Total Pancreatectomy With Islet Autotransplantation Research Articles

Quality of Life Following TPIAT: A Patient Experience Survey.

Total pancreatectomy with islet autotransplantation (TPIAT) is performed to improve the quality of life (QOL) of patients with chronic pancreatitis. Few reports have documented QOL following TPIAT, with none using the pancreatitis-specific Pancreatitis Quality of Life Instrument (PANQOLI). We surveyed patients at our center who underwent TPIAT to document postoperative QOL. We collected survey data from 18 adult patients who underwent TPIAT at our medical center from 2012 to 2020. Patients were asked questions assessing QOL following TPIAT and completed the Short Form (SF)-12 and PANQOLI instruments. Forty-three patients who underwent TPIAT were mailed surveys, and 18 were returned. The mean age was 45 years, and 67% of respondents were female. Almost half (44%) had hereditary pancreatitis. Sixty-seven percent believed their overall QOL had improved after surgery. The mean post-operative SF-12 physical score was 38.9 and mean mental score was 44. The mean PANQOLI score was 66 (physical function 20, role function 16, emotional function 14, self-worth 15). Following surgery, 33% were using opiate medications and 67% were using anti-hyperglycemic medications. TPIAT resulted in improved self-reported QOL in most patients, although post-operative physical and mental QOL are less compared to the average healthy United States adult.

Addressing long-term mortality risk in patients undergoing total pancreatectomy with islet autotransplant (TPIAT): causes of death and risk factors

BackgroundTotal pancreatectomy with islet autotransplant (TPIAT) can improve quality of life for individuals with pancreatitis but creates health risks including diabetes, exocrine insufficiency, altered intestinal anatomy and function, and asplenia. MethodsWe studied survival and causes of death for 693 patients who underwent TPIAT between 2001 and 2020, using the National Death Index with medical records to ascertain survival after TPIAT, causes of mortality, and risk factors for death. We used Kaplan Meier curves to examine overall survival, and Cox regression and competing-risks methods to determine pre-TPIAT factors associated with all-cause and cause-specific post-TPIAT mortality. ResultsMean age at TPIAT was 33.6 years (SD = 15.1). Overall survival was 93.1% (95% CI 91.2, 95.1%) 5 years after surgery, 85.2% (95% CI 82.0, 88.6%) at 10 years, and 76.2% (95% CI 70.8, 82.3%) at 15 years. Fifty-three of 89 deaths were possibly related to TPIAT; causes included chronic gastrointestinal complications, malnutrition, diabetes, liver failure, and infection/sepsis. In multivariable models, younger age, longer disease duration, and more recent TPIAT were associated with lower mortality. ConclusionsFor patients undergoing TPIAT to treat painful pancreatitis, careful long-term management of comorbidities introduced by TPIAT may reduce risk for common causes of mortality.

Peri-Transplant Inflammation and Long-Term Diabetes Outcomes Were Not Impacted by Either Etanercept or Alpha-1-Antitrypsin Treatment in Islet Autotransplant Recipients.

The instant blood-mediated inflammatory response (IBMIR) causes islet loss and compromises diabetes outcomes after total pancreatectomy with islet autotransplant (TPIAT). We previously reported a possible benefit of etanercept in maintaining insulin secretion 3months post-TPIAT. Here, we report 2-year diabetes outcomes and peri-operative inflammatory profiles from a randomized trial of etanercept and alpha-1 antitrypsin (A1AT) in TPIAT. We randomized 43 TPIAT recipients to A1AT (90mg/kg IV x6 doses, n = 13), etanercept (50mg then 25mg SQ x 5 doses, n = 14), or standard care (n = 16). Inflammatory cytokines, serum A1AT and unmethylated insulin DNA were drawn multiple times in the perioperative period. Islet function was assessed 2years after TPIAT with mixed meal tolerance test, intravenous glucose tolerance test and glucose-potentiated arginine induced insulin secretion. Cytokines, especially IL-6, IL-8, IL-10, and MCP-1, were elevated during and after TPIAT. However, only TNFα differed significantly between groups, with highest levels in the etanercept group (p = 0.027). A1AT increased after IAT in all groups (p < 0.001), suggesting endogenous upregulation. Unmethylated insulin DNA ratios (a marker of islet loss) and 2years islet function testing were similar in the three groups. To conclude, we found no sustained benefit from administering etanercept or A1AT in the perioperative period.

