H7N9 FLU VIRUS BECOMING PANDEMIC?

China is investigating the possibility of human-to-human transmission of a new strain of bird flu that has killed 17 people and is examining "family clusters" of people infected with the virus, a top health official was quoted as saying.

Authorities have slaughtered thousands of birds and closed some live poultry markets to slow the rate of human infection. But many aspects of this new variety of bird flu remain a mystery, particularly whether the H7N9 strain is being transmitted between people.

China has warned that the number of infections, 82 so far, could rise. Most of the cases and 11 of the deaths have been in the commercial capital Shanghai.

Feng Zijian, the director of the health emergency center at the Chinese Center for Disease Control and Prevention, told reporters on Wednesday that "we are paying close attention to these cases of family clusters.

"(We) are still analyzing in-depth to see which has the greatest possibility -- did it occur first from avian-to-human transmission, and then a human-to-human infection, whether they had a common history of exposure, were exposed to infected objects or whether it was caused by the environment," Feng said.

His comments were reported in a statement posted on the website of the National Health and Family Planning Commission.

One of the families that China is studying is made up of two brothers and their father who died of the virus, Feng said.

"This family cluster case still doesn't change our understanding of the characteristics of the disease in general -- that it is transmitted from birds to people and there's no evidence of human-to-human transmission," Feng said.

CONTACT WITH POULTRY

Efforts to determine the nature of the H7N9 virus are also hampered by a lack of accurate information from the victims on whether they have had contact with poultry, Feng said.

The World Health Organization said on Wednesday that a number of people who have tested positive for the new strain appear to have had no contact with poultry.

The WHO had previously reported two suspected "family clusters", but the first turned out to be a false alarm and the second was inconclusive.

Zeng Guang, chief scientist in charge of epidemiology at the China Disease Prevention and Control Centre (CDPCC), said about 40 percent of human victims had no clear history of poultry exposure, the Beijing News reported.

Feng said that not all patients "can recall the history of exposure. Just like with the H5N1 avian influenza, 50 percent of the patients knew exactly their history of exposure, the other 50 percent can't recall it at all."

He was referring to a an especially virulent strain of bird flu that had raised the threat of a global pandemic in 2003.

Feng said that as most patients were in critical condition, the government was encountering delays in obtaining information about their exposure to poultry.

The WHO said a team of experts going to China soon would examine whether the virus can be spread between people, although there was "no evidence of sustained human-to-human transmission".

The state-run China Daily newspaper, citing an unnamed source, said the team's talks with Chinese representatives would be held on Thursday. The experts would then visit affected areas.

LIVER TRANSPLANTATION FOR LOW GRADE NEUROENDOCRINE TUMORS

Liver transplantation is effective when liver metastases from neuroendocrine tumors are unresectable, according to a European Liver Transplant Registry study.

But transplant should be reserved for selected cases, when all other options have been exhausted, Dr. Yves Patrice Le Treut from Hopital de la Conception, Marseille, France told Reuters Health in an email.

Those cases include patients with "unresectable liver metastases, well differentiated neuroendocrine tumor (NET) and no need of extra hepatic resection at the time of (transplant)," he said.

Using data from the European Liver Transplant Registry, Dr. Le Treut and colleagues reviewed the short- and long-term outcomes of 213 patients who underwent liver transplantation for neuroendocrine tumors. They published their findings online March 25th in Annals of Surgery.

Mortality in the three months after transplantation was 10%, driven mostly by surgery-related complications. The median postoperative hospital stay was 25 days and the median ICU stay was 10 days. Twenty-four patients required retransplantation, including 16 within the first three months.

The mean follow-up overall was 56 months (range, 0-283 months). Among the 192 patients who survived at least three months after transplant, 103 died later. Eighty-six of these later deaths were due to recurrent disease; the remainder were due either to late postoperative complications (six patients), late retransplant complications (four patients), infectious complications (three patients), or other causes (four patients).

At the end of follow-up, 63 patients were alive without recurrence, and 26 were alive with recurrence. The median survival for patients who died without recurrent disease was eight months.

Median overall survival after liver transplantation was 67 months. Overall survival rates were 81% at one year, 65% at three years, and 52% at five years.

Five-year overall survival did not differ between patients whose primary tumor was undetected at the time of liver transplantation, those whose primary tumor was discovered and removed during or after liver transplantation, and those whose primary tumor was never identified.

Median disease-free survival was 24 months. Disease-free survival rates were 65% at one year, 40% at three years, and 30% at five years.

Independent predictors of poor prognosis included major resection in addition to liver transplantation, poor tumor differentiation, and hepatomegaly. Age over 45 years also independently predicted poor prognosis among patients treated since 2000.

"The most striking finding is that (the) overall survival rate in the whole series was more than 50% at five years, thus validating the use of liver transplantation for patients with cancer," the researchers note. "Despite this validation, the actual benefit of liver transplantation needs to be proven."

The timing of transplant in asymptomatic patients is very controversial, Dr. Le Treut noted. "This retrospective work cannot give any answer to this question," he said. "But my personal point of view is that liver transplantation must be indicated when asymptomatic patients present (with) a progressive tumor load (after a period of stable disease) that became refractory to all other treatments."

Dr. Mark Bloomston from The Ohio State University's Division of Surgical Oncology, Columbus, Ohio agreed. He told Reuters Health, "Given the scarcity of available livers, transplantation should still be reserved for patients proving to have indolent disease affecting only the liver. In other words, enough time must pass to prove the disease is not very aggressive but should not wait so long that the patient is in dire straits."

Dr. Bloomston added, "Evaluation for liver-directed therapies (including resection, transplantation, or chemoembolization) should take place early in disease course for metastatic NET, preferably when the disease is at its best (e.g., low volume, slow growth, or even stable disease). Liver-directed therapy should not be undertaken in desperation as it is doomed to failure and could be dangerous."

Dr. Gabriel Chan from the University of Montreal in Canada offered a somewhat different view. "I believe until there is further prospective evidence, liver transplantation should be reserved for patients who are symptomatic, with hepatic only, low grade NET," he said. "There is currently no proof that there is a survival benefit over the current treatments including arterial therapy, hormone therapy, and even no treatment in such patients."

Good prospective trials "are absolutely essential," Dr. Chan told Reuters Health, "and as a result of the rare situation where it is indicated, national and international cooperation is essential to provide the essential numbers and statistically significant evidence of benefit, either symptomatic or survival."

"The future may feature better situations where recurrence is diminished if the everolimus experience in metastatic NET expands over the next few years, and if the therapeutic ranges of the oncological and immunosuppressive modalities cross over," Dr. Chan concluded.