
Philadelphia, PA, September 1, 2011 –
The first report of the presence of alternative lengthening of telomeres (ALT) in cancers arising from the bladder, cervix, endometrium, esophagus, gallbladder, liver, and lung was published today in The American Journal of Pathology. The presence of ALT in carcinomas can be used as a diagnostic marker and has implications for the development of anti-cancer drug therapies.
Telomeres are nucleoprotein complexes located at the ends of chromosomes. During normal cell division, these telomeres become shorter with each division, potentially resulting in cell death. In some cancers, however, this shortening is counteracted by the ALT mechanism, thus allowing the unlimited growth of the cancer cells.
"The present study offers a springboard to guide future investigations in larger cohorts that specifically focus on the tumor types exhibiting ALT to more precisely determine the prevalence and potential prognostic value of this phenotype," commented lead investigator Christopher Heaphy, PhD, a postdoctoral research fellow at The Johns Hopkins School of Medicine.
"These results may have therapeutic consequences, given that cancers using the ALT pathway are predicted to be resistant to anti-telomerase therapies, some of which have entered phase I/II clinical trials. Further understanding of the molecular mechanisms of ALT will be paramount in designing novel anti-cancer therapeutics targeting cancers utilizing the ALT pathway," observed corresponding author Alan K. Meeker, PhD, Assistant Professor of Pathology at Johns Hopkins.
Meeker and co-investigators have assessed the prevalence of the ALT mechanism in a wide range of human cancer subtypes. Analyzing 6,110 tumor samples from 94 different cancer subtypes, 541 benign neoplasms, and 264 normal tissue samples, researchers found that the overall prevalence of the ALT phenotype was 3.73%. It was not observed in benign neoplasms or normal tissues.
Additionally, this is the first report of ALT in medulloblastomas, oligodendrogliomas, meningiomas, schwannomas, and pediatric glioblastoma multiformes.
The authors also note that they were able to identify many tumor types that apparently may not use the ALT pathway for telomere maintenance. In particular, they assessed hundreds of cases of adenocarcinomas arising from the prostate, colon, pancreas, or small intestine and did not observe a single ALT-positive tumor.
Previous studies have shown associations between ALT status and prognosis in some tumor types. The authors suggest that further studies are warranted to assess the potential prognostic significance and unique biology of ALT-positive tumors.
###
The article is "Prevalence of the Alternative Lengthening of Telomeres Telomere Maintenance Mechanism in Human Cancer Subtypes" by Christopher M. Heaphy, Andrea P. Subhawong, Seung-Mo Hong, Michael G. Goggins, Elizabeth A. Montgomery, Edward Gabrielson, George J. Netto, Jonathan I. Epstein, Tamara L. Lotan, William H. Westra, Ie-Ming Shih, Christine A. Iacobuzio-Donahue, Anirban Maitra, Qing K. Li, Charles G. Eberhart, Janis M. Taube, Dinesh Rakheja, Robert J. Kurman, T.C. Wu, Richard B. Roden, Pedram Argani, Angelo M. De Marzo, Luigi Terracciano, Michael Torbenson, and Alan K. Meeker. (doi: 10.1016/j.ajpath.2011.06.018). It will appear in The American Journal of Pathology, Volume 179, Issue 4 (October 2011) published by Elsevier.
Cancer-killing viruses zero in on tumor cells
Doctors have known for nearly a century that when cancer patients catch a virus the infection can help to beat back their tumors. But developing therapies hinged upon this idea has not been easy. Researchers first have to engineer the viruses to discriminately attack only the cancer cells. Then the virus has to actually reach those tumor cells and kill them. Despite these barriers, research has plunged forward, with several viruses in late-stage clinical development (see ‘Recent deal highlights hopes for cancer-killing viruses’).
Clinicians typically inject these so-called ‘oncolytic viruses’ into the tumors themselves using a syringe. But this delivery approach lacks precision. Thus, researchers have long sought cancer-killing viruses that can hone in on their own on cancerous cells while leaving healthy tissue intact. (Scientists are similarly trying to develop bacteria that serve the same purpose, as we reported in March.) Now, for the first time, researchers have engineered a virus that, when injected into people’s bloodstreams, preferentially attacks only cancer cells.
“This data set really puts oncolytic virotherapy on the map as a very, very promising experimental approach to the systemic treatment of metastatic cancer,” Stephen Russell, director of the molecular medicine program at the Mayo Clinic in Rochester, Minnesota who was not involved with the research, wrote in an email
Family history of cancer
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Researchers in the US investigated the importance for doctors of obtaining knowledge of a family's cancer history to assess risks and initiate appropriate early interventions, that is screening recommendations, etc. Read Transcript
A step toward a saliva test for cancer
American Chemical Society 242nd National Meeting & Exposition;
A new saliva test can measure the amount of potential carcinogens stuck to a person's DNA -- interfering with the action of genes involved in health and disease -- and could lead to a commercial test to help determine risks for cancer and other diseases, scientists reported here today during the 242nd National Meeting & Exposition of the American Chemical Society (ACS).
Diabetes
Expert Discussion: The Continuing Challenge of Effectively Managing Type 2 Diabetes, Part I
Defining Prediabetes and Diabetes
Editor's Note: This is the first in a two-part series on the detection and treatment of type 2 diabetes mellitus focused on the educational needs of physicians. It is based on a live expert discussion, audio segments of which are available online at http://www.mdmag.com/. Part two of the series will appear in our September issue.
