Robot-assisted pancreatoduodenectomy with preservation of the vascular supply for autologous islet cell isolation and transplantation: a case report

<p>Abstract</p> <p>Introduction</p> <p>For patients with chronic pancreatitis presenting with medically intractable abdominal pain, surgical intervention may be the only treatment option. However, extensive pancreatic resections are typically performed open and are associated with a substantial amount of postoperative pain, wound complications and long recovery time. Minimally invasive surgery offers an avenue to improve results; however, current limitations of laparoscopic surgery render its application in the setting of chronic pancreatitis technically demanding. Additionally, pancreatic resections are associated with a high incidence of diabetes. Transplantation of islets isolated from the resected pancreas portion offers a way to prevent post-surgical diabetes; however, preservation of the vascular supply during pancreatic resection, which determines islet cell viability, is technically difficult using current laparoscopic approaches. With recent advances in the surgical field, robotic surgery now provides a means to overcome these obstacles to achieve the end goals of pain relief and preserved endocrine function. We present the first report of a novel, minimally invasive robotic approach for resection of the pancreatic head that preserves vascular supply and enables the isolation of a high yield of viable islets for transplantation.</p> <p>Case presentation</p> <p>A 35-year old Caucasian woman presented with intractable chronic abdominal pain secondary to chronic pancreatitis, with a stricture of her main pancreatic duct at the level of the ampulla of Vater and distal dilatation. She was offered a robotic-assisted pylorus-preserving pancreatoduodenectomy and subsequent islet transplantation, to both provide pain relief and preserve insulin-secretory reserves.</p> <p>Conclusion</p> <p>We present a novel, minimally invasive robotic approach for resection of the pancreatic head with complete preservation of the vascular supply, minimal warm ischemia time (less than three minutes) and excellent islet recovery (134,727 islet equivalent). Our patient is currently pain-free with normal glycemic control. Robot-assisted pylorus-preserving pancreatoduodenectomy and autologous islet transplantation can be safely performed and has the potential to minimize operative traumas as well as to partially preserve endocrine function. Results from this case report suggest that this dual procedure should be considered as a treatment option for patients with chronic pancreatitis at earlier stages of the disease, before irreversible islet loss occurs.</p

Reduction in Carotid Intima-Media Thickness after Pancreatic Islet Transplantation in Patients with Type I Diabetes

OBJECTIVE Determine the impact of islet transplantation on carotid intima-media thickness (CIMT), a marker for atherosclerosis, in type 1 diabetes without kidney disease. RESEARCH DESIGN AND METHODS Consecutive case series of 15 adults (mean age [SD], 49 years [10 years]; 87% female) with type 1 diabetes for ≥5 years (mean duration [SD], 30 years [12 years]; mean HbA(1c) [SD], 7.2% [0.9%]), without kidney disease, presenting with severe hypoglycemic unawareness to undergo allogeneic pancreatic islet transplant(s) (one to three each) in a phase 1/2 and 3 clinical trial. Current follow-up ranges from 1 to 5 years (2005-2011). CIMT of the common and internal carotid arteries was measured before and every 12-16 months after the first transplant (two to six CIMTs each) by one ultrasonographer and one blinded reader. CIMT was analyzed as change from baseline to 12- and 50-month follow-up; a combined CIMT score was calculated as the sum of the standardized IMT scores (SD units [SDs]) of both arteries. RESULTS All patients achieved insulin independence after one to three transplants. CIMT decreased at 12 months (n = 15) for the common carotid (-0.058 mm; P = 0.006) and combined score (-1.28 SDs; P = 0.004). In those with 50-month follow-up (n = 7), the decrease in the combined score continued from 12 (-1.59 SDs; P = 0.04) to 50 months (-0.77 SDs; P = 0.04). During follow-up, the decreasing slope of change in CIMT was associated with decreasing slopes of change in HbA(1c), lipoproteins, and cardiovascular/inflammatory markers. CONCLUSIONS Islet transplantation may ameliorate diabetes-related atherosclerosis through improved glycemic control consequent to restoring endogenous insulin secretion, and optimal lipid management posttransplant also contributes

Highly Purified versus Filtered Crude Collagenase: Comparable Human Islet Isolation Outcomes

