Pelvic Exenteration Surgery: the evolution of radical surgical techniques for advanced and recurrent pelvic malignancy

Abstract

This thesis explores my interest in the assessment of surgical outcomes following pelvic exenteration for recurrent rectal cancer and advanced primary rectal cancer. This interest has evolved over more than 20 years of clinical and research practice with potential application into management of other malignant, pelvic conditions. “Pelvic exenteration” refers to radical multi-visceral resection of locally advanced or recurrent tumours of the pelvis. En-bloc resection of all contiguously involved anatomical structures is performed with a view to achieving a complete oncological resection (R0 resection status). The primary justification for such surgery is the reasonable chance of cure, which is now achieved in up to 63% of patients. An R0 resection margin is the key factor in predicting survival and quality of life after surgery and is now considered the optimal outcome of this surgery. Although most contemporary exenteration surgical units focus on advanced and recurrent rectal cancer, there remains a role for pelvic exenteration in managing various other tumours arising from the gastrointestinal or genitourinary tract. When pelvic exenteration was first described in 1948 by Alexander Brunschwig in New York for recurrent carcinoma of the cervix the survival outcomes were poor and the operative mortality rates as high as 23-35%. Over more than 20 years this doctorate describes my evolution of pelvic exenteration predominantly for recurrent and advanced rectal cancer and has demonstrated that it can be done safely with low operative mortality, survival data comparable and in some cases better than the resection of metastatic disease. The quality of life studies have demonstrated a fairly rapid return to baseline levels which increase progressively over 1-2 years and is good in the long term survivors. What does remain a major concern for exenteration surgery is the significant morbidity associated with such a physically and mentally daunting procedure despite perioperative mortality (30-day) excellent with only 3 deaths in 539 exenterations performed at RPA as of October 2016. We have started a major preoperative reconditioning program to improve nutrition, obtain better pain control, increase physical fitness as well as mentally better prepare patients and 2 their carers for what lies ahead. These are all currently being scientifically assessed. Improving septic, urologic, wound and vascular complications continues to be a focus of endeavour and research in our broader exenteration service. Improved interposition graft techniques, predictors of wound and flap complications, use of biologic mesh to reconstruct the pelvic floor muscle, cover raw bone surfaces from small bowel and conduits and reconstruction of large bone defects are being trialled to try and prevent small bowel complications such as fistula and obstruction. Perioperative morbidity remains the immediate challenge for the future My involvement in pelvic exenteration has traced the evolution of radical pelvic surgery from its description in 1948 and in this thesis I have identified the key technical breakthroughs since I started the exenteration service at Royal Prince Alfred Hospital (RPAH). Pelvic exenteration is now the procedure of choice for locally advanced and recurrent rectal cancer and is practiced globally in specialised units. Nearly all publications that comprise this thesis have wholly or in part derived from data collated from information in the pelvic exenteration database at the Surgical Outcomes Research Centre (SOuRCe) in RPAH of which I initiated and Head. I initiated this database and I am the principal treating surgeon in 80% of the patients included (400 of 502 as of March 2016) and contributed in part to the remaining one fifth. I wholly designed the following surgical techniques: lateral neurovascular approach, abdominolithotomy resection of the sacrum, excision of the pubic bone and perineal urethrectomy and the selective criteria for the utilisation of flaps. I have contributed in collaboration with other surgeons the development of the prepelvic tunnel for flap placement, the spiral saphenous graft interposition, the sacral segmental disconnection techniques and the utilisation of colonic conduits. The first published report of total pelvic exenteration in Australia was in 1955 after it was performed at RPAH, by a gyneacologist J. Cameron Loxton who had spent just three months with Dr Alexander Brunschwig in New York. Loxton subsequently reported in the Medical Journal of Australia in 1958 commenting on 3 the medical community’s lack of support for this operation and for his and Brunschwig’s work: “…this work initially received rather mixed reception. Dr Brunschwig was much applauded in some quarters and much maligned in others. There were some who considered that these operations exceeded the bounds of propriety.” This attitude persisted until the 1990s when I commenced consultant surgical practice. It became obvious to me that if we were to embark on an exenteration program, it needed to be performed meticulously with methodical, multidisciplinary, surgical planning. Over the past 20 years this has been the approach of the Pelvic Exenteration program at RPAH which has evolved into an internationally recognised centre for pelvic exenteration surgery with the highest volume of procedures performed per year worldwide (>60) and one of the largest series with now over 500 exenterations documented as of March 16, 2016. My concept and development of the Colorectal Research Department in 1996, the Surgical Outcomes Research Centre (SOuRCe) in 2002, Masters of Surgery by coursework 2004 and the Institute of Academic Surgery at RPA in 2014 has allowed me to perform outcomes research which has included a major focus on pelvic exenteration including supervision of medical students, interns, residents, registrars and fellows. I have supervised and co-supervised at the University of Sydney through these research bodies 8 PhD, 18 Masters of Surgery, 6 Masters of Medicine, 4 Masters of Philosophy and 6 Honours or equivalent projects undertaken by medical students. I am indebted to their collaboration with my own research over more than 20 years which some have contributed to the work presented in this thesis. This thesis includes 38 of some 250 career peer reviewed publications. The thesis has been organized into 12 chapters, each addressing a component of the overarching topic of determining whether pelvic exenteration is safe, whether there is a survival advantage for this radical procedure and its impact on quality of life. 4 Chapter 1 describes the historical