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Solid pseudopapillary tumor of the pancreas: emphasis on differential diagnosis from aggressive tumors of the pancreas.

Solid pseudopapillary tumor is an unusual primary tumor of the pancreas with a low potential for malignancy and unknown cell origin, seen mostly in young women. Although it is discussed among pancreatic epithelial tumors, many cases do not express cytokeratin but show neuroendocrine differentiation. Three cases (2 female, 1 male, aged 24, 45 and 50 years, respectively) of solid pseudopapillary tumor localized in the pancreas are presented. All cases displayed a well-circumscribed tumor, with an average diameter of 6 cm and a red-brown colored, hemorrhagic, cystic cut surface. Microscopically they were encapsulated with large areas composed of thin papillary formations and solid areas focally. Tumor cells were dyscohesive with small, round- to-oval, central nuclei, and vacuolated, clear or eosinophilic cytoplasm without mitotic activity. NSE, vimentin, synaptophysin, ER, PR, Ki-67, S-100, Pan CK, a1-antitrypsin, a2-antichymotrypsin, and antibodies were used in the immunohistochemical study. Vimentin, synaptophysin, NSE, PR, and a1-antitrypsin showed expression in all cases, while Pan-CK was expressed in two cases. Ki-67 expression was below 1% in all cases. Morphologic features of solid pseudopapillary tumor may be confused with pancreatic endocrine neoplasm and ductal adenocarcinoma. All cases showed features of histiocytic and neuroendocrine differentiation. Epithelial differentiation was identified in two cases. We conclude that immunohistochemistry is incapable of giving additional information for the diagnosis of solid pseudopapillary tumor due to different lines of differentiation of tumor cells. We believe that macroscopic and microscopic features (using hematoxylin and eosin stain) are more important for the diagnosis and differential diagnosis of this tumor.

Adult↗

[Excretory pancreas function. Secretion of protein, calcium and citrate in probands with a normal pancreas and in patients with chronic pancreatitis].

Recent studies described an increased concentration of protein and calcium in association with a decreased concentration of citrate in pancreatic juice of patients suffering from chronic pancreatitis. These secretory changes may be of importance in the pathogenesis of chronic pancreatitis. The present study investigates pancreatic juices of 18 patients without pancreatic disease and 12 patients in an early phase of chronic pancreatitis in order to detect changes of the exocrine function of the pancreas in an early stage of the disease. In all persons the pancreatic juice was collected by endoscopic cannulation of the main pancreatic duct after i.v. stimulation with secretin and pancreozymin. The outputs and concentrations of protein, calcium and citrate were estimated. All of these parameters did not differ in control subjects and patients with chronic pancreatitis by univariate statistical analysis. However, a multivariate analysis detects differences in the biochemical composition of the secretions of controls and patients with chronic pancreatitis (efficiency of discrimination = 100%). Both in controls and in patients with chronic pancreatitis two calcium fractions were found after secretin stimulation: one secretory protein-associated fraction of 94 nmol calcium/mg protein and a protein-independent calcium fraction of 0.248 mmol/l, which diffuses paracellularly from the interstitium into the pancreatic juice. The results show that the secretory function of the exocrine pancreas is already disturbed in an early phase of chronic pancreatitis, whereas an increased lithogenity of the pancreatic juice cannot be detected.

Adult↗

Adenovirus infection of the renal allograft with sparing of pancreas graft function in the recipient of a combined kidney-pancreas transplant.

We report a case of adenovirus infection of the renal allograft in a combined kidney/pancreas transplant recipient. The clinical presentation was renal allograft failure, which eventually reversed. The pancreatic graft function remained stable. A renal biopsy showed massive tubular necrosis associated with a prominent granulomatous reaction. The process had a striking regional distribution within the kidney with the injury and inflammation limited to the outer medulla. Adenovirus type 11 was isolated from renal tissue by culture, and adenovirus was demonstrated by immunofluorescence and electron microscopy in the kidney biopsy. Immunosuppression may result in unusual patterns of response to infectious agents. This case demonstrated tropism of the adenovirus to only selected tubules within the kidney, with sparing of other organ function including, specifically, the pancreas allograft. The differential diagnosis of a granulomatous reaction in the transplant kidney must be expanded to include viral infection, in particular, adenovirus.

