Research
Original Investigation
Laparoscopic Lavage vs Primary Resection
for Acute Perforated Diverticulitis
The SCANDIV Randomized Clinical Trial
Johannes Kurt Schultz, MD; Sheraz Yaqub, MD, PhD; Conny Wallon, MD, PhD; Ljiljana Blecic, MD; Håvard Mjørud Forsmo, MD;
Joakim Folkesson, MD, PhD; Pamela Buchwald, MD, PhD; Hartwig Körner, MD, PhD; Fredrik A Dahl, PhD; Tom Øresland, MD, PhD;
for the SCANDIV Study Group
Editorial page 1343
IMPORTANCE Perforated colonic diverticulitis usually requires surgical resection, which is
associated with significant morbidity. Cohort studies have suggested that laparoscopic lavage
may treat perforated diverticulitis with less morbidity than resection procedures.
OBJECTIVE To compare the outcomes from laparoscopic lavage with those for colon
Related articles pages 1346
and 1356
Supplemental content at
jama.com
resection for perforated diverticulitis.
DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized clinical superiority trial recruiting
participants from 21 centers in Sweden and Norway from February 2010 to June 2014. The last
patient follow-up was in December 2014 and final review and verification of the medical records
was assessed in March 2015. Patients with suspected perforated diverticulitis, a clinical indication
for emergency surgery, and free air on an abdominal computed tomography scan were eligible.
Of 509 patients screened, 415 were eligible and 199 were enrolled.
INTERVENTIONS Patients were assigned to undergo laparoscopic peritoneal lavage (n = 101)
or colon resection (n = 98) based on a computer-generated, center-stratified block
randomization. All patients with fecal peritonitis (15 patients in the laparoscopic peritoneal
lavage group vs 13 in the colon resection group) underwent colon resection. Patients with a
pathology requiring treatment beyond that necessary for perforated diverticulitis (12 in the
laparoscopic lavage group vs 13 in the colon resection group) were also excluded from the
protocol operations and treated as required for the pathology encountered.
MAIN OUTCOMES AND MEASURES The primary outcome was severe postoperative
complications (Clavien-Dindo score >IIIa) within 90 days. Secondary outcomes included
other postoperative complications, reoperations, length of operating time, length of
postoperative hospital stay, and quality of life.
RESULTS The primary outcome was observed in 31 of 101 patients (30.7%) in the laparoscopic
lavage group and 25 of 96 patients (26.0%) in the colon resection group (difference, 4.7%
[95% CI, −7.9% to 17.0%]; P = .53). Mortality at 90 days did not significantly differ between
the laparoscopic lavage group (14 patients [13.9%]) and the colon resection group (11 patients
[11.5%]; difference, 2.4% [95% CI, −7.2% to 11.9%]; P = .67). The reoperation rate was
significantly higher in the laparoscopic lavage group (15 of 74 patients [20.3%]) than in the
colon resection group (4 of 70 patients [5.7%]; difference, 14.6% [95% CI, 3.5% to 25.6%];
P = .01) for patients who did not have fecal peritonitis. The length of operating time was
significantly shorter in the laparoscopic lavage group; whereas, length of postoperative
hospital stay and quality of life did not differ significantly between groups. Four sigmoid
carcinomas were missed with laparoscopic lavage.
CONCLUSIONS AND RELEVANCE Among patients with likely perforated diverticulitis and
undergoing emergency surgery, the use of laparoscopic lavage vs primary resection did not
reduce severe postoperative complications and led to worse outcomes in secondary end points.
These findings do not support laparoscopic lavage for treatment of perforated diverticulitis.
TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01047462
JAMA. 2015;314(13):1364-1375. doi:10.1001/jama.2015.12076
1364
Author Affiliations: Author
affiliations are listed at the end of this
article.
Group Information: The SCANDIV
(Scandinavian Diverticulitis) Study
Group investigators are listed at the
end of this article.
Corresponding Author: Johannes
Kurt Schultz, MD, Department of
Gastrointestinal Surgery, Akershus
University Hospital, PB 1000, 1478
Lørenskog, Norway (josc@ahus.no).
(Reprinted) jama.com
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Fundacio Parc Tauli User on 12/14/2015
Laparoscopic Lavage vs Primary Resection for Perforated Diverticulitis
P
erforated colonic diverticulitis is common, having an
incidence of 3 to 4/100 000 people per year, is highly
morbid, and can be lethal.1,2 The severity of perforated
colonic diverticulitis is proportional to the degree of abdominal contamination (Table 1),3 and the extent of disease can be
assessed by computed tomographic (CT) imaging.4,5 Depending on what is found as a result of the CT imaging, treatments
will differ. If the perforation results in a contained abscess, it
can be managed with percutaneous drainage and intravenous antibiotics. If there is perforation with uncontained
purulent or fecal contamination, surgery is required.6,7 The
standard operative approach is to resect the perforated segment of colon along with as much diverticula-diseased colon
as possible. In general, the colon is not anastomosed back
together and a colostomy is created. During the last 2
decades, surgeons have been restoring colonic continuity
with a primary anastomosis when the peritonitis is not too
severe.7,8
Resection for perforated diverticulitis has a high morbidity rate (30%-50% complications) and a mortality rate of 10%
to 20%.9-11 Laparoscopic approaches to treating surgical conditions are generally associated with lower morbidity than open
approaches and have been tried for the treatment of perforated colonic diverticulitis.12,13 Laparoscopic lavage without resection seems feasible because on some occasions, perforations are already sealed when surgery is performed and the only
intervention that seems necessary is to lavage the abdominal
cavity to remove debris. This approach, when performed laparoscopically, was reported to have lower rates of morbidity and
mortality. However, the series showing this were likely affected by selection bias, ie, with optimal patients selected for
the new procedure and more severely ill patients being treated
with open colon resections, making the laparoscopic approach appear to have better outcomes.14
Only a randomized clinical trial (RCT) can overcome selection bias and definitively answer the question of whether
laparoscopic lavage is an adequate operation for perforated diverticulitis. To our knowledge, only 1 such trial has been performed. However, it involved a small number of patients
(N = 90), was terminated early, and may have been underpowered to definitively answer this question.15,16 In the present
RCT, we tested the hypothesis that laparoscopic lavage was superior to colon resection in patients with perforated diverticulitis and purulent peritonitis, with respect to severe postoperative complications within 90 days of surgery.
Original Investigation Research
tial participant hospitals in Scandinavia. After a thorough
review, all participating hospitals consented to the final protocol (Supplement 2), which was made accessible at the
study web page. The trial was approved by the regional ethics
committee in southeastern Norway (reference number 2009/
177) and by the regional ethical review board in Stockholm,
Sweden (protocol 2010/3:2, number 2010/113-31/3).
Patients
Between February 5, 2010, and June 28, 2014, we enrolled
patients older than 18 years who were suspected clinically of
having perforated diverticulitis requiring urgent surgery. Participating hospitals joined the study at different times (eTable
1 in Supplement 1). Inclusion criteria included patient ability
to tolerate general anesthesia and diagnostic imaging results
(via an abdominal CT scan) showing free air and findings
compatible with perforated diverticulitis (usually including
colonic wall thickening and pericolic inflammation). The
indication for surgery was presence of clinical peritonitis.
The decision to operate was made by the surgeon in charge, a
position that varied between hospitals from senior surgical
residents to colorectal attending surgeons. Exclusion criteria
were bowel obstruction and pregnancy. Written informed
consent was obtained by the surgeon before study enrollment. In Sweden, consent to undergo surgery and for study
enrollment was provided by the next of kin for some patients
who could not self-provide consent (approved by the Swedish ethical board). In Norway, patients not capable of providing consent were not enrolled.
