Pilot Study of Robotic-Assisted Harvest of the Latissimus Dorsi Muscles
Phase: NA
Conditions: Other Reconstructive Surgery, Failure of Muscle Graft, Cancer, Complications, Surgical Procedure, Unspecified
Sponsor: M.D. Anderson Cancer Center

     
 
Pilot Study of Robotic-Assisted Harvest of the 
Latissimus Dorsi Muscles 
 
CLINICAL PROTOCOL:  Study ID Number: 2013-0232,  
Version 10 (2 May 2016) 
 
A Single-Center, Non-Randomized, Prospective Study of the da Vinci® surgical 
system in Latissimus Dorsi Muscle Harvest Procedures 
 
PRINCIPAL INVESTIGATOR: 
Jesse C. Selber, MD 
The University of Texas MD Anderson Cancer Center 
Julie Kyte Center for Reconstructive Surgery 
1400 Pressler, Unit 1488, Houston, TX 77030 
 
 

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TABLE OF CONTENTS 
 
1 
PROTOCOL SUMMARY ........................................................................................................................... 4 
2 
INTRODUCTION ........................................................................................................................................ 7 
3 
BACKGROUND ......................................................................................................................................... 8 
3.1 
WORLDWIDE CLINICAL USAGE OF THE DA VINCI® ROBOTIC SURGICAL SYSTEM ........................................ 8 
3.2 
LITERATURE REVIEW - LATISSIMUS DORSI MUSCLE HARVEST PROCEDURES ............................................ 8 
3.3        CONCLUSION ...................................................................................................................................... 11 
4 
PRIOR INVESTIGATIONS ...................................................................................................................... 11 
4.1        CADAVER EVALUATION ........................................................................................................................ 11 
4.2 
INITIAL CLINICAL EXPERIENCE .............................................................................................................. 12 
5 
INTENDED USE ...................................................................................................................................... 13 
6 
STUDY DEVICE ....................................................................................................................................... 13 
6.1 
DESCRIPTION ...................................................................................................................................... 13 
6.2 
DEVICE REQUIREMENTS ...................................................................................................................... 14 
7 
STUDY OBJECTIVES ............................................................................................................................. 14 
8 
STUDY ENDPOINTS ............................................................................................................................... 15 
8.1 
PRIMARY SAFETY ENDPOINT: ............................................................................................................... 15 
8.2 
PRIMARY EFFICACY ENDPOINT: ........................................................................................................... 15 
8.3 
SECONDARY ENDPOINTS: .................................................................................................................... 15 
9 
METHODS ............................................................................................................................................... 15 
9.1 
STUDY DESIGN ................................................................................................................................... 15 
9.2 
STUDY DURATION ............................................................................................................................... 16 
9.3 
NUMBER OF SUBJECTS ........................................................................................................................ 16 
9.4 
ELIGIBILITY CRITERIA .......................................................................................................................... 16 
9.5 
WITHDRAWAL OF SUBJECTS ................................................................................................................ 17 
9.6 
EVALUATION TESTS ............................................................................................................................. 17 
10 
RISK-BENEFIT ASSESSMENT .............................................................................................................. 18 
10.1 
RISKS ................................................................................................................................................. 18 
10.2 
BENEFITS ........................................................................................................................................... 19 
11 
STUDY PROCEDURES .......................................................................................................................... 19 
11.1 
SUBJECT SCREENING AND BASELINE EVALUATION (VISIT 1)................................................................... 19 
11.2 
TREATMENT (VISIT 2) .......................................................................................................................... 20 
11.3 
FOLLOW UP EVALUATIONS (VISITS 3-6) ................................................................................................ 20 
11.4 
SCHEDULE OF EVENTS ........................................................................................................................ 21 
12 
STATISTICAL ANALYSIS PLAN ............................................................................................................ 21 
12.1 
STUDY POWER AND SAMPLE SIZE ........................................................................................................ 23 
12.2 
PERFORMANCE ANALYSIS COHORTS .................................................................................................... 23 
12.3 
ENDPOINT ANALYSIS AND REPORTING OF RESULTS .............................................................................. 24 
13 
ADVERSE EVENT REPORTING ............................................................................................................ 24 
14 
GOOD CLINICAL PRACTICES (“GCP”)................................................................................................ 27 
14.1 
INSTITUTIONAL REVIEW BOARD (IRB) APPROVAL .................................................................................. 27 

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14.2 
INFORMED CONSENT ........................................................................................................................... 27 
14.3 
SUBJECT CONFIDENTIALITY ................................................................................................................. 27 
14.4. DATA COLLECTION .............................................................................................................................. 27 
14.5 
DATA MONITORING AND QUALITY CONTROL ......................................................................................... 28 
14.6 
RECORD RETENTION ........................................................................................................................... 29 
14.7  PROTOCOL MONITORING PLAN ............................................................................................................ 29 
15 
PROTOCOL DEVIATIONS ...................................................................................................................... 29 
16 
DEVICE ACCOUNTABILITY ................................................................................................................... 29 
17 
SPONSOR RESPONSIBILITIES ............................................................................................................. 29 
18 
INVESTIGATOR RESPONSIBILITIES .................................................................................................... 30 
19 
STUDY MONITORING............................................................................................................................. 30 
20 
COMPENSATION IN THE EVENT OF INJURY ..................................................................................... 30 
21 
REFERENCES ......................................................................................................................................... 31 
 
 
 
 
 
 
 
 
 
 

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1 
PROTOCOL SUMMARY  
 
Title:  
Pilot Study of Robotic-Assisted Harvest of the Latissimus 
Dorsi Muscles. 
Design: 
Single-Center, Non-Randomized, Prospective Study of the 
da Vinci® surgical system in Latissimus Dorsi Muscle Flap 
Harvest Procedures. 
 
Purpose: 
To evaluate the safety and feasibility of the da Vinci® 
surgical system in minimally invasive muscle flap harvest 
procedures.   
 
Enrollment and Sites: 
A maximum of 15 subjects requiring a muscle flap harvest 
for subsequent breast, scalp, upper extremity, or lower 
extremity reconstructive surgery will be enrolled at The 
University of Texas MD Anderson Cancer Center (MD 
Anderson) in Houston, Texas.     
 
Study Duration: 
 
 
 
Subject Follow up:  
Initial Enrollment:  Q1’15 
Last Enrollment:  Q2’17 
Last Follow up:  Q4’17 
 
0-2 weeks, 2-4 weeks, 1-3 months, and 3-6 months post-
procedure. 
 
Study Endpoints: 
 
Primary Safety Endpoint:   
The primary safety endpoint is muscle flap failure. 
 
Secondary Endpoints: 
1. Evaluation of donor site complications through 6 months 
post-procedure. 
 
2. If the flap is for external use, interval viability with a 
Doppler proximally and distally will be checked at 3 
months post-procedure. 
3. If the flap is for pedicled, internal use over an implant, no 
additional evaluation will be possible unless planned or 
unplanned reoperation exposes the muscle, at which 

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time a Doppler evaluation would be undertaken. 
4. Conversion rate (i.e., completion of the latissimus dorsi 
harvest procedure with the da Vinci® Robotic Surgical 
system without converting to an open procedure). 
5. The validated QuickDASH questionnaire to evaluate 
postoperative shoulder function as compared to 
preoperative QuickDASH shoulder function. 
6. Postoperative pain assessed by validated visual analog 
scale (VAS). 
7. Physical therapy assessment of range of motion and 
strength of the affected shoulder using the validated 
American Shoulder and Elbow Surgeons (ASES) 
assessment tool. 
8. Length of stay and analgesic use to be compared to 
historical controls of the open procedure. 
 
