The HAC trial (harmonic for acute cholecystitis): a randomized, double-blind, controlled trial comparing the use of harmonic scalpel to monopolar diathermy for laparoscopic cholecystectomy in cases of acute cholecystitis
World Journal of Emergency Surgery
The HAC trial (harmonic for acute cholecystitis): a randomized, double-blind, controlled trial comparing the use of harmonic scalpel to monopolar diathermy for laparoscopic cholecystectomy in cases of acute cholecystitis
Fausto Catena 0
Salomone Di Saverio 2
Luca Ansaloni 1
Federico Coccolini 1
Massimo Sartelli 3
Carlo Vallicelli 2
Michele Cucchi 2
Antonio Tarasconi 0
Rodolfo Catena 0
GianLuigi De' Angelis 0
Hariscine Keng Abongwa 0
Daniel Lazzareschi 2
Antonio Pinna 2
0 Department of Emergency Surgery, Parma University Hospital , Parma , Italy
1 Bergamo Hospital , Bergamo , Italy
2 St. Orsola - Malpighi University Hospital , Bologna , Italy
3 Macerata Hospital , Macerata , Italy
Background: The HARMONIC SCALPEL (H) is an advanced ultrasonic cutting and coagulating surgical device with important clinical advantages, such as: reduced ligature demand; greater precision due to minimal lateral thermal tissue damage; minimal smoke production; absence of electric corrents running through the patient. However, there are no prospective RCTs demonstrating the advantages of H compared to the conventional monopolar diathermy (MD) during laparoscopic cholecystectomy (LC) in cases of acute cholecystitis (AC). Methods: This study was a prospective, single-center, randomized trial (Trial Registration Number: NCT00746850) designed to investigate whether the use of H can reduce the incidence of intra-operative conversion during LC in cases of AC, compared to the use of MD. Patients were divided into two groups: both groups underwent early LC, within 72 hours of diagnosis, using H and MD respectively (H = experimental/study group, MD = control group). The study was designed and conducted in accordance with the regulations of Good Clinical Practice. Results: 42 patients were randomly assigned the use of H (21 patients) or MD (21 patients) during LC. The two groups were comparable in terms of basic patient characteristics. Mean operating time in the H group was 101.3 minutes compared to 106.4 minutes in the control group (p=ns); overall blood loss was significantly lower in the H group. Conversion rate was 4.7% for the H group, which was significantly lower than the 33% conversion rate for the control group (p<0.05). Post-operative morbidity rates differed slightly: 19% and 23% in the H and control groups, respectively (p=ns). Average post-operative hospitalization lasted 5.2 days in the H group compared to 5.4 days in the control group (p=ns). Conclusions: The use of H appears to correlate with reduced rates of laparoscopic-open conversion. Given this evidence, H may be more suitable than MD for technically demanding cases of AC.
Acute cholecystitis; Laparoscopic cholecistectomy; Harmonic scalpel; Biliary surgery; Safety; CBD complications; Conversion rate; Randomized controlled trial
Acute cholecystitis is an acute inflammatory disease of
the gallbladder. It is often attributable to gallstones, but
many factors, such as ischemia, motility disorders, direct
chemical injury, collagen disease, allergic reactions, and
bacterial, protozoic, and parasitic infections can also play
a direct role in pathogenesis [
Video-laparo-cholecystectomy (VLC) is a procedure
used to treat patients with acute cholecystitis (AC); in
15-20% of cases, AC is the first clinical appearance of
AC occurs due to persistent obstruction of the cystic
duct, followed by gallbladder distension and acute
inflammation. In approximately 20-40% of cases, a
bacterial superinfection occurs from microorganisms of
the intestinal flora [
] (Table 1).
