Circulating tumour cells as a biomarker for diagnosis and staging in pancreatic cancer.

BACKGROUND: Current diagnosis and staging of pancreatic ductal adenocarcinoma (PDAC) has important limitations and better biomarkers are needed to guide initial therapy. We investigated the performance of circulating tumour cells (CTCs) as an adjunctive biomarker at the time of disease presentation. METHODS: Venous blood (VB) was collected prospectively from 100 consecutive, pre-treatment patients with PDAC. Utilising the microfluidic NanoVelcro CTC chip, samples were evaluated for the presence and number of CTCs. KRAS mutation analysis was used to compare the CTCs with primary tumour tissue. CTC enumeration data was then evaluated as a diagnostic and staging biomarker in the setting of PDAC. RESULTS: We found 100% concordance for KRAS mutation subtype between primary tumour and CTCs in all five patients tested. Evaluation of CTCs as a diagnostic revealed the presence of CTCs in 54/72 patients with confirmed PDAC (sensitivity=75.0%, specificity=96.4%, area under the curve (AUROC)=0.867, 95% CI=0.798-0.935, and P<0.001). Furthermore, a cut-off of ⩾3 CTCs in 4 ml VB was able to discriminate between local/regional and metastatic disease (AUROC=0.885; 95% CI=0.800-0.969; and P<0.001). CONCLUSION: CTCs appear to function well as a biomarker for diagnosis and staging in PDAC.

Risk of malignancy in resected cystic tumors of the pancreas < or =3 cm in size: is it safe to observe asymptomatic patients? A multi-institutional report.

Recent international consensus guidelines propose that cystic pancreatic tumors less than 3 cm in size in asymptomatic patients with no radiographic features concerning for malignancy are safe to observe; however, there is little published data to support this recommendation. The purpose of this study was to determine the prevalence of malignancy in this group of patients using pancreatic resection databases from five high-volume pancreatic centers to assess the appropriateness of these guidelines. All pancreatic resections performed for cystic neoplasms < or =3 cm in size were evaluated over the time period of 1998-2006. One hundred sixty-six cases were identified, and the clinical, radiographic, and pathological data were reviewed. The correlation with age, gender, and symptoms (abdominal pain, nausea and vomiting, jaundice, presence of pancreatitis, unexplained weight loss, and anorexia), radiographic features suggestive of malignancy by either computed tomography, magnetic resonance imaging, or endoscopic ultrasound (presence of solid component, lymphadenopathy, or dilated main pancreatic duct or common bile duct), and the presence of malignancy was assessed using univariate and multivariate analysis. Among the 166 pancreatic resections for cystic pancreatic tumors < or =3 cm, 135 cases were benign [38 serous cystadenomas, 35 mucinous cystic neoplasms, 60 intraductal papillary mucinous neoplasms (IPMN), 1 cystic papillary tumor, and 1 cystic islet cell tumor], whereas 31 cases were malignant (14 mucinous cystic adenocarcinomas and 13 invasive carcinomas and 4 in situ carcinomas arising in the setting of IPMN). A greater incidence of cystic neoplasms was seen in female patients (99/166, 60%). Gender was a predictor of malignant pathology, with male patients having a higher incidence of malignancy (19/67, 28%) compared to female patients (12/99, 12%; p < 0.02). Older age was associated with malignancy (mean age 67 years in patients with malignant disease vs 62 years in patients with benign lesions (p < 0.05). A majority of the patients with malignancy were symptomatic (28/31, 90%). Symptoms that correlated with malignancy included jaundice (p < 0.001), weight loss (p < 0.003), and anorexia (p < 0.05). Radiographic features that correlated with malignancy were presence of a solid component (p < 0.0001), main pancreatic duct dilation (p = 0.002), common bile duct dilation (p < 0.001), and lymphadenopathy (p < 0.002). Twenty-seven of 31(87%) patients with malignant lesions had at least one radiographic feature concerning for malignancy. Forty-five patients (27%) were identified as having asymptomatic cystic neoplasms. All but three (6.6%) of the patients in this group had benign disease. Of the patients that had no symptoms and no radiographic features, 1 out of 30 (3.3%) had malignancy (carcinoma in situ arising in a side branch IPMN). Malignancy in cystic neoplasms < or =3 cm in size was associated with older age, male gender, presence of symptoms (jaundice, weight loss, and anorexia), and presence of concerning radiographic features (solid component, main pancreatic duct dilation, common bile duct dilation, and lymphadenopathy). Among asymptomatic patients that displayed no discernable radiographic features suggestive of malignancy who underwent resection, the incidence of occult malignancy was 3.3%. This study suggests that a group of patients with small cystic pancreatic neoplasms who have low risk of malignancy can be identified, and selective resection of these lesions may be appropriate.

