Quality of Life Following TPIAT: A Patient Experience Survey.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Excess adiposity contributes to higher ambulatory central blood pressure and arterial stiffness in physically inactive young adults.

BACKGROUND: It remains unknown if physical inactivity and excess adiposity increases 24-h central blood pressure and arterial stiffness in young adults. This study examined 24-h central blood pressure and indirect measures of arterial stiffness (e.g., central pulse pressure) in physically inactive young adults with and without excess adiposity. METHODS: Body fat and ambulatory 24-h blood pressure were measured in 31 young adults (men: 22±4 years, N.=15; women: 22±5 years, N=16). Multi-frequency bioelectrical impedance measured body fat. Normal adiposity was defined as <20% body fat in men and <32% body fat in women, whereas excess adiposity was defined as ≥20% and ≥32% in men and women, respectively. Ambulatory 24-h central blood pressure was calculated based on brachial blood pressure and volumetric displacement waveforms. RESULTS: By design, the normal adiposity group had a lower body fat percentage (men: 15.5±4.6%; women: 20.8±2.5%) compared to the physically inactive excess adiposity group (men: 29.8±5.4%; women: 34.3±7.5%). Men and women with excess adiposity group had elevated central blood pressure (central systolic, P<0.05 vs. normal adiposity groups). Central pulse pressure was elevated in the excess adiposity group (men: 45±5 mmHg; women: 41±9 mmHg) compared to normal adiposity groups (men: 36±4 mmHg; women: 32±3 mmHg, P<0.05 for both), while other arterial stiffness (augmentation index and ambulatory arterial stiffness index) measures trended toward significance only in men with excess adiposity. CONCLUSIONS: Physically inactive men and women with excess adiposity have increased 24h central blood pressure and pulse pressure compared to physically inactive young adults with normal adiposity.

Effectiveness of Intraoperative Versus Dedicated Islet Cell Laboratory Isolation for Total Pancreatectomy With Islet Autotransplant.

Background: Total pancreatectomy with islet autotransplantation (TPIAT) requires a complex islet isolation process of the explanted pancreas. Islet isolation has historically required a specialized laboratory to perform islet isolation. We report our experience with a novel technique of intraoperative islet isolation that does not require a specialized islet laboratory, thereby making the isolation process simpler, more accessible, and less costly. Methods: We performed a retrospective, comparative effectiveness analysis of 50 adult patients who underwent TPIAT from 2012 to 2020 (TPIAT with remote isolation [n = 20] versus intraoperative isolation of islet cells [n = 30]). The primary outcome was islet equivalents per body weight (IEQ/kg) for patients in each group. Results: Mean IEQ/kg's (4294 remote group versus 3015 intraoperative group, P = 0.06) and 1-y postoperative C-peptide levels (1.51 ng/mL remote group versus 0.91 ng/mL intraoperative group, P = 0.10) were not different between groups. Mean 1-y HbA1c levels (7.7% in the remote group versus 7.1% intraoperative group, P = 0.67) and 1-y insulin requirements (P = 0.31) were not statistically different. Lower average cost of hospitalization was seen in the intraoperative group, although this was not statistically significant ($104 398 remote versus $78 986 intraoperative, P = 0.81). Conclusions: Intraoperative islet isolation has similar effectiveness in regard to glycemic outcomes compared with the use of a dedicated islet cell isolation laboratory at a lower cost.

Targeting CXCR1/2 in the first multicenter, double-blinded, randomized trial in autologous islet transplant recipients.

Several cytokines and chemokines are elevated after islet infusion in patients undergoing total pancreatectomy with islet autotransplantation (TPIAT), including CXCL8 (also known as interleukin-8), leading to islet loss. We investigated whether use of reparixin for blockade of the CXCL8 pathway would improve islet engraftment and insulin independence after TPIAT. Adults without diabetes scheduled for TPIAT at nine academic centers were randomized to a continuous infusion of reparixin or placebo (double-blinded) for 7 days in the peri-transplant period. Efficacy measures included insulin independence (primary), insulin dose, hemoglobin A1c (HbA1c ), and mixed meal tolerance testing. The intent-to-treat population included 102 participants (age 39.5 ± 12.2 years, 69% female), n = 50 reparixin-treated, n = 52 placebo-treated. The proportion insulin-independent at Day 365 was similar in reparixin and placebo: 20% vs. 21% (p = .542). Twenty-seven of 42 (64.3%) in the reparixin group and 28/45 (62.2%) in the placebo group maintained HbA1c ≤6.5% (p = .842, Day 365). Area under the curve C-peptide from mixed meal testing was similar between groups, as were adverse events. In conclusion, reparixin infusion did not improve diabetes outcomes. CXCL8 inhibition alone may be insufficient to prevent islet damage from innate inflammation in islet autotransplantation. This first multicenter clinical trial in TPIAT highlights the potential for future multicenter collaborations.

