27
Članek prispel / Received
2. 9. 2020
Članek sprejet / Accepted
20. 5. 2021
Abstract
Purpose: Large loop excision of the 
transformation zone (LLETZ) under lo-
cal anaesthesia has almost replaced cold 
knife conisation in the treatment of cer-
vical squamous intraepithelial dysplasia 
(SIL). Thermal artefacts in specimens 
after LLETZ may be so severe, that they 
prevent histopathological interpretation 
and evaluation of the radicality of the 
procedure. There are limited data regar-
ding the prevalence of severe thermal 
artefacts after LLETZ and their clinical 
relevance regarding the need for reope-
ration.
Methods: In this retrospective study, 
we included 314 consecutive patients 
who were treated with LLETZ or cold 
knife conisation for cervical SIL in 2016 
Izvleček
Namen: Pri zdravljenju ploščatocelične 
intraepitelijske lezije (PIL) maternične-
ga vratu je odstranitev transformacijske 
cone v lokalni anesteziji z diatermično 
zanko (ang. LLETZ) skoraj nadome-
stila klasično konizacijo s skalpelom. 
Po LLETZ je lahko prisotna termična 
okvara vzorca, ki je lahko tako obsežna, 
da preprečuje histopatološko interpreta-
cijo in oceno radikalnosti postopka. V 
literaturi je trenutno malo podatkov o 
prevalenci obsežnih termičnih poškodb 
po LLETZ in njihovi klinični pomemb-
nosti glede potrebe po ponovni operaciji.
Metode: V retrospektivno raziskavo 
smo vključili 314 zaporednih bolnic, ki 
so bile v letu 2016 zdravljene na naši 
kliniki zaradi PIL, in sicer z LLETZ ali 
Ključne besede: 
predrakave spremembe 
materničnega vratu, pooperativni 
zapleti, kirurški rob preparata.
Key words: 
precancerous lesions of the uterine 
cervix, postoperative complications, 
surgical margins.
Klinični pomen obsežno termično poškodovanih 
robov stožca po LLETZ 
The clinical relevance of severe thermal 
artefacts in specimens after LLETZ
Avtor / Author Andrej Cokan1, Ivan Žebeljan2, Tamara Serdinšek3, Maja Pakiž1,4
Ustanova / Institute 1Univerzitetni klinični center Maribor, Klinika za ginekologijo in perinatologijo, Oddelek za 
ginekološko onkologijo in onkologijo dojk, Maribor, Slovenija; 2Zdravstveni dom Lenart, 
Dispanzer za ženske, Lenart, Slovenija; 3Univerzitetni klinični center Maribor, Klinika za 
ginekologijo in perinatologijo, Oddelek za splošno ginekologijo in ginekološko urologijo, 
Maribor, Slovenija, 4Univerza v Mariboru, Medicinska fakulteta, Katedra za ginekologijo in 
porodništvo, Maribor, Slovenija;
1University Medical Centre Maribor, Clinic for Gynaecology and Obstetrics, Department 
for Gynaecological Oncology and Breast Oncology, Maribor, Slovenia; 2Health Centre 
Lenart, Clinic for Women, Lenart, Slovenia; 3University Medical Centre Maribor, Clinic for 
Gynaecology and Obstetrics, Department for General Gynaecology and Urogynaecology, 
Maribor, Slovenia, 4University of Maribor, Faculty of Medicine, Department for Gynaecology 
and Obstetrics, Maribor, Slovenia;
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INTRODUCTION
Cervical cancer is the fourth most common cancer 
and the fourth most common cause of death due 
to cancer in women worldwide (1). Following the 
introduction of screening programmes, the incidence 
and mortality of cervical cancer have decreased. During 
screening, the Papanicolaou (Pap) smear and HPV tests 
are used. In the case of an abnormal screening test, 
colposcopy with biopsy is indicated (2) and in the case 
of high–grade squamous (HSIL) or glandular lesions, 
treatment is indicated. Either ablation or excision of 
klasično konizacijo. Primarni cilj razi-
skave je bil ugotoviti pojavnost obsežnih 
termičnih poškodb robov po LLETZ in 
vpliv na ponovitev bolezni ali potrebo po 
ponovni operaciji. Sekundarni cilj razi-
skave je bil ugotoviti pojavnost poopera-
tivnih in kratkoročnih zapletov.