Adenovirus Infections, Human↗

Fetal pancreas transplantation in miniature swine. II. Survival of fetal pig pancreas allografts cultured at room temperature.

Islet-allograft survival has been shown to be markedly prolonged in rodents when donor tissue has been precultured at 24 degrees C. In this study, the feasibility of this approach was tested in NIH minipigs transplanted with fetal pancreases. Collagenase-digested fetal pig pancreatic tissues survived in culture at 24 degrees C for 6-7 days and continued to grow in vitro at 37 degrees C after being transferred. These tissues no longer stimulated allogeneic lymphocytes in vitro, although some tissues cultured at 37 degrees C did. This allogeneic stimulation did not correlate to the number of major histocompatibility complex (MHC) class II-positive cells in stimulator pancreatic cultures. When transplanted into an omentum pouch of normal, nonimmunosuppressed minipigs, fresh fetal pancreatic tissues were rejected within 14 days. Tissues cultured at 24 degrees C grew, and beta-cells proliferated in minipigs treated daily with cyclosporin A (CsA) and azathioprine. Twelve normal minipigs were transplanted with 24 degrees C-cultured fetal pancreases: 8 pigs received no treatment, 2 received 14 mg.kg-1.day-1 CsA for 14 days, and 2 received 6-7 intravenous injections of platelets prepared from pooled farm-pig blood before grafting. Strong lymphocytic infiltration was detected in all grafts removed between 30 and 90 days posttransplantation. However, beta-cells were found on day 45 in one of five minipig pancreas grafts incompatible at the MHC loci and on days 60-90 in all three grafts compatible at MHC but incompatible at minor histocompatibility loci. Short-term CsA treatment did not prolong survival of allografts from farm pigs into minipigs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Application of glycerol to freezing bovine pancreas. Part 1. Effect of cryoprotector on activity of certain enzymes in frozen minced pancreas.

Effects of different concentrations of glycerol on the activity of amylase, lipase, and proteases in frozen minced pancreas were studied. A 15% glycerol addition was found to decrease the proteolytic enzyme activity and to increase the activity of amylase. Moreover, accelerated freezing was shown to enhance the activity of all the enzymes studied.

Amylases↗

Application of glycerol to freezing bovine pancreas. Part 2. Effects of glycerol and grinding on frozen pancreas quality.

Effects of glycerol on the quality of ground and whole pancreas stored frozen at -30 degrees C were studied. The quality was assessed from quantitative changes in soluble proteins, proteolytic enzyme activity, and insulin content. Grinding was found to enhance the effects of the cryoprotector due to its uniform distribution in the tissue. A relationship between proteolytic enzyme activity and protein solubility was demonstrated.

Animals↗

Application of glycerol to freezing bovine pancreas. Part 3. Effects of freezing rate and glycerol addition on changes in pancreas proteins.

Changes in protein solubility, amino nitrogen and activity of proteases in bovine pancreas frozen at -70 and -18 degrees C after soaking in various aqueous glycerol solutions were studied. Reduction of freezing temperature causes decrease of value in all studied parameters. Additionally, an inhibitory effect of glycerol on protease activity was demonstrated.

Animals↗

Acute starvation and suckling rat pancreas. Effect on exocrine pancreas and role of corticosteroids.

Starving of rat pups at the 5th or 10th day of life for three days led to lower body and pancreatic weights compared to age-matched controls. When compared to the weights before fasting, only the 5-day-old pups showed increases in pancreatic protein and DNA contents despite food deprivation. Pancreatic acinar responsiveness to carbachol stimulation was not affected. Accumulations of amylase and lipase in the pancreas of the rat pups were increased by fasting, with an accompanied surge in the level of serum corticosterone. In 10-day-old rat pups, injection with aminoglutethimide (AG), a drug which suppresses steroidogenesis, prevented the enzymatic increases and concomitantly suppressed the serum total corticosterone levels at 12 and 24 hr after the onset of fasting. These results strongly support the role of corticosterone in the modulation of the pancreatic adaptation to food deprivation in the suckling rat.

