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The discovery of a cystic lesion in the pancreas implies a challenge for the physician. Approximately 10% are cystic tumors, benign to highly malignant, or true cysts, showing all stages of cellular differentiation, from benign to highly malignant tumors. Malignant cystic tumors are rare and comprise only about 1% of all pancreatic malignancies, they are potentially curable. Therefore, correct diagnosis and treatment of these lesions are of great importance. It is usually not possible to separate a pseudocyst from a benign cyst or a cystic tumor, but there are some signs and findings that could be helpful in the clinical decision. The diagnosis of a cystic pancreatic tumor requires different imaging techniques, including ultrasonography, computerized tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography, but to distinguish a pseudocyst or a benign cyst from a potentially malignant lesion can be very difficult. The usefulness of blood tests and investigations of cyst fluid can be questionable. Today, surgical treatment of cystic pancreatic tumors can be performed with low morbidity. Therefore, we conclude that an active strategy with resection of cystic tumors of the pancreas should be recommended.

CCK is a physiological inhibitor of gastric emptying and food intake. The pancreatic peptide amylin exerts similar actions, yet its physiological importance is uncertain. Objectives were to compare the dose-dependent effects of intravenous infusion of amylin and CCK-8 on gastric emptying and food intake in rats, and to assess whether physiological doses of amylin are effective. Amylin and CCK-8 inhibited gastric emptying with mean effective doses (ED50s) of 3 and 35 pmol · kg−1 · min−1 and maximal inhibitions of 60 and 65%, respectively. Amylin and CCK-8 inhibited food intake with ED50s of 8 and 14 pmol · kg−1 · min−1 and maximal inhibitions of 78 and 69%, respectively. The minimal effective amylin dose for each effect was 1 pmol · kg−1 · min−1. Our previous work suggests that this dose increases plasma amylin by an amount comparable to that produced by a meal. These results support the hypothesis that amylin acts as a hormonal signal to the brain to inhibit gastric emptying and food intake and that amylin produces satiety in part through inhibition of gastric emptying.

Sir, We thank the authors of this letter for their interest in our manuscript “Diffusion-weighted magnetic resonance imaging of pancreas tumours” [1] and for their valuable and interesting comments. The aim of our study was not to evaluate whether diffusion-weighted (DW)MR imaging of the pancreas can differentiate between pancreas cancer and mass-forming pancreatitis. As a part of the “Discussion” section in our manuscript, we considered it valuable to comment on the false positive findings of the comprehensive MR examination in two patients with mass-forming pancreatitis where DWI was correct in characterizing these lesions as non-malignant. Furthermore we stressed, in the “Discussion” section, that the issue of whether DW MRI can help in distinguishing between these two entities needs to be examined in studies with larger patient groups. The role of DW MRI in differentiation of pancreas cancer and massforming pancreatitis is currently a “hot topic” and there are many reports in the literature with variable results. For example, there are studies showing that ADC values of mass-forming pancreatitis are higher [2, 3] or lower [4, 5] than ADC values of pancreas cancer. Additionally, one study shows that ADC values of mass-forming pancreatitis are indistinguishable from ADC values of the remaining gland [6]. The variability of the ADC values of mass-forming pancreatitis compared with those of pancreas cancer in the aforementioned reports may be explained by the nature of inflammation in the cases of mass-forming pancreatitis, which may happen in the form of either acute relapsing pancreatitis in the setting of chronic pancreatitis that may show increased ADC values or predominant fibrosis that will reveal lower ADC values [6]. Regarding the use of the selected b value of 500 mm/s, we do agree that the T2 shine-through effect might be present, as is not the case in DW images when higher b values (800 or 1,000 mm/s) are selected. But this effect is eliminated in the corresponding ADC map [7, 8], whose use combined with the DW images with b values of 0 and 500 mm/s was a part of the evaluation in the present study. In that way, we did not encounter difficulties with the T2 shine-through effect in benign lesions in DW images with a b value of 500 mm/s. We would like to thank the authors of this letter once again for their interesting comments and express even our belief that the possible role of DW MR imaging in differentiating between pancreas cancer and massforming pancreatitis has to be thoroughly examined. This reply refers to Letter to the Editor available at http://dx.doi.org/10.1007/ s00330-010-1729-3