Antibiotic regimens should be initiated as early as
possible; these regimens should be selected and implemented
according to the WSES (World Society of Emergency
Surgery) guidelines on the treatment of intra-abdominal
Nearly 20% of patients with AC require emergency
], and several meta-analyses have demonstrated
that early VLC can decrease the length of hospital stay
(LOS) and prevent disease recurrence without increasing
the risk of complications [
At the outset of the laparoscopic era, VLC was thought
to be contraindicated in cases of AC, and as such, it was
considered “unsafe” or “technically difficult” to perform
laparoscopic cholecystectomies in order to treat acute
With increasing exposure to laparoscopic surgery, a
number of centers have adopted routine use of
laparoscopic cholecystectomy for cases of acute cholecystitis,
suggesting that it is technically feasible despite the risk of
intra-operative laparoscopic-open conversion (occurring
in 35% of cases [
]) and common bile duct lesions [
More recently, the mainstream medical community
has recognized VLC as a viable treatment option for AC, as
demonstrated by several prospective RCTs (Randomized
Controlled Trials) comparing laparoscopic and open
]. It should be noted, however,
first stage (2–4 days)
Necrotizing cholecystitis: second
stage (3–5 days)
Suppurative cholecystitis: third
stage (7–10 days)
that these trials reported difficulties associated with
While the surgeon’s experience plays a vital role in the
treatment of acute or chronic inflammation, the employed
surgical technology is also of crucial importance.
The HARMONIC SCALPEL® (H) is the leading
ultrasonic cutting and coagulating surgical device, ensuring
minimal charring, desiccation, and lateral thermal tissue
Harmonic scalpel technology reduces ligature demand
during simultaneous cutting and coagulation. Additionally,
unlike conventional monopolar diathermy, patients are not
exposed to electric currents to complete the device circuit,
which increases the instrument’s safety. The harmonic
scalpel features greater precision near vital structures and
produces minimal smoke, thereby improving visibility in
the immediate surgical field [
Several retrospective studies have demonstrated
important advantages of harmonic scalpel use in laparoscopic
cholecystectomies, including more effective hemostatic
and biliostatic support [
However, there are currently no prospective randomized
controlled trials (RCTs) investigating the advantages of the
harmonic scalpel (H) compared to conventional monopolar
diathermy (MD) during laparoscopic cholecystectomies
(LC) in cases of acute cholecystitis (AC).
Our preliminary experience with a series of 101 cases
of H-mediated laparoscopic cholecystectomy to address
acute cholecystitis (AC) demonstrated a lower conversion
rate (without significantly increasing morbidity rates)
compared to a control group of 100 patients who
underwent VLC for AC without H [
]. In this study,
the mean VLC operating time for the H group was
71.4+/−14.3 minutes (range: 42–112 minutes) compared
to 87.4+/−10.8 minutes for the control group (P < 0.001).
Similarly, blood loss was significantly lower in the H group
than it was in the MD control group. For the H group, the
intra-operative conversion rate was 4.9%; the mortality
rate was 1%; and the post-operative morbidity rate was
7.9%, all of which were less than or equal to the
conversion, mortality, and morbidity rates of the control group:
12%, 1%, and 9%, respectively (p = ns).
The gallbladder wall has white blood cells present, with areas of necrosis and suppuration. In this stage,
the active repair process of inflammation is evident. The enlarged gallbladder begins to contract and the
wall is thickened due to fibrous proliferation. Intrawall abscesses are present and involve the entire
thickness of the wall. Pericholecystic abscesses are present.
Given this encouraging preliminary data, we designed
and implemented the HAC Trial to verify these results.
This RCT was designed to test the hypothesis that,
compared to conventional monopolar diathermy (MD), the
harmonic scalpel (H) can effectively reduce intra-operative
laparoscopic-open conversion rates for laparoscopic
cholecystecomies in cases of acute cholecystitis without
adversely affecting rates of post-operative morbidity.
Materials and methods
The HAC study is a prospective, single-center,
randomized controlled trial (RCT). The study was conducted in
the Department of General, Emergency, and Transplant
Surgery of St. Orsola-Malpighi University Hospital
(Bologna, Italy) by surgeons who willingly participated
in the investigation (FC, LA, SDS, ADP.).
