Randomized Multicenter Study Protocol: Application of 3D Reconstruction for Preoperative Strategy of Locally Advanced Colon Cancer
Phase: NA
Conditions: Colon Neoplasms, Locally Advanced Colon Cancer, 3D Reconstruction
Sponsor: Fundació d'investigació Sanitària de les Illes Balears

RANDOMIZED MULTICENTER STUDY PROTOCOL: APPLICATION OF 3D 
RECONSTRUCTION 
FOR 
PREOPERATIVE 
STRATEGY 
OF 
LOCALLY 
ADVANCED COLON CANCER 
 
 
 
 
NCT Number NCT ID not yet assigned  
Unique Protocol Id IB 5113/23 PI  
Protocol Date: March 29th 2026 
Version: 2.0 
 
Main Investigator: Sebastian Jeri Mc Farlane (MD, PhD) 
Institution: Hospital Universitario Son Espases / Instituto de Investigación de las Islas 
Baleares (IdISBa) 
 
 
 

RANDOMIZED MULTICENTER STUDY PROTOCOL: APPLICATION OF 3D 
RECONSTRUCTION 
FOR 
PREOPERATIVE 
STRATEGY 
OF 
LOCALLY 
ADVANCED COLON CANCER 
 
INTRODUCTION 
Colon cancer surgery is based on the central ligation of the tumor nutrient vessels, an intestinal 
margin free of tumor infiltration of 10 cm proximal and distal as well as dissection through 
embryological plane between the mesocolon and the retroperitoneum (1). 
In locally advanced colon cancer (LACC) (T3-T4a-T4b according to TNM classification), the concept 
of circumferential margins free of infiltration or R0 surgery is essential. If tumor infiltration of 
neighboring structures is suspected, partial or total en bloc resection of the structure should be 
performed (2–5).  
This type of surgery represents a challenge for colorectal surgeons since the risk of complications 
(25%) and postoperative mortality (5%) increases (4,6). As well as the risk of resections with affected 
surgical margins or R1 resection (11%) and as a consequence the rate of tumor recurrence and 
decreased survival at 5 years (6).  
Due to its technical difficulty and the risks mentioned, the percentage of laparoscopic surgeries for 
this type of tumour is around 20% and the conversion rate is high (10%), which also increases the 
risk of postoperative complications (5,7,8).  
The resection of this type of tumors is based on a preoperative surgical strategy based on extension 
computed tomography (CT scan). However, diagnosing infiltration of neighboring structures in colon 
cancer is also challenging for radiologists. In fact, its diagnostic accuracy is close to 40% (9,10). 
For this reason, it is currently questionable whether it is correct to perform a tailor-made surgery in 
the LACC from the CT scan. In fact, in many cases the decision whether to resect or not a 
neighboring structures is decided according to the intraoperative findings, increasing the risk of 
positive margins and/or tumor perforation.  
Currently, in addition to the direct resection of this type of tumor, there are two other therapeutic 
strategies with medical evidence. Adjuvant chemotherapy has been shown to increase the chance 
of R0 in T4b tumors and intraoperative chemotherapy that may decrease the occurrence of 
carcinomatosis in T4 tumors. However, both studies conclude that the application of these two 
strategies encounters the problem of over-staging by CT, with a percentage of 20-30% of T3 tumors 
preoperatively classified as T4 (11).  
The research group of the current project leads a line of work of applying mathematical algorithms 
of 3D reconstruction to imaging techniques to improve surgical results in rectal and colon cancer. 
The result of this line of research are several publications in prestigious international journals (12–
19). Specifically in colon cancer, the research guidelines considered to propose this randomized 
multicentre project. In which perioperative and oncological outcomes will be compared between two 
groups. In the control group (Group A) the surgical strategy will be established in a traditional way 
with the CT and the study group (Group B) will develop the strategy based on 3D-IPR.  