Insulin-like growth factor-I (IGF-I) has been demonstrated to exert a nitrogen sparing effect, both experimentally and in patients after abdominal surgery. IGF-I is a major mediator for the anabolic effects of growth hormone (GH). Whether elevated circulating IGF-I levels are the sole mediator of the anabolic effects following GH has not been clarified. IGF-I influences glucose metabolism, both through its own specific receptor and by activating the insulin receptor, and has also been proposed to influence pancreatic islet secretion directly. In the present study, the postoperative effects of IGF-I on plasma levels of other gastrointestinal and pancreatic islet hormones and growth factors were measured in patients after abdominal surgery. Fifteen patients who were candidates for large bowel resection were randomly divided into two groups: IGF-I-treated (n=8) and placebo-treated (n=7). The IGF-I group received daily two s.c. injections of human recombinant IGF-I (80 microg/kg body weight) for five days, beginning on the morning of the first postoperative day. The other group received placebo injections. Fasting plasma levels of gastrointestinal growth factors (epidermal growth factor, transforming growth factor-alpha, IGF-II), gastrointestinal hormones (gastrin, enteroglucagon, peptide YY), and islet hormones (insulin, islet amyloid polypeptide (IAPP) and pancreatic glucagon) were determined by RIA preoperatively and after five days of treatment. No significant effects of IGF-I on other growth factors or gastrointestinal hormones were seen. A marked increase in plasma insulin postoperatively compared with the preoperative levels (42+/-3 vs 61+/-5 pM, P

Islet amyloid polypeptide (IAPP) is produced in pancreatic beta cells. Intraislet function of IAPP is still uncertain. In the present study, we investigated effects of IAPP and somatostatin on stimulus-secretion coupling of beta cells in isolated rat pancreatic islets. Insulin secretion induced by 22.2 mM glucose was increased by an IAPP antiserum (0.1%) or an IAPP antagonist (IAPP8-37, 10 microM). Pretreatment of islets with pertussis toxin (PTX) abolished the stimulating effect of IAPP8-37 on glucose-induced insulin secretion. In contrast, IAPP antiserum and IAPP8-37 did not change insulin secretion induced by 30 mM KCl. Somatostatin (1 nM) inhibited insulin secretion induced by 22.2 mM glucose, 10 mM L-arginine, 25 microM forskolin, and 200 microM carbachol. IAPP (10 microM) enhanced the inhibitory effect of somatostatin on insulin secretion induced by L-arginine or forskolin. PTX pretreatment abolished the effects of somatostatin and IAPP on arginine-induced insulin secretion. In conclusion, IAPP regulates multiple steps in signal transductions of beta cells. The effects of IAPP on beta cells are mediated by PTX-sensitive regulatory G proteins.

Starvation induces an increase in intestinal permeability that can be of importance to intestinal integrity. Glutamine is the principal energy source for intestinal enterocytes and is considered essential for gut metabolism, structure and function. The aim of this study was to investigate whether glutamine could improve the ATP content of the mucosa of starved rats and attenuate the permeability perturbation during incubation in vitro in Ussing chamber.Segments of jejunum from rats starved for 48 h were mounted in Ussing chambers. Glutamine was added to Krebs-buffer at 0.6mM, 3mM, 6mM and 30mM concentrations on the mucosal side. Cr-EDTA permeation, ATP content of the epithelium mucosa and electrophysiology were studied during 180 min of incubation in Ussing chambers.These was a negative linear correlation between ATP content and(51)Cr-EDTA permeability in stripped mucosa. ATP content was reduced in all groups during the experiment. When 30 mM glutamine was added on the mucosal side there was an increase in(51)Cr-EDTA permeability (P0.001). There was no effect of glutamine on transepithelial resistance but higher concentrations of glutamine (3mM) significantly increased the short circuit current.Supplementing glutamine to the mucosal side in the Ussing chamber led to an increase in ion pump activity and to an increase in paracellular permeability at the 30mM glutamine concentration. Glutamine did not restore the intracellular ATP level. The increase in permeability was inversely correlated to the mucosal ATP content.