Nutrition challenges following total pancreatectomy with islet autotransplantation.

Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical treatment option for patients with chronic pancreatitis who have not responded to other therapies. TP offers pain relief whereas IAT preserves beta cell mass to reduce endocrine insufficiency. During the surgical procedure, the entire pancreas is removed. Islet cells from the pancreas are then isolated, purified, and infused into the liver via the portal vein. Successful TPIAT relieves pain for a majority of patients but is not without obstacles, specifically gastrointestinal, exocrine, and endocrine challenges. The postoperative phase can be complicated by gastrointestinal symptoms causing patients to have difficulty regaining adequate oral intake. Enteral nutrition is frequently provided as a bridge to oral diet. Patients undergoing TPIAT must be monitored for macronutrient and micronutrient deficiencies following the procedure. Exocrine insufficiency must be treated lifelong with pancreatic enzyme replacement therapy. Endocrine function must be monitored and exogenous insulin provided in the postoperative phase; however, a majority of patients undergoing TPIAT require little or no long-term insulin. Although TPIAT can be a successful option for patients with chronic pancreatitis, nutrition-related concerns must be addressed for optimal recovery.

Current status of total pancreatectomy with islet autotransplantation for chronic and recurrent acute pancreatitis.

Total pancreatectomy with islet autotransplantation (TPIAT) is an established and effective treatment modality for patients diagnosed with intractable chronic pancreatitis (CP) and recurrent acute pancreatitis (RAP). TPIAT primarily aims to manage debilitating pain leading to impaired quality of life among patients with CP or RAP, which can be successfully managed with medical, endoscopic, or surgical interventions. TPIAT is significantly successful in relieving pain associated with CP and improving health-related quality of life outcomes. Furthermore, the complete loss of pancreatic endocrine function attributed to total pancreatectomy (TP) can be compensated by autologous islet transplantation (IAT). Patients receiving IAT can achieve insulin independence or can be less dependent on exogenous insulin compared with those receiving TP alone. Historically, TPIAT has been mainly used in the United States, and its outcomes have been improving due to technological advancements. Despite some challenges, TPIAT can be a promising treatment for patients with CP-related intractable pain. Thus far, TPIAT is not commonly performed in Japan. Nevertheless, it may improve health-related quality of life in Japanese patients with CP, similar to Western patients. This review article aimed to provide an overview of the indications, related procedures, and outcomes of TPIAT and to discuss future prospects in Japan.

Endocrine Management and Clinical Outcomes in a Cohort of Pediatric Patients Undergoing Total Pancreatectomy with Islet Autotransplantation.

Objective: To describe management strategies that contributed to optimal outcomes in pediatric recipients of a total pancreatectomy with islet autotransplantation (TPIAT). Research Design and Methods: We provide a comprehensive report of the approach to endocrine management of the pediatric TPIAT recipient from initial evaluation through the first 4 years postsurgery. We performed a retrospective review of the endocrine outcomes of TPIAT recipients to describe the impact of this approach on post-TPIAT glycemic management. Results: Outcome data from 86 TPIAT recipients were reviewed. At 12 months post-TPIAT (n = 82), the median HbA1C was 6.0% (25-75th percentile 5.6-6.7), at 18 months (n = 56) HbA1C was 6.4% (5.6-7.5), at 2 years (n = 46) HbA1C was 6.4% (5.6-7.4), at 3 years (n = 31) HbA1C was 6.5% (5.5-8.1), and at 4 years (n = 16) HbA1C was 7.2% (6.2-8.3). Conclusions: Pediatric patients at our institution have favorable endocrine outcomes as evidenced by median HbA1C under the goal of 6.5% through the initial 3 years by following our modified management protocols.

337.2: The Epidemiology of Hereditary Pancreatitis in Australia and its effect on patient of Total Pancreatectomy with Islet Auto-Transplantation (TPIAT).

