Long-term results of total pancreatectomy and autologous islet transplantation for chronic pancreatitis: total pancreatectomy with autologous islet transplantation (TPAIT) preserves long-term islet graft functions in 10-year follow-up

I have read with great interest the paper by Pollard et al. (1) published in Hepatobiliary Surgery and Nutrition. This is a retrospective single-center study presenting 10-year follow-up of 60 patients undergoing total pancreatectomy with autologous islet transplantation (TPAIT) in the University Hospital of Leicester, one of the most experienced in TPAIT centers in the world. The patients had undergone TPAIT between September 1994 to May 2011 (1). The completed 10-year assessment was achieved in 17 patients who were grouped by the authors using the modified Auto-Igls criteria; good response, n=5 (insulin-independent for first 5 years post-TPAIT); partial response, n=6 (insulin requirements <20 IU/day post-TPAIT) and poor response, n=6 (insulin requirements ≥20 IU/day post-TPAIT). In addition, C-peptide, hemoglobin A1c (HbA1c) and oral glucose tolerance test (OGTT) were examined preoperatively, and postoperatively at 3, 6 months and then yearly for 10 years. Based on this study results, the authors concluded that TPAIT preserved long-term islet graft functions in 10-year follow-up. Even in patients in the poor response group, the authors reported C-peptide release (>0.5 ng/mL) after OGTT stimulation that potentially prevents long-term diabetes-related complications. Moreover, in the commented study, C-peptide levels remained remarkably stable for more than 10 years in the “good response” group. For patients in the “partial response” group, C-peptide levels rose significantly following glucose stimulation confirming that a degree of islet function was preserved. It should be added that even in the “poor response” patients by 120 minutes C-peptide levels rose following stimulation. Islet cell graft failure was defined by the International Islet Transplant Registry as C-peptide levels below 0.3 ng/mL. These results showed that TPAIT with an adequate islet cell mass could prevent graft failure and ensure a clinically significant level of graft function (mean C-peptide levels more than 0.3 ng/mL) in all patients (1).

TPAIT is a surgical procedure that is performed to prevent postoperative diabetes secondary to endocrine pancreatic insufficiency and its serious multi-organ complications (2). Chronic pancreatitis (CP), as a progressive inflammatory disease of the pancreas characterized by destruction of the pancreatic parenchyma with subsequent fibrosis, leads to exocrine and endocrine pancreatic insufficiency (3). In the advanced disease caused by total pancreatic destruction, intractable pain resistant to conservative, endoscopic and surgical treatment as well as endocrine pancreatic insufficiency, TPAIT seems to be an optimal option of the management (4). Generally, TPAIT is performed for prevention of postoperative diabetes and its serious complications following total pancreatectomy. Total pancreatectomy without islet transplantation potentially can lead to poorly controlled labile diabetes which leads to secondary multi-organ complications. The current indications for this TPAIT include mainly small-duct painful CP, hereditary/genetic pancreatitis (HGP), as well as less frequent indications such as benign/borderline pancreatic tumors [intraductal papillary mucinous neoplasms (IPMNs), neuroendocrine neoplasms] and “high-risk pancreatic stump” following partial pancreatectomy (5,6). In CP patients, TPAIT is recommended in cases when other non-surgical treatment methods were not effective. Pancreatectomy relieves the pain as well as synchronous autologous islet transplantations prevents postoperative diabetes. Therefore, this procedure improves significantly a quality of life (5,7).

The commented study by Pollard et al. involved only patients with CP (100%), including the most frequent idiopathic CP [n=43 (71.7%)], followed by CP secondary to alcohol [n=11 (18.3%)], gallstones [n=3 (5.0%)], and pancreas divisum [n=3 (5.0%)] (1). The three patients’ groups, distinguished depending on clinical response (good, partial, and poor response) according to Auto-Igls criteria, were characterized and compared in terms of patients’ age, body mass index (BMI), CP etiology, pancreas weight, total islet equivalents (IEQ), % cleavage and islet volume. According to the authors, patient’s age, BMI and the pancreatitis etiology were not significantly different in these three groups while transplanted IEQ/kg were different in the compared groups but meaningful conclusions could not be extracted from these data due to the small sample size (1). It should be pointed that this research did not show the correlation between islet yield and islet graft function in contrast to previous studies which had demonstrated a strong association between islet yield and islet graft function although the size of the cohort available for assessment was likely to be responsible (1,8,9).

The strength of this study is a long-term continuous follow-up of operated patients, with a standard clinical and laboratory control, including not only HbA1c and OGTT, but also C-peptide that it a good and marker for pancreatic islet function. While the study has got some limitations, such as a single-center observation and small cohort size. It should be pointed that among a total of 60 patients undergoing TPAIT, completed follow-up was possible only in 17 patients. Therefore, a meaningful statistical comparative analysis and conclusions are not possible, although the size of the cohort was larger compared to some other recent single-center studies, such as a study by Barthold et al. (n=43) (7) and Fröberg et al. (n=24) (10), Haddad et al. (n=46) (11). On the other side, some single-center studies presenting TPAIT outcomes of larger cohorts have been published, such as studies by Avula et al. (n=629) (12), Darden et al. (n=237) (13), and Down et al. (n=197) (14). Some of these studies included pediatric and adult patients. In a meta-analysis [2020] by Zhang et al. (15), including 17 studies (1,024 patients), the median cohort size was 21 patients (range, 5–409) (15). In a recent multi-center study by Mattke et al. (16), the authors determined predictive factors of islet isolation outcomes. This multicenter Prospective Observational Study of TPIAT (POST) enrolled 406 patients undergoing TPAIT at 12 participating centers, including 130 children and 276 adults. The authors reported that only elevated hemoglobin A1c was significantly related to worse post-TPAIT outcomes (16). In addition, the authors of the presented study precisely analyzed pancreatic islet function that is strongly related with postoperative diabetes. Taking into account the fact that the aim of TPAIT in CP patients is not only prevention of diabetes-related serious complications, but also pain relief and improvement of quality of life, assessment of quality of life and pain reduction in patients following TPAIT would be performed.

