Factors Associated with Insulin and Narcotic Independence after Islet Autotransplantation in Patients with Severe Chronic Pancreatitis

doi:10.1016/j.jamcollsurg.2005.06.268

Journal of the American College of Surgeons

Volume 201, Issue 5, November 2005, Pages 680-687

Presented at the American College of Surgeons 90th Annual Clinical Congress, New Orleans, LA, October 2004.

https://doi.org/10.1016/j.jamcollsurg.2005.06.268 Get rights and content

Background

For patients who suffer from severe chronic pancreatitis, total pancreatectomy can alleviate pain, and islet autotransplantation (IAT) might preserve endocrine function and circumvent the complications of diabetes. Factors that determine success after this operation have not been clearly defined.

Study design

From 2000 to 2004, 45 total or subtotal pancreatectomies with IAT were performed. Patient characteristics, narcotic usage and insulin requirements were recorded at routine followup. Narcotic usage was standardized by conversion to morphine equivalents (MEs). Univariate and multivariate statistical analyses were performed to determine factors associated with insulin and narcotic independence.

Results

Forty-five patients (30 women, 15 men), with a mean age of 39 years (range 16 to 62 years) underwent total or completion (n = 41) or subtotal (n = 4) pancreatectomies with IAT. Forty percent of patients were insulin free after a mean followup of 18months (range 1 to 46months). Factors associated in univariate analyses with insulin independence included female gender (p = 0.004), lower body weight (kg) (p = 0.04), more islet equivalents per kg body weight (IEQ/kg) transfused (<0.05), lower mean insulin requirement for the first 24hours postoperation (p = 0.002), and lower mean insulin requirement at discharge (p = 0.0005). A multiple logistic regression using gender, body mass index, and IEQ/kg identified female gender as the only notable variable associated with insulin independence. There was a notable reduction (p < 0.0001) of postoperative MEs (mean 90 mg) compared with preoperative MEs (mean 206 mg) for the entire cohort; 58% of patients are narcotic independent. In the subset of patients with > 5months followup (n = 32), 23 (72%) are narcotic free, with a substantial decrease in ME usage (p = 0.01).

Conclusions

The likelihood of glycemic control after IAT is related to both patient characteristics and islet cell mass. Based on these data, more islet cells may be required for insulin independence than previously thought.

Section snippets

Patients

All patient data in this study were collected and reported in strict compliance with patient confidentiality guidelines put forth by the University of Cincinnati Institutional Review Board. Between July 2000 and June 2004, the multidisciplinary Pancreatic Disease Center referred 45 patients for total or completion pancreatectomy with IAT. The diagnosis of CP was based on individualized characteristics of the patient’s history, index operation, response to endoscopic stenting, laboratory tests,

Patients

From July 2000 to June 2004, 45 patients (30 women, 15 men), with a median age of 39 years (range 16 to 62 years) underwent total (n = 29), completion (n = 12), or near total (n = 4) pancreatectomies with IAT at the University of Cincinnati Medical Center (Table 1). In our series, the mean weight was 74 kg and BMI was 26. The etiology of CP was idiopathic (n = 39), alcohol (n = 2), trauma (n = 1), ERCP (n = 1), hereditary (n = 1), and drug toxicity (n = 1). Of the 39 patients with idiopathic CP, 8 were

Discussion

CP is a progressive inflammatory process that causes permanent damage to both the exocrine and endocrine pancreas. This process often impairs insulin secretory function, and insulin-dependent diabetes evolves in 20% to 30% of all patients with CP.¹⁴ Most patients are treated initially with a combination of narcotics and endoscopic interventions. Unfortunately, greater than 50% develop progressive symptoms and require additional interventions.¹⁵ For these patients, several surgical options are

Acknowledgment

We wish to thank Kate Trulock and Debbie Soldano for collecting information and data for this study.