Rezultati: Zaradi PIL smo operirali 
314 bolnic. V 95,2 % primerov smo 
naredili LLETZ, od teh smo v 89,3 
% posegov opravili v lokalni anesteziji. 
Ponovno operacijo smo morali izvesti v 
3,8 % primerov. Pozitivni ali obsežno 
termično poškodovani robovi so bili pri-
sotni v 20,4 % primerov. V 10,7 % pri-
merov so bili termični artefakti po LLE-
TZ tako obsežni, da jih ni bilo mogoče 
natančno histopatološko interpretirati, 
vendar je v tej skupini le ena od bolnic 
potrebovala ponovno operacijo. Zara-
di patološkega izcedka ali krvavitve je 
bilo v pooperativnem obdobju potrebno 
obravnavati 4,7 % oz. 6,7 % bolnic.
Zaklju~ek: Čeprav je imelo približno 
10 % bolnic po LLETZ–u termično 
obsežno poškodovane robove, so le 3 % 
bolnic potrebovale ponovno operacijo. 
Po naših izkušnjah obsežno termično 
poškodovani robovi niso povezani z 
večjo potrebo po ponovni operaciji. Za 
odločitev o ponovni operaciji je tako 
pomembnejše redno sledenje, in sicer s 
citološkimi brisi, testiranjem na prisot-
nost visokorizičnih HPV in kolposkopijo 
z biopsijo.
at our clinic. The primary outcome of the 
study was to determine the prevalence of 
severely damaged surgical margins after 
LLETZ and if these thermal artefacts 
can predict residual disease or the need 
for reoperation. The secondary outcome 
was the prevalence of postoperative and 
short–term complications.
Results: Three hundred and fourteen 
women underwent surgery for cervical 
SIL. In 95.2% of cases, we performed 
LLETZ, and 89.3% of women had this 
procedure under local anaesthesia. The 
reoperation rate was 3.8%. Positive or 
inconclusive margins were present in 
20.4% of specimens. In 10.7% of all 
LLETZ cases, thermal artefacts were 
so severe that they interfered with histo-
pathological interpretation. However, 
only one of these patients needed reope-
ration. Postoperative vaginal discharge 
and mild bleeding requiring therapeu-
tic intervention occurred in 4.7% and 
6.7% of cases, respectively.
Conclusion: Although approximately 
10% of patients had severe thermally 
damaged margins after LLETZ, only 3% 
required reoperation. In our experience, 
severely damaged margins were not associ-
ated with higher reoperation rate. On the 
other hand, a carefully planned follow–up 
visit with cytology, human papillomavirus 
(HPV) testing and colposcopy with biopsy 
after the procedure is of utmost importan-
ce in the evaluation of residual disease..
Naslov za dopisovanje /  
Correspondence
Asist. Andrej Cokan, dr. med., 
Univerzitetni klinični center Maribor, 
Klinika za ginekologijo in perinatologijo, 
Oddelek za ginekološko onkologijo in 
onkologijo dojk, Ljubljanska ulica 5, 
2000 Maribor, Slovenija
Telefon: +386 23212195
E–pošta: cokan.andrej@gmail.com
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the transformation zone where the lesion is located is 
performed. However, ablation techniques are rarely 
used since they have only a few advantages compared 
to excisional techniques (3). The excisional procedures 
performed are cold knife conisation or large loop 
excision of the transformation zone (LLETZ). These 
procedures provide a diagnostic specimen, which is a 
significant advantage. Although cold knife conisation 
usually removes a larger volume of tissue than LLETZ 
(4) and avoids thermal damage of the cone margins, 
LLETZ under local anaesthesia has almost completely 
replaced cold knife conisation, which is traditionally 
performed under general anaesthesia. Several studies 
have shown that patients with negative margins after 
excision are at significantly lower risk of residual 
disease (5–7). Although studies have evaluated thermal 
artefacts of margins after LLETZ (8–12), the data on 
the effect of severe thermal artefacts which interfere 
with pathological interpretation and their impact on 
the need for reoperation are scarce. Therefore, the aim 
of the present study was to determine the prevalence of 
severe thermally damaged surgical margins after LLETZ 
and to evaluate if these thermal artefacts can predict 
residual disease or the need for reoperation.