337.2: The Epidemiology of Hereditary Pancreatitis in Australia and its effect on patient of Total Pancreatectomy with Islet Auto-Transplantation (TPIAT).

203.1: Total pancreatectomy with islet auto-transplantation (TPIAT): Improving quality of life for patients with chronic pancreatitis at OHSU

203.1: Total pancreatectomy with islet auto-transplantation (TPIAT): Improving quality of life for patients with chronic pancreatitis at OHSU

Improved Quality of Life Among Chronic Pancreatitis Patients Undergoing Total Pancreatectomy With Islet Autotransplantation-Single Center Experience With Large Cohort of Patients.

Total pancreatectomy with islet autotransplantation (TPIAT) is the treatment of choice to preserve pancreatic endocrine function, alleviate pain, and improve quality of life (QoL) when other strategies are ineffective for chronic pancreatitis (CP) patients. This study utilized pancreatic disease-specific surveys developed by the European Organisation for Research and Treatment of Cancer (EORTC) to conduct a comprehensive, single-center examination of a large cohort of patients to gain understanding of QoL post-TPIAT. Two validated QoL surveys of the EORTC-QLQ-C30 and QLQ-PAN26-were administered in a prospective cohort of CP patients during pre-and post-operative scheduled visits. A total of 116 patients responded to the preoperative survey and were included in this study. The global health scale of QLQ-C30 was significantly improved after TPIAT when compared to baseline with delta scores of 24.26, 20.54, and 26.7 at 1, 2, and 3years post-TPIAT (p < 0.001). The EORTC-PAN26 revealed significant improvements in symptom scales for pancreatic pain, bloating, digestive symptoms, taste, indigestion, weight loss, body image, and future worries. The comprehensive surveys in such a large cohort expands the QoL criterion in CP patients and indicates significant improvement in QoL post-TPIAT, further validating TPIAT as a treatment option for refractory CP.

Islet graft function by mixed meal tolerance testing is sustained over 4years in young children undergoing total pancreatectomy with islet autotransplantation.

Children with intractable chronic pancreatitis may require total pancreatectomy with islet autotransplantation (TPIAT) for pain relief. The IAT reduces the severity of post- pancreatectomy diabetes. We analyzed 635 mixed meal tolerance tests (MMTT) in 134 children undergoing TPIAT to determine whether superior survival of islet grafts explains higher rates of insulin independence previously reported in young children (n=52, age 3-11years) versus adolescents (n=82, age 12-18years). For MMTT, children consumed Boost HP and we sampled C-peptide and glucose repeatedly over 2h. The trajectory of outcomes before and after TPIAT was compared between children and adolescents using data from pre-TPIAT and 3, 6months, 1, 2, 3, and 4years post-TPIAT and mixed linear models with a random effect for child. Cox regression was used to analyze time outcomes (e.g., time to first off insulin). Islet mass transplanted, measured as islet equivalents (IEQ), was higher in adolescents (p=.003) but IEQ/kg was higher in young children (p<.001) because of their lower weight. AUC C-peptide in young children increased somewhat over 4years, but was stable in adolescents (p=.0013). AUC glucose increased more in adolescents over time post-TPIAT (p=.0024). Islet function by AUC C-peptide:AUC glucose ratio was better preserved in young children (p<.001). Adolescents were less likely to wean off insulin (hazard ratio .44 [95% CI .28, .69]). These data support an advantage of young age in islet graft survival after TPIAT. The greater likelihood of insulin independence in young children may be driven by better islet survival after transplant.

Total pancreatectomy with islet autotransplantation reduces opioid use and improves nutritional support in children with debilitating pancreatitis.