Randomization
Patients were randomly assigned to undergo either laparoscopic lavage or colon resection (Figure). Patients were not informed about the randomization result until after surgery. A
center-stratified block randomization was achieved with a webbased randomization and data collection system, developed
and administered by the Unit of Applied Clinical Research,
Institute of Cancer Research and Molecular Medicine,
Norwegian University of Science and Technology, Trondheim,
Norway. The first block per center was 2 + 2 and the subsequent blocks were randomly assigned 1 + 1 or 2 + 2. Neither participants nor investigators were informed about the block
sizes. A web-based case report form (CRF) was completed for
all participants during the hospital stay and at 3 and 12 months
postoperatively. The items covered by the CRF are accessible
online (eBox 1 and eBox 2 in Supplement 1).
Trial Interventions
Methods
Study Design
The Scandinavian Diverticulitis trial (SCANDIV) was designed
as a 2-group, open-labeled, pragmatic, superiority, multicenter RCT. A total of 21 surgical units were included in the
trial (9 in Sweden and 12 in Norway), ranging from small
community hospitals to tertiary referral centers. These units
covered a catchment population of approximately 5 million
people (eTable 1 in Supplement 1). A protocol draft was written by the principal investigators and distributed to all poten-
All patients were administered intravenous antibiotics,
according to local practices, after a diagnosis of peritonitis
was established. Because the trial design was pragmatic, the
intention was that the surgeons who normally operate on
these patients would do so in the study. There was no
requirement for minimum number of cases performed before
joining the trial. All surgeons had basic laparoscopic skills.
Surgical techniques were not monitored other than the monitoring surgeon reviewing the operation report. All patients
were marked preoperatively for potential stoma placement
jama.com
(Reprinted) JAMA October 6, 2015 Volume 314, Number 13
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Fundacio Parc Tauli User on 12/14/2015
1365
Research Original Investigation
Laparoscopic Lavage vs Primary Resection for Perforated Diverticulitis
Table 1. Hinchey Classification for Perforated Diverticulitisa
Hinchey Stages
a
b
Grade Ib
Walled-off pericolic abscess
Grade II
Walled-off pelvic abscess
Grade III
Free purulent contamination of the peritoneal space
Grade IV
Free fecal contamination of the peritoneal space
Data were adapted from Hinchey et al.3 Although Hinchey stages were
originally used as an intraoperative classification system with 4 clinical stages,
computed tomography (CT) has made nonoperative staging of the disease
possible.4,5 Most walled-off abscesses can thus be treated without surgery.
Free intraabdominal air on CT imaging indicates a perforation in the abdominal
cavity with purulent or feculent contamination (Hinchey grade III or IV).
Patients showing free air but no pus in the abdomen were graded Hinchey I in
this study.
on the left and right lower abdominal quadrants. Preexisting
comorbidities were assessed and scores for an American
Society of Anesthesiologists (ASA) physical status and Charlson Comorbidity index were determined.17 A Hinchey grade
was assigned after the abdomen was entered. In this study,
an assessment of a Hinchey grade III was defined as free air
detected on a preoperative CT scan and an intraoperative
finding of localized or generalized pus in the abdominal cavity. Irrespective of preoperative randomization, the Hartmann procedure was performed on all patients with feculent
peritonitis (Hinchey grade IV), including patients with a visible defect in the colon wall. If conditions other than perforated diverticulitis were found during abdominal exploration, the surgeons, using their clinical judgement, treated for
that condition.
In the resection group, the choices of laparoscopic vs open
resection, and also of Hartmann procedure vs primary resection and anastomosis (PRA) were determined by surgeon preference and local practices. The diseased colon segment was
resected to the level of the rectum (determined as that part of
the colon not having taenia coli), with or without mobilization of the splenic flexure. The Hartmann procedure was performed by closing the rectum with a stapling device and marking the blind rectal pouch with a nonabsorbable suture. A
colostomy was created through the stoma site, which was
marked preoperatively. For PRA, the choice of whether to protect the anastomosis with a diverting stoma or not was determined by the surgeon’s discretion. In all cases, at least 1 drain
was placed in the pelvis (either suction or nonsuction per the
surgeon’s discretion).
In laparoscopic lavage, pneumoperitoneum was preferably obtained by an open transumbilical technique with a
12-mm trocar, using at least 2 additional 5-mm trocars for abdominal access. All quadrants were rinsed before placing a nonsuction drain on each side of the pelvis. Adhesions to the sigmoid were not to be dissected.
In both groups, the time to drain removal was determined by the surgeon. According to the protocol, the abdominal cavity in all patients was rinsed with at least 4 L of saline
or until drainage was clear. All resected specimens were examined by a pathologist.
1366
Follow-up
Follow-up at 3 months and 1 year postoperatively was performed at an outpatient clinic, by a telephone interview, or with
a form sent by mail. The protocol required that a colonoscopy
be performed within 3 months after surgery for patients treated
with laparoscopic lavage, and before stoma reversal for patients operated with the Hartmann procedure. Patients with incorrect preoperative diagnosis were included in the follow-up
for the primary outcome, but otherwise excluded from the study.
Outcomes
The primary outcome variable for this study was having severe complications at 90 days after surgery. All complications
classified greater than Clavien-Dindo IIIa were defined as severe; ie, any complications that led to a reintervention requiring general anesthesia (IIIb), a life-threatening organ dysfunction (IV), or death (V).18 Secondary outcomes were the length
of operating time; length of postoperative hospital stay; postoperative complications individually, including those resulting in reoperations; and 90-day postoperative quality of life
(measured using the Cleveland Global Quality of Life
instrument).19 The Cleveland Global Quality of Life questionnaire includes 3 items (current quality of life, current quality of
health, and current energy level) each scaled from 0 (worst) to
10 (best). The total calculated score ranges from 0 (worst) to 1
(best). We considered a change of 0.1 as clinically important.
Data and Safety Monitoring
To ensure the accuracy of the collected data, a colorectal surgeon from a hospital different than the one in which the study
procedure was performed reviewed patient files and completed a monitor CRF. In case of discrepancies between the
original CRF and the monitor CRF, the main study coordinator requested a settlement between the monitoring surgeon
and the local study coordinator. The final decision was made
by the monitor. To ensure conformity between groups, the
evaluation of Hinchey grading was a substantial part of the
monitoring process. Evaluations were based on criteria including free air on CT and free pus in the abdomen (Hinchey III),
and fecal contamination or visible hole in the colon (Hinchey
IV) (Table 1). An independent radiologist, who was blinded to
patients’ randomization, reevaluated all CT scans obtained during each patient’s enrollment in the study.
As part of a local quality control effort, participating hospitals registered data for all patients who underwent operations for perforated diverticulitis during the study period. These
data were reviewed, but only at the center level, because they
included patients who were not in the trial and who had not
consented.
A safety committee was appointed, consisting of 3 Scandinavian professors (in colorectal surgery) who were not involved in the study. The safety committee, which completed
a safety analysis after 75 patients were enrolled, was supplied
with all patient data including patient characteristics and primary and secondary outcomes. The trial was to be terminated if there was a statistically significant difference in primary outcome between the study groups with a P value less
than .01.
