化疗药物在血液和胰液中的动态分布及其相关性研究

化疗目前仍然是胰腺癌辅助治疗的重要手段之一，但常用的化疗药物５－氟尿嘧啶（５－ＦＵ），丝裂霉素（ＭＭＣ）是否能够通过胰腺组织，并达到有效治疗浓度，尚不清楚。作者以狗为实验对象，于测定多种抗生素在血液和胰液中浓度比的工作基础上，研究了快速静脉推注５－ＦＵ及ＭＭＣ后血液和胰液中药物分布及相关性，同时对术后有胰支架管的部分胰十二肠切除患者进行了上述观察。结果显示血中５－ＦＵ及ＭＭＣ能够穿透胰腺组织，通过血－胰屏障。作者认为５－ＦＵ和ＭＭＣ可适用于胰腺癌的辅助化疗。     

环丙沙星和头孢哌酮透入人类胰液的研究

通过７例胰十二指肠切除术后患者胰管内置管获得的纯胰液，用高效液相色谱法测定环丙沙星和头孢哌酮在血清及胰液中的浓度。结果显示：环丙沙星和头孢哌酮的平均胰液渗透率分别为４３％和１６％，两药在胰液中的浓度均在大多数胰腺感染率病菌的ＭＩＣ－９０以上。     

环丙沙星和头孢哌酮透入人类胰液的研究

通过7例胰十二指肠切除术后患者胰管内置管获得的纯胰液，用高效液相色谱法测定环丙沙星和头孢哌酮在血清及胰液中的浓度。结果显示：环丙沙星和头孢哌酮的平均胰液渗透率分别为43％和16％，两药在胰液中的浓度均在大多数胰腺感染致病菌的MIC－90以上。     

应用石蕊试纸检查胰腺断面和纤维蛋白胶预防胰空肠吻合口漏

本组共 15例 ,其中男 8例 ,女 7例 ;年龄 38～ 6 7岁 ,平均5 2岁。均以梗阻性黄疸入院 ,其中胰头癌 7例 ,下段胆管癌5例 ,十二指肠乳头癌 2例 ,壶腹癌 1例。施行传统胰十二指肠切除术 4例 ,保留幽门胰十二指肠切除术 11例。胰腺断端慢性纤维化 5例 ,基本正常 10例。主胰管直径 >4mm者9例 ,≤ 4mm者 6例。手术方法 :完成胰十二指肠切除之后 ,将胰腺残端游离大约 2 5～ 3 0cm ,先用干纱布包绕胰腺断端 ,再经静脉注射5 0U的促胰液素刺激胰液分泌 ,1～ 2min后胰液自断面快速溢出 ,用干纱布和滤纸反复拭净 ,尔后用红色石蕊试纸覆盖胰腺断面 ,开…     

胆胰液分流预防胰十二指肠切除术后胰瘘的价值

目的：探讨胆胰液分流预防胰十二指肠切除术后胰瘘的价值。方法；对91例胰十二指肠切除术患胰、胆、胃消化直重建时分别采用改良Roux-en—Y吻合术、总胆管放置T型引流管和胰管内放置引流管3种胆胰液分流术治疗，同时用未行胆胰液分流术45例作对照。结果：胰十二指肠切除术后行胆胰液分流术91例的胰瘘发生率为2．2％(2／91)，未行胆胰液分流术45例的胰瘘发生率为15．5％(7／45)（P＝0.00065)。应用改Roux－en—Y吻合术6例，胰管内放置引流管26例，无1例出现胰瘘；总胆管放置T型引流管59例，2例出现胰瘘。结论：胆胰液分流是预防胰十二指肠切除术后胰瘘发生的重要环节。     

胰十二指肠切除术胰瘘的防治

近二十年来由于手术技术和围手术期处理的改善，胰十二指肠切除术的手术死亡率已明显下降，但术后并发症率仍很高。胰瘦是胰十二指肠切除术最严重和最常见的并发症。近年来其发生率仍在10％左右，发生后死亡率达50％[1]。主要是由于胰瘘可造成腹腔内严重感染和大出血。因此防止胰瘘的发生是降低术后死亡率的关键之一。胰十二指肠切除术残留胰腺的大小、质地，胰管的直径、以及胰液排出量与胰瘘的发生有明显的关系。残留胰腺质地柔软、胰液分泌率相对高而且通过未扩张胰管时易引起吻合口瘘，因此残胰可分为正常、柔软、脆弱而且胰管未扩张和…     

