Pancreatic cancer–Palliative therapy: surgery (bypass/resection)

Objective: We compare the outcome of palliative pancreaticoduodenectomy and palliative surgical bypass in patients with advanced pancreatic carcinoma in our hospital. Recent published related articles are also reviewed. Methods: A respective analysis was performed comparing the perioperative parameters and outcome of 20 patients who underwent pancreaticoduodenectomy with a gross suspected cancer residue and 30 patients who underwent a surgical bypass, all of the patients were diagnosed as in advanced stages intra-operatively. Results: The two groups were comparable with patient characteristics, including age, gender, initial symptoms and concomitant major organ diseases. Tumors are similar in size and intra-operatively diagnosed as in advanced stages in both groups. All of the patients in the resection group were microscopically proved having cancer residue. One postoperative mortality occurred in the resection group (5%), zero in the bypass group (P > 0.05). Overall complications were significantly higher in the resection group (30% vs. 0, P < 0.01), including 2 patients developed Acute Respiratory Distress Syndrome (ARDS), zero in the bypass group (P < 0.01); hemorrhage and transfusions in the resection group were much more than that in the bypass group (P < 0.05). Hospital stay after resection was significantly longer than bypass (20 vs. 12 days, P < 0.01). Hospital fee after resection was 4 times more than after bypass (median 61.500 vs. 15. 300 yuan, P < 0.01). Survival was significantly longer after resection (median 12.2 vs. 7.1 months, P < 0.01). Conclusion: Our results show that palliative resection in advanced pancreatic carcinoma lengthens the survival time of the patients, but this is paid for significantly higher complications than bypass.     

Bacterial ghosts (BGs)—Advanced antigen and drug delivery system

Bacterial ghosts (BGs) are empty bacterial envelopes of Gram-negative bacteria produced by controlled expression of cloned gene E, forming a lysis tunnel structure within the envelope of the living bacteria. BGs are devoid of cytoplasmic content and possess all bacterial bio-adhesive surface properties in their original state while not posing any infectious threat. BGs are ideally suited as an advanced drug delivery system (ADDS) for toxic substances in tumor therapy. The inner space of BGs can be loaded with either single components or combinations of peptides, drugs or DNA which provides an opportunity to design new types of (polyvalent) drug delivery vehicles. Uptake of BGs loaded with Doxorubicin (Dox) by CaCo2 cells led to effective Dox release from endo-lysosomal compartments and accumulation in the nucleus. Viability and proliferative capacity of the cells were significantly decreased (2–3 orders of magnitude) after internalization of Dox loaded BGs as compared to cells incubated with free Dox. The same effect was observed with leukemia cells. Melanoma cells also revealed a high capability to internalize BGs. These results indicate that BGs are able to target a range of types of cancer. BGs have also been investigated as DNA delivery vectors. Studies show DNA loaded BGs are efficiently phagocytosed and internalized by both professional APCs and tumor cells with up to 82% of cells expressing the plasmid-encoded reporter gene. Our studies with BGs as an ADDS system contribute (i) to optimize drug delivery for the treatment of cancer; (ii) define specific conditions for selection and preparation of BG formulations; (iii) and provide a background for the clinical application of BGs in cancer therapy.     

Sudden Death and Staged Therapy for Hemodynamic Stabilization in Patients Enrolled in a Heart Transplantation Program

To investigate the impact of staged therapy for advanced heart failure on therapeutic endpoints, 236 consecutive patients (coronary artery disease/dilated cardiomyopathy in 61/175 patients, left ventricular ejection fraction 14%± 5%, New York Heart Association Class IIl/IIIIV in 102/79/55 patients, respectively) with advanced heart failure were prospectively followed. One hundred thirtyseven patients enrolled from January 1989 to December 1991 were treated conventionally with digoxin, furosemide, and low dose angiotension converting enzyme (ACE) inhibition. Patients refractory to this therapy underwent urgent heart transplantation. Ninetynine patients enrolled from January 1992 to August 1993 underwent staged therapy: stage 1: maximal tolerated ACE inhibition; stage 2: therapy with PGE₁ for preand afterload reduction to achieve hemodynamic stabilization; or stage 3: refractory patients bridged to heart transplantation with continuous outpatient dobutamine. Sudden death was defined as death within 1 hour of symptoms if heart failure symptoms remained stable over the previous 7 days. Conventionally treated patients were followed for 10 ± 9 months; patients who underwent staged therapy for 9 ±5 months. In the group of patients that underwent standard therapy, 39 of 137 (28%) patients died: 5 (13%) deaths occurred suddenly, and death due to progressive pump failure occurred in the remaining 34 (87%) patients. In the group of patients that underwent staged therapy, 25 of 99 (25%) patients died: 13 (52%) deaths occurred suddenly, and 12 (48%) deaths occurred due to progressive pump failure. Thus, patients who underwent staged therapy were at increased risk for sudden death (P = 0.01, relative risk 3.4, 95% confidence interval 1.2–9.7) but were at lower risk for death from pump failure (P = 0.009, relative risk 0.44, 95% confidence interval 0.22–0.84). In patients who underwent therapy with continuous outpatient PGE₁ (n = 7) or dobutamine (n= 21), risk for sudden death (P = NS by log rank test) did not increase. In conclusion, staged therapy significantly reduced death from pump failure; however, patients who could be stabilized and considered too well for heart transplantation were at increased risk for sudden death. Thus, overall survival did not improve. Of note, outpatient dobutamine did not increase the risk for sudden death.     

