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The handle http://hdl.handle.net/1887/48097 holds various files of this Leiden University dissertation.

Author: Schaafsma , B.E.

Title: Near-infrared image guidance in cancer surgery

Issue Date: 2017-04-19

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Part I: Clinical translation of image-guided surgery in sentinel lymph node mapping

Part II: Clinical translation of optical tumor imaging

Summary

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Chapter 1

Introduction:  e clinical use of near- infrared uorescence imaging for image- guided oncologic procedure or treatment evaluation

Adapted from

Journal of Surgical Oncology 2011;104:323-332

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INTRODUCTION

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Table I.

Imaging system Excitation source Working

distance Field of view White light illumination of

surgical eld

NIR-colour overlay

Fig. 1. Chemical and optical characteristics of ICG: A.

B.

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NIR FLUORESCENCE IMAGING

Clinically available NIR imaging systems

Indocyanine green

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SENTINEL LYMPH NODE MAPPING

Breast cancer

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Fig. 2. Near-infrared uorescence sentinel lymph node mapping:

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Skin cancer

Gastro-intestinal cancer

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Conclusions sentinel lymph node mapping

TUMOUR IMAGING

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Fig. 3. ICG uptake and retention in liver tumours:

Imaging of hepatobiliary cancer

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Marking tumours

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Other solid tumours

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CONCLUSION AND OUTLINE OF THE THESIS

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REFERENCES

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PART I

Clinical translation of image-guided

surgery in sentinel lymph node mapping

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Chapter 2

Near-infrared uorescence sentinel lymph node biopsy in vulvar cancer: a randomized comparison of lymphatic tracers

British Journal of Obstetrics and Gynaecology 2013;120:758-764

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ABSTRACT

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INTRODUCTION

MATERIALS AND METHODS

Tracer Preparation

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Clinical Trial

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Characteristic ICG:HSA (n = 12) ICG alone (n = 12) P

Table 1.

Power Calculation and Statistical Analysis

RESULTS

Characteristics of participants

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Fig 1. Patient enrollment

Fig 2. NIR Fluorescence-Based SLN Mapping.

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Sentinel lymph node detection

Comparison between treatment groups

COMMENT

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Characteristic Total (24 subjects)

ICG:HSA (12 subjects)

ICG alone (12 subjects)

P

Table 2.

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ACKNOWLEDGMENTS

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REFERENCES

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Chapter 3

Randomized comparison of near-infrared uorescence lymphatic tracers for sentinel lymph node mapping of cervical cancer

Gynecologic Oncology 2012;127:126-130

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ABSTRACT

Objective

Methods

Results

Conclusions

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INTRODUCTION

METHODS

Preparation of Indocyanine Green adsorbed to Human Serum Albumin

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Intraoperative Near-Infrared Imaging System (Mini-FLARE)

Clinical Trial

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Power Calculation and Statistical Analysis

RESULTS

Patient characteristics

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Table 1.

Characteristic ICG:HSA

(N = 9)

ICG alone (N = 9)

P

NIR Fluorescence Imaging

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Table 2.

Characteristic Total

(18 subjects)

ICG:HSA (9 subjects)

ICG alone (9 subjects)

P

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Fig 1. NIR Fluorescence-Based SLN Mapping using ICG:HSA and Mini-FLARE:

Comparison between treatment groups

DISCUSSION

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ACKNOWLEDGMENTS

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REFERENCES

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Chapter 4

Clinical trial of combined radio- and

uorescence-guided sentinel lymph node biopsy in breast cancer

British Journal of Surgery 2013;100:1037-1044

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ABSTRACT

Background

Methods

Results

Conclusion

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INTRODUCTION

METHODS

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Tracer preparation

Study design

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Statistical analysis

RESULTS

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Fig. 1. Patient enrolment.

Fig. 2. Near-infrared (NIR) uorescence imaging during sentinel lymph node (SLN) mapping in breast cancer.

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Sentinel lymph node detection Table 1.

Characteristic Low-dose group

(16 patients)

High-dose group (16 patients)

P

N N

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Characteristic Total (32 patients)

Low-dose (16 patients)

High-dose (16 patients)

P

N N N

Fig. 3. Intraoperative detection of lymphatic vessels using near-infrared (NIR) uorescence imaging.

