Sentinel Lymph Node Detection in Endometrial Cancer: A Consolidation Study
Phase: NA
Conditions: Sentinel Lymph Node, Endometrial Cancer, Lymphedema
Sponsor: Region Skane

Title page 
Version 1.2  
Date February 6 2019 
Sentinel lymph node detection in endometrial cancer. A consolidation study. 

1 
 
 
Appendix to:  
Persson J et al 
Sentinel lymph node detection in endometrial cancer. A consolidation study. 
 
 
 
 
Table 1. Participating Sites and Site-Principal Investigators 
 
Site 
         Site-PI 
                  # patients enrolled 
1.Department of Obstetrics and         Jan Persson MD, PhD                     XX 
Gynecology, Skåne University 
Hospital and Lund University, 
Lund, Sweden 
2. To be decided 

  
 
 
 
Supplementary appendix 
 
Persson J et al 
Sentinel lymph node detection in endometrial cancer. A consolidation study. 
 
 
Coordinating Center: Department of Obstetrics and Gynecology, Skåne, Lund University 
Hospital and Lund University, Lund Sweden. 
   
 
Lead Principal Investigator:   Jan Persson MD PhD Associate Professor  
Department of obstetrics and Gynecology, Division of Gynecologic Oncology 
Skåne University Hospital Lund 
SE-22185 Lund, Sweden 
(ph) +46733522080 
(fax) +4646156868 
Email: jan.persson@med.lu.se 
 
Local Principal Investigator:  
 
Study Coordinator: Michele Bollino MD 
Department of obstetrics and Gynecology, Division of Gynecologic Oncology 
Skåne University Hospital Lund 
SE-22185 Lund, Sweden 
(ph)+4646172093 
(fax) +4646156868 
Email: Michele.bollino@med.lu.se 
 
 
Study Statistician: 
Filip Mörk. Faculty of Engineering, Lund University. 
 

  
 
Overview study plan. 
 
Consecutive eligible high and low risk endometrial cancer planned for robotic surgery, 
clinically with the primary tumor confined to the uterus (uterine stage I-II).  
High risk defined as at least either of deep (>=50%) myometrial invasion, cervical stromal 
invasion, endometrioid cancer FIGO grade 3, or a non-endometrioid histology. FIGO grade 
1-2 endometrioid cancer with no myometrial invasion are defined as low risk. 
 
                                                      Consenting women  
 
 
Preoperative bilateral measurement of leg volume. Preoperative QOL lymphatic system. 
(attachment) 
 
 
 
 
                                                      Cervical injection of ICG 
 
 
 
 
Registration of adverse events during insufflation and placement of port including 
necessary adhesiolysis.  
 
 
 
 
Surgery according to the preoperative assignment :  
 
 
 
 
 

  
 
 
Define/ plan also as of below: 
 
1. □  FIGO grade 1-2 endometrioid cancers regardless of myometrial invasion.  
SLN UPP and parametria. Ipsilateral reinjection only if non-display of UPP. No frozen 
section of SLN unless macro. Removal of nodes at typical positions for SLN (External, 
obturator, common) in case of non-display of UPP uni or bilaterally 
 
2. □  FIGO grade 3, undifferentiated or non-endometrioid cancers.  
SLN UPP, parametria and LPP. Ipsilateral reinjection if non-display of UPP. Removal of 
nodes at typical positions for SLN (External, obturator, common) in case of non-display of 
UPP uni or bilaterally. Full uni-bilateral presacral LND if non-display of LPP. No frozen 
section of SLN unless macro. 
 
3. □    Any endometrial cancer with cancer suspect pelvic or paraaortic nodes 
according to RECIST criteria ( >=16 mm short axis). SLN detection/reinjection as for 2 
above. Frozen section of SLN. Patient upfront surgery planned for pelvic and paraaortic 
lymphadenectomy. Pelvic and paraaortic LND if frozen section verifies cancer. 
 
UPP- Upper paracervical pathway 
LPP- Lower paracervical pathway 
Parametria= upper lymphovascular paracervical tissue medial of the umbilical artery, dorsal 
of the supravesical artery, lateral of the medial broad ligament and ventral of the ureter. 
 
 
 
. 
 
 
 
 
Pelvic SLN identification with near infrared technique for identification of Indocyanine 
green (ICG) in lymphatics and lymph nodes. Ipsilateral cervical reinjection of ICG as of 
above 1-3. Registration of SLN- associated intraoperative adverse events. 

  
 
 
 
Complete pelvic lymphadenectomy and a Querleu-Morrow Type A to C1 hysterectomy and 
bilateral adnexectomy. Registration of associated intraoperative adverse events. 
 
 
SLN’s for ultrasectioning and immunohistochemistry. Any remaining nodes 
for standard pathological bisectioning and staining with hematoxylin/Eosine.   
    
                                                                              
                                                                               
 
Restaging surgery in case of a positive SLN. US and IHC of restaged nodes if compatible 
with department of pathology. 
 
 
Registration of postoperative adverse events until 30 days after surgery 
 
                                               
 
At one year postop or at symptoms. Postoperative bilateral measurement of leg volume. 
Preoperative QOL lymphatic system and symptom score. 
 
 
Table of contents  
 
1.0 
OBJECTIVES 
 
 
2.0 
BACKGROUND  
 
 
3.0 
PATIENT AND SURGEON ELIGIBILITY 
 
 
4.0 
STUDY MODALITIES 
 

  
 
5.0 
TREATMENT PLAN 
 
 
6.0 
TREATMENT MODIFICATIONS 
 
 
7.0 
STUDY CRITERIA 
 
 
8.0 
EVALUATION CRITERIA 
 
 
9.0 
DURATION OF STUDY 
 
 
10.0 
STUDY MONITORING AND REPORTING PROCEDURES 
 
 
11.0 
STATISTICAL CONSIDERATIONS 
 
 
12.0 
BIBLIOGRAPHY 
 
 

  
1. OBJECTIVES 
 
To estimate the efficacy of a pelvic sentinel lymph node (SLN)  concept for diagnose of 
pelvic nodal metastases in patients with low and- high risk endometrial cancer using  a 
cervical injection of  Indocyanine Green (ICG) as tracer and robot assisted near infrared 
(NIR) imaging using an anatomically based surgical algorithm and definition of sentinel 
lymph nodes. The observed percentage of metastatic sentinel nodes will be evaluated from 
a non-inferiority perspective based on an assumed percentage of pelvic nodal metastases 
estimated from final detailed histological data (myometrial invasion, cervical stromal 
invasion, histological type and grade)  
 
To estimate the proportion of low- and high risk endometrial cancer patients suitable for the 
SLN concept in conjunction with robotic surgery 
 
To estimate time for the SLN procedure  and intraoperative complications associated with 
detection of SLN as such (study intervention) and postoperative adverse events until 30 
days as well as objective measurement of leg volume and lymphedema symptoms by the 
use of a validated questionnaire up and until two years after surgery.  
 
To estimate health economy aspects of the SLN concept. 
 