 
Study Inclusion 
Criteria: 
1. The subject must be equal to or greater than 18 years of 
age. 
2. The subject must be willing and able to provide informed 
consent. 
3. The subject is willing and able to comply with the study 
protocol.  
4. The subject is undergoing one of the following 
reconstructive procedures that requires latissimus dorsi 
muscle harvest:  
a. Post-mastectomy breast reconstruction procedure 
(either nipple or skin sparing) in which a female 
subject needs additional muscle coverage over an 
implant, but does not need additional skin (i.e., 
patient is a candidate for a pedicled latissimus 
dorsi muscle flap procedure); OR,  
b. Scalp reconstruction procedure in which the 
subject needs a free latissimus dorsi muscle flap 
for wound coverage; OR, 
c. Upper extremity reconstruction procedure in 
which the subject needs a free latissimus dorsi 
muscle flap for wound coverage; OR, 
d. Lower extremity reconstruction procedure in 
which the subject needs a free latissimus dorsi 

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muscle flap for wound coverage. 
5. The subject agrees to follow up examinations out to 6 
months post-procedure.   
 
Study Exclusion 
Criteria: 
1. The subject has a BMI > 35. 
2. The subject has a history of significant bleeding 
disorders.  
3. The subject is diabetic. 
4. The subject is known or suspected to be pregnant or 
lactating.  
5. The subject has a history of peripheral vascular 
disease.   
6. The subject is a current smoker (has smoked within 4 
weeks prior to surgery). 
7. The subject has had prior back or axillary surgeries 
which could compromise the blood supply of the flap. 
 
Study Monitor: 
The University of Texas MD Anderson Cancer Center, 
Monitoring Services – IND Office 
1515 Holcombe Blvd., Houston, TX  77030 
 
Principal Investigator:  Jesse C. Selber, MD 
Board Certified, Plastic and Reconstructive Surgery 
The University of Texas MD Anderson Cancer Center 
Julie Kyte Center for Reconstructive Surgery 
1400 Pressler, Unit 1488, Houston, TX 77030 
 
Data Analysis: 
The University of Texas MD Anderson Cancer Center 
Department of Plastic Surgery, Unit 1488 
Lei Feng, Principal Statistical Analyst, 
Jun Liu, Metrics Analyst 
1400 Pressler, Houston, TX  77030 
 
 
2 
INTRODUCTION 
The purpose of this clinical study is to evaluate the safety and feasibility of the da Vinci® 
surgical system used in minimally invasive muscle harvest of either a free or pedicled 

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latissimus dorsi muscle.  In this study, the harvested muscle will be used in breast, scalp, 
upper extremity or lower extremity reconstruction procedures as these are anticipated to 
be the highest volume use for these muscle flaps.  However, the procedure under study is 
for robotic-assisted muscle harvest only, not the subsequent manually performed surgical 
reconstruction.  Any type of reconstruction for which a free or pedicled latissimus dorsi flap 
is deemed to be medically necessary would benefit from this potentially less invasive 
harvest.  As such, the endpoints of the study are aimed at evaluating safety, donor site 
morbidity, and the integrity and viability of the harvested muscle prior to the reconstruction 
procedure.  The da Vinci® robotic surgical system is intended to assist in the accurate 
control of surgical endoscopic instruments.  The system is currently FDA cleared for a 
variety of urologic, gynecologic, cardiothoracic and transoral otolaryngologic procedures.  
However, the device has not been specifically evaluated for latissimus dorsi muscle flap 
harvest.  As such, the purpose of this study is to evaluate the safety and feasibility of the 
da Vinci® robotic surgical system for use in this specific procedure. 
 
This is a prospective, non-randomized, single-arm study that will be conducted at The 
University of Texas MD Anderson Cancer Center (MD Anderson) in Houston, Texas.  Up 
to 15 subjects requiring latissimus dorsi muscle harvest in conjunction with breast, scalp, 
upper extremity or lower extremity reconstructive procedures will be enrolled.  The primary 
safety objective of this study is to evaluate the muscle flap failure.  The efficacy endpoint is 
to assess flap viability at harvest via doppler and clinical examination.  Secondary efficacy 
endpoints include postoperative assessment through quantitative (QuickDASH 
questionnaire), pain assessment (VAS), and a Physical Therapy assessment of the 
patient's range of motion and strength of the shoulder from which the latissimus dorsi 
muscle was harvested.  All enrolled subjects will have four follow up visits (at 0-2 weeks, 2-
4 weeks, between 1-3 months, and between 3-6 months post-procedure.  The following 
section provides background information regarding current surgical methods for muscle 
flap harvest procedures. 
3 
BACKGROUND 
3.1 Worldwide Clinical Usage of the da Vinci® Robotic Surgical system 
The da Vinci® surgical system (s) is a robotic platform for minimally invasive surgery 
initially cleared by the U.S. Food and Drug Administration (FDA) for use in general 
laparoscopic surgery in 2000.  Since then, it has received numerous clearances for a 
variety of indications for use, including general surgery, urologic, gynaecologic, thoracic, 
cardiac, and pediatric surgery.  The da Vinci® robotic surgical system(s) has provided 
surgeons with the clinical and technical capabilities of traditional open surgery while 
enabling them to operate through small incisions.  Each tiny incision (approximately 1cm), 
or port, involves insertion of an instrument which may be independently controlled by a 

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robotic arm on the da Vinci® robotic surgical system’s patient-side cart.  Robotic-assisted 
surgery may provide benefits to the patient including, but not limited to, shorter hospital 
stays, reduced rates of complications and a quicker return to normal activities as 
compared to open surgery. 
 
From 2000 to present, over 800,000 robotic procedures facilitated by da Vinci® surgical 
system have been performed across a broad spectrum of surgical specialties around the 
world.  Over 40 510(k) s have been FDA cleared for various device modifications and new 
indications for use.  This commercial experience demonstrates the wide applicability of the 
system for use in common surgical tasks such as grasping, cutting, dissection, 
coagulation, etc.  No new types of surgical tasks, or new instrument types will be required 
for use of the system in latissimus dorsi flap harvest procedures. 
3.2 Literature Review - Latissimus Dorsi Muscle Harvest Procedures 
Plastic surgeons frequently transport vascularized muscle from one part of the body to 
another, either as a free flap, in the case of lower extremity or scalp coverage, or as a 
pedicled flap, in the case of breast reconstruction and chest wall reconstruction.  One of 
the most common muscle flaps employed to this end is the latissimus dorsi muscle flap.  
One problem with the harvest of this large muscle during an open surgical procedure is 
that the donor incision required to remove it from the orthotopic position is generally 
around 25 cm – 30 cm.  For reconstructing, when overlying skin is a necessary part of the 
intended reconstruction, the harvest incision doubles as the skin harvest site.  However, 
where only the muscle is required, the large skin incision is only for access and affords no 
benefit to the patient.  Such procedures leave an unnecessary, long, conspicuous scar on 
the patient’s back or flank. 
 
In an effort to reduce unnecessary donor site incisions and related morbidity, endoscopic 
techniques for latissimus dorsi muscle harvest have been developed to reduce the amount 
of scarring associated with open procedures.  Several authors have reported on these 
endoscopic techniques for free and pedicled flap harvesting1,5.  The endoscopic approach 
has been abandoned in many centers as a result of technical challenges posed by 
cumbersome instrumentation, and more sophisticated instrumentation has been deemed 
necessary to facilitate the endoscopic approach in the subcutaneous space7. 
 
The following two sections discuss the current literature on endoscopic harvest of 
latissimus dorsi flaps and the utility of pedicled and free latissimus dorsi (muscle only) 
flaps, respectively. 
 
Endoscopic Pedicled Latissimus Dorsi Flap for Breast Reconstruction 

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In 2007, Missana, et al reported on the results from a study of 52 patients who underwent 
latissimus dorsi endoscopic harvest for immediate breast reconstruction after a skin-
sparing mastectomy1.  The authors developed this technique to decrease the morbidity of 
the donor site.  The technique involves preparation of the site with lighted forceps, followed 
by endoscopic dissection after a neocavity is formed by insufflating CO2.  The mean 
surgical endoscopic time was 64 minutes and there was one procedure that converted to 
an open procedure.  Complications included:  2 hematomas, 6 inflammatory syndromes 
and 1 pulmonary embolism.  While 4 patients had skin flap necrosis during the 
reconstruction portion of the case, none of the patients had donor site necrosis 
complications during the latissimus dorsi flap harvest. The average length of hospital stay 
was 5.6 days.  The dorsal drain was removed 15 days post-procedure.  The authors 
concluded that endoscopic harvesting of the latissimus dorsi flap performed using the 
prescribed technique is feasible, reproducible and permits a significant reduction of 
incision size (2 cm as compared 20 cm with open surgery) and postoperative pain with 
good aesthetic results.  The authors noted that this procedure was not recommended for 
patients who are overweight or in patients who smoke because of the significant rate of 
necrosis in the anterior thoracic cutaneous flaps. 
 
