JURNAL

READING

Perioperative epidural analgesia for major

abdominal surgery and recurrence-free
survival: randomised trial
Paul S Myles, Philip Peyton, Brendan Silbert, Jennifer Hunt,
John R A Rigg, Daniel I Sessler
Oleh:
Halim Sudono
Pembimbing:
Prof. Dr. dr. Nancy Margarita Rehatta, SpAn. KIC. KNA.
Departemen / SMF Anestesiologi dan Reanimasi
Fakultas Kedokteran Universitas Airlangga / RSU dr. Soetomo
Surabaya
2015

Introduction
Complete surgical eradication of cancer:
Surgery
release cancer cells into the
circulation
depresses cell mediated immunity
reduces circulating concentrations
of tumor related antiangiogenic
factors
increases concentrations of proangiogenic factors
releases growth factors that
promote local and distant growth
of malignant tissue

Anesthesia
- Impairs many immune
function
Opioids
- Inhibit cellular and
humoral immune function
in humans
- pro-angiogenic and
promotes growth of
breast
tumours in rodents

Introduction
Regional anesthesia and analgesia:
- prevents the neuroendocrine stress response to surgery by
blocking afferent neural transmission from reaching the CNS and
by blocking descending efferent activation of the sympathetic
nervous system volatile anesthetics and sparing
postoperative opioids
- release of endogenous opioids
- opioid induced immune impairment
In animals reduce the metastatic burden in animals inoculated
with breast adenocarcinoma cells
In humans
two reported beneficial effects in breast cancer and prostate
cancer
three reported no beneficial effects in colon cancer, prostate
cancer, and cervical cancer
one equivocal results in prostate cancer

METHODS
This is an follow up study of MASTER trial
MASTER was a multicentre randomised clinical
trial designed to test the hypothesis that
combined epidural and general anesthesia
reduces the frequency of a composite end point
of mortality and major postoperative
complications compared with general
anasthesia and opioid analgesia

METHODS
Study design and participants
Design : Long term follow-up of prospective randomised
controlled clinical trial in which patients were randomly
assigned to receive general anesthesia with or without
epidural block for at least three postoperative days
Participants : 503 adult patients who had potentially
curative surgery for cancer (complete surgical excision
of cancer) esophagectomy, gastrectomy,
hepatectomy, pancreatectomy, colectomy,
nephrectomy, cystectomy, radical hysterectomy,
and open prostatectomy
Setting : 23 hospitals in Australia, New Zealand, and
Asia

METHODS
Study Profile

METHODS
Follow up data : the patients medical record from
the source hospital, hospital surgery or pathology
databases (or both), the patient s general
practitioner, state based cancer registry or national
death index (or both), letter of introduction followed
by telephone contact of the patient, and letter of
introduction followed by telephone contact of the
patient s next of kin
Cause of death : cancer, cardiovascular disease,
sepsis, and other causes

METHODS
Study end points:
primary end point of the study : cancer-free survival after
surgery
the secondary endpoint : survival (all cause mortality)
Statistical analysis:
Intention to treat principle
Kaplan Meier survival estimates and log-rank test
Outcomes of cancer (five year survival and five year
disease-free survival) 2 test and multivariate logistic
model
SPSS for Windows, version 18 for analyses

RESULT

RESULT

RESULT

RESULT

RESULT

RESULT

RESULT

DISCUSSION

Host defense is well established as the primary determinant

of progression of cancer, and function of NK cells is the
single most important component.
The stress response to surgery, volatile anesthesia, and
opioid administration all directly impair natural killer cell
function, and each effect is ameliorated by spinal/epidural
anesthesia.
In vitro, animal, and some observational human data
suggested
that epidural block would substantially reduce the risk of
recurrence of cancer, but this study fail to support this
hypothesis: recurrence-free survival and mortality were
nearly identical in both groups and any subgroup included
in the analysis.
This study identified other factors that were associated with
poorer cancer-free survival after surgery : older age, female
sex, tumor-nodes metastases status (results not shown),