background and my viewpoint of this evolution of pelvic exenteration surgery since the first exenteration was performed in NYC for cervical cancer Alexander Bruschwig in 1948. This paper has been written largely for the purpose of this thesis and to re-assess and appraise in my mind where the exenteration program should move towards the future by assessing the progress of the past and will also contribute to Kilian’s own thesis focusing on the complications of pelvic exenteration which I am his supervisor. Chapter 2 describes the results of survival and safety of surgery when performed for patients with recurrent rectal cancer which is a uniformly fatal condition that first led to my interest in pelvic exenteration. Chapter 3 describes articles dealing with results of exenteration in the largest published series of advanced primary rectal cancer for which historically patients have not been offered curative surgery. Chapter 4 describes publications of two studies on quality of life in pelvic exenteration surgery together with information on cost effectiveness, cost utility data as well as health service utilisation. Chapter 5 covers the preoperative decision making and assessment of pelvic exenteration patients from a world-wide perspective as well as studies on the nutritional considerations and the “needs” of exenteration patients. The subsequent three chapters describe the novel surgical approaches and surgical anatomy which I have described and are used in my department to approach the most difficult compartments of the pelvis. Chapter 6 includes two publications of the world’s largest experience of sacrectomy as well as the largest experience of sacrectomy for recurrent rectal cancer. Two articles also describe two new approaches to less radical sacrectomy, the abdomino-lithotomy approach for lower (S3 down) sacrectomy and the segmental prone disconnection prior to abdominal resection for higher lumbosacral involvement during pelvic exenteration. 5 Chapter 7 describes a novel and radical approach to the neurovascular structures of the lateral pelvic compartments. In 2009, I described the technique and anatomy in early cases and in 2015 I published the largest series of 200 lateral compartment pelvic exenterations with an improvement in R0 rate from our early experience of 21 % in 2000 to 53% in the 2009 publication (which described the more radical technique to 68% for recurrent rectal cancer in the 2015 publication). A series of lateral compartment exenterations requiring vascular reconstruction was published in 2015 and I have also contributed to publications on novel techniques of vascular reconstruction, notably the spiral saphenous graft which tailors the long saphenous vein into an autologous variable diameter graft matching the size of the patient’s iliac vessels. In chapter 8, I draw attention to three issues of the anterior compartment exenteration. Firstly, the urine leak rate with conduits and in particular the type of conduit utilised (ileal versus colonic) as well as an algorithm for the management and prevention of urine leaks post exenteration. More recently we compared the outcomes of total cystectomy in pelvic exenteration compared with resection for primary bladder cancer. I describe two alternative approaches to improve the RO rate of the anterior compartment. Secondly, the resection of the pubic bone, both partial and complete, to give a greater anterior bone margin and thirdly, the perineal approach of transection of the urethra to give a wider soft tissue anterior and inferior margin in the male. Both the technical article and the clinical results are presented in separate articles and have not been published by any centre previously. Chapter 9 includes two of the largest series of “non rectal cancer” pelvic exenteration patients. A series of salvage exenteration for re-recurrent and advanced recurrent cloacal SCC as well as a publication of a large series of pelvic exenteration for recurrent advanced gynaecological malignancy. Finally, in chapter 10 I describe the Unit’s progressive development of different techniques and approaches to plastic surgical reconstruction of the large defects created by such extensive tissue removing surgery. From the early experience with gracilis myocutaneous flap in the 1990’s, to techniques of pre-pelvic tunnelling of VRAM 6 flaps to the safety and results of a selective approach to flap surgery following pelvic exenteration. Chapter 11 is a summary overview of the evolution in this approach to pelvic exenteration surgery as conducted at RPAH and future directions. Chapter 12 includes 10 chapters in books. The success of the pelvic exenteration program at RPAH is reflected in both the number of publications and the number of overseas surgeons who visit and have trained in our department. Many of these surgeons have been funded by their own institutions and governments to learn the exenteration techniques developed that are incorporated in this thesis and exchange international ideas and promote collaborative research programs. The 38 articles included in this thesis and published in the peer reviewed literature represent a significant part of my more that 250 publication record and contributes to my current h-index of 51, i10 index of 148 and 8883 citations and reflects the importance of this body of work. Of the 502 pelvic exenterations performed at the pelvic exenteration unit by the end March 2016, I was the principal treating surgeon in 400 exenterations and provided the momentum for the evolution of exenteration and the creation of a specialist Unit at RPAH. I am conscious that, over time, my principal clinical research role evolved from being the initiator of the exenteration program, writer and first author into being the supervisor of medical students, residents and fellows wanting to write up my experience in pelvic exenteration over time. My main functions thereby became those of mentoring, supervising and providing proper welfare and resources. The selected publications present a cohesive theme from my work performed with numerous colleagues including postgraduate. Most importantly, I thank the whole exenteration clinical team at RPA over more than 20 years and I dare not mention any one individual by name hoping not to underestimate another’s contribution to the team which is so broad and an honour for me to be a part of a great team and to lead this program. The surgeons from many specialties including particularly my colorectal colleagues, anaesthetists, intensivists, oncologists, radiologists to name only some. The contribution of specialised nursing and allied 7 health as well as hospital administration has been enormous and also made the journey not only possible but an enjoyable challenge.