Transcript in bariatric surgery. - 埼玉医科大学総合医療センター 内分泌・糖尿病内科

Journal Club
Birkmeyer NJ, Dimick JB, Share D, Hawasli A, English WJ, Genaw J, Finks JF, Carlin
AM, Birkmeyer JD; Michigan Bariatric Surgery Collaborative.
Hospital complication rates with bariatric surgery in Michigan.
JAMA. 2010 Jul 28;304(4):435-42.
Topol EJ, Bousser MG, Fox KA, Creager MA, Despres JP, Easton JD, Hamm CW,
Montalescot G, Steg PG, Pearson TA, Cohen E, Gaudin C, Job B, Murphy JH, Bhatt
DL; CRESCENDO Investigators.
Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised,
multicentre, placebo-controlled trial.
Lancet. 2010 Aug 14;376(9740):517-23.
2010年8月19日 8:30-8:55
８階 医局
埼玉医科大学 総合医療センター 内分泌・糖尿病内科
Department of Endocrinology and Diabetes,
Saitama Medical Center, Saitama Medical University
松田 昌文
Matsuda, Masafumi
Bariatric Surgery
a reduction in mortality of 23% from 40%!
some obese young adults may lose up to 20 years of life
expectancy if they do not reduce their weight
Department of Surgery, and Center for Healthcare Outcomes and
Policy (CHOP) (Drs N. Birkmeyer, Dimick, Finks, and J. Birkmeyer),
and Department of Family Medicine (Dr Share), University of Michigan,
Ann Arbor; Department of Surgery, St John Hospital and Medical Center,
Detroit, Michigan (Dr Hawasli); Department of Surgery, Marquette
General Hospital, Marquette, Michigan (Dr English); and Department of
Surgery, Henry Ford Hospital, Detroit, Michigan (Drs Genaw and Carlin).
Corresponding Author: Nancy J. O. Birkmeyer, PhD, Michigan
Surgical Collaborative for Outcomes Research and Evaluation (MSCORE), Department of Surgery, University of Michigan, 211 N Fourth
Ave, Ste 2A and 2B, Ann Arbor, MI 48104 (nbirkmey@umich .edu).
JAMA. 2010;304(4):435-442
Background
Context Despite the growing popularity of
bariatric surgery, there remain concerns
about perioperative safety and variation in
outcomes across hospitals.
Objective To assess complication rates of
different bariatric procedures and
variability in rates of serious complications
across hospitals and according to
procedure volume and center of
excellence (COE) status.
Methods
Design, Setting, and Patients Involving 25 hospitals
and 62 surgeons statewide, the Michigan Bariatric
Surgery Collaborative (MBSC) administers an
externally audited, prospective clinical registry. We
evaluated short-term morbidity in 15 275 Michigan
patients undergoing 1 of 3 common bariatric
procedures between 2006 and 2009. We used
multilevel regression models to assess variation in riskadjusted complication rates across hospitals and the
effects of procedure volume and COE designation (by
the American College of Surgeons or American Society
for Metabolic and Bariatric Surgery) status.
Main Outcome Measure Complications occurring
within 30 days of surgery.
Adjustable gastric banding
Biliopancreatic diversion
Roux-en-Y gastric bypass
Sleeve gastrectomy
Vertical banded gastroplasty
with duodenal switch
A meta-analysis from University of California, Los Angeles reports the
following weight loss at 36 months
Biliopancreatic diversion - 53 kg
Roux-en-Y gastric bypass (RYGB) - 41 kg
Open - 42 kg
Laparoscopic - 38 kg
Adjustable gastric banding - 35 kg
Vertical banded gastroplasty - 32 kg
Sleeve gastrectomy ?
It is estimated that in 2005, the number of
procedures performed in the United States was
more than 10 times as great as the number
performed in 1994, an increase from approximately
16,200 procedures to 171,000, and the number is
still rising. (N Engl J Med 2009; 361:520-521)
The American College of Surgeons and
the American Society for Metabolic and
Bariatric Surgery— have implemented
programs for accrediting hospitals as
centers of excellence (COE) in bariatric
surgery.
