Laparoscopic Peritoneal Lavage vs Laparoscopic Sigmoidectomy in Perforated Acute Diverticulitis: a Multicenter Prospective Observational Study
Conditions: Acute Diverticulitis
Sponsor: Azienda Ospedaliero, Universitaria Pisana

1 
 
 
 University Hospital of Pisa 
University Operative Emergency Surgery unit 
Director: Prof. M. Chiarugi 
 
 
PROJECT EXPERIMENTAL NON-PROFIT CLINICAL STUDY 
 
Pisa, January 18
th, 2017 
 
Principal Investigator 
Prof. Massimo Chiarugi 
 
Co-Investigator 
Dr. Dario Tartaglia 
 
 
Clinical Study Title 
 
 
 
Laparoscopic peritoneal lavage versus laparoscopic 
sigmoidectomy in perforated Acute diverticulitis: A 
multicentric, prospective and observational study 
 
 
 
NCT number :03008707 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

2 
 
Summary of the clinical 
study project 
The aim of the study is to evaluate which surgical strategy between 
laparoscopic peritoneal lavage (LPL) and laparoscopic sigmoidectomy 
(SL) can give better results in patients with acute perforated 
diverticulitis (APD), identifying the pre-operative characteristics
of patients undergone LPL and SL and investigating data obtained 
during the surgical interventions, the hospitalization and the 
follow-up. 
 
 
Rationale 
of 
clinical Study 
LPL has been recently emerging as an effective alternative to SL in 
patients with APD
1, (GRADE II and III of the Hinchey’s
2 scale). In the 
literature, there is no consensus regarding the role of laparoscopic 
lavage in the management of patients with complicated acute 
diverticulitis
3. Several studies have reported a high success rate of LPL 
(even higher than 95%) with a mortality of less than 5%
4, although other
studies have shown an important morbidity value (more than 30%) and a 
high rate of re-intervention
5. In addition, it has been reported that LPL 
can significantly improve the clinical course of the patient and reduce 
hospitalization costs
6. 
Although there are several international guidelines that confirm that 
LPL represents a safe approach in acute diverticulitis
7.8, many surgeons 
continue to prefer the standard approach, represented by laparoscopic
sigmoidectomy 

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Objectives, 
materials 
and 
methods of the 
clinical study 
This project consists of a clinical, prospective, observational experimental 
study on patients undergoing surgical treatment for APD (Hinchey II-III
stage) at hospital general surgery units involved in the study, during the
period between December 2015 and Dicember 2018. During this period, two 
groups will be identified: Group A, which includes patients undergoing LPL 
and group B who consider those who will undergo SL. All clinical, laboratory,
radiological and surgical parameters will be systematically recorded, 
patient-by-patient, within 
a 
Database (Microsoft 
Excel, 
Microsoft 
Corporation, Redmond, Washington, US), which was created specifically for 
this study. 
Both techniques are routinely used in the treatment of complicated acute
diverticulitis. These surgical procedures, the choice of which depends 
mainly on the patient's clinical conditions, are performed by experienced 
surgeons, or under their supervision, in accordance with national and 
international Guidelines on treatment of acute diverticulitis. 
The inclusion criteria include: acute abdominal pain, signs of diffuse 
peritonitis in the presence of a radiologically suspected condition of acute
perforated diverticulitis and signature of a consent form by the patient. 
Each patient with acute abdominal pain will undergo routine bloods
examinations (cell blood count, urea, creatinine, electrolytes, liver 
function exams, coagulative profile, C-reactive protein and Procalcitonin),
radiological examinations such as X-Ray of the abdomen, chest X Ray,
ultrasound of the abdomen, abdominal CT scan. Radiological criteria needed 
to define a condition of acute diverticulitis perforate are: intraperitoneal
free air, diffuse peritoneal collection, pelvic abscess in the presence of 
diffuse colonic diverticulosis. 
Every single patient considered for this study, as is the case in routine 
clinical practice, will undergo a rigorous pre-operative evaluation of the
anaestheological risk. 
Criteria for exclusion and/or exit from the study are: previous surgical
interventions, septic shock, important comorbidities, immunodepression, 
elevated levels of C reactive protein (> 10 mg/L), Grade IV according to
Hinchey’s classification (diffuse fecal peritonitis), Mannheim Peritonitis 
Index > 22 and age groups under 18 years and higher than 85 years, withdrawal 
of consent. 
With regard to the surgical techniques described in this study, these will 
follow the principles outlined in the guidelines of the most important 
international surgery companies, including those of the Society of 
Gastrointestinal and endoscopic surgeons American (SAGES). LPL is performed 
by induction of pneumoperitoneum, subsequent irrigation of all the quadrants
of the abdominal cavity with at least 6 liters of saline and then positioning
of a drainage in silastic through one of the positioned trocars. SL is 
performed according to the traditional technique adopted at the operative
Unites involved and the eventual protective ileostomy is decided at the 
discretion of the operator surgeon. 
The primary variables considered are: Average operative time, morbidity and 
mortality, clinical and laboratory control of sepsis. Secondary variables: 
Average duration of post-operative hospitalization, incisional hernia rate, 
re-intervention rate; Recurrence rate of acute diverticulitis in patients 
undergoing LPL over a follow-up of about 6 months,including eventual 
remissions and re-interventions. All these data will be collected in a 
database, analyzed and compared according to the appropriate statistical 
surveys. 