Introduction: Enterocyte proliferation and cellular energy status are important to intestinalintegrity after starvation and trauma. The proliferative response to nutrients is expressed in the activity of ornithine decarboxylase (ODC), but ODC activity and ATP level in the intestinal mucosa the first hours after surgery and immediate refeeding are not known. Methods: Male Wistar rats (240–280 g) were starved for 48 h and submitted to laparotomy with distalileal transection, gastrostomy and jejunal instillation of either enteral formula or saline. The ODC activity and ATP content of the jejunal mucosa were analysed in samples taken at 1, 2, 4 and 6 h after surgery. Results: ODC activity increased and reached the highest peak at 2 h in the refed animals. ATP concentrationand energy charge of jejunal mucosa were significantly reduced 6 h after surgery compared to initial levels, but there were no differences between animals that were refed or not. Intestinal transection did not stimulate ODC activity. Conclusion: ATP levels in intestinal mucosa decreased after surgery, and early enteral feeding did not seem to prevent this decrease during the first 6 h. Refeeding immediately after surgery elicits an early but transient increase of ODC activity in rat jejunal mucosa.

Abnormal insulin and islet amyloid polypeptide (IAPP) secretion are usually seen in patients with exocrine pancreatic cancer. The beta-cell dysfunction is a characteristic of the glucose intolerance found in pancreatic cancer patients. The effects of pancreatic cancer cells on insulin and IAPP secretion from beta cells are unclear. In this study, isolated rat pancreatic islets were cocultured with two human pancreatic adenocarcinoma cell lines (Panc-1 and HPAF) and a human colonic adenocarcinoma cell line (HT-29). As a control, islets were incubated in the absence of malignant cells. The accumulation of insulin and IAPP in culture media was measured by radioimmunoassay. Output of insulin and IAPP was decreased in islets cocultured with each malignant cell line. Molar ratio of secreted IAPP and insulin (IAPP/insulin) was increased in the islets cocultured with Panc-1 or HPAF cells, but not HT-29 cells. The decreased insulin and IAPP secretion were partly recovered after Panc-1, HPAF, or HT-29 cells were removed. The IAPP/insulin ratio was normalized after the removal of Panc-1 or HPAF cells. This study indicates that insulin and IAPP secretion are altered by the human adenocarcinoma cells investigated. The impairment induced by pancreatic adenocarcinoma cells is associated with a hypersecretion of IAPP relative to insulin on a molar basis.

Maintenance of intestinal integrity is essential after major abdominal surgery in malnourished subjects. The purpose of this experimental study was to investigate factors affecting small-bowel mucosa permeability in vitro in the immediate postoperative period in starved rats.Male Wistar rats were randomly placed in five groups: Controls, Anesthesia, Resection, Starvation, and Starvation + resection. Controls consisted of fed rats. Anesthesia was induced intraperitoneally with xylazine and ketamine. Resection was 5 cm of the mid-jejunum, and the starvation period was 48 h. Two hours after surgery stripped mucosal segments from the jejunum and the ileum were mounted in Ussing chambers, and the transmucosal permeation of 51Cr-labeled ethylenediaminetetraacetic acid (EDTA) and dextran (40,000 Da) was studied for 120 min while electrophysiology was monitored.Starvation increased permeability to 51Cr-EDTA in both the jejunum and ileum. In the jejunum permeability was further increased by starvation + resection. Resection or anesthesia alone did not increase permeability. The villous height in the jejunum was reduced by starvation. Mucosal permeability was correlated to the change in transepithelial resistance during experiments.Starvation was the main cause of increased mucosal permeability in both intestinal segments of the rat, but surgical trauma had an additive effect, which was most pronounced in the jejunum.

A 30-year-old previously healthy woman was diagnosed as having a vasoactive intestinal polypeptide (VIP)-producing tumour of the pancreas. Her medical history was typical for neuroendocrine gastrointestinal tumours, presenting initially with non-specific symptoms but eventually she developed life-threatening manifestations requiring intensive care due to severe dehydration. She immediately recovered following surgical resection. The patient had elevated serum concentrations of VIP as well as pancreastatin, and post-operatively elevated concentrations of three growth factors, IGF-I, EGF and TGF-alpha, were seen. The importance of the alterations in plasma concentrations of the different peptides for her symptomatology are discussed.

