Abstract
Background:
Chronic pancreatitis (CP) is associated with poor quality of life. Total pancreatectomy with islet autotransplantation (TPIAT) has traditionally been reserved for patients with refractory disease. We hypothesized TPIAT would lead to decreased costs and resource utilization after operation in children.
Methods:
Retrospective review of 39 patients who underwent TPIAT at a single children’s hospital was performed. All inpatient admissions, imaging, endoscopic procedures, and operations were recorded for the year prior to and following operation. Costs were determined from Centers for Medicare and Medicaid Services.
Results:
Median hospital admissions before operation was 5 (IQR:2–7) and decreased to 2 (IQR:1–3) after (p < 0.01). Median total cost for the year before operation was $36,006 (IQR:$19,914-$47,680), decreasing to $24,900 postoperatively (IQR:$17,432-$44,005, p = 0.03). Removing cost of TPIAT itself, total cost was further reduced to $10,564 (IQR:$3096-$29,669, p < 0.01).
Conclusion:
In children with debilitating CP, TPIAT has favorable impact on cost reduction, hospitalizations, and invasive procedures. Early intervention at a specialized pancreas center of excellence should be considered to decrease future resource utilization and costs among children.
Keywords: Pancreatitis, Opioid, Insulin, TPIAT, Resource utilization
Introduction
Chronic pancreatitis (CP) is associated with significant morbidity and poor quality of life in children. The rate of development of CP in children has risen over the past few decades and is nearing the incidence in the adult population.1 Pancreatitis was found to be the top gastrointestinal cause of hospital admissions in children and adults, resulting in an annual cost of approximately 2.6 billion dollars in the United States.2,3 Additionally, in the pediatric population, CP has been associated with poor quality of life, high opioid usage, and multiple hospitalizations with pain and pancreatitis attacks.4,5 Although studies have found that chronic pancreatitis leads to high resource utilization in the adult population, little is known about the financial burden of this disease process in the pediatric population.6–8
While not all pediatric patients who develop acute pancreatitis progress to develop acute recurrent pancreatitis (ARP) or CP, those who do are often debilitated by their disease course. As patients develop chronic pain and debilitation and have increasing opioid requirements, total pancreatectomy with islet autotransplantation (TPIAT) has been offered as a method to achieve opioid independence and to restore quality of life.9–15 However, TPIAT has typically been considered for these patients after years of recurrent admissions to the hospital and numerous procedures,16,17 likely leading to high and unnecessary resource utilization.6,8
The primary objective of our study was to determine the overall resource utilization for pediatric patients with chronic pancreatitis before and after TPIAT. The secondary objective of our study was to predict the likelihood that patients would become opioid or insulin dependent prior to the operation and likelihood that they would become opioid or insulin independent after the operation. We hypothesized that TPIAT in children would lead to decreased overall costs and resource utilization, as well as allow for opioid independence after the operation.
Methods
Study population
We performed a retrospective review of pediatric patients who underwent TPIAT at a single tertiary care children’s hospital from 2015 to 2018. All patients had at least one year of follow up before and after the operation. All operations were performed by a single surgeon and patients were cared for using a multidisciplinary approach with a team comprised of the surgeon, gastroenterologists, endocrinologists, pain specialists, psychologists, and nutritionists. This study received IRB approval from the Cincinnati Children’s Hospital Medical Center (#2016–9510).
Perioperative information
Patients are required to meet with each member of the multidisciplinary team before the operation as part of their multidisciplinary evaluation. Once they are deemed eligible for the TPIAT, they are assigned an operative date within a few months from the initial evaluation. Postoperative care is protocolized and all patients are initially admitted to the intensive care unit for continuous glucose monitoring, insulin infusion, and heparin infusion. As previously reported by our institution, all patients are regularly maintained on insulin postoperatively and transitioned to an insulin pump for at least 2–3 months to allow maximal survival and engraftment of the islets.5 Patients receive a postoperative chest radiograph to visualize position of the central venous catheter and the endotracheal tube (as patients remain intubated immediately postoperatively). Per our protocol as surveillance for portal vein thrombosis, patients receive a Doppler ultrasound immediately postoperatively, as well as on postoperative days 1 and 7.