The study abided by the guidelines of Good Clinical
Practice and followed the recommendations of the
Declaration of Helsinki. Additionally, the Ethics Committee of
St. Orsola-Malpighi University Hospital formally approved
the study on June 24, 2008. Both the study protocol and
its Informed Consent documents were deemed ethically
and scientifically satisfactory by the Committee, as were
its objectives and general scope. Follow-up assessment of
patient outcomes concluded one year after surgery.
The trial was registered with ClinicalTrials.gov and
given the following identifier code: NCT00746850 [
Participating patients were randomly divided into two
groups: in the first group, patients underwent H-mediated
LC within 72 hours of diagnosis, while in the second group
patients underwent MD-mediated LC within 72 hours of
diagnosis. Given the conventional use of monopolar
diathermy, the MD group served as the control.
Patients were randomly divided into treatment groups
using computer-generated assignments. Blocked
randomization was employed to ensure balance of numbers in the
two groups at any given time during the study. The results
of the randomized assignments were sealed in numbered
envelopes, concealing the enclosed contents. If all
inclusion criteria were adequately met, patients diagnosed with
acute cholecystitis were asked to participate in the study.
If the patient agreed, he/she would review and sign
Committee-approved Informed Consent documents.
Following verification of consent, the patient was randomly
assigned to one of two treatment groups. The attending
surgeon recorded the patient's name and treatment
]. All eligible patients were recorded [
Statistical methods and power calculations
A sample size of 21 patients for each group (42 patients
for the entire study) was calculated using StatCal of the
Epi INFO 2000 software package (Centers for Disease
Control and Prevention, Atlanta, GA, USA) to ensure a
confidence level of 95% with a power > 80%.
To calculate the power a parameter with a statistically
significant difference found in our preparatory
retrospective study was used [
In particular the mean intraoperative blood loss was
chosen because there was an highly statistically difference
in our preparatory retrospective study and this parameter
had also and high clinical importance [
The data were analyzed on an intention-to-treat basis.
All deviations from randomized allocation, false inclusions,
or missing outcomes were properly recorded.
Thorough follow-up assessment served as a safeguard
measure for verifying data, as some individuals were
retroactively excluded from the study based on subsequent
Missing outcomes were incorporated as baseline values,
assuming the same risk as the observed participants in the
The data are expressed as percentages (%) and means
(±SD). The results of the compared groups were
analyzed using the Pearson's Chi-Square and Fisher Exact
tests, as appropriate, for proportions involving discrete
data. The Fisher Exact test was used when the data were
unequally distributed among the cells of the table, when
the expected frequency of any cell was less than 5, or
the when the total number (N) was less than 50.
For means involving continuous numerical data, the
independent sample T test and the Mann–Whitney U-test
were used for normally and abnormally distributed
data, respectively (the data had been previously tested
for normality using the Kolmogorov-Smirnov test). A
p-value < 0.05 was considered statistically significant.
The primary outcome was based on intra-operative
laparoscopic-open conversion rates. Secondary outcomes
were based on intra- and post-operative morbidity and
mortality rates, operating time, and intra-operative blood
All secondary outcomes, including morbidity and
mortality rates, operating time, and blood loss, were adjusted
for qualitative imbalances (i.e. age, previous comorbidities,
anticoagulant therapies, etc.).
Normal coagulation tests were determined before
patients were cleared for surgery.
Inclusion criteria included the following:
Adult patients (>18 years of age)
Clinical (pain, fever > 37.5°C, WBC > 10.000/microL)
and ultrasound evidence of cholecystitis
ASA I-III patients
Less than 72 hours from onset of symptoms
By contrast, exclusion criteria included the following:
Refusal of informed consent
Previous abdominal surgical procedures
Patients with intra-operative findings indicative of non-cholecystitic pathology were retroactively excluded from the study
Apache II score > 10
Pre-operative data included patient demographic
information, comorbidity conditions (Apache II scores),
and a detailed history of symptom onset.
