Dataset Information

Islet Harvest in Carbon Monoxide-Saturated Medium for Chronic Pancreatitis Patients Undergoing Islet Autotransplantation.

ABSTRACT: Stresses encountered during human islet isolation lead to unavoidable ?-cell death after transplantation. This reduces the chance of insulin independence in chronic pancreatitis patients undergoing total pancreatectomy and islet autotransplantation. We tested whether harvesting islets in carbon monoxide-saturated solutions is safe and can enhance islet survival and insulin independence after total pancreatectomy and islet autotransplantation. Chronic pancreatitis patients who consented to the study were randomized into carbon monoxide (islets harvested in a carbon monoxide-saturated medium) or control (islets harvested in a normal medium) groups. Islet yield, viability, oxygen consumption rate, ?-cell death (measured by unmethylated insulin DNA), and serum cytokine levels were measured during the peri-transplantation period. Adverse events, metabolic phenotypes, and islet function were measured prior and at 6 months post-transplantation. No adverse events directly related to the infusion of carbon monoxide islets were observed. Carbon monoxide islets showed significantly higher viability before transplantation. Subjects receiving carbon monoxide islets had less ?-cell death, decreased CCL23, and increased CXCL12 levels at 1 or 3 days post transplantation compared with controls. Three in 10 (30%) of the carbon monoxide subjects and none of the control subjects were insulin independent. This pilot trial showed for the first time that harvesting human islets in carbon monoxide-saturated solutions is safe for total pancreatectomy and islet autotransplantation patients.

SUBMITTER: Wang H

PROVIDER: S-EPMC7016471 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Islet Harvest in Carbon Monoxide-Saturated Medium for Chronic Pancreatitis Patients Undergoing Islet Autotransplantation.

Wang Hongjun H Gou Wenyu W Strange Charlie C Wang Jingjing J Nietert Paul J PJ Cloud Colleen C Owzarski Stefanie S Shuford Betsy B Duke Tara T Luttrell Louis L Lesher Aaron A Papas Klearchos K KK Herold Kevan C KC Clark Pamela P Usmani-Brown Sahar S Kitzmann Jennifer J Crosson Craig C Adams David B DB Morgan Katherine A KA

Cell transplantation 20191230 1_suppl

Stresses encountered during human islet isolation lead to unavoidable β-cell death after transplantation. This reduces the chance of insulin independence in chronic pancreatitis patients undergoing total pancreatectomy and islet autotransplantation. We tested whether harvesting islets in carbon monoxide-saturated solutions is safe and can enhance islet survival and insulin independence after total pancreatectomy and islet autotransplantation. Chronic pancreatitis patients who consented to the st ...[more]

PMID: 31885286

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Project description:ImportancePain management of patients with chronic pancreatitis (CP) can be challenging. Laparoscopy has been associated with markedly reduced postoperative pain but has not been widely applied to total pancreatectomy with islet autotransplantation (TPIAT).ObjectiveTo examine the feasibility of using laparoscopic TPIAT (L-TPIAT) in the treatment of CP.Design, setting, and participantsThirty-two patients with CP presented for TPIAT at a tertiary hospital from January 1, 2013, through December 31, 2015. Of the 22 patients who underwent L-TPIAT, 2 patients converted to an open procedure because of difficult anatomy and prior surgery. Pain and glycemic outcomes were recorded at follow-up visits every 3 to 6 months postoperatively.Main outcomes and measuresOperative outcomes included operative time, islet isolation time, warm ischemia time, islet equivalent (IE) counts, estimated blood loss, fluid resuscitation, and blood transfusions. Postoperative outcomes included length of stay, all-cause 30-day readmission rate, postoperative complications, mortality rate, subjective pain measurements, opioid use, random C-peptide levels, insulin requirements, and glycated hemoglobin level.ResultsOf the 32 patients who presented for TPIAT, 20 underwent L-TPIAT (8 men and 12 women; mean [SD] age, 39 [13] years; age range, 21-58 years). Indication for surgery was CP attributable to genetic mutation (n = 9), idiopathic pancreatitis (n = 6), idiopathic pancreatitis with pancreas divisum (n = 3), and alcohol abuse (n = 2). Mean (SD) operative time was 493 (78) minutes, islet isolation time was 185 (37) minutes, and warm ischemia time was 51 (62) minutes. The mean (SD) IE count was 1325 (1093) IE/kg. The mean (SD) length of stay was 11 (5) days, and the all-cause 30-day readmission rate was 35% (7 of 20 patients). None of the patients experienced postoperative surgical site infection, hernia, or small-bowel obstruction, and none died. Eighteen patients (90%) had a decrease or complete resolution of pain, and 12 patients (60%) no longer required opioid therapy at a median follow-up period of 6 months. Postoperative random insulin C-peptide levels were detectable in 19 patients (95%) at a median follow-up of 10.4 months. At a median follow-up of 12.5 months, 5 patients (25%) were insulin independent, whereas 9 patients (45%) required 1 to 10 U/d, 5 patients (25%) required 11 to 20 U/d, and 1 patient (5%) required greater than 20 U/d of basal insulin. The mean (SD) glycated hemoglobin level was 7.4% (0.5%).Conclusions and relevanceThis study represents the first series of L-TPIAT, demonstrating its safety and feasibility. Our approach enables patients to experience shorter operative times and the benefits of laparoscopy, including reduced length of stay and quicker opioid independence.