In 2023, the pilot study entitled Application of 3D reconstruction and artificial intelligence for complete 
excision of mesocolon and D3 lymphadenectomy was published (20) Subsequently, in 2024, the 
single-centre prospective study funded by the Asociación Española de Coloproctología (AECP) was 
carried out, showing promising results from the application of this technology in the surgical strategy 
for locally advanced colon cancer. From this last work, the protocol entitled: Prospective 
observational non-randomized trial protocol for surgical planner 3D image processing & 
reconstruction for locally advanced colon cancer  was published (13) These results have been 
presented at the following scientific meetings and the results have already been published in the 
European Journal of Surgical Oncology (21). 
The aim of this study is to assess the usefulness of a mathematical model of three-dimensional 
image process and reconstuction (3D-IPR) as a surgical planner in locally advanced colon cancer. 
In addition to comparing the diagnostic accuracy of this planner with that of the CT regarding the 
infiltration of neighbouring structures. 
 
JUSTIFICATION AND OBJECTIVES 
HYPOTHESIS: A 3D reconstruction model based on mathematical algorithms from CT scan could 
decrease perioperative morbidity and mortality, increase the percentage of minimally invasive 
approaches, and increase the probability of R0 resections in LACC. In addition, it may increase the 
diagnostic accuracy of suspected tumor infiltration of neighboring structures in advanced colon 
tumors.  
 
OBJECTIVES:   
Primary Objective: 
To evaluate whether mathematical models of three-dimensional reconstruction (3D-IPR) enable 
R0 resection in patients with threatened surgical margins (TSM) in locally advanced colon cancer 
(LACC). 
 
Secondary Objectives: 
1. To determine the effect of 3D-IPR on perioperative complications.  
2. To evaluate its impact on the use of minimally invasive surgical approaches.  
3. To assess its influence on conversion rates from minimally invasive to open surgery.  
4. To compare the diagnostic accuracy of 3D-IPR with standard CT radiological reports for 
assessing infiltration of adjacent structures.  
5. To analyze survival outcomes, including overall survival (OS) and disease-free survival 
(DFS).  
6. To evaluate locoregional and distant recurrence rates over a 5-year follow-up. 
 
 
OUTCOMES 
Primary Outcome: 

• 
R0 resection rate: Defined as microscopically margin-negative resection in patients with 
TSM undergoing surgery planned using 3D-IPR.  
 
Secondary Outcomes: 
• 
Perioperative complications: Incidence and severity within 30 days post-surgery, classified 
by the Clavien-Dindo grading system.  
• 
Conversion to open surgery: Rate of patients requiring intraoperative conversion from 
minimally invasive to open surgery following 3D-IPR planning.  
• 
Minimally invasive surgery utilization: Proportion of patients undergoing laparoscopic or 
robotic surgery.  
• 
Diagnostic performance: Sensitivity, specificity, positive and negative predictive values, and 
overall accuracy of 3D-IPR versus CT; agreement measured by Cohen’s kappa coefficient.  
• 
Survival outcomes: OS (time from surgery to death from any cause) and DFS (time from 
surgery to recurrence or death, whichever occurs first).  
• 
Recurrence: Proportion of patients with locoregional or distant recurrence over 5 years. 
 
Justification: 
If greater diagnostic accuracy is observed for this mathematical method of 3D reconstruction with 
respect to infiltration of neighboring structures in locally advanced colon tumors: 
- 
The radiologist would have an objective tool to delimit the tumor extension. 
- 
The surgeon would have an objective tool to plan the type of surgical intervention with the least 
probability of modifying intraoperatively. In addition, this 3D tool facilitates the preoperative 
visualization of the tumor location. 
-  
The preoperative simulation of different surgical routes to resect the tumour would allow the 
ideal one to be selected to do so in a minimally invasive approach. This fact has shown 
advantages over traditional laparotomy.  
-  
Mutilating surgeries due to a false positive diagnosis of infiltration of neighbouring structures 
could be avoided.  
- 
This type of intervention could require the collaboration of other specialties such as 
gynaecology, urology, vascular surgery, traumatology and plastic surgery. Correct scheduling 
of the type of extended resection to be performed is essential. To this end, this tool would 
provide the necessary data for this purpose. 
- 
The discussion of this type of pathology in a Multidisciplinary Committee (MDC) within reference 
Colorectal Units is frequent and knowing the exact degree of infiltration of anatomical structures 
facilitates decision-making. At present, there are different therapeutic lines for locally advanced 
colon tumours. Among them we find direct surgery and subsequent adjuvant chemotherapy.  
There is also evidence of neoadjuvant chemotherapy and subsequent resection, and finally 
recent studies propose surgery with intraoperative hypertemic peritoneal chemotherapy 
(HIPEC). For this reason, correct staging is essential to avoid overtreatment. 