Background.Interactions have been found between exocrine pancreatic adenocarcinoma and islets of Langerhans. Growth of pancreatic adenocarcinoma cells can be regulated by islet hormones such as insulin and somatostatin. Conversely, dysfunction of endocrine pancreas frequently accompanies the exocrine malignancy. The mechanisms underlying these interactions have not been defined. Materials and methods.Human pancreatic adenocarcinoma cells (HPAF cells) were cocultured with isolated rat pancreatic islets in two-compartment wells. HPAF cells and islets cultured in separate wells served as controls. In separate experiments, HPAF cells were incubated with two concentrations of exogenous insulin, including one reflecting the levels of insulin secretion seen in the coculture experiments. Results.Proliferation of HPAF cells was increased by about 50% following a 2- or 5-day incubation with pancreatic islets (P< 0.05). Coculture of HPAF cells and pancreatic islets was associated with a greater reduction in glucose concentrations (P< 0.01) and an increase in lactate accumulation (P< 0.05) in the culture media. Insulin concentrations in the media were significantly decreased during the first 2–3 days of the coculture incubation (P< 0.05). In contrast, insulin secretion from control islets was not significantly decreased until the fifth day of the experiment. The growth of HPAF cells was stimulated by both concentrations of exogenous insulin (P< 0.05). The insulin-stimulated HPAF cells also showed an enhanced glucose consumption and lactate production (P< 0.05). Conclusions.Pancreatic islets regulate both growth and glucose metabolism of adjacent exocrine cancer cells. β-cell-derived insulin may be one of the factors inducing these effects. Insulin release from islet β-cells is compromised in the presence of exocrine cancer cells.

In this study, we investigated the presence of islet amyloid polypeptide (IAPP) in somatostatin cells of rat endocrine pancreas and the effect of exogenous IAPP and somatostatin, separate or combined, on in vitro insulin secretion. By immunocytochemistry, IAPP was found in both B and D cells of rat pancreatic islets. Furthermore, the labeling density of IAPP in D cells was nearly four times higher than in B cells. After a 2-day preincubation in RPMI 1640 (11.1 mM glucose), isolated rat pancreatic islets were exposed to IAPP and/or somatostatin for 90 min in modified Krebs-Ringer bicarbonate (KRB) buffers containing 11.1 or 22.2 mM glucose, or 11.1 mM glucose + 10 mM L-arginine, respectively. At 11.1 mM glucose, insulin secretion was not affected by IAPP and/or somatostatin at concentrations investigated. Insulin response to 22.2 mM glucose was inhibited by exogenous somatostatin. Arginine-stimulated insulin secretion was also inhibited by somatostatin, and the effect was significantly potentiated with additional 10(-5) M IAPP. The study shows that rat pancreatic D cells have higher IAPP density than B cells in the same islets and that IAPP and somatostatin may cooperate on rat pancreatic B cells to regulate the insulin secretion in response to potent stimulation.

Six healthy volunteers showed significantly higher plasma islet amyloid polypeptide levels following an oral glucose tolerance test compared to fasting levels. The urine IAPP concentration before and after the OGTT was comparable to that in plasma. Reverse phase HPLC and radioimmunoassay analysis of urine samples revealed a single IAPP-immunoreactive peak. Before hemodialysis, the plasma levels of IAPP and C-peptide, but not of insulin, were significantly elevated in eight fasting patients with chronic renal failure, compared to eight healthy matched control subjects. After hemodialysis, there was a tendency for decreased IAPP levels compared to before dialysis. In summary, elevated levels of plasma IAPP were found in patients with chronic renal failure and the peptide is eliminated by hemodialysis. Furthermore, immunoreactive IAPP is normally present in the urine. These results suggest that IAPP is, at least in part, renally eliminated from the plasma by excretion (glomerular filtration and/or tubular secretion.