In 2000, Ramakrishnan et al reported on 12 patients requesting breast reconstruction of a 
“high-risk” chest wall4.  Endoscopic latissimus dorsi muscle harvest was conducted to 
cover an expander placed within an endoscopically created chest wall pocket.  Of the 11 
patients who underwent an oncological procedure, 8 of these patients received radiation 
therapy and 5 received chemotherapy.  Additionally, 5 of these patients were smokers who 
smoked more than 10 cigarettes per day.  Five of the 12 operations were performed 
through single-port access and the remaining 7 were performed with the addition of a bra 
strap port.  Based on this case series, the authors advocated the use of two ports for 
operational ease and efficiency.  The best muscle harvest time achieved was 60 minutes.  
Five of the 12 patients received blood transfusions; in all of these patients, the procedure 
had been initially attempted through a single port.  While the authors noted acceptable 
results with their endoscopic technique, they concluded that improved instrumentation 
concerning the creation and maintenance of optical space would need to be developed 
before this technique was widely adopted. 
 
In 2004, Losken, et al reported on their experience with endoscopic-assisted harvest of 
latissimus dorsi muscles for reconstructing partial mastectomy defects2.  The authors 
sought to evaluate the risks and benefits associated with immediate versus delayed 
muscle flap transfers.  Thirty-nine cancer patients with an average follow up of 3.67 years 
were included in this review.  Donor site complications occurred in 12 patients and 
included:  seromas (7), hypertrophic scarring (1), skin loss (1) and wound dehiscence (1).  
One patient experienced postoperative lymphedema and another had a persistent sinus 

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tract requiring excision with pectoralis muscle flap reconstruction.  To reduce the risk of 
cancer recurrence following mastectomy procedures, the authors recommended 
confirmation of negative margins prior to latissimus dorsi muscle transfer. 
 
In 1998, Masuoka, et al reported on 7 patients who underwent breast reconstruction 
surgery with the latissimus dorsi muscle flap combined with a saline implant using an 
endoscopic approach for muscle harvest6.  The authors employed the use of a modified 
endoscopic technique performed through a larger incision due to former surgery.  This 
approach proved easier than standard endoscopy because the procedures were 
performed under direct visualization.  As such, this methodology maximized acquisition of 
optical space, a limitation of subcutaneous endoscopic surgery.  The authors concluded 
that harvesting a latissimus dorsi muscle flap using an endoscope was a useful method to 
avoid additional scarring. 
 
Free Latissimus Dorsi Flap Literature 
In a 1990 review conducted by Furnas, 18 patients underwent scalp reconstructions of 
complicated scalp wounds with 21 free flaps: 11 from the latissimus dorsi, 3 scalp transfers 
between identical twins, 3 groin, 1 combined latissimus dorsi and serratus anterior, 2 
serratus anterior, and 1 omentum3.   All of the flaps survived with follow up ranging from 3 
weeks to 7 years.  The latissimus dorsi was shown to be their first choice for free flap 
reconstruction of scalp wounds because of its large size, predictable blood supply, ease of 
harvesting, and provision of excellent vascularity to compromised beds. 
 
Many other additional studies since then have confirmed the popular use of the latissimus 
dorsi free flap for scalp reconstruction.  The complication rate is low and cosmesis was 
satisfactory10. 
 
In 1997, Cho, et al reported on 10 patients with lower extremity reconstructive procedures 
which utilized free latissimus dorsi muscle flaps7.  Muscle harvest was accomplished 
endoscopically with a 5-6 cm incision.  The largest harvested muscle was 15 x 25 cm.  An 
average time of 2-3 hours was required for muscle flap harvest.  No donor site 
complications such as hematomas or seromas were observed.  The patients were satisfied 
with the short donor site scars and reported decreased postoperative pain.  The authors 
concluded that endoscopic harvesting techniques had several limitations.  Specifically, 
they opined that the key to successful endoscopic free flap transfer is operative dexterity, 
experience and access to proper instrumentation.  They also emphasized the need for 
good visualization and proper hemostasis to avoid complications. 

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3.3 Conclusion 
Endoscopic approaches for either a pedicled or free latissimus dorsi muscle flap harvest 
have been successfully employed.  However, there are a variety of problems with the 
endoscopic approach7.  One problem is that the optical window is very tight, preventing 
visualization of the appropriate anatomic structures that allow for safe harvest.  
Instrumentation presents a second issue; endoscopic instruments are long and unwieldy, 
making precise dissection and hemostatic management challenging, particularly in the 
context of difficult retraction and poor visualization.  These impediments have impaired 
widespread adoption of minimally invasive techniques for muscle harvest procedures. 
 
In this study, we hypothesize that the da Vinci® robotic surgical system may offer distinct 
advantages for enabling surgical harvest of the latissimus dorsi flap through small 
incisions.  The advantages of the robotic platform are precision and visualization which are 
anticipated to address many of the reported issues such as bleeding and flap necrosis by 
allowing the surgeon to better monitor and control their surgical technique.  By creating an 
optical window with the use of insufflation, camera and instruments can be comfortably 
positioned within tight spaces to operate using very precise movements.  Because 
incisions are limited to three ports, the largest of which is 1.2 cm, this technology is well 
suited to minimally invasive muscle harvest, and solves some of the challenges that 
endoscopic flap harvest presents. 
 
In summary, a variety of endoscopic surgical techniques have been proposed over the 
past 15 years to harvest latissimus dorsi muscle flaps but none have achieved widespread 
adoption despite a strong patient benefit.  It is hoped that robotic-assisted latissimus dorsi 
flap procedures will help overcome some of the limitations inherent in the current 
endoscopic approaches.  This study seeks to evaluate the safety and feasibility of this 
robotic-assisted approach and will evaluate donor site complications and flap survival in 
patients requiring latissimus dorsi muscle harvest for subsequent breast, scalp, upper 
extremity, and lower extremity reconstructive procedures. 
4 
PRIOR INVESTIGATIONS 
Robotic-assisted latissimus dorsi muscle flap harvests have been completed using the da 
Vinci® robotic surgical system in 10 cadavers and 15 clinical patients.  All procedures 
were completed by the Principal Investigator for this proposed study.  A summary of the 
procedures completed by Jesse Selber, MD, is provided below. 
4.1 Cadaver Evaluation 
Ten robotic latissimus dorsi muscle harvests were performed in 10 cadavers from 2009 to 
20108.  All dissections were performed by the study’s principal investigator, Jesse Selber, 

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MD, using the da Vinci® robotic surgical system.  All 10 latissimus dorsi muscles were 
harvested successfully in their entirety.  The goal of these cadaveric studies was to 
develop and refine the port placement, workflow and operative technique.  Dr. Selber 
concluded that the robotic-assisted endoscopic harvest technique was both feasible and 
reproducible. 
4.2 Initial Clinical Experience 
Following the cadaveric studies of 7 cases9, 15 patients underwent robotic-assisted 
harvest of the latissimus dorsi muscle at MD Anderson.  The harvested muscles were used 
as free flaps for scalp reconstruction in 3 patients and as pedicled flaps for breast 
reconstruction in 12 patients.  The procedures were completed using a total of 3 ports.  
The latissimus dorsi muscles were fully dissected with robotic instruments along the 
superficial and deep surfaces of the muscle with good hemostatic control and then 
disinserted along the inferior and posterior borders for delivery into the axilla.  At this 
stage, the axillary incision was then re-opened and the muscle delivered through the short 
incision.  The robot was then undocked.  An endoscope was introduced to confirm 
adequate hemostasis and drains were positioned in the donor site, brought out of the port 
sites, and sutured into place.  The reconstructive portion of the procedure then 
commenced manually. 
 