To estimate complications associated with ICG as tracer 
 
 
 
 
 
 
 
 
 
 
 
 
 

  
 
 
2. BACKGROUND  
 
The surgical approach for endometrial cancer staging has changed from conventional 
laparotomy to a more minimally invasive technique with proven advantages in terms of less 
perioperative morbidity. In endometrial cancer, nodal involvement is a strong prognostic 
factor and also determines adjuvant treatment.  Therefore information on nodal metastases 
is important and in many countries a full pelvic and paraaortic lymphadenectomy is 
recommended despite an increased risk for lymphatic complications in form of 
lymphedema, lymphocysts and in rare cases lymphatic ascites. The concept of identifying 
nodal metastases by detection of sentinel lymph nodes as a marker of nodal metastatic 
disease or not therefore is appealing. 
Recent  data from the department of Obstetrics and Gynecology in Lund shows that robot 
assisted surgery with detection of sentinel lymph nodes with the use of ICG is feasible 84% 
of unselected endometrial cancer patients selected for primary surgery using the inclusion 
criteria in this study. Recent data also shows a 94% bilateral detection rate of sentinel nodes 
(technical success rate) and a 98% sensitivity for the SLN-ICG concept for detecting pelvic 
nodal metastases. 
By the use of Indocyanine green, a fluorescent tracer, we have also previously demonstrated 
two bilateral separate pelvic pathways, the upper paracervical pathway (UPP) running along 
the upper lymphovascular  parametrium usually to  external iliac and/ or obturator nodes 
and the further lateral to the common iliac artery to paraaortic nodes and the lower 
paracervical pathway (LPP) running via the sacrouterine ligament to nodes medial of the 
internal iliac artery and/ or presacral nodes then further medial to the common iliac artery to 
paraaortic nodes. Hence there are two bilateral pelvic pathways draining further to the 
paraaortic region below as well as above the inferior mesenteric artery. Therefore we 
believe that lower paraaortic SLN can only be defined in the absence of pelvic SLN along 
the pathways but with clear filling of pelvic lymphatic channels up to the aorta. In previous 
studies and pilot studies at our institution we have never observed this situation. 
Alternatively, lymph nodes cranial of the inferior mesenteric artery but caudal of the left 
renal vein (infrarenal, supramesenteric nodes)   theoretically may be dyed via the 
infundibulopelvic ligament and may then be considered as true paraarotic SLN but only in 
the absence of dyed node more caudally. Neither this situation has been observed after a 
cervical injection of tracer rarely filling the infundibulopelvic ligament. Moreover, attempts 

  
to find paraaortic SLN would be a step away from decreasing surgery in endometrial 
cancer.  Although detection of pelvic SLN may miss paraaortic skip metastases we 
hypothesize that ultrasectioning of SLN and including a presacral dissection of SLN may 
decrease the incidence of true paraaortic skip metastases.  
 
Surgical competence and experience is necessary to achieve a high technical success rate 
and a low false negative rate for SLN.  
This study aims to evaluate the pelvic sentinel node concept based on a defined surgical 
algorithm and with a clear definition of SLN based on described uterine lymphatic 
anatomy. The study setting includes only high volume accredited surgeons enabling an 
evaluation of the true potential of the pelvic SLN concept in endometrial cancer.   
 
This study aims to include consecutive low and high endometrial cancer patients fulfilling 
criteria to ensure the results are representative for the endometrial cancer population. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

  
 
3. PATIENT ELIGIBILITY 
 
Inclusion Criteria 
-Women of age 18 years and older at the time of informed consent. 
-Women with a pathologically proven endometrial carcinoma of any histologic subtype or 
grade, clinically stage I-II planned for primary surgery 
-A uterine size allowing minimally invasive surgery 
-Women must be able to understand and sign an informed consent in Swedish language.  
-Absence of any exclusion criteria 
 
Exclusion Criteria 
-Non consenting patients 
-Ongoing pregnancy 
-Inability to understand written and/or oral study information  
-WHO performance status or conditions contraindicating adjuvant oncological treatment 
(WHO III or more with no BMI limit) 
-Previous lower limb lymphedema (only for the lymphedema part of study) 
-Evidence of locally advanced disease or intraabdominal/distant metastases at preoperative 
CT, MRI or ultrasonography. 
-Surgical contraindication to a laparoscopic approach or lymphadenectomy at surgeons 
discretion. 
-Anesthesiologic contraindication to a laparoscopic approach at the anesthetist’s discretion  
-Allergy to Iodine  
-Patients with a known liver disease 
-Patients with a bleeding disorder or mandatory antithrombotic treatment.  
 
 
 
 
 
 
 
 
 

  
WHO Performance status 
 
Grade Explanation of activity 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and 
about more than 50% of waking hours 
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours 
4 
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair 
5 
Dead 
 
 
Surgeon eligibility     
All included surgeons outside the primary investigating center must have had a case 
observation at the primary investigating center  followed by a an approved site visit by the 
principal  investigating surgeon at their home center ensuring adherence to protocol.  All 
included surgeons at the primary investigating center were approved by the principal 
investigating surgeon.  
All included surgeons must have a previous experience of at least 100 robot-assisted 
procedures. 
 
In case of additional centres later including patients: The departments of pathology shall be 
coordinated in terms of principles for ultra sectioning and immunohistochemistry of SLN 
and management on non-sentinel lymph nodes. 
 
 
  
 
 
 
 
 
 
 
 

  
 
 
4.0/5.0  STUDY MODALITIES/ TREATMENT 
 
Surgical Procedures 
 
All patients; plan for QM B2 or C1 hysterectomy stage II), adnexectomy. Omentectomy in 
non-endometrioid or undifferentiated cancers 
 
Define/ plan also as of below: 
 
1. □  FIGO grade 1-2 endometrioid cancers regardless of myometrial invasion.  
SLN UPP and parametria. Ipsilateral reinjection only if non-display of UPP. No frozen 
section of SLN unless macro. Removal of nodes at typical positions for SLN (External, 
obturator, common) in case of non-display of UPP uni or bilaterally 
 
2. □  FIGO grade 3, undifferentiated or non-endometrioid cancers.  
SLN UPP, parametria and LPP. Ipsilateral reinjection if non-display of UPP. Removal of 
nodes at typical positions for SLN (External, obturator, common) in case of non-display of 
UPP uni or bilaterally. Full uni-bilateral presacral LND if non-display of LPP. No frozen 
section of SLN unless macro. 
 
3. □    Any endometrial cancer with cancer suspect pelvic or paraaortic nodes 
according to RECIST criteria  ( >=16 mm short axis). SLN detection/reinjection as for 2 
above. Frozen section of SLN. Patient upfront surgery planned for pelvic and paraaortic 
lymphadenectomy. Pelvic and paraaortic LND if frozen section verifies cancer. 
 
UPP- Upper paracervical pathway 
LPP- Lower paracervical pathway 
Parametria= upper lymphovascular paracervical tissue medial of the umbilical artery, dorsal 
of the supravesical artery, lateral of the medial broad ligament and ventral of the ureter. 
 
 
 
 

  
Typical positions of SLN for definition of  “SLN-anatomy” 
 
 
 
 
 
 
Drug Information: 
Indocyanine Green solution  (ICG) 2.5mg/mL. 
Description: ICG (Pulsion medical system, PICG0025SE, Feldkirchen Germany) is a 
sterile, lyophilized green powder containing 25 mg of Indocyanine green with no more than 
5% sodium iodide.  
The ICG solution is prepared immediately before surgery and intended for single patient 
use. For preparation, 10mL of sterile water is injected directly into the lyophilized ICG in 
its glass vial. Invert the vial multiple times to ensure thorough mixing. Draw up 0,25 mL in 
six 1 mL syringes from the vial with ICG solution (2,5mg/mL) for the cervical injection. A 
0.6x38mm 23Gx1 ½  needle. The content of four of the syringes are used for the initial 
injection and in case of non-display of any pathway one or two of the other are used for an 
ipsilateral re-injection.  
The ICG solution is stored at room temperature. The solution is active for 6 hours, and 
should be discarded after that period of time. 

  
Manufacturer: Pulsion medical system, Feldkirchen Germany 
Availability: ICG will be provided by the manufacturer to each site. 
 