4 
 
Description 
of 
surgical 
techniques 
considered, 
risk/benefit 
of 
SL and LPL 
Both of these patient groups will receive the same type of treatment in the
post-operative course with regard to the infusion of liquids, the type of 
antibiotics used, the passive and active mobilization, blood exams, in order
to reduce the possible presence of bias in the evaluation of short-term
clinical outcomes. The patients operated will be assessed daily by the 
medical staff and will undergo blood examinations every day. Any radiological 
investigations, such as abdominal X-Ray, US, and CT scan with contrast, will
be performed in relation to the general clinical conditions of the patients.
After the hospital discharge, each patient will be visited at a distance of
about 6 months, at the operative units of the hospitals involved in the 
study. 
Laparoscopic 
peritoneal 
lavage 
started 
with 
the 
induction 
of 
pneumoperitoneum by using a Verress needle at the umbilicus or Hasson's open 
technique and CO2 with an intraperitoneal pressure of 14 mmHg. Three trocars 
were used: a 5-mm trocar in the supra-umbilical area for the advance of the
laparoscope (30-degree, 10 mm), another 5-mm trocar in the right flank and 
a further 5-mm one in the right iliac fossa. Exploration of the peritoneal 
cavity was accurate and included a gentle blunt dissection of the inflamed
sigmoid colon. Gross fecal finding in the cavity and /or the identification
of a bowel perforation were considered valid reasons to change strategy. 
Once the presence of the purulent collection in the peritoneal cavity was 
identified, a sample for bacteriological examination was taken and, 
consequently, a complete evacuation was performed. Hence, irrigation and 
suction with 3 to 6 L of warm saline were carried out until clear fluid was
returned. In case of dubious integrity of the colonic wall, an air test was
performed to confirm the absence of leakage. The operation ended with an 
accurate revision of the hemostasis and the placement of two large silastic
drains in the pelvis, respectively along the medial and lateral sides of the 
sigma. 
Pneumoperitoneum was obtained as previously described. After placing a 12-
mm trocar at the umbilicus, a 30°-10mm laparoscope was introduced. 
Subsequently, other three trocars were positioned under vision: two 5 mm 
respectively in the left and the right flank and one 12 mm in the right 
iliac fossa. A careful exploration of the abdominal cavity was performed. 
If present, peritoneal adhesions were lysed. The inferior mesenteric vein 
(IMV) was dissected free below the inferior pancreatic margin, ligated with
Hem-o'-lok® clips (Teleflex, Morrisville, NC, USA) and divided. A cautious 
mobilization from the left colonic flexure to the sigma, along with the 
Toldt’ s avascular plane, was then carried out  with the help of 
radiofrequency or ultrasound devices. After the identification and
preservation of the left ureter, the inferior mesenteric artery (IMS) was 
clipped with Hem-o’-Lok ® clips and then divided distally. In case of 
intense phlogosis, the clipping of the artery could be performed distally 
from the origin of the left colic artery. The proximal rectum was then 
stapled and divided by using a laparoscopic articulated stapler. Resection 
was completed and the specimen delivered through a supra-pubic wound-
protected mini-laparotomy. At this point, the decision to perform the 
anastomosis or not (Hartmann's procedure), was established by the surgeon 
according 
to 
patient's 
previous 
co-morbidities 
(i.e.: 
diabetes, 
immunosuppression, malnutrition, severe cardiac disease), patient's 
hemodynamical status (septic shock requiring vasopressors) and the grade of 
perfusion of the two intestinal stumps. In case of anastomosis, a colorectal 
end-to-end or side-to-end mechanical anastomosis was done. A hydropneumatic 