Chronic pancreatitis (CP) can result in opioid dependence and nutritional challenges in children. Total pancreatectomy with islet autotransplantation (TPIAT) is a viable surgical option in appropriately selected patients. We examined differences between children who met criteria for TPIAT versus those who did not and continued with non-operative management. Retrospective observational cohort study of patients evaluated for TPIAT between August 2014 and July 2020 was performed. Cohort-based analyses between TPIAT and non-TPIAT groups were performed. Analyses included 121 patients, 69 of whom underwent TPIAT. Demographics, genetic risk factors, and anatomic variants did not differ between groups. TPIAT patients were more likely to have CP (88% vs 71%; p = 0.02), had higher median number of endoscopic retrograde cholangiopancreatography procedures (2.0 vs 1.0; p = 0.0001), and had higher likelihood of opioid use (61% vs 42%; p = 0.04) and nutritional supplementation (23% vs 4%; p = 0.004), compared to non-TPIAT. At 6 months post-TPIAT, patients had lower use of any analgesic pain medications (39% vs 73%; p = 0.0002) and lower use of opioids (9% vs 39%; p = 0.0006), compared to non-TPIAT patients at 6 months after evaluation. At 6 months post-TPIAT, rate of exclusively oral nutrition increased from 77% to 86%, and total parenteral nutrition use decreased from 13% to 0% (p = 0.02). In children referred for TPIAT evaluation, there is greater burden of disease in those selected for operation, compared to patients who do not undergo operation. TPIAT achieves lower analgesic pain medication use compared to continuation with non-TPIAT management and achieves freedom from nutritional supplementation. Level of evidence: Retrospective comparative study, Level III.

Diffuse calcification of pancreas impairs endocrine function and predicts poor outcome in total pancreatectomy with islet autotransplantation

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.

Diabetes-Related Quality of Life Assessment in Children following Total Pancreatectomy with Islet Autotransplantation

Total pancreatectomy with islet autotransplantation (TPIAT) can improve pain and reduce functional impairment associated with acute recurrent or chronic pancreatitis. However, long-term glucose monitoring and insulin therapy are often required, which can adversely affect the quality of life. We sought to evaluate diabetes-related quality of life (DR-QOL) in youth who underwent TPIAT and compare it to the youth with new-onset type 1 diabetes (T1D). The Pediatric Quality of Life Inventory™ 3.2 Diabetes Module (PedsQL™ DM) was used to assess DR-QOL in 46 youth (&lt;20 years old) who underwent TPIAT. The PedsQL™ DM scores were analyzed for statistically significant changes and minimally important clinical differences (MCID) over time post-TPIAT. Scores at 12 months (n = 29) and 24 months (n = 16) were then compared to PedsQL™ DM scores from a historical cohort of demographically similar (age and sex) youth with a 12 months (n = 52) and 24 months (n = 58) after diagnosis of T1D. The diabetes symptoms summary score (mean 65 to 57 and p = 0.03 ) and the total score (mean 74 to 68 and p &lt; 0.05 ) decreased (worsened) during the first 24 months post-TPIAT and met the MCID threshold, suggesting the decrease in these scores was clinically significant. Post-TPIAT PedsQL™ DM scores were not significantly different than youth new diagnosis of T1D after 24 months (all p &gt; 0.2 ). In youth who underwent TPIAT, DR-QOL worsened over the first two years, mostly attributable to the diabetes symptoms score. Compared to children with T1D, post-TPIAT DR-QOL was similar two years after diabetes onset.

1481-P: Islet Cell Autoantibody Formation and Its Effect on Insulin Requirement after Total Pancreatectomy with Islet Autotransplantation (TPIAT)