Fifteen muscle flaps were harvested in 15 patients without converting to an open 
procedure.  Both free flaps were successfully transferred.  All pedicled flaps resulted in 
successful breast reconstructions.  Robotic harvest times averaged 1 hour and 51 minutes.  
Flap harvest complications included a single instance of transient and partial contralateral 
radial nerve palsy resulting from inadequate axillary support in the context of lateral 
decubitus positioning.  This patient had full recovery within 2 weeks.  All patients reported 
moderate back/flank discomfort during hospitalization and minimal to no discomfort during 
the first follow up visit at 1 week post discharge.  One patient required occupational 
therapy of 2 weeks duration postoperatively.  There were no donor site hematomas or 
seromas.  There were no reports of injuries to the overlying skin, and there are no records 
of any skin injuries or delayed wound healing in clinic notes. 
 
Dr. Selber concluded that the robotic-assisted technique offered technical advantages over 
endoscopic harvest and cosmetic advantages over the open technique.  Additionally, this 
case series demonstrated that robotic-assisted harvest is useful for both pedicled and free 
flap reconstructive procedures. 

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5 
INTENDED USE 
The da Vinci® robotic surgical system is intended to assist in the accurate control of 
Intuitive Surgical endoscopic instruments during latissimus dorsi muscle flap harvest 
procedures in patients scheduled to undergo subsequent reconstruction procedures which 
require a muscle only flap (free or pedicled).  In this study the free flaps will be used for 
scalp, upper extremity, and lower extremity reconstruction and pedicled flaps will be used 
for breast reconstruction.  The da Vinci® robotic surgical system is intended for use by 
trained physicians in an operating room environment in accordance with the system User 
Manual (Appendix I) and this clinical protocol. 
6 
STUDY DEVICE 
6.1 Description 
The da Vinci® robotic surgical system is a computer assisted device designed to facilitate 
complex surgery using a minimally invasive approach.  The system consists of the 
following 3 main components: 1) Surgeon Console; 2) Patient Cart; and, 3) Vision System 
Cart.  These components are described below and depicted in Figure 1. 
 
Surgeon Console:  is the control center for the system.  While seated at the surgeon 
console (outside of the sterile field) and as observed through the console’s stereo viewer, 
the surgeon controls critical aspects of the surgical procedures, including movement of the 
endoscopic instruments and endoscope within the operative field.  Instrument and camera 
movements are controlled by the surgeon through the use of 2 hand operated controllers 
residing in the console and foot pedals at the console's base.  These features allow the 
surgeon to be as dexterous as in “open” surgery, while operating in a minimally invasive 
environment.  The surgeon at the console also has the option to change the surgical view 
from full screen mode to a multi-image mode, which displays the 3-dimentional (3-D) 
image of the operative field. 
 
Patient-Side Cart:  is the operative component of the surgical system within the sterile 
field.  Its primary function is to support the EndoWrist® instrument arms and camera arm 
during surgical procedures.  EndoWrist instruments are designed to provide surgeons with 
natural dexterity and a greater range of motion than the human hand.  This allows for 
greater precision when operating in a minimally invasive environment.  EndoWrist 
instruments are designed to support rapid and precise suturing, dissection and tissue 
manipulation in surgical procedures. 
 
Vision System Cart:  houses the system’s imaging processing equipment and is operated 
by a person outside of the sterile field during surgery.  The cart provides space for an 

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optional touch screen monitor as well as ancillary surgical equipment.  The cart consists of 
a stereo endoscope, endoscopic camera and various accessories including a light source 
and light guides.  The Insite Vision System provides 2 independent images that are 
relayed to the viewer located in the surgeon console, where they are used to form a 3D 
image (or alternatively 2D) of the surgical field for the surgeon’s reference. 
 
Figure 1:  Overview of the da Vinci® System (Console, Patient-side Cart and Vision System) 
 
6.2 
Device Requirements 
The da Vinci® robotic surgical system is available commercially for a variety of cleared 
indications.  MD Anderson currently has the da Vinci® Si system at their facility in use for 
transoral robotic surgery (TORS), prostatectomy, hysterectomy, thoracic procedures, and 
general surgeries.  The existing da Vinci® Si system will be used in conjunction with 
standard commercially available da Vinci® instruments including: monopolar curved 
scissors, Maryland with bipolar, Cadiere grasping forceps, and 3D endoscopes. 
7 
STUDY OBJECTIVES 
The objective of this study is to evaluate the safety and feasibility of the da Vinci® robotic 
surgical system in 15 subjects undergoing latissimus dorsi muscle flap harvest procedures 
in conjunction with breast, scalp, upper extremity, and lower extremity reconstruction 
procedures.  Donor site complications and flap viability will be assessed intraoperatively 
and through 6 months post-procedure, and length of stay and analgesic use as an 
inpatient will be compared to historical controls of the open approach. 

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8 
STUDY ENDPOINTS 
8.1  Primary Safety Endpoint: 
The primary safety endpoint is muscle flap failure. 
8.2  Primary Efficacy Endpoint: 
Latissimus dorsi muscle flap viability evaluated by clinical assessment and doppler 
examination at the end of the muscle harvest portion of the surgical procedure. 
8.3  Secondary Endpoints: 
1. Evaluation of donor site complications through 6 months post-procedure. 
2. If the flap is for external use, interval viability with a Doppler proximally and distally will 
be checked at 3 months post-procedure. 
3. If the flap is for pedicled, internal use over an implant, no additional evaluation will be 
possible unless planned or unplanned reoperation exposes the muscle, at which time a 
Doppler evaluation would be undertaken. 
4. Conversion rate (i.e., completion of the latissimus dorsi harvest procedure with the da 
Vinci® Robotic Surgical system without converting to an open procedure). 
5. The validated QuickDASH questionnaire to evaluate postoperative shoulder function as 
compared to preoperative QuickDASH shoulder function. 
6. Postoperative pain assessed by validated visual analog scale (VAS). 
7. Physical therapy assessment of range of motion and strength of the affected shoulder 
using the validated American Shoulder and Elbow Surgeons (ASES) assessment tool. 
8. Length of stay and analgesic use to be compared to historical controls of the open 
procedure. 
9 
METHODS 
9.1  Study Design 
This is a prospective, non-randomized, single-arm study of the da Vinci® robotic surgical 
system in subjects undergoing latissimus dorsi muscle flap harvest procedures in 
conjunction with breast, scalp, upper extremity and lower extremity reconstructive 
procedures.  This study will be conducted at MD Anderson in Houston, Texas.  Muscle flap 
failure and donor site complications will be assessed through 6 months post-procedure.   
Flap viability will be assessed following completion of the robotic-assisted harvest 
procedure.  Flap viability is defined as having a pink, non-congested appearance and an 
audible arterial and venous Doppler signal.  Additional assessments of viability will include 
bleeding at the distal extremes of the muscle when cut sharply, and an audible Doppler 
signal detected in the distal third of the muscle. 

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9.2  Study Duration 
This study is expected to commence in the first quarter of 2015.  Enrollment of all subjects 
is expected to be completed in the second quarter of 2017.  Six month clinical follow up is 
expected to be completed within the fourth quarter of 2017. 
9.3  Number of Subjects 
Fifteen subjects ≥ 18 years of age, meeting all inclusion and exclusion criteria will be 
enrolled.  Subjects will undergo robotic-assisted latissimus dorsi muscle harvest in 
conjunction with a standard surgical breast, scalp, upper extremity, or lower extremity 
reconstructive procedure requiring free or pedicled flaps. 
9.4  Eligibility Criteria 
9.4.1  Inclusion Criteria 
Subjects must meet all of the following criteria to be eligible for enrollment in this trial: 
 
1) The subject must be equal to or greater than 18 years of age. 
2) The subject must be willing and able to provide informed consent. 
3) The subject is willing and able to comply with the study protocol.  
4) The subject is undergoing one of the following reconstructive procedures that 
requires latissimus dorsi muscle harvest: 
a. Post-mastectomy breast reconstruction procedure (either nipple or skin 
sparing) in which a female subject needs additional muscle coverage over an 
implant, but does not need additional skin (i.e., patient is a candidate for a 
pedicled latissimus dorsi muscle flap procedure); 
b. Scalp reconstruction procedure in which the subject needs a free latissimus 
dorsi muscle flap for wound coverage; 
c. Upper extremity reconstruction in which the subject needs a free latissimus 
dorsi muscle flap for wound coverage; or, 
d. Lower extremity reconstruction in which the subject needs a free latissimus 
dorsi muscle flap for wound coverage. 
5) The subject agrees to follow up examinations out to 6 months post-treatment. 
9.4.2  Exclusion Criteria 
Subjects will be excluded from this trial if any of the following criteria are met: 
 
1) The subject has a BMI > 35. 
2) The subject has a history of significant bleeding disorders. 
3) The subject is diabetic. 