Aminoglutethimide↗

[Foreign body granuloma of the head of the pancreas caused by a fish bone--a rare differential diagnosis in head of the pancreas tumor].

Despite highly developed scanning methods there is no absolute certainty of delineating malignant pancreatic tumor from chronic pancreatitis. Pancreatitis caused by foreign bodies has occasionally been mentioned in literature. Our report is on the first case of a foreign body granuloma of the pancreatic head caused by a fish-bone transduodenally perforating the pancreas. On preoperative CT and ultrasound as well as by intraoperative inspection and palpation the lesion appeared malignant, so we saw the indication for Whipple's operation. Although the histological examination showed a benign state, taking into account the generally bad prognosis, in case of suspected malignant pancreatic tumor we plead for resection as the only possible form of curative therapy.

Animals↗

Studies on the endogenous phosphatides of mammalian pancreas and their hydrolysis by endogenous phospholipases - I. The lipids of dog pancreas and their in vitro hydrolysis, primed by trypsin, by phospholipase A2.

1. The phosphoglyceride and sphingolipid content of dog pancreas has been determined and their in vitro response to the endogenous lipolytic enzymes, initiated by trypsin, at pH 7.4 was examined by TLC technology. 2. The glyceryl ether phosphatides were found to consist primarily of PE and PC, each with alkyl and alk-1-enyl components both of which were hydrolyzed to their respective 1-radyl lyso derivatives under the described incubation conditions. 3. A new TLC visualizing reaction for lipids, OSPAS, is described.

Animals↗

Cancer of the pancreas. Pylorus-preserving resection of the pancreas.

Pylorus-preserving pancreaticoduodenectomy represents an important advance in the history of pancreatic surgery. The operation can be performed with a low operative mortality and morbidity, is technically easier than the standard Whipple resection, and it minimizes the long-term physiological disturbance to the patient. Clinical and experimental evidence has substantiated the view that preservation of the pylorus reduces the incidence of marginal anastomotic ulceration following pancreatectomy. Although gastric emptying may be prolonged transiently in the immediate postoperative period, this complication is easily managed, and is hardly a frequent long-term problem. PPPD is associated with a lower incidence of enterogastric reflux, dumping and diarrhoea than the classical Whipple operation, and patients who have had PPPD are more likely to regain their preoperative and preillness weight. Initial concerns about the use of PPPD in malignant disease have not been borne out, and should now be considered for curative or palliative resections of lesions in the periampullary region including the head of the pancreas. Present data suggest that PPPD does not compromise the long-term survival in patients with periampullary cancers. There is little doubt that the excellent results reported with this procedure as with other forms of major pancreatic surgery, are not simply related to improvements in surgical technique but to establishment of specialist pancreatic surgery.

Anastomosis, Surgical↗

Effect of chronic unpredictable mild stress on brain-pancreas relative protein in rat brain and pancreas.

Brain-pancreas relative protein (BPRP) is a novel protein whose biological function remains unknown. Here, we report a possible role of BPRP in male rats exposed to chronic unpredictable mild stress (CUMS) to induce depression for 3 weeks. Compared to unstressed rats, those exposed to CUMS showed significantly less weight gain with age, decreased consumption of (and preference for) sucrose without a change in total fluid consumption. Exposure to CUMS significantly reduced open-field exploration, rearing and grooming indicative of lethargy, apathy and bodily neglect, respectively. Brain MAO-A and MAO-B activity were both significantly increased in the stressed rats. These results verified induction of depressive symptoms by CUMS. The stressed animals showed a significant reduction in pancreatic BPRP, which was accompanied by an increase in levels of blood sugar and a decrease of insulin. But they showed no apparent alteration in levels or distribution of BPRP in the hippocampal formation, which nevertheless displayed a thinner dentate granule cell layer perhaps related to elevated MAO-B activity. These findings suggest that stress-induced reduction of pancreatic BPRP may cause diabetic symptoms. Whether those symptoms in turn contribute to the onset of depression requires further study.