Introduction: Long term insulin requirements following TPIAT range from insulin independence to full (high) dose daily insulin (&amp;gt;0.5 units/kg/day). Markers of islet cell autoimmunity are used in children to predict type 1 diabetes risk. However, no studies have explored whether an association exists between islet cell autoimmunity and insulin requirement following TPIAT in children. We hypothesized that children with islet cell autoantibody formation were more likely to have a persistent insulin requirement following TPIAT. Methods: All children who underwent TPIAT between 2015 and 2021 at our institution were eligible for inclusion. Islet cell autoimmunity was defined as positive islet cell autoantibody screen for one or more of the following types of autoantibodies: Glutamic Acid Decarboxylase (GAD), Islet Antigen-2 (IA-2), Insulin (IAA), or Zinc Transporter 8 (ZnT8). Patients were screened prior to TPIAT and every six months following TPIAT for up to three years. In all, 73 patients were included in the analysis. Total daily insulin dose was determined for each patient at each time interval. Chi-square or Fisher’s exact tests were used to compare proportions. Results: Of patients with 12-month data (n=38), 47% of islet cell autoantibody negative patients were off insulin vs 26% of antibody positive patients (p=0.19). This trend was significant at 18, 24, and 36 months after TPIAT. At 18 months, 90% (9/10) of antibody negative patients were off insulin vs 29% (4/14) of antibody positive patients (p=0.005). At 24 months, 73% (8/11) of antibody negative patients were off insulin vs 23% (3/13) of antibody positive patients (p=0.04). At 36 months, 100% (8/8) of antibody negative patients were off insulin compared to 0% (0/9) of antibody positive patients (p&amp;lt;0.0001). Conclusions: The presence of pancreatic islet cell antibodies was associated with persistent insulin requirement after TPIAT. Disclosure A.R.Lavik: None. C.M.O.Lowe: None. S.E.Tellez: None. L.Hornung: None. C.Heinzman: None. J.D.Nathan: None. M.Abu-el-haija: None. D.A.Elder: None.

242-OR: Defining Targets for Continuous Glucose Monitoring (CGM) after Total Pancreatectomy with Islet Autotransplantation (TPIAT)

Targets for continuous glucose monitoring (CGM) are well established for type 1 and type 2 diabetes. In total pancreatectomy with islet auto-transplant (TPIAT), stricter glycemic targets are needed to avoid metabolic stress on transplanted islets, but no guidelines exist for CGM targets. We aimed to determine CGM targets for TPIAT clinical management by associating CGM metrics with goal hemoglobin A1c (HbA1c) ≤6.5%. Targets for time in range (TIR) 70-140, TIR 70-180, mean CGM glucose, and time in hyperglycemia (&amp;gt;140, &amp;gt;180, &amp;gt;250 mg/dL) were chosen to give good sensitivity and specificity for identifying HbA1c ≤6.5%. We included 256 episodes of 14-day CGM metrics with a concurrent HbA1c value (n=82 patients, age 32.8 [SD 16.6] years at surgery, 70% female) who were ≥0.5 years post TPIAT (median 4.1 years) and wearing Dexcom G6. Most patients had more than 1 HbA1c and corresponding CGM available (median 3.1 per patient). As expected, CGM metrics correlated highly with each other. Table 1 shows “best” (Youden criterion) CGM thresholds and sensitivity for HbA1c ≤6.5%. TIR 70-140 mg/dL ≥50% and TIR 70-180 mg/dL ≥75% may be reasonable targets for patients and providers using CGM data to manage diabetes long-term after TPIAT. Also, time in hyperglycemia should be kept to &amp;lt;20% above 180 mg/dL and &amp;lt;3% above 250 mg/dL. Failure of these goals should prompt re-starting or adjusting insulin therapy. Disclosure Z.Somani: None. J.S.Hodges: None. K.Ramanathan: None. S.Chinnakotla: None. G.Beilman: None. M.Bellin: Consultant; Insulet Corporation, Vertex Pharmaceuticals Incorporated, Research Support; Dexcom, Inc., ViaCyte, Inc.

161-LB: Diagnosis and Treatment of Diabetes Mellitus in Pediatric Patients with Pancreatitis Followed in a Multidisciplinary Clinic