3,6-(二甲氨基)-二苯骈碘杂六环葡萄糖酸盐对AGEP引起的大鼠主动脉平滑肌细胞增殖及牛主动脉内皮细胞内皮素和一氧化氮改变的影响

目的 :观察 3 ,6 (二甲氨基 ) 二苯骈碘杂六环葡萄糖酸盐对AGEP引起的大鼠主动脉平滑肌细胞增殖及牛主动脉内皮细胞内皮素和一氧化氮改变的影响。方法 :采用牛血清白蛋白 (BSA)与不同浓度葡萄糖 (0 ,2 0 ,5 0 ,80mmol·L-1)体外孵育制备糖基化终产物 (AGEP) ,应用 [3 H] TdR掺入法和MTT比色法观察I-93对重度糖化的AGEP诱导的大鼠主动脉平滑肌细胞 (ASMC)增殖的影响 ;应用放射免疫技术及Greiss法观察I -93对AGEP引起的牛主动脉内皮细胞 (BAEC)释放内皮素 1(ET 1)和一氧化氮 (NO)的影响。结果 :I-93 10 -7～ 10 -5mol·L-1能明显抑制AGEP引起的ASMC增殖 ,其 [3 H] TdR掺入量和MTT比色法的最大抑制率分别为79 .4%和 44 .2 %。随AGEP糖浓度的增加 (2 0～ 80mmol·L-1) ,BAEC培养液中ET 1含量亦逐渐上升 [(4 93± 63 )～ (779± 10 5 )ng·L-1] ,I -93 10 -7～ 10 -5mol·L-1能明显抑制重度糖化的AGEP促进ET 1释放的作用 ;I -93对AGEP灭活NO的作用有剂量依赖性抑制效应。结论 :I -93有抑制ASMC增殖的作用 ;对AGEP诱导的BAEC释放ET 1和NO间平衡失调有调节作用 ,在防治阻塞性血管疾病方面I -93具有潜在的应用价值     

Biocompatibility pattern of a bicarbonate/lactate-buffered peritoneal dialysis fluid in APD: a prospective, randomized study.

BACKGROUND: In chronic ambulatory peritoneal dialysis, bicarbonate-buffered fluids, with their neutral pH and less advanced glycosylation end-products (AGE) and glucose degradation products (GDP), have better biocompatibility than conventional peritoneal dialysis (PD) solutions. That difference may be more beneficial in automated peritoneal dialysis (APD), due to its more frequent exchanges and longer contact times with fresh dialysate. We performed a prospective, randomized study in APD patients to compare the biocompatibility of conventional and bicarbonate/lactate-buffered PD fluids. METHODS: We randomized 14 APD patients to have APD with either conventional or bicarbonate/lactate-based fluids. After 6 months, both groups changed to the other solution. The overall observation period was 12 months. After 1 and 5 months and again after 7 and 11 months, phagocytotic and respiratory burst capacities of effluent peritoneal macrophages were determined. Plasma interleukin (IL)-6 and C-reactive protein (CRP) as well as effluent IL-6, CRP, transforming growth factor (TGF)-beta 1, AGE and CA125 concentrations were measured. Inflow pain was quantified using a patient questionnaire. RESULTS: Respiratory burst capacity remained unchanged and phagocytotic activity increased significantly during APD (P<0.001) with the bicarbonate/lactate fluid. Effluent IL-6 release was significantly lower than with the lactate fluid (P<0.05). While in the effluent TGF-beta 1 was unaffected, AGE concentration was lower after bicarbonate/lactate treatment (P<0.05). Effluent CA125 concentration, an indicator of mesothelial cell integrity, was higher (P<0.05) in neutral effluents. Finally, patients' inflow pain diminished (P = 0.05) when using the neutral fluid. CONCLUSIONS: The use of a neutral PD fluid in APD improved patients' inflow pain as well as biocompatibility parameters reflecting enhanced phagocytotic activity of peritoneal macrophages, reduced constitutive inflammatory stimulation (IL-6), reduced AGE accumulation in the peritoneal cavity and better preservation of the mesothelial cell integrity. From the biocompatibility point of view, a neutral fluid with low GDP content can be recommended as the primary choice for APD.     