Infectious Disease & Viruses
The New Generation of Microbe Hunters
Gina Kolata(The New York Times, August 29, 2011)
"New methods of quickly sequencing entire microbial genomes are revolutionizing the field [microbiology]...Today researchers can sequence the DNA that constitutes a micro-organism’s genome in a few days or even, with the latest equipment, a day. (Analyzing it takes a bit longer, though.) They can simultaneously get sequences of all the microbes on a tooth or in saliva or in a sample of sewage. And the cost has dropped to about $1,000 per genome, from more than $1 million…One group [of molecular epidemiologists] is starting to develop what it calls disease weather maps. The idea is to get swabs or samples from sewage treatment plants or places like subways or hospitals and quickly sequence the genomes of all the micro-organisms. That will tell them exactly what bacteria and viruses are present and how prevalent they are...[and] take precautions against ones that are starting to emerge…Others are sequencing bacterial genomes to find where diseases originated."
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Pharmaceuticals
Vertex Scores Big With Hepatitis Drug
The company's medication is outselling its rival
Aug 31, 2011, 12:20 pm EDT By Barry Cohen, Health Care Writer
Physicians and patients evidently like the advantages Incivek has over Victrelis, including data showing the Vertex drug had nearly an 80% cure rate and offers the possibility of even shorter treatment. In addition, Incivek is considered easier to use
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Indians sitting ducks as drug trials turn fatal
In last 4 yrs, 1,725 persons have died in clinical trials; weak law compounds risks
Aditi Tandon/TNSTribune News Service
New Delhi, August 7
For the first time since 2010 when six tribal girls from Gujarat and Andhra Pradesh involved in the clinical trials of anti-cervical cancer HPV vaccine died, the government has admitted that 1,725 persons have lost their lives to drug trials in the last four years.
The number of deaths has risen from 132 in 2007 and 288 in 2008 to 637 in 2009 and 668 last year, indicating the complete ineffectiveness of regulatory controls over the $400 million sector. Last year, the government gave compensation in just 22 cases out of the 668 that resulted in deaths due to “serious adverse events” during drug trials, Health Minister Ghulam Nabi Azad told Parliament this week.
Stem Cells
Stem cell properties of hepatoma cells *Full Text Available
BMC Gastroenterology 2011, 11:71
Tumor spheres produced from hepatoma cell lines cultured in stem cell conditioned medium exhibit liver cancer stem cell (CSC) properties, and the CSL-independent Notch signalling pathway may play a role in the differentiation and propagation of liver CSCs.
Parents in India Bank on Stem-cells, Not the 'Tooth Fairy'
Stephanie Nolen
"In India, a fascination with stem-cell medicine combined with a growing demographic of affluent parents...have consumerized the stem-cell banking industry like nowhere else…India has no laws, and only unenforceable guidelines on what stem-cell research is permitted...The Indian stem-cell industry…is worth an estimated $500-million a year. As a consequence, there is a comparatively high level of awareness of stem-cell medicine in the general population…At the same time, as technological processes for the preservation of cells are 'indigenized,' they are becoming considerably cheaper to operate in India than they are in the West. That, combined with the sheer size of the Indian market, makes a practice such as banking baby teeth or menstrual cells suddenly feasible as a mainstream pursuit."
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Pioneering UK stem cell trial passes safety test
By Paul Sandle
LONDON Thu Sep 1, 2011 4:25am EDT
LONDON (Reuters) - A pioneering clinical trial to inject stem cells into the brains of patients disabled by stroke has been cleared to progress to the next stage after the treatment raised no safety concerns in the first three candidates.
ReNeuron Group PLC, the British biotech behind the trial, said the independent Data Safety Monitoring Board had reviewed safety data from its ReN001 stem cell therapy and recommended the trial advance to the higher dose.
"Data from the laboratory safety tests, neurological examinations and neurofunctional tests conducted thus far indicate that the ReN001 treatment is safe and well-tolerated at the initial dose," the company said in a statement on Thursday.
The procedure involves injecting ReNeuron's neural stem cells into patients' brains in the hope they will repair areas damaged by stroke, thereby improving both mental and physical function.
It uses stem cells derived from human fetuses rather than embryos, which were used in a stem cell trial to treat patients with spinal cord injuries by Geron Corp of the United States.
ReNeuron's chief executive Michael Hunt said the clearance was an important milestone, and the preliminary data also backed up the group's other therapeutic programs using the CTX neural stem cell line that formed the basis of the ReN001 stroke treatment.
The principal investigator for the trial, Keith Muir from the University of Glasgow's Institute of Neuroscience and Psychology, said he looked forward to evaluating further patients at a higher dose.
"ReN001 has the potential to address a very significant unmet medical need in disabled stroke patients and I am pleased that our team is involved in this pioneering clinical trial," he said.
Shares in ReNeuron rose 3.3 percent in early trade.
Analysts at Matrix said ReNeuron was making excellent progress within the trial, which it believed could set the company apart from other stem-cell companies in the field, given the other advantages it has in terms of manufacturing, scalability and the off-the-shelf nature of the technology.
"The data generated thus far are all the more remarkable, in our view, given the fact that the patients receiving the cells have not been subject to immunosuppression" they said in a note.
"We look forward to the data from the next cohort within this study."
(Reporting by Paul Sandle; Editing by Helen Massy-Beresford)
US Health Care
Who Are the Most Powerful People in American Medicine?
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