Journal Club: Sept 29, 2010

M.L.M. Lanting, MDBRH-Surgery

Scenario• 45/M• Diagnosed with rectal

adenocarcinoma, 6-7cms from anal verge

• For elective LAR• With protective ileostomy?

P : Patients from all hospitals in Sweden operated on with low anterior resection of the rectum for cancer from December 1999 to June 2005

I: Low anterior resection WITH FECAL DIVERSION through a defunctioning stoma (either loops ileostomy or transverse loop colostomy)

C: Low anterior resection WITHOUT A DEFUNCTIONING STOMA

O: rate of symptomatic anastomotic leakage and the need for urgent reoperation

M: randomized controlled multicenter trial

Keywords:• Rectal cancer• Low anterior resection• Ileostomy

Defunctioning Stoma Reduces Defunctioning Stoma Reduces Symptomatic Anastomotic Symptomatic Anastomotic Leakage after Low Anterior Leakage after Low Anterior Resection of the Rectum for Resection of the Rectum for CancerCancer

Annals of Surgery, Volume 246, Number 2, August 2007

Peter, Matthiesen MD, PhD; Olof Hallbook MD, PhD; Jorgen Rutegard MD, PhD; Goran Simert MD, PhD: Rune Sjodahl MD, PhD

Departments of SurgeryOrebro University HospitalLinkoping University Hospital Sweden

Abstract

Background Total mesorectal excision surgery as the surgical

technique of choice for carcinoma in the lower and mid rectum decreased local recurrence and improved oncological results

Despite these advances, perioperative morbidity still remains, with symptomatic anastomotic leakage as the the most feared

Abstract

Patients and methods: December 1999-June 2005 234 patients randomized to a defunctioning loop

stoma or no loop stoma (loop ileostomy or transverse loop colostomy)

Inclusion criteria:• Expected survival > 6months• Informed consent• Anastomosis ≤ 7 cms above the anal verge• Negative air leakage test• Intact anastomotic rings• Absence of major intraoperative adverse

events

Abstract

Results: Overall leak rate: 19.2% (45/234)

• With a defunctioning stoma: 10.3% (12/116)• No stoma: 28% (33/118)

Need for urgent abdominal reoperation: • With a defunctioning stoma: 8.6% (10/116)• No stoma: 25.4% (30/118)

Median age: 65 years (range 32-86)• Females: 45.3% (106/234)

Preoperative RT: 79.1% (185/234) Level of anastomosis: median 5cm Intraoperative blood loss: 550 mL

Abstract

Conclusion: Defunctioning loop stoma decreased the rate of

symptomatic anastomotic leakage and is therefore recommended in low anterior resection for rectal cancer.

ARE THE RESULTS OF THE STUDY VALID?

Primary Guides• Was the assignment of patients to treatments

randomized? YES- Randomization was done by opening a sealed envelope after construction and testing of the anastomosis.- 21 hospitals: 234/821 randomized (28.5%)

Primary Guides• Were all patients who entered the trial properly

accounted for & attributed at its conclusion?1. Was follow up complete? YES, all patients were followed up,

median 42 months.

2. Were patients analyzed in the groups to which they were randomized? YES Inclusion criteria Exclusion criteria

ARE THE RESULTS OF THE STUDY VALID?

INCLUSION CRITERIA

Preoperative Biopsy proven adenocarcinoma of the rectum

located at ≤ 15 cm above the anal verge measured with a rigid rectoscope

Ability to understand the study information Estimated survival >6 months as judged by the

surgeon

INCLUSION CRITERIA

Intraoperative Anastomosis at ≤7 cm above the anal verge Negative air leakage test Intact anastomotic stapler rings Absence of any major intraoperative adverse events

as judged by the operating surgeon

EXCLUSION CRITERIA

Secondary Guides Were patients, health workers, and study

personnel “blind” to treatment? NO• The surgeon was not blinded.• Patients were also not blinded since the informed

consent is part of the inclusion criteria.

ARE THE RESULTS OF THE STUDY VALID?

Secondary Guides• Were the groups similar at the start of the trial?

YES

ARE THE RESULTS OF THE STUDY VALID?

Secondary Guides Aside from the experimental intervention, were

the groups treated equally? YES• All patients had preoperative bowel preparation

and prophylactic antibiotics according to the standard treatment of each hospital.