 
Adverse Effects if ICG: All adverse effects are allergic in nature and occur in <1% of 
patients. Anaphylactic or urticarial reactions have been reported in patients with or without 
a history of allergy to iodides. If such reactions occur, treatment with the appropriate agents 
(e.g. adrenalin, antihistamines, corticosteroids) should be initiated. 
Contraindications: Known hypersensitivity to iodine containing compounds. Known liver 
failure. Radioactive iodine uptake studies should not be performed for at least 1 week 
following the use of ICG. 
 
Please refer to the current ICG package insert for complete prescribing information 
 
 
Injection of Indocyanine Green (ICG) 
- The ICG is prepared by thorough mixing of 10mL of sterile water with the lyophilized 
ICG in its vial creating a 2.5mg/mL concentration. The lot number, expiration date and dose 
injected (mg) will be recorded. 
- Six separate sterile 1mL syringes is prepared with  0.25 mL ICG solution (0.625 mg 
ICG)in each syringe is prepared. 
-  A 0.6x38 mm 23G needle is attached to each syringe for the injection. A separate back 
table is used for the syringes. 
- The ICG injection will be performed immediately before placement of surgical port and 
docking the robot. 
- Half the ICG volume in each syringe is injected submucosally and half the volume 3 cm 
into the cervical stroma at 2-4-8-and 10 O’clock respectively to a total dose of 2.5mg ICG 
and a total volume of 1 mL. Time for injection is recorded. 
- After injection of dye, a fornix presenter without an intracervical device is placed 
- A second ipsilateral injection of 0,25mL ICG is performed in case of non-display  of 
either of the upper (UPP) or lower (LPP) paracervical pathways after a minimum of 10 
minutes observation time after ICG injection. The injection is done at 3 and 9 O’clock 
respectively, half the volume submucosally and half the volume 3 cm into the cervix.   
- Display of the separate lymphatic pathways (UPP, LPP and IPP will be recorded after the 
first and if performed after the second injection). 

  
 
 
Sentinel Node Identification 
The bilateral technical success rate of SLN identification is important to determine if this 
technique can be transferred to clinical practice. A clear anatomically definition of what is a 
SLN and a strict surgical algorithm as described in this study is important. Based on recent 
results from our institution on cervical and endometrial cancer we expect that the bilateral 
pelvic SLN identification (defined as at least one SLN per hemipelvis) will be 94%. A 
lower than expected detection rate will not be an incentive for premature stop of accrual.  
Importantly, accreditation of surgeons will be performed as described and is likely 
important to achieve a similar success rate as in previous studies. 
 
 
The sentinel nodes are defined as the juxtauterine ICG positive node with an afferent ICG 
positive lymphatics in each of the UPP and LPP respectively on each pelvic side with the 
potential of parallel lymphatics in the UPP to the external and obturator areas. These SLN 
are defined as SLN type 1.  
In case of a ICG positive lymph vessel where no nodes are ICG positive in that pathway, 
the node where the ICG positive lymphatic channel ends is defined as SLN type 2.  
Nodes macroscopically suspect of metastatic disease will be defined as SLN Macro 
regardless of ICG uptake but with information on ICG positivity or not. 
In case of no defined SLN 1-2 macro along the UPP and no SLN macro (low and high risk 
EC) nodes at typical positions shall be removed and regarded as SLN-anatomy and treated 
as SLN by the department of pathology. Likewize all endometrial cancers of FIGO grad III, 
undifferentiated or of non-endometrioid histology shall have a full presacral dissection in 
case of non-display. Those node shall be treated as SLN by the department of pathology. 
Importantly, to secure accuracy, the positions and types of SLN will be marked on an 
anatomical chart, recorded on a list with anatomical locations and placed in pre-labeled jars 
with corresponding anatomical positions and numbers. This list is used by the department 
of pathology for reporting the results to minimize the risk of errors in location of nodes and 
which nodes are SLN’s and non-SLN’s. A copy of the list is kept in the patients study file. 
Nodes defined as SLN will have red labels on the jars, other nodes will have black labels. 
SLN’s will be sent for final histological evaluation including ultrasectioning and 
immunohistochemistry as described. SLN’s will not be sent for frozen section unless 
clinically motivated. 

  
 
The display of ICG along the UPP shall be evaluated a minimum 10 minutes after the 
injection of ICG, first transperitoneally, and if not seen, after opening of the retroperitoneal 
avascular planes. An ipsilateral reinjection shall be performed in case of non-display of the 
UPP in both low risk (LREC) and high risk (HREC) endometrial cancers. A non-display of 
the LPP shall not motivate reinjection but in HREC a full presacral lymphadenectomy 
(LND). No presacral dissection shall be performed in LREC. 
In case if non-display of the UPP despite reinjection a full lymphadenectomy in the external 
iliac and obturator areas shall be performed in HREC whereas In LREC LND a selective 
LND shall be performed including all macroscopically enlarged nodes and lymph nodes 
proximal in the obturator fossa and external iliac nodes in the bifurcation / between the 
external and internal iliac artery (typical positions of SLN’s along the UPP). 
To minimize disturbance by leaking ICG identification and removal of SLN’s starts 
cranially, presacrally (along the LPP, HREC only) and continues at the pelvic side walls 
along the UPP. In both HREC and LREC and after removal of SLN’s the upper 
lymphovascular parametrial tissue is removed separately (defined as the tissue along the 
uterine artery, medial to the obliterated umbilical artery and caudal of the supravesical 
artery) as it may contain lymph nodes that may not be separated from the green 
lymphovascular tissue and hence be the juxtauterine lymph node.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

  
  
Anatomic boundaries of lymph node compartments in the female pelvis 
 
Lymph node 
compartment 
Proximal limit 
Lateral limit 
Distal limit 
Medial limit 
External iliac 
area 
Bifurcation of 
external and 
internal iliac 
artery 
Genitofemoral 
nerve 
Cloquets lymph 
node 
External iliac 
vein 
Obturator fossa 
Internal iliac 
vein 
Ileopsoac muscle 
Os pubis, 
obturator nerve 
Obliterated 
umbilical artery 
Common iliac  
Aortic 
bifurcation 
Genitofemoral 
nerve 
Bifurcation of 
external and 
internal iliac 
artery 
Common iliac 
artery 
Presacral 
Aortic 
bifurcation 
Common iliac 
artery 
Lower 
promontory 
Hypogastric 
nerve (as 
distinction 
between right 
and left) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

  
Anatomic description of lymphatic pathways draining the uterus 
 
 
The upper paracervical pathway (UPP) follows the uterine artery to the pelvic side wall 
draining primarily to the external iliac and obturator nodal compartments, then running 
lateral to the common iliac artery further to the paraaortic area. 
The lower paracervical pathway (LPP) follows the ventral rim of the sacrouterine 
ligament, primarily to internal iliac and presacral nodes, then running medial of the 
common iliac artery further to the paraaortic area. 
The infundibulopelvic ligament pathway (IPP) runs via the Ip-ligament further to the 
supramesenteric paraaortic area. 
For the pelvic SLN concept, ideally one SLN should be identified per LPP and UPP per 
pelvic side wall. 