METHODS 
This was a single–centre retrospective study, which 
was conducted at the Department for Gynaecological 
Oncology and Breast Oncology, University Medical 
Centre  (UMC)  Maribor, Slovenia. The primary 
outcome of the study was determination of the 
prevalence of severely damaged surgical margins after 
LLETZ and if these thermal artefacts can predict 
residual disease or the need for reoperation. The 
secondary outcome was the occurrence of immediate 
postoperative and short–term complications, which 
were assessed at an unscheduled visit at our outpatient 
clinic.
All consecutive patients who were surgically treated for 
squamous (SIL) or glandular cervical intraepithelial 
lesions at our clinic from January 1st to December 
31st, 2016 were included in the study. Patients were 
treated with one of two excisional techniques, either 
LLETZ or cold knife conisation. Cold knife conisation 
was used in cases with large lesions, which could not 
be sufficiently excised with an electrical loop. The 
indication for treatment (high–grade glandular lesions, 
persistent low–grade squamous or glandular lesions 
or mismatch between high–grade cytological and 
low–grade histological preoperative diagnosis with 
unsatisfactory colposcopy with transformation zone 
2 or 3) was based on Slovenian national guidelines 
(13). LLETZ was performed in an outpatient setting 
under local anaesthesia with 0.5–1% lidocaine or 
under general anaesthesia in patients who did not 
consent to local anaesthesia. The procedure was 
performed using KLS Martin Maxium® with loop 
devices ranging from 10 mm to 20 mm in size, using 
a monopolar current with the cut frequency set to 
100–150 W. The wound surface was then coagulated 
with the coagulation frequency set from 60 W to 80 
W. Cold knife conisation was performed under general 
anaesthesia. After the procedure, histopathological 
analysis of the surgical specimen (conus) was performed 
by a team of experienced pathologists from the same 
hospital. Short–term postoperative complications (30 
days after procedure) were determined. Following our 
national guidelines, colposcopy with Pap smear with or 
without biopsy was performed at the first follow–up 6 
months after the procedure. In the case of high–grade 
dysplasia, either squamous or glandular, reoperation 
was performed. We obtained written informed consent 
forms from the patients who agreed to the use of 
their medical records for research purposes, quality 
control and retrospective statistical analysis of the data. 
Statistical analysis was performed using SPSS Statistics 
software 25.0 (IBM, United States of America). 
Descriptive statistics were calculated based on the 
patients’ characteristics. The Chi–square test, Fisher’s 
exact test, Mann Whitney and Kappa tests were used 
to compare data between groups. Statistical significance 
was set at a p–value <0.05.
RESULTS 
In 2016, we surgically treated 314 patients with SIL 
or glandular cervical intraepithelial lesions. Of these 
patients, 95.2% (299/314) underwent LLETZ and 4.8% 
(15/314) underwent cold knife conisation. The median 
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age of the patients was 38±12.5 years (range 20–77 
years). LLETZ under local anaesthesia was performed 
in 89.3% (267/299) of patients, while the remaining 
10.7% (32/299) had general anaesthesia. All cold knife 
conisations were performed under general anaesthesia. 