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4) The subject is known or suspected to be pregnant or lactating. 
5) The subject has a history of peripheral vascular disease. 
6) The subject is a current smoker (has smoked within 4 weeks prior to surgery). 
7) The subject has had prior back or axillary surgeries which could compromise the 
blood supply of the flap. 
9.5  Withdrawal of Subjects 
Subjects may voluntarily withdraw their participation from the study at any time.  
Investigators may withdraw a subject from the study as deemed appropriate per safety 
measures and/or if the subject’s medical condition contraindicates further study 
participation.  All subjects withdrawn from the study will undergo a final study visit 
consisting of a safety evaluation. 
9.6  Evaluation Tests 
The disabilities of the arm, shoulder and hand (QuickDASH) questionnaire is a self-
administered outcome instrument developed as a measure of self-rated upper extremity 
disabilities and symptoms (Appendix E). The QuickDASH consists of 11 items scored 0 
(no difficulty) to 5 (unable/extreme) with 8 optional occupational questions.  It has been 
validated for longitudinal construct and been rated effective as a post-surgery 
measurement tool. 11 
 
The validity of VAS has been well studied for eliciting reproducible pain 
assessments12,13,14.  In pain research VAS are considered 'the gold standard' for pain 
assessments. Subjects report their level of pain through the scale.  A copy of the VAS is 
located in Appendix F. 
 
The functional evaluation of the shoulder uses the American Shoulder and Elbow 
Surgeons (ASES) method which is a standardized form for shoulder assessment17.  The 
physical therapy assessment section includes range of motion and strength.  While a 
comparison is regularly made between the operated versus non-operated shoulder, for this 
study, the subject will have an initial baseline test done preoperatively to compare with the 
postoperative evaluation.  The measurement of active and passive range of motion and 
the manual muscle-testing will be performed on all subjects by a member of the Physical 
Therapy staff.  Shoulder mobility is expressed in degrees with abduction, adduction, intra-
rotation and extra-rotation measured both actively and passively. A sample of the range of 
motion and strength forms are located in Appendix G. 

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10  RISK-BENEFIT ASSESSMENT 
10.1  Risks 
As part of the robotic-assisted muscle harvest procedure the thoracodorsal nerve may 
sometimes be intentionally sacrificed resulting in a known risk of impaired range of motion 
(internal rotation and abduction of the arm <90 degrees).  Pneumothorax from 
unintentional entrance into the pleural space is also a potential risk but very rarely occurs 
in either open or endoscopic muscle harvest1,5,16.  Clinically detectable postoperative 
pneumothorax will be managed in consultation with the thoracic surgery service.  
Management will include chest tube placement and monitoring with serial upright and 
lateral chest x-rays.  Pneumothorax has not been present in the over 30 clinical cases thus 
far.  In order to detect unintended pneumothorax, the muscle donor site cavity will be 
subjected to positive pressure ventilation by the anesthesiologist to insure that no small 
pneumothorax has occurred.  In the event of a pneumothorax detected intraoperatively, 
the anesthesiologist will be made aware immediately and an intraoperative consult to a 
thoracic surgeon will immediately result.  If a chest tube or catheter is deemed necessary, 
it will be placed at that time under direct vision by a board certified thoracic surgeon. 
 
In addition, there are other standard risks associated with any latissimus dorsi harvest 
procedure independent of the method of harvest.  These include: 1) postoperative pain; 2) 
bleeding which may require transfusion; 3) infection at the donor or transfer site; 4) 
numbness or tingling; 5) thrombosis of the pedicle; 6) scarring, wound dehiscence, or 
delayed wound healing at the incision site; 7) partial or total flap necrosis or loss; 8) 
pulmonary embolism; 9) inflammatory syndrome; and, 10) swelling, seroma or hematoma 
at the donor site.  These will all be managed according to standard hospital procedures. 
 
Potential risks that are unique to endoscopic harvest include subcutaneous emphysema as 
a result of insufflation, and bleeding which cannot be managed endoscopically.  
Subcutaneous emphysema with CO2 requires no additional postoperative management as 
it resolves quickly and is not in a position to impinge on the airway18,15.  Bleeding that 
cannot be managed endoscopically may be controlled with direct external pressure and 
conversion to open techniques, when necessary.  This has not occurred in any of the 
robotic harvests to date, and it is believed that hemostasis will be easier to maintain and 
regain with robotic instruments than with standard endoscopic techniques. 
 
Additional risks presented by use of the da Vinci® robotic surgical system other than those 
listed above include the possibility of a device malfunction which may require a conversion 
to an open procedure.  If the system is unavailable for use or other clinical factors 
proscribe system use, the physician may convert to a standard open surgical procedure.  

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There are also small additional risks associated with the patient being under anesthesia for 
a longer period of time which will be required given the slightly longer length of time 
expected for robotic-assisted procedures when compared with open techniques.  However, 
early clinical work has already shown lower operative times with the da Vinci® robotic 
surgical system than previously reported endoscopic harvests. 
 
The above referenced risks will be mitigated in two ways.  First, Dr. Selber and Dr. 
Clemens, both experienced plastic and reconstructive surgeons, who have been 
extensively trained on the da Vinci® robotic surgical system, will be the only two surgeons 
performing procedures under this study protocol.   
10.2  Benefits 
There is no proven benefit related to use of the da Vinci® robotic surgical system for 
latissimus dorsi muscle harvest surgical procedures.  It is hoped that the investigational 
device will permit a simpler, minimally invasive harvest technique with smaller incisions, 
decreased postoperative time and a quicker return to normal activities.  However, the 
device has not yet been studied to demonstrate its utility in this regard.  Subjects may 
benefit from the additional clinical monitoring and follow up evaluations required by this 
study protocol. 
11 STUDY PROCEDURES 
11.1  Subject Screening and Baseline Evaluation (Visit 1) 
Subjects will be recruited for this study from MD Anderson.  All subjects requiring 
latissimus dorsi muscle harvest procedures in conjunction with breast, scalp, upper 
extremity, or lower extremity reconstruction procedures will be screened for eligibility.  The 
Investigator or a member of the research team will review the subject’s medical history for 
eligibility and inclusion into the study.  If all inclusion criteria are met and no exclusion 
criteria are present, the Investigator will inform the subject about the purpose of the study 
and will obtain written informed consent.  The background of the proposed study along 
with the benefits and risks will be explained to the subject and questions will be answered.  
The subject must sign an informed consent that has been approved by the MD Anderson 
Institutional Review Board (IRB).  Failure to provide informed consent renders the subject 
ineligible for the study. 
 