The procedure was performed by experienced
surgeons who had performed at least 50 laparoscopic
Upon admission, patients received cefotaxime, 2 grams
intra-venously every 12 hours (2 g/IV/12 h), which
continued post-operatively in accordance with patients’ NNISS
Surgeons employed the standard four-trocars
technique for laparoscopic cholecystectomies to address
While the gallbladder was distended, its fluid content
was aspirated. Large clamps were inserted through a
5 mm right lower port to achieve a secure hold on the
gallbladder. In the MD (control) group, the cystic artery
and duct were clip-ligated; however, in the H group, the
cystic artery and duct were closed directly by H-mediated
action. There was no instrumental “cross over” between
the experimental (H) and control (MD) groups; for
patients in the control group, surgeons only used
monopolar diathermy, while in the H group, surgeons used
the harmonic scalpel exclusively. The gallbladder and
intra-peritoneally "dropped" stones were collected in
an endoscopic retrieval bag and extracted through the
umbilical port site, which was widened for removal if
necessary. A closed system suction drain was placed
intra-abdominally and later removed on post-operative
day 1. Fascial closure was only applied at the umbilical
port site, while dermal incisions at all other port sites
were closed with staples. The decision to undergo
intra-operative conversion to laparotomy was made by
the attending surgeon, and the circumstances of each
conversion were documented in detail. (Distortion of
Calot’s triangle anatomy, Excessive bleeding. Time of
surgery exceeding two hours).
Patients' files contained demographic information as
well as pre-, peri-, and post-operative data.
Complications were classified as either surgical
morbidity (wound infection, subphrenic or subhepatic abscess,
bile duct injury, hemorrhage) or non-surgical morbidity
(remote infections, atelectasis, deep vein thrombosis,
AMI, CVA, etc.). This information was then entered
into continuous or categorical variable databases, as
appropriate, for further statistical analysis. Following
the surgical procedure, a normal sterile dressing was
applied to cover the abdomen. A second surgical team,
aware of the intra-operative findings but blind to the
surgical dissection instrument, then assumed care of
the patient. This second team was also responsible for
post-operative care and hospital discharge, evaluating the
clinical outcome of patients during their recovery. During
the recovery phase, the initial surgical team was always
available for consultation in the event of an emergency.
Patients were deemed ready for discharge upon
fulfillment of comprehensive evaluation criteria: 1) apyrexia, 2)
absence of diseases requiring hospitalization, 3) return of
bowel function, and 4) patient compliance. No placebo
drugs were used in the course of this study. No incentives
were offered to the patients to encourage surgery or
follow-up assessments. The patients were free to withdraw
from the study at any time.
The study’s primary objective was to demonstrate the
ability of the harmonic scalpel (H) to reduce
intraoperative conversion rates compared to the conventional
monopolar diathermy (MD) approach during laparoscopic
cholecystectomies (LC) in cases of acute cholecystits
(AC); it also sought to highlight any significant differences
regarding morbidity and mortality rates, operating time,
and hospitalization. The primary endpoints of our study
include the following:
A).To evaluate conversion rates
B).To evaluate morbidity rates, mortality rates, and operating time
C).To evaluate the duration of hospital stay
The onset of any complications were recorded at
several time intervals: intra-operatively, post-operatively at
time of discharge on post-operative day 7, 1 month after
surgery, and 6 months after surgery.
The observed side effects did not differ significantly
between the study’s control (MD) and experimental (H)
Follow-up assessments were conducted 1 month,
6 months, and 1 year after surgery.
All aforementioned data were recorded in case report
forms and stored in a database for the duration of the
study. Statistical analysis was performed at the conclusion
of the study after all particpating patients had completed
the final 1-year follow-up assessment.
Of 61 potentially eligible patients, 19 were ultimately
excluded: 16 subjects did not meet the inclusion criteria
and 3 patients refused consent (Figure 1).
42 patients were randomized to one of two treatment
groups, undergoing laparoscopic cholecystectomy using
either the harmonic scalpel (21 patients) or monopolar
diathermy (21 patients, control group) (Figure 2).