JAMA October 6, 2015 Volume 314, Number 13 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Fundacio Parc Tauli User on 12/14/2015
jama.com
Laparoscopic Lavage vs Primary Resection for Perforated Diverticulitis
Original Investigation Research
Figure. Patient Flowchart of the SCANDIV Trial
509 Patients assessed for eligibility a
94 Ineligible
43 Preoperatively other diagnosis suspected b
24 Unable to give informed consent
23 Operated without CT, or no free air on CT
4 Other reasons
415 Eligible patients
216 Excluded
162 Not approached by the surgeon
35 Advanced malignancy or severe comorbidity
13 Declined to participate
3 Difficulties with online randomization
3 Hinchey grade IV c suspected on CT
199 Randomized
101 Randomized to the laparoscopic peritoneal
lavage group
85 Received per-protocol intervention
70 Laparoscopic lavage
15 Resection because of Hinchey grade IV c
16 Did not undergo intervention as randomized
1 Protocol violation (open peritoneal lavage)
3 Conversion to laparatomy because of
technical difficulties
1 PRA
2 Open lavage
12 Other intervention (incorrect preoperative
diagnosis)
9 Other perforations not caused by colonic
diverticulitis
3 Visible cancer (oncologic resection performed)
98 Randomized to the primary colon resection group
81 Received per-protocol intervention
68 Resection (18 PRA, 50 Hartmann procedure)
13 Resection because of Hinchey grade IV c
17 Did not undergo intervention as randomized
3 Protocol violation
2 Laparoscopic lavage
1 Open lavage
13 Other intervention (incorrect preoperative
diagnosis)
10 Other perforations not caused by colonic
diverticulitis
3 Visible cancer (oncologic resection performed)
1 Randomized without consent
0 Lost to follow-up
1 Lost to follow-up
101 Included in primary intention-to-treat analysis
96 Included in primary intention-to-treat analysis
2 Excluded
1 Randomized without consent
1 Lost to follow-up
89 Included in modified intention-to-treat analysis
12 Excluded because of incorrect diagnosis d
83 Included in modified intention-to-treat analysis
13 Excluded because of incorrect diagnosis d
74 Included in assessment of secondary outcomes
(Hinchey grades I-III)c
3 Hinchey grade I
1 Hinchey grade II
69 Hinchey grade III
1 Protocol violation (Hinchey grade III)
15 Hinchey grade IV included in separate assessment
of secondary outcomes c
70 Included in assessment of secondary outcomes
(Hinchey grades I-III)c
2 Hinchey grade I
4 Hinchey grade II
61 Hinchey grade III
3 Protocol violation (Hinchey grade III)
13 Hinchey grade IV included in separate assessment
of secondary outcomes c
Sample Size
The sample size was based on 80% statistical power and a total
2-tailed type 1 error α = .05 distributed to α = .01 for the safety
analysis and α = .045 for the final analysis. Previous metaanalyses for resection surgery in perforated diverticulitis have
shown mortality rates9 ranging between 10% and 20%, and
morbidity rates 10 between 20% and 30%, while Myers et al12
reported a 3% mortality rate and a 4% morbidity rate following laparoscopic lavage. Being aware of the probable selection bias in earlier trials, we deliberately estimated a smaller
CT indicates computed tomography;
PRA, primary resection and
anastomosis; SCANDIV, Scandinavian
Diverticulitis.
a
Includes all patients undergoing
operations for perforated
diverticulitis, continuously reported
data by all participating centers,
and patients identified through
diagnostic code search and review
of patient files at the end
of the study.
b
Perforated diverticulitis diagnosed
at surgery but not suspected
preoperatively.
c
See Table 1 for explanation of
Hinchey classification stages.
d
Primary outcome assessment only,
otherwise excluded from analysis
difference in primary outcome than could be expected. We postulated that the proportion of severe complications within 90
days would be 30% in the resection group vs 10% in the laparoscopic lavage group and calculated a sample size of 130 patients (65 in each group). To account for patients with free fecal contamination of the peritoneal space (Hinchey grade IV)
who could not be treated with the trial intervention, we
planned to include 150 patients. In May 2013, the SCANDIV
Study Group agreed to slightly increase the sample size because of the unexpected high number of included patients with
jama.com
(Reprinted) JAMA October 6, 2015 Volume 314, Number 13
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Fundacio Parc Tauli User on 12/14/2015
1367
Research Original Investigation
Laparoscopic Lavage vs Primary Resection for Perforated Diverticulitis
Table 2. Patients Operated for Perforated Diverticulitis per Center
Randomization Groups, No.
Not Included, No.
Lavage
(n = 89)
Resection
(n = 85)
Total
(n = 174)
Eligible Patients
(n = 216)a
Ineligible Patients
(n = 94)b
No. per 100 000
Person-Yearsc
1
14
13
27
10
12
2.3
2
11
12
23
24
1
3.8
3
12
8
20
5
1
1.5
4
9
5
14
17
3
2.7
5
8
5
13
3
4
1.9
6
5
5
10
17
1
7
3
6
9
11
8
2
6
8
15
6
2.9
9
3
4
7
6
4
3.7
10
1
5
6
10
6
2.9
11
3
3
6
6
10
2.0
12
1
4
5
5
3
1.6
13
3
2
5
11
8
2.0
14
3
1
4
6
15
2
2
4
3
5
2.4
16
1
2
3
21
3
3.2
17
3
0
3
29
4
2.0
18
1
1
2
3
1
1.3
19
2
0
2
2
8
2.1
20
1
1
2
2
9
1.2
21
1
0
1
10
5
3.6
Center
a
All centers reported eligible but excluded patients.
b
Ineligible patients who underwent operations for perforated diverticulitis
were reported from 19 of 21 centers.
incorrect preoperative diagnoses. Inclusion was to be continued until at least 65 patients with Hinchey grades I, II, or III
had undergone treatment per protocol in each study group.
Statistical Analysis
Statistical analysis was performed on an intention-to-treat basis using IBM SPSS Statistics version 21. We included the 2-sided
Fisher exact test for proportions and a nonparametric test
(Mann-Whitney) for continuous variables. The hypothesis testing was 2-sided with a significance level of .045, and for all
other analyses, it was .05. The 95% CIs for differences in proportions for the primary outcome were calculated with the
Wilson score method without continuity correction, according to Newcomb.20 Primary outcome analysis was performed
according to intention-to-treat principles. A modified intentionto-treat analysis was performed, which included patients who
at the time of surgery were believed to have perforated diverticulitis and no other diseases such as cancer (macroscopically evaluated). Secondary outcomes were assessed without
correction for multiple comparison. All participants, including crossover patients and those with protocol violations, were
analyzed strictly in the groups to which they were randomized. An analysis for possible site effects was performed using
mixed-effects models. Additionally, logistic regression was
used to explore the relationship between various clinical features and outcomes. Patients who were lost to follow-up were
1368
2.0
1.7
3.2
c
The overall median (range) of patients per 100 000 person-years was 2.1
(1.2-3.8).
excluded from all analyses. Patients with missing data were
excluded only from analysis of the particular item.
Results
Inclusion and Analysis
The 90-day follow-up data on the last enrolled patient were
obtained on December 12, 2014, and data monitoring was completed in March 2015. A total of 199 patients were randomly
assigned to undergo laparoscopic lavage (n = 101) or primary
resection (n = 98). Participating hospitals enrolled between 1
and 27 patients (Table 2). In the resection group, 1 patient was
lost to follow-up and 1 was randomized without consent
(Figure). Both patients were excluded from the intention-totreat analysis because of lack of primary outcome data. For 12
patients in the lavage group and 13 patients in the resection
group, perforated diverticulitis was not found at the time of
surgery (eTable 2 in Supplement 1).
Of 415 eligible patients, 216 were not enrolled. The main
reasons for patients not enrolling were because of the on-call
surgeon not asking (n = 162), previously diagnosed advanced
malignancies or severe comorbidities (n = 35), and patients declining to participate (n = 13). Of the 94 patients who did not
meet the inclusion criteria but who underwent operations for
perforated diverticulitis during the study period, most were
JAMA October 6, 2015 Volume 314, Number 13 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Fundacio Parc Tauli User on 12/14/2015
jama.com
Laparoscopic Lavage vs Primary Resection for Perforated Diverticulitis
Original Investigation Research
Table 3. Characteristics of All Patients Who Underwent Operations for Perforated Diverticulitis During the Study Perioda
Modified Intention-to-Treat Populationb
(n = 172)
Age, mean (SD), y
BMI >30
e
Missing data, No.