The Investigator or a member of the research team will record the subjects’ medical history 
and demographic information on a case report form tool.  Protocol specific data and 
adverse events will be entered into the MD Anderson REDCap™ database.  The first 
assessment of adverse events will take place in the operating suite at the time of surgery 

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and will continue for 6 months following surgery.  The medical history will include 
information about previous treatments to further ensure compliance with the inclusion and 
exclusion parameters.  The Investigator will conduct a medical history review and a 
physical exam.  A pre-anesthesia appointment will also be coordinated.  The Investigator 
or a member of the research team and subject will also complete a QuickDASH 
questionnaire.  The subject will also undergo a physical therapy assessment to test the 
range of motion and strength of the shoulder to be used as a baseline postoperatively.  As 
standard of care for patients undergoing these procedures, a pregnancy test will be 
ordered by the Anesthesia Department for appropriate female patients.  This visit may be 
completed within 30 days prior to treatment/surgery. 
11.2  Treatment (Visit 2) 
The subject will be taken to the operating room for surgery under general anesthesia with 
no muscle paralysis. The robotic-assisted latissimus dorsi harvest procedure will be 
performed as described in the protocol and will be videoed and/or photographed.  
Medications used, port placements, procedural details, adverse events and device details 
will be documented on the CRFs (Appendix H).  Muscle flap viability will be assessed by 
clinical examination and doppler assessment prior to the reconstruction procedure.  Such 
assessments will be documented in the CRFs (Appendix H) prior to the standard surgical 
breast, scalp, upper extremity, or lower extremity reconstruction procedure. 
11.3 Follow Up Evaluations (Visits 3-6) 
Patients will be seen in the office for a visit within 0-2 weeks and then within 2-4 weeks 
after the surgical procedure.  The next visit will be between 1-3 months after the 
procedure. The final visit will be between 3-6 months after the procedure.  At these 
postoperative visits, incisions and drain sites will be checked and donor sites will be 
evaluated for adverse events.  Additionally, pain assessments, the QuickDASH 
questionnaires, and the range of motion and strength tests will be administered.  Drains 
will be removed as appropriate at approximately 2 to 3 weeks after the procedure. 
11.4  Schedule of Events 
The protocol does not require any clinic visits other than those that are standard of care for 
patients undergoing robotic-assisted harvest of the latissimus dorsi muscles. 
 
Study Events 
Screening 
& Baseline 
Evaluation 
(Visit 1)1 
Procedure / 
Treatment 
(Visit 2) 
Post Op 
Follow Up 
(Visits 3-6)2,3 
Eligibility Screening 
X 
  
  
Secure Informed Consent 
X 
  
  
Medical History and Physical Exam (to include BMI) 
X 
  
  

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Pre-Anesthesia Appointment (to include Urine 
Pregnancy Test - if appropriate per Anesthesia) 
X 
  
  
Baseline QuickDASH Questionnaire 
X 
  
  
Baseline Physical Therapy Assessment (to include 
testing range of motion and strength of the shoulder) 
X 
  
  
Robotic-Assisted Latissimus Dorsi Flap Harvest 
Procedure & Non-robotic Reconstruction Procedure 
  
X 
  
Flap Viability Assessment via Clinical and Doppler 
Examinations 
  
X 
  
Adverse Event Assessment 
  
X 
X 
Postoperative QuickDASH Questionnaire 
  
  
X 
Postoperative Physical Therapy Assessment (to include 
testing of range of motion and strength of the shoulder) 
  
  
X 
Patient Questionnaire of Pain via VAS 
  
  
X 
Drains Removed 
  
  
X 
1 Occurs within 30 days prior to surgery. 
2 Visit 3 (occurs between 0-2 weeks), Visit 4 (occurs between 2-4 weeks), Visit 5 (occurs between 1-
3 months) 
3 Final Visit (occurs between 3-6 months) 
 
 
12 STATISTICAL ANALYSIS PLAN 
This is a prospective, non-randomized, single-arm study designed to assess the safety and 
feasibility of the da Vinci® robotic surgical system in latissimus dorsi muscle flap harvest 
procedures.  A maximum of 15 subjects requiring latissimus dorsi flap harvest procedures 
in conjunction with breast, scalp, upper extremity, or lower extremity reconstruction 
procedures will be enrolled at MD Anderson in Houston, Texas. 
 
The muscle flap failure will be monitored using the Bayesian stopping boundaries 
calculated based on beta-binomial distribution. We will consider that the da Vinci® robotic 
surgical system is promising in latissimus dorsi flap harvest if the muscle flap failure rate is 
below 10%.  With a sample size of 15 patients, the probability of observing at least one 
muscle flap failure is 79.4%.  The prior probability of muscle flap failure is modeled by beta 
distribution (Beta (0.1, 0.9)). Denoting the probability of muscle flap failure by θ, and it is 
compared to fixed target of 10%. The following decision criterion will be applied: Stop if 
Prob{ θ > 0.10 | data} > 0.75. 
 
Patients will be monitored by a cohort size of 5 according to the following stopping 
boundaries for muscle flap failure.  The patient enrollment will be halted for this safety 
monitoring because the status of muscle flap failure can be obtained right after surgery. 

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Number of patients evaluated 
Stop if >= muscle flap failure observed 
5 
2-5 
10 
2-10 
15 
Always stop with this many patients 
 
The operating characteristics are summarized in the following table (based on simulations 
from 10,000 trials). 
 
True DLT Rate 
Prob (stop the trial early) 
0 
0 
0.05 
0.0861 
0.10 
0.2639 
0.15 
0.4557 
0.20 
0.6242 
0.25 
0.7560 
0.30 
0.8507 
 
The above stopping boundaries and operating characteristics are calculated using 
MultcLean (v.2.1.0) design software downloaded from 
http://biostatistics.mdanderson.org/SoftwareDownload. 
 
The muscle flap failure rate and its 95% confidence interval (CI) will be calculated using 
the exact method.  Other outcome data to be collected will include:  pain assessment using 
a validated VAS, QuickDASH score, and physical therapy assessment. 
 
Patient information including age, gender, body mass index (BMI), medical history, history 
of radiation, history of smoking, defect characteristics (such as "partial breast, scalp, upper 
extremity, or lower extremity"), donor site morbidity, and functional deficits will be 
summarized.  The rate of donor site morbidity and their 95% confidence interval will be 
reported. 
 
Operative Variables:  Length of surgery, type of defect, size of defect, type of 
reconstruction, length of incision used, length of robotic portion of the procedure, robotic 
instrumentation used, port placement.  This information will be documented by the OR staff 
during surgery, and collected by the research team after surgery on standardized CRFs. 
 
Outcome Variables:  Length of stay, pain medication requirements, postoperative 
complications (such as seroma, wound dehiscence, delayed wound healing, or flap loss), 
length of time drains are required in donor site, and postoperative return to normal 
function, as well as, any residual functional deficits, defined as a subjective decrease in 
strength, range of motion or restriction in activities of daily living will be assessed at 

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between week 0-2, and between week 2-4 after the procedure.  The subject will then have 
an evaluation at 3 months after the procedure.  The subject’s last follow up visit will occur 6 
months post-procedure. 
 
The safety of the robotic-assisted latissimus dorsi procedure will also be evaluated based 
on adverse events related to the donor site through 6 months post-procedure.  Acute 
complications include but are not limited to:  seroma; hematoma; overlying skin damage; 
and, injury to the muscle or vascular pedicle.  All adverse events will be further categorized 
and documented according to section 13 of this clinical protocol. 
 
The feasibility of the procedure will be evaluated based on the number of successfully 
completed robotic-assisted latissimus dorsi harvest procedures among the total attempted 
procedures.  Any procedure that is abandoned or converted to an open surgical or 
endoscopic technique after being initiated with the da Vinci® robotic surgical system will 
be considered a failed da Vinci® procedure.  The rate of successfully completed harvest 
procedure will be calculated along with its 95% CI. 
 