Islet autotransplantation improves glycemic control in patients undergoing elective distal pancreatectomy for benign inflammatory disease.

Islet autotransplantation (IAT) is increasingly being performed to mitigate against the diabetic complications of pancreatic resection in patients with benign inflammatory pancreatic disorders; however, the glycemic benefit of IAT in patients undergoing partial pancreatic resection is not known. We aimed to determine whether IAT improved glycemic outcomes in patients undergoing distal pancreatectomy for benign inflammatory disease. We performed a multicenter, retrospective case-control study of patients who underwent distal pancreatic resection with IAT at two U S tertiary care centers. The primary outcome was the mean change in pre- vs post-operative HgA1c following transplant as well as the development of new post-operative diabetes. Nine patients requiring distal pancreatectomy for benign disease underwent IAT and were compared to 13 historical controls without IAT. Baseline characteristics were similar between groups. With a median follow-up of 22 months, those who received an IAT had a smaller increase in their pre- vs post-operative HgA1c (0.42 vs 2.83, P = .004), and one case patient (14.3%) vs three control patients (23.1%) developed new post-operative diabetes (P = .581). We conclude that patients undergoing distal pancreatic resection for benign inflammatory disease should be considered for IAT, as long-term glycemic outcomes appear to be improved in those undergoing transplant.

Long-Term Glycemic Control in Adult Patients Undergoing Remote vs. Local Total Pancreatectomy With Islet Autotransplantation.

OBJECTIVES: Total pancreatectomy with islet autotransplantation (TPIAT) is increasingly performed with remote islet cell processing and preparation, i.e., with islet cell isolation performed remotely from the primary surgical site at an appropriately equipped islet isolation facility. We aimed to determine whether TPIAT using remote islet isolation results in comparable long-term glycemic outcomes compared with TPIAT performed with standard local isolation. METHODS: We performed a retrospective cohort study of adult patients who underwent TPIAT at three tertiary care centers from 2010 to 2013. Two centers performed remote isolation and one performed local isolation. Explanted pancreata in the remote cohort were transported ∼130 miles to and from islet isolation facilities. The primary outcome was insulin independence 1 year following transplant. RESULTS: Baseline characteristics were similar between groups except the remote cohort had higher preoperative hemoglobin A1c (HbA1c; 5.43 vs. 5.25, P=0.02) and there were more females in the local cohort (58% vs. 76%, P=0.049). At 1 year, 27% of remote and 32% of local patients were insulin independent (P=0.48). Remote patients experienced a greater drop in fasting c-peptide (-1.66 vs. -0.64, P=0.006) and a greater rise in HbA1c (1.65 vs. 0.99, P=0.014) at 1-year follow-up. A preoperative c-peptide >2.7 (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.6-14.3) and >3,000 islet equivalents/kg (OR 11.0, 95% CI 3.2-37.3) were associated with one-year insulin independence in the local group. CONCLUSIONS: At 1 year after TPIAT, patients undergoing remote surgery have equivalent rates of long-term insulin independence compared with patients undergoing TPIAT locally, but metabolic control is superior with local isolation.

Islet Cell Yield Following Remote Total Pancreatectomy With Islet Autotransplant is Independent of Cold Ischemia Time.

OBJECTIVES: Total pancreatectomy with islet autotransplantation is increasingly being performed remotely, that is, removing the pancreas in 1 location, isolating the islet cells in another location, then returning the islets to the original location for reimplantation into the patient. We determined the influence of extended cold ischemia time on key clinical outcomes in remote islet autotransplantation. METHODS: We evaluated patients who underwent remote islet autotransplantation at 2 centers from 2011 to 2014. Patients were divided into 2 groups: those with and those without a decrease in C-peptide greater than 50% from baseline. The primary clinical outcome was the quantity of isolated islet equivalents per kilogram body weight (IEQs/kg). RESULTS: Twenty-five patients met inclusion criteria; 15 had a decrease in C-peptide greater than 50% from baseline and had lower corresponding IEQs/kg compared with those without a decrease greater than 50% (4045 vs 6654 IEQs/kg, P = 0.01). There was no difference in cold ischemia time between the 2 groups (664 vs 600 minutes, P = 0.25). Daily insulin use at 1 year nearly met statistical significance (25.3 vs 8 U, P = 0.06), as did glycated hemoglobin (8.07 vs 6.69 mmol/L, P = 0.06). CONCLUSIONS: Cold ischemia time does not influence islet yield in patients undergoing pancreatectomy with remote isolation.

Use of a glucose management service improves glycemic control following vascular surgery: an interrupted time-series study.

