Secretagogue effects on intracellular calcium in pancreatic duct cells

Regulation of intracellular free calcium ([Ca²⁺]_i) in single epithelial duct cells of isolated rat and guinea pig pancreatic interlobular ducts by secretin, carbachol and cholecystokinin was studied by microspectrofluorometry using the Ca²⁺-sensitive, fluorescent probe Fura-2. Rat and guinea pig duct cells exhibited mean resting [Ca²⁺]_i of 84 nM and 61 nM, respectively, which increased by 50%–100% in response to carbachol stimulation, thus demonstrating the presence of physiologically responsive cholinergic receptors in pancreatic ducts of both species. The carbachol-induced increase in [Ca²⁺]_i involved both mobilization of Ca²⁺ from intracellular stores and stimulation of influx of extracellular Ca²⁺. In contrast, neither cholecystokinin nor secretin showed reproducible or sizeable increses in [Ca²⁺]_i. Both rat and guinea pig duct cells showed considerable resting Ca²⁺ permeability. Lowering or raising the extracellular [Ca²⁺]_i led, respectively, to a decrease or increase in the resting [Ca²⁺]_i. Application of Mn²⁺ resulted in a quenching of the fluorescence signal indicating its entry into the cell. The resting Ca²⁺ and Mn²⁺ permeability could be blocked by La³⁺ suggesting that it is mediated by a Ca²⁺ channel.     

Pathogenesis of pancreatic perilobular necrosis in patients with liver disease.

We often see perilobular necrosis of the pancreas in patients with liver disease at autopsy. This study was undertaken to determine the frequency and the mechanism of development of pancreatic perilobular necrosis in patients with liver disease. Pancreatic perilobular necrosis was seen in 21 per cent of 261 autopsied patients: in 41 per cent of 73 autopsied patients with liver disease and in 13 per cent of 188 autopsied patients without liver disease. Moreover, splanchnic congestion was present in 90 per cent of 30 pancreatic perilobular necrosis patients with liver disease. These data indicate that patients with liver disease develop perilobular necrosis of the pancreas more often than patients without liver disease, and that the high frequency may be a sequela of splanchnic congestion; that is, congestion of the pancreas and endotoxaemia due to congestion of the gut.     

Fine-needle aspiration biopsy of the pancreas: a study of 61 cases

Eighty-six fine-needle aspirates (FNAs) of pancreas from 74 patients were reviewed. Histological confirmation or clinical follow-up of the final diagnosis was available in 61 aspirates from 49 patients. Of 42 proven malignant cases, FNAs were diagnosed as positive in 21 (50%), suspicious in 4 (9.5%), negative in 12 (28.6%), and unsatisfactory in 5 (11.9%). Of 19 proven benign cases, FNAs were diagnosed as negative in 15 (78.9%) and unsatisfactory in 4 (21%). This resulted in a 50% sensitivity, a 100% specificity, a diagnostic efficiency of 59%, a predictive value of a positive test of 100%, and a predictive value of a negative test of 55.6%. Thirty-six primary pancreatic adenocarcinomas and six metastatic tumors to the pancreas were encountered. Benign cases were attributed to anatomical pancreatic variants, acute pancreatitis, abscess, chronic pancreatitis, and pseudocysts. Pancreatic FNA was safe, accurate, and relatively inexpensive, but it was relatively insensitive in the diagnosis of malignancy.     

DNA ploidy and cell-cycle analysis in pancreatic and ampullary carcinoma: flow cytometric study of formalin-fixed paraffin-embedded tissue

Summary The cellular DNA content of formalin-fixed, paraffin-embedded specimens from 47 ductal adenocarcinomas of the pancreas and 5 adenocarcinomas of the ampulla of Vater was analysed using flow cytometry. Ploidy and the fraction of cells in the S and G2M phases were determined and correlated with tumour stage and grade as well as patients' survival. Cell populations with aneuploid DNA content were observed in 15% of the tumours. The S + G2M fractions ranged between 1% and 10%. Compared to non-neoplastic tissue of the pancreas the S + G2M fraction was significantly higher in the carcinomas. Cox regression analysis revealed the S + G₂M fraction as an independent prognostic factor (p< 0.05). Ploidy was of no prognostic value for survival, but correlated weakly with tumour stage and tumour grade. All patients without lymph node metastases at time of surgery had diploid tumours. Aneuploidy was restricted to tumours in advanced stages and tended to be more frequent in high-grade tumours.     

Masked excitatory action of noradrenaline on rat islet β-cells via activation of phospholipase C

The effect of noradrenaline (NE) on rat islet -cells was examined. NE reduced insulin secretion from rat islets exposed to extracellular solutions containing glucose at 5.5 or 16.6 mM. In islets treated with pertussis toxin (PTX), however, NE increased insulin secretion. The NE-induced augmentation of insulin secretion was inhibited by prazosin. In intact islets, NE increased phospholipase C (PLC) activity, an effect that was prevented by treatment of islets with U-73122. NE elevated intracellular [Ca²⁺] ([Ca²⁺]_i) in isolated -cells independently of PTX. Although this NE effect was inhibited by prazosin, phenylephrine did not mimic it. The [Ca²⁺]_i response to NE was also prevented by the treatment of cells with U-73122. NE produced depolarization of -cells followed by nifedipine-sensitive action potentials. NE reduced the whole-cell membrane currents through ATP-sensitive K⁺ channels (K_ATP), responsible for the depolarization. This NE effect was prevented by treatment of -cells with U-73122 or BAPTA/AM. Although at least some of our results imply the presence of ₁-adrenoceptors, -cells were not stained by a polyclonal IgG antibody recognizing all adrenergic ₁-receptor subtypes so far identified. These results suggest that an interaction of NE with an unknown type of receptor activates rat islet -cells via a PLC-dependent signal pathway. This effect is, however, masked by the inhibitory action via a PTX-sensitive pathway also activated by NE.     