-  
An R0 surgery decreases the risk of oncological recurrence. This fact decreases the number of 
patients who require chemotherapy treatment for this reason, long-term follow-ups, number of 
face-to-face consultations and complementary tests.  
 
In this way, 3D reconstruction is a tool that could provide digital solutions for health and care, 
promoting the development and use of these innovative techniques to improve the quality of life of 
patients. For this reason, it is necessary to highlight the need to promote the development of these 
technologies taking into account interoperability, security, confidentiality and standardization 
systems, for the improvement of health care. 
Surgery for locally advanced colon tumors has a rate of postoperative complications that can be 
high, as well as a positive surgical margin risk. This tool could improve these results considerably.  
An important advantage is the fact that the patient is not summited to a new diagnostic test to obtain 
this reconstruction, since it is performed using CT scan images done during staging oncologic 
protocols. 
 
 
Material and methods 
 A randomized prospective multicenter  study will be carried out in 5 Colorectal Surgery Units of the 
following 3rd level of care hospitals, over a period of two years. 
1. 
Son Espases University Hospital, Balearic Island, Spain. 
2. 
Hospital Álvaro Cunqueiro, Galicia, Spain. 
3. 
Reina Sofía General University Hospital, Murcia, Spain. 
4. 
Josep Trueta University Hospital, Girona, Spain. 
5. 
Ramón y Cajal Hospital, Madrid, Spain. 
 
Inclusion criteria:  
1. 
Patients of both sexes, aged ≥18 years.  
2. 
Adenocarcinoma of the right, left, sigmoid and recto-sigmoid junction that have cT3 or cT4a/b 
according to the eighth TNM edition of the American Joint Committee on Cancer (AJCC). Pre-
treatment diagnosis by imaging (CT) test.  
3. 
Lymph node extension: cN0, the presence of cN1/2 according to AJCC TNM 8th edition is 
allowed as long as they can be resected. Pretreatment diagnosis by imaging (CT) test. 
4. 
Patients who access and sign informed consent for the surgical intervention.  
 
Exclusion criteria: 
1. 
Suspected carcinomatosis on preoperative CT or intraoperative finding 
2. 
Suspected distant metastasis on preoperative CT or intraoperative finding 
3. 
Patients with tumors with infiltration considered to be unresectable (pre-surgical or 
intraoperatively), since the anatomical-pathological analysis will not be available.   
 
Mathematical method of 3D reconstruction (3D-IPR)  

- 
3D mathematical reconstruction from the extension CT, which is performed on all patients with 
colon neoplasms, to assess the location of the primary colon tumor and possible infiltration of 
neighboring/retroperitoneal structures. 
- 
Assessment of the same parameters presented for the CT scan of the abdomen. 
- 
The mathematical reconstruction will be based on two concepts:  
1. Preprocessing of extension CT using "Polarization Field Correction" algorithms and 
radiomics-based anisotropic diffusion filters of the image.  
2. Segmentation of medical image in the different sequences provided using sequence of 
algorithms based on active contour methods, modified dynamic search and based on atlases. 
Finally, the 3D surface will be reconstructed using modified "marching cube" algorithms. 
 
Utilities of the 3D Reconstruction surgical planner: 
1. 
Exact tumor size 
2. 
Exact tumor location 
3. 
Mathematical extension of 10 cm proximal and distal resection area. 
4. 
Arterial and venous vascularization of the resection area 
5. 
Location of possible lymphadenopathies 
6. 
Minimum distance of the tumor from the different anatomical structures 
7. 
Location of possible areas of tumour infiltration 
8. 
Tumor infiltration volume in cm3 
9. 
Simulation of surgical resection with a margin of 5 and 10 mm.  
 
 
Figure 1: Locally advanced right colon cancer. CT scan on the left with no parietocolic or 
retroperitoneal infiltration. 3D-IPR on the right with infiltration of the parietocolic ligament and 

retroperitoneum. The detailed vascularization of the colon is also observed, as well as the 
mathematical location of the tumor.  
 
