Large Loop Excision of the Transformation Zone (LLETZ) With vs Without IntraOperative Application of Lugol's Iodine

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05132114

Studienbeginn:
Januar 2022

Letztes Update:
26.04.2024

Wirkstoff:
-

Indikation (Clinical Trials):
Uterine Cervical Dysplasia

Geschlecht:
Frauen

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Ruhr University of Bochum

Collaborator:
-

Studienleiter

Clemens B Tempfer, MD, MBA
Principal Investigator
Ruhr-Universität Bochum / Marien Hospital Herne

Kontakt

Clemens B Temfper, MD, MBA
Kontakt:
Phone: +492323499
Phone (ext.): 1801
E-Mail: clemens.tempfer@rub.de» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

Gynäkologisches Krebszentrum der Ruhruniversität Bochum am Marien Hospital Herne
Hölkeskampring 40
44625 Herne
DeutschlandRekrutierend» Google-Maps
Ansprechpartner:
Clemens B Tempfer, MD, MBA» Ansprechpartner anzeigen

Studien-Informationen

Detailed Description:

1. Background 1.1. HPV and dysplasias of the cervix uteri Human papillomaviruses (HPV) are

the most common sexually transmitted pathogens worldwide. The prevalence in both male

and female populations is high. Epidemiological estimates suggest that 85-91% of

sexually active adults acquire at least one genital HPV infection by the age of 50, with

approximately 95% of HPV infections being spontaneously eliminated within 2 years in

terms of HPV immunological clearance. HPV preferentially infects the epithelial cells of

the anogenital area and, through incorporation of HPV DNA into the host genome of the

basal cells of the squamous epithelium of the cervix and subsequent expression of viral

components, causes dysplastic changes in the cervical epithelium that, if left

untreated, can develop into invasive carcinoma of the cervix (cervical carcinoma).

Cervical carcinoma is the fourth most common cancer as well as the fourth leading cause

of cancer-related death in women worldwide, responsible for 6.6% (570,000) of all new

cancer cases and 7.5% (311,000) of cancer-related deaths in women in 2018. The precursor

of squamous cell carcinoma of the uterine cervix (approximately 80% of all cervical

cancers) is cervical intraepithelial neoplasia (CIN), which has three grades of

expression (CIN1, CIN 2, and CIN 3). Compared with invasive cervical carcinoma, the

incidence of precancerous lesions of the cervix uteri is much higher. It is estimated

that approximately 100,000 women in Germany develop high-grade dysplasia (CIN2/CIN3)

annually.

1.2. Surgical treatment If precancerous lesions with the potential to develop into an

invasive cervical tumor are detected, conization (= surgical removal of a cone of tissue

from the cervix) is the method of choice for removing the diseased tissue. Worldwide

standard as surgical procedure for conization is LLETZ-conization (Large Loop Excision

of the Transformation Zone). In addition to the risk of local persistence of the

precancerous lesion if the cervical dysplasia is incompletely removed, LLETZ also

increases the risk of preterm birth in a subsequent pregnancy. This risk increases with

increasing volume of removed tissue. To reduce or avoid the aforementioned

complications, conization should be performed under colposcopic vision and as little

healthy cervical tissue as possible should be removed. One method of LLETZ that is as

tissue-conserving as possible is the intraoperative use of the so-called 'iodine test'.

1.3. The iodine test For the identification of healthy squamous epithelium of the cervix

uteri, the so-called Schiller's iodine test can be used, which has been part of the

clinical routine in the context of colposcopy of cervical dysplasias for decades. In the

iodine test, a 5% iodine solution (so-called Lugol's solution) is dabbed onto the cervix

uteri, resulting in an intense and characteristic brown staining of the healthy cervical

epithelium. Sites without staining are termed iodine negative and may contain dysplastic

cells. The strength of iodine testing lies in its high specificity, i.e., the reliable

ability to exclude false-positive results. Not all iodine-negative areas contain CIN,

but iodine-positive areas are almost certainly healthy. In some centers, because of

these characteristics of the iodine sample, it is used during LLETZ to define the

resection line of LLETZ. The aim of this approach is to select the resection line with a

high degree of certainty in healthy (i.e., iodine-positive) tissue in order to reduce

the rate of cervical dysplasia that is not completely removed (so-called 'non-in-sano

resection' or 'R1 resection'). Systematic survey data from the dysplasia units certified

in Germany on the question of the use of intraoperative iodine testing in Germany are

lacking. The current S3 guideline of the German Society of Gynecology and Obstetrics on

the diagnosis and therapy of cervical dysplasia (as of March 2020) also refers to

intraoperative iodine testing as a possible option for performing LLETZ. However, exact

figures from controlled studies on the usefulness of iodine test-guided LLETZ are

lacking in the literature (PubMed search on 10/15/2021; search terms: cervical

dysplasia, colposcopy, Lugol's test, iodine test, Lugol's staining; LLETZ; LEEP;

conization). At our certified dysplasia center, it is the decision of the respective

surgeon whether an additional intraoperative iodine test is performed or not.

2. Aim of the study The aim of this study is to answer the question under prospective

randomized conditions whether LLETZ performed with the aid of iodine assay with

selection of the resection line in the iodine-positive region leads to a lower rate of

R1 resections compared with standard LLETZ without iodine assay.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Written consent

- Colposcopy performed preoperatively

- Histologically (by previously performed colposcopy) confirmed dysplasia (CIN 1, CIN 2

or CIN 3)

- Age >18 years

Exclusion Criteria:

- Pregnant patients

- Patients with insufficient knowledge of the German language

- Treatments already performed on the cervix uteri, in particular conization

- Blood coagulation disorders

- Taking blood thinning substances

- Iodine allergy

Studien-Rationale

Primary outcome:

1. Rate of R1 resections (Time Frame - Specimen from surgery (result expected 1-2 days after surgery)):
The primary outcome parameter is the rate of R1 resections, defined as the presence of a CIN I, CIN II, or CIN III at the ectocervical and/or endocervical resection margin, as indicated in the histopathologic report.

Secondary outcome:

1. Cone mass (Time Frame - During surgery, immediately after the excision):
The weight of the cone specimen (measured in grams in the unfixed state)

2. Procedure duration (Time Frame - At surgery):
Duration of the procedure (from start until complete hemostasis is achieved)

3. Rate of complications (Time Frame - During surgery up to 14 days post surgery):
The occurring intra- and postoperative complications in a period within 14 days after surgery

4. Surgeon's rating of handling (Time Frame - Immediately after surgery):
The assessment of the surgeon's handling of the surgical technique (LLETZ with/without intraoperative iodine assay) (11-item numerical rating scale [NRS]; 0 = very cumbersome, 10 = very easy)

5. Surgeon's satisfaction (Time Frame - Immediately after surgery):
The surgeon's satisfaction with the course of the operation in general (11-item NRS; 0 = no satisfied at all, 10 = very satisfied)

6. Time to complete hemostasis (Time Frame - During surgery):
The time from start of electro-coagulation until complete hemostasis (seconds)

7. Blood loss (Time Frame - At surgery):
The intraoperative blood loss (measured as the difference between preoperative and 3-5 hours postoperative Hb levels).

Studien-Arme

No Intervention: Control Group
LLETZ (without intraoperative Lugol's iodine)
Experimental: Iodine group
LLETZ after the intraoperative application of Lugol's iodine

Geprüfte Regime

Lugol's iodine test:
Intraoperative application of Lugol's iodine (i.e. staining of the cervix with Lugol's iodine solution)

Quelle: ClinicalTrials.gov

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