Radiation therapy for pancreatic cancer: eleven year experience at the JCRT

Radiation therapy (XRT) for 41 patients with unresectable pancreatic cancer resulted in a median survival of 7.0 months. There was no difference in median survival for patients receiving external beam alone (3500 to 5600 cGy) (n = 28), intraoperative (IORT) boost plus external beam (5040 to 6750 cGy) (n = 9), or a gold-198 implant +/- external beam radiation (n = 4). A pilot study using orthovoltage IORT boost indicates no acute toxicity with doses of 1250 to 1750 cGy. Serious late damage has not been observed in any patients followed to 2 years. Local recurrence in patients treated post-operatively after "radical" surgery occurred in one of 10 (10%). This adjuvant treatment is safe and appears to improve local control rates compared to historical data, but survival is still poor. The median survival for the post-operative group is 10 months; three patients are alive without disease 8 months to 8.3 years after treatment.     

胰岛的血液引流与胰腺外分泌的机能和临床意义

目的　研究胰岛的血液引流与胰腺外分泌的机能联系与临床意义。方法　运用微血管树脂 /墨汁灌注扫描电镜 /光镜观察法、保留动态及组织信息在静态样本的微循环观察法、FITC标记红细胞 (FITC- RBC)荧光活体显微镜观察法以及计算机图像处理微血管三维重建法 ,对 11例男性尸体、40只猴、2 4只狗、62只鼠、2 4只兔的胰岛血液引流通道与胰腺外分泌腺泡的关系进行了系统研究。结果　不同动物的内分泌胰岛血液主要经胰岛的三种类型输出血管引流至不同的外分泌腺泡区域 ,灵长类的部分胰岛血液还引流至邻近的小胰岛 ,研究者根据胰岛引流系统的特征对其进行了分类及命名 :1连续型引流系统 ,所有胰岛具有这类引流 (输出 )管道 ,其管径细 ,行程短、引流至胰岛周围的腺泡毛细血管区域。 2聚合型引流系统 ,为部分胰岛所有 ,其管径粗、行程长 ,引流至远离胰岛的腺泡毛细血管区域。 3跨越型引流系统 ,为部分胰岛所有 ,其输出管道越过小叶间隔引流至另一胰腺小叶的腺泡毛细血管区域 ,而这一小叶往往没有胰岛存在。 4胰岛 -胰岛型引流系统 ,灵长类部分胰岛的血液通过胰岛 -胰岛型引流通道回流至邻近的小胰岛。结论　胰岛具有完善联系外分泌腺泡的引流系统 ,提示含有高浓度胰岛内分泌激素的胰岛血液可能对外分泌腺泡的机能     

Comparison of benign and malignant insulinoma

BackgroundHow malignant insulinomas present relative to benign insulinomas is unknown.MethodsA single-institution retrospective study identified patients with insulinoma. Malignancy was defined by distant metastases, positive lymph node(s), T stage of 4, direct invasion into surrounding peripancreatic tissue, or presence of lymphovascular invasion. Wilcoxon Rank Sum tests and Kaplan-Meier analysis were used.ResultsA total of 311 patients were identified: 51 malignant and 260 benign. Patients with malignant insulinoma presented with higher levels of insulin, proinsulin, and c-peptide. Malignant lesions were larger: 4.2 ± 3.2 vs 1.8 ± 0.8 cm in benign lesions, p < 0.01. Overall survival at 5 years was 66.8% vs 95.4% for malignant and benign insulinoma respectively, p < 0.01.ConclusionsLarger size of insulinoma and increased serum β-cell polypeptide concentrations were associated with malignancy. Malignant insulinoma has poorer survival. Further work-up to rule out malignancy may be indicated for larger pancreatic lesions and for patients with higher pre-operative insulin and pro-insulin.     

Duodenopancreatectomía cefálica y tutorización externa del conducto de Wirsung. Resultados de una serie de 80 casos consecutivos

IntroductionThere is controversy regarding the ideal pancreaticojejunostomy technique after pancreaticoduodenectomy. Many authors consider the external Wirsung stenting technique to be associated with a low incidence of fistula, morbidity and mortality. We analyse our experience with this technique.Patients and methodsA retrospective analysis of the morbidity and mortality of a series of 80 consecutive patients who had been treated surgically over a 6.5-year period for pancreatic head or periampullary tumors, performing pancreaticoduodenectomy and pancreaticojejunostomy with external Wirsung duct stenting.ResultsMean patient age was 68.3 ± 9 years, and the resectability rate was 78%. The texture of the pancreas was soft in 51.2% of patients and hard in 48.8%. Pylorus-preserving resection was performed in 43.8%. Adenocarcinoma was the most frequent tumor (68.8%), and R0 was confirmed in 70% of patients. Biochemical fistula was observed in 11.2%, pancreatic fistula grade B in 12.5% and C in 2.5%, whereas the abdominal reoperation rate was 10%. Median postoperative hospital stay was 16 days, and postoperative and 90-day mortality was 2.5%. Delayed gastric emptying was observed in 36.3% of patients, de novo diabetes in 12.5%, and exocrine insufficiency in 3. Patient survival rates after 1, 3 and 5 years were 80.2, 53.6 and 19.2%, respectively.ConclusionsAlthough our low rates of postoperative complications and mortality using external Wirsung duct stenting coincides with other more numerous recent series, it is necessary to perform a comparative analysis with other techniques, including more cases, to choose the best reconstruction technique after pancreaticoduodenectomy.