 
Figure 2: Locally advanced sigmoid colon cancer. CT scan on the left with unclear definition of the 
plane of separation between tumor, bladder and uterus. 3D-IPR on the right showing uterine 
infiltration, no bladder intration as well as exact tumoral size and location.  

 
Figura 3: Locally advanced sigmoid colon cancer with an abscess and fistula between colon and 
bladder. To the left, CT scan does not show plane of separation between tumor and bladder. 3D-IPR 
shows abscess and fistula bewtween sigmoid and bladder, no tumor infiltration.  
 
Anatomopathological study: 
1. 
The surgical specimens are processed and fixed in 10% formaldehyde and the quality of the 
complete excision of the mesocolon and tumor staging will be evaluated according to current 
anatomopathological clinical guidelines.  
2. 
4mm thick cross-sections will be made on the piece (each of the sections are digitally 
photographed) from the proximal portion, including the tumor area, to visualize the relationship 
of the cancer with the circumferential margin of resection. Thus, the location of the tumor is 
evaluated in relation to the retroperitoneal margin: above, at or below it; and with the rest of the 
adjacent resected structures. 
3. 
For the microscopic study, sections are included by quadrants in blocks, choosing the sections 
with the greatest infiltrative component in the intestinal wall, closest to the circumferential 
margin painted with Indian or orange ink. 
4. 
Samples are included and stained with hematoxylin-eosin following the standard methodology 
for histological evaluation. 
5. 
The parameters analyzed are those of the protocol already established in the reference unit. 
 
Variables 

The following will be considered a tumor infiltration zone after the anatomopathological study: Presence 
of infiltrating tumor cells in the neighboring anatomical structure. Need for a photograph of the 
anatomopathological study sheet.  
 
Assessment of diagnostic accuracy of 3D-IPR with respect to tumor infiltration in the group of 
randomized patients in whom 3D-IPR was performed: 
Microscopic analysis of each of the structures marked as infiltrated by 3D-IPR. Need for a picture 
photograph of the pathological study. 
 
CT Scan report comparison respect to: 
Tumor infiltration of neighboring structures: Comparison by microscopic study of each of the anatomical 
structures. 
 
Comparison with the CT scan report regarding: 
Suspected or not of being infiltrated areas according to the CT and 3D-IPR.  
 
Sample size: 
The sample size will be determined by considering all cases that meet the established inclusion and 
exclusion criteria, over a period of two years in the participating centers. Based on previously published 
data with R0 rates of 89% in cases of LACC (10,22,23)  
The sample size of this study was calculated with the aim of evaluating the efficacy of mathematical 
models of three-dimensional reconstruction (3D-IPR) in improving the rate of R0 resections in patients 
with threatened surgical margin (TSM) in locally advanced colon cancer. 
The following parameters were assumed: 
1. 
R0 resection rate in the control group (Group A): Based on previous studies, a rate of 89% is 
considered when using traditional surgical strategies. 
2. 
Expected R0 resection rate in the intervention group (Group B): An improvement is expected, 
reaching at least 95% R0 rate by using the 3D-IPR 
3. 
Level of significance (α): It was established at 0.05, which corresponds to 95% confidence. 
4. 
Statistical power (1−β1): It was set at 90%, to ensure a high probability of detecting real 
differences between the groups. 
5. 
Allocation ratio: An equal allocation (1:1) was used between the control group and the 
intervention group. 
 
 
When the formula is applied, it results in a sample size of 67 patients in each group.  

On the other hand, it is expected that each center will intervene between 12 and 14 patients annually 
who meet the characteristics defined in the methodology. This estimates that the five centers will 
perform approximately 84 interventions per year, resulting in a projected total of 168 cases at the end 
of the two years of study, which is compatible to reach the desired sample size to statistically validate 
the results.  
 
Randomization method: 
Participants will be assigned to two groups using a 1:1 randomization process. The control group (Group 
A) will follow the conventional procedure to establish the surgical strategy, using the images obtained 
by computed tomography (CT) as a basis. On the other hand, the study group (Group B) will implement 
surgical planning using the 3D-IPR surgical planning.  
To ensure an unbiased and standardized assignment, we will employ a website specifically designed 
for the study and this type of randomization (https://www.sealedenvelope.com/). This page will allow 
the users to enter an anonymized code for each patient, guaranteeing data protection and data 
confidentiality. Once the code has been entered, the system will determine which group the patient will 
be assigned to, following the previously configured 1:1 randomization scheme. This assignment will 
allow the number of patients to be balanced equally between both groups, minimizing biases and 
optimizing the statistical validity of the results. 
 