Eligible but Excluded
(n = 216)
Ineligiblec
(n = 94)
66.7 (14.3)
67.1d
72.5d
39 (24)
30 (19)
14 (18)
54
16
8
Previous episode of diverticulitis
134 (78)
172/208 (83)f
Single
20 (12)
f
20/208 (10)
2/88 (2)f
Multiple
18 (10)
16/208 (8)f
3/88 (3)f
None
116 (67)
152/211 (72)f
63/90 (70)f
Single
38 (22)
45/211 (21)f
15/90 (17)f
Multiple
18 (10)
14/211 (7)f
7/90 (8)f
9 (5)
26/182 (14)f
14/78 (18)f
III
134 (78)
136/215 (63)f
58/92 (63)f
IV
28 (16)
55/215 (26)f
21/92 (23)f
None
78/88 (89)f
Previous abdominal surgery
ASA physical status score >IIIg
Hinchey gradeh
Procedures
Laparoscopic lavage
72 (42)
28 (13)
8 (9)
Hartmann
75 (44)
148 (69)
67 (71)
PRA
21 (12)
24 (11)
8 (9)
4 (2)
15 (7)
10 (11)
Other
Severe complications within 90 d
Clavien Dindo score >IIIai
46 (27)
69/205 (34)f
39/88 (44)f
Mortality
19 (11)
45/205 (22)f
20/88 (23)f
Abbreviations: ASA, American Society of Anesthesiologists; BMI, body mass
index; ICU, intensive care unit; PRA, primary resection and anastomosis.
a
Data are reported as No. (%) unless otherwise indicated.
b
Includes patients with findings of perforated diverticulitis at abdominal
inspection only; patients with deviant diagnoses were not considered.
c
Reported from 19 of 21 participating centers.
d
No individualized data available.
e
BMI was calculated as weight in kilograms divided by height in meters
squared.
f
Data are reported as numerator/denominator (%) because of missing data.
preoperatively thought to have another cause of peritonitis
(n = 43) or were unable to provide informed consent (n = 24),
thus they were not enrolled (Figure and Table 2). Demographic characteristics of these patients are reported in Table 3.
The center-specific operation rate for perforated diverticulitis varied between 1.2 and 3.8 patients per 100 000 inhabitants per year (Table 2). The monitor CRF was completed for
97% of the patients with perforated diverticulitis. Discrepancies from the original CRF, mostly of minor importance, were
found in approximately 18% of the listed items. The major disagreements between monitors and investigators were on
Hinchey grading; as a result, the grade was changed in 17% of
patients. The radiologist’s review of the CT scans, which formed
the basis for inclusion, showed extraluminal air in all patients. In 16% of the cases, there were only air bubbles in close
proximity of the diseased colon. Baseline characteristics were
similar between the groups (Table 4). The protocol allowed for
a laparoscopic approach to resection in the resection group,
which was performed in 3 patients.
g
ASA Physical Status Classification System score range is I-VI (I indicates
completely healthy, V indicates moribund and not expected to survive without
the operation, and VI indicates a patient who has been declared brain dead
whose organs are being removed for donor purposes).
h
See Table 1 for explanation of Hinchey classification stages.
i
Clavien-Dindo Classification of Surgical Complications scores range from I to V
(I, minor complication; >IIIa includes complications leading to reoperation
while under general anesthesia [IIIb]; IVa, life-threatening complications
[including central nervous system] and single organ dysfunction [including
dialysis] needing ICU management; IVb, life-threatening complications and
multiorgan dysfunction needing ICU management; and V indicates death).
Outcomes
The primary outcome of severe complications within 90 days
after surgery did not statistically differ between patients in the
laparoscopic lavage group (30.7% [31 of 101]) and patients in
the resection group (26.0% [25 of 96]) (difference, 4.7% [95%
CI, −7.9% to 17.0%]; P = .53; Table 5). The rate of death was
13.9% (14 patients) in the laparoscopic lavage group and 11.5%
(11 patients) in the resection group (difference, 2.4% [95% CI,
−7.2% to 11.9%]; P = .67). In contrast to our hypothesis, the observed severe complication and mortality rates were lower in
the resection group than in the laparoscopic lavage group. In
the modified intention-to-treat analysis of patients with
macroscopic findings of perforated diverticulitis, the rate of
severe complications in the laparoscopic lavage group was
31.5% (28 of 89 patients) vs 21.7% (18 of 83 patients) in the resection group (difference, 9.8% [95% CI, −3.5% to 22.5%];
P = .17), and 90-day mortality in the laparoscopic lavage group
was 13.5% (12 of 89 patients) vs 8.4% (7 of 83 patients) in the
resection group (difference, 5.1% [95% CI, −4.7% to 14.7%];
jama.com
(Reprinted) JAMA October 6, 2015 Volume 314, Number 13
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Fundacio Parc Tauli User on 12/14/2015
1369
Research Original Investigation
Laparoscopic Lavage vs Primary Resection for Perforated Diverticulitis
Table 4. Baseline Characteristics of the Intention-to-Treat Population
No. (%)
Laparoscopic Lavage
(n = 101)
Resection
(n = 96)
Men
44 (44)
45 (47)
Women
57 (56)
51 (53)
Sex
Age, mean (SD), y
69.9 (13.5)
65.7 (15.2)
Body mass index, mean (SD)a
26.6 (4.9)a
26.0 (4.4)a
None
67 (66)
60 (62)
Single
23 (23)
25 (26)
Multiple
11 (11)
11 (11)
None
82 (81)
72 (75)
Single
10 (10)
13 (14)
9 (9)
11 (11)
Previous abdominal surgery
Previous episode of diverticulitis
Multiple
Comorbidity
None
18 (18)
16 (17)
Antiinflammatory medicationsb
22 (22)
18 (19)
Chronic obstructive pulmonary disease or asthma
18 (18)
19 (20)
Ischemic heart disease or heart failure
15 (15)
25 (26)
Cigarette smokingc
9 (9)
14 (15)
Active malignancy
6 (6)
3 (3)
Insulin-treated diabetes
5 (5)
3 (3)
Alcoholism or drug abuse
2 (2)
7 (7)
Immunodeficiency or chronic hepatitis
1 (1)
2 (2)
Uremia demanding dialysis
1 (1)
0
Other comorbidity
65 (64)
62 (65)
ASA physical status scored
I
12 (12)
15 (16)
II
47 (48)
37 (39)
III
33 (33)
39 (41)
IV
9 (9)
4 (4)
V
0
1 (1)
4.3 (2.2)
4.0 (2.1)
Charlson Comorbidity Index score, mean (SD)
P = .34; Table 5 and eTable 3 in Supplement 1). Among
patients without fecal peritonitis, the target population of
this trial, statistically significant differences were only
observed in the secondary outcomes (Tables 5 and 6). Considerably more patients in the laparoscopic lavage group
(15 of 74 [20%]) than in the resection group (4 of 70 [6%])
required a secondary surgical procedure because of complications (difference, 14.6% [95% CI, 3.5% to 25.6%]; P = .01;
Table 6). The main reasons for reoperation included secondary peritonitis in the lavage group and wound dehiscence in
the resection group. Furthermore, intraabdominal infections
(secondary peritonitis and abscesses) occurred more frequently in the laparoscopic lavage group. Primary resection
was associated with more superficial wound infections, longer operating times, and a higher proportion of patients with
a stoma 90 days after primary surgery.