Analysis of Variance↗

Heterotopic pancreas mimicking carcinoma of the head of the pancreas: a rare cause of obstructive jaundice.

A 61-year-old man developed obstructive jaundice and had ultrasonographic and cholangiopancreatographic findings consistent with carcinoma of the pancreas. However, pathologically the obstruction proved to be from heterotopic pancreatic tissue compressing the common bile duct. This patient and eight previously reported patients with a similar problem are the subjects of this report.

Adult↗

Assessment of renal function in type I diabetic patients after kidney, pancreas, or combined kidney-pancreas transplantation.

The long-term kidney function (KF) in the three categories of diabetic type 1 pancreas (P) transplant recipients (simultaneous P and kidney [SPK]; P after K [PAK]; PTx alone [PTA] was studied sequentially over a 2-year period in 62 patients who received a bladder-drained allograft that functioned for at least 1 year. Fifty-three (85%) patients were analyzed at 1 month, 42 (68%) at 1 year, and 16 (26%) at 2 years posttransplant. Comparison of KF was made within each recipient category and between categories. In addition, the KF in the SPK and PAK patients was compared to a matched group of diabetic type 1 recipients of KTx alone (functioning at least 1 year). In the SPK group, KF was stable over time: the mean +/- SD serum creatinine (mg/dl) was 1.5 +/- 0.5 at 1 month, 1.8 +/- 1.0 at 1 year, and 1.7 +/- 0.5 at 2 years. In the PAK category, the pre-PTx serum creatinine value was 1.4 +/- 0.5, and then remained stable after the PTx (1.3 +/- 0.2 at 1 month, 1.3 +/- 0.4 at 1 year, and 1.2 +/- 0.4 at 2 years). In the recipients of a PTA, the values at 1 month (1.1 +/- 0.4), 1 year (1.4 +/- 0.5), and 2 years (1.3 +/- 0.5) were significantly higher (P less than or equal to 0.03) than the pre-PTx value (0.9 +/- 0.2); and results at 1 month and 2 years were lower than those at 1 year, a significant difference compared to the 1-month value (P = 0.01). Comparisons between the categories of PTx recipients demonstrated that the pre-PTx value in the PTA group (0.9 +/- 0.2) was significantly lower (P = 0.01) than in the PAK group (1.4 +/- 0.5). At 1 month the serum creatinine value in the PTA category (1.1 +/- 0.4) was significantly lower (P = 0.02) than in the SPK category (1.5 +/- 0.5), but thereafter (1 and 2 years) the difference was not significant (P greater than 0.1). KF in recipients of KTx alone was similar at each post-Tx time point when compared to the SPK and PAK categories. We concluded that a PTx can be performed in diabetics without a detrimental effect on a simultaneously or a previously transplanted kidney and that a statistically significant, albeit minimal to moderate, initial but not progressive deterioration in native KF occurs in recipients of a PTx alone.

Creatinine↗

Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer.