Cost and frequency analysis
All inpatient admissions, imaging procedures, endoscopic procedures, and operations were recorded for each month during the year prior to and one year following TPIAT, including those use for pre-operative and post-operative evaluation. Cost of procedures and hospitalizations were determined using data obtained from the Centers for Medicare and Medicaid Services in U.S. dollars (Table 1). The cost of admissions, operations, and complications were determined using the Diagnosis-Related Group codes. The type of complication and indication for reoperation were used to determine appropriate costs and our institution has previously published this data.18 The cost of imaging and procedures were determined using the Current Procedural Terminology codes. Cost of daily insulin and opioid use were not included given the variability in daily use and difficulty in accurately recording this information in the outpatient setting. In this study, approximately 50% of patients exhibited pancreatic exocrine insufficiency prior to requiring TPIAT. Again, given the lack of consistent documentation in assessing outpatient doses and amount of enzyme taken, we were unable to calculate the specific cost of these medications preoperatively. However, since majority of patients required this before operation or were moving towards needing enzyme replacement, this cost was offset with post-operative needs for replacement.18
Table 1.
Costs per medicare.
| CPT code | DRG | Cost | |
|---|---|---|---|
| Medical Admission | 439 | $ 5235.52 | |
| Pancreatic Surgery | 407 | $ 14,336.43 | |
| Surgery with Clavien Complication Grade 1–2 | 406 | $ 20,669.88 | |
| Surgery with Clavien Complication Grade 3–4 | 405 | $ 41,340.40 | |
| Exploratory Laparotomy/Lysis of Adhesions | 337 | $ 9779.14 | |
| Xray (Kidney, Ureter, Bladder Without Contrast) | 74241 | $ 201.00 | |
| Xray (Chest) | 71045 | $ 62.00 | |
| CT Abdomen/Pelvis with Contrast | 74177 | $ 385.00 | |
| MRI Abdomen/Pelvis | 74182 | $ 385.00 | |
| Ultrasound (Single Organ/Quadrant) | 76705 | $ 112.00 | |
| Endoscopic Ultrasound | 43259 | $ 1483.00 | |
| Endoscopic Retrograde Cholangiopancreatography | 43260 | $ 2824.00 | |
| Esophagogastroduodenoscopy | 43235 | $ 761.00 | |
| Interventional Radiology Gastrojejunostomy Tube Exchange | 761 | $ 761.00 | |
| Operating Room Central Line Removal | 36589 | $ 620.00 | |
| CPT: Current Procedural Terminology; DRG: Diagnosis-Related Group |
Markov modeling
A Markov model was built using the R msm package19 to estimate the six-month likelihood of transitioning opioid usage states before and after surgery based on data from this cohort. Briefly, the Markov model is a state-transition model to predict prognosis or long-term outcomes.20 This model assumes there are only a certain number of states and one must only transition between these predefined states. This model takes into consideration incidence, progression, and regression of disease and allows extrapolation of future risk. In this study, patients could be in one of two states before and after the operation: (+) opioid usage or (−) opioid usage. States were evaluated at five time points: the start of the study, six months into the first year, immediately prior to the operation, immediately after the operation, six months after the operation, and one year after the operation. The two transition probabilities for the before and after states were compared using a one-tailed two-proportion z-test and a p-value <0.05 was considered a significant transition probability. Given the small number of transitions before surgery regarding insulin requirement, a separate Markov model was created to determine the probability of transitioning insulin states after surgery.