AIM: To examine whether rendezvous endoscopic retrograde cholangiopancreatography (ERCP) is associated with less pancreatic damage, measured as leakage of proenzymes, than conventional ERCP. METHODS: Patients (n = 122) with symptomatic gallstone disease, intact papilla and no ongoing inflammation, were prospectively enrolled in this case-control designed study. Eighty-one patients were subjected to laparoscopic cholecystectomy and if intraoperative cholangiography suggested common bile duct stones (CBDS), rendezvous ERCP was performed intraoperatively (n = 40). Patients with a negative cholangiogram constituted the control group (n = 41). Another 41 patients with CBDS, not subjected to surgery, underwent conventional ERCP. Pancreatic proenzymes, procarboxypeptidase B and trypsinogen-2 levels in plasma, were analysed at 0, 4, 8 and 24 h. The proenzymes were determined in-house with a double-antibody enzyme linked immunosorbent assay. Pancreatic amylase was measured by an enzymatic colourimetric modular analyser with the manufacturer's reagents. All samples were blinded at analysis. RESULTS: Post ERCP pancreatitis (PEP) occurred in 3/41 (7%) of the patients cannulated with conventional ERCP and none in the rendezvous group. Increased serum levels indicating pancreatic leakage were significantly higher in the conventional ERCP group compared with the rendezvous ERCP group regarding pancreatic amylase levels in the 4- and 8-h samples (P = 0.0015; P = 0.03), procarboxypeptidase B in the 4- and 8-h samples (P < 0.0001; P < 0.0001) and trypsinogen-2 in the 24-hour samples (P = 0.03). No differences in these markers were observed in patients treated with rendezvous cannulation technique compared with patients that underwent cholecystectomy alone (control group). Post procedural concentrations of pancreatic amylase and procarboxypeptidase B were significantly correlated with pancreatic duct cannulation and opacification. CONCLUSION: Rendezvous ERCP reduces pancreatic enzyme leakage compared with conventional ERCP cannulation technique. Thus, laparo-endoscopic technique can be recommended with the ambition to minimise the risk for post ERCP pancreatitis. (C) 2013 Baishideng. All rights reserved. (Less)

Islet amyloid polypeptide (IAPP) is a hormonal peptide that at high doses has been shown to reduce food intake. In the present study, the dose-response effects of subcutaneous infusion of IAPP (0, 2, 7, and 25 pmol.kg-1.min-1) for 8 days on food intake and meal patterns in rats were investigated. At the end of the experiment, plasma was obtained and levels of IAPP were measured by radioimmunoassay. IAPP dose-dependently and transiently inhibited food intake. The minimal effective dose (2 pmol.kg-1.min-1) caused a small but significant (up to 14%, P < 0.01) inhibition of food intake that lasted 5 days. The highest dose administered (25 pmol.kg-1.min-1) had the greatest effect (up to 44%, P < 0.001), which lasted throughout the 8-day period. Reductions in feeding during light and dark phases occurred through a decrease in number of meals consumed rather than meal size or meal duration. IAPP also decreased body weight gain and water intake dose dependently. IAPP infusion of 2, 7, and 25 pmol.kg-1.min-1 increased plasma IAPP concentrations from a basal level of 10.3 +/- 0.7 pM to 35.1 +/- 5.4, 78.1 +/- 11.2, and 236.6 +/- 23.6 pM, respectively, values that are likely to be close to physiological and within the pathophysiological ranges. Thus IAPP may play an important physiological or pathophysiological role in control of food intake.