Modification of pancreatic carcinogenesis in the hamster model. XII. Dose-related effect of ethanol.

Ethanol (E) was given to outbred Syrian golden hamsters in drinking water at a 5% (wt/vol) concentration for life beginning either before or after a single dose of N-nitrosobis(2-oxopropyl)amine (BOP). No effects on tumor induction were seen in the pancreas or in other BOP target tissues (e.g., the common duct and gallbladder), whether E was given immediately after or 4 weeks before and immediately after BOP. These results sharply conflicted with our previous findings in which a higher concentration of E (25% wt/vol) inhibited BOP-induced pancreatic lesions, and they indicated a dose-related action of E on pancreatic carcinogenesis. Development of a few acinar cell foci in hamsters treated with BOP and E, but not in those treated with E alone or BOP alone, indicated that E in this concentration alters pancreatic functions without modifying carcinogenesis.

Pancreatic secretion in hamsters with pancreatic cancer.

Pancreatic secretory abnormalities develop in most persons with pancreatic cancer and have been attributed to ductal obstruction. These experiments investigated whether abnormal secretion results instead from carcinogen-induced changes in the secreting cells. Fifty male Syrian Golden hamsters (40 to 100 grams) received weekly injections of di-isopropyl-nitrosamine (250 mg/kg, subcutaneously), and survivors and age-matched controls were studied after 3.5 to 6.5 months of treatment. Pancreatic secretion was stimulated by secretin or cholecystokinin (2 units/kg, intravenously, as a bolus). After each stimulus four 15-minute collections of pancreatic juice were analyzed for HCO3- and Cl- or total protein, amylase, trypsin, and chymotrypsin. The organs were examined histologically. Pancreatic ductal adenocarcinoma developed in 30% of the animals at 5 months, 56% at 5.5 months, and 100% at 6.5 months. The animals without cancer either had hyperplasia of the duct epithelium or were histologically normal. The histologic appearance of acinar tissue and protein secretion were normal in all groups. The tumors did not obstruct the major ducts. In all treated animals the pancreatic secretory response to secretin was of low volume, low maximal [HCO3-] and HCO3- output, and low [Cl- + HCO3-]; these changes progressed with time. The secretory abnormalities antedated the appearance of the neoplasms and were not caused by obstruction.

Treatment of acute pancreatitis with beta-adrenergic agonist drugs.

An increase in microvascular permeability may be important in the pathogenesis of acute pancreatitis. beta-adrenergic receptor agonist drugs are known to inhibit the increase in microvascular permeability induced by histamine and related vasoactive substances. These inflammatory mediators have been shown to be released during the course of experimental and human pancreatitis. We investigated the effect of isoproterenol and terbutaline sulfate on the development of acute edematous (AEP) and acute hemorrhagic (AHP) pancreatitis in a feline model of biliary pancreatitis. When given at the time of pancreatic insult, isoproterenol prevented the development of both AEP and AHP. Both isoproterenol and terbutaline sulfate reduced the severity of pancreatic inflammation, even when given up to 12 hours after the onset of AEP. Although neither drug was effective in treating established AHP, our findings suggest that, if given early in the course of the disease, they may be useful in preventing the progression of AEP to AHP.