DISCUSSION
Other studies:
Benefit:
Exadaktylos AK, Buggy DJ, Moriarty DC, Mascha E, Sessler DI.
Can anesthetic technique for primary breast cancer surgery
affect recurrence or metastasis?
Biki B, Mascha E, Moriarty DC, Fitzpatrick JM, Sessler DI, Buggy
DJ Anesthetic technique for radical prostatectomy surgery
affects
cancer recurrence: a retrospective analysis.
No benefit:
Gottschalk A, et al. Association between epidural analgesia and
cancer recurrence after colorectal cancer surgery.
Tsui BC, Rashiq et al. Epidural anesthesia and cancer
recurrence rates after radical prostatectomy.
Ismail H, Ho KM, Narayan K, Kondalsamy-Chennakesavan S.
Effect of neuraxial anaesthesia on tumour progression in
cervical cancer patients treated with brachytherapy: a
retrospective cohort study

DISCUSSION
Strength:
compared its 9-15 years outcomes in a relatively large group of patients
who were randomly assigned to general anesthesia combined with
epidural anesthesia and analgesia versus general anesthesia and opioid
analgesia
well powered to detect a one third treatment effect but lacked power to
reliably detect smaller effects that might still be of considerable clinical
importance, particularly for individual types of cancer

Limitation
This study does not provide information on the effects of regional blockade
on non-abdominal (for example, breast) cancers.

CONCLUSION
Even though this study could not identify
any reduction in recurrence of cancer or
survival when epidural block was used for
surgery for abdominal cancer, it doesnt
meant that Regional analgesia (especially
epidural block) is an inferior choice
because it still provide a good post
operative pain treatment, can limit opioid
related side effects and reduce the risk of
hypotension.

CRITICAL APPRAISAL

CLINICAL QUESTION
Can regional anesthesia reduce the
risk of recurrence in patient
undergoing cancer surgery compared
to general anesthesia?

PICO
PICO Clinical Question

Journal

Patient undergoing
cancer surgery

503 adult patients who had

potentially
curative surgery for cancer

Regional anesthesia

general anaesthesia with epidural

block for at least three postoperative
days

GA

GA

risk of recurrence

long term recurrence of cancer and

survival of patients

Design, Journal Focus & Worksheet

Design : prospektif cohort
Fokus Jurnal : prognosis
Worksheet : prognosis

Telaah Kritis Jurnal : Validity

RAMMBO

Telaah Validitas

Jawaban Sesuai
Worksheet

Recruitment

Apakah sampel yang

Ya.
Penelitian ini adalah
follow up dari
MASTER trial

mewakili pasien
dimasukkan dalam
penelitian pada waktu
perjalanan
penyakitnya
sama?

Telaah Kritis Jurnal : Validity

RAMMBO

Telaah Validitas

Jawaban Sesuai
Worksheet

Allocation

Bagaimana pasien

Ya.

diperlakukan? Jika
ada subkelompok
dengan prognosis
berbeda, apakah
dilakukan
penyesuaian untuk
faktor prognosis yang
penting?

Telaah Kritis Jurnal : Validity

RAMMBO

Telaah Validitas

Jawaban Sesuai
Worksheet

Maintenance

Apakah status
kelompok
dipertahankan tetap
sebanding dengan
manajemen yang
sama? dan follow up
yang memadai?

Ya

Telaah Kritis Jurnal :

Validitity
RAMMBO

Telaah Validitas

Jawaban Sesuai
Worksheet

Measurement
Blinding
Outcome

Apakah subjek dan

penilai "disamarkan"
terhadap perlakuan
yang diterima
dan/atau
pengukurannya
objektif?

Ya.

Telaah Kritis Jurnal :

Importancy
Telaah Importancy

Jawaban Sesuai Worksheet

Apakah kemaknaan statistik &

kemaknaan klinis dari hasil
penelitian
tergambar dengan baik?

Ya

Pengukuran apa yang digunakan

dan seberapa dampak
perlakuannya?

Cancer free survival (hazard

ratio)

Mungkinkah dampak terjadi

karena kebetulan?

Tidak.

Telaah Kritis Jurnal :

Applicability
Telaah Applicability
Jawaban
Apakah PICO jurnal yang
diperoleh
sesuai PICO pertanyaan klinis?

Ya.

Apakah pasien anda cukup mirip

dengan
pasien dalam penelitian?

Ya.

Apakah intervensi dalam

penelitian ini dapat diterapkan
untuk manajemen pasien di
lingkungan anda?

Ya.

Akankah potensi manfaat lebih

besar
dibanding potensi merugikan bila
intervensi ini diaplikasikan pada
pasien anda?

Ya.

Apakah hasil penelitian ini dapat

diintegrasikan dengan nilai-nilai

Ya.