• Preoperative irradiation, chemotherapy and the use of pelvic drainage were the choice of the surgeon.

• All anastomoses were made with a circular stapler device.

ARE THE RESULTS OF THE STUDY VALID?

WHAT ARE THE RESULTS?

• How large was the treatment effect?• How precise was the estimate of the treatment

effect?

Task

1. Determine Risk

2. Determine Relative Risk, RRR or RRI

3.3. Comparing the Risks between GroupsComparing the Risks between Groups

4. Interpreting the Comparisons

(+) Symptomatic anastomotic

leakage

(-) Symptomatic anastomotic

leakage

Total

I (Group 1-DS) A 12 B 104 116

C (Group 2-NS) C 33 D 118 118

Total 43 222 234

Risk in I (DS) : a/ a + b =

• Symptomatic anastomotic leak in Group 1-DS: 0.10

Risk in C (NS) : c / c + d =

• Symptomatic anastomotic leak in Group 2-NS: 0.28

Determining Risk - Symptomatic anastomotic leakage

• Relative Risk (RR): a / a + b c / c + d= 0.36

• Relative Risk Reduction (RRR) or Relative Risk Increase (RRI):

(1 – RR) x 100

= 64

Determining Relative Risk, RRR or RRI

(+) Symptomatic anastomotic

leakage

(-) Symptomatic anastomotic

leakage

Total

I (Group 1-DS) A 12 B 104 116

C (Group 2-NS) C 33 D 118 118

Total 43 222 234

• Risk Difference: Absolute Risk Reduction (ARR) or Increase (ARI)

(c / c + d) - (a / a + b) = 0.18

(risk of dev.outcome w/o tx) - (risk of dev.outcome w/ tx)

• Number needed to treat (NNT)

1 / ARR = 5.5 patients

Comparing the Risks between GroupsComparing the Risks between Groups(+) Symptomatic

anastomotic leakage

(-) Symptomatic anastomotic

leakage

Total

I (Group 1-DS) A 12 B 104 116

C (Group 2-NS) C 33 D 118 118

Total 43 222 234

Interpreting the ComparisonsIF OUTCOME IS DISEASE: • RR = outcome in exptal grp / outcome in control grp

If numerator > denominator, RR > 1, tx is harmful.If numerator < denominator, RR < 1, tx is beneficial.If numerator = denominator, RR = 1, tx is useless.

• ARR= Outcome in control grp – Outcome in exptal grpIf ARR > 0, tx is beneficialIf ARR < 0, tx is harmfulIf ARR = 0, tx has no effect RR= 0.36 beneficial

ARR = 0.18 beneficial

IF OUTCOME IS CURE: (disease free interval) • RR = outcome in exptal grp / outcome in control grp

If numerator > denominator, RR > 1, tx is beneficial.If numerator < denominator, RR < 1, tx is harmful.If numerator = denominator, RR = 1, tx is useless.

• ARR= Outcome in control grp – Outcome in exptal grpIf ARR > 0, tx is harmfulIf ARR < 0, tx is beneficialIf ARR = 0, tx has no effect

• Symptomatic anastomotic leak in Group 1-DS: 0.10• Symptomatic anastomotic leak in Group 2-NS: 0.28• RR= 0.36 beneficial• ARR = 0.18 beneficial

• NNT = 5.5 patients

SUMMARY of Results – SUMMARY of Results – Symptomatic anastomotic leakage

(+) Symptomatic anastomotic

leakage

(-) Symptomatic anastomotic

leakage

Total

I (Group 1-DS) A 12 B 104 116

C (Group 2-NS) C 33 D 118 118

Total 43 222 234

Determining Risk – Reoperations

(+) Reoperation (-) Reoperation Total

I (Group 1-DS) A 10 B 106 116

C (Group 2-NS) C 30 D 88 118

Total 40 194 234

• Risk in I (DS) : a/ a + b =• Reoperations in Group 1-DS: 0.09

• Risk in C (NS) : c / c + d = • Reoperations in Group 2-NS: 0.25

• Relative Risk (RR): a / a + b c / c + d= 0.36

• Relative Risk Reduction (RRR) or Relative Risk Increase (RRI):