The influence of ethanol on pancreatic blood flow in cats with chronic pancreatitis.

BACKGROUND: The mechanism by which ethanol predisposes to acute pancreatitis, especially in established chronic pancreatitis, is not known. Here we studied the effects of acute ethanol ingestion on pancreatic blood flow in chronic pancreatitis, a setting characterized by diminished basal blood flow to the pancreas. METHODS: Obstructive pancreatitis was created by partial duct ligation for 3 weeks in nine cats. Controls (n = 8) were not operated on. Blood flow was measured in anesthetized animals with a hydrogen gas clearance technique and an intraductal electrode. Pancreatic interstitial pressure, systemic and portal blood pressures, and serum ethanol levels were recorded, and pancreatic vascular resistance was calculated. Measurements were made before and for 2 hours after 20 cc of 40% (wt/vol) ethanol was instilled into the stomach. RESULTS: Basal flow was reduced in the obstructed pancreas to 51% of normal. Both groups showed an acute decrease in blood flow when ethanol was given. A more steep (50% of baseline) and a more prolonged (120 minutes) fall was observed in the pancreatitis group than in controls (31% and 60 minutes, respectively). The decline in blood flow correlated with increases in interstitial pressure and vascular resistance. CONCLUSIONS: Acute ethanol ingestion sharply reduces pancreatic blood flow, especially in glands with chronic pancreatitis.

Delayed gastric emptying after operation for obstructing peptic ulcer disease: the influence of cimetidine.

We studied the factors related to delayed gastric emptying after operation for obstructing peptic ulcer disease. The records of 76 consecutive patients who underwent operation for obstructing peptic ulcer were examined retrospectively. Delayed gastric emptying (unable to tolerate solid food for at least 2 weeks after operation) occurred in 11 of 76 patients (14.5%). It was not related to the type of operation performed, including procedures that employed truncal vagotomy. It did not correlate with the preoperative severity of obstruction, duration of preoperative nasogastric decompression, or the nutritional status of the patient. Delayed emptying occurred in four of six patients (66.7%) with insulin-dependent diabetes mellitus but only 10 of 70 patients (14%) without insulin-dependent diabetes (p less than 0.001). It was seen in six of 16 patients (37.5%) receiving long-term cimetidine therapy (more than 3 months) but only five of 60 patients (8.3%) not receiving long-term cimetidine therapy (p less than 0.01). Patients receiving long-term cimetidine therapy had an average number of 2.3 prior hospitalizations for ulcer disease while those not receiving long-term cimetidine therapy had an average of 1.4 prior admissions (p less than 0.01). Thus we advise against the long-term use of cimetidine in chronic peptic ulcer disease complicated by obstruction. Patients with diabetes mellitus who require insulin appear to be at particular risk for delayed gastric emptying after operation for obstructing peptic ulcer.

The creation of a surgical endoscopy training program--is there sufficient clinical material?

The American Board of Surgery now requires surgical training programs to provide instruction in gastrointestinal endoscopy. In order to demonstrate that an independent Surgical Endoscopy Service could generate sufficient patient volume for an endoscopy training program, we reviewed our experience before and after the organization of such a service. In the year before formation of the Surgical Endoscopy Service (1981), surgical endoscopists performed 134 upper gastrointestinal (UGI) endoscopies and 25 colonoscopies for a total of 159 procedures. This represented 17% of the total institutional endoscopies performed. Further analysis indicated that 30.5% of UGI endoscopies and 24% of colonoscopies were performed on patients referred from surgical services. During the first year of the Surgical Endoscopy Service (1982), we performed 322 UGI endoscopies and 102 colonoscopies for a total of 424 procedures. This represented an increase to 36.5% of the total institutional endoscopies. During this time 41% of the UGI endoscopies and 33% of the colonoscopies were performed on patients referred from surgical services. Thus, with the formation of a Surgical Endoscopy Service we were able to dramatically increase our procedure volume and to provide effective gastrointestinal endoscopic training for our residency program. This confirmed our premise that in a typical university training program there is sufficient clinical material to provide training in surgical endoscopy.