Statistical analysis
Continuous data are represented as median and interquartile range (IQR). Categorical data are reported as frequencies (n) and percentages (%). Comparison of costs before and after the operation was performed using paired t-tests. Random-effects logistic regression was used to determine the likelihood of requiring procedures before compared to after surgery, adjusting for sex and age at TPIAT, and are reported as odds ratios and standard error. Participants were considered as random effects to account for correlation among data collected from participants in a repeated measures design. Markov modeling data are displayed as a percentage which represents the six-month transition probabilities before and after surgery. A p-value <0.05 was considered statistically significant. All statistical analyses were performed using JMP Pro 14.0 (SAS Institute, Cary, NC) and R program 3.5.1 (R Development Core Team 2018).
Results
Demographics
Thirty-nine children underwent TPIAT and had a minimum of one-year follow-up over the study period. Etiologies varied with 20 (51.3%) children undergoing TPIAT due to genetic causes, seven (17.9%) for genetic and anatomic causes, seven (17.9%) with idiopathic causes, and five (12.8%) with anatomic. Five (12.8%) patients had ARP while the remaining 34 (87.2%) had CP. The median duration of their disease process from CP diagnosis to surgery was 42 months (IQR 19–89 months). Twenty-five (64.1%) patients required daily opioids pre-operatively and two (5.4%) patients regularly required insulin.
Admissions and procedures
In the year prior to operation, the median number of hospital admissions was five (IQR 2–7). This decreased to two in the year following the operation (IQR 1–3, p < 0.01), however, there was no significant difference in total length of stay over all admissions before (26 days, IQR 7–45) compared to after the operation (29 days, 22–36) (p = 0.64). Of note, the TPIAT admission was included in the data for after the operation.
Patients underwent more plain film radiographs after (9, IQR 6–13) the operation compared to before (3, IQR 1–6) (p < 0.01), as well as more ultrasounds (4 [IQR 3–7] after vs 2 [IQR 0–4] before; p = 0.03). Patients had fewer MRIs after the operation (0 [IQR 0–0] after vs 1 [IQR 1–3] before; p < 0.01), but no difference in number of CT scans (Table 2). Regarding endoscopic procedures, patients had fewer endoscopic retrograde cholangiopancreatography (ERCP) procedures after the operation, (0 [IQR 0–0] after vs 2 [IQR 1–3] before; p < 0.01).
Table 2.
Hospital admissions and procedures before and after operation.
| Before operation (n) Median (IQR) | Including and after operation (n) Median (IQR) | p-value | |
|---|---|---|---|
| Medical Admission | 5 (2–7) | 2 (1–3) | <0.01 |
| Length of Stay (Days) | 26 (7–45) | 29 (22–36) | 0.64 |
| Radiographs (Chest and KUB) | 3 (1–6) | 9 (6–13) | <0.01 |
| CT Abdomen/Pelvis with Contrast | 1 (0–2) | 1 (0–2) | 0.57 |
| MRI Abdomen/Pelvis | 1 (1–3) | 0 (0–0) | <0.01 |
| Ultrasound (Single Organ/Quadrant) | 2 (0–4) | 4 (3–7) | 0.03 |
| Esophagogastroduodenoscopy | 0 (0–1) | 0 (0–1) | 0.79 |
| Endoscopic Ultrasound | 0 (0–0) | 0 (0–0) | 0.06 |
| ERCP | 2 (1–3) | 0 (0–0) | <0.01 |
IQR: Interquartile Range; KUB: Kidney, Ureter, and Bladder; ERCP: Endoscopic Retrograde Cholangiopancreatography.
Random-effects logistic regression was then utilized to determine the probability of requiring an admission, imaging, or procedure comparing equivalent times for each month prior to and after operation (Table 3). The likelihood of requiring an admission after the operation became significantly less than before the operation at the four-month post-TPIAT (compared to eight months before surgery) time-point (OR 0.46, SE 0.09, p < 0.01). The same was seen for imaging at the six-month post-TPIAT time-point (OR 0.27, S.E. 0.058, p < 0.01). Finally, the probability of requiring an endoscopic procedure after the operation decreased by the two-month post-TPIAT time-point (OR 0.305, S.E. 1.29, p < 0.01). These findings are represented in Fig. 1A–C.