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Cited by (143)

Diffuse calcification of pancreas impairs endocrine function and predicts poor outcome in total pancreatectomy with islet autotransplantation
2023, American Journal of Transplantation
In patients with chronic pancreatitis, pancreatic calcification is a risk factor for diabetes development, poor islet yield, and metabolic outcomes after total pancreatectomy with islet autotransplantation (TPIAT). We investigated whether calcification pattern based on computed tomography is associated with outcomes using our database of 200 consecutive TPIAT procedures. Three groups were compared: noncalcification (NC); focal calcification, limited to the pancreas head, body, or tail; and diffuse calcification (DC), with calcification in >2 sections. Maximum changes in outcomes were seen in the DC vs focal calcification group. In the DC group, preoperative hemoglobin A1c levels were higher (P < .01), and stimulated C-peptide levels were lower (P < .01) than in the NC group. Islet isolation from the DC pancreas resulted in the lowest islet equivalent (IEQ) yield and IEQ/kg among the 3 groups (P < .0001), with no insulin independence 12 months posttransplant (P < .05 vs NC group). Notably, at 12 months, the DC group was 91.7% narcotic-free, significantly higher than the NC group (P < .05). Although DC is a sign of diabetes risk after TPIAT, the DC group showed exceptional pain relief. These findings suggest that TPIAT can be beneficial for patients with chronic pancreatitis with severe calcification.
Total Pancreatectomy with Islet Auto-Transplantation: Surgical Procedure, Outcomes, and Quality of Life
2023, Advances in Surgery
Minimally invasive surgery versus open surgery for total pancreatectomy: a bibliometric review and meta-analysis
2023, HPB
Minimally invasive total pancreatectomy (MITP) is considered safe and feasible with limited evidence on this procedure. The aim of this study was to systematically analyze the current literature on MITP compared to open TP (OTP).
Randomized controlled trials and prospective non-randomized comparative studies were sought systematically in MEDLINE, Web of Science and CENTRAL from their inception until December 2021. Outcome measures included operative time, length of hospital stay (LOH), spleen-preservation rate, estimated blood loss (EBL), need for transfusion, venous resection rate, delayed gastric emptying (DGE), biliary leakage, postpancreatectomy hemorrhage (PPH), reoperation rate, overall 30-day morbidity (Clavien-Dindo > IIIa), 90-day mortality, 90-day readmission, examined lymph nodes (ELN). Pooled results are presented as odds ratios (OR) or mean difference (MD) with 95% confidence interval (CI).
7 observational studies with a total of 4212 patients were included. MITP had a decreased EBL and transfusion rate, lower 30-day morbidity and 90-day mortality with a longer LOH compared to OTP. There were no significant differences regarding operative time, spleen preservation rate, DGE, biliary leakage, venous resection rate, PPH, reoperation, 90-day readmission and ELN.
Based on the available studies, MITP is safe and feasible compared to OTP in highly experienced hands from high-volume centers. Further high-quality studies are needed to verify the conclusion.
A randomized controlled pilot trial of etanercept and alpha-1 antitrypsin to improve autologous islet engraftment
2023, Pancreatology
In total pancreatectomy with islet auto-transplantation, successful diabetes outcomes are limited by islet loss from the instant blood mediated inflammatory response. We hypothesized that blockade of the inflammatory response with either etanercept or alpha-1-antitrypsin would improve islet function and insulin independence.
We randomized 43 participants to receive A1AT (90 mg/kg x 6 doses, n = 13), or etanercept (50 mg then 25 mg x 5 doses, n = 14), or standard care (n = 16), aiming to reduce detrimental effects of innate inflammation on early islet survival. Islet graft function was assessed using mixed meal tolerance testing, intravenous glucose tolerance testing, glucose-potentiated arginine-induced insulin secretion studies, HbA1c, and insulin dose 3 months and 1 year post-TPIAT.
We observed the most robust acute insulin response (AIRglu) and acute C-peptide response to glucose (ACRglu) at 3 months after TPIAT in the etanercept-treated group (p ≤ 0.02), but no differences in other efficacy measures. The groups did not differ overall at 1 year but when adjusted by sex, there was a trend towards a sex-specific treatment effect in females (AIRglu p = 0.05, ACRglu p = 0.06), with insulin secretion measures highest in A1AT-treated females.
Our randomized trial supports a potential role for etanercept in optimizing early islet engraftment but it is unclear whether this benefit is sustained. Further studies are needed to evaluate possible sex-specific responses to either treatment.
This study was performed under an Investigational New Drug Application (IND #119828) from the Food and Drug Administration and was registered on clinicaltrials.gov (NCT#02713997).
Total pancreatectomy and islet cell autotransplantation: a 10-year update on outcomes and assessment of long-term durability
2022, HPB
Total pancreatectomy and islet cell autotransplantation (TPIAT) offers an effective, lasting solution for the management of chronic pancreatitis up to 5-years post-operatively. Our aim was to assess durability of TPIAT at 10-years.
Patients undergoing TPIAT for chronic pancreatitis eligible for 10-year follow-up were included. Primary outcomes, including endocrine function and narcotic requirements, were reported at 5-, 7.5-, and 10-years post-operatively.
Of the 231 patients who underwent TPIAT, 142 met inclusion criteria. All patients underwent successful TPIAT with an average of 5680.3 islet equivalents per body weight. While insulin independence tended to decrease over time (25.7% vs. 16.0% vs. 10.9%, p = 0.11) with an increase in HbA_1C (7.6% vs. 8.2% vs. 8.4%, p = 0.09), partial islet function persisted (64.9% vs. 68.0% vs. 67.4%, p = 0.93). Opioid independence was achieved and remained durable in the majority (73.3% vs. 72.2% vs. 75.5%, p = 0.93). Quality of life improvements persisted, with 85% reporting improvement from baseline at 10-years. Estimated median overall survival was 202.7 months.
This study represents one of the largest series reporting on long-term outcomes after TPIAT, demonstrating excellent long-term pain control and durable improvements in quality of life. Islet cell function declines over time however stable glycemic control is maintained.
Risk factors associated with hypoglycemic events after total pancreatectomy: A nationwide multicenter prospective study in Japan
2022, Surgery (United States)
The number of total pancreatectomy cases have increased worldwide, expanding the need for new insulin products and high-titer pancrelipases. However, the current data that is focused on hypoglycemic events after a total pancreatectomy from large nationwide series are still lacking. This study is aimed to assess the risk factors associated with hypoglycemic events after a total pancreatectomy.
Data were prospectively collected from 216 consecutive patients who underwent total pancreatectomies between August 2015 and December 2017 from 68 Japanese centers. Of the 216 patients, 166 with a follow-up period of 1 year were analyzed. The risk factors for hypoglycemic events at 6 and 12 months (postoperative months 6 and 12) were investigated based on the results of a nationwide multicenter prospective study.
Of the 166 patients, 57 (34%) and 70 (42%) experienced moderate or severe hypoglycemic events or hypoglycemia unawareness on a monthly basis at postoperative months 6 and 12, respectively. Multivariate analysis revealed that body weight loss after surgery ≥0.3 kg and total cholesterol level ≤136 mg/dL at postoperative month 6, and glycated hemoglobin level ≤8.9% and rapid-acting insulin use at postoperative month 12 were independent risk factors for hypoglycemic events after a total pancreatectomy. There were different independent risk factors depending on the postoperative period.
Patients with body weight loss after surgery, low total cholesterol level, strict glycemic control, and using rapid-acting insulin should be aware of the occurrence of hypoglycemic events after their total pancreatectomy. In order to prevent hypoglycemic events after a total pancreatectomy, we need to consider optimal nutritional and glycemic control according to the postoperative period.

