Pancreas Resection and Islet Autotransplantation for End-Stage Chronic Pancreatitis

Abstract

ObjectiveTo assess the safety and efficacy of islet autotransplantation (IAT) combined with total pancreatectomy (TP) to prevent diabetes. Summary Background DataThere have been recent concerns regarding the safety of TP and IAT. This is thought to be related to the infusion of large volumes of unpurified pancreatic digest into the portal vein. Minimizing the volume of islet tissue by purifying the pancreatic digest has not been previously evaluated in terms of the postoperative rate of death and complications, pain relief, and insulin independence. MethodDuring a 54-month period, 24 patients underwent pancreas resection with IAT. Islets were isolated using collagenase and a semiautomated method of pancreas digestion. Where possible, islets were purified on a density gradient and COBE processor. Islets were embolized into the portal vein, within the spleen and portal vein, or within the spleen alone. The total median volume of digest was 9.9 mL. ResultsThe median number of islets transplanted was 140,419 international islet equivalents per kilogram. The median increase in portal pressure was 8 mmHg. Early complications included duodenal ischemia, a wedge splenic infarct, partial portal vein thrombosis, and splenic vein thrombosis. Intraabdominal adhesions were the main source of long-term problems. Eight patients developed transient insulin independence. Three patients were insulin-independent as of this writing. Patients had significantly decreased insulin requirements and glycosylated hemoglobin levels compared with patients undergoing TP alone. Of the patients alive and well as of this writing, four had failed to gain relief of their abdominal pain and were still opiate-dependent. ConclusionCombined TP and IAT can be a safe surgical procedure. Unfortunately, almost all patients were still insulin-dependent, but they had decreased daily insulin requirements and glycosylated hemoglobin levels compared with patients undergoing TP alone. A prospective randomized study is therefore needed to assess the long-term benefit of TP and IAT on diabetic complications.Chronic pancreatitis is a progressive inflammatory disease causing irreversible structural damage to the pancreatic parenchyma. It culminates in permanent impairment of pancreatic exocrine function and, in severe cases, diabetes mellitus. The incidence has quadrupled in the past 30 years, and patient management remains a major challenge.1 Patients generally have chronic, intractable abdominal pain that is often relieved only by large quantities of opiates, to which many patients develop tolerance and dependence. There is no agreement as to the best management strategy. Conservative approaches combine medical and supportive modalities (e.g., exocrine enzyme supplements, Octreotide, and antioxidants), nerve blockade (e.g., celiac plexus block, thoracoscopic splanchnic nerve division), or partial resection when the disease is localized. Although these management strategies can be successful, most reports Supported by the Leicester General Hospital NHS Trust.

Gene expression profiles of progressive pancreatic endocrine tumours and their liver metastases reveal potential novel markers and therapeutic targets

“…QGP and CM cells were cultured in RPMI and BON in E4 media (Cancer Research UK Media Production, Clare Hall Laboratories) supplemented with 10% heatinactivated FCS (GibcoBRL, Life Technologies, Paisley, Strathclyde, UK). Human pancreatic islet cells, used as a reference throughout the experiments, were provided with appropriate ethical approval from the University of Leicester (Leicester, UK) and purified as described elsewhere (Ricordi et al 1988, White et al 2001. In brief, islets were prepared by digestion with either collagenase P or HI liberase in a Ricordi chamber, followed by separation using Ficoll sodium diatrizoate density gradient on a COBE 2991 cell processor (GAMBRO.…”

Total Pancreatectomy and Islet Autotransplantation for Chronic Pancreatitis

“…1). The world literature as of 2011 contains reports of about 700 IATs, including the 400 UMN cases cited previously and those done elsewhere (Ahmad et al, 2005;Argo et al, 2008;Clayton et al, 2003;Dixon et al, 2008;Farkas & Pap, 1997;Garcea et al, 2009;Jindal et al, 1998;Oberholzer et al, 2000;Rodriguez et al, 2003;Sarbu et al, 2005;Sutton et al, 2010;Takita et al, 2010;Takita et al, 2011a;Teuscher et al, 1998;Watkins et al, 2003;Webb et al, 2008;White et al, 1998;White et al, 2001;) [2622]. After UMN, the next largest series are at the University of Cincinnati (more than 100) and the University of Leicester (more than 60).…”

“…The largest series published to date on patients undergoing pancreatectomy and IAT have come from the University of Minnesota (Farney et al, 1991;Gores et al, 1992;Gruessner et al, 2004;Jie et al, 2005;Najarian et al, 1979;Najarian et al, 1980;Sutherland et al, 1978;Sutherland et al, 1980a;Sutherland et al, 2004a;Sutherland et al, 2009a;Sutherland et al, 2009b;Sutherland et al, 2011b;Wahoff et al, 1995a) (>400), the University of Cincinnati (Ahmad et al, 2005;Rodriguez et al, 2003;Sutton et al, 2010) (>100), the University of Leicester (Clayton et al, 2003;;Garcea et al, 2009;White SA et al, 1998;White SA et al, 2001;Webb et al, 2008) (>50 cases), but there are many center that are building their series (Argo et al, 2008;Berney T et al, 2000;Desai et al, 2011;Dixon et al, 2008;Jahansouz et al, 2011;Takita et al, 2010;Takita et al, 2011b;Valente et al, 1986) The reports from these centers largely focus on metabolic outcomes, QOL, and pain reduction., but there are many publications on specialized aspects of TP-IAT as have been referenced in this chapter.…”

Surgery for Chronic Pancreatitis

“…Although a high percentage of these patients eventually need insulin, diabetes mellitus can be prevented in some and delayed in others. Most of these diabetics are stable and easier to manage as compared with the patients undergoing total pancreatectomy and no autotransplant [68,69].…”