Study Variables:  
 
 
VARIABLE 
VALORES 
Demographic Variables 
HOSPITAL 
Text 
ID – 3D 
Numeric/Text 
Sexo 
0: Female 
1: Male 
Date of birth 
Numeric 
Age 
Cuantitative discreta (años) 
ASA 
0: ASA I 
1: ASA II 
2: ASA III 
3: ASA IV 
4: ASA V 
5: ASA VI 
BMI 
Numeric 
Aleatorization 
0: Group A (Control Group) 
1: Group B (3D Group) 
Pre-Operative Variables 
Diagnosis 
0: Right colon neoplasm 
1: Hepatic flexure neoplasm 
2: Transverse colon neoplasm 
3: Splenic flexure neoplasm 
4: Descending colon neoplasm 
5: Sigmoid colon neoplasm 
Neoadjuvant chemotherapy 
0: No 

1: Yes 
Neoadjuvant radiotherapy 
0: No 
1: Yes 
Neoadjuvant immunotherapy 
0: No 
1: Yes 
Resectable disease defined in 
multidisciplinary committee? 
0: No 
1: Yes 
CT scan variables 
Neighbouring structures infiltration 
(Confirmed or suspicion) in CT scan?  
0: No 
1: Yes 
Infiltrated structures in CT scan 
 
0: Retroperitoneal fascia 
1: Parietal fascia 
2: Uterus 
3: Bladder 
4: Duodenum 
5: Kidney 
6: Urether 
7: Others 
Other infiltrated structures in CT scan 
Text 
Distant Metastasis 
0: No 
1: Yes 
cT stage 
0: cT0 
1: cT1 
2: cT2 
3: cT3 
4: cT4a 
5: cT4b 
6: Not reported 
cN Stage 
0: N0 
1: N (+) 
2: Not reported 
3D Reconstruction 
variables 
Neighbouring structures infiltration in 
3D-IPR? 
0: No 
1: Yes 
Infiltrated structures in 3D-IPR 
 
0: Retroperitoneal fascia 
1: Parietal fascia 
2: Uterus 
3: Bladder 
4: Duodenum 
5: Kidney 
6: Urether 
7: Others 
Other infiltrated structures in 3D-IPR 
Text 
Total Infiltration volumen in 3D-IPR 
 
 
Numeric (mm3) 
 
Intraoperative variables 
Surgery date 
Numeric 
Surgical Approach 
0: Laparotomy 
1: Minimally invasive 
Conversion to open surgery 
0: No 
1: Yes 
Type of surgical procedure 
0: Right colectomy 
1: Extended right colectomy 
2: Splenic flexure segmentary resection 
3: Left colectomy 
4: Sigmoidectomy   
5: Extended left colectomy 
6: Subtotal colectomy 
Intraoperative carcinomatosis 
0: No 
1: Yes 

Resectable tumor? 
0: No 
1: Yes 
Surgical time 
Numeric (Minutes) 
Extended resection 
0: No 
1: Yes 
Partial or total en bloc resection of 
neighbouring structures 
0: Partial 
1: Total 
Neighbouring structure resected 
0: Retroperitoneal fascia 
1: Parietal fascia 
2: Uterus 
3: Bladder 
4: Duodenum 
5: Kidney 
6: Urether 
7: Others 
Other neighbouring structures resected Text 
Discharge date 
Numeric (date) 
Postoperative stay 
Numeric (days) 
Anatomopathology 
Variables 
Histology 
0: Adenocarcinoma 
1: Other 
Differentiation 
0: G1 Well differentiated 
1: G2 Moderately differentiated 
2: G3 Poorly differentiated 
pT stage 
0: cT0 
1: cT1 
2: cT2 
3: cT3 
4: cT4a 
5: cT4b 
pN Stage 
0: N0 
1: N (+) 
Total number of lymphnodes 
Numeric 
Total of positive lymphnodes 
Numeric 
Lymphnode ratio 
Numeric = Positive lymphnodes/Total 
number of lymphnodes 
Vascular infiltration 
0: No 
1: Yes 
Lympathic infiltration 
0: No 
1: Yes 
Perineural infiltration 
0: No 
1: Yes 
Tumoral deposits 
0: No 
1: Yes 
Stage 
1: Stage 1 
2: Stage 2 
3: Stage 3 
4: Stage 4 
Infiltrated structures in pathology? 
0: No 
1: Yes 
Neighbouring structure infiltrated 
0: Retroperitoneal fascia 
1: Parietal fascia 
2: Uterus 
3: Bladder 
4: Duodenum 
5: Kidney 
6: Urether 
7: Others 