Table 3.
Odds ratios of an outcome comparing each month after to each month before surgery.
| Outcome | Month | Odds Ratio | S.E. | p-value |
|---|---|---|---|---|
| Admission | 2 | 1.460 | 0.361 | 0.13 |
| 4 | 0.466 | 0.091 | <0.01 | |
| 6 | 0.149 | 0.035 | <0.01 | |
| 8 | 0.048 | 0.016 | <0.01 | |
| 12 | 0.005 | 0.003 | <0.01 | |
| Imaging | 2 | 4.650 | 1.217 | <0.01 |
| 4 | 1.138 | 0.224 | 0.51 | |
| 6 | 0.279 | 0.058 | <0.01 | |
| 8 | 0.068 | 0.020 | <0.01 | |
| 12 | 0.004 | 0.002 | <0.01 | |
| Gastrointestinal Procedure | 2 | 0.305 | 0.120 | <0.01 |
| 4 | 0.208 | 0.062 | <0.01 | |
| 6 | 0.142 | 0.039 | <0.01 | |
| 8 | 0.097 | 0.032 | <0.01 | |
| 12 | 0.045 | 0.026 | <0.01 |
S.E.: Standard Error.
Fig. 1.
Predicted probabilities before and after the operation of (A) requiring an admission, (B) undergoing imaging, and (C) undergoing a gastrointestinal procedure.
Overall and component cost
The cost of all admissions before the operation was $26,178 (IQR $10,471–36,649) which decreased to $19,572 (IQR $14,336–24,807) (p < 0.01) after TPIAT. Costs of radiograph utilization and ultrasounds were significantly higher after the operation, but the cost of MRIs was higher before the operation (p < 0.01 for each) (Table 4). There was no significant difference in cost before and after the operation for esophagogastroduodenoscopy, but the cost of endoscopic ultrasounds (p = 0.03) and ERCPs was higher before the operation (p < 0.01). The overall cost of care prior to the operation was $36,006 (IQR $19,914–47,680) which decreased by over $11,000 to $24,900 ($17,432–44,005) after the operation (p = 0.03). Given the cost of the index operation would not be recurring, we then compared the total costs excluding the cost of the operation, which decreased by over $25,000 to $10,564 (IQR $3096–29,669) (p < 0.01).
Table 4.
Component costs before and after operation.
| Cost ($) before operation Median (IQR) | Cost ($) after and including operation Median (IQR) | p-value | |
|---|---|---|---|
| Medical Admission | 26,178 (10,471–36,649) | 19,572 (14,336–24,807) | <0.01 |
| Radiographs (Chest and KUB) | 603 (201–1206) | 1809 (1206–2613) | <0.01 |
| CT Abdomen/Pelvis with Contrast | 385 (0–770) | 385 (0–770) | 0.57 |
| MRI Abdomen/Pelvis | 385 (385–1155) | 0 (0–0) | <0.01 |
| Ultrasound (Single Organ/Quadrant) | 224 (0–448) | 448 (336–784) | 0.01 |
| Esophagogastroduodenoscopy | 0 (0–761) | 0 (0–761) | 0.39 |
| Endoscopic Ultrasound | 0 (0–0) | 0 (0–0) | 0.03 |
| ERCP | 5648 (2824–8472) | 0 (0–0) | <0.01 |
| Total Cost (including TPIAT cost) | 36,006 (19,914–47,680) | 24,900 (17,432–44,005) | 0.03 |
| Total Cost (excluding TPIAT cost) | 36,006 (19,914–47,680) | 10,564 (3096–29,669) | <0.01 |
IQR: Interquartile Range; KUB: Kidney, Ureter, and Bladder; TPIAT: Total Pancreatectomy and Islet Autotransplantation; ERCP: Endoscopic Retrograde Cholangiopancreatography.