The efficacy of the procedure will be determined based on the rate of subjects who 
demonstrate a viable flap assessed by clinical and doppler examinations at the end of the 
harvest procedure.  It is recognized that the overall success of the surgery from the 
patient's and surgeon’s perspectives includes the success of the harvest and 
reconstruction procedures.  However, the objective of this investigational protocol is to 
evaluate the robotic-assisted muscle harvest technique only.  As such, flap viability prior to 
reconstruction is the most relevant outcome for this study.  Additional secondary 
assessments will include:  long term survival of the flap and flap necrosis at the 
postoperative visits.  These assessments will not be employed to adjudicate the primary 
efficacy endpoint. 
12.1  Study Power and Sample Size 
The specific sample size for this investigation is not based on the testing of a specific 
hypothesis with a degree of power to detect a difference.  As such, a maximum of 15 
subjects will be enrolled in the study with the intent of establishing baseline outcomes for 
this procedure. 
12.2  Performance Analysis Cohorts 
12.2.1  Intent to Treat Analysis 
All subjects who enroll in the study and are treated with the da Vinci® robotic surgical 
system will be included in the Intent-to-Treat analysis.  Subjects who terminate prior to 
completing the study will have their score set to their last available value for the visits after 

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they terminated from the study with missing data.  No other special data handling 
algorithms will be used for imputing missing data. 
12.2.2  Per Protocol Analysis 
All subjects who complete the study according to the protocol will be included in the Per-
Protocol analysis.  No special data handling algorithms will be used for imputing missing 
data for subjects included in the Per-Protocol analysis. 
12.3  Endpoint Analysis and Reporting of Results 
All statistical analysis will be performed using SAS Version 9.3 (SAS Institute Inc., Cary, 
NC). 
13 ADVERSE EVENT REPORTING 
Adverse Event 
An Adverse Event (AE) is any untoward medical occurrence, unintended disease or injury, 
or untoward clinical signs (including abnormal laboratory findings) in subjects, users or 
other persons, whether or not related to the investigational medical device.  Note: This also 
includes events related to the study device and/or the study procedure.  The U.S. 
Department of Health and Human Services, National Institutes of Health, National Cancer 
Institute, Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03, will be 
used to grade adverse events. 
 
All AEs related to the surgery that are observed by the Investigator or staff during a 
procedure, physical or laboratory examination, or mentioned by the subject either 
spontaneously or upon questioning will be recorded in REDCap™.  Information pertaining 
to the recorded AE will be reviewed and verified by the IRB or its designated 
representative.  The Investigator is responsible for assessing the severity of the AE, the 
causal relationship between any events and the clinical study procedure, activities or 
device.  Additionally, the Investigator is responsible for providing appropriate treatment for 
the event and for adequately following the event until resolution.  The following categories 
of adverse event severity are to be used by the Investigator: 
 
 Mild:  Awareness of a sign or symptom that does not interfere with the subject’s 
usual activity or is transient, resolved without treatment and with no clinical 
sequelae; 
 Moderate:  Interferes with the subject’s usual activity; and, 
 Severe:  Any fatal or immediately life-threatening clinical experience that requires a 
subject to be hospitalized, or hospitalization is unduly prolonged because of a 

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potential disability or danger to life or because an intervention has been 
necessitated.  This includes any permanently disabling event. 
 
The following categories of AE relatedness to the study device and procedure will be used 
by the Investigator: 
 
 Possibly Related – may be related to study agent/device. 
 Probably Related – is likely related to study agent/device. 
 Definitely Related – is clearly related to study agent/device. 
 
Adverse Device Effect (ADE) 
An Adverse Device Effect (ADE) is defined as an adverse event related to the use of an 
investigational medical device.  Note: This definition includes adverse events resulting 
from insufficient or inadequate instructions of use, deployment, installation, operation or 
any deficiency of the investigational medical device. 
 
Serious Adverse Event (SAE) 
The following events (including laboratory results and outcome events) will be considered 
SAEs and must immediately (within 1 working day [24 hours] from the time the research 
team becomes aware of the event) be reported to the IRB as set forth in the MD Anderson 
AE Policy (Chapter 15 of the Human Subject Research Manual).  These events must be 
reported whether or not the Investigator believes they are related to the study procedures 
or the device. 
 
A serious adverse event is any adverse event that: 
 results in death; 
 is life-threatening, (places the subject at immediate risk of death from the event as 
it occurred); 
 results in inpatient hospitalization or prolongation of existing hospitalization; 
 results in persistent or significant incapacity or substantial disruption of a person’s 
ability to conduct normal life functions; 
 results in a congenital anomaly/birth defect; or 
 based upon appropriate medical judgment, may jeopardize the subject’s health and 
may require medical or surgical intervention to prevent one of the other outcomes 
listed in this definition. 
 
Serious Adverse Device Effect (SADE) 
An adverse device effect that has resulted in any of the consequences of a serious 
adverse event.  This includes SADE’s which by its nature, incidence, severity or outcome 

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has not been identified for the investigational study device.  SADE’s must be reported to 
Intuitive Surgical within 24 hours by telephone, fax and/or email. 
 
Unanticipated Serious Adverse Device Effect (USADE) 
This includes SADE’s which by its nature, incidence, severity or outcome has not been 
identified for the investigational study device.  USADE’s must be reported to the IRB in 
accordance with Chapter 15 of MD Anderson’s IRB Policy on Adverse Event Reporting 
and Management. 
 
Unanticipated Adverse Device Effect (UADE) 
Any serious adverse effect on health or safety or any life-threatening problem or death 
caused by, or associated with, a device, if that effect or problem, was not previously 
identified in nature, severity, or degree of incidence in the investigational plan or 
application (including a supplementary plan or application), or any other unanticipated 
serious problem associated with a device that relates to the rights, safety, or welfare of 
subjects (21 CFR 812.3(s)).   
 
Because no investigational drugs or regimens are used in this study, only Unanticipated 
Adverse Device Effects will be reported to the IRB and the IND Office.  Events that are 
related to the neoadjuvant therapy or surgery will not be reported or recorded in the case 
report form. 
 
All UADE will be reported to the IRB in accordance with the timeframes and procedures 
outlined in “The University of Texas M. D. Anderson Cancer Center Institutional Review 
Board Policy for Investigators on Reporting Unanticipated Adverse Events for Drugs and 
Devices”.  
 
Unless otherwise noted, the electronic SAE application (eSAE) will be utilized for safety 
reporting to the IND Office and IRB.  Unanticipated Adverse Device Effects will be 
forwarded to FDA by the IND Sponsor (Safety Project Manager IND Office) according to 
21 CFR 812.150. 
 
It is the responsibility of the PI and the research team to ensure unanticipated adverse 
device effects are reported according to the Code of Federal Regulations, Good Clinical 
Practices, the protocol guidelines, the MD Anderson guidelines, and Institutional Review 
Board policy. 
 
Device failure 

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Device failures which occur at the time of participant evaluation and which may prevent a 
participant from receiving therapy on trial will be kept on a log and will be reported as part 
of the annual report.  Device failures at this point are not expected to affect patient safety, 
as participants may still receive appropriate therapy as determined by their attending 
physician. 
14 GOOD CLINICAL PRACTICES (“GCP”) 
14.1  Institutional Review Board (IRB) Approval 
Prior to study initiation, this protocol, the informed consent and any advertisements for 
subject recruitment must be submitted to the IRB for written approval.  The IRB’s written 
notification of approval will be provided to the MD Anderson IND Office prior to study 
commencement.  Any changes to the protocol that may increase study risks or present 
new risks to the subject or may adversely affect the outcome of the study must be 
approved in writing by the MD Anderson IND Office and the site IRB before the change is 
made. 
14.2  Informed Consent 
Subjects must provide informed consent in writing after having adequate time to consider 
their participation in the study pursuant to the Declaration of Helsinki requirements and 
local / US regulations.  Consent must be obtained prior to any protocol-related procedures 
that are not part of the subject’s standard care.  Written documentation of consent must be 
provided on the signature page in addition to a note in the study records indicating the date 
that consent was obtained.  The subject or his/her legal representative should receive a 
signed copy of the consent form according to international GCP guidelines. 
14.3  Subject Confidentiality 
All information concerning subjects or their participation in this trial will be considered 
confidential.  Only authorized personnel and designated consultants will have access to 
these confidential files.  Authorized regulatory personnel have the right to inspect and copy 
all records pertinent to this trial.  Enrolled subjects will be assigned a unique identifier that 
will be used to maintain confidentiality of subjects’ medical information.  Subject names 
and other protected health information will not be captured on the case report forms. 
14.4  Data Collection 
The Case Report Form (CRF) is the primary data collection instrument for the study.  
REDCap™ will be used as the electronic case report form.  Primary data collection based 
on source documented hospital chart reviews will be performed clearly and accurately by 
the site personnel on the CRF.  All missing data will be explained.  If the item is not 

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applicable to the individual case, “N/A” will be written in the field.  All entries will be printed 
legibly in black ink.  To correct an error that has been made, a single line will be drawn 
straight across the incorrect entry and the correct data will be entered above it.  All 
changes will be initialed and dated.  A copy of the completed Case Report Forms will 
remain on site at the participating institution. 
 
