Chapter I Introduction
1.4 Research Scope and Limitation
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part of the case study consisted of an analysis of medical records of all patients with abdominal aortic aneurysm treated either with traditional open surgery or with EVAR in the case hospital in the study period. The results concerning the medical and the financial aspects were analyzed. The second part of the case study consisted of an in-depth interview of two surgeons and seven industry persons. The interview results were analyzed for meanings. Compiling the results from the literatures reviewed and conjectures deduced from those observed facts in the case study, an explanatory conclusion was achieved.
This thesis is divided into five chapters: the introduction, review of literatures, research methodology, case description and analysis, and conclusions and future perspectives.
1.4 Research Scope and Limitation
The author intends to figure out the reasons underlying the process of a certain radical innovation in the case hospital through case study and in-depth interview. The conclusions are theoretically valid only concerning the case hospital in this limited period of time. However, as a service and innovation study, I hope there is a category effect — the conclusions could be extrapolated to similar categories of medical service and innovations.
Of course, there must be imperfections in the analysis and conclusions. Future studies are needed to answer those remaining questions.
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Chapter II
Review of Literature
This is a service and innovation study in which conclusions are deduced from facts directly observed in daily medical practice or from comprehensive review of literatures. Related research works and literatures from both the medicine and the business study field were reviewed to formulate the theoretical bases of this service and innovation study.
We first briefly introduced the pathophysiology of abdominal aortic aneurysm and choices of treatment, focusing on the traditional open surgical repair and the innovative endovascular repair (2.1), followed by comparison of the two different treatment modalities concerning clinical results and cost-effectiveness (2.2). How patients make decision on treatment modality can be found from review of literatures on patients‘ decision-making process (2.3). In section 2.4 and 2.5, the innovation and dissemination process of endovascular repair are thoroughly discussed about.
2.1 Abdominal Aortic Aneurysm (AAA)
2.1.1 Introduction of Abdominal Aortic Aneurysm
Gloviczki, and Ricotta, (2011) wrote in Textbook of Vascular Surgery that the term aneurysm is derived from the Greek word aneurysma which means ―widening‖
and can be defined as a permanent and irreversible localized dilation of a blood vessel, having at least a 50% increase in diameter compared with the expected normal diameter. Ectasia is defined as a dilation less than 50% of the normal diameter.
Normal diameter of the aorta and the arteries depends on age, gender, body size, and
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other factors. In men, the infrarenal aorta is normally between 14 and 24 mm, and in women, it is between 12 and 21 mm. Therefore, an abdominal aortic aneurysm (AAA) is diagnosed if the diameter is 3 cm or larger in a man or 2.6 cm or larger in a woman.
The most frequent site of extracranial arterial aneurysms is the infrarenal aorta.
In one large autopsy series of patients with aortoiliac aneurysms, the most frequent location was the abdominal aorta alone (65%), followed by the thoracic aorta alone (19%), the abdominal aorta and iliac arteries (13%), the thoracoabdominal aorta (2%) and iliac arteries alone (1%). Peripheral arterial aneurysms are much less common.
Popliteal aneurysms account for about 70% of all peripheral aneurysms, femoral aneurysms are less frequent, and carotids constitute less than 4%. Visceral (splanchnic) and renal artery aneurysms have been considered rare, although their reported incidence due to frequent abdominal imaging has increased recently. Fig. 2.1 demonstrated the anatomy of AAA.
Figure 2.1 Illustration of abdominal aortic aneurysm. (source: “MedlinePlus‖)
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frequent and lethal complication of AAAs. In the United States, aneurysm rupture is the cause of death in 1.2% of men and 0.6% of women. About 15,000 deaths each year are caused by ruptured AAAs, making AAA the 13th leading cause of death in the United States. It is the 10th leading cause of death in men. In a study of 231 ruptured aneurysms, 71% of patients did not know before rupture that they had an aneurysm. Most ruptures occur into the retroperitoneal space, but free rupture of the anterior wall can result in herald bleeding into the abdominal cavity; rupture into the inferior vena cava or iliac vein causes aortocaval or aortoiliac arteriovenous fi stula, whereas rupture into the duodenum results in massive gastrointestinal bleeding due to a primary aortoduodenal fistula.After rupture of an AAA, only half of patients arrive at the hospital alive. In one study, 50% reached the hospital alive, 7% died before surgery, 17% died during the operation, and 37% died within 30 days of surgery for an overall mortality rate for open surgical repair of 45%. Although initial results of EVAR for ruptured AAA have been encouraging, about 25% to 30% of patients with a ruptured AAA will eventually survive. Occasionally, AAAs can lead to life- and limb-threatening conditions because of acute thromboembolism.