  
 
 
Anatomic plan for localization of sentinel lymph nodes 
 
Injection site of ICG  cervix                                     Reinjection cervix:  yes  no 
 
Display after first injection 
                                            Display after second injection  
 
                                                                                        
 
UPP 
LPP 
IP-
ligament 
Right 
 
 
 
Left 
 
 
 
 
 
 
 
 
 
Mark position and type of SLN on anatomical chart with number corresponding to position and 
number at list and on separate jars for each SLN.  
○ = ICG positive juxtauterine Sentinel node (SLN1) 
 
      = ICG neg juxtauterine lymph node with afferent lympahtic vessel (SLN 2) 
 
X =  Tumor suspect lymph nodes regardless of mapping (SLN makro) 
 
 
UPP 
LPP 
IP-
ligament 
Right 
 
 
 
Left 
 
 
 

  
 
List of nodal specimens (swedish)   Endometrial cancer             pat-id date 
 
 
Om preparat saknas från station stryks raden i listan.  Burknumrering behålls för övriga prep. 
KK 
Burk 
nr 
Körtelposition 
Patol 
burk
nr 
Dosa nr 
Antal bitar 
Mikro 
Antal 
körtlar 
Varav 
med 
metast 
1 
Uterus, höger ovarium & tuba, 
vänster ovarium & tuba 
 
 
 
 
 
2 
Lgl Iliaca Externa höger ICG NEG 
 
 
 
 
 
3 
Lgl Iliaca Externa höger ICG POS 
 
 
 
 
 
4 
Lgl Obturatorius höger ICG NEG 
 
 
 
 
 
5 
Lgl Obturatorius höger ICG POS 
 
 
 
 
 
6 
Lgl Iliaca Communis höger ICG 
NEG 
 
 
 
 
 
7 
Lgl Iliaca Communis höger ICG 
POS 
 
 
 
 
 
8 
Lgl Presacralt höger ICG NEG 
 
 
 
 
 
9 
Lgl Presacralt höger ICG POS 
 
 
 
 
 
10 
Lgl Iliaca Externa vänster ICG NEG 
 
 
 
 
 
11 
Lgl Iliaca Externa vänster ICG POS 
 
 
 
 
 
12 
Lgl Obturatorius vänster ICG NEG 
 
 
 
 
 
13 
Lgl Obturatorius vänster ICG POS 
 
 
 
 
 
14 
Lgl Iliaca Communis vänster ICG 
NEG 
 
 
 
 
 
15 
Lgl Iliaca Communis vänster ICG 
POS 
 
 
 
 
 
16 
Lgl Presacralt vänster ICG NEG 
 
 
 
 
 
17 
Lgl Presacralt vänster ICG POS 
 
 
 
 
 
18 
Lgl Paraaortalt nedom IMA ICG 
NEG 
 
 
 
 
 
19 
Lgl Paraaortal nedom IMA ICG 
POS 
 
 
 
 
 
20 
Lgl Paraaortal ovan IMA ICG NEG 
 
 
 
 
 
21 
Lgl Paraaortalt ovan IMA ICG POS 
 
 
 
 
 
22 
SLN Parametrium höger 
 
 
 
 
 
23 
SLN Parametrium vänster 
 
 
 
 
 
24 
SLN typ 1 presacralt höger 
 
 
 
 
 
25 
SLN typ 1 presacralt vänster 
 
 
 
 
 
26 
SLN typ 1 iliaca externa höger 
 
 
 
 
 
27 
SLN typ 1 obturatorius höger 
 
 
 
 
 
28 
SLN typ 1 iliaca externa vänster 
 
 
 
 
 
29 
SLN typ 1 iliaca obturatorius 
vänster 
 
 
 
 
 
30 
SLN typ 1 
 
 
 
 
 
31 
SLN typ 1 
 
 
 
 
 

  
 
 
 
Numbers 30-35 will be used for describing locations outside the most common sites and for SLN 
type 2 and SLN macro as appropriate. The locations will be written by hand on list and labels for 
jars. 
 
 
 
Histopathologic evaluation of the sentinel nodes and the non-sentinel nodes. 
All macroscopically identified SLN lymphoid tissue will be embedded and bisected if the 
minimum thickness exceeded 3 mm. If no macroscopically lymphoid tissue is identified in 
SLN or parametrial tissue the most suspicious find will be embedded and microscopically 
investigated. Ultrastaging using hematoxylin/ Eosin staining will be performed in five 
sections at three different levels, separated by 200 µm, if the maximum diameter of the 
SLN tissue exceeds one mm. From first and second level immunohistochemistry (pan-
cytokeratin, MNF 116) will be performed. If no macroscopically lymphoid tissue is 
identified in SLN or parametrial tissue the most suspicious find will be embedded and 
microscopically investigated. ITC can be detected by Hematoxylin/Eosin or by 
Immunohistochemistry alone. 
Non-SLN will be bisected. Non-SLN less than 3 mm in thickness will be embedded whole, 
and from nodes thicker than 3 mm at least half the node will be embedded. The slides will 
be evaluated after hematoxylin/Eosin staining. 
Classification of tumor size in SLN’s 
Sentinel nodes will be classified according to a modification of the AJCC staging for 
axillary nodes from breast cancer as follows: 
32 
SLN typ 2 
 
 
 
 
 
33 
SLN typ 2 
 
 
 
 
 
34 
SLN makro  ICG pos   ICG neg 
 
 
 
 
 
35 
SLN makro   ICG pos  ICG neg 
 
 
 
 
 
36 
SLN anatom  iliaca externa höger 
 
 
 
 
 
37 
SLN anatom Iliaca externa vänster 
 
 
 
 
 
38 
SLN anatom obturatorius höger 
 
 
 
 
 
39 
SLN anatom obturatorius vänster 
 
 
 
 
 
40 
SLN anatom communis höger 
 
 
 
 
 
41 
SLN anatom communis vänster 
 
 
 
 
 
42 
SLN anatom presacralt höger 
 
 
 
 
 
42 
SLN anatom presacralt vänster 
 
 
 
 
 

  
Macrometastases = tumor greater than 2.0 mm in diameter. 
Micrometastases = tumor cell aggregates between 0.2 and 2.0 mm in diameter. 
Isolated tumor cells =individual tumor cells or aggregates that are less than 0.2mm in 
diameter, usually detected by immunohistochemistry. 
Tumor absent – no tumor cells identified in H&E (or immunohistochemically, if applicable) 
stained sections. 
Non-sentinel lymph nodes will be reported as positive or negative for metastases based 
upon routine sectioning and examination of a single H&E stained section. 

  
 
5.0 TREATMENT PLAN/ FOLLOW UP 
 
Patients with metastatic SLN’s shall be planned for a restaging procedure including pelvic 
and paraaortic lymph nodes. 
Importantly, all intraoperative adverse events associated with the study intervention and the 
study drug (ICG) will be recorded in protocol as the separate time used for the detection 
and removal on SLN’s. Likewize, complications associated with the restaging procedure 
shall be included on an intention to treat basis.(additional CRF) 
All adverse events, including postoperative until 30 days, hall be evaluated whether 
attributable to the study intervention or not. 
Measurement of leg volume as an objective parameter of lymphedema shall be performed at 
one and two year follow up and at symptoms.  
Symptoms associated with lymphedema shall be evaluated by a designated QoL Form used 
before surgery, after surgery at symptoms, and at one and two years after surgery. A 
symptoms score shall be used at every follow up. 
  
 
NOTE: Surgeons’ skill and adherence to protocol will be verified as described above. 
 
 
 

  
 
 
6.0  TREATMENT MODIFICATIONS 
 
In case of conversion to open surgery before identification and removal of SLN’s the 
patients should be included in evaluation of adverse events and feasibility on an intention to 
treat basis but not included in the calculation of sensitivity and negative predictive values 
for the sentinel node concept. 
A pelvic lymphadenectomy shall be performed based on definition of “SLNmacro” and/or 
“SLN-anatomy”. SLN macro shall be evaluated with frozen section and if positive a 
paraaortic lymphadenectomy shall be performed unless contraindicated. 
 