PATIENTS WITH CLINICAL and US EVIDENCE OF ACUTE CHOLECYSTITIS and ONSET <72 hours
Assessed for Elegibility
Patients with diffuse peritonitis (n=2),
previous multiple abdominal surgery (n=4),
CBD stones (n=3),
Apache II score >10 (n=3),
refused to participate (n=3)
intra-operative findings of different disease (n=4),
4 patients randomized and
excluded for IO findings
of different disease
(H - study group)
cholecystectomy with monopolar
(MD control group)
MD (n= 21)
The two groups were comparable in terms of basic
patient characteristics (p = n.s.) (Table 2).
The time between diagnosis and surgery was
comparably long in both groups, encroaching closely on the fixed
time limit of 72 hours.
Intra-operative parameters did not differ significantly
between the two groups, with two notable exceptions:
both blood loss (p < 0.05) and the conversion rate (p < 0.05)
were found to be significantly lower for H-mediated
surgery than they were for the conventional MD-mediated
procedure (Table 2).
There were no major morbidities and only 2 minor
surgical morbidities: 1 mild biliary leak resolved with
conservative treatment (delayed abdominal drain removal
after 3 days) and 1 wound infection was conservatively
treated in an outpatient clinic.
Conversion rates were 4.7% and 33.4% in the H and
MD (control) groups, respectively: the sole conversion
to laparotomy in the H group occurred following
distortion of Calot’s triangle anatomy (Table 3) whereas the
MD group experienced 3 conversions due to excessive
The mortality rate was 0% for both groups, and the
postoperative morbidity rates differed only slightly – 23.8% in
the H group compared to 19% in the MD group – with no
underlying statistical difference (Table 2).
The average length of post-operative hospital stay was
5.2 days for the H group compared to 5.4 days for the
control group, again without underlying statistical
difference (Table 2).
Pathology reports demonstrated a comparably high
incidence of necrotizing cholecystitis in both groups without
statistically significant difference (Tables 1 and 4).
Surgery is typically required in the event of acute
cholecystitis due to the high risk of recurrence (30-40%) [
and several studies have analyzed the timing of surgical
intervention; early surgery is defined as a procedure
performed within 72 hours of the onset of symptoms,
while a delayed procedure is one performed 6–12 weeks
The studies with the strongest evidence were reported
in a series of 4 meta-analyses [
The first meta-analysis (conducted by Siddiqui [
reported the results of 4 RCT’s involving 375 patients;
no statistically significant differences were observed in
terms of the conversion rate and post-operative
complications between early and delayed cholecystectomy
treatment groups. Both the duration of surgery and the
length of post-operative hospitalization were lower in
the delayed cholecystectomy group, while the length of
PATIENTS WITH ACUTE CHOLECYSTITIS and ONSET <72 hours
GENERALIZED peritonitis or CBD stones
Conversion to open
overall hospital stay was lower in the early cholecystectomy
The meta-analysis conducted by Gurusamy [
the results of 5 RCT’s involving a total of 451 patients. No
statistically significant differences were reported in the
outcomes of the 2 groups; even the conversion rates and
the incidence of iatrogenic lesions of CBD were
comparable. 17.5% of the patients in the late VLC group
developed recurrent cholecystitis and, among them, 40% had
undergone intra-operative conversion to an open
procedure. Additionally, post-operative hospitalization was on
average 3 days shorter in the early VLC group compared
to the late VLC group. However, it should be noted
that the power of these studies was not strong enough
to determine the rarest outcomes, such as those involving
The meta-analysis conducted by Lau [
] in 2007
included 204 patients and discovered evidence of failed
non-surgical treatment in 23% of cases in the late VLC
group; the study also found a statistically significant
decrease in hospitalization (1.12 days) for patients in the
early VLC group with no significant differences in duration
of surgery, conversion rate, or morbidity rates.
The latest meta-analysis was conducted by Shikata [
and overviewed 1,014 cases. No statistically significant
differences were reported in the conversion rates between
the early and late treatment groups, but post-operative
hospitalization was significantly shorter for patients in the
early VLC group.