Children with recurring acute or chronic pancreatitis are at risk for pancreatitis related diabetes mellitus (DM). Pancreatic endocrine and exocrine concerns are managed by different subspecialists. Our center has a unique pediatric pancreatitis multidisciplinary clinic (MDC) with pediatric gastroenterology, endocrinology, pain, and nutrition experts. We obtain point-of-care (POC) HbA1c during clinic check-in for immediate DM screening. Our study describes the utility of POC HbA1c testing in our MDC. We analyzed a retrospective chart review of MDC patients from 2018-2023 with a diagnosis of pancreatitis and DM (n=27). Twelve were diagnosed with DM prior to presentation and 2 presented after total pancreatectomy with islet autotransplantation (TPIAT). Eight patients eventually developed DM and 5 later underwent TPIAT resulting in DM. We evaluated baseline characteristics at presentation to our MDC and longitudinal follow up. Of the 12 patients with previously diagnosed DM, 42% were Hispanic/Latino, 50% were female. On presentation to the MDC, patients were 15.4±2.1 years old with BMI 23.2±4.0 kg/m2 and HbA1c 9.6±2.9%. Eight patients developed DM within 1.1±1.2 years of follow up. Six were diagnosed by POC HbA1c in our MDC. Of all whom developed DM, 88% were Hispanic/Latino, 88% were female. DM was diagnosed at 14.3±1.6 years old with BMI 34.5±4.8 kg/m2 and HbA1c 8.5±2.5%. Of our 27 patients with DM, 4 had type 1 DM autoantibodies. At most recent visit HbA1c was 8.9±3.2%. DM treatment involved oral agents (15%), insulin (85%) and nutrition counseling for all patients. Total daily dose of insulin was 0.75±0.53 u/kg/day and 48% of patients used continuous glucose monitors. Instituting POC HbA1c screening in pancreatitis clinic identifies patients with new onset DM, supporting multidisciplinary care. Despite intensive care, HbA1c for these patients remains above guideline goals. More research is needed in providing DM care for children with pancreatitis. Disclosure E. Vargas: None. J. Mark: None. G. P. Forlenza: Advisory Panel; Medtronic, Consultant; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc., Lilly Diabetes, Research Support; Medtronic, Abbott, Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc. T. M. Triolo: None.

Metabolic Outcomes in Pediatric Patients One-Year Post-Total Pancreatectomy with Islet Autotransplantation after Early Pump Initiation.

We previously published that insulin pump initiation immediately after IV insulin therapy was associated with improved post-surgical glycemic outcomes compared to multiple daily injections (MDI) in pediatric patients following a total pancreatectomy with islet autotransplantation (TPIAT). We investigated metabolic outcomes of this population at one-year post-TPIAT to assess if the improved outcomes in the early pump group were sustained over time. We retrospectively reviewed 40 patients post-TPIAT previously studied at 10-days post-surgery (15 used MDI and 25 used pump therapy immediately post-ICU, and all were discharged on pump therapy). Data analyzed included: demographics, islet equivalents per kilogram (IEQ/kg) transplanted, exogenous insulin use, and baseline vs. one-year (via mixed meal testing) HbA1c, fasting glucose, insulinogenic index, and the area under the curve (AUC) for insulin and c-peptide. More patients were off insulin at one year in the early pump group compared to the MDI group (45% vs. 13%, p = 0.07). Of all patients off insulin, 100% of the early pump users weaned off by six months post-TPIAT compared to 30% of the MDI users. Two known variables associated with favorable insulin outcomes, lower age and higher IEQ/kg, were not significantly different between groups. Fasting glucose was lower in the early pump group compared to the MDI group (median 97 vs. 122 mg/dL, p = 0.003), while AUC c-peptide was greater in early pump users at one-year post-TPIAT but did not reach significance (median 57.0 vs. 50.3 ng/mL × minutes, p = 0.14). Other metabolic outcomes did not differ between groups. Despite lower median age and higher IEQ/kg in the MDI group, the early pump group had a lower fasting glucose. Younger TPIAT age (p = 0.02) and early pump users (p = 0.04) were significantly associated with insulin independence at one year. This study was limited by sample size. Early pump use may have long-term benefits in post-TPIAT endogenous insulin secretion.

Comment on "Total Pancreatectomy With Islet Autotransplantation As an Alternative to High-Risk Pancreatojejunostomy After Pancreaticoduodenectomy: A Prospective Randomized Trial".