胰十二指肠切除术后胰瘘预防的研究进展

目的总结胰十二指肠切除术后胰瘘的预防方法。方法通过检索近年来国内外关于胰十二指肠切除术后胰瘘预防方法的相关文献并做一综述。结果胰瘘是胰十二指肠切除术后常见并发症之一,其主要由于术前持续高黄疸,术中吻合方式的选择,术后早期大量胰液的分泌,胰蛋白酶原被碱性肠液激活,从而消化附近的组织造成胰瘘,胰液流入腹腔而消化腹腔组织,造成严重并发症,甚至死亡。通过药物、术前减黄、术中吻合方式的选择等方面的预防,术后胰瘘的发生率有所下降。结论胰十二指肠切除术后胰瘘的预防是一个综合过程,需贯穿整个围手术期。     

福爱乐医用胶在胰腺切除术中的应用

胃上部癌常浸润胰体尾 ,治疗往往须采用全胃联合脾、胰体尾切除术 ;胃下部癌如浸润胰头 ,须联合行胰头十二指肠切除术。此类手术的术后常见并发症是胰腺残端瘘。其渗漏的胰液中含有多种消化酶 ,与腹腔渗液混合造成化学性腹膜炎及腹腔感染。经多种治疗往往长期不愈 ,为控制感染而置放腹腔的引流管也长期不能拔去 ,给病人带来很大的精神负担。既往 ,为预防术后胰腺瘘的发生 ,临床医生多把注意力集中在胰腺断端的缝合上。有学者主张严密缝合胰腺残端 ,预防胰液渗漏 ;也有学者认为 ,严密缝合胰腺残端更易使缝扎处的胰腺组织坏死脱落 ,增加胰瘘发…     

胰液内引流胰腺断端半开放式胰腺空肠吻合术

我们从１９９２年起在胰十二指肠切除术（ｐａｎｃｒｅａｔｉｃｏｄｕｏｄｅｎｅｃｔｏｍｙ,ＰＤ）中在主胰管内置入长的胰液内引流管,胰腺断端半开放式胰腺空肠吻合,胰瘘发生率为１－２５％（１／８０）。现就该吻合技术介绍如下。一、临床资料本组８０例,男５３例,女２７例。年龄２１～７５岁,平均５６岁。壶腹癌２３例,胆管癌２４例,胰头癌２５例,十二指肠癌５例,先天性胆总管囊肿恶变２例,胆囊癌１例。术后腹腔感染７例,切口感染４例;其中同时合并有胰瘘、胆瘘和切口裂开、急性心肌梗死死亡各１例。二、手术方法及技术改进…     

尼莫地平对胰腺疾病患者血胰屏障通透性的影响

为探讨尼莫地平对胰腺疾病患者血胰屏障通透性的影响，采用反相高压液相色谱法对１５例胰腺疾病患者在口服尼莫地平后不同时段胰液标本中的尼莫地平浓度进行了检测。结果：在用药后０．５、１、１．５、２、２．５、３、３．５和４小时，该１５例受试者胰液中的尼莫地平平均浓度分别为４．７９、７．３１、９．２１、８．０４、６．０５、５．１１、３．３７和１．１９ｎｇ／ｍｌ；尼莫地平的胰液浓度高峰时间为用药后１．５～２小时，最高浓度为９．２１ｎｇ／ｍｌ。由此提示尼莫地平可以穿透血胰屏障，这也是它在胰腺组织内发挥药理作用的生理基础     

Intravenously administered human epidermal growth factor in the rat. Biliary excretion and influences on pancreatic secretion

BACKGROUND/AIM: Epidermal growth factor (EGF) is known to exert mitogenic effects in different tissues, including the digestive tract and pancreas. EGF is also found in high concentrations in pancreas. Infusion of human EGF has been shown to induce proliferation of cells in exocrine pancreas, and to increase the thickness of the small intestine. The aim of this study was to investigate the influence of intravenously administered human EGF on pancreatic and biliary secretions in the rat. MATERIALS AND METHODS: Rats were fasted overnight and were given human EGF intravenously, either as a bolus dose of 5 microg or as a continuous infusion in increasing doses from 0.5 to 10 microg/h. Bile and pancreatic juice were either collected together or separately. The concentration of human EGF in bile and pancreatic juice was measured. RESULTS: After a bolus dose of EGF increased bile/pancreatic secretion was seen after 60 and 90 min when the bile and pancreatic secretions were not separated. Continuous infusion of EGF increased the joint secretion rate of bile and pancreatic juice in a dose-dependent manner. No effect on secretion rate was seen when bile and pancreatic juice were collected separately. After intravenous infusion of human EGF a 1,000-fold increase of human EGF excretion was found in bile but not in pancreatic juice. CONCLUSION: Intravenously administered human EGF was excreted in high concentrations in bile and increased the secretion rate of pancreatic juice when collected together with bile. The results suggest that EGF, at least partly, exerts its effect on the pancreas and the proximal gastrointestinal tract after excretion with bile and stimulates pancreatic secretion via this route.     

