DIABETES/LIPIDS/OBESITY Metabolic and target organ outcomes after total pancreatectomy: Mayo Clinic experience and meta-analysis of the literature Ajay K. Parsaik*, Mohammad Hassan Murad†, Airani Sathananthan*, Vetriselvi Moorthy*, Patricia J. Erwin‡, Suresh Chari§, Rickey E. Carter–, Michael B. Farnell**, S. S. Vege§, Michael G. Sarr** and Yogish C. Kudva* *Endocrinology, †Preventive Medicine, ‡Knowledge and Encounter Research Unit, §Gastroenterology, –Biomedical Statistics and Informatics and **Gastroenterologic and General Surgery, Mayo Clinic, Rochester, MN, USA Summary Introduction Total pancreatectomy (TP) has been associated with substantial metabolic abnormalities and poor glycaemic con- trol limiting its use. Because data reported to date are limited, we evaluated outcomes related to the diabetes mellitus obligated by TP. Methods A case series study of all patients who underwent TP from 01/01/1985 to 12/31/2006 at Mayo Clinic was conducted. TP cases were summarized according to perioperative procedures, mortality and morbidity after TP. To complement this retrospec- tive examination, a survey was developed to measure DM treat- ment modality, target organ failure and complications in patients alive in 2007. We performed a meta-analysis to compare our results with similar previous studies and provide overall estimates of out- comes. Results A total of 141 cases were studied (97 malignant diseases, 44 benign diseases). The median survival was much less for malig- nant pathology (2Æ2 vs 8Æ7 years, Log rank P =0Æ0009). In 2007, there were 59 patients that were presumed alive and 47 (80%) responded to the survey. Mean HbA1c at last follow-up was 7Æ5% with 89% of respondents on a complex insulin programme (mean daily insulin requirement 35 ± 13 units). Episodic hypoglycaemia was experienced by 37 (79%); 15 (41%) experienced severe hypo- glycaemia. In contrast, diabetic ketoacidosis developed in only 2 (4%). Target organ complications and chronic diarrhoea devel- oped in 13 patients (28%) each. Conclusion The primary factor determining survival after TP is the aetiology necessitating TP, i.e. pancreatic malignancy. Most respondents used complex insulin programmes, but hypoglyca- emia continues to be a problem. (Received 12 April 2010; returned for revision 5 May 2010; finally revised 27 July 2010; accepted 27 July 2010) Introduction The frequency of and indications for total pancreatectomy (TP) have changed over time. First performed in 1942, 1 TP was utilized over the next three decades for malignant disease involving the pancreas under the erroneous assumption that ductal adenocarci- noma of the pancreas was a multicentric disease. Less common rea- sons for TP included concerns about the safety of an enteric anastomosis of the pancreatic remnant or at the time of ‘salvage’ surgery for a nonreconstructable, dehisced pancreato-enteric anas- tomosis. 1,2 More recently, TP has been utilized for an expanded series of indications including hereditary pancreatitis, end-stage chronic pancreatitis with disabling pain and in situ neoplasia with malignant potential, such as intraductal papillary mucinous tumours (IPMN) and multifocal islet cell neoplasm. 3–6 For chronic pancreatitis, TP has been used traditionally as a last resort proce- dure after other surgical and nonsurgical treatment attempts have failed. The morbidity and mortality of the apancreatic state affecting patients after TP continues to be a concern. Many factors may affect the duration and quality of survival of the patients after TP, with an important factor being the nature of the underlying pancreatic disease that led to the need for TP; pancreatic carci- noma has been associated with the greatest mortality. Respon- dents of TP are affected by diabetes mellitus obligated by the TP (apancreatic diabetes) and pancreatic exocrine insufficiency, both of which affect morbidity and quality of life. In theory, the com- plete absence of pancreatic hormones, including insulin, glucagon and other islet regulatory peptides, increases the risk of glycaemic variability and severe hypoglycaemia. 7,8 To our knowledge, there is a paucity of data about metabolic crises such as severe hypo- glycaemia and diabetic ketoacidosis (DKA) after TP. Further, detailed descriptions of episodes of severe hypoglycaemia are not available. Apancreatic diabetes may also be a potential cause for microvas- cular complications, including retinopathy, neuropathy, nephrop- athy and macrovascular complications, but limited long-term data address glycaemic control and target organ complications in such patients. To our knowledge, there is no previous study addressing these questions after TP, which prompted us to address these short- comings. Correspondence: Yogish C. Kudva, MBBS, Gastroenterologic and General Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA. Tel.: 5072843964; Fax: 507 284 5745. E-mail: kudva.yogish@mayo.edu Clinical Endocrinology (2010) 73, 723–731 doi: 10.1111/j.1365-2265.2010.03860.x Ó 2010 Blackwell Publishing Ltd 723