Analysis of the primary outcome with mixed-effects models, including random effects for centers, showed an estimated center-level variance of 0 (eTable 4 in Supplement 1).
1370
Abbreviations: ASA, American
Society of Anesthesiologists; CCI,
Charlson Comorbidity Index.
a
Body mass index was calculated as
weight in kilograms divided by
height in meters squared. Data were
missing for 6 patients in the
laparoscopic lavage group and for 4
patients in the resection group.
b
Steroids or anti–tumor necrosis
factor medication.
c
More than 10 cigarettes per day.
d
ASA Physical Status Classification
System score range is I-VI
(I indicates completely healthy,
V indicates moribund and not
expected to survive without the
operation, and VI indicates a patient
who has been declared brain dead
whose organs are being removed
for donor purposes).
With different combinations of fixed effects (age, sex, ASA
score, body mass index [BMI, calculated as weight in kilograms divided by height in meters squared]), the estimated
center-level random effect was still 0 in all cases. Logistic regression of other possible confounding factors, including age,
sex, ASA score, BMI, center catchment population, center size
(number of operations), and whether the most experienced surgeon on the team was a specialist, did not affect outcomes as
shown by logistic regression analysis. The only statistically significant predictor was the ASA score, with higher scores predicting worse outcome, as would be expected (eTable 5 in
Supplement 1).
Three patients in each group underwent oncological resection rather than a diverticulitis procedure when colon cancers were found at the time of the study procedure. These patients were excluded from the modified intention-to-treat
analysis. Six patients with sigmoid cancers that were not detected during the study procedure were retained in the modified intention-to-treat analysis because cancer diagnosis was
JAMA October 6, 2015 Volume 314, Number 13 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Fundacio Parc Tauli User on 12/14/2015
jama.com
Laparoscopic Lavage vs Primary Resection for Perforated Diverticulitis
Original Investigation Research
Table 5. Primary Outcome: 90-Day Severe Complications (Clavien-Dindo Score >IIIa)
a
No. (%)
Laparoscopic
Lavage
(n = 101)
Resection
(n = 96)
All >IIIaa
31 (30.7)
25 (26.0)
IIIb
13 (12.9)
8 (8.3)
IVa
2 (2.0)
4 (4.2)
IVb
2 (2.0)
2 (2.1)
14 (13.9)
11 (11.5)
(n = 89)
(n = 83)
All >IIIaa
28 (31.5)
18 (21.7)
IIIb
13 (14.6)
5 (6.0)
IVa
2 (2.2)
4 (4.8)
IVb
1 (1.1)
2 (2.4)
12 (13.5)
7 (8.4)
(n = 74)
(n = 70)
All >IIIaa
19 (25.7)
10 (14.3)
IIIb
11 (14.9)
4 (5.7)
IVa
1 (1.4)
1 (1.4)
IVb
1 (1.4)
0
V
6 (8.1)
5 (7.1)
(n = 15)d
(n = 13)
Difference in Proportion,
% (95% CI)
P Value
Intention-to-Treat Population
Patients by Clavien-Dindo score
V
4.7 (−7.9 to 17.0)
.53
2.4 (−7.2 to 11.9)
.67
9.8 (−3.5 to 22.5)
.17
Modified Intention-to-Treat Analysisb
All Hinchey gradesc
Patients by Clavien-Dindo score
V
c
Hinchey grades I, II, and III
5.1 (−4.7 to 14.7)
.34
11.4 (−1.8 to 24.1)
.10
1.0 (−8.5 to 10.4)
>.99
−1.5 (−33.5 to 31.4)
>.99
a
Clavien-Dindo Classification of
Surgical Complications scores range
from I to V (I, minor complication;
>IIIa includes complications
leading to reoperation while
under general anesthesia [IIIb];
IVa, life-threatening complications
[including central nervous system]
and single organ dysfunction
[including dialysis] needing ICU
management; IVb, life-threatening
complications and multiorgan
dysfunction needing ICU
management; and V indicates
death).
b
Excludes patients with incorrect
preoperative diagnosis.
c
See Table 1 for explanation of
Hinchey classification stages.
d
After initial laparoscopy, patients
were treated with resection
according to protocol.
Patients by Clavien-Dindo score
Hinchey grade IVc
Patients by Clavien-Dindo score
All >IIIaa
9 (60.0)
8 (61.5)
IIIb
2 (13.3)
1 (7.7)
IVa
1 (6.7)
3 (23.1)
IVb
0
2 (15.4)
V
6 (40.0)
2 (15.4)
not known at the time of surgery (4 patients in the laparoscopic lavage group [diagnosed within 90 days after surgery
by reoperation or colonoscopy] and 2 patients in the resection group [1 diagnosed when specimen was opened and 1 diagnosed during histopathological examination of the specimen]). In 48 of 63 patients (76%) treated with lavage who were
alive but did not undergo reoperation after 3 months, a postoperative colonoscopy or CT colonography was performed
(missing data n = 3). In 21 of these patients (33%), the colon was
examined within 3 months and in another 15 of these patients (24%) within 6 months after surgery. A specialist in colorectal surgery was involved in more operations in the resection group.
Some patients with signs of generalized peritonitis and free
air on the CT scan had minimal contamination of the abdominal cavity (Table 6). Patients with Hinchey I and Hinchey II
grades were all treated according to randomization. One of
these in the lavage group underwent reoperation because of
a missed sigmoid carcinoma. In the lavage group, an abscess
was drained in the patient with a Hinchey II grade; the patients with Hinchey I grades (free air and localized inflamma-
24.6 (−9.0 to 51.3)
.22
tion only) were treated with lavage only. In all patients with
fecal peritonitis (Hinchey grade IV), irrespective of randomization, the diseased bowel was resected according to the study
protocol. Procedures and outcomes for these patients are displayed in Tables 5 and 7 After reviewing the data of the first
75 included patients, the safety committee concluded that it
was safe to continue the trial.
Discussion
No statistically significant difference was found between the
lavage and resection groups for the 90-day primary outcome
of having severe complications. Statistically significant differences between the 2 study groups were only observed for
secondary outcomes. Laparoscopic lavage was associated with
a greater need for reoperations. However, patients in the laparoscopic lavage group had shorter operating times, less blood
loss, and fewer patients had a stoma after 3 months. Because
these findings were not adjusted for multiple comparisons,
they should be interpreted as exploratory.
