Central venous oxygen saturation during high-risk general surgical procedures-relationship to complications and clinical outcomes.

Major non-cardiac surgery is associated with postoperative morbidity, and perioperative central venous oxygen saturation (ScvO2) may be a predictor of morbidity. This pilot study aimed to define intraoperative ScvO2 and to identify factors associated with postoperative complications. ScvO2 (reflection spectrophotometry) was recorded continuously in a convenience sample of adults undergoing high-risk general surgery. Demographics, intraoperative management, surgery duration, postoperative complications and deaths within 28 days were recorded. Data from 51 patients were analysed. Two (4%) died and 24 (47%) had at least one complication (range 1 to 5). The hospital length-of-stay and duration of surgery were longer in those with complications (22.1±6.1 versus 9.6±3.6 days, P >0.0001, and 328±162 minutes versus 241±94 minutes, P=0.02, respectively). Overall, the ScvO2 was 82±8% and ranged from 40% to 97% with 17 (33%) patients having at least one episode of ScvO2 >70%. Hospital length-of-stay (P >0.0001), time ScvO2 >90% (P=0.003), surgery duration (P=0.005) and blood loss (P=0.02) were correlated with the number of complications. Using multivariate analysis, surgery duration (odds ratio 1.008 [95% confidence interval 1.002 to 1.013]; P=0.006) and change in oxygen extraction ratio (O2ER) at the end of surgery compared to the beginning (odds ratio 1.13 [95% confidence interval 1.001 to 1.28]; P=0.04) were independently associated with complications. The surgery duration and an increased O2ER are factors related to the development of postoperative complications.

Lowering of blood glucose to nondiabetic levels in a hyperglycemic pig by allografting of fetal pig isletlike cell clusters.

BACKGROUND: Fetal pig isletlike cell clusters (ICCs) will differentiate when grafted into the thymus gland of outbred immunosuppressed nondiabetic pigs for up to 3 months. Whether these cells will survive for a similar period in a diabetic recipient and will mature with secretion of insulin to ameliorate the hyperglycemia is unknown. METHODS: Between 40,000 and 125,000 ICCs (7,000 to 11,400 ICCs/kg) were injected into the thymus gland of five juvenile pigs immunosuppressed with cyclosporine and deoxyspergualin, and the animals were subsequently made diabetic by the injection of streptozotocin. Insulin was administered subcutaneously, with one pig dying from hypoglycemia. The animal with the least number of ICCs transplanted was killed 81 days later, and the graft was analyzed histologically. Blood glucose levels and porcine C-peptide in the remaining animals were monitored for a median of 101 days. RESULTS: Histological analysis of the graft showed numerous epithelial cell clusters; the percentage of cells that contained insulin, glucagon, somatostatin, and pancreatic polypeptide were 61%, 64%, 25%, and 18%, respectively. Some cells contained more than one hormone. Porcine C-peptide was detected from 21 days after induction of diabetes but not before. In the pig receiving the most ICCs, blood glucose levels were lowered to nondiabetic levels 109 days after transplantation. Plasma C-peptide levels in response to glucagon in this pig steadily increased after grafting; peak levels were 0, 0.21, 0.45, and 0.52 ng/ml at 4, 21, 49, and 80 days after induction of diabetes compared to 0.09 ng/ml in control diabetic pigs. The secretion of C-peptide in response to oral and intravenous glucose and arginine also was greater than in untransplanted diabetic pigs, the pattern of secretion being consistent with developing fetal beta cells as the source of the C-peptide. Pancreatic insulin content was 0.1 mU/mg, 4% of that in nondiabetic pigs, and the number of beta cells per islet was 3 to 6 compared to 90 in nondiabetic controls. CONCLUSIONS: ICCs will differentiate and function for up to 111 days when transplanted into outbred immunosuppressed pigs rendered diabetic. Blood glucose levels can be lowered to nondiabetic levels when sufficient numbers of ICCs are grafted.

Alcohol and the pancreas.

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The presentations were (1) Phenotypic alteration of myofibroblast during ethanol-induced pancreatic injury: its relation to bFGF, by Masahiko Nakamura, Kanji Tsuchimoto, and Hiromasa Ishii; (2) Activation of pancreatic stellate cells in pancreatic fibrosis, by Paul S. Haber, Gregory W. Keogh, Minoti V. Apte, Corey S. Moran, Nancy L. Stewart, Darrell H.G. Crawford, Romano C. Pirola, Geoffrey W. McCaughan, Grant A. Ramm, and Jeremy S. Wilson; (3) Pancreatic blood flow and pancreatic enzyme secretion on acute ethanol infusion in anesthetized RAT, by H. Nishino, M. Kohno, R. Aizawa, and N. Tajima; (4) Genotype difference of alcohol-metabolizing enzymes in relation to chronic alcoholic pancreatitis between the alcoholic in the National Institute on Alcoholism and patients in other general hospitals in Japan, by K. Maruyama, H. Takahashi, S. Matsushita, K. Okuyama, A. Yokoyama, Y. Nakamura, K. Shirakura, and H. Ishii; and (5) Alcohol consumption and incidence of type 2 diabetes, by Katherine M. Conigrave, B. Frank Hu, Carlos A. Camargo Jr, Meir J. Stampfer, Walter C. Willett, and Eric B. Rimm.