Project description:Background & aimsTherapeutic options are limited for patients with recurrent acute pancreatitis who have intractable symptoms despite maximal endoscopic and medical treatment, but equivocal or no morphologic or functional evidence of chronic pancreatitis. We performed a prospective observational cohort study to determine the efficacy of total pancreatectomy with islet autotransplantation (TPIAT) for these patients.MethodsWe collected data from all patients undergoing TPIAT at the University of Minnesota from 2007 through 2013; 49 patients (42 female; mean age, 32.8 ± 7.8 years) had a diagnosis of recurrent acute pancreatitis not provoked by intervention, with negative or equivocal findings from nondiagnostic imaging or pancreatic function tests for chronic pancreatitis, and intractable pain between episodes. Data on insulin use, narcotic requirements, pain scores, and health-related quality of life were collected before TPIAT; 3 months, 6 months, and 1 year afterward; and then yearly.ResultsAll 49 patients studied required narcotics before TPIAT (45 daily users and 4 intermittent users); 2 had insulin-treated diabetes. At 1 year after TPIAT, 22 out of 48 patients (46%) reported no use of narcotic pain medications (P < .001 vs baseline). Health-related quality of life score, measured by the physical and mental component summary score, increased by approximately 1 standard deviation from the population mean (P < .001 for the physical component summary; P = .019 for the mental component summary). At 1 year after TPIAT, 21 out of 48 patients (45%) were insulin independent; their mean percent glycosylated hemoglobin A1c at 1 year after TPIAT was 6.0% ± 0.9% (5.2% ± 0.6% pre-TPIAT).ConclusionsPatients with recurrent acute pancreatitis but lacking clear chronic pancreatitis benefit from TPIAT, with outcomes similar to those previously described for patients with chronic pancreatitis (improved quality of life and reduced narcotic use). For these patients who have otherwise limited surgical treatment options, TPIAT can be considered when medical and endoscopic therapies have failed.

Project description:Total pancreatectomy with islet cell autotransplantation (TPIAT) is a surgical treatment modality used for the management of painful chronic pancreatitis when medical and endoscopic therapies fail. Total pancreatectomy (TP) results in a number of clinical implications. However, the glucose-responsive insulin secretion can be preserved by combining TP with islet cell autotransplant (IAT). Despite the known clinical implications of TPIAT, the systemic molecular effects of TPIAT remains poorly investigated. Therefore, we performed the first hypothesis-generating study of the urinary proteome before and after TPIAT. The RAW- and processed data from the analysis can be found in this repository. Twenty-two chronic pancreatitis patients eligible for TPIAT were prospectively enrolled in the study at the University of Minnesota Medical Center between September 2011 and February 2014. Urine was collected within the week pre-TPIAT and 12-18 months post-TPIAT, resulting in 44 paired samples. The paired experimental design allowed us to subtract interpersonal differences. The unique set of urine samples were prepared for bottom-up label-free quantitative proteomics using the in-house developed ‘MStern’ protocol for the 96-well plate compatible processing of the urine samples. The samples were analyzed by LC-MS/MS and 2477 proteins were identified (FDR<0.01%). Five samples were found to have less than 30% of the cumulated list of proteins (<743 proteins) and so these samples and their respective matching sample were thus removed from the analysis. This resulted in a complete dataset with 17 matched pre- and post-TPIAT sample pairs. The final list of recommended included pairs for future analysis are indicated in the PX_TPIAT_Metadata.csv file. Note that extended clinical information only was available for the included samples. Furthermore, the information is only listed for the pre-TPIAT sample but applies to both the pre- and post-TPIAT participant sample. The data allows for studying the systemic molecular impact of the TPIAT procedure.

Dataset Information

Islet Harvest in Carbon Monoxide-Saturated Medium for Chronic Pancreatitis Patients Undergoing Islet Autotransplantation.

Publications

Islet Harvest in Carbon Monoxide-Saturated Medium for Chronic Pancreatitis Patients Undergoing Islet Autotransplantation.

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