 
Oncological variables analyzed at 3 and 5 years: 
1. 
Locoregional recurrence: intraluminal growth of the tumor near the suture or inside the cavity 
near the previously operated location.  
2. 
Distant recurrence: Distant metastasis outside the abdominal cavity. 
3. 
Peritoneal carcinomatosis: Carcinomatosis will be considered when there are tumour implants 
in at least two different areas of the abdominal cavity with an anatomopathological diagnosis of 
the presence of tumour cellularity. This allows it to be differentiated from regional loco 
recurrence.  
4. 
Disease-free survival: Time from surgery to the date recurrence is documented.  
Other neighbouring structures 
infiltrated 
Text 
Type of resection? 
0: R0 
1: R1/R2 
Infiltration of proximal margin 
0: No 
1: Yes 
Infiltration of distal margin 
0: No 
1: Yes 
Infiltration of circumferential margin 
0: No 
1: Yes 
Post-Operative 
Variables 
Complications: Clavien-Dindo 
Classification 
0: 0 
1: 1 
2: 2 
3: 3 
4: 4 
5: 5 
Surgical Re-intervention 
0: No 
1: Yes 
Cause of surgical re-intervention 
0: Anastomotic leak 
1: Hemoperitoneum 
3: Evisceration 
4: Intestinal obstruction from adhesions 
5: Other 
Other causes of surgical re-
intervention 
Text 
Adjuvant chemotherapy 
0: No 
1: Yes 
Follow-up Variables 
Date of last follow-up 
Date 
Local recurrence 
0: No 
1: Yes 
Date of local recurrence 
Date 
Distant recurrence 
0: No 
1: Yes 
Date of distant recurrence 
0: No 
1: Yes 
Recurrence as Peritoneal 
carcinomatosis 
0: No 
1: Yes 
Date of recurrence as peritoneal 
carcinomatosis 
Date 
Death 
0: No 
1: Yes 
Death secondary to disease 
progression 
0: No 
1: Yes 
Death date 
Date 

5. 
Overall survival: time from admission to death from any cause (includes 90-day postoperative 
mortality).  
6. 
Mortality due to oncological progression. 
 
All patients with recurrent disease should be confirmed, if possible, histologically or by radiological 
imaging or resurgical intervention.  
 
Statistical method  
The qualitative variables will be expressed by sample size and percentage. The categorical variables 
will be expressed by the median and the range.  
In the nonparametric univariate analysis, continuous variables will be compared using the Kruskal-
Wallis test, while categorical variables will be compared with the Fisher Exact test. A p< value 0.05 will 
be considered statistically significant.  
 
Database Data Protection:  
Database (DB) Data Storage and Access Policy Report.  
A database will be created, for which each collaborator will have a unique username and password to 
be able to include the patients in the study. The main investigator will be the only one who will be able 
to have access to the aggregated patients of each center. Collaborators will only be able to add and 
modify their own patients, without access to patient information from the other hospitals. In this way, it 
is the main researcher who will be in charge of collecting information from all the centers in order to 
analyze the results.  
The information will be stored on cloud servers owned by Oracle. The information is encrypted in the 
database so any direct access to it is useless, unless the private key is known. Data that could be used 
to locate the patient such as name, surname, ID, etc., is not requested. The only data that could be 
used is the Chart history number, which is cut, so that the user who reports data can locate the 
correspondence in his hospital, that is, he must have the real data written down in a place controlled 
only by him (such as the hospital's own management program) in order to locate that patient. 
In the case of access to the application by someone who is not authorised, but who has obtained a 
username and password with access to read patients from their own and other hospitals, the available 
information does not serve to "de-anonymize" the data. Accesses to the application, writes, reads, etc. 
are recorded by the application so that any access without express authorization can be located. 
On the other hand, the coordinator of the Simulation and 3D Printing Unit of the Son Espases University 
Hospital, and the coordinator of each research centre, will be in charge of anonymizing the data of the 
patients in the study.  In this way, they can be provided to the company CELLA MEDICAL SOLUTIONS 
®, anonymously and safely, to carry out the three-dimensional reconstructions necessary for the study.  
 