Pancreatic interstitial pH regulation: effects of secretory stimulation.

BACKGROUND: Bicarbonate secretion by pancreatic ducts presumably releases an equivalent amount of acid into the parenchyma. The purpose of this study was to determine the effects of this acid load on pancreatic interstitial pH (pHI). In addition, we examined the relationship of pHI to changes in pancreatic blood flow (PBF), which may be important in acid disposal. METHODS: After validation of a microelectrode method for measurement of pHI in anesthetized cats, the effects of secretin (2 IU/kg intravenously) and cholecystokinin (0.08 microgram/kg intravenously) were examined. PBF was measured simultaneously by the H2 gas clearance technique. RESULTS: Secretory stimulation with secretin produced an increase in pancreatic bicarbonate secretion (146 +/- 23 microEq/15 minutes, p < 0.01). This secretion was associated with a fall in pHI from 7.36 +/- 0.02 to 7.31 +/- 0.02 (p < 0.001), which returned to baseline after 25 minutes. There was an accompanying increase in PBF from 118 +/- 32 to 148 +/- 35 ml/min/100 gm (p < 0.01). In contrast, stimulation with cholecystokinin only slightly increased pancreatic secretion (49 +/- 19 microliters/15 minutes) and had no significant effects on pH or blood flow. CONCLUSIONS: These results suggest that pancreatic secretion of bicarbonate, but not protein, releases H+ into the interstitium, an acid tide comparable to the alkaline tide during acid secretion by the stomach. This interstitial acidosis was accompanied by an increase in PBF. The increase in blood flow may be important in pH homeostasis, contributing to the disposal of this acid.

Stenting does not decompress the pancreatic duct as effectively as surgery in experimental chronic pancreatitis.

BACKGROUND: In humans with chronic pancreatitis (CP), pancreatic interstitial pressure (IP) is elevated and pancreatic blood flow (PBF) is reduced. The efficacy of surgical decompression (SD) of the pancreatic duct (ie, pancreaticojejunostomy) is believed to be due to its ability to decrease IP and pancreatic vascular resistance (Rp), which increases PBF. Pancreatic duct stenting (STE) also probably reduces IP and Rp, which may explain its efficacy. The purpose of this study was to compare the efficacy of SD with STE. METHODS: CP in cats was created by narrowing the main pancreatic duct. Six weeks later, CP and normal pancreata were isolated and perfused ex vivo under basal conditions and after secretin stimulation. In normal and CP glands, IP and perfusion pressure were measured and Rp (U) was calculated. In two additional groups, the pancreatic duct was decompressed, either by stenting or by complete transection of the duct with a longitudinal capsulotomy. RESULTS: In CP glands, IP and Rp were increased and secretory output was markedly reduced compared with the normal (0.65 +/- 0.30 mm Hg and 0.46 +/- 0.04 U vs 3.90 +/- 0.80 mm Hg and 1.68 +/- 0.05 U; P < .05). Secretin administration (2 units) increased IP and Rp in CP glands (6.60 +/- 1.10 mm Hg and 2.87 +/- 0.07 U; P < .05), but these values did not chang in normal glands (0.81 +/- 0.20 and 0.53 +/- 0.03 U; NS). STE and SD decreased IP and Rp in CP glands (2.20 +/- 0.20 to 1.0 +/- 0.40 mm Hg and 1.20 +/- 0.015 to 0.90 +/- 0.01 U, respectively; P < .05). Both methods prevented an increase of IP and Rp after secretin administration. IP and Rp decreased to a greater degree following SD, compared with STE (P < .05). CONCLUSIONS: Both STE and SD decreased IP and Rp in this experimental model of CP. However, SD was significantly more effective than STE.