After the procedure, histopathological analysis of the 
cone was performed, and the excision margins were 
assessed. The excision margins were negative in 79.6% 
(250/314) of cases, positive in 9.9% (31/314) of cases 
and inconclusive in 10.5% (33/314) of cases. Of the 
33 specimens with inconclusive margins, 32 were after 
LLETZ (10.7% (32/299) of all patients after LLETZ) 
in which severe thermal artefacts of the specimen 
interfered with histopathological interpretation. The 
remaining one specimen with inconclusive margins was 
after cold knife conisation due to severe fragmentation 
of the specimen. 
Altogether, 3.8% (12/314) of patients underwent 
reoperation, 10 after LLETZ and 2 after cold knife 
conisation. When analysing patients who were 
reoperated after LLETZ, 21.4% (6/28) of them were 
Table 1. Comparison between LLETZ and classical conisation regarding number of procedures, type of anaesthesia, 
margin status, postoperative complications and the need for reoperation.
LLETZ N (%) Conisation N (%) Total N (%)
Variable 299 (95.2) 15 (4.8) 314 (100)
Anaesthesia 
Local 267 (89.3) 0 (0) 267 (85.0)
General 32 (10.7) 15 (100) 47 (15.0)
Margin status 
Negative 239 (79.9) 11 (73.3) 250 (79.6)
Positive 28 (9.4) 3 (20.0) 31 (9.9)
Inconclusive 32 (10.7) 1 (6.7) 33 (10.5)
Postoperative 
complications
Isolated vaginal 
bleeding 10 (3.3) 1 (6.7) 11 (3.5)
Isolated vaginal 
discharge 5 (1.7) 0 (0) 5 (1.6)
Vaginal bleeding and 
discharge 9 (3.0) 1 (6.7) 10 (3.2)
Total 24 (8.0) 2 (13.3) 26 (8.3)
Reoperation 10 (3.3) 2 (13.3) 12 (3.8)
reoperated after showing positive margins, 1.3% 
(3/239) after showing negative margins and only 3.1% 
(1/32) after severe thermal artefacts in the primary 
specimens (Table 1). In the group of patients who 
underwent reoperation after cold knife conisation, 
one patient had positive margins, and another had 
a severely fragmented specimen. Two patients were 
reoperated immediately after the first LLETZ due to 
cervical carcinoma, and the others were reoperated six 
months after the primary procedure when a scheduled 
follow–up visit was performed and histological HSIL 
was confirmed. 
In the postoperative period, the most frequently 
observed complications were vaginal bleeding and 
discharge. Overall, complications occurred in 8.3% 
(26/314) of cases. Isolated bleeding occurred in 3.5% 
(11/314) of cases, isolated discharge in 1.6% (5/314) 
of cases, and both symptoms in 3.2% (10/314) of 
cases (Table 1). With regard to the impact of the 
type of procedure on the occurrence of postoperative 
complications, we discovered that the type of 
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procedure (LLETZ or cold knife conisation) did not 
significantly affect vaginal bleeding (6.4% vs 13.3%, 
respectively, p=0.265) or vaginal discharge (4.7% vs. 
6.7%, respectively, p=0.528). However, we found that 
bleeding occurred more often in younger (U=3033; 
p=0.914) and discharge (U=1994; p=0.469) in older 
patients, but the impact was not statistically significant.
DISCUSSION 
In this retrospective study, 10.7% of patients after 
LLETZ had severe thermal artefacts in the specimen 
that interfered with histopathological evaluation. 
However, only one of these patients (3.1%) required 
reoperation. In comparison, in patients with positive 
margins after LLETZ, the reoperation rate was 21.4%, 
and in patients with negative margins, the reoperation 
rate was 1.3%. The overall reoperation rate was 3.8% 
and most patients (58.3%) who needed reoperation 
had positive margins after the primary procedure.