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: Competing Interests Declared: None.

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Original scientific articleFactors Associated with Insulin and Narcotic Independence after Islet Autotransplantation in Patients with Severe Chronic Pancreatitis

Background

Study design

Results

Conclusions

Section snippets

Patients

Patients

Discussion

Acknowledgment

Surg Clin North Am

Surg Clin North Am

J Gastrointest Surg

J Am Coll Surg

Metabolism

Pancreatoduodenectomy for chronic pancreatitisanatomic selection criteria and subsequent long-term outcome analysis

Ann Surg

Long-term results of distal pancreatectomy for chronic pancreatitis in 90 patients

Ann Surg

Extended drainage versus resection in surgery for chronic pancreatitisa prospective randomized trial comparing the longitudinal pancreaticojejunostomy combined with local pancreatic head excision with the pylorus-preserving pancreatoduodenectomy

Ann Surg

Autotransplantation of dispersed pancreatic islet tissue combined with total or near-total pancreatectomy for treatment of chronic pancreatitis

Surgery

Pancreas resection and islet autotransplantation for end-stage chronic pancreatitis

Ann Surg

Autologous islet transplantation to prevent diabetes after pancreatic resection

Ann Surg

The risks of total pancreatectomy and splenic islet autotransplantation

Cell Transplant

Original scientific article
Factors Associated with Insulin and Narcotic Independence after Islet Autotransplantation in Patients with Severe Chronic Pancreatitis