Proposed thresholds for pancreatic tissue volume for safe intraportal islet autotransplantation after total pancreatectomy

Abstract

The simple question of how much tissue volume (TV) is really safe to infuse in total pancreatectomy-islet autotransplantation (TP-IAT) for chronic pancreatitis (CP) precipitated this analysis. We examined a large cohort of CP patients (n = 233) to determine major risk factors for elevated portal pressure (PP) during islet infusion, using bivariate and multivariate regression modeling. Rates of bleeding requiring operative intervention and portal venous thrombosis (PVT) were evaluated. The total TV per kilogram body weight infused intraportally was the best independent predictor of change in PP (ΔPP) (p < 0.0001; R(2) = 0.566). Rates of bleeding and PVT were 7.73% and 3.43%, respectively. Both TV/kg and ΔPP are associated with increased complication rates, although ΔPP appears to be more directly relevant. Receiver operating characteristic analysis identified an increased risk of PVT above a suggested cut-point of 26 cmH2O (area under the curve = 0.759), which was also dependent on age. This ΔPP threshold was more likely to be exceeded in cases where the total TV was >0.25 cm(3)/kg. Based on this analysis, we have recommended targeting a TV of <0.25 cm(3)/kg during islet manufacturing and to halt intraportal infusion, at least temporarily, if the ΔPP exceeds 25 cmH2O. These models can be used to guide islet manufacturing and clinical decision making to minimize risks in TP-IAT recipients.

Keywords: Bleeding; chronic pancreatitis; intraportal infusion; islet autotransplantation; portal hypertension; portal vein thrombosis; postoperative complications.

Figure 1. Current predictive model of portal hypertension based on transplanted tissue normalized to patient body weight

Increase of portal pressure from baseline is best predicted by a second-order relationship with tissue transplanted per kg recipient body weight, according to the equation shown (p<0.0001; R2 = 0.566). Recommended thresholds of 0.25 cc/kg and 25 cmH20 are indicated, as well as 95% confidence and prediction intervals. Incidence of complications are also indicated for bleeding (“B”/red) or portal venous thrombosis (“T”/blue).

Figure 2. Receiver operating characteristic curve analysis of portal pressure changes and age for incidence of thrombosis with cut-off plot

An overall cut-off of 26 cmH20 maximized sensitivity at 89.2% and specificity at 62.5%, PPV and NPV of 0.08 and 0.99, with an area under the curve of 0.759 (not shown). When performed multivariately, the cut-off was also dependent on age with a recommended logit of 0.040 according to cut-off plot analysis (right panel), and with higher portal pressure potentially tolerated by younger donors (see Table 4). Sensitivity and specificity were 75.0 and 76.0%, with PPV and NPV of 0.10 and 0.98. Similar ROC analysis for bleeding or tissue volume did not produce statistically significant models.