The LABS writing group assumes responsibility for the content of this article. Members of the LABS writing group
are listed in the Appendix. Address reprint requests to Dr. David R. Flum at the Surgical Outcomes Research
Center, Department of Surgery, University of Washington, Box 356410, Seattle, WA 98195-6410
N Engl J Med 2009;361:445-54.
Why COE accreditation by professional organizations or payers might not necessarily
identify safer hospitals with bariatric surgery?
 First, although COE applications often ask hospitals for rates
of specific outcomes ( eg, postoperative venous
thromboembolism), such outcomes data are generally not
audited for accuracy or completeness and are often loosely
defined.
 Second, aside from minimum case loads, most requirements
for bariatric COE accreditation, including the availability of
specific protocols and resources form an aging morbidly
obese patients, are easily met by most hospitals with bariatric
programs and likely have little bearing on surgical
complication rates.
 Finally, given the highly competitive market place for bariatric
surgery, COE accreditation programs may be attracting
hospitals motivated as much by marketing advantage as by
the desire to demonstrate and improve their quality.
Results
Results Overall,7.3%of patients experienced perioperative complications,
most of which were wound problems and other minor complications. Serious
complications were most common after gastric bypass (3.6%;95%confidence
interval [CI], 3.2%-4.0%), followed by sleeve gastrectomy (2.2%; 95% CI,
1.2%-3.2%), and laparoscopic adjustable gastric band (0.9%; 95% CI, 0.6%1.1%) procedures (P<.001). Mortality occurred in 0.04% (95% CI, 0.001%0.13%) of laparoscopic adjustable gastric band, 0 sleeve gastrectomy, and
0.14% (95% CI, 0.08%-0.25%) of the gastric bypass patients. After adjustment
for patient characteristics and procedure mix, rates of serious complications
varied from1.6% (95%CI,1.3-2.0) to3.5%(95%CI, 2.4-5.0) (risk difference,
1.9;95%CI, 0.08-3.7) across hospitals. Average annual procedure volume was
inversely associated with rates of serious complications at both the hospital
level (<150cases, 4.1%;95%CI,3.0%-5.1%;150- 299 cases, 2.7%;95%CI, 2.23.2; and ≧300 cases, 2.3%;95%CI, 2.0%-2.6%;P=.003) and surgeon level
(<100 cases, 3.8%;95%CI, 3.2%-4.5%; 100-249 cases, 2.4%;95% CI, 2.1%2.8%; ≧ 250 cases, 1.9%;95%CI, 1.4%-2.3%; P=.001). Adjusted rates of
serious complications were similar in COE and non-COE hospitals
(COE,2.7%;95%CI,2.5%- 3.1%; non-COE, 2.0%; 95% CI, 1.5%-2.4%; P=.41).
Conclusion
Conclusions The frequency of serious
complications among patients
undergoing bariatric surgery in
Michigan was relatively low. Rates of
serious complications are inversely
associated with hospital and surgeon
procedure volume, but unrelated to
COE accreditation by professional
organizations.
Message/Comments
FDAが糖尿病の治療で有効と認めている治
療の第一は減量手術！
日本では保険適用もないし一般的ではない
が、今後の課題である。
「いい外科医紹介します．．．」
On March 31st 2010, Orexigen submitted a New
Drug Application (NDA) to the U.S. Food and
Drug Administration (FDA) for Contrave.
www.thelancet.com Published online July 30, 2010 DOI:10.1016/S0140-6736(10)60888-4
Novo Nordisk now plans to re-initiate the global phase 3
programme in the first half of 2011 in clinical trials comprising
approximately 5,000 patients (June 22, 2010)
www.thelancet.com Published online October 23, 2009 DOI:10.1016/S0140-6736(09)61375-1
Lancet 2005; 365: 1389–97
rimonabant
In 2006, the European Medicines Agency approved the
marketing of rimonabant in Europe. In 2007, however, new
contraindications were formulated by the Agency. Also in
2007, the US Food and Drug Administration denied
approval in the USA. Reasons for concern were
neuropsychiatric side effects, including depression and
suicide attempts.