In addition, analysis of data collected from a larger cohort could allow to statistically compare the above mentioned three patients’ groups depending on clinical response using the modified Auto-Igls criteria. This comparison would show the association between patient’s age and BMI, as well as pancreatitis etiology, pancreatic IEQ and post-TPAIT long-term outcomes. This knowledge, especially regarding the impact of modifiable factors on postoperative outcomes could allow to improve long-term results in patients following TPAIT by adequate modification of factors influencing adversely on islet graft functions and postoperative outcomes.

In summary, the study by Pollard et al. has made a significant contribution to the available literature on long-term results of TPAIT in CP patients. The study showed preservation of long-term islet graft functions in 10-year follow-up what was confirmed by laboratory tests, including mean C-peptide levels more than 0.3 ng/mL even in the poor response group classified using the modified Auto-Igls criteria. These results confirm that TPAIT is an optimal option for patients with CP with intractable pain resistant to other methods of treatment, because it relieves the pain and prevents postoperative diabetes for a long-time following operation. The authors should continue their observations to perform further studies involving a larger cohort as well as analysis of more postoperative parameters and associations, including patients’ quality of life.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, HepatoBiliary Surgery and Nutrition. The article did not undergo external peer review.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2024-659/coif). The author has no conflicts of interest to declare.

Ethical Statement: The author is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Pollard CA, Chung WY, Garcea G, et al. Assessment of long-term graft function following total pancreatectomy and autologous islet transplantation: the Leicester experience. Hepatobiliary Surg Nutr 2023;12:682-91. [Crossref] [PubMed]
2. Jabłońska B, Mrowiec S. Total Pancreatectomy with Autologous Islet Cell Transplantation-The Current Indications. J Clin Med 2021;10:2723. [Crossref] [PubMed]
3. Jabłońska B. Is endoscopic therapy the treatment of choice in all patients with chronic pancreatitis? World J Gastroenterol 2013;19:12-6. [Crossref] [PubMed]
4. Jabłońska B, Mrowiec S. Pancreatectomy and Pancreatic Surgery. Life (Basel) 2023;13:1400. [Crossref] [PubMed]
5. Bellin MD, Freeman ML, Gelrud A, et al. Total pancreatectomy and islet autotransplantation in chronic pancreatitis: recommendations from PancreasFest. Pancreatology 2014;14:27-35. [Crossref] [PubMed]
6. Piemonti L, Melzi R, Aleotti F, et al. Autologous Pancreatic Islet Cell Transplantation Following Pancreatectomy for Pancreas Diseases Other Than Chronic Pancreatitis: A 15-y Study of the Milan Protocol. Transplantation 2024;108:1962-75. [Crossref] [PubMed]
7. Barthold L, Smith KD, Chaidarun SS, et al. Quality of Life Following Total Pancreatectomy With Islet Autotransplantation: A Patient Experience Survey. Pancreas 2024;53:e652-6. [Crossref] [PubMed]
8. Ahmad SA, Lowy AM, Wray CJ, et al. Factors associated with insulin and narcotic independence after islet autotransplantation in patients with severe chronic pancreatitis. J Am Coll Surg 2005;201:680-7. [Crossref] [PubMed]
9. Sutherland DE, Radosevich DM, Bellin MD, et al. Total pancreatectomy and islet autotransplantation for chronic pancreatitis. J Am Coll Surg 2012;214:409-24; discussion 424-6. [Crossref] [PubMed]
10. Fröberg K, Halimi A, Vujasinovic M, et al. Outcome after total pancreatectomy with islet autotransplantation: A European single-center study. Scand J Surg 2024;113:80-7. [Crossref] [PubMed]
11. Haddad EN, Lansang MC, Xiao H, et al. Preoperative and Postoperative Predictors of Insulin Independence From Total Pancreatectomy and Islet Autotransplantation. Endocr Pract 2024;30:752-7. [Crossref] [PubMed]
12. Avula N, Hodges JS, Beilman G, et al. Increased kidney stone risk following total pancreatectomy with islet autotransplantation. Pancreatology 2024;24:1167-73. [Crossref] [PubMed]
13. Darden CM, Mohammed ARH, Kirkland J, et al. Total pancreatectomy with islet autotransplantation outcomes in patients with pancreatitis of genetic etiology: A single-center experience with a large cohort of patients. J Gastrointest Surg 2024;28:1309-18. [Crossref] [PubMed]
14. Downs EM, Hodges JS, Trikudanathan G, et al. Essential Fatty Acid Deficiency Is Common After Total Pancreatectomy and Islet Autotransplantation. Pancreas 2024;53:e689-93. [Crossref] [PubMed]
15. Zhang YJ, Duan DD, Yuan H. Efficacy and safety of islet autotransplantation after total pancreatectomy in chronic pancreatitis: A systematic review and meta-analysis including 17 studies. Clin Res Hepatol Gastroenterol 2020;44:598-608. [Crossref] [PubMed]
16. Mattke J, Eaton A, Wijkstrom MIslet Isolation Outcomes in Patients Undergoing Total Pancreatectomy With Islet Autotransplantation in the POST Consortium, et al. Transplantation 2025;109:207-16. [Crossref] [PubMed]