We have read with interest the recent publication by Balzano et al,1 proposing total pancreatectomy with islet autotransplantation (TPIAT) as an alternative to high-risk pancreaticojejunostomy in patients undergoing pancreatic resection for neoplastic disease of the pancreatic head. The control group in the randomized trial included patients undergoing a classical pancreatoduodenectomy. Among the indications for resections listed in Supplemental Digital Content 1 (https://links.lww.com/SLA/E272) were patients with pancreatic ductal adenocarcinoma and various other neoplastic disorders. Although the main endpoint in this study was the morbidity (number of patients with 1 or more complications), the authors also studied mortality in some detail and emphasized that that total pancreatectomy may prevent long-lasting decline of patients’ general condition associated with clinically relevant postoperative pancreatic fistula, and in particular, in patients with adenocarcinoma, where a complicated clinical course could impact oncological outcome (delay the start of adjuvant therapy). They even implied that (although as stated by the authors themselves, the study was underpowered to detect any statistically significant difference in survival), their therapeutic attitude may have contributed to the observed better survival in TPIAT (“a trend toward a reduction of mortality, even for patients with malignancy”). We would kindly like to point out that (1) such a statement can be likened to “SPIN”2 and (2) in this study, the proportion of patients with ductal adenocarcinoma differed remarkedly between the groups: 29.0% (9/31) versus 16.7% (5/30) for the pancreaticoduodenectomy and total pancreatectomy groups, respectively. Even if the proper methodology were applied to this underpowered subgroup analysis,3 as overall survival would be highly dependent on the number of patients with pancreatic ductal adenocarcinoma, the outcome for the patients with pancreatic ductal adenocarcinoma versus patients with milder neoplastic diseases should be analyzed before implying that TPIAT could have a role in overall survival after resection for adenocarcinoma.

Outcomes of total pancreatectomy with islet autotransplantation: A systematic review and meta-analysis.

Despite the increased use of total pancreatectomy with islet autotransplantation (TPIAT), systematic evidence of its outcomes remains limited. To evaluate the outcomes of TPIAT. We searched PubMed, EMBASE, and Cochrane databases from inception through March 2019 for studies on TPIAT outcomes. Data were extracted and analyzed using comprehensive meta-analysis software. The random-effects model was used for all variables. Heterogeneity was assessed using the I2 measure and Cochrane Q-statistic. Publication bias was assessed using Egger's test. Twenty-one studies published between 1980 and 2017 examining 1011 patients were included. Eighteen studies were of adults, while three studied pediatric populations. Narcotic independence was achieved in 53.5% [95% Confidence Interval (CI): 45-62, P < 0.05, I2 = 81%] of adults compared to 51.9% (95%CI: 17-85, P < 0.05, I2 = 84%) of children. Insulin-independence post-procedure was achieved in 31.8% (95%CI: 26-38, P < 0.05, I2 = 64%) of adults with considerable heterogeneity compared to 47.7% (95%CI: 20-77, P < 0.05, I2 = 82%) in children. Glycated hemoglobin (HbA1C) 12 mo post-surgery was reported in four studies with a pooled value of 6.76% (P = 0.27). Neither stratification by age of the studied population nor meta-regression analysis considering both the study publication date and the islet-cell-equivalent/kg weight explained the marked heterogeneity between studies. These results indicate acceptable success for TPIAT. Future studies should evaluate the discussed measures before and after surgery for comparison.

Follow-up of Patients After Total Pancreatectomy and Islet Cell Autotransplantation at Off-Site Islet Isolation Facility.

Total pancreatectomy with islet autotransplantation (TPIAT) is a definitive management for intractable pain in patients with chronic pancreatitis. Islet autotransplantation (IAT) allows for the preservation of beta-cells to prevent complications of long-term diabetes. Our study follows TPIAT recipients for up to 12 years to determine the procedure's efficacy completed with an off-site islet isolation facility. Patient demographics, mixed meal tolerance test measures, glycosylated hemoglobin, insulin requirements, and homeostatic model assessment for insulin resistance values were collected prior to surgery and at the most recent follow-up. Forty-four patients (median age, 46.0 years; range, 20-78 years) underwent TPIAT for CP. At an overall median follow-up time of 845.5 days (range, 195-4470 days) 8 patients were insulin independent and 36 patients were insulin dependent. At the most recent follow-up, islet yield per kilogram was the strongest indicator of insulin independence. Homeostatic model assessment for insulin resistance values were comparable between insulin independent and dependent cohorts. Our long-term follow-up data suggest that IAT can effectively reduce insulin requirements and improve post-operative glycemic control.