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Rifampicin reduces infections in neutropenia
THE LANCET
Clinical surveillance recommendations adopted for HNPCC
T
he International Collaborative Group on Hereditary Non Polyposis Colorectal Cancer (ICGHNPCC) recently adopted a set of guidelines for the clinical surveillance of HNPCC family members (panel). These are designed, said Hans Vasen (Leiden, The Netherlands), president of the group, to maximise detection of early stage and premalignant lesions in the principal organ sites affected in the HNPCC phenotype. HNPCC is an autosomal dominant condition characterised by early age of onset (mean 47 years) colorectal cancer and extra-colonic malignancies that include endometrial, urinary tract, and upper gastrointestinal adenocarcinoma. HNPCC may account for up to 12% of total world incidence of colorectal cancer, but considerable clinical controversy surrounds optimal surveillance methods for members of HNPCC families. The recommendations adopted last week in Buffalo, USA, at the 8th annual meeting of the ICG-HNPCC include index colonoscopy at age 20-25 with repeat colonoscopy every 2 years and gynaecological examination, including transvaginal sonography at age 30-35 with follow up every 1-2 years. There was a broad consensus that frequent observations of rapid progression from premalignant adenomas to invasive adeno-
carcinomas warranted colonoscopic surveillance at a greater frequency than that required for other at risk groups. Founding member Henry Lynch (Omaha, USA) reminded the group that insurance companies
Site
Procedure
Lower age limit (YE)
lnteirval (yrs)
Colon Endometrium (and ovaries)
Colonoscopy Gynaecologicalexam, transvaginal sonography, CA-125 measurement Gastroscopy Sonography, urine analysis
20-25
30-35
2 1-2
30-35 30-35
1-2 1-2
Stomach* Urinary tract*
*only if it runs in the family
and national health insurance agencies must be informed of the new recommendations in order to gain their funding support for the increased surveillance. Scientific presentations at the meeting detailed the growing number of mutations in the recently identified DNA mismatch repair genes hMSH2 and hMLHl that segregate with HNPCC. These now total over 110, distributed between the two genes. 70% of mutations in HNPCC pedigrees are attributable to hMLH1, said Paivi Peltomaki (Helsinki, Finland) who presented up-to-date results from the Mismatch Repair Gene Mutation Data Bank. Reports of mutations in PMSl and PMS2,
Rifampicin reduces infec ions in neutropenia
T
.
he benefit of oral quinolonebased antibacterial prophylaxis in neutropenic patients with cancer can now be augmented, according to the findings of a recent randomised multicentre trial in Canada. The addition of an agent with an increased anti-gram-positive effect to a quinolone with broader activity against gram-positive bacteria significantly reduces overall infection rates in such patients. In their investigation, Eric Bow and colleagues (National Cancer Institute of Canada Clinical Trials Group) evaluated three oral antibacterial prophylactic regimens in 111 patients with severe neutropenia in 14 centres (Ann Intern Med 1996; 125: 183-90). The study bears out earlier research showing that the addition of rifampicin to ofloxacin in neutropenic rats reduced bacteraemia due to both viridans streptococci and staphylococci. The NCIC Clinical Trials
two further DNA mismatch repair genes, remained unchanged from a year ago (1 and 2 mutations respectively). ICG-HNPCC plans to expand its mutation database network in collaboration with other gene
mutation databases, said Albert de la Chapelle (Helsinki, Finland). Miguel Rodriguez-Bigas (Buffalo, USA) noted that the evidence presented at the meeting strongly suggests that DNA mismatch repair gene mutations are not restricted to families that meet strict phenotypic criteria for HNPCC, and that clinicians should be aware that cancer-prone families, particularly those with early age of onset colorectal or endornetrial carcinoma, may harbour mismatch repair gene mutations. These families should be considered for the increased clinical surveillance methods adopted by the group, he said. Thomas Weber
News In Brief
Group found that overall infection rates with nortloxacin, ofloxacin, and ofloxacin plus rifampicin were 47%, 24%, and 9%, respectively, with the pattern of bacteraemia suggesting that rifampicin was especially effective against coagulase-negative staphylococci. This benefit was offset by an increase in the rate of unexplained fever (24%, 53%, and 49%), and a trend towards a greater risk for colonisation with opportunistic fungi among patients receiving ofloxacin plus rifampicin. No increase in invasive fungal superinfections was seen. The full benefit of such antibacterial regimens, say Bow and colleagues, may require the use of additional antifungal prophylaxis, and the clinical significance of their overall findings will not be evident ‘‘untilwe better understand unexplained fevers”.
HIV-1 urine test approval The US Food and Drug Administration has approved Calypte Biomedical’s test, which detects HIV-1 antibodies in urine. The enzyme immunoassay diagnostic test is not as accurate as a blood test, and was not approved as a first-line screen. Those who test positive with the urine specimen must be reconfirmed with a second urine specimen, and a blood specimen if the second urine sample is positive. The test will distributed in the UK by Seradyne. Health of the British nation Good progress is being made towards 11 of 27 health targets set by the UK government in 1992 but for obesity, sensible drinking levels in women, and smoking in 11-15 year olds the trends are in the wrong direction, says a progress report (Aug 14).