BACKGROUND: The optimal method for obtaining good blood glucose control in noncritically ill patients undergoing peripheral vascular surgery remains a topic of debate for surgeons, endocrinologists, and others involved in the care of patients with peripheral arterial disease and diabetes. A prospective trial was performed to evaluate the impact of routine use of a glucose management service (GMS) on glycemic control within 24 hours of lower-extremity revascularization (LER). METHODS: In an interrupted time-series design (May 1, 2011-April 30, 2012), surgeon-directed diabetic care (Baseline phase) to routine GMS involvement (Intervention phase) was compared following LER. GMS assumed responsibility for glucose management through discharge. The main outcome measure was glycemic control, assessed by (1) mean hospitalization glucose and (2) the percentage of recorded glucose values within target range. Statistical process control charts were used to assess the impact of the intervention. RESULTS: Clinically important differences in patient demographics were noted between groups; the 19 patients in the Intervention arm had worse peripheral vascular disease than the 19 patients in the Baseline arm (74% critical limb ischemia versus 58%; p = .63). Routine use of GMS significantly reduced mean hospitalization glucose (191 mg/dL Baseline versus 150 mg/dL Intervention, p < .001). Further, the proportion of glucose values in target range increased (48% Baseline versus 78% Intervention, p = .05). Following removal of GMS involvement, measures of glycemic control did not significantly decrease for the 19 postintervention patients. CONCLUSIONS: Routine involvement of GMS improved glycemic control in patients undergoing LER. Future work is needed to examine the impact of improved glycemic control on clinical outcomes following LER.

Treatment with novel galactomannan derivative reduces 2-hour postprandial glucose excursions in individuals with type 2 diabetes treated with oral medications and/or insulin.

Galactomannan is an insoluble polysaccharide that has been shown to reduce postprandial excursions. We assessed the impact of a novel galactomannan derivative (PAZ320) on the magnitude of 2-hour postprandial glucose excursions in individuals with type 2 diabetes who were being treated with oral medication and/or insulin. Investigators recently reported findings from a single-center, open-label, prospective study that evaluated the efficacy of PAZ320 in 24 subjects with type 2 diabetes who were treated with oral antidiabetic agents and/or insulin. End points included adverse events and area under the curve during 3-hour postprandial glucose excursion (gAUC). Subjects consumed a test meal without PAZ320 at baseline and then ingested low-dose (8 g) and high-dose (16 g) PAZ320 with test meals at subsequent intervention visits. A post hoc analysis was conducted to determine changes in 2-hour postprandial glucose excursions. Among the 20 subjects for whom data were available for all clinic visit test meals, 15 (75%) responded to low-dose, high-dose, or both medication dosages. Low-dose responders (n = 8) experienced clinically significant improvements in 2-hour postprandial glucose excursions from baseline excursions compared with nonresponders (-28.00 ± 25.97 mg/dL vs 23.42 ± 11.45 mg/dL, P = .005). Similar differences were seen in high-dose responders (-28.82 ± 24.26 vs 33.89 ± 20.56 mg/dL, P < .0001). PAZ320 was shown to be safe in all patients studied and effective in controlling postprandial glucose in a large portion of the study population. Additional studies are needed to determine its long-term effects on HbA1c and to further define which subpopulation(s) may respond to PAZ320 therapy.

Gonadotropinomas.

Advances in immunocytochemistry, electron microscopy, cell culture, and molecular techniques have demonstrated that 80 to 90% of the clinically nonfunctioning pituitary adenomas are gonadotrope-derived and recently recognized as gonadotropinomas, which account for as many as 40 to 50% of all pituitary macroadenomas. Patients usually present with mass effects including visual field loss and headache, hypogonadism, and hypopituitarism. Commonly, the tumor is found incidentally. Recently, a few patients with gonadotropinomas were reported to have hormonal hypersecretion syndromes such as ovarian hyperstimulation, testicular enlargement, and precocious puberty. The tumors can be divided into two broad categories: functioning gonadotropinomas with positive immunostaining for follicle-stimulating hormone, leutinizing hormone, and/or their subunits; and nonfunctioning gonadotropinomas or null cell tumors with negative immunostaining for all pituitary hormones but positive nuclear immunostaining for steroid factor-1 or DAX-1 characteristic of gonadotrope differentiation, with evidence of gonadotropin production or gene expression at the mRNA level. Gonadotropinomas are monoclonal in origin but the pathogenesis of these tumors is unknown and factors that stimulate clonal proliferation not yet determined. A new pituitary oncogene, pituitary tumor transforming gene, has recently been found to be overexpressed in about two thirds of these tumors but it is also detected in all other pituitary tumor subtypes. Alterations of tumor hormone receptors and local growth factors may also play a role in the tumor development and/or progression. Transphenoidal surgery remains the principal therapy for the macroadenomas. Radiosurgery using gamma knife, the linear accelerator, or proton beam therapy showed promising results, especially for controlling the residual or recurrent tumors. Medical therapy with somatostatin analogs, dopamine agonists, and gonadotropin-releasing hormone agonists and antagonists are rarely effective in reducing tumor size. Experimental therapy with intraoperative local chemotherapy or potential gene therapy requires further investigation.