 
 
 

  
 
7.0  STUDY CRITERIA 
 
Observations and Tests 
 
The following observations and tests are to be performed and, where appropriate, recorded 
on the designated form(s) (Appendix A): 
 
 
PARAMETER 
Pre-operative 
Intraoperative 
Postoperative 
Log on approached patient   
X 
 
Log on included patients and 
patients’ withdrawal from study 
before surgery 
X 
History & Physical examination 
Examination and evaluation by 
surgeon and anesthetist 
X 
Measurement of  
leg volume 
X 
 X 
Lymphedema Quality of Life  
questionnaire 
X 
X 
Lymphedema symptoms score 
X 

  
 
 
 
Adverse Events will be captured from time of ICG administration until 30 days aftger 
surgery. See section 10. 
 
Laboratory test 
Hb, S-electrolytes, S-kreatinine 
CRP, Trc, coagulation test when 
appropriate  
X  
X 
Injection data for ICG including 
drug related adverse events  
X 
X 
X 
Sentinel nodes identification 
X 
Recording of intraoperative 
adverse events  
X   
Histologic evaluation of sentinel 
nodes and non-sentinel nodes 
X 
Recording of  post-op 
complications until 30 days after 
surgery ( Claviden Dindo) 
X 

  
 
 
8.0  EVALUATION CRITERIA 
 
- All patients who are injected with ICG with at least one SLN type1-2, macro and SLN 
anatomy and not converted to open surgery before detection and removal of SLN’s will be 
included for evaluation of detection rate of metastatic pelvic nodes all together and with 
evaluation of ICG defined (SLN type1-2) separately. 
 
-  Time used for the study intervention (Injection and reinjection of ICG  and detection / 
removal of SLN’s) shall be separately recorded 
 
- All patients included, regardless of conversion to open surgery and mapping of ICG will 
be included in the overall evaluation of feasibility and safety. 
 
- Intraoperative adverse associated with the detection and removal of SLN will be evaluated 
and reported separately on all patients who have at least one SLN removed regardless of 
type, i.e all patients in whom SLN were removed separately. 
 
- Postoperative complications until 30 days after surgery will be reported.  
 
-Perioperative and postoperative complications related restaging will be evaluated on an 
intention to treat basis. 
 
-An increase in leg volume of 10 % or more compared with the preoperative volume will be 
defined as a new onset of lymphedema. 
 
 
 
 
 
 
 
 
 

  
 
 
 
9.0  DURATION OF STUDY 
 
The study includes hysterectomy with identification of sentinel lymph nodes on 
consecutive LREC and HREC patients.  
The patient may withdraw from the protocol at any time prior to surgery or at any time until 
retrieval of postoperative data until 2 year after surgery.  
 
The study was initiated at Lund university hospital (From january 2019) with potential  
later inclusion of a second or mores investigating centers which will motivate a revision of 
the study protocol related estimated time for enrollment of patients and for accreditation of 
the second centre and surgeons. The annual volume of endometrial cancer patients in Lund 
is close to 200 with an estimated 85% suitable for minimally invasive surgery and inclusion 
in the study. 
Related statistical analyses below a total of 362 patients will need to be included with an 
interim analysis after 150 patients. 
 
 

  
10 STUDY MONITORING AND REPORTING PROCEDURES 
 
ADVERSE EVENT REPORTING 
 
The study protocol has been revised related principles study monitoring and for reporting 
adverse events to the principal investigating center after inclusion of the second center.  
 
Definitions 
 
An adverse event (AE) is any new medical problem or exacerbation of an existing problem 
experienced by a subject enrolled in the study, whether or not it is considered drug-related 
by the investigator. 
 
This study will utilize the Adverse Events Logs (Tables 10.1-5). Any SAE will be reported 
to the study coordinator (Michele.bollino@med.lu.se) using the SAE log. (appendix 1).  
 
Adverse events related to the study drug (ICG). 
All adverse events occurring from the first dose of study drug until hospital discharge 
(whether or not attributed to the study drug) will be reported on the Adverse Event Log. In 
addition, any adverse event reported by the subject to the investigator after discharge and 
determined to be reasonably associated with the study drug should also be captured and 
followed until resolution. 
 
Adverse events related to the sentinel node procedure as such (excluding AE related 
the study drug, ICG)  
All intraoperative events related to the SLN procedure will be reported on the adverse 
events log.  
 
Adverse events related the surgical procedure (excluding the SLN part) including AE 
until 30 postoperative days. 
All adverse events will be reported on the adverse events log. 
 
 
 
 

  
Serious adverse event (SAE):  
An adverse event that results in one or more of the following: 
-Any death occurring prior to the postoperative outpatient evaluation 30 days 
postoperatively. 
-Any life-threatening event until and including 30 postoperative days. 
-Any medical event requiring inpatient hospitalization or prolongation of existing 
hospitalization beyond five postoperative days  
 
NOTE: Hospitalizations that are not considered SAE are: 
-Hospitalization planned prior to first administration of study drug 
-Hospitalization for elective treatment of a pre-existing condition unrelated to the study 
medication  
- Hospitalization due to social / practical reasons such as an untimely coordination with 
local community home care services.  
 
Attribution: Attribution is the determination of whether an adverse event is related to a 
medical treatment or procedure. The categories of attribution are: 
 
Definite: The adverse event is clearly related to the study drug  
Probable: The adverse event is likely related to the study drug. 
Possible: The adverse event may be related to the study drug. 
Unlikely: The adverse event is doubtfully related to the study drug. 
Unrelated: The adverse event is clearly NOT related to the study drug. 
 
Unexpected Adverse Event: An unexpected adverse event is an event not mentioned in the 
package insert/ manufacturer’s instructions or the specificity or severity of which is not 
consistent with the package insert/ manufacturer’s instructions. 
The grading described beneath and the attribution described above will be used for 
cathegorization of unexpected adverse events. 
 
 
 
 
 
 

  
Participating Center Reporting Responsibilities 
 
Reporting to the study coordinator 
Any SAE’s must be reported to study Coordinator at Lund University Hospital within 3 
working days of discovery of the incident, using the study-specific SAE Form. 
Email: Michele.bollino@med.lu.se 
 
The lead and local principal investigators and the study coordinator shall conduct 
continuous review of data and patient safety for a monthly summary of the included 
number of patients, patient safety and significant AE’s described in the protocol.  
 
All SAE’s potentially associated with the study drug, the sentinel node procedure as such or 
deaths shall be evaluated by a  
 
 
Reporting to the IRB: 
Each participating center will report adverse events to their IRB per local guidelines. 
 
Coordinating Center Reporting Responsibilities 
 
Reporting to the study coordinator, Lund University Hospital 
Same criteria as above. 
 
Reporting to the IRB: 
Same criteria as above. 
 
The Study Coordinator will distribute reports which are serious, unexpected and associated 
with the study intervention (possibly, probably or definitely) to all participating 
investigators. Copies of all serious adverse event reports will be kept on file the department 
of Obstetrics and Gynecology, Lund University Hospital. 
 
The study coordinator will also report all individual SAE’s related to study drug, the 
sentinel node procedure as such, are life threatening or resulting in death (defined above 
and in table 10.6) to the Safety Monitoring Committee (SMC) for clinical studies at Skåne 
University Hospital for an independent evaluation. 

  
 
At any time during the conduct of the trial, if it is the opinion of the investigators that the 
risks (or benefits) to the patient warrant early closure of the study, this recommendation 
should be made in writing to the SMC.  Alternatively, the SMC may initiate suspension or 
early closure of the study based on its review of the investigator reports. 
 