(1 – RR) x 100

= 64

Determining Relative Risk, RRR or RRI(+) Reoperation (-) Reoperation Total

I (Group 1-DS) A 10 B 106 116

C (Group 2-NS) C 30 D 88 118

Total 40 194 234

• Risk Difference: Absolute Risk Reduction (ARR) or Increase (ARI)

(c / c + d) - (a / a + b) = 0.16

(risk of dev.outcome w/o tx) - (risk of dev.outcome w/ tx)

• Number needed to treat (NNT)

1 / ARR = 6 patients

Comparing the Risks between GroupsComparing the Risks between Groups(+) Reoperation (-) Reoperation Total

I (Group 1-DS) A 10 B 106 116

C (Group 2-NS) C 30 D 88 118

Total 40 194 234

Interpreting the ComparisonsIF OUTCOME IS DISEASE: • RR = outcome in exptal grp / outcome in control grp

If numerator > denominator, RR > 1, tx is harmful.If numerator < denominator, RR < 1, tx is beneficial.If numerator = denominator, RR = 1, tx is useless.

• ARR= Outcome in control grp – Outcome in exptal grpIf ARR > 0, tx is beneficialIf ARR < 0, tx is harmfulIf ARR = 0, tx has no effect RR= 0.36 beneficial

ARR = 0.16 beneficial

IF OUTCOME IS CURE: (disease free interval) • RR = outcome in exptal grp / outcome in control grp

If numerator > denominator, RR > 1, tx is beneficial.If numerator < denominator, RR < 1, tx is harmful.If numerator = denominator, RR = 1, tx is useless.

• ARR= Outcome in control grp – Outcome in exptal grpIf ARR > 0, tx is harmfulIf ARR < 0, tx is beneficialIf ARR = 0, tx has no effect

• Urgent Reoperations in Group 1-DS: 0.09• Urgent Reoperations in Group 2-NS: 0.25• RR= 0.36 beneficial• ARR = 0.16 beneficial

• NNT = 6 patients

SUMMARY of Results – SUMMARY of Results – Urgent Reoperation

(+) Reoperation (-) Reoperation Total

I (Group 1-DS) A 10 B 106 116

C (Group 2-NS) C 30 D 88 118

Total 40 194 234

WILL THE RESULTS HELP ME IN CARING FOR MY PATIENTS?

• Can the results be applied to my patient care? YES

• Were all clinically important outcomes considered? YES

• Are the likely treatment benefits worth the potential harms & costs? YES

WILL THE RESULTS HELP ME IN CARING FOR MY PATIENTS?

Scenario: 45/M, diagnosed with rectal adenocarcinoma 6-7 cms from anal verge, for elective LAR, with protective ileostomy?

Research Question: Can a defunctioning stoma reduce symptomatic anastomotic leakage after low efunctioning stoma reduce symptomatic anastomotic leakage after low anterior resection of the rectum for cancer?anterior resection of the rectum for cancer?

Citation: Defunctioning Stoma Reduces Symptomatic Anastomotic Leakage after Low Anterior Defunctioning Stoma Reduces Symptomatic Anastomotic Leakage after Low Anterior Resection of the Rectum for CancerResection of the Rectum for Cancer

Annals of Surgery, Volume 246, Number 2, August 2007

P- patients who underwent low anterior resection for rectal adenocarcinoma from December 1999-June 2005 in all hospitals in Sweden

RCT? Y

I- LAR with fecal diversion Ff-up adeq? Y

C LAR with no diverting stoma ITT? Y

Blinding? No

O- rate of symptomatic anastomotic leakage and need for urgent reoperation Baseline same? Y

M- randomized controlled trial Equal tx? Y

CAT - TREATMENT

RATE OF ANASTOMOTIC LEAKAGE

Outcome RRR RR ARR NNT p

With stoma 64 0.36 0.18 5.5

Author's conclusion: A defunctioning stoma after a low anterior resection in patients with rectal adenocarcinoma decreases the rate of symptomatic anastomotic leakage as well as the need for urgent reoperation.Reviewer's conclusion: Agree w/ authors

Resolution of scenario: : I think this can be applied in our setting

Reviewer's name: Mark Louie M. Lanting, MD Date: Sept 29, 2010

CAT - TREATMENT

NEED FOR URGENT REOPERATION

Outcome RRR RR ARR NNT p

With stoma 64 0.36 0.16 6

Thank you.