We have investigated whether a possible dysregulation of the storage and function of islet amyloid polypeptide (IAPP) in the endocrine pancreas of 4-month-old spontaneously diabetic Goto-Kakizaki (GK) rats might contribute to the impairment of glucose-induced insulin secretion previously reported in these rats. Immunocytochemical studies indicated a significantly lower degree of labeling per beta-cell granule of insulin but not of IAPP in GK islets compared to control islets. Further, the GK rats displayed lower plasma levels of both insulin and IAPP in the fasting state. The pancreatic concentrations of both IAPP and insulin were also significantly lower in the GK rats than in the controls. Following an intraperitoneal glucose injection, the plasma IAPP and insulin concentration of the GK rats did not increase at all, whereas a significant increase in both IAPP and insulin concentration was recorded in the control animals. However, the plasma IAPP/insulin ratio was significantly higher in the GK rats at both 30 and 60 min after glucose injection, which may be a reflection of an increased negative feedback effect of IAPP on insulin release. A relative hypersecretion of IAPP might be one of several factors contributing to the impairment of glucose-induced insulin secretion in this rat model of non-insulin-dependent diabetes mellitus. This is further supported by our electron microscopic observations showing disproportionate IAPP/insulin labeling of beta-cell granules in the GK islets.

PURPOSE: It has been shown in several studies that a colonic J-pouch obviates much of the early dysfunction after a low anterior resection in terms of urgent and frequent bowel movements. In search for specific mediators of the postoperative functional adaptation, two gut peptides, peptide YY and enteroglucagon, were studied. METHODS: Plasma and “neorectal” mucosal levels of both peptides were measured in 12 patients with a straight coloanal anastomosis and in 11 patients with a colonic J-pouch anastomosis. Patients were part of a randomized trial comparing straight and colonic pouch anastomosis. Fasting plasma samples of both peptides were collected intraoperatively, after one week, before loop ileostomy closure, and at 1, 3, and 12 months after loop ileostomy closure. RESULTS: There was no difference between the straight and the pouch groups in plasma concentrations of either peptide at any time period postoperatively. The only longitudinal hormonal changes were transient increases in mucosal peptide YY content at one-month follow-up and in mucosal enteroglucagon content before loop ileostomy closure. CONCLUSION: Peptide YY and enteroglucagon responses in these patients appear not to be major factors for improved out-come after formation of a colonic pouch in low anterior resection.

Insulin-like growth factor I (IGF-I) has been shown experimentally to exert a nitrogen-sparing effect in both animals and humans. Its effects on protein metabolism during the first 5 days after radical large bowel resection were investigated. Nineteen patients were randomly allocated to receive either human recombinant IGF-I (2 × 80 μ/kg body weight subcutaneously, n = 10) or placebo (n = 9) starting on the morning of the first day after operation. All patients received parenteral nutrition (glucose 3 g and nitrogen 0.1 g/kg/day). The mean(s.e.m.) urinary nitrogen: creatinine ratio was significantly reduced in patients who received IGF-I compared with those given placebo (275.0(17.1) compared with 386.3(23.6), P

The diabetes mellitus that occurs in patients with pancreatic cancer is characterized by marked insulin resistance that declines after tumor resection. Islet amyloid polypeptide (IAPP), a hormonal factor secreted from the pancreatic beta cells, reduces insulin sensitivity in vivo and glycogen synthesis in vitro. In this study, we examined the relation between IAPP and diabetes in patients with pancreatic cancer.We measured IAPP in plasma from 30 patients with pancreatic cancer, 46 patients with other cancers, 23 patients with diabetes, and 25 normal subjects. IAPP immunoreactivity and IAPP messenger RNA were studied in pancreatic cancers, pancreatic tissue adjacent to cancers, and normal pancreatic tissue.Plasma IAPP concentrations were elevated in the patients with pancreatic cancer as compared with the normal subjects (mean [+/- SD], 22.3 +/- 13.6 vs. 8.0 +/- 5.0 pmol per liter; P0.001), normal in the patients with other cancers, and normal or low in the patients with diabetes. Among the patients with pancreatic cancer, the concentrations were 25.0 +/- 8.7 pmol per liter in the 7 patients with diabetes who required insulin, 31.4 +/- 12.6 pmol per liter in the 11 patients with diabetes who did not require insulin, and 12.2 +/- 2.4 pmol per liter in the 9 patients with normal glucose tolerance (3 patients had impaired glucose tolerance; their mean plasma IAPP concentration was 11.7 +/- 5.5 pmol per liter). Plasma IAPP concentrations decreased after surgery in the seven patients with pancreatic cancer who were studied before and after subtotal pancreatectomy (28.9 +/- 16.4 vs. 5.6 +/- 3.4 pmol per liter, P = 0.01). Pancreatic cancers contained IAPP, but the concentrations were lower than in normal pancreatic tissue (17 +/- 16 vs. 183 +/- 129 pmol per gram, P0.001). In samples from the patients with both pancreatic cancer and diabetes, immunostaining for IAPP was reduced in islets of pancreatic tissue surrounding the tumor; in situ hybridization studies suggested that transcription occurred normally in these islets.Plasma IAPP concentrations are elevated in patients with pancreatic cancer who have diabetes. Since IAPP may cause insulin resistance, its overproduction may contribute to the diabetes that occurs in these patients.