jama.com
(Reprinted) JAMA October 6, 2015 Volume 314, Number 13
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Fundacio Parc Tauli User on 12/14/2015
1371
Research Original Investigation
Laparoscopic Lavage vs Primary Resection for Perforated Diverticulitis
Table 6. Secondary Outcomes in Patients With Hinchey Grades I to IIIa
Laparoscopic Lavage
(n = 74)
Resection
(n = 70)
P Value
Symptom onset to surgery time, median (IQR), d:h
2:09 (1:07-3:17)
2:15 (3:12)
.18
Admission to surgery time, median (IQR), h:min
10:29 (7:09-18:48)
11:55 (17:21)
.25
Perioperative Results
Hinchey grade Ia
3
2
Hinchey grade IIa
1
4
Hinchey grade IIIa
70
64
Grade of purulent contamination, No. (%)
Fibrin only, no pus
Pus in 1 quadrant only
Pus in ≥2 quadrants
Procedures
Resection
Laparoscopic lavage
2/73 (3)
1/69 (1)
28/73 (38)
25/69 (36)
43/73 (59)
43/69 (62)
74
70
0
67b
70
3c
Conversion to laparotomy
Protocol violationsd
1
Operating time, mean (SD), min
0
0
3
72 (26)
149 (54)
Registrar
24 (32)
8 (11)
General surgeon
16 (22)
8 (11)
Colorectal surgeon
34 (46)
54 (77)
Most experienced surgeon on operating team, No. (%)
<.001
.001
Saline used to rinse, mean (SD), L
4.7 (2.0)e
3.7 (2.0)
.003
Estimated blood loss, median (IQR), mL
3 (0-50)
175 (100-300)
<.001
Blood units given postoperatively, median (range)
Maximum postoperative CRP, mean (SD), mg/L
0 (0-8)
256 (96)
Lowest postoperative hemoglobin, mean (SD), g/dL
11.2 (2.0)
Reoperation at index admission, No. (%)
12 (16)
0 (0-4)
275 (84)
11.2 (1.7)
3 (4)
.96
.16
.77
.03
Surgery to discharge time, median (IQR), df
6.5 (4.2-15.0)
7.5 (5.5-11.5)
.19
Mortality at index admission, No. (%)
2 (3)
3 (4)
.68
90-Day Results
Complications, No. (%)g
Superficial wound infection
Intra-abdominal abscess
1 (1)
9 (13)
.008
16 (22)
7 (10)
.07
Antibiotics only
4
4
Drained percutaneously
8
2
Drained under general anesthesia
1
1
Reoperation
3
0
Secondary peritonitis
9 (12)
0
Bleeding
1 (1)
1 (1)
>.99
Pneumonia
4 (5)
6 (9)
.53
Heart and lung complications
4 (5)
8 (11)
Urinary tract infection
1 (1)
0
Deep vein thrombosis or thromboembolus
Other
Underwent reoperation, No. (%)
.003
.24
>.99
1 (1)
2 (3)
.61
18 (24)
15 (21)
.70
15 (20)
4 (6)
.01
Secondary peritonitis
6
0
Sigmoid carcinoma
4h
0
Feculent drainage
2
0
Intra-abdominal abscessi
2
0
Wound dehiscence
1
3
Small-bowel obstruction
0
1
(continued)
1372
JAMA October 6, 2015 Volume 314, Number 13 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Fundacio Parc Tauli User on 12/14/2015
jama.com
Laparoscopic Lavage vs Primary Resection for Perforated Diverticulitis
Original Investigation Research
Table 6. Secondary Outcomes in Patients With Hinchey Grades I to IIIa (continued)
Unplanned readmissionsj
Single
Laparoscopic Lavage
(n = 74)
Resection
(n = 70)
19/70 (27)k
11/66 (17)k
16
Multiple
3
2
43/62 (69)k
Stoma complications, No. (%)
3 (4)
2 (3)
Cleveland Global Quality of Life score, mean (SD)m
0.75 (0.19)
0.73 (0.17)
Abbreviations: CRP, C-reactive protein; IQR, interquartile range; PRA, primary
resection and anastomosis.
a
See Table 1 for explanation of Hinchey classification stages.
b
Of these resection operations, 49 were Hartmann and 18 were PRA
procedures.
c
Of these conversions to laparotomy, 1 was a PRA and 2 were lavage
procedures.
d
The protocol violation in the laparoscopic lavage group was an open lavage.
The 3 violations in the resection group were lavage-only procedures.
e
Missing data for 1 patient.
f
Patients who died during index admission not accounted (2 in the laparoscopic
lavage group; 3 in the resection group).
.15
9
11/64 (16)k,l
Patients with stoma
P Value
<.001
>.99
.32
g
There were 0 complications in either group for cerebrovascular events.
h
One patient underwent reoperation because of persisting abscess, 1 for bowel
obstruction, and for 2, carcinomas were found at sigmoideoscopy.
i
Abscess not amendable to percutaneous drainage.
j
Patients who died during index admission not accounted (19 in the
laparoscopic lavage group; 11 in the resection group).
k
Data are reported as numerator/denominator (%) because of missing data.
l
Patients underwent reoperation using the Hartmann procedure.
m
Missing data for 11 patients in the laparoscopic lavage group and 12 in the
resection group, including patients who died during index admission. The
Cleveland Global Quality of Life score range is 0 to 1 (0 worst, 1 best).
Table 7. Secondary Outcomes in Patients With Hinchey Grade IVa
Laparoscopic Lavage
(n = 15)
Resection
(n = 13)
P Value
Perioperative Results
2b
PRA procedure
Hartmann procedure
13
Operating time, mean (SD), min
157 (44)
0
13
133 (45)
.13
Most experienced surgeon on operating team
Registrar
1
General surgeon
1
0
13
12
Colorectal surgeon
Estimated blood loss, median (IQR), mL
Blood units given postoperatively, median (range)
Maximum postoperative CRP, mean (SD), mg/L
200 (100-300)
0 (0-4)
344 (152)c
1
200 (150-325)
0 (0-7)
300 (101)
.34
.56
.41
Lowest postoperative hemoglobin, mean (SD), g/dL
9.9 (1.8)c
9.8 (1.7)
.92
Mortality at index admission
5 (33)
2 (15)
.40
Superficial wound infection
4 (27)
4 (31)
>.99
Intra-abdominal abscess
1 (7)
1 (8)
>.99
Secondary peritonitis
1 (7)
1 (8)
>.99
Bleeding
1 (7)
0
>.99
Pneumonia
1 (7)
3 (23)
.31
Heart and lung complications
4 (27)
4 (31)
>.99
90-Day Results
Complications, No. (%)d
Stoma complications
0
1 (8)
.47
Other
8 (53)
8 (62)
>.99
3 (20)
4 (31)
.67
1
3
Underwent reoperation, No. (%)
Wound dehiscence
Incarcerated hernia
1
0
Ischemic bowel
1
0
Intra-abdominal abscesse
0
1
Unplanned readmissions, No. (%)f
5 (50)
3 (27)
Single
5
2
Multiple
0
1
jama.com
.39
Abbreviations: CRP, C-reactive
protein. IQR, interquartile range;
PRA, primary resection and
anastomosis.
a
See Table 1 for explanation of
Hinchey classification stages.
b
Patients with a visible hole in the
bowel, but little fecal
contamination.
c
Missing data for 1 patient.
d
There were 0 complications in
either group for urinary tract
infection, deep vein
thrombosis/thromboembolus, or
for cerebrovascular events.
e
Abscess not amendable to
percutaneous drainage.
f
Patients who died during index
admission not accounted (5 in the
laparoscopic lavage group; 2 in the
resection group).
(Reprinted) JAMA October 6, 2015 Volume 314, Number 13
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Fundacio Parc Tauli User on 12/14/2015
1373
Research Original Investigation
Laparoscopic Lavage vs Primary Resection for Perforated Diverticulitis
This did not confirm findings from previous non RCTs suggesting that laparoscopic lavage was associated with better outcomes than colon resection procedures.13,21 Results similar to
ours were recently published in a preliminary report from a
small Swedish-Danish study.22 Our results are similar to those
of the LOLA (Laparoscopic Peritoneal Lavage or Resection for
Generalised Peritonitis for Perforated Diverticulitus [Ladies])
trial, which was terminated early and only enrolled a small
number of patients. Both the SCANDIV and LOLA trials found
the need for more reoperations in the laparoscopic lavage than
the resection group.15 SCANDIV was completed, reached the
intended sample size, and included considerably more patients in fewer centers than LOLA.
Our methodology differed from other lavage studies
that randomized patients after laparoscopic Hinchey
staging.15,22 The preoperative allocation in the present trial
resulted in the inclusion of patients with Hinchey grade IV
and patients with diagnoses other than perforated diverticulitis. However, making the decision to randomize after
inspecting the abdominal cavity risks creating selection bias
because clinicians might deem some patients unsuitable for
the study. Preoperative randomization in our current study
resulted in similar numbers of patients with feculent peritonitis and number of incorrect preoperative diagnoses
between the 2 study groups.
