Long-Term Outcomes of Total Pancreatectomy and Islet Auto Transplantation for Hereditary/Genetic Pancreatitis

Abstract

Background Chronic-pancreatitis is a debilitating-disease resulting from many etiologies. The-subset with hereditary/genetic defects (HGP) not only has chronic-pain, but also an increased-risk for pancreatic-cancer. The long-term-outcomes of TP-IAT for chronic pancreatitis due-to-HGP are not clear. Study Design Review of a prospectively-maintained-database of 484 TP-IAT-from-1977-2012 at a single-center. The-outcomes (pain-relief, narcotic-use, β cell-function, health-related quality of-life-measures of patients-that-received TP-IAT for hereditary/genetic-defects (PRSS1 (n=38), SPINK1 (n=9), CFTR (n=14) and Familial (n=19) were-evaluated-and-compared to those with non-hereditary/genetic-etiology. Results All 80 patients with HGP were narcotic-dependent and failed-endoscopic-management or direct-pancreatic-surgery. Post TP-IAT, 90% of the patients-were-pancreatitis-pain-free with sustained-pain-relief; over 65% had partial or full β-cell-function.-Compared to non-hereditary etiologies, HGP were-younger (22 yrs vs.38 yrs p=<0.001), had-pancreatitis-pain of longer-duration (11.6±1.1 vs. 9.0±0.4 yrs p=0.016), had a higher-pancreas-fibrosis-score (7±0.2 vs. 4.8±0.1 p=<0.001), and-trended-toward-lower-Islet-yield (3,435 ± 361 IEQ vs. 3850± 128 IEQ p=0.28). Using-multivariate-logistic-regression, (1) non-HGP-etiology (p value=0.019) (2) lower severity-of-pancreas-fibrosis (p value < 0.001), (3) shorter-duration-of-years with pancreatitis (p value = 0.008) and (4) higher-transplant IEQ per KG body-weight (p value =<0.001) were-more likely-to-achieve-insulin-independence (p value < 0.001). There was a significant-improvement in HRQoL from-baseline, by SF-36, in physical-and-mental-component HRQoL scores (p <0.001). None-of-the-patients in the entire-cohort-developed-cancer of pancreatic-origin in the liver or elsewhere during 2,936 person-years of follow-up. Conclusions TP-IAT in patients with chronic pancreatitis due to HGP etiology provides long-term pain relief (90%) and preservation-of-beta-cell-function. Patients with chronic-painful pancreatitis due to HGP with a high-life-time-risk of pancreatic-cancer should be considered earlier for TP-IAT before pancreatic-inflammation results in higher-degree of pancreatic-fibrosis and islet-cell-function-loss.

Total Pancreatectomy With Islet Autotransplantation

“…Thus, limitations in diagnostic testing and difficulty in distinguishing pancreatitis from other sources of pain complicate the selection of candidates. In addition, there are emerging limited data suggesting that pain responses might be better in those CP patients with genetic mutations (13) compared to those who are alcoholics (14). The risks of insufficient islet mass and central sensitization of pain along with the likelihood of progression of disease should be considered in the timing of intervention.…”

“…Dosing of pancreatic enzymes in patients with exocrine insufficiency is highly variable, and many patients are undertreated. Monitoring of nutrition in CP or after TPIAT (fat soluble vitamins, vitamin B12, weight, muscle mass, and bone health) is performed sporadically, depending on the individual center (13, 63). …”

Islet autotransplantation: past, present and future. Chapter II: the role of islet autotransplantation for the treatment of chronic pancreatitis

“…These results confirmed the fact that TP-IAT is effective in preserving b-cell function in patients with CP due to hereditary cases. However, the authors suggested that TP-IAT should be considered earlier in the course of disease, before pancreatic inflammation results in a higher degree of pancreatic fibrosis and deterioration of islet cells function [62].…”

Hereditary Pancreatitis

“…As with other forms of pancreatitis, endoscopic or surgical interventions may also be indicated to alleviate pain. There is growing use of total pancreatectomy with islet autotransplantation (TP-IAT) in the United States, and this appears to be an effective (and radical) treatment in some patients (8,14) (see below).…”

“…Total pancreatectomy with islet autotransplantation may be considered in younger patients for unmanageable pain (13,14). Older patients with longstanding CP may benefit from total pancreatectomy without islet autotransplantation for pain alleviation and to reduce the risk of pancreatic cancer (13,71).…”