糖基化终末产物对大鼠肾系膜细胞纤溶酶原激活物抑制物-1表达韵影响

目的：观察糖基化终末产物（AGEs）对大鼠肾系膜细胞纤溶酶原激活物抑制物-1（PAI-1）表达的影响及其与细胞外基质（ECM）成分含量的关系。方法：体外培养正常大鼠肾系膜细胞，分别用糖化牛血清白蛋白（AGEs）及未经糖化的牛血清白蛋白（BSA）处理，以常规培养的肾系膜细胞作为对照，检测不同时间、不同浓度AGEs对纤维连接蛋白（FN）、Ⅳ型胶原、PAI-1表达的影响。MTT法检测AGEs对系膜细胞增殖的作用，ELISA测定条件培养基中FN、Ⅳ型胶原及PAI-1蛋白含量，逆转录聚合酶链式反应（RT—PCR）检测系膜细胞PAI-1 mRNA的表达。结果：与相应浓度的BSA比较，AGEs（0—200mg／L）对系膜细胞增殖无明显影响，但可不同程度地刺激系膜细胞FN、Ⅳ型胶原、PAI-1蛋白的产生。RT—PCR检测显示，给予AGEs（100mg／L）的系膜细胞PAI-1 mRNA的表达明显增加（P〈0．01）。结论：AGEs促进系膜细胞PAI—1的表达，提示AGEs通过上调PAI-1的表达而减少细胞外基质降解，可能是糖尿病肾病细胞外基质积聚的原因之一。     

全植入式药泵行肝血管灌注治疗晚期肝癌

对２４例不能切除的晚期肝癌采用完全植入式药泵行肝动脉和门静脉双灌注化疗。结果：部分缓解（ＰＲ）１５例（６２．５％），稳定（Ｓ）８例（３３．３％），进展（Ｐ）１例。平均生存期为９．１７月，半年生存率为６６．７％，１年为２５％。在ＡＦＰ＞４００μｇ／Ｌ的１０例中，５例下降。     

易误诊为神经肿瘤的一种疾病——肿块型中枢神经系统原发性血管炎

背景与目的：由于缺乏特异性临床和影像表现，肿块型中枢神经系统原发性血管炎（primary angiitris of central nervous system，PACNS）常被误诊为胶质瘤．本文旨在探讨肿块型PACNS的诊断与鉴别诊断。方法：回顾性分析手术治疗的37例肿块型PACNS患者的临床及影像表现。结果：85．3％的患者出现局灶性神经功能减退，55．9％患者有不同程度皮层高级功能减退症状。70．6％的颅内病变累及脑皮层：73．5％患者的正常区域脑血管周围间隙增宽，其中76％出现血管强化；病变出现特征性的“C”形强化。结论：局灶性神经功能和高级功能减退、病变累及皮层和“C”形强化等特征．有助于诊断肿块型PACNS。     

TIL／rIL－2免疫过继疗法治疗晚期瘤性胸水初探

７例晚期瘤性胸水的肿瘤浸润淋巴细胞（ＴＩＬ）经体外诱导培养３～１２ｄ，扩增１～９倍．其ＣＤ８及ＩＬ－２Ｒ阳性细胞百分率增加２．４３和２．７６倍；ＮＫ活力增加３．２９倍，与培养前后比较有显著差异。ＴＩＬ／ｒＩＬ－２（重组人白细胞介素２）胸腔内回输后，４例胸水及胸水中肿瘤细胞消失，癌胚抗原（ＣＥＡ）回至正常水平，２例胸水减少，１例因多房性胸水停止治疗，ＣＥＡ水平上升。经１～８个月随访患者心、肝、肾功能正常。