Our findings do not exclude the possibility that there are
harms associated with laparoscopic lavage for the treatment
of purulent perforated diverticulitis. When the modified
intention-to-treat analysis was restricted only to patients
with this clinical problem, the difference in serious complication rates between the lavage and resection procedures was
11.4% (95% CI, −1.8% to 24.1%; P = .10; Table 5). With the
lower bound of the CI being reasonably close to zero, it is possible that a study with more patients would have concluded
that more harm than good could result from the lavage of
purulent perforated diverticulitis as compared with treatment by colon resection. Based on the results of the current
study, approximately 300 patients in each group are needed
to adequately study this possibility.
To date, 6 RCTs have been published on surgical approaches for perforated diverticulitis,15,22-26 2 of which investigated the role of laparoscopic lavage.15,22 The largest trial before SCANDIV included only 105 patients.25 Four of these trials
were prematurely terminated,15,23,24,26 limiting the conclusions that can be drawn from them.16
Strengths of SCANDIV include its generalizability, because many surgeons were involved and they operated at 21
different hospitals ranging from community hospitals to academic medical centers. We also had a high degree of enrollment, with nearly 50% of all eligible patients enrolled in the
ARTICLE INFORMATION
Author Affiliations: Department of
Gastrointestinal Surgery, Akershus University
Hospital, Lørenskog, Norway (Schultz, Øresland);
Faculty of Medicine, University of Oslo, Oslo,
Norway (Schultz, Øresland); Department of
Gastrointestinal Surgery, Oslo University Hospital,
1374
study. We were able to obtain clinical information from the patients with perforated diverticulitis treated in the participating hospitals who were not enrolled in the study.
A limitation of SCANDIV is that patients not enrolled in the
study had a numerically higher ASA score, reflective of having more severe disease and worse postoperative outcomes.
Thus, SCANDIV’s results may not pertain to patients with perforated diverticulitis who are very ill.
Despite the strict inclusion criteria, the spectrum of abdominal contamination varied greatly within the groups. However, the prerequisite for inclusion was a need for urgent surgery based on clinical findings, which usually included clinical
signs of generalized peritonitis. The determination of the
Hinchey grade was not as straightforward as expected. We
could not rule out the possibility of some discrepancies in grading. This was the main reason patients with all Hinchey grades
were included in the modified intention-to-treat analysis of the
primary outcome.
The study design was pragmatic and compared a standard, well-established treatment for perforated diverticulitis
(resection) to a newer approach, laparoscopic lavage. Both of
these treatments are reasonably common in clinical practice
and most surgeons are very familiar with technical aspects of
these operations. The study protocol for SCANDIV precluded
dissection of inflammatory adhesions to the sigmoid colon during the laparoscopic lavage procedure. These adhesions might
have influenced the study’s results in 2 ways. The adhesions
might have served to seal small perforations or to conceal larger
defects in the colon that would never close and, therefore, require resection. Missed malignancies were another major concern associated with laparoscopic lavage. In SCANDIV, 12 patients had a perforated colon carcinoma. Leaving 4 carcinomas
in the laparoscopic lavage group unresected may have impaired the prognosis for these patients. Distinguishing between diverticulitis and cancer was not always possible when
performing urgent operations for what was thought to be diverticulitis. Because of the relatively high rate of missed colon carcinomas in the lavage group, it was essential to perform a colonoscopy after a patient recovered from the
perforation.
Conclusions
Among patients with likely perforated diverticulitis undergoing emergency surgery, the use of laparoscopic lavage compared with primary resection did not reduce the rate of severe postoperative complications and led to worse outcomes
in secondary end points. These findings do not support laparoscopic lavage for treatment of perforated diverticulitis.
Oslo, Norway (Yaqub); Department of Surgery,
University Hospital, Linköping, Sweden (Wallon);
Department of Gastrointestinal Surgery, Østfold
Hospital, Fredrikstad, Norway (Blecic); Department
of Gastrointestinal and Emergency Surgery,
Haukeland University Hospital, Bergen, Norway
(Forsmo); Colorectal Unit, Department of Surgical
Sciences, Uppsala University, Uppsala, Sweden
(Folkesson); Colorectal Unit, Department of
Surgery, Helsingborg Hospital, Helsingborg,
Sweden (Buchwald); Department of
Gastrointestinal Surgery, Stavanger University
Hospital, Stavanger, Norway (Körner); Health
Services Research Unit, Akershus University
Hospital, Lørenskog, Norway (Dahl).
JAMA October 6, 2015 Volume 314, Number 13 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Fundacio Parc Tauli User on 12/14/2015
jama.com
Laparoscopic Lavage vs Primary Resection for Perforated Diverticulitis
Author Contributions: Dr Schultz had full access to
all of the data in the study and takes responsibility
for the integrity of the data and the accuracy of the
data analysis.
Study concept and design: Schultz, Yaqub, Wallon,
Forsmo, Folkesson, Buchwald, Körner, Dahl,
Øresland.
Acquisition, analysis, or interpretation of data:
Schultz, Yaqub, Wallon, Blecic, Forsmo, Folkesson,
Buchwald, Körner, Dahl, Øresland.
Drafting of the manuscript: Schultz, Yaqub,
Øresland.
Critical revision of the manuscript for important
intellectual content: Schultz, Yaqub, Wallon, Blecic,
Forsmo, Folkesson, Buchwald, Körner, Dahl,
Øresland.
Statistical analysis: Schultz, Dahl.
Obtained funding: Schultz, Yaqub, Øresland.
Administrative, technical, or material support:
Schultz, Yaqub, Wallon, Blecic, Forsmo, Folkesson,
Buchwald, Körner, Dahl, Øresland.
Study supervision: Schultz, Yaqub, Wallon, Forsmo,
Folkesson, Buchwald, Körner, Dahl, Øresland.
Conflict of Interest Disclosures: All authors have
completed and submitted the ICMJE Form for
Disclosure of Potential Conflicts of Interest and
none were reported.
SCANDIV Study Group Collaborators, Sweden:
András Papp, MD, Urban Ersson, MD, Tilman Zittel,
MD, Niklas Fagerström, MD, Dan Gustafsson, PhD
(Hudiksvalls Hospital, Hudiksvall); George Dafnis,
PhD (Eskilstuna County Hospital, Eskilstuna); Maria
Cornelius, MD (Helsingborg Hospital, Helsingborg);
Monika Egenvall, PhD, Per Olof Nyström, PhD
(Karolinska University Hospital, Stockholm); Ingvar
Syk, PhD, Dadi Vilhjalmsson, MD (Skåne University
Hospital, Malmö); Lars Påhlman, PhD (Uppsala
University, Uppsala); Gunnar Arbman, PhD
(Vrinnevis Hospital, Linköping University,
Norrköping); and Abbas Chabok, PhD (Västmanland
Hospital, Västerås). SCANDIV Study Group
Collaborators, Norway: Merete Helgeland, BSc
(Akershus University Hospital, Lørenskog); Johan
Bondi, PhD (Bærum Hospital, Vestre viken HF);
Anders Husby, MD (Diakonhjemmet Hospital, Oslo);
Ronny Helander, MD (Drammen Hospital, Vestre
viken HF, Drammen); Arnulf Kjos, MD, Hilde
Gregussen, MD (Innlandet Hospital, Hamar); Aras
Jamal Talabani, MD, Gerd Tranø, PhD (Levanger
Hospital, North-Trøndelag Hospital Trust,
Levanger); Inge Holm Nygaard, MD (Molde
Hospital, Helse Møre og Romsdal, Molde); Gro
Wiedswang, PhD, Ole Helmer Sjo, PhD (Oslo
University Hospital, Oslo); Kari Festøy Desserud,
MD (Stavanger University Hospital, Stavanger); Stig
Norderval, PhD, Mads Vikhammer Gran, MD
(University Hospital of North Norway, Tromsø);
Torkil Pettersen, MD, and Arild Sæther, MD (Østfold
Hospital, Fredrikstad).