5-氟脲嘧啶对胰腺外分泌的影响

目的 探讨5-氟脲嘧啶(5-FU)对人胰腺外分泌功能的影响。方法 通过8例胰十二肠切除术后患者胰管内置管获得的纯胰液观察5-FU对人胰腺外分泌功能的作用。术后第10天开始，静脉缓慢滴注5-FU500mg／d，连续3天。检测5-FU使用前和使用后1d、2d及3d胰液中淀粉酶、pH、HCO3^-、Na^ 、K^ 、Cl^-、Ca^2 及Mg^2 水平，并记录胰液量变化。结果使用5-FU前、后胰液量及胰液中淀粉酶、pH、HCO3^-、Na^ 、K^ 、Cl^—、Ca^2 及Mg^2 水平均无显著变化。结论 短期内使用5—FU对胰腺外分泌功能未见明显影响，5-FU是否通过抑制胰酶的合成治疗急性胰腺炎有待进一步探讨。     

Acute edematous pancreatitis impairs pancreatic secretion in rats.

There are few observations of in vivo pancreatic secretory changes that accompany acute pancreatitis. We hypothesized that acute pancreatitis impairs pancreatic exocrine function. We developed a conscious-rat experimental preparation with gastric, duodenal, bile, and pancreatic fistulas. We studied cholecystokinin-stimulated pancreatic secretion in conscious rats before and after inducing acute pancreatitis with supramaximal administration of caerulein--5 micrograms/kg/hr intravenously for 6 hours. Marked hyperamylasemia developed in all rats immediately after administration of caerulein. Basal and cholecystokinin-stimulated pancreatic juice flow and protein (enzyme) secretion decreased significantly 24 hours after acute pancreatitis was induced even though plasma amylase returned to basal levels. We conclude that acute pancreatitis markedly impairs pancreatic secretion.     

Pharmacokinetics of excretory passage of 5-fluorouracil (i.v.) into the pancreatic juice of patients with pancreatic or biliary carcinoma: Evaluation of possible adjuvant chemotherapy

The drug, 5-fluorouracil (5-FU), is thought to be efficacious in treating human pancreatic or biliary carcinomas; therefore, to determine the optimal dosage for chemotherapeutic use in these conditions, we performed this pharmacokinetic study in which we investigate the passage of various doses of intravenously administered 5-FU into the pancreatic juice of 11 patients with pancreatic or biliary carcinoma. Whenever possible, all 11 patients, who had undergone a pancreaticoduodenectomy and had an external drainage tube, received the following three regimens: (1) a bolus injection of 5-FU, 185 mg/m² per day; (2) a continuous infusion of 5-FU, 185 mg/m² per day over 48h (CIV-I), and (3) a continuous infusion of 5-FU, 370 mg/m² per day over 48 h (CIV-II), with a sufficient wash-out period of 2 weeks between each regimen. The major findings were: (i) the percentage of the administered 5-FU dose excreted (pancreatic passage fraction; Fp) was strongly correlated with the total amount of pancreatic juice excreted over the 24-h period (Vp) of drug testing; (ii) the Fp per 100 ml Vp (Fp') was greater after the bolus treatment than after either CIV treatment; (iii) 90% of the 5-FU excreted into the pancreatic juice was present within 30min of the bolus injection; and (iv), the entire body clearance (CL_total) of 5-FU was significantly lower after the bolus injection than after either CIV treatment. It was concluded that the Fp' value was dependent on the method of 5-FU administration, that a 5-FU bolus injection probably inundates the hepatic metabolic capacity, and that the Fp' of 5-FU largely depends on the patient's ability to metabolize the drug. Therefore, the efficacy of 5-FU as an anticancer agent appears to be time-rather than dose-dependent.     

区域动脉灌注5-氟尿嘧啶对急性坏死性胰腺炎大鼠胰腺血流的改善作用

目的　探讨区域动脉灌注5-氟尿嘧啶(5-Fu)对急性坏死性胰腺炎(ANP)大鼠胰腺血流(PBF)的改善作用。方法　SD大鼠144只,随机分为对照组(A组)、ANP组(B组)、5-Fu外周静脉注射治疗组(C组)、5-Fu区域动脉灌注治疗组(D组)。用多普勒超声检测PBF,取血测内皮素-1(ET-1)水平、血栓素B2(TXB2)和6-酮-前列腺素F1α(6-K-PGF1α)(T/P)比值,观察胰腺病理变化。结果　术后12h,D组血浆ET-1水平、T/P比值211.08±26.23、6.39±0.65较C组245.17±34.37、7.20±0.83下降明显（P值均＜0.05）,PBF波幅0.21±0.07较C组0.14±0.05改善显著（P＜0.05）,胰腺病理损害程度较C组明显减轻。结论　区域动脉灌注5-Fu能有效逆转ANP大鼠的病理损害,并改善PBF。     