Work plan 
During the first 2 months, coordination will be carried out between all the centres involved, as well as 
the creation of the digital database.  

During the following two years, the surgical centers will perform: 
- Identification of patients who are candidates for the study according to material and methods.  
- Referral of the pre-operative CT scan to Innovación y Tecnología Médicas Cella (proprietary software) 
for the elaboration of the 3D-reconstruction and assessment of tumor infiltration. 
- Surgical intervention. 
- Detailed microscopic study of the surgical specimen and definitive anatomopathological report. 
- Incorporation of data into the prospective database. 
- Forwarding of all microscopic images to the main investigator for storage. 
 
During the following 6 months, the result analysis will be carried out, evaluation of strategies and results 
communications.  
The dissemination of the results will be carried out in the main congresses of General Surgery and the 
Digestive System, such as the National Congress of Surgery of the Spanish Association of Surgeons 
(AEC), the National Congress of the Association of Coloproctology (AECP), the International Congress 
of the European Society of Coloproctology (ESCP), as well as the International Conference on 
Coloproctology that is held annually in Baiona.  Galicia.  
On the other hand, to extend the dissemination of the results, the articles that may come from this 
research will be sent for publication to international journals if possible, in Q1 according to the Journal 
Citation Reports (JCR).  
 
This study will comprise the following stages:   
1. 
Phase 1. Knowledge of the different centers in the study protocol. Each of the centers must 
present perfect coordination with four different specialties: colorectal surgery, pathological 
anatomy, radiology, oncology.  
1. 
To establish this coordination, two digital workshops will be held in which a member of 
each of these specialties from each of the centers involved will participate.  
2. 
Phase 2. Each of the centres will carry out the action protocol test for three cases. These cases 
will not be included in the assessment of results.  
3. 
Phase 3. Choice of cases. For the choice of cases, the guidelines set out in the protocol will be 
followed. If there are any doubts, the main coordinator of the study will provide a contact 
telephone number and e-mail. 
4. 
Phase 4. Surgical intervention of patients.  
5. 
Phase 5. Analysis of the surgical specimen by pathological anatomy. For the pathological study 
of the cases, the guidelines set out in the protocol will be followed.  
6. 
Phase 6. Incorporation of results into the database. Database created especially online for this 
study. A specific workshop will be held to explain how the database works. If there is any doubt, 
the main coordinator of the study will provide a contact telephone number and email of the 
creator of the database as a reference. 
7. 
Phase 7. Analysis of results by the main coordinator of the study.  
8. 
Phase 8. Analysis of survival outcomes at 3 years. 

9. 
Phase 9. Analysis of 5-year survival outcomes.  
 
Ethical considerations 
The present study does not intend to change the current standards of quality surgery in colon cancer. 
The research seeks to give surgeons tools so that interventions can be performed with better 
oncological results that ultimately translate into greater survival.  On the other hand, data such as 
names or medical history that could be used to identify patients will not be included.  
Likewise, the therapeutic strategy to be used will be decided during the multidisciplinary colorectal 
oncology committee and ultimately based on the intraoperative findings. The radiologist will perform 
the report independently of the 3D reconstruction. The 3D reconstruction will be used by the surgeon 
to assess the surgical strategy. 
 