The larger the aneurysm diameter is, the greater the risk for rupture is. The annual risk for rupture of an AAA between 4 and 5.4 cm in size is about 0.5% to 1%.
For AAAs between 5.5 and 6 cm, the annual rupture risk is estimated between 5% and 10%. AAAs between 6 and 7 cm have an estimated yearly rate of rupture of 10% to 20%.
In 2003, a consensus statement was issued by the Society for Vascular Surgery regarding screening for AAAs. It recommended baseline ultrasound screening for AAA in men aged 60 to 85 years, women 60 to 85 years with cardiovascular risk
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factors, and men and women older than 50 years with a family history of AAA.
Subsequent ultrasound is recommended annually for AAAs 4.0 to 4.5 cm and every 6 months for AAAs larger than 4.5 cm. The United States approved the Screening Abdominal Aortic Aneurysms Very Efficiently (SAAAVE) Act to provide AAA screening at age 65, for male ever-smokers and men and women with a family
history of AAA, as recommended by the U.S. Preventive Services Task Force.
For patients with low-risk AAAs (small diameter without other risk factors for rupture) being followed with serial size measurements, attempts are made to reduce expansion rate and rupture risk. This can be accomplished with risk factor modifications, including smoking cessation, blood pressure control, and reduction of cholesterol, triglycerides, and lipoproteins.
The goal of elective AAA repair is to prevent rupture and prolong life. Careful assessment of factors that influence rupture risk, operative mortality, and life expectancy is essential, and patient preference receives increasing importance.
2.1.2 Open Surgical Repair (OSR)
For open repair, several exposures can be used, each with its own merits and disadvantages. Options include a transperitoneal approach, through a long midline incision or through a mini-laparotomy, or the retroperitoneal approach through a left flank incision. Though the incisions and exposures may vary, the aim of the operation is to exclude or resect the aneurysmally dilated abdominal aorta and to replace it with a straight or a bifurcated graft.
If the iliac arteries are not aneurysmal, a straight collagen or gelatin-coated zero porosity polyester (Dacron) graft is used for repair, usually 16 or 18 mm in diameter.
Both proximal and distal anastomoses are performed with 3-0 polypropylene running sutures. When the common iliac arteries are involved, a 16- or 18-mm bifurcated graft
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is used and sutured to the distal common iliac arteries in an end-to-end fashion, using 4-0 polypropylene running sutures (Fig. 2.2).
Early mortality for open elective AAA repair has greatly improved during the past 2 decades because of improvements in preoperative evaluation, intraoperative techniques, and perioperative care. Mortality rates of elective open infrarenal AAA repair in good-risk patients can be expected to be less than 5%; in high-volume centers, the mortality rate is between 1% and 3%. (Rutherford 2004)
Figure 2.2 Operative techniques of trasnperitoneal abdominal aortic aneurysm repair with a straight or a bifurcated prosthetic graft. (source: Sabiston Textbook of Surgery, 18th Edition)
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The 2003 Guidelines for the treatment of abdominal aortic aneurysms published by the Joint Council of the Vascular Societies noted that treatment of AAAs is individualized and recommended operative repair for AAAs with a diameter of 5.5 cm or greater in men. Those aneurysms that expand at a rate of more than 1 cm/year or that are symptomatic must be repaired. However, subsets of younger, low-risk
patients, with long projected life expectancy, may prefer earlier repair. If the surgeon‘s operative mortality rate is low, repair may be indicated at smaller sizes (4.5-5.4 cm) if that is the patient‘s preference. For women and patients with a greater than average rupture risk, an AAA diameter of 4.5 to 5.0 cm is an appropriate threshold for elective repair. Atypical aneurysms (dissecting, pseudoaneurysms, mycotic, saccular, and penetrating ulcers) may be an indication for surgical treatment regardless of size. For high-risk patients, delay in repair until larger diameter is warranted, especially if EVAR is not possible. The guidelines recommended EVAR as the most appropriate option for patients at increased risk with conventional open repair. EVAR is preferred for older, high-risk patients; those with ―hostile‖ abdomens; and patients with other clinical circumstance likely to increase the risk of open repair, if their anatomy is appropriate. It was emphasized that patient preference is of great importance.
It is essential that the patients be well informed to make such choices.