 
 Study Monitoring / study accrual oversight 
 
The study principal investigator, any local principal investigator and study coordinator will 
conduct meetings (teleconferenced) every 6 months to discuss the protocol. The Study-PI 
and local-PI can call a meeting to convene at additional times if deemed necessary, for 
example following statistical review at the interim period if stopping the study for either 
achieved goals or futility. Apart from the monitoring described below, the number of node 
positive patients and potential false negative SLN’s will be monitored continuously by e-
mail to the study coordinator by the use of the study number assigned to each patient.  
 
In case of identified inconsistencies or missing data, additional source documents 
(identified only by unique patient number) will be requested from the site to resolve 
ongoing inconsistencies. 
 
The principal investigator and/or the study coordinator will, if deemed necessary by the 
principal or second participating center perform audits of informed consents and subject 
eligibility. 
 
Data Management 
Preoperative, intraoperative and postoperative data from each surgery will be recorded on 
the standardized study sheets. These study sheets will be made available to each study site. 
Each study site will be allocated a study number which will serve as the prefix to the case 
number. For example, Lund university Hospital will be allocated the prefix “Lu” and the 
first study patient will have the study number “LU-001. Each investigating center will hold 
a record with the full identification of patients whereas data otherwise should only identify 
the patient by the study number (see above). 
Staff at the individual centers will be responsible for completing the data collection sheet 
for each patient and all data will continuously be entered into a common secured password 

  
secured database  using the designated study numbers.  Upon interim analysis the full data 
will be monitored by the study coordinator, the principal investigator, local principal 
investigator and study statistician.  
Separate analysis of patient data from individual sites can only be performed with the 
written permission of the study principal investigator.

  
 
Early Study Closure 
Death will be reported according to section 10.1 above and per local IRB reporting guidelines. The 
SMC will review all reported deaths monthly. Early closure of the study will be based on 
judgement of the SMC. 
The study will be stopped for futility reasons as described under the statistics section. 
 
10.1.8. Protocol Deviations 
Major protocol deviations shall be reported by mail to the study coordinator. 
Michele.bollino@med.lul.se and filed at Lund University Hospital using the designated study 
number. Major protocol deviations include, but are not limited to, violations to inclusion/ exclusion 
criteria, erroneous preparation of ICG or surgery by a non-accredited surgeon.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

  
 
Table 10.1. Adverse Events before docking the robot (during injection of ICG, insufflation, port 
placement and adhesiolysis) including conversions to open surgery for any reason.  
 
 
 
 
STUDY NUMBER 
AE/SAE 
DESCRIPTION 
Grade 
Attribution 
Example LU001 
AE 
Converted adhesions 
1 
No 
Example LU002 
AE 
Allergic reaction on ICG 
3 
Yes 

  
Table 10. 2. Adverse Events during sentinel node dissection
STUDY NUMBER 
AE/SAE 
DESCRIPTION 
Grade 
Attribution 
LU001   examples 
AE 
Bleeding requiring suture 
2 
Yes 
LU002 
AE 
Obturator nerve damage 
3 
Yes 

 
 
 
 
Table 10.3. Adverse events during pelvic/ pelvic + paraaortic  lymphadenectomy 
 
 
 
 
 
 
 
 
STUDY NUMBER 
AE/SAE 
DESCRIPTION 
Grade 
Attributio
LU001   examples 
AE 
Bleeding requiring suture or 
2 
No 

 
 
 
 
Table 10.4. Adverse events during hysterectomy / omentectomy.  
  
 
 
 
 
 
 
 
STUDY NUMBER 
AE/SAE 
DESCRIPTION 
Grade 
Attributio
LU001 
AE 
Ureteral damage 
3 
No 
LU002 
AE 
Bowel damage 
3 
No 

 
 
 
 
Table 10.5. Postoperative adverse events until 30 postoperative days (all events, also potentially 
unrelated). Clavien Dindo classification 
 
 
 
 
 
 
 
STUDY NUMBER 
AE/SAE 
DESCRIPTION 
Grade 
Attributio
LU001 
AE 
Port hernia 
IIIb 
No 
LU002 
AE 
Fever of unknown origin 
II 
No 

 
 
 
 
 
Table 10.6  Intraoperative Adverse events will be graded according to the following scale: 
 
 
Grade 
Description 
Grade 1 
Mild; asymptomatic; not interfering with function. 
Grade 2 
Moderate; symptomatic; interfering with function but not 
ADL; medical intervention indicated. 
Grade 3 
Severe; symptomatic; interfering with ADL; 
operative intervention indicated; IV intervention 
indicated  
Grade 4 
Life-threatening; major urgent intervention indicated; 
disabling. 
Grade 5 
Death 
 
 
 
 
 

 
 
 
 
 
 
Postoperative adverse events will be graded according to the Clavien Dindo classification 
 
Grade I 
 Any deviation from the normal postoperative course without the need for pharmacological 
treatment or surgical, endoscopic and radiological interventions 
Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgetics, diuretics 
and electrolytes and physiotherapy. This grade also includes wound infections opened at the 
bedside. 
Grade II 
 Requiring pharmacological treatment with drugs other than such allowed for grade I 
complications. 
Blood transfusionsand total parenteral nutritionare also included. 
Grade III 
 Requiring surgical, endoscopic or radiological intervention 
       - IIIa 
 Intervention not under general anesthesia 
       - IIIb 
 Intervention under general anesthesia 
Grade IV 
 Life-threatening complication (including CNS complications)* requiring IC/ICU-
management 
       - IVa 
 single organ dysfunction (including dialysis) 
       - IVb 
 multiorgandysfunction 
Grade V 
 Death of a patient 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
11. STATISTICAL CONSIDERATIONS 
This study is designed to evaluate the ability of the sentinel node (SLN) technique to determine 
pelvic lymph node metastases in patients with low- and high risk endometrial cancer as a 
replacement for a full lymphadenectomy in the latter and as an increased diagnostic procedure in the 
former. 
The main statistical endpoint will be to evaluate the SLN concept by a non-inferiority analysis, i.e its 
ability to detect nodal metastastic disesase compared with an estimated proportion which with a 
50/50% distribution of LREC and HREC result in approximately 12% of women having pelvic nodal 
metastases. This will be tested against 8% metastastic SLN’s as null-hypothesis. With a one-sided 
analysis (Alfa-error of 5% and 80% power) 362 patients need to be included with a planned interim 
analysis after 150 patients. 
If then 22 or more patients are identified as SLN-node positive the hull-hypothesis will be rejected 
and the study closed. If 12 or fewer patients are identified as SLN node positive the study will be 
closed for futility. If the number of node positive patients is between 12 and 21 the study will 
continue to enroll a total of 362 patients (Fleming, 1982). 
 
The measurements of leg volume/lymphedema are based on an estimated risk for lymphedema 
following SLN only of 1% (null hypothesis) compared with the group of SLN positive (HREC and 
LREC) with an estimated risk of 4% (20% node positive with 20 risk of lymphedema) with an 
estimated distribution between group of 88% SLN negative and 12% SLN positive with restaging 
(SLN+LND). A total of 169 patients need to be included with a planned interim analysis after 65 
patients. If 3 or more patients in the SLN+LND group have lymphedema the null hypothesis can be 
rejected provided no more than one patient in the SLN only group have developed lymphedema.  
 
 
              
 
 
 

 
 
 
 
 
 
 
 
 
 
 
BIBLIOGRAPHY 
 
1. Querleu D, Morrow CP. Classification of radical hysterectomy. 
Lancet Oncol. 2008 Mar;9(3):297-303. doi: 10.1016/S1470-2045(08)70074-3.  
 