DISCUSION 
3D reconstruction could help colorectal surgeons plan the optimal surgical strategy in the LACC.  
Its diagnostic difficulty, its surgical challenge and the different therapeutic options make this type of 
tumour a challenge in the multidisciplinary oncology committees. 
According to some series with a high number of patients, the risk of major complications is 25% and 
mortality rate is 5% (3,5) In the study carried out in the single center series, no patient presented major 
complications or mortality at 30 days. In addition, minimally invasive surgery was performed in 70% of 
the cases compared to 25% observed in the literature (21).  
The decision of this approach must be correct, since conversion to laparotomy increases the risk of 
complications and R1 surgeries. In the current literature, the conversion rate is 10% for these tumors, 
while in the present series it was 0%.  
These excellent results in terms of morbidity and mortality have been achieved thanks to good 
preoperative planning. So far, this planning has been carried out based on the imaging test of 
oncological staging such as CT. However, some authors have already proposed the usefulness of 3D 
reconstruction models obtained from imaging tests as surgical tools to help plan the best approach 
method and the best surgical route.  
There are different types of 3D reconstruction, depending on the type of segmentation: manual, semi-
automatic and automatic.  
Some authors already doubt whether surgeries should be planned based on CT for LACC due to its 
poor diagnostic accuracy compared to infiltration of neighboring structures (35-50%) and highlight the 
need to incorporate new technologies. As has been published in previous pilot studies of rectal cancer, 
mathematical image processing algorithms could improve these diagnostic parameters (2,4,9,24–32). 
The decision of en bloc or partial resection of a structure neighboring the tumor due to suspected 
infiltration should be made before starting surgery, since if not, the risk of R1-R2 type resection 
increases. This fact will directly influence patient survival since disease-free survival at 5 years changes 
from 40% in patients classified as R1 to 75% in those classified as R0. The published percentage of R1 
resections in LACC is 11%, while in the present unicenter series it was 0%. A high positive predictive 
value will help to make the decision to resect neighboring structures.  

On the other hand, overstaging causes unnecessary resections that can decrease the patient's quality 
of life unnecessarily.  
LACC can present infiltration of multiple structures. Special mention must be made of the retroperitoneal 
fascia. Ascending and descending colon tumors are a challenge for radiologists, surgeons, and 
pathologists alike. If this structure is infiltrated, it should be considered as cT4b in the staging CT, 
however as pT3 in the pathological study if it does not perforate to and invade retroperitoneal structures. 
On the other hand, the surgeon must modify the proposed surgery in the complete mesocolic excision  
(CME) technique and use what is beginning to be defined as Extended-Mesocolic excision (EME) That 
is, incorporating the retroperitoneal fascia into the surgical specimen to achieve an infiltration-free 
retroperitoneal margin (33,34).  
Finally, the different therapeutic strategies proposed in the literature for LACC are based on correct 
preoperative staging. On one hand, as we have mentioned, the direct approach through surgery and 
obtaining R0 and subsequent chemotherapy is for the moment the treatment of choice. However, some 
authors have shown that in T4 tumors neoadjuvant chemotherapy could increase the possibility of 
obtaining R0 surgery and others defend the usefulness of intraoperative chemotherapy to reduce the 
risk of developing carcinomatosis. These last two therapeutic options have the same limitation, which 
is the 30% of patients classified as T4 in the CT scan who will be T3 in the pathology report and will 
therefore be overtreated. 
 
CONCLUSIONS 
If greater diagnostic accuracy is observed for this 3D-IPR with respect to infiltration of neighboring 
structures in locally advanced colon tumors: 
- 
The radiologist would have an objective tool to delimit the tumor extension. 
- 
The surgeon would have an objective tool to program the type of surgical intervention with the 
least probability of modifying it during the operative time. In addition, this 3D tool facilitates the 
preoperative visualization of the tumor location. 
- The preoperative simulation of different surgical routes to resect the tumour would allow the ideal 
one to be selected to do so in a minimally invasive way.  
- Mutilating surgeries could be avoided due to a false positive diagnosis of infiltration of neighboring 
structures.  
- An R0 surgery decreases the risk of oncological recurrence. This fact decreases the number of 
patients who require chemotherapy treatment for this reason, long-term follow-ups, number of 
face-to-face consultations and complementary tests.  
 
In this way, 3D reconstruction is a tool that could provide digital solutions for health and care, 
promoting the development and use of these innovative techniques to improve the quality of life of 
patients. For this reason, it is necessary to highlight the need to promote the development of these 
technologies taking into account interoperability, security, confidentiality and standardization 
systems, for the improvement of health care. 
 

 
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