2.1.3 Endovascular Aortic Repair (EVAR)
In contrary to open surgical repair, in which the aneurysm is resected and the aorta was replaced with a prosthesis graft through a generous laparotomy or a flank incision, during EVAR, the stent-graft of which the mechanism of treatment is to exclude the blood from flowing into the aneurysm sac is introduced into the aneurysm through the femoral arteries and fixed in place to the nonaneurysmal aortic neck and iliac arteries with self-expanding or balloon-expandable stents. Some of the
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stent-grafts have barbs, pins, or hooks to secure the stent, whereas some others have suprarenal fixation with self-expanding stents. A major abdominal incision is thus avoided, and procedure-related morbidity is reduced. An endovascular stent-graft excludes the aneurysm from blood flow and extends from the infrarenal aorta to both common iliac arteries, preserving flow to the internal iliac arteries.
This procedure can be performed in a surgery-capable catheterization laboratory or a surgical suite equipped with a fixed or mobile angiography C-arm. This can be performed under general, regional, spinal, or local anesthesia. Both common femoral arteries are cannulated either percutaneously or more commonly with femoral artery cutdowns. Vascular sheaths are placed over guidewires under fluoroscopic guidance into both external iliac arteries. The patient is systemically heparinized, and a diagnostic aortogram is performed through a marker pigtail catheter placed just above the renal arteries. Appropriate measurements are taken. Super-stiff guidewires are then inserted into the thoracic aorta through both femoral sheaths. The endograft device is advanced into the aorta, usually through its own deployment sheath. A multi-sidehole catheter is advanced from the contralateral side to mark the level of the renal arteries, and the main body device is deployed just below the lowest renal artery.
Distally, it is deployed to just above the iliac bifurcation, taking care not to cover the hypogastric artery unless preoperatively planned. The contralateral limb gate is then cannulated, and an appropriately chosen contralateral iliac limb endograft device is deployed from within the main device to just above the iliac bifurcation. Balloon dilation is performed of all attachment sites, and completion angiogram is done with attention paid to position and sealing of the graft attachment sites.
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Figure 2.3 Techniques of endovascular aortic repair. (source: Sabiston Textbook of Surgery, 18th Edition)
2.2 Evaluation of Different Treatment Modalities 2.2.1 Clinical Results of Different Treatment Modalities
Since the advent of endovascular aortic repair techniques for surgical treatment of abdominal aortic aneurysm in the early 1990‘s, many meticulous amendments of the implantation techniques and a lot of technological improvement of endovascular stentgrafts have been observed. There are many clinical studies focusing on the short-term and long-term results of EVAR in comparison to OSR.
Within 10 years, Seelig (1999) reported in Mayo Clinic Procedings that in light of the potential to reduce morbidity and mortality associated with open surgical repair, endoluminal grafting offers therapeutic options to patients who are not surgical candidates because of comorbidities.
The United Kingdom EVAR Trial Investigators published the trial result in New England Journal of Medicine in 2010. From 1999 through 2004 at 37 hospitals in the United Kingdom, they randomly assigned 1252 patients with large abdominal aortic aneurysms (≥5.5 cm in diameter) to undergo either endovascular or open repair; 626 patients were assigned to each group. Patients were followed for rates of death,
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graft-related complications, reinterventions, and resource use until the end of 2009.
Logistic regression and Cox regression were used to compare outcomes in the two groups. The 30-day operative mortality was 1.8% in the endovascular-repair group and 4.3% in the open-repair group (adjusted odds ratio for endovascular repair as compared with open repair, 0.39; 95% confidence interval [CI], 0.18 to 0.87; P = 0.02). The endovascular repair group had an early benefit with respect to aneurysm-related mortality, but the benefit was lost by the end of the study, at least partially because of fatal endograft ruptures (adjusted hazard ratio, 0.92; 95% CI, 0.57 to 1.49; P = 0.73). By the end of follow-up, there was no significant difference between the two groups in the rate of death from any cause (adjusted hazard ratio, 1.03; 95% CI, 0.86 to 1.23; P = 0.72). (Fig. 2.4) The rates of graft-related
Figure 2.4 Kaplan–Meier Estimates for Total Survival and Aneurysm-Related Survival during 8 Years of Follow-up. (source: United Kingdom EVAR Trial Investigators 2010.)
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Figure 2.5 Kaplan–Meier Estimates for the Time to the First Graft-Related Complication or Reintervention during 8 Years of Follow-up. (source: United Kingdom EVAR Trial Investigators 2010.)
complications and reinterventions were higher with endovascular repair, and new complications occurred up to 8 years after randomization, contributing to higher overall costs. (Fig. 2.5) They concluded in this large, randomized trial, that
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endovascular repair of abdominal aortic aneurysm was associated with a significantly lower operative mortality than open surgical repair. However, no differences were seen in total mortality or aneurysm-related mortality in the long term. Endovascular repair was associated with increased rates of graft-related complications and reinterventions and was more costly.