奥沙利铂联合亚叶酸钙和5-氟尿嘧啶一线治疗晚期胃肠道肿瘤的研究

目的：评价奥沙利铂（OXA）联合亚叶酸钙（LV）和5-氟尿嘧啶（5-Fu）一线治疗晚期胃肠道肿瘤疗效与安全性。方法：OXA130mg／m^2，第1天；LV200mg，第1～5天；5-Fu450mg／m^2，第1～5天。每3周为1周期，至少2周期后评价疗效。结果：58例，均为术后转移或不能手术切除患者，其中CR2例（3．4％）。PR26例（44．8％），SD21例（36．2％），PD9例（15．5％），总有效率（CR＋PR）48．3％。有手术史者有效率54．5％，不能手术者有效率40．0％；胃癌有效率44．4％，大肠癌有效率51．6％。主要不良反应为恶心呕吐、轻度周围神经毒性及白细胞和血小板减少，无化疗相关死亡。结论：OXA联合LV和5-Fu一线治疗晚期胃肠道肿瘤有较好的疗效和耐受性。     

胰腺损伤的诊治体会

１９８６年１月～１９９４年１月我们共收治胰腺损伤２４例，虽有许多辅助诊断手段，但受病情限制胰腺损伤的性质和部位往往要在手术探查时确定。浅表裂伤的８例经清创、缝合和引流治愈；胰体尾部较重裂伤的１０例中有８例行胰体尾部切除治愈。Ｒｏｕｘ－Ｙ胰肠吻合治疗胰头颈部损伤４例；合并十二指肠破裂的２例胰头部损伤用十二指肠憩室化治疗。对较重的胰腺损伤放置空肠造瘘管，从造瘘管滴入要素饮食；发生胰瘘时除加重吸引外，使用６５４－２和５－Ｆｕ以抑制胰液分泌。本组治愈２０例，死亡４例，死亡率为１６．７％。     

表阿霉素在大鼠血浆和胰腺组织中的分布

目的　研究表阿霉素在大鼠胰腺和血液中的分布规律。方法　经颈静脉推注表阿霉素７．５ ｍｇ／ｋｇ 体重，在规定的时间点处死大鼠，用高效液相色谱法测定血浆及胰腺组织中表阿霉素的含量。结果　血浆浓度在５ 分钟时达到最高点为１７２０ μｇ／Ｌ；胰腺中表阿霉素的含量在１０ 分钟时达到最高点为１４４８ ．８５ ｎｇ／ｇ，此后两者均迅速下降。穿透比率（ＰＲ） 在５ 分钟时最低为０ ．３９９，９ 小时后上升到５．６０６，此后逐渐下降，２４ 小时为１．９３１。结论　静脉推注表阿霉素后药物未能维持在有效杀伤肿瘤细胞的浓度，这可能是胰腺癌化疗反应性不理想的原因之一。     

Usefulness of dynamic magnetic resonance pancreatography with secretin [correction of secretion] injection for evaluating pancreatic exocrine function after pancreatogastric reconstructive surgery

Background/Purpose: The usefulness of dynamic magnetic resonance pancreatography (MRP) with secretin injection as a new method of assessing pancreatic exocrine function was evaluated in patients undergoing pancreatogastrostomy. Methods: A series of 12 patients who had undergone pancreatogastrostomy were classified into group 1 (9 patients whose pancreas was normal preoperatively) and group 2 (3 patients with a firm pancreas accompanied by distended pancreatic ducts). The pancreatic exocrine function was evaluated using the changes in maximum pancreatic duct diameter and the intensity ratio calculated by tracing the contour line on the images of pancreatic juice secretion newly occurring after dynamic MRP with prior secretin injection. Results: Clear visualization of the pancreatic duct by MRP was achieved in all 12 patients, and a decrease in pancreatic duct diameter was evident postoperatively in group 2. Pancreatic juice secretion was well visualized on MRP images following secretin injection in 10 patients but not in 2 patients of group 2. Higher intensity ratios were noted in group 1 than in group 2. Conclusions: Dynamic MRP with secretion injection enables clear verification of pancreatic juice secretion on images and permits objective evaluation of pancreatic exocrine function. It therefore is a useful procedure for assessing pancreatic exocrine function after resection of the pancreas. Received: August 16, 2001 / Accepted: August 5, 2002 Acknowledgments. The authors extend their gratitude to Ms. Megumi Nakajima for her helpful collaboration in MRP image processing. Offprint requests to: S. Ohhigashi