This study was designed to retrospectively compare the impact of crude Sigma V collagenase (Sigma V, n=52) with high-purified Serva NB1 collagenase (Serva NB1, n=42) on human islet isolation outcomes. A three-step filtration was applied to the crude Sigma V to remove endotoxin contamination and impurities; in addition, this process was used as a lot prescreening tool. Isolation outcomes were determined by digestion efficacy, islet yields, purity, viability, glucose-stimulated insulin release, and endotoxin content. The digestion efficacy between Sigma V and Serva NB1 was statistically significant (Sigma V: 64.71% vs. Serva NB1: 69.71%, p=0.0014). However, the islet yields were similar (Sigma V: 23422.58 vs. Serva NB1: 271097 IEq, p=0.23) between groups. There was no significant purity difference observed in fractions with purities greater than 75%. Viability (Sigma V: 93.3% vs. Serva NB1: 94.8%, p=0.061) and stimulation indexes (Sigma V: 3.41 vs. Serva NB1: 2.74, p=0.187) were also similar between the two groups. The impact of cold ischemia and age on the isolation outcome in the Sigma V group was comparable to the Serva NB1 group. The endotoxin content of the final products in the filtered Sigma V group was significantly less than that in the high-purified Serva NB1 group (0.022 EU/ml vs. 0.052 EU/ml, p=0.003). Additionally, in the Sigma V group there was minimal lot to lot variation and no significant loss of enzymatic activity after filtration. These findings indicate that the use of Sigma V or other crude enzyme blends for research pancreata is warranted to reduce isolation costs and increase the amount of islets available for critical islet research. These findings also validate the need for a systematic enzyme analysis to resolve these inconsistencies in overall enzyme quality once and for all

Histidine-Tryptophan-Ketoglutarate and University of Wisconsin Solution Demonstrate Equal Effectiveness in the Preservation of Human Pancreata Intended for Islet Isolation: A Large-Scale, Single-Center Experience

We previously reported a small-scale study on the efficacy of histidine-tryptophan-ketoglutarate (HTK) solution versus University of Wisconsin (UW) solution on pancreas preservation for islet isolation. In this large-scale, retrospective analysis (n=252), we extend our initial description of the impact of HTK on islet isolation outcomes and include pancreatic digestion efficacy, purification outcomes, and islet size distribution. Multivariable linear regression analysis, adjusted for donor age, sex, BMI, cold ischemia time, and enzyme, demonstrated similar results for the HTK group (n=95) and the UW group (n=157), including postpurification islet yields (HTK: 289,702 IEQ vs. UW: 283,036 IEQ; p=0.76), percentage of digested pancreatic tissue (HTK: 66.9% vs. UW: 64.1%; p=0.18), and islet loss from postdigestion to postpurification (HTK: 24,972 IEQ vs. MAT: 39,551 IEQ; p=0.38). Changes in islet size between the postdigestion and postpurification stages were comparable within each islet size category for HTK and UW (p=0.14-0.99). Tissue volume distribution across purification fractions and islet purity in the top fractions were similar between the groups; however, the HTK group had significantly higher islet purity in the middle fractions (p=0.003-0.008). Islet viability and stimulation indices were also similar between the HTK and the UW groups. In addition, we analyzed a small sample of patients transplanted either with HTK (n=7) or UW (n=8) preserved islets and found no significant differences in posttransplant HbA(1e), beta-score, and frequency of insulin independence. This study demonstrates that HTK and UW solutions offer comparable pancreas preservation for islet transplantation. More in vivo islet outcome data are needed for a complete analysis of the effects of HTK on islet transplantation

Highly Purified versus Filtered Crude Collagenase: Comparable Human Islet Isolation Outcomes

This study was designed to retrospectively compare the impact of crude Sigma V collagenase (Sigma V, n=52) with high-purified Serva NB1 collagenase (Serva NB1, n=42) on human islet isolation outcomes. A three-step filtration was applied to the crude Sigma V to eliminate endotoxin contamination and impurities; in addition this process was used as a lot prescreening tool. Isolation outcomes were determined by digestion efficacy, islet yields, purity, viability, glucose-stimulated insulin release, and endotoxin content. The difference of the digestion efficacy between Sigma V and Serva NB1 was very small, however, statistically significant (Sigma V: 64.71% vs. Serva NB1: 69.71%, p <0.05). Islet yields were similar (Sigma V: 23422.58 vs. Serva NB1: 271097 IEq, p>0.05) between groups. No significant purity differences were observed for fractions with purities greater than 75%. Viability (Sigma V: 93.3% vs. Serva NB1: 94.8%, p>0.05), and stimulation indexes (Sigma V: 3.41 vs. Serva NB1: 2.74, p>0.05) were similar between the two groups. The impact of cold ischemia and age on the isolation outcome in the Sigma V group was comparable to the Serva NB1 group. However, we were intrigued to find that the endotoxin content of the final products in the filtered Sigma V group was significantly less than that in the high-purified Serva NB1 group (0.022 EU/ml vs. 0.052 EU/ml, p<0.05). In addition, we found that there was minimal lot to lot variation after filtration and no significant loss of enzymatic activity. These finding indicate that using this or other crude enzyme blends for research pancreata is warranted to reduce isolation costs and increase the amount of islets available for critical islet research. These findings also validate the need for a systematic enzyme analysis to resolve these inconsistencies in overall enzyme quality once and for all