2. Cibula D, Abu-Rustum NR, Benedetti-Panici P, Köhler C, Raspagliesi F, Querleu D, Morrow 
CP.New classification system of radical hysterectomy: emphasis on a three-dimensional anatomic 
template for parametrial resection. Gynecol Oncol. 2011 Aug;122(2):264-8. doi: 
10.1016/j.ygyno.2011.04.029. Epub 2011 May 17. 
 
3.Abu-Rustum N, Khoury-Collado F, Pandit-Taskar N, Soslow R, Dao F, Sonoda Y, Levine D, 
Brown C, Chi D, Barakat R, Gemignani M. Sentinel lymph node mapping for grade 1 endometrial 
cancer: Is it the answer to the surgical staging dilemma? Gynecol Oncol 113(2009)163-169. 
 
4. Rossi EC, Ivanova A, Boggess JF. Robotically assisted fluorescence-guided lymph node mapping 
with ICG for gynecologic malignancies: A feasibility study. Gynecol Oncol. 2011. Oct 11. 
 
5. Geppert B1, Persson J1. Robotic infrarenal paraaortic and pelvic nodal staging for endometrial 
cancer: feasibility and lymphatic complications. Acta Obstet Gynecol Scand. 2015 Oct;94(10):1074-
81.  
 
6..  Geppert B, Lönnerfors C, Bollino M, Arechvo A, Persson J. 
A study on uterine lymphatic anatomy for standardization of pelvic sentinel lymph node detection in 
endometrial cancer. Gynecol Oncol. 2017 May;145(2):256-261. doi: 10.1016/j.ygyno.2017.02.018. 
Epub 2017 Feb 10. 

 
 
 
7. Fleming TR (1982). One-sample multiple testing procedure for phase II clinical trials. Biometrics 
38: 143-151.  
 
8. Jung SH, Lee TY, Kim KM, George S (2004). Admissible two-stage designs for phase II cancer 
clinical trials, Statistics in Medicine 23: 561-569. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
Appendices  
 
Sentinel lymph node detection in endometrial cancer. A consolidation study.

 
 
Serious adverse events log.  Mail to Michele.bollino@med.lu.se 
 
Per definitions of SAE and attributions as outlined in protocol 
 
Patients study number  
Date for SAE  
Type of SAE 
Yes /no 
Attribution 
Death  
 
 
Life Threatening 
 
 
Drug /ICG related 
 
 
Intraoperative related the 
SLN procedure as such 
 
 
Intraoperative related the 
full LND/ hysterectomy 
 
 
Postoperative 
 
 
Unexpected AE 
 
 
 
Description / outcome of the SAE  
 
 
 
 
 
 
 
 
 
 
 
 
Serious adverse event (SAE):  
An adverse event that results in one or more of the following: 
-Any death occurring prior to the postoperative outpatient evaluation 30 days 
postoperatively. 
-Any life-threatening event until and including 30 postoperative days. 

 
 
-Any medical event requiring inpatient hospitalization or prolongation of existing 
hospitalization beyond five postoperative days  
 
NOTE: Hospitalizations that are not considered SAE are: 
-Hospitalization planned prior to first administration of study drug 
-Hospitalization for elective treatment of a pre-existing condition unrelated to the study 
medication  
- Hospitalization due to social / practical reasons such as an untimely coordination with 
local community home care services.  
 
Attribution: Attribution is the determination of whether an adverse event is related to a 
medical treatment or procedure. The categories of attribution are: 
 
Definite: The adverse event is clearly related to the study drug  
Probable: The adverse event is likely related to the study drug. 
Possible: The adverse event may be related to the study drug. 
Unlikely: The adverse event is doubtfully related to the study drug. 
Unrelated: The adverse event is clearly NOT related to the study drug. 
 
Unexpected Adverse Event: An unexpected adverse event is an event not mentioned in the 
package insert/ manufacturer’s instructions or the specificity or severity of which is not 
consistent with the package insert/ manufacturer’s instructions. 
The grading described beneath  and the attribution described above will be used for 
cathegorization of unexpected adverse events. 
 
 
 
 
 
 
 
 
 
 
 

 
 
Appendix 1. Basic data 
 
 
Sentinel node EC consolidation study  
 
Studie Sentinel node med ICG vid Endometriecancer 
Patientuppgifter 
Sida 1/2 
 
 
 
Date:……………………. Personal identification number:………………………. 
 
 
CRF number  ( by study coordinator)  
 
 
Endometrial cancer: 
 
Histological type/ FIGO grade: ……………………. 
DNA-analyes:      diploid / non-diploid 
 
Tumor size   US/MR    Length_____ Anteriopost ________width__________mm   
 
Myometrial invasion >50% enligt MR / ultraljud: 
□ yes 
□ no 
 
Uterine serosal involvement/ locally advanced tumor  
□ yes 
□ no 
 
Cervical stromal invasion MR /US/preop hist: 
□ yes 
□ no 
 
Enlarged pelvic nodes / RECIST >=16mm short axis 
□ yes* 
□ no 
 
Enlarged paraarotic nodes / RECIST>=16mm short axis  
□ yes* 
□ no 
 
Locally advanced cancer/distant metastases  
□ yes** 
□ no 
 
 
 
 
 
 
Comorbidity:                                 Overall WHO performance grade:    
 
□  None 
□ 
Hypertension 
□  
Heart disease 
 
 
□ 
Diabetes mellitus 
□ 
COL 
□ 
Thromboembolic 
 
 
□ 
Ongoing anticoag treatm 
□ 
Neurologic disorder 
□ 
Other specify  
 
 
 

 
 
Studie Sentinel node med ICG vid Endometriecancer 
Patientuppgifter 
Sida 2/2 
 
 
Previous intrabdominal surgery  
 
□  no 
 
□  Upper/ lower midline incision …………………………………………………………. 
 
□   Pfannenstiel incision………………………………………………………………. 
 
□  Laparoskopy/ robot:……………………………………………………………………. 
 
□  Other, specify……………………………………………………………………. 
 
 
 
 
Parity / vaginal deliveries ………………………………………………………. 
 
Heredity  cancer: 
no/ yes: specify…………………………… 
 
Length meter 
………… 
Weight ……………………………… 
 
 
* Plan for frozen section of SLN and SLN macro and full staging. See inclusion criteria file.  
 
**Exclude from study 
 
WHO Performance status 
 
Grade Explanation of activity 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and 
about more than 50% of waking hours 
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours 
4 
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair 
5 
Dead 
 
___________________________________________________________________________  
 
 
 

 
 
 
Consolidation study Sentinel node in endometrial cancer   CRF number  ( by study coordinator)  
 
 
Appendix 2 Surgical protocol         
 
Date       
Surgeon………………………Assisting surgeon…………………….. 
OR nurse……………………..Circulating nurse……………………….                     
 
Included as/ planned surgery 
 
  Low risk endometrial cancer. SLN only  
 
  High risk endometrial cancer, SLN only   
 
 High/ low risk endometrial cancer  SLN+ pelvic+ paraaortic LND due to preop/ intraop suspect 
nodes  
 
 
 
Reason for an intraoperative deviation from a planned surgery  
__________________________________________________________ 
 
 
 
 
Previous surgery  
 
1 
2 
3 
4 
5 
6 
7 
  No 
 App 
 Pfannenstiel 
 Midline upper 
 Midline lower 
 Laparoscopy/ robot 
 other, specify  
Vikt (kg) 
 
 
Längd (m) 
 
 
  
Surgery 
 
(specify all) 
 
 
1 
 Radical hysterectomy+adnex  , QM type   
 
2 
 Enkel hysterektomi+ adnex 
 
3 
 Sentinel node  UPP +LPP 
 
4 
 Sentinel node UPP only 
 
5 
 Full pelvic LND 
 
6 
 Paraaortic LND to LRV  
 
7 
 Paraaortic LND to IMA 
 
8 
 Omentectomy  
 
 
 Other specify  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
Pat in OR 
time. 
 