Table 2.

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Comparison between treatment groups

Fig. 4. I

DISCUSSION

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ACKNOWLEDGMENTS

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REFERENCES

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Chapter 5

Ex vivo sentinel node mapping in colon cancer combining blue dye staining and

uorescence imaging

Journal of Surgical Research 2013;183:253-257

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ABSTRACT

Background

Materials and methods

Results

Conclusions

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INTRODUCTION

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MATERIALS AND METHODS

Preparation of lymphatic tracers

Intraoperative NIR imaging system (Mini-FLARE)

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Table 1.

Characteristic N %

Clinical trial

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Characteristic N %

Table 2.

Fig. Sentinel lymph node mapping using NIR uorescence and blue dye in colon cancer.

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RESULTS

DISCUSSION

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ACKNOWLEDGMENTS

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REFERENCES

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PART II

Clinical translation of optical tumor

imaging

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Chapter 6

Optical mammography using diff use optical spectroscopy for monitoring tumour response to neoadjuvant

chemotherapy in women with locally advanced breast cancer

Clinical Cancer Research 2014;21;577–584

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ABSTRACT

Purpose

Experimental Design

Results

Conclusions

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INTRODUCTION

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MATERIALS AND METHODS

Clinical trial

Fig. 1.

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MRI- and pathologic assessment of tumour response to neoadjuvant chemotherapy DCE-MRI response assessment.

Pathology.

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Diff use optical spectroscopy assessment of neoadjuvant chemotherapy

Characteristic All patients (N=22)

N

Responders (N=18) N

Non-responders (N=4) N

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Patient and tumour characteristics

Data and statistical analysis

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Fig. 2.

RESULTS

MRI and pathologic assessment of tumour response

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Fig. 3.

Comparison between responders and nonresponders Diff use optical spectroscopy.

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Dynamic contrast enhanced MRI.

DOS Measurements

Hb Baseline 1 Cycle 3 Cycles 6 Cycles

HbO2 Baseline 1 Cycle 3 Cycles 6 Cycles

MRI volume measurements

Baseline 3 Cycles 6 Cycles

Table 2

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Fig. 4.

Predictive power of diff use optical spectroscopy and MRI

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DISCUSSION

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ACKNOWLEDGMENTS

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REFERENCES

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Chapter 7

Near-infrared uorescence-guided resection of colorectal liver metastases

Cancer 2013;119:3411-3418

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ABSTRACT

Background

Methods

Results

Conclusions

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INTRODUCTION

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MATERIALS AND METHODS

Preparation and Administration of ICG IC

Clinical Trial

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Table 1.

Characteristic Median [Range] or (%)

Fluorescence Microscopy

Statistical Analysis

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RESULTS

Study Subjects

Fig. 1. Near-infrared (NIR) uorescence imaging of colorectal liver metastases is shown.

Table 2.

Modality Number of hepatic

metastases identi ed*(%)

Number of patients

Size of metastases (mm)

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Optimization of ICG Dose and Injection Timing (N=16 Patients)

Intraoperative Detection of Colorectal Liver Metastases (N=40 Patients)

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Fig.3.

Fig. 2. Methods of detection of colorectal liver metastases are shown.

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Ex Vivo Detection of Colorectal Liver Metastases

Immunohistochemistry and Fluorescence Microscopy

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DISCUSSION

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ACKNOWLEDGMENTS

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REFERENCES

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Chapter 8

Summary and Future perspectives

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(Chapter 1)

Part 1

Part 2

PART 1. Sentinel lymph node mapping

Chapter 2

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Chapter 3

Chapter 4

Chapter 5

PART 2. Tumour detection Chapter 6

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Chapter 7

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FUTURE PERSPECTIVES

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REFERENCES

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NEDERLANDSE SAMENVATTING

(Hoofdstuk 1)

Deel 1

Deel 2

DEEL 1. Schildwachtklierprocedure

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hoofdstuk 2 hoofdstuk 3

hoofdstuk 4

hoofdstuk 5

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DEEL 2. Tumor detectie Deel II hoofdstuk 6

Hoofdstuk 7

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Conclusie

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LIST OF PUBLICATIONS

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CURRICULUM VITAE

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DANKWOORD

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