Interleukin-10 prevents death in lethal necrotizing pancreatitis in mice.

BACKGROUND: Cytokines derived from macrophages may play an integral role in the evolution of acute pancreatitis. Interleukin-10 (IL-10), a potent antiinflammatory cytokine, prevents the activation of macrophages and their release of inflammatory cytokines. The aim of this study was to determine whether treatment with IL-10 decreased the severity of experimental acute pancreatitis. METHODS: Thirty female Swiss Webster mice were divided into three groups. Acute pancreatitis was induced by using a choline-deficient, 0.5% ethionine supplemented (CDE) diet. Group A (controls) received CDE diet alone. Group B was pretreated with 10,000 units of intraperitoneal IL-10 at the onset of feeding and every 8 hours thereafter. Group C received IL-10 33 hours after beginning the CDE diet and every 8 hours thereafter. One half of the animals in each group was killed at 54 hours; the remaining living animals were killed at 80 hours. Serum amylase levels (units per liter) were determined at 54 and 80 hours. Pancreata were harvested and fixed in formalin. Histologic characteristics were graded on a scale from 0 to 4 (normal to most abnormal) in a blinded fashion by two investigators. RESULTS: Serum amylase level and histologic score (edema, inflammation, hemorrhage, and necrosis) were significantly reduced when IL-10 was administered either prophylactically or therapeutically (p < 0.01). At 54 hours all animals were alive. Mortality was reduced at 80 hours in both groups treated with IL-10 compared with those fed the CDE diet alone (p < 0.001). CONCLUSIONS: These results suggested that macrophages play an integral role in determining the severity of acute pancreatitis in this animal model. The finding that IL-10 decreased inflammation and prevented death, even when given after acute pancreatitis was established, suggests that it may have potential for clinical use.

Acute hypercalcemia, pancreatic duct permeability, and pancreatitis in cats.

We investigated the effects of hypercalcemia on pancreatic duct permeability and pancreatitis in cats. Acute hypercalcemia was maintained by an infusion of calcium gluconate; controls received saline solution. Chronic hypercalcemia was maintained by diet and by vitamin D and dihydrotachysterol injections. Portal venous blood was analyzed for large dextran molecules that had been perfused through the pancreatic duct. In a separate group of hypercalcemic animals, we perfused the duct with activated pancreatic enzymes to induce acute pancreatitis. After 24 hours of hypercalcemia, dextrans were detected in the portal venous blood of 6 of 11 hypercalcemic and none of the 6 control animals (p less than 0.05). After 12 hours of hypercalcemia, dextrans were detected in all 7 hypercalcemic and 1 of 7 control animals (p less than 0.001). The degree of pancreatic inflammation was greater in the 12-hour animals than in the controls (p less than 0.001). After 14 days of hypercalcemia, however, there were no differences in dextran permeability or pancreatitis in experimental or control animals. Our results indicate that acute hypercalcemia increases the permeability of the pancreatic duct to molecules the size of pancreatic enzymes. This could be important in the pathogenesis of acute pancreatitis associated with hypercalcemic states.

Interleukin-10 reduces the systemic inflammatory response in a murine model of intestinal ischemia/reperfusion.

BACKGROUND: Intestinal ischemia/reperfusion (I/R) is known to increase systemic cytokine levels, as well as to activate neutrophils in distant organs. This study was designed to investigate the effect of interleukin-10 (IL-10) on cytokine release, pulmonary neutrophil accumulation, and histologic changes in a murine model of I/R. METHODS: Forty female Swiss-Webster mice were divided into four groups. Group 1 underwent 45 minutes of superior mesenteric artery occlusion followed by 3-hour reperfusion (I/R). Group 2 underwent laparotomy alone (Sham). Group 3 underwent I/R, but was treated with IL-10, 10,000 units IP every 2 hours, starting 1 hour before reperfusion (Pretreatment). Group 4 was treated with an equal dose of IL-10, starting 1 hour after reperfusion (Posttreatment). All animals were killed at 3 hours, standard assays were performed for serum cytokine levels, and lung myeloperoxidase activity and intestinal histology were scored. RESULTS: Serum cytokines (TNF-alpha and IL-6), lung myeloperoxidase levels, and histologic score were significantly reduced when IL-10 was administered either before or after reperfusion. CONCLUSIONS: IL-10 reduced the severity of local and systemic inflammation in a murine model of intestinal I/R when given before or after reperfusion injury. These observations suggest that IL-10 may exert its effect by blocking cytokine production and distant organ neutrophil accumulation.