SMAD4 is inactivated in the majority of pancreatic ductal adenocarcinomas (PDAC) with concurrent mutational inactivation of the INK4A/ARF tumor suppressor locus and activation of the KRAS oncogene. Here, using genetically engineered mice, we determined the impact of SMAD4 deficiency on the development of the pancreas and on the initiation and/or progression of PDAC-alone or in combination with PDAC--relevant mutations. Selective SMAD4 deletion in the pancreatic epithelium had no discernable impact on pancreatic development or physiology. However, when combined with the activated KRAS(G12D) allele, SMAD4 deficiency enabled rapid progression of KRAS(G12D)-initiated neoplasms. While KRAS(G12D) alone elicited premalignant pancreatic intraepithelial neoplasia (PanIN) that progressed slowly to carcinoma, the combination of KRAS(G12D) and SMAD4 deficiency resulted in the rapid development of tumors resembling intraductal papillary mucinous neoplasia (IPMN), a precursor to PDAC in humans. SMAD4 deficiency also accelerated PDAC development of KRAS(G12D) INK4A/ARF heterozygous mice and altered the tumor phenotype; while tumors with intact SMAD4 frequently exhibited epithelial-to-mesenchymal transition (EMT), PDAC null for SMAD4 retained a differentiated histopathology with increased expression of epithelial markers. SMAD4 status in PDAC cell lines was associated with differential responses to transforming growth factor-beta (TGF-beta) in vitro with a subset of SMAD4 wild-type lines showing prominent TGF-beta-induced proliferation and migration. These results provide genetic confirmation that SMAD4 is a PDAC tumor suppressor, functioning to block the progression of KRAS(G12D)-initiated neoplasms, whereas in a subset of advanced tumors, intact SMAD4 facilitates EMT and TGF-beta-dependent growth.

Alleles↗

Laparoscopic donor distal pancreatectomy for living donor pancreas and pancreas-kidney transplantation.

With the proliferation and expanding applications of laparoscopic techniques, we determined the applicability of the laparoscopic approach to living pancreas donation. We performed the first laparoscopic donor distal pancreatectomy in 1999. We herein present our initial experience with five hand-assisted laparoscopic donor pancreatectomies. Three donors underwent distal pancreatectomy alone; two underwent a simultaneous left nephrectomy. The mean donor age was 48.4+/-8.7 years with a body mass index of 23.7 kg/m2. The donor and recipient survival rate was 100% at up to 3 years of follow-up. There were no episodes of pancreatitis, leaks, or pseudocysts. All donors returned to their preoperative state of health and to work. None of the donors have required oral anti-diabetic medications or insulin. We conclude that laparoscopic donor distal pancreatectomy is a safe and efficient procedure; hand-assisted laparoscopic distal pancreatectomy appears to be preferable, because of the added margin of safety from increased tactile feedback and ease of pancreatic dissection. The procedure can be accomplished with a single 6-cm periumbilical incision and only two 12-mm ports, resulting in excellent cosmesis and high donor satisfaction.

Humans↗

Bioartificial endocrine pancreas (Bio-AEP) for treatment of diabetes: effect of implantation of Bio-AEP on the pancreas.

Recently, we described a diffusion chamber for a bioartificial endocrine pancreas (Bio-AEP). Pancreatic islet cells in the Bio-AEP device were isolated from the immune system of the host by an artificial barrier, while nutrients, electrolytes, oxygen, and bioactive secretory products were exchanged across this barrier. This experiment was designed to evaluate whether the diffusion chamber could be useful as a Bio-AEP in the treatment of diabetes. Six streptozotocin (STZ)-induced diabetic rats each received a diffusion chamber containing 8 x 10(6) MIN6 cells as a xenograft Bio-AEP. In the STZ diabetic rats with Bio-AEPs, a return to normoglycemia was observed up to 30 weeks after implantation, without the use of any immunosuppressant. A gradual increase in the body weight of the rats was also observed. In three STZ diabetic rats, diffusion chambers without MIN6 cells were implanted as a sham operation. The fasting blood glucose levels in these three rats remained higher than 600 mg/dl, after implantation, and they lost weight. Thirty-five weeks after implantation, the pancreata were removed from the rats that underwent xenoimplantation, those that had the sham operation, and the normal control rats. In the sham-operated animals, the exocrine tissues of the pancreata were vacuolated and pancreatic B cells were not seen in the islets. In contrast, in the pancreata from the xenoimplantation, the exocrine tissues were normal, and a few pancreatic B cells were seen in the islets. These results indicated that xenoimplantation using the Bio-AEP might retard the progress of diabetes.

Animals↗