Original Investigation Research
approval of the manuscript; and decision to submit
the manuscript for publication.
Additional Contributions: We would like to thank
the following individuals for their kind assistance:
Berit Marianne Bjelkåsen, Cand Mag, Unit of
Applied Clinical Research, Institute of Cancer
Research and Molecular Medicine, Norwegian
University of Science and Technology, Trondheim,
Norway; Claes Johansson, PhD, Danderyd Hospital,
Stockholm, Sweden. Mitra Rashidi, MD, Oslo
University Hospital, Oslo, Norway. Frode ReierNilsen, MD, Akershus University Hospital,
Lørenskog, Norway. The Safety Committee: Rune
Sjödahl, PhD, University of Linköping, Sweden;
Arild Nesbakken, PhD, University of Oslo, Norway;
and Søren Laurberg, PhD, University of Århus,
Denmark. Computed tomography monitoring:
Peter Mæhre Lauritzen, MD, Radiologist,
Department of Clinical Research, Akershus
University Hospital, Norway. Website support:
André Øien, BSc, University of Oslo, Oslo, Norway.
Valuable advice on the manuscript: Michael
Bretthauer, PhD, University of Oslo, Oslo, Norway.
None of these individuals received compensation in
association with their work on this article.
REFERENCES
1. Morris CR, Harvey IM, Stebbings WS, Hart AR.
Incidence of perforated diverticulitis and risk
factors for death in a UK population. Br J Surg.
2008;95(7):876-881.
2. Mäkelä J, Kiviniemi H, Laitinen S. Prevalence of
perforated sigmoid diverticulitis is increasing. Dis
Colon Rectum. 2002;45(7):955-961.
3. Hinchey EJ, Schaal PG, Richards GK. Treatment
of perforated diverticular disease of the colon. Adv
Surg. 1978;12:85-109.
4. Morris AM, Regenbogen SE, Hardiman KM,
Hendren S. Sigmoid diverticulitis: a systematic
review. JAMA. 2014;311(3):287-297.
12. Myers E, Hurley M, O’Sullivan GC, Kavanagh D,
Wilson I, Winter DC. Laparoscopic peritoneal lavage
for generalized peritonitis due to perforated
diverticulitis. Br J Surg. 2008;95(1):97-101.
13. Toorenvliet BR, Swank H, Schoones JW,
Hamming JF, Bemelman WA. Laparoscopic
peritoneal lavage for perforated colonic
diverticulitis. Colorectal Dis. 2010;12(9):862-867.
14. Regenbogen SE, Hardiman KM, Hendren S,
Morris AM. Surgery for diverticulitis in the 21st
century. JAMA Surg. 2014;149(3):292-303.
15. Vennix S, Musters GD, Mulder IM, et al.
Laparoscopic peritoneal lavage or sigmoidectomy
for perforated diverticulitis with purulent peritonitis
[published online July 21, 2015]. Lancet. doi:10.1016
/S0140-6736(15)61168-0.
16. Bassler D, Briel M, Montori VM, et al. Stopping
randomized trials early for benefit and estimation of
treatment effects. JAMA. 2010;303(12):1180-1187.
17. Charlson ME, Pompei P, Ales KL, MacKenzie CR.
A new method of classifying prognostic
comorbidity in longitudinal studies. J Chronic Dis.
1987;40(5):373-383.
18. Dindo D, Demartines N, Clavien PA.
Classification of surgical complications. Ann Surg.
2004;240(2):205-213.
19. Kiran RP, Delaney CP, Senagore AJ, et al.
Prospective assessment of Cleveland Global Quality
of Life (CGQL) as a novel marker of quality of life
and disease activity in Crohn’s disease. Am J
Gastroenterol. 2003;98(8):1783-1789.
20. Newcombe RG. Improved confidence intervals
for the difference between binomial proportions
based on paired data. Stat Med. 1998;17(22):26352650.
21. Afshar S, Kurer MA. Laparoscopic peritoneal
lavage for perforated sigmoid diverticulitis.
Colorectal Dis. 2012;14(2):135-142.
5. Gielens MP, Mulder IM, van der Harst E, et al.
Preoperative staging of perforated diverticulitis by
computed tomography scanning. Tech Coloproctol.
2012;16(5):363-368.
22. Angenete E, Thornell A, Burcharth J, et al.
Laparoscopic lavage is feasible and safe for the
treatment of perforated diverticulitis with purulent
peritonitis [published online December 8, 2014].
Ann Surg. doi:10.1097/SLA.0000000000001061.
6. Vennix S, Morton DG, Hahnloser D, Lange JF,
Bemelman WA, et al. Systematic review of evidence
and consensus on diverticulitis. Colorectal Dis.
2014;16(11):866-878.
23. Binda GA, Karas JR, Serventi A, et al. Primary
anastomosis vs nonrestorative resection for
perforated diverticulitis with peritonitis. Colorectal
Dis. 2012;14(11):1403-1410.
7. Feingold D, Steele SR, Lee S, et al. Practice
parameters for the treatment of sigmoid
diverticulitis. Dis Colon Rectum. 2014;57(3):284-294.
24. Kronborg O. Treatment of perforated sigmoid
diverticulitis: a prospective randomized trial. Br J Surg.
1993;80(4):505-507.
8. Andeweg CS, Mulder IM, Felt-Bersma RJ, et al.
Guidelines of diagnostics and treatment of acute
left-sided colonic diverticulitis. Dig Surg. 2013;
30(4-6):278-292.
25. Zeitoun G, Laurent A, Rouffet F, et al.
Multicentre, randomized clinical trial of primary
versus secondary sigmoid resection in generalized
peritonitis complicating sigmoid diverticulitis. Br J
Surg. 2000;87(10):1366-1374.
9. Constantinides VA, Tekkis PP, Athanasiou T, et al.
Primary resection with anastomosis vs Hartmann’s
procedure in nonelective surgery for acute colonic
diverticulitis. Dis Colon Rectum. 2006;49(7):966-981.
Funding/Support: The study was funded by the
South-Eastern Norway Regional Health Authority
with a fellowship awarded to Johannes Kurt Schultz
(PNR 2719011). The study was also sponsored with
research funding by Akershus University Hospital,
which covered running expenses (PNR 2619041,
2629038, and 2649054).
10. Salem L, Flum DR. Primary anastomosis or
Hartmann’s procedure for patients with diverticular
peritonitis? Dis Colon Rectum. 2004;47(11):19531964.
Role of Funder/Sponsor: The funders of the study
had no part in design and conduct of the study;
collection, management, analysis, and
interpretation of the data; preparation, review, or
11. Krukowski ZH, Matheson NA. Emergency
surgery for diverticular disease complicated by
generalized and faecal peritonitis. Br J Surg. 1984;71
(12):921-927.
jama.com
26. Oberkofler CE, Rickenbacher A, Raptis DA, et al
A multicenter randomized clinical trial of primary
anastomosis or Hartmann's procedure for
perforated left colonic diverticulitis with purulent or
fecal peritonitis. Ann Surg. 2012;256(5):819-826.
(Reprinted) JAMA October 6, 2015 Volume 314, Number 13
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Fundacio Parc Tauli User on 12/14/2015
1375