Scripps Translational Science Institute, La Jolla, CA, USA (Prof E J Topol MD); Hopital Lariboisiere, Paris,
France (Prof M-G Bousser MD); University of Edinburgh, Edinburgh, UK (Prof K A A Fox MBCh); Brigham
and Women’s Hospital and Harvard University, Boston, MA, USA (M A Creager MD); Centre de
Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Quebec, Canada (Prof JP Despres MD); Rhode Island Hospital and Brown University, Providence, RI, USA (Prof J D Easton MD);
Kerckhoff Klinik, Bad Nauheim, Germany (Prof C W Hamm MD); Centre Hospitalier Universitaire PitieSalpetriere, Paris, France (Prof G Montalescot MD); INSERM U-698, Universite Paris 7 and Hopital Bichat,
AP-HP, Paris, France (Prof P G Steg MD); University of Rochester, Rochester, NY, USA (Prof T A Pearson
MD); Sunnybrook Health Sciences Centre, Toronto, ON, Canada (E Cohen MD); Sanofi -Aventis, Paris,
France (C Gaudin MD, B Job MD, J H Murphy MD); and VA Boston Healthcare System, Boston, MA, USA
(D L Bhatt MD)
Lancet 2010; 376: 517–23
Background
Blockade of the endocannabinoid
receptor reduces obesity and
improves metabolic abnormalities
such as triglycerides, HDL
cholesterol, and fasting blood
glucose. We assessed whether
rimonabant would improve major
vascular event-free survival
Methods
This double-blind, placebo-controlled trial was
undertaken in 974 hospitals in 42 countries. 18 695
patients with previously manifest or increased risk
of vascular disease were randomly assigned to
receive either rimonabant 20 mg (n=9381) or
matching placebo (n=9314). Randomisation was
stratified by centre, implemented with an
independent interactive voice response system, and
all study personnel and participants were masked to
group assignment. The primary endpoint was the
composite of cardiovascular death, myocardial
infarction, or stroke, as determined via central
adjudication. Analysis was by intention to treat.
This study is registered with ClinicalTrials.gov, number NCT00263042.
Follow-up in the trial was prematurely ended on Nov 6, 2008, because of a request
by the regulatory agency for cessation of clinical research of rimonabant in Ireland,
France, and Germany. At that time, the mean exposure to the drug had been 13・8
months (95% CI 13・6–14・0)
The frequency of serious psychiatric side-effects also differed significantly,
occurring in 232 (2・5%) of patients in the rimonabant group compared with 120
(1・3%) in the placebo group (p<0・0001). There were four suicide events in the
rimonabant group versus one in the placebo group, and nine versus five
patients, respectively, attempted suicide.
A study showed that single nucleotide variants in a tyrosine
kinase receptor gene (NTRK2) involved in neurotrophic
signalling were associated with more than four-fold
increased risk of suicide. Furthermore, the clinical benefit of
endocannabinoid-1 blockade could have been manifest in
patients with a particular gene variant in the
endocannabinoid-1 or related pathways.
Results
At a mean follow-up of 13・8 months (95% CI 13・6–14・0), the
trial was prematurely discontinued because of concerns by
health regulatory authorities in three countries about suicide
in individuals receiving rimonabant. All randomised
participants were analysed. At the close of the trial (Nov 6,
2008), the composite primary endpoint of cardiovascular
death, myocardial infarction, or stroke occurred in 364 (3・9%)
patients assigned to rimonabant and 375 (4・0%) assigned to
placebo (hazard ratio 0・97, 95% CI 0・84–1・12, p=0・68). With
rimonabant, gastrointestinal (3038 [33%] vs 2084 [22%]),
neuropsychiatric (3028 [32%] vs 1989 [21%]), and serious
psychiatric side-effects (232 [2・5%] vs 120 [1・3%]) were
significantly increased compared with placebo. Four patients
in the rimonabant group and one in the placebo group
committed suicide.
Conclusion
The premature termination of this trial
has important lessons for drug
development. A drug that was being
marketed for weight loss, but being
tested for improving cardiovascular
outcomes, induced a level of serious
neuropsychiatric effects that was
deemed unacceptable by regulatory
authorities, and both the drug and the
trial were abruptly terminated.
Message
Rimonabantはヨーロッパで数年使われていたが、
少数例だが自殺が増えるようで販売中止となっ
た。
体重が減ることで心血管障害が予防できるよう
なこともなかったので当然の処置であろう。
減量の薬物介入はなかなか難しい。