Markov modeling for insulin and opioid usage
A Markov model was then created for insulin and opioid usage to predict the six-month probability of transitioning states using data from this cohort. As discussed in the Methods, only two patients required daily insulin at any point prior to the operation and as such, a Markov model was not created for prior to surgery. However, we found that after operation, all patients required insulin initially (per our programmatic protocol) and the six-month probability of transitioning off of insulin was 26.8%, while the probability of remaining on insulin was 73.2% (Table 5).
Table 5.
Six-month transition probability for insulin states after TPIAT.
| Transition Probability | ||
|---|---|---|
| From | Transition To | |
| + | − | |
| + | 73.2% | 26.8% |
| − | 0% | 100% |
A separate model was created for opioid usage. Before surgery, the six-month probability of remaining opioid naïve was 57.2%, while the probability of transitioning to regular opioid usage was 42.8% (Fig. 2A). After surgery, all patients required opioids at discharge. For those who became opioid independent throughout the post-operative period, they had a 100% probability of remaining without regular usage of opioids after transitioning. For those who were discharged on opioids, the six-month probability of remaining on opioids was 10.9% and the probability of transitioning to opioid-free was 89.1% (Fig. 2B). The comparisons of the before and after transition probabilities for each transition state of opioid use based on the operation were significant (Fig. 2C).
Fig. 2.
Markov model of opioid status. (A) Six-month likelihood of transitioning opioid states before operation (B) Six-month likelihood of transitioning opioid states after operation (C) Opioid transition probability comparing before to after the operation.
Discussion
In this single center study, we found that TPIAT in pediatric patients with ARP and CP led to decreased resource utilization and overall annual cost. Patients required fewer admissions and procedures in the year following the operation compared to the year before the operation. Patients also had a high likelihood (43%) of becoming opioid dependent prior to the operation and once these patients developed a need for opioids, there was only a 7% probability of becoming opioid independent without operation. Of those who required opioids for post-operative pain, nearly all (90%) were opioid independent by six months post-TPIAT. While the operation and protocols for post-operative management led to insulin requirements in all patients, a significant number of patients were able to achieve insulin independence throughout the year following operation. Consideration should be given to performing this operation early in pediatric patients with debilitating CP to reduce the financial burden of the disease and to improve overall quality of life.
Although the prevalence of CP in pediatric patients is approaching that of the adult population, there is a paucity of literature assessing the disease in children and its financial impact on the medical system. Wilson et al. found that in adults with minimal change CP, TPIAT led to a $40,000 reduction in annual medical costs per patient while also increasing quality-adjusted life years.8 Another study conducted in the United Kingdom found that compared to total pancreatectomy alone or medical management, TPIAT was cost neutral but led to a higher rate of insulin independence.6 Recently, results from INSPPIRE (International Study Group of Pediatric Pancreatitis: In Search for a Cure), an international consortium studying pediatric pancreatitis, found that annual costs of care were an estimated average of nearly $39,000 per year.3 Our study found similar results, with a median cost of $36,000 per patient in the year prior to operation. Similar to the adult population,8 TPIAT led to an $11,000 reduction in cost in the year following surgery and a predicted $26,000 reduction for each year thereafter. Although we were unable to include the exact costs of opioids, insulin, and pancreatic enzymes due to logistical challenges, our Markov model showed that most patients would eventually become dependent on these expensive medications without surgery but were likely to no longer need insulin and opioids post-operatively. Children still require surveillance (eg, nutrition and growth) and have minor setbacks after TPIAT, but the overall cost including these interventions is still significantly lower than the cost prior to surgery.