The United Kingdom EVAR Trial Investigators also published in New England Journal of Medicine in 2010 data on the question of whether endovascular repair reduces the rate of death among patients who were considered to be physically ineligible for open surgical repair. From 1999 through 2004 at 33 hospitals in the United Kingdom, they randomly assigned 404 patients with large abdominal aortic aneurysms (≥5.5 cm in diameter) who were considered to be physically ineligible for open repair to undergo either endovascular repair or no repair; 197 patients were assigned to undergo endovascular repair, and 207 were assigned to have no intervention. Patients were followed for rates of death, graft-related complications and reinterventions, and costs until the end of 2009. Cox regression was used to compare outcomes in the two groups. The 30-day operative mortality was 7.3% in the endovascular-repair group. The overall rate of aneurysm rupture in the no-intervention group was 12.4 (95% confidence interval [CI], 9.6 to 16.2) per 100 person-years.
Aneurysm-related mortality was lower in the endovascular-repair group (adjusted hazard ratio, 0.53; 95% CI, 0.32 to 0.89; P = 0.02). This advantage did not result in any benefit in terms of total mortality (adjusted hazard ratio, 0.99; 95% CI, 0.78 to 1.27; P = 0.97). A total of 48% of patients who survived endovascular repair had graft-related complications, and 27% required reintervention within the first 6 years.
During 8 years of follow-up, endovascular repair was considerably more expensive than no repair (cost difference, £9,826 [U.S. $14,867]; 95% CI, 7,638 to 12,013 [11,556 to 18,176]). The concluded that patients who were physically ineligible for
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open repair, endovascular repair of abdominal aortic aneurysm was associated with a significantly lower rate of aneurysm-related mortality than no repair. However, endovascular repair was not associated with a reduction in the rate of death from any cause. The rates of graft-related complications and reinterventions were higher with endovascular repair, and it was more costly.
2.2.2 Cost-effectiveness of Different Treatment Modalities
We know from the previous section on clinical result that endovascular aortic repair is more costly that open surgical repair. Yet, we still don‘t know the cost-effectiveness and quality of life issue.
Young (2010) reported in the Journal of Vascular surgery an evaluation of the cost-effectiveness of endovascular repair (EVAR) for small abdominal aortic aneurysms (AAA). Outcomes were reported as quality-adjusted life-years (QALYs).
The model demonstrated that early EVAR for 4.0 cm-5.4 cm AAAs led to fewer QALYs at greater costs when compared with observational management with elective repair at 5.5 cm. With a >70% probability, observational management until AAA diameter is 5.5 cm will be the cost-effective option. However, EVAR for small AAAs may become cost-effective when differences in quality of life and mortality are considered.
When EVAR was compared with OSR, Blackhouse‘s group reported in 2008 and 2009 that based on commonly quoted willingness-to-pay thresholds, EVAR was not found to be cost-effective compared to OSR. EVAR may be a cost-effective strategy compared with OSR for high-risk patients. Longer-term data are needed to decrease the uncertainty associated with the results.
In Chambers‘ review paper (2009), they concluded that open repair is more likely to be cost-effective than EVAR on average in patients considered fit for open
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surgery. EVAR is likely to be more cost-effective than open repair for a subgroup of patients at higher risk of operative mortality. These results are based on extrapolation of mid-term results of clinical trials. Evidence does not currently support EVAR for the treatment of ruptured aneurysms. Further follow-up of the existing UK trials should be undertaken and the relative costs of procedures and devices should be investigated further.
2.3 Factors Influencing Choice of Treatment
Every clinician has been taught and trained to consider a patient‘s best benefit as the first priority. Can this aim be always achieved? This has been and still will be true for a certain percentage of clinical scenarios: one ill, one pill, and one bill. A patient was prescribed with a pill to treat a disease by a physician who was compensated for the treatment. However, as medical knowledge and technology are progressing explosively, not only patients but also clinicians are more frequently encountering puzzling clinical situations that can oftentimes be managed with more than one treatment modalities, of which each treatment modality carries its specific anticipated results, at the tradeoff of potential side-effects and complications, of course.
Is there always a straight forward best solution? If there is, who‘s going to make the decision out of the complex clinical situation? Is it easy for a patient to choose the
Is there always a straight forward best solution? If there is, who‘s going to make the decision out of the complex clinical situation? Is it easy for a patient to choose the