First Dr’s procedure  
 
time                                                                            
 
Time for SLN 
Onset dissection 
incl reinj 
Minutes:   
Last stich  
time                                                                                                                                              
                                                                                 
Pat out OR 
time 
 
 
 
Uterus weight (g) 
 
 
 
 
Insufflation 
technique 
 Palmer point direct entry         
 Hasson      
 Verress needle          
 
Adhesiolysis before 
onset of surgery 
no 
Yes 
Total Time for adhesiolysis ( before and after docking) ( minutes)……….. 
 
Nr robot instuments  
 
2           
3           
4            
5 
6 
 
 
Assistant trocar 
 
 
1                                               12mm   disp   non-disp 
2                                               15 mm  disp non-disp 
3                                               18 mm  disp   non-disp 
4                                               5 mm    disp  non-disp 
 
  
Additonal 
instruments  
 
 
  Endobag,nr____________ 
  Tachyseal,/ floseal, nr__________________ 
  Other specify________________________ 
 
Bleeding 
ml_____________________ 
 
Transfusion 
 No  
 Yes    nr units:______________________ 
 
 
´ 
 
 
 
Conversion 
 
no 
Yes to laparotomy   
 
 
 

 
 
 
 
Cause of conversion 
 
 
 Robot, technical problem,; specify:_____________________ 
 
 Surgery, specify:________________________________ 
 
 Anesthesiologically cause; specify:_____________________ 
 
 
Complications during 
insufflation 
or adhesiolysis  
 
 
 None 
 
 Yes. Specify:__________________________________ 
 
Complications during 
SLN removal  
 
 
Complications during 
remaining pelvic LND 
 
 
Complications during 
remaining paraaortic 
LND 
 
 
Complications during 
hysterectomy  
 
 
 
 No 
 
 Yes. Specify:_______________________________ 
 
 
 No             Not performed 
 
 Yes. Specify:________________________________ 
 
 
 No             Not performed 
 
 Yes. Specify:________________________________ 
 
 
 No             Not performed 
 
 Yes. Specify:________________________________ 
 
 
 
Technique for 
removal of uterus  
 
 
 
 
 
 
 
 
 
 
Technique for 
removal of nodes 
 
 
 
Nodal tissue divided 
in abdomen to an 
 vaginally without bag   vaginally with Endobag 
 
 Though abdominal wall in bag, specify why and where. 
_________________________________________________             
 
 
 
 
 
 
 
 
 Trough assistant port in bag/container 
 vaginally in bag 
 
 
 
  No             yes   specify  
 

 
 
enable removal 
through port? 
 
 
Closure of fascia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Assistant port 
 
 Optics port ( SI robot)  
 
 Other ports, specify;_________________________________ 
 
 
 

 
 
Appendix 3. Postoperative symptoms score 
Komplikationer 
 
 
 
 
Komplikationer vid 
 
 
Diagnos 
 
 
Månader postop 
 
Avliden  
 
Om ja, antal månader efter 
Operation= 
Nej 
Ja,, ”dead in disease” 
Ja,  “ dead by treatment” 
Ja, död av orelaterad orsak 
 
Postoperativa 
Komplikationer efter 
hemgång 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nej 
Ja. Återinläggning pga:  
 
Ja. Re-operation pga:  
Ja. Hematom vaginaltopp  
Ja, hematom bukvägg 
Ja,  infektion vaginaltopp 
Ja, urinvägsinfektion 
Ja, oklar feber 
Ja, ileus 
Ja, bråck 
Ja,  trombos / emboli 
Ja, annat:         
 
 Inom 30 
dagar 
> 30 dagar 
 
 
Recidiv 
 
Nej 
Suspekt/ under utredning 
Ja  
Recidiv-diagnos månader 
postop 
 
 
Diagnossätt 
Diagnos av vem 
 
(fritext) 
 
Lokalisation av recidiv 
 
(fritext) 
 
Pågående 
recidivbehandling 
Vad ? 
 
(fritext) 
 

 
 
uppföljning  
 
Vaginaltopp 
 
välläkt 
defektläk 
Ruptur,                mån postop= 
Vault prolaps     mån postop= 
Kort vagina 
 
Vaginalt ultraljud 
Fri vätska i buken? 
 
Om ja, diameter största pöl: 
 
Lymfcysta:  unilateralt / bilateralt (höger / vänster) 
 
Storlek (mm): 
 
Symtom: nej/ja : ange vilka 
 
 
Lymfkörtlar supraklavikulär 
Ua / ej ua 
 
Lymfkörtlar axillärt 
Ua / ej ua 
Lymfkörtlar inguinalt 
Ua / ej ua 
 
 
 

 
 
Bukvägg 
 
 
 
 
Fritext  (naturalförlopp, ev 
reop mm 
Ingen 
Port-hernia, ange vilken port= 
Portmetastas, ange vilken port= 
Ruptur rectusmuskel, ange vid vilken port= 
 
Info= 
 
 
 
Blåstömningsproblem 
Nej 
Ja, ej RIK krävande 
Ja, RIK krävande 
 
UVI senaste 6 mån 
Inga 
Cystit, ange antal 
Pyelonefrit: ange antal 
 
Andra komplikationer 
Obehag, problem med defekation, smärta…? 
 
 
 
 Distala lymfödem   
 
Nej 
Ja 
Debut när? (mån postop) 
 
 
 
Lokalisering  
Gradering enligt CTC 3.0 
Def se längst bak i pärmen 
Om ej ena sidan; ange = 0  
Höger = 
Vänster = 
Kvarstående vid dagens 
uppföljning ? 
Nej 
Ja; oförändrade 
Ja; förbättrade 
Ja; försämrade 
Nej 
Ja; oförändrade 
Ja; förbättrade 
Ja; försämrade 
Behandling 
 
Nej 
Ja, kompr underben 
Ja, kompr helben 
Ja, kompr+ lymfoterapi 
Nej 
Ja, kompr underben 
Ja, kompr helben 
Ja, kompr+ lymfoterapi 
Kompressionsstrumpor, klass 
 
 
 
Pittingödem 
Nej 
Ja 
Nej 
Ja 
Info/ fritext 
 
 
Proximala lymfödem 
 
Nej 
Ja 
Debut när: ( mån postop) 
 
 
 
Lokalisering 
 
Höger= 
Vänster= 
Kvarstående vid dagens 
uppföljning ? 
Nej 
Ja;  oförändrade 
Ja; förbättrade 
Nej 
Ja;  oförändrade 
Ja; förbättrade 

 
 
Ja;  försämrade 
Ja;  försämrade 
Info / fritext 
 
 
 
 
Nervpåverkan 
 
Höger 
Vänster 
 
n. genitofemoralis 
Om ingen; ange= 0 
 
 
n. obturatorius 
Om ingen; ange= 0 
 
 
n cut fem lat 
Om ingen; ange= 0 
 
 
 
Rosfeber 
 
Nej 
Ja, antal gånger= 
 
Nej 
Ja, antal gånger= 
 
Antibiotika profylax 
Ja 
 
Nej 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Appendix 4. Lymphedema QoL life questionnaire