Study data will be collected and managed using REDCap 
(Research Electronic Data Capture) electronic data capture tools hosted at MD 
Anderson. [ref] REDCap (www.project-redcap.org) is a secure, web-based application with 
controlled access designed to support data capture for research studies, providing: 1) an 
intuitive interface for validated data entry; 2) audit trails for tracking data manipulation and 
export procedures; 3) automated export procedures for seamless downloads to common 
statistical packages; and 4) procedures for importing data from external sources. In the 
case of multi-center studies REDCap uses Data Access Groups (DAGs) to ensure that 
personnel at each institution are blinded to the data from other institutions. REDCap 
(https://redcap.mdanderson.org) is hosted on a secure server by MD Anderson Cancer 
Center's Department of Research Information Systems & Technology Services. REDCap 
has undergone a Governance Risk & Compliance Assessment (05/14/14) by MD 
Anderson's Information Security Office and found to be compliant with HIPAA, Texas 
Administrative Codes 202-203, University of Texas Policy 165, federal regulations outlined 
in 21CFR Part 11, and UTMDACC Institutional Policy #ADM0335. Those having access to 
the data file include the study PI and research team personnel. All protected health 
information (PHI) will be removed from the data when it is exported from REDCap for 
analysis. All dates for a given patient will be shifted by a randomly generated number 
between 0 and 364, thus preserving the distance between dates. Dates for each patient 
will be shifted by a different randomly generated number. Following publication study data 
will be archived in REDCap. 
 
14.5  Data Monitoring and Quality Control 
All collected data will be verified for accuracy with source documents including, but not 
limited to, medical records, office/clinic notes, procedure reports, laboratory results, 
physician and nursing progress notes.  Verification and quality of data, monitoring of 
clinical study progress and Investigator compliance with the approved protocol will be 
conducted by the MD Anderson IND Office or a designated representative. 
 
The MD Anderson IND Office or its designated representative will be allowed to visit the 
clinical site and have direct access to all study records throughout the duration of the 
study.  The monitor will review all source data and compare them to the data documented 
in the case report forms, in addition to performing a review of the Regulatory Binder, and 
conducting device accountability.  The Investigator and/or institution will provide direct 

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access to source data/documents for trial-related monitoring, audits, IRB review and 
regulatory inspection. 
14.6  Record Retention 
The Study Sponsor and Investigator will retain essential documents relating to this clinical 
study for at least two (2) years after study completion or two (2) years post marketing 
approval, whichever is longer.  Records may be retained for a longer period as agreed to 
by the Study Sponsor and Investigator. 
14.7  Protocol Monitoring Plan 
This is a single-arm study and, therefore, does not require MD Anderson’s Data Safety 
Monitoring Board (DSMB) review.  This study will be monitored by the MD Anderson IND 
Office and the Principal Investigator.  A protocol-specific monitoring plan will be followed. 
 
The trial will be stopped if flap failures are observed in 2 of the first 5 patients treated.  The 
trial will also be stopped if flap failures are observed in 2 of the second set of 5 patients 
treated.  Flap failure is defined as irreversible arterial and venous thrombosis detected by 
implantable or surface doppler signal within 72 hours after surgery.  Notice will be provided 
to the Principal Investigator, the IRB, and the FDA should early termination of the trial be 
recommended.  The trial will not restart until a thorough risk analysis has been completed 
and the FDA and IRB provide their written approval to restart the study. 
15  Protocol Deviations 
Dr. Selber and Dr. Clemens will not deviate from the protocol except in medical 
emergencies.  If a medical emergency occurs, prior approval will not be required but the 
IRB must be notified of the deviation in accordance with Chapter 25, Reporting 
Requirements and Timeframes of MD Anderson’s IRB Policy on Reporting Protocol 
Deviations. 
16 Device Accountability 
The da Vinci® robotic surgical system and the corresponding instruments that will be used 
in this study have been FDA cleared for a variety of surgical indications.  Dr. Selber and 
Dr. Clemens will use the da Vinci® robotic surgical system and instruments that are 
currently in use at MD Anderson for other cleared clinical indications.  MD Anderson will 
ensure that the Investigator and clinical site personnel are aware they must report any 
device malfunction related to this study to Intuitive Surgical within 24 hours.  In addition, 
clinical site personnel must complete the Device Performance Issue-Malfunction case 
report form (Appendix H). 

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17 SPONSOR RESPONSIBILITIES 
As the Study Sponsor, MD Anderson is committed to the following activities pursuant to 
international GCP guidelines: 
 
1) Securing the necessary IRB and government approvals for this protocol; 
2) Obtaining all required approvals prior to device usage under this investigational 
protocol; 
3) Selecting a qualified investigator; 
4) Ensuring proper investigator training; 
5) Ensuring proper clinical site monitoring; 
6) Ensuring that the IRB is informed of any significant new information about the  
study; 
7) Maintaining accurate and complete study records and submitting required reports; 
8) Obtaining a signed clinical trial / investigator agreement; 
9) Providing case report forms and ensuring that the completed forms match source 
documentation; 
10) Ensuring protocol compliance; and 
11) Ensuring proper reporting of all AEs. 
18 INVESTIGATOR RESPONSIBILITIES 
Dr. Selber will sign a Clinical Trial Agreement affirming that he will adhere to the following 
activities pursuant to international GCP guidelines: 
 
1) Ensuring that enrolled subjects comply with the inclusion/exclusion criteria; 
2) Obtaining written IRB approval prior to study initiation; 
3) Obtaining written informed consent from each subject prior to enrollment; 
4) Performing the study evaluations as described in this protocol; 
5) Maintaining source documentation in the subject’s medical files; 
6) Completing case report forms corroborated by source documentation; 
7) Submitting required reports to the Study Sponsor, IRB and regulatory authorities; 
8) Complying with the study protocol and reporting any deviations in advance of their 
occurrence; 
9) Maintaining study related records;  
10) Maintaining accurate records related to device accountability; and 
11) Ensuring proper reporting of all AEs. 
19 STUDY MONITORING 
The study monitor is a Clinical Research Monitor employed by the IND/IDE sponsor (MD 
Anderson).  The Clinical Research Monitor will monitor the clinical study and report the 

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findings directly to the Medical Monitor and Vice President of Clinical Research.  There will 
be one Clinical Research Monitor monitoring the study. 
20 COMPENSATION IN THE EVENT OF INJURY 
If the subject suffers injury as a direct result of taking part in this study, MD Anderson 
health providers will provide medical care.  However, this medical care will be billed to the 
subject’s insurance provider or the subject in the ordinary manner.  The subject will not be 
reimbursed for expenses or compensated financially by MD Anderson for this injury. 
 
The subject may also contact the Chair of MD Anderson’s IRB at 713-792-2933 with 
questions about study-related injuries.  By signing the consent form, the subjects are not 
giving up any of their legal rights. 
 
Certain tests, procedures, and/or drugs that the subject may receive as part of this study 
may be without cost to the subject because they are for research purposes only.  However, 
the subject’s insurance provider and/or the subject may be financially responsible for the 
cost of care and treatment of any complications resulting from the research tests, 
procedures, and/or drugs, including hospitalization, nausea, vomiting, low blood cell 
counts, and dehydration.  Standard medical care that the subjects receive under this 
research study will be billed to the subject’s insurance provider and/or the subject in the 
ordinary manner.  Before taking part in this study, the subject may ask about which parts of 
the research-related care may be provided without charge, which costs the subject’s 
insurance provider may pay for, and which costs may be the subject’s responsibility.  The 
subject may ask that a financial counselor be made available to the subject to talk about 
the costs of this study. 
 
There are no plans to compensate the subject for any patents or discoveries that may 
result from the subject’s participation in this research.  
The subject will receive no compensation for taking part in this study. 
21 REFERENCES 
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