27 patients admitted for elective abdominal surgery were allocated to receive postoperative total parenteral nutrition supplemented with glutamine (glycyl-glutamine) and tyrosine (glycyl-tyrosine) containing dipeptides (DP-Gln 20; 0.16 g glutamine/kg BW/24 h) or isonitrogenous Vamin 18 for 5 days. The aim was to evaluate safety and effects on short-life plasma proteins, nitrogen balance, 3-methylhistidine excretion and alimentary growth factors in plasma. No differences in transthyretin or retinol binding protein levels, nitrogen balance or 3-methylhistidine excretion were found in patients receiving DP-Gln 20 compared to Vamin 18. There were higher plasma levels of peptide YY in the dipeptide group 5 days after surgery (p0.05). A correlation between insulin levels and nitrogen balance was found only in DP-Gln 20 treated patients day 6 (r = 0.91, p0.01). DP-Gln 20 is a glutamine dipeptide (Gly-Gln) containing amino acid solution which is considered safe in the postoperative state in man. No beneficial effects on whole body protein metabolism were found by adding DP-Gln 20 to total parenteral nutrition.

Thirty-eight human pancreatic cancer specimens were studied for the reactivity of cancer cells with monoclonal antibodies against insulin, glucagon, somatostatin, pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP), gastrin, calcitonin, and with argyrophilic reactivity. Immunoreactivity with one or several antibodies or argyrophilic reactivity were found in 30 (79%) cases. In 17 cases, the number of endocrine cells was excessive and morphologically consistent with the mixed ductal-islet tumor. Although most immunoreactive cells were located at the base of the malignant glands, some had intraepithelial location and were also present in the invasive portion of cancers, indicating their malignant nature. Endocrine cell proliferation were found in the pancreatic tissue adjacent to the carcinoma in 8 out of 12 specimens examined. In these cases, the immunoreactive cells were either distributed among the acinar cells or ductal cells. More endocrine cells were found in the hyperplastic ducts; however, no correlation was found between the degree of hyperplasia and the occurrence of any type of immunoreactive cells. Although several types of endocrine cells occurred in different pancreatic regions (head, body, and tail), PP cells were restricted to tissues taken from the head of the pancreas. Experimental data and similar observations by other investigators led us to conclude that participation of endocrine cells in ductal-type carcinomas is a general phenomenon and does not justify the classification of these lesions to mixed ductal-islet entity. However, because immunoreactive cells were more common and numerous in well-differentiated carcinomas, they may have some prognostic values.

Alterations of glucose metabolism occur frequently in association with pancreatic cancer. Whether diabetes predisposes or is a consequence of pancreatic cancer has not been settled. We have found that induced diabetes prevents development of pancreatic cancer in the hamster model and that genetically diabetic Chinese hamsters resist pancreatic cancer induction, whereas the nondiabetic strain does not. Also, preliminary clinical data indicates that diabetes is associated with pancreatic cancer and that the two conditions develop simultaneously. We have found diabetes or impaired glucose tolerance in 76% of the pancreatic cancer patients at the time of cancer diagnosis. The diabetic condition improved after 75% pancreatectomy. Although the preliminary observations suggest that diabetes accompanies the disorder of pancreatic cancer, additional data are needed before any conclusion can be drawn.