Although the financial implications of this operation are important, the reduction in cost is a reflection of a greater outcome, the decreased number of invasive procedures and hospital admissions. Pediatric patients in our study had a median of five admissions during the year prior to the operation. While some admissions were for shorter lengths than others, patients ultimately were still admitted in the hospital for nearly one month. In addition to missing school and falling behind in educational endeavors, the consequences of leaving this disease inadequately treated are poor physical, mental, and psychosocial health. TPIAT has previously been shown to improve physical and mental health scores, as well as overall quality of life when evaluated by the Short Form 36-item Health Survey.4,5 However, given the potential morbidity associated with TPIAT, further work should be undertaken to understand how post-operative outcomes and complications impact quality of life.
A large portion of patients with CP suffer from chronic pain requiring daily analgesics. Institutions have largely attempted to reduce opioid usage for analgesia and progress has been made with non-opioid medications.21 Nonetheless, patients’ pain is often unbearable to the point where opioids may be necessary. In fact, the consensus guidelines regarding treatment of CP in pediatric patients supports the use of opioids given the insufficient relief provided by peripherally-acting analgesia.22,23 The INSPPIRE group found that 94% of physicians treating ARP or CP utilized morphine or an equivalent medication.24 More so, one criterion for patients to be considered for TPIAT is pain or debilitation for six months or greater, demonstrated by either chronic opioid dependence or severely impaired quality of life.25 This is problematic given prior studies have found that frequent opioid use is associated with constant pain, more health care use, and persistent pain even after surgery due to the development of central sensitization.26,27 In the current study, the six-month probability of becoming opioid dependent prior to the operation was 43%. While most patients were able to become opioid independent after TPIAT, a small subset (10%) of these patients are at higher risk for chronic pain and prolonged use after the operation.26 While opioids may be necessary to appropriately treat pain prior to TPIAT, consideration for earlier intervention, perhaps after three months of opioid use, should be given to reduce the risk associated with prolonged opioid usage.
Our study has limitations. First, the modeling performed in our study utilizes cohort data to make predictions on a greater population. The total number of patients in this study is small which limits the ability for making some predictions, however, this cohort represents the largest group studied. Additionally, most patients have just passed their first year after surgery, which limits our analysis of longer-term follow-up. While all procedures, admissions, and imaging were included in the study, outpatient clinic visits were not. However, all patients had continuous close follow up in clinic before and after surgery. Future studies analyzing multiple years of follow up or a study with a matched control group that has not undergone TPIAT would be beneficial. Second, we used Medicare reimbursement data to determine cost estimates. This may not represent reimbursement from all insurance systems or patient populations. Specifically, Medicare does not consistently reimburse for the cost of islet autotransplantation, specifically, and these costs were not included in the overall comparison. Finally, given the variability in how patients take pain medication compared to prescribed, and the frequently changing dosing of these medications over time, we were not logistically able to include the cost of daily opioid and insulin usage. However, the nearly $26,000 reduction in cost of care after surgery is likely far more substantial than the annual total cost of these medications, and our Markov model showed that most patients would require opioids and many would require insulin without operation.
Conclusion
In summary, we found that patients with CP and ARP who undergo TPIAT have a high likelihood of becoming opioid independent after the operation and there is a significant reduction in resource utilization and cost after surgery. TPIAT should be considered given the stark reduction in invasive procedures, hospital admissions, and longevity of opioid usage. While TPIAT is a major operation with potential morbidity, early intervention at National Pancreas Foundation-designated specialized pancreas centers of excellence with multidisciplinary care should be considered to decrease future resource utilization and overall costs among these patients. Further work is needed to understand the impact of TPIAT on health-related quality of life in this population and long-term cost benefit.
Grant support
This research did not receive any funding.
Abbreviations:
- CP
Chronic pancreatitis
- TPIAT
Total pancreatectomy with islet autotransplantation
- IQR
Interquartile range
- ARP
Acute recurrent pancreatitis
- ERCP
Endoscopic retrograde cholangiopancreatography
Footnotes
Declaration of competing interest
The authors have no disclosures to report.
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