As previously noted, these meta-analyses demonstrate
that early VLC correlates with shorter hospitalization and
reduced recurrence rates without increasing morbidity
The Tokyo Guidelines confirmed the clinical
advantages of early VLC. These guidelines also
introduced a classification system of cholecystitic severity
in incremental stages, highlighting the importance
of draining high risk patients while allowing for
delayed surgery for patients with mild, early stage,
cholecystitis due to the scheduling constraints of surgical
These meta-analyses endorse a laparoscopic approach
to treating acute cholecystitis; evidence supporting this
approach is derived from 2 prospective RCTs comparing
open and laparoscopic cholecystectomies.
The first of these studies (Johansson [
]) noted no
difference in post-operative pain, morbidity, or recovery
time. The intra-operative laparoscopic-open conversion
rate was 22.8%; this metric was, by definition, only
applicable to the laparoscopic treatment group. Further,
the duration of surgery proved significantly longer in
the laparoscopy group than in the open group (90 and
Apache II score
Time between admission and surgery (hours)
Mean operating time (minutes)
Mean intra-operative blood loss (cc)
Patients with RBC transfusions
Post-operative hospitalization (mean)
Mean follow-up period (months)
80 minutes, respectively) without differences in the median
post-operative length of hospitalization (2 days in both
The second study (Kiviluoto [
]) reported an
intraoperative conversion rate of 16%, which was likely
attributable to distortion of the cystohepatic (Calot’s)
triangle. Post-operative hospital stay and recovery time
were both shorter in the laparoscopic group, while
post-operative complications were more prevalent in the
open group; no CBD iatrogenic lesions were reported in
either treatment group.
Recently, a Randomized Controlled Multicenter Trial
was conducted by the Italian Polispecialistic Society of
Young Surgeons (Acute Cholecystitis Trial Invasive Versus
Endoscopic Trial; ACTIVE) [
], whose results will soon
As previously noted, all of the RCTs cited in this study
demonstrate high conversion rates, which have been
confirmed by other retrospective studies [
A recent review from the UK [
] involving 43,821
laparoscopic cholecystectomies reported a 9.4% conversion
rate for emergency procedures. Similarly, in a US-based
study of intra-operative laparoscopic-open conversion in
cases of acute cholecystitis, the national conversion rate
ranged from 5% to 10% [
Statements by Kiviluoto [
] define the AC-driven
cholecystectomy as a technically demanding surgical
procedure requiring experienced hands. This issue of
technical difficulty in laparoscopically treated cases of
acute cholecystitis continues to strain the surgical
community. Similar statements were confirmed by the Tokyo
In cases of acute (early VLC) or chronic inflammation
(delayed VLC), even minor bleeding can obscure
anatomical structures and lead to intra-operative
conversion. Minor bleeding is one of the most common
causes of laparoscopic-open conversion [
the demanding technical proficiency required of
laparoscopic intervention, the surgeon’s prior experience
greatly influences the course and outcome of the
Ultrasonically activated scalpels have proved safe and
effective for laparoscopic cholecystectomies, beginning
with their earliest use in 1995 [
Several retrospective studies [
] have demonstrated
the harmonic scalpel’s usefulness during VLC in providing
hemostatic and biliostatic support, as well as addressing
malacia of the cystic duct. Further, the harmonic scalpel
can facilitate clip-mediated closure with reliable sealing
]. A study by Power et al. further demonstrated the
clinical efficacy of laparoscopic cholecystectomies
performed with the harmonic scalpel; in a case series,
duration of surgery and blood loss were both minimal,
the conversion rate was low (3.9%), and no bile duct
injuries occurred. The researchers concluded that use
of the harmonic scalpel greatly facilitated dissection,
thereby reducing operating time and decreasing the
likelihood of conversion to open surgery [
]. Given its
reliable technical precision in difficult cases, the
harmonic scalpel also facilitates the so-called dome-down
]. Another recent study compared
laparoscopic cholecystectomies performed with either
the harmonic scalpel or clip and cautery; while bile
leaks and bile duct-related injuries were not observed in
either group, the laparoscopic group featured shorter