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Statistical 
analysis 
Data management 
Purpose of the 
study 
test or a test with trans-anal irrigation with blue of methylene stained 
saline solution was performed to rule out the presence of a leak of the 
suture line. Before wound closure, the pelvis was drained, and the creation
of a protective ileostomy was decided case by case at the discretion of the
surgeon. 
The benefits of LPL are associated with minor post-operative pain, early 
mobilization and early resumption of intestinal function. Laparoscopic
sigmoidectomy offers, instead, a radical solution to complications related 
to acute diverticulitis, reducing the risks of recurrence in the short and
long term. 
The execution of one of these two surgical procedures exposes the following
risks: 
-In the case of laparoscopic peritoneal lavage: general-order complications 
(pneumonia, deep venous thrombosis, pulmonary embolies, acute cardiac and/or 
cerebral events, etc), wound infections, abdominal abscesses, visceral 
perforations, bleeding, acute diverticulitis recurrence, incisional hernia.
-In the case of laparoscopic sigmoidectomy with/without protective 
ileostomy: general-order complications (pneumonia, deep venous thrombosis, 
pulmonary emboli, acute cardiac and/or cerebral events, etc), wound 
infections, abdominal abscesses, anastomosis dehiscence, anastomotic
stenosis, bleeding, incisional hernias and psychological discomfort due to 
the presence of a stoma. 
We expect to consider about 25-30 patients per group in the time period 
considered on the basis of the case studies of the General surgery units of 
the hospitals involved in the study. For statistical analysis, the T Test 
or the Mann-Whitney U Test (if the data are not normally distributed) will
be used for the determination of the parametric data. The Pearson's chi
square test or the Fisher's exact test will be used for the analysis of 
categorical and dichotomic. The differences will be considered statistically 
significant in case of p < 0.05. The statistical analysis will be conducted
using the software SPSS 20.0 software (IBM SPSS Inc., Chicago, IL, USA). 
The data will be collected in an Excel database (Redmond, WA, USA).As regards
the anonymity of patients, only the patient's code (patient's initials), 
sex, date of birth and age will be reported. The Principal Investigator, 
Prof Massimo Chiarugi, is responsible for the preservation of this data. The 
data will be stored for seven years. 
The aim of this study is to collect and analyze the data of the two techniques 
taken into account, in relation to the following parameters: mean operating
time, morbidity, mortality, clinical and laboratory control of sepsis, 
average postoperative hospital stay, incisional hernia rate, re-intervention
rate, acute diverticulitis recurrence rate in patients undergoing LPL over 
a follow-up of about 6 months and total costs associated with 
hospitalization. 