Since its introduction in 1989, LLETZ has become the 
most commonly used method for the surgical treatment 
of cervical high–grade squamous or glandular cervical 
lesions. The idea behind LLETZ was to combine the 
advantages of local destructive techniques with those 
of classic cold knife conisation (14). One of the biggest 
concerns when performing LLETZ is inadequate 
histopathological interpretation due to thermal injury 
of the tissue that occurs due to the use of electricity 
which simultaneously cuts and cauterizes the lesion. In 
1994, Messing et al. divided thermal injury of the tissue 
into three grades (slight, moderate and severe). Slight 
thermal injury was defined as a thermal alteration that 
allowed histological evaluation to be performed without 
any difficulty. Moderate thermal injury was defined as 
thermal alterations that resulted in some difficulty in 
correctly interpreting the severity of the neoplasia and 
in evaluating the actual involvement of the resection 
margins. Severe thermal injury was defined as intense 
thermal damage in which histopathological evaluation 
of the specimen was not possible (15). Although a slight 
degree of thermal injury can be seen in almost all LLETZ 
specimens (8), the prevalence of severe thermal injury is 
much lower, up to 26%, depending on the  loop size, 
speed of cutting, electrical energy, tissue conductivity 
and perhaps even the surgeon’s experience (8,15,16).
Many studies have emphasized the importance of 
surgical margins after surgical treatment of cervical 
lesions. The presence of high–grade dysplasia in 
the margin (endocervical, ectocervical and lateral) is 
associated with a higher risk of disease relapse and the 
need for additional surgical treatment in the future. 
Therefore, the aim of the surgeon should be to excise 
the lesion completely (5,7,17), but in the case of severe 
thermal artefacts, we suggest that follow–up visits are 
performed in an experienced colposcopy centre as 
colposcopy with biopsy is crucial in determining the 
success of treatment. In addition, there is known inter– 
and intra–observer variability in colposcopy, cytology 
and pathology, causing different predictive values of 
the methods (18–20). Nevertheless, our experience 
shows that patients with artefacts due to severe thermal 
damage are not at increased risk for reoperation. We 
hypothesise that this might be due to complete thermal 
destruction of the cells around the cut surface of the 
cone. Therefore, even if the precancerous cells were 
located close to the surgical margin, the thermal energy 
of the loop would destroy them. 
Surgical treatment is associated with the possibility of 
postoperative complications. In our study, the overall 
incidence of postoperative complications was low 
(4.7−6.7%) and there were no statistically significant 
differences in postoperative vaginal bleeding or 
discharge between the types of surgical procedure. 
Patients who developed bleeding were younger 
and patients who presented with discharge were 
older; however, there were no statistically significant 
differences between the groups. Some studies have 
shown that classical conisation is associated with a 
higher incidence of postoperative bleeding and vaginal 
discharge than LLETZ (5−15% vs. 0−8% and 0.2−6.8% 
vs. 0−2%, respectively) (10,21–27), but others have not 
confirmed these results (28). Other possible short–term 
side effects reported in the literature such as pelvic 
pain and stenosis of the cervical canal (29) were not 
observed in our group of patients. Also, long–term side 
effects or complications such as preterm labor were 
not an endpoint of this study; therefore, they were not 
included in the analysis. 
The major limitations of this study are its retrospective 
nature and the relatively small number of included 
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patients. Moreover, the patients were not equally 
distributed between the groups and the number of 
postoperative complications was low. These drawbacks 
restricted the statistical analysis, and major conclusions 
should be drawn with caution.
Although every tenth patient after LLETZ had severe 
thermal artefacts that prevented histopathological 
interpretation, only 3% of them required reoperation. 
In our experience, severely damaged margins were not 
associated with higher reoperation rate; therefore, a 
carefully planned follow–up visit with colposcopy and 
cytology 6 months after the procedure is of utmost 
importance in the evaluation of residual disease.
FUNDING ACKNOWLEDGMENT
This research received no specific grant from any 
funding agency in the public, commercial and not–for–
profit sectors.
CONFLICTS OF INTEREST
The authors declare there are no conflicts of interest. 
Some of the results were presented as a poster at the 
26th European Congress of the European Board & 
College of Obstetrics and Gynaecology in Paris, France, 
March 8–10, 2018.
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