operating time and a lower incidence of gallbladder
The preliminary results of our prospective series of
101 cases of acute cholecystitis treated laparoscopically
using the harmonic scalpel [
] confirmed that the use
of this instrument effectively reduced the intra-operative
laparoscopic-open conversion rate without adversely
affecting post-operative morbidity and mortality, although
it should be noted that the difference in the conversion
rate did not achieve statistical significance (p = 0.08). This
discrepancy may be attributable to the higher incidence
of second-stage necrotizing cholecystitis observed in the
harmonic scalpel treatment group; such cases were
included among those treated with early laparoscopic
cholecystectomy given that they did not violate the 72-hour
window between diagnosis and surgery. Higher incidence
of necrotizing cholecystitis leads to a higher degree of
anatomical distortion, thereby increasing the risk of
conversion. As such, it can be inferred that an even
lower conversion rate might have been observed in the
H group had the treatment groups featured comparable
These preliminary results were used to design the
We hypothesize that the improved hemostatic and
biliostatic support achieved using the harmonic scalpel
reduces the incidence of intra-operative bleeding and
biliary complications, which leads to lower rates of
This reduction is likely more evident in technically
demanding cases with a higher degree of
anatomicalrelated difficulty, such as those involving necrotizing
Our results demonstrate that patients in the H and
MD groups with delayed admission to surgery featured
comparable characteristics, namely a higher incidence of
Of these difficult cases, those in the harmonic scalpel
group featured a lower conversion rate and a reduced
mean intra-operative loss.
While there were no statistically significant differences
in morbidity rates between the H and MD groups, this is
likely attributable to the “protective effect” of the
increased rate of intra-operative laparoscopic-open
conversion in the MD group.
It should be noted, however, that the reduced
conversion rate did not necessarily result in shorter
post-operative hospitalization, as evidenced by 20%
of non-surgical morbidities in both treatment groups
involving older patients (mean age of 71 years) with
severe cholecystitis (necrotizing cholecystitis in 70% of
While instances of non-surgical morbidity influenced
both treatment groups, they may have had a greater affect
on the H group.
In the MD group conversion rate was 33% and this
value was higher than 12% reported for MD group in
the preparatory retrospective study [
Probably this outcome could be explained by the
difference in necrotizing AC rate reported in the present RCT
(70%) compared to necrotizing AC rate in the preparatory
retrospective study (10%) [
In necrotizing AC the procedure is more difficult and
the conversion rate using MD can reach 75% as reported
also by other Authors [
Despite the low level of statistically significant
difference (p = 0.04), the HAC Trial successfully demonstrated
the usefulness of the harmonic scalpel in laparoscopic
cholecystectomies for necrotizing cholecystitis.
The use of H appears to correlate with lower
intraoperative conversion rates during VLC procedures in
cases of acute cholecystitis (AC) without significant
increases in morbidity rates or decreases in post-operative
hospitalization. The harmonic scalpel may be most useful
in technically demanding cases. The use of H is
recommended in cases of gangrenous AC in order to expedite
the surgical procedure and reduce the likelihood of
bleeding and intra-operative conversion.
To ensure cost-effectiveness, the decision to use the
harmonic scalpel should be based on the results of
diagnostic laparoscopy. Use of the harmonic scalpel is also
recommended in cases of gangrenous cholecystitis [
The authors declare that they have no competing interests.
FC: conception and design of the study; SDS: writing the article and data
analysis; LA: critical revision; FC: data collection; MS: data interpretation and
critical revision; CV: data collection; MC: data collection; AT: literature review;
RC: English revision; GDA: critical revision; HKA: literature review; DL: data
collection; AP: Supervision and coordination. All authors read and approved
the final manuscript.
Source of financial support: all costs of the study were financed by St.
Orsola-Malpighi University Hospital in Bologna, Italy.
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