Pia Pini
Vol348 -August 17,1996
465
Clinical surveillance recommendations adopted for HNPCC
T
he International Collaborative Group on Hereditary Non Polyposis Colorectal Cancer (ICGHNPCC) recently adopted a set of guidelines for the clinical surveillance of HNPCC family members (panel). These are designed, said Hans Vasen (Leiden, The Netherlands), president of the group, to maximise detection of early stage and premalignant lesions in the principal organ sites affected in the HNPCC phenotype. HNPCC is an autosomal dominant condition characterised by early age of onset (mean 47 years) colorectal cancer and extra-colonic malignancies that include endometrial, urinary tract, and upper gastrointestinal adenocarcinoma. HNPCC may account for up to 12% of total world incidence of colorectal cancer, but considerable clinical controversy surrounds optimal surveillance methods for members of HNPCC families. The recommendations adopted last week in Buffalo, USA, at the 8th annual meeting of the ICG-HNPCC include index colonoscopy at age 20-25 with repeat colonoscopy every 2 years and gynaecological examination, including transvaginal sonography at age 30-35 with follow up every 1-2 years. There was a broad consensus that frequent observations of rapid progression from premalignant adenomas to invasive adeno-
carcinomas warranted colonoscopic surveillance at a greater frequency than that required for other at risk groups. Founding member Henry Lynch (Omaha, USA) reminded the group that insurance companies
Site
Procedure
Lower age limit (YE)
lnteirval (yrs)
Colon Endometrium (and ovaries)
Colonoscopy Gynaecologicalexam, transvaginal sonography, CA-125 measurement Gastroscopy Sonography, urine analysis
20-25
30-35
2 1-2
30-35 30-35
1-2 1-2
Stomach* Urinary tract*
*only if it runs in the family
and national health insurance agencies must be informed of the new recommendations in order to gain their funding support for the increased surveillance. Scientific presentations at the meeting detailed the growing number of mutations in the recently identified DNA mismatch repair genes hMSH2 and hMLHl that segregate with HNPCC. These now total over 110, distributed between the two genes. 70% of mutations in HNPCC pedigrees are attributable to hMLH1, said Paivi Peltomaki (Helsinki, Finland) who presented up-to-date results from the Mismatch Repair Gene Mutation Data Bank. Reports of mutations in PMSl and PMS2,
Rifampicin reduces infec ions in neutropenia
T
.
he benefit of oral quinolonebased antibacterial prophylaxis in neutropenic patients with cancer can now be augmented, according to the findings of a recent randomised multicentre trial in Canada. The addition of an agent with an increased anti-gram-positive effect to a quinolone with broader activity against gram-positive bacteria significantly reduces overall infection rates in such patients. In their investigation, Eric Bow and colleagues (National Cancer Institute of Canada Clinical Trials Group) evaluated three oral antibacterial prophylactic regimens in 111 patients with severe neutropenia in 14 centres (Ann Intern Med 1996; 125: 183-90). The study bears out earlier research showing that the addition of rifampicin to ofloxacin in neutropenic rats reduced bacteraemia due to both viridans streptococci and staphylococci. The NCIC Clinical Trials
two further DNA mismatch repair genes, remained unchanged from a year ago (1 and 2 mutations respectively). ICG-HNPCC plans to expand its mutation database network in collaboration with other gene
mutation databases, said Albert de la Chapelle (Helsinki, Finland). Miguel Rodriguez-Bigas (Buffalo, USA) noted that the evidence presented at the meeting strongly suggests that DNA mismatch repair gene mutations are not restricted to families that meet strict phenotypic criteria for HNPCC, and that clinicians should be aware that cancer-prone families, particularly those with early age of onset colorectal or endornetrial carcinoma, may harbour mismatch repair gene mutations. These families should be considered for the increased clinical surveillance methods adopted by the group, he said. Thomas Weber
News In Brief
Group found that overall infection rates with nortloxacin, ofloxacin, and ofloxacin plus rifampicin were 47%, 24%, and 9%, respectively, with the pattern of bacteraemia suggesting that rifampicin was especially effective against coagulase-negative staphylococci. This benefit was offset by an increase in the rate of unexplained fever (24%, 53%, and 49%), and a trend towards a greater risk for colonisation with opportunistic fungi among patients receiving ofloxacin plus rifampicin. No increase in invasive fungal superinfections was seen. The full benefit of such antibacterial regimens, say Bow and colleagues, may require the use of additional antifungal prophylaxis, and the clinical significance of their overall findings will not be evident ‘‘untilwe better understand unexplained fevers”.
HIV-1 urine test approval The US Food and Drug Administration has approved Calypte Biomedical’s test, which detects HIV-1 antibodies in urine. The enzyme immunoassay diagnostic test is not as accurate as a blood test, and was not approved as a first-line screen. Those who test positive with the urine specimen must be reconfirmed with a second urine specimen, and a blood specimen if the second urine sample is positive. The test will distributed in the UK by Seradyne. Health of the British nation Good progress is being made towards 11 of 27 health targets set by the UK government in 1992 but for obesity, sensible drinking levels in women, and smoking in 11-15 year olds the trends are in the wrong direction, says a progress report (Aug 14).
Pia Pini
Vol348 -August 17,1996
465