6 
 
Flow-Chart of the 
study 
Ethical 
considerations 
Summary of the 
work plan of the 
clinical study 
 
Time 
0 
– 
Hospitalization 
Time 1- 
Follow up to 6 
months 
Average operating time 
X 
 
Clinical and laboratoristic 
control of sepsis 
X 
 
Morbidity 
X 
 
Mortality 
X 
X 
Re-intervention rate 
X 
 
Average post-operative stay 
X 
 
Incisional hernia rate 
 
X 
Acute diverticulitis 
recurrence rate 
 
X 
 
 
 
Before starting the study, the Protocol and the various attached documents 
will be subject to approval by the local Ethics Committee of the Coordinating
Centre. Any amendments to the Protocol which substantially could alter the
study will be subject to the evaluation of the local Ethics Committee 
coordinator before their implementation. 
The principal investigator undertakes to ensure that this study is conducted
in accordance with international law [Dir. EU 2001/20/EC] and national [DM 
15/07/1997; D.L. 211/2003; D.L. 46/1997]. 
The experimental study will follow the principles drafted in the Helsinki 
Declaration, comply with the International Conference Guidelines for the 
Good Clinical Practice and guidelines for Standard Operating Procedures 
(SOPs). 
Participation in the study of each patient will be established on the basis
of the overexposed criteria. Of fundamental importance will be the signature 
of the informed consent of the candidate to the study, one whose signed copy
will be provided to the same or to his legal representative. Each patient 
will be exhaustively informed about the treatment of their personal data, 
in accordance with the current privacy regulations [D. Lvo. 196/2003]. Any 
person carrying out an adverse event shall be examined by a physician as
soon as possible; Any anomalies will be followed until complete healing or 
clinical stabilization. Each adverse event will be described in the Clinical
Chart using standard medical terminology in order to study its severity and
any actions to be undertaken. 
First, two groups undergo LPL and SL respectively for acute perforated 
diverticulitis (stage II-III according to Hinchey’s classification) at the
hospital general surgery units involved in the study in the period December
2015- December 2018. 
We will then create a database with the primary and secondary variables, 

7 
 
Bibliography 
with appropriate systems of statistical investigation. 
We expect to consider about 25-30 patients for each group. All patients 
included in this study will be evaluated at a distance of approximately 6 
months after surgery. 
1. Rogers AC, Collins D, O'Sullivan GC, Winter DC. Laparoscopic lavage for 
perforated diverticulitis: a population analysis. Dis Colon Rectum 2012;
55:932-938 
2. Wasvary H, Turfah F, Kadro O, et al. Same hospitalization resection for 
acute diverticulitis. Am Surg. 1999; 65:632 – 635 
3. Regenbogen SE, Hardiman KM, Hendren S, Morris AM. Surgery for 
Diverticulitis in the 21st Century: a systematic review. JAMA Surg 2014; 
149:292-303 
4. Swank HA, J Vermeulen, Lange JF, et al. The ladies trial: Laparoscopic 
peritoneal lavage or resection for purulent peritonitis and Hartmann's 
procedure or resection with primary coloanal for purulent or faecal 
peritonitis in perforated diverticulitis (NTR2037). BMC Surg 2010; 10:29. 
5. Vennix S, Musters GD, Mulder IM, Laparoscopic peritoneal lavage or 
sigmoidectomy for perforated diverticulitis with purulent peritonitis: 
amulticentre, parallel-group, randomised, open-label trial. Lancet. 2015 26;
386 (10000): 1269-77 
6. Afshar S, Kurer MA. Laparoscopic peritoneal lavage for perforated sigmoid 
colon diverticulitis. Colorectal Dis 2011; 14:135-142. 
7. Andersen JC, Bundgaard L, Elbrond H, et al. Danish national guidelines
for treatment of diverticular disease. Dan Med J 2012; 59: C4453. 
9. Agresta F, Ansalabdomen from the Consensus Development Conference of the 
Italian Society of Endoscopic Surgery and new technologies (SICE), 
Association of Italian Hospital Surgeons (ACOIoni L, Baiocchi GL, et al. 
Laparoscopic approach to acute), Italian Society of Surgery (SIC), Italian 
Society of Emergency Surgery and Trauma (SICUT), Italian Society of Surgery
in private hospitaliality (SICOP), and the European Association for 
Endoscopic Surgery (EAES). Surg Endosc 2012; 26:2134 – 64. 

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In Faith 
 
 
_________________________________________ 
Signature of the Promotor 
 
 
 
 
 
In Faith 
 
 
_________________________________________ 
Signature of the Co-Investigator