An ETa/ETb endothelin antagonist ameliorates systemic inflammation in a murine model of acute hemorrhagic pancreatitis.

BACKGROUND: Endothelin peptides are polykines with strong vasoconstrictor properties. We have previously shown that endothelin antagonism (PD145065) reduces the local severity of acute pancreatitis. We now investigated the effect of endothelin antagonism on systemic inflammation in a model of acute hemorrhagic pancreatitis. METHODS: Forty-two mice were divided into four groups. Group 1 was fed standard food plus PD145065 every 8 hours. Group 2 was fed a choline-deficient ethionine (CDE) supplemented diet and given saline every 8 hours. Group 3 was fed a CDE diet and treated with PD145065 every 8 hours from initiation of diet. Group 4 was fed a CDE diet and given PD145065 from 48 hours after initiation of diet. Animals were killed at 70 hours. Serum was collected. Pancreata and lung tissue were harvested. RESULTS: Histology score, serum amylase level, lung myeloperoxidase, and interleukin (IL)-10 were all significantly reduced in both treatment groups (groups 3 and 4) (p < 0.05). IL-6 levels were reduced in group 3 only (p < 0.05). The mortality rate did not differ among any of the groups. CONCLUSIONS: Endothelin antagonism decreased the severity of acute pancreatitis and reduced markers of systemic inflammation. Late treatment at 48 hours failed to prevent the rise in IL-6. Mortality rates were unaffected by treatment.

Histologic changes after stenting of the pancreatic duct.

The placement of stents has been proposed as a possible modality to treat pancreatic diseases. Ductal changes observed on endoscopic retrograde cholangiopancreatography during stenting are believed to be reversible when the stents are removed. We describe a patient with normal anatomy on baseline pancreatograms who underwent endoscopic sphincterotomy, followed by stent placement for 9 months. Symptoms progressed, leading to a pancreaticoduodenectomy. Histologic evaluation of the head of the pancreas revealed more extensive inflammatory changes in the duct and parenchyma drained by the stent. This suggests that stent-induced changes noted on pancreatography correspond to parenchymal changes that may be severe and irreversible.

Primary duodenal adenocarcinoma: a 40-year experience.

HYPOTHESIS: In patients with duodenal adenocarcinoma, certain pathologic features of the tumor will have prognostic significance. DESIGN: Retrospective case series. PATIENTS: Forty-nine patients diagnosed with duodenal adenocarcinoma between 1957 and 1998. RESULTS: The tumors of 31 (63%) of the 49 patients underwent resection, 18 (37%) had surgical palliation or underwent biopsy. Mean (+/- SEM) survival for all patients was 49 +/- 9 months. The patients whose tumors were resected had longer survival than those who underwent palliation (mean +/- SEM, 66 +/- 13 months vs 18 +/- 6 months, P =.02). Multivariate analysis revealed large tumor size (P =.01), transmural invasion (P =.004), and moderate to poor tumor grade (P =.03) were negatively correlated with survival. Lymph node status did not influence survival. CONCLUSIONS: Our 40-year experience with duodenal adenocarcinoma demonstrates that large tumor size, advanced histological grade, and transmural invasion are associated with decreased survival. These results underscore the importance of early diagnosis, and suggest the presence of nodal spread is not a contraindication to resection.

Pylorus-preserving Whipple resection for pancreatic cancer. Is it any better?