15073 Background: The optimal care for patients with irresectable, non-metastatic pancreatic carcinoma (PAC) is debated. We treated 17 consecutive cases with preop radiochemotherapy (RCT) as a means for downstaging their tumors and compared outcome with 35 patients undergoing direct surgery for primarily resectable PAC during the same time period. Methods: The patients had biopsy proven, irresectable, non-metastatic PAC which engaged >50% of the circumference of a patent mesenteric/portal vein for a distance >2 cm and/or No significant financial relationships to disclose.

About 80% of pancreatic cancer patients have glucose intolerance or frank diabetes. This observation has led to the following two hypotheses: i. pancreatic cancer causes the associated diabetes and ii. the conditions associated with diabetes promote the development of pancreatic cancer. Evidence supporting both hypotheses has been accumulated in previous studies. This article reviews these studies, especially those that have been conducted recently.

Our studies have shown that almost all preneoplastic and neoplastic tumors induced in hamsters contain endocrine cells. Because the induced pancreatic cancer resembles the human disease in many respects, it was of interest to find out whether human pancreatic cancer also produce endocrine cells. To examine the participation of the endocrine cells in the exocrine pancreatic cancer, we first examined 32 human pancreatic cancers with the antibodies against insulin, glucagon, somatostatin, PP, VIP, gastrin, and calcitonin or by argyrophilic reaction (1). Thirty (79%) cancers showed ei therfew or many ceils immunoreactive with all but anti-gastrin-, -VIP, and -calcitoniu. Many cells showed an argyrophilic reaction. In 17 cases, the number of stained cells was excessive and the morphology of tumors was consistent with mixed ductal-islet tumor. Argyrophilic ceils and cells immunoreactive with antiinsulin and -glucagon were the predominant in such cases. However, becat~se the biopsy material we used was small and only a few sections from each tumor were examined, it was not possible to determine whether several types of immunoreactive cells reside at the same location, or whether some cells produce more than one peptide. In subsequent studies, we examined larger sections of surgical material from 9 pancreatic cancer patients by serial sections and by using a multilabeled immunohistochemical technique developed at our institute. With this method, we visualized 4 peptides in the same islet. In this study, we also included antibodies against other pancreatic hormones, including pancreastatin, chromogranin A, serotonin, and neuron-specific enolase (NSE). We found that all 9 cancers contained cells immunoreactive with all of the antibodies used, except for pancreastatin, which was missing in 3 cases ,and for PP, which was not detectable in two cases, Here again, insulin was the predominant cell type, followed by glucagon and somatostatin ceils. Many of these hor-mones were found within the same glands. Colocalization of some hormones, such as insulin and serotonin and NSE and glucagon, was indicated. Similar to the situation in hamsters, most endocrine cells were localized on the base of the glands, but many were also within the epithelium and some seem to reach the lumen by a slender neck. In several cases, accumulation of endocrine cells was found in the papillary projections of the malignant epithelium. Because endocrine cells are found at different levels of the malignant epithelium and within the lumen, it seemed that the endocrine ceils migrated within the epithelium, were shed into the lumen like the tumor cells and were replaced by new endocrine cells at the base of the malignant glands. Although many of these endocrine cells resembled the corresponding endocrine cells in the normal islets, some of these endocrine cells were atypical. Some had granules on the supranuclear cell portion. A few endocrine cells were found in the invasive portion of the cancers, including those that had invaded the periuneural space. There were also atypical cells with cytoplasmic vacnolization and irregular granular distribution, possibly as a reflection of the altered synthesis, storage, or release of the granules. On the other hand, differences in the staining intensity could indicate their endocrine activity. Consequently, it appears that in both humans and hamsters, endocrine cells participate in the development of exocrine pancreatic cancer, and these endocrine cells seem to be malignant and have endocrine activity. Nevertheless, participation of endocrine cells in the exocrine pancreatic cancer is conceptually and practically important, particularly in view of epidemiological studies, which link pancreatic cancer with diabetes. In fact, it has been established that more than 80% of pancreatic cancer patients develop frank diabetes or altered glucose tolerance. Our immunohistochemical and experimental studies, as well as clinical studies by Permert and associates (2-4), have led us to believe that endocrine cell proliferation in exocrine pancreatic cancer may cause alteration in hormonal homeostasis leading to glucose metabolic abnormalities. However, studies are required to substantiate this view.