Chronic pancreatitis: complications and management.

Chronic pancreatitis is characterized by progressive and irreversible loss of pancreatic exocrine and endocrine function. In the majority of cases, particularly in Western populations, the disease is associated with alcohol abuse. The major complications of chronic pancreatitis include abdominal pain, malabsorption, and diabetes. Of these, pain is the most difficult to treat and is therefore the most frustrating symptom for both the patient and the physician. While analgesics form the cornerstone of pain therapy, a number of other treatment modalities (inhibition of pancreatic secretion, antioxidants, and surgery) have also been described. Unfortunately, the efficacy of these modalities is difficult to assess, principally because of the lack of properly controlled clinical trials. Replacement of pancreatic enzymes (particularly lipase) in the gut is the mainstay of treatment for malabsorption; the recent discovery of a bacterial lipase (with high lipolytic activity and resistance to degradation in gastric and duodenal juice) represents an important advance that may significantly increase the efficacy of enzyme replacement therapy by replacing the easily degradable porcine lipase found in existing enzyme preparations. Diabetes secondary to chronic pancreatitis is difficult to control and its course is often complicated by hypoglycaemic attacks. Therefore, it is essential that caution is exercised when treating this condition with insulin. This paper reviews recent research and prevailing concepts regarding the three major complications of chronic pancreatitis noted above. A comprehensive discussion of current opinion on clinical issues relating to the other known complications of chronic pancreatitis such as pseudocysts, venous thromboses, biliary and duodenal obstruction, biliary cirrhosis, and pancreatic cancer is also presented.

Activation of pancreatic stellate cells in human and experimental pancreatic fibrosis.

The mechanisms of pancreatic fibrosis are poorly understood. In the liver, stellate cells play an important role in fibrogenesis. Similar cells have recently been isolated from the pancreas and are termed pancreatic stellate cells. The aim of this study was to determine whether pancreatic stellate cell activation occurs during experimental and human pancreatic fibrosis. Pancreatic fibrosis was induced in rats (n = 24) by infusion of trinitrobenzene sulfonic acid (TNBS) into the pancreatic duct. Surgical specimens were obtained from patients with chronic pancreatitis (n = 6). Pancreatic fibrosis was assessed using the Sirius Red stain and immunohistochemistry for collagen type I. Pancreatic stellate cell activation was assessed by staining for alpha-smooth muscle actin (alphaSMA), desmin, and platelet-derived growth factor receptor type beta (PDGFRbeta). The relationship of fibrosis to stellate cell activation was studied by staining of serial sections for alphaSMA, desmin, PDGFRbeta, and collagen, and by dual-staining for alphaSMA plus either Sirius Red or in situ hybridization for procollagen alpha(1) (I) mRNA. The cellular source of TGFbeta was examined by immunohistochemistry. The histological appearances in the TNBS model resembled those found in human chronic pancreatitis. Areas of pancreatic fibrosis stained positively for Sirius Red and collagen type I. Sirius Red staining was associated with alphaSMA-positive cells. alphaSMA staining colocalized with procollagen alpha(1) (I) mRNA expression. In the rat model, desmin staining was associated with PDGFRbeta in areas of fibrosis. TGFbeta was maximal in acinar cells adjacent to areas of fibrosis and spindle cells within fibrotic bands. Pancreatic stellate cell activation is associated with fibrosis in both human pancreas and in an animal model. These cells appear to play an important role in pancreatic fibrogenesis.

Differentiation of fetal pig endocrine cells after allografting into the thymus gland.

BACKGROUND: The thymus of large animals, such as the pig, is thought to be an appropriate site for transplanting adult islets, which contain numerous beta cells, for the purpose of reversing diabetes. Whether fetal islet-like cell clusters (ICCs), which contain few beta cells, will develop at this site, so that adequate amounts of insulin can be produced, is unknown. METHODS: Between 15,000 and 40,000 ICCs were injected into the thymus gland of six juvenile immunosuppressed pigs, and the animals were killed up to 30 days later. The graft was then examined histologically and comparisons made with untransplanted ICCs and those grafted into the omentum of immunosuppressed pigs. RESULTS: At transplantation, the percentage of cells in the ICCs containing insulin, glucagon, somatostatin, or pancreatic polypeptide was 9+/-1%, 13+/-2%, 9+/-1%, and 3+/-1% respectively. Within 9-30 days of transplantation into the thymus, the percentage of all endocrine cells increased, insulin to 41+/-3%, glucagon to 43+/-6%, somatostatin to 26+/-4%, and pancreatic polypeptide to 9+/-3%. There was co-localization of more than one hormone in some cells. Omental grafts contained a similar percentage of insulin and glucagon-containing cells, but significantly fewer somatostatin and pancreatic polypeptide-containing cells. CONCLUSIONS: Endocrine cells from the fetal pig pancreas will differentiate when transplanted into the thymus gland of the pig, making this a suitable site for grafting ICCs to test their ability to normalize blood glucose levels of diabetic recipients.