OBJECTIVE: To compare the short- and long-term morbidity and mortality rates of the standard Whipple pancreatoduodenectomy (SW) and its pylorus-preserving modification (PPW) in patients with malignant periampullary disease. DESIGN: Retrospective medical record review and quality of life assessment by telephone interview. SETTING: University medical center. STUDY PARTICIPANTS: Sixty-seven patients who underwent pancreatoduodenectomy (52 SW and 15 PPW) from June 1988 to January 1994. INTERVENTION: The SW and PPW. MAIN OUTCOME MEASURES: Operative features and short- and long-term complications were analyzed with respect to the type and stage of cancer and the kind of pancreatic resection. Mean follow-up was 32 months (range, 1 to 5 years). RESULTS: The operative mortality rate for all patients who had a pancreatic resection was 1.5%. The diagnoses in the PPW vs SW groups were pancreatic cancer (four vs 27 patients), ampullary cancer (six vs seven patients), duodenal cancer (zero vs six patients), and bile duct cancer (five vs one patient). Operative mortality rates (0% vs 1.55%) and operative times (2 minutes longer for SW) were similar. Delayed gastric emptying (61% vs 41%) was more common in the PPW group, resulting in a longer hospitalization (24 vs 18 days) and a greater cost in the PPW group (P = .04). In the PPW group, a mean of five lymph nodes was removed compared with 10 in the SW group (P = .04). CONCLUSIONS: The data provided no evidence of any advantage for the PPW in patients with malignant periampullary tumors. We continue to advocate the SW for pancreatic cancer.

Treatment of acute alcoholic pancreatitis in cats.

We created acute pancreatitis in cats by instilling ethanol (20 ml of a 40% solution) into the stomach and then perfusing activated pancreatic enzymes through the main pancreatic duct. Edematous pancreatitis developed within 24 h as the enzymes leaked out of the duct into the surrounding pancreatic parenchyma. We tested the effects of a number of agents on the amelioration of the severity of the pancreatic inflammation. Cimetidine (an H2 receptor blocker) and Benadryl (an H1 receptor blocker) given in combination decreased the incidence of pancreatic hemorrhage but not the overall degree of inflammation. Indomethacin (a cyclooxygenase inhibitor) had a similar effect. Terbutaline (a beta-agonist) given alone decreased the overall degree of inflammation, including the incidence of hemorrhage. All of the drugs given together were no more effective than terbutaline alone. The combination was effective even when given up to 12 h after the onset of pancreatitis.

New perspectives in the surgical management of chronic pancreatitis.

Although the etiology of pain in chronic pancreatitis remains uncertain, that symptom remains the most common indication for surgery in these patients. Current endoscopic and imaging techniques now permit accurate definition of the morphology of the disease. Thus, surgical intervention can be more selectively applied to address specific abnormalities. Pancreaticojejunostomy should be the first line of surgical therapy if the ductal system is dilated. When, in addition, the head of the pancreas is enlarged and inflamed, the operation should include a localized resection of the head, preserving the stomach and duodenum. If the duct is not dilated, some form of pancreatic resection is indicated. The resection should be limited to the most severely diseased part of the pancreas. Efforts should be made to preserve as much pancreatic tissue as possible, while maintaining normal gastrointestinal continuity. In this way, the nutritional and metabolic consequences of pancreatic resection will be minimized.

Pancreatic cystic endocrine neoplasms.

A rare case of cystic pancreatic endocrine tumor is presented, and the literature is reviewed. The patient was initially misdiagnosed as having a pancreatic pseudocyst, and that condition was managed accordingly. Persistence of the cystic lesion and reoperation led to the correct diagnosis and management. The neoplasm stained positive for glucagon and pancreatic polypeptide, but there were no clinical abnormalities that suggested hyperfunction. All cystic lesions of the pancreas should undergo biopsy at operation, to avoid an erroneous diagnosis of benign pseudocyst. Neoplastic lesions should be resected, not internally drained.