内镜下光动力治疗在胆管癌及壶腹癌治疗中的作用研究

目的 探讨内镜下光动力治疗（photodynamic therapy, PDT）联合支架置入治疗胆管癌及壶腹癌的临床疗效。方法 回顾性分析2013年9月—2016年12月东方肝胆外科医院收治的60例胆管癌及壶腹癌患者资料，支架组（n=36）单纯置入胆道支架，PDT组（n=24）行PDT联合胆道支架置入。记录临床资料及随访情况，统计分析2组临床成功率、并发症发生率、支架通畅期及生存期。结果 支架组和PDT组基线资料比较差异无统计学意义（P均＞0.05）。2组临床成功率[94.4%（34/36）比95.8%（23/24）， χ2=0.060, P=1.000]及术后并发症发生率比较[41.7%（15/36）比62.5%（15/24），χ2=2.50, P=0.187]差异无统计学意义。PDT组术后第1、3、6个月Karnofsky行为评分均较支架组高（P均<0.001）。支架组与PDT组支架中位通畅期分别为102.0 d（95%CI:73.9~130.1 d）与119.0 d（95%CI:96.8~141.2 d）（P=0. 634），中位生存期分别为162.0 d（95%CI:125.0~199.0 d）与327.0 d（95%CI:215.9~438.1 d）（P=0.006）。Cox回归多因素分析显示，PDT是患者生存时间的保护因素(P=0.012)，而胆总管癌(P=0.016)与更高TNM分期(P=0.001)是患者生存时间的危险因素。结论 内镜下PDT联合支架置入可有效延长胆管癌及壶腹癌患者的生存时间。PDT、病变部位与TNM分期是影响生存时间的独立预后因子。     

猪尾型鼻胆引流管改制新型胆管塑料支架在肝门部胆管癌中的应用

目的　比较猪尾型鼻胆引流管改制的新型胆管塑料支架与普通胆管塑料支架在姑息治疗肝门部胆管癌中的有效性和安全性。方法　收集2018年6月—2020年12月于北部战区总医院内窥镜科因肝门部胆管癌导致的梗阻性黄疸行经内镜逆行胰胆管造影术姑息性治疗的38例患者资料,其中20例患者使用猪尾型鼻胆引流管改制支架（新型组）,18例患者使用普通塑料支架（普通组）。随访至2021年5月30日,比较两组的操作时间、住院时间、术后胆管炎发生率、胆红素下降水平、支架通畅时间等指标。结果　新型组和普通组的操作时间分别为（19.85±1.07） min和（22.00±3.38） min, 差异无统计学意义（t=1.26,P=0.607）。新型组和普通组的住院时间分别为（11.45±2.39）d和（11.33±3.51） d,差异无统计学意义（t=-0.52,P=0.938）。新型支架与普通支架术后第5天较术前总胆红素降低幅度中位数分别为122.85 μmol/L 和 96.25 μmol/L,差异有统计学意义（Z=-2.03,P=0.042）。新型组远期胆管炎发生率低于普通组［10.0%（2/20）比44.4%（8/18）］,差异有统计学意义（P=0.027）。新型组支架引流通畅时间高于普通组［（109.45±32.67）d比（82.11±20.95）d］,差异有统计学意义（t=2.23,P=0.032）。结论　相比普通胆管塑料支架,猪尾型鼻胆引流管改制的新型胆管塑料支架在姑息性治疗肝门部胆管梗阻时,可降低远期胆管炎发生率、延长胆管支架通畅期。     

塑料胆管支架置入方式对不可切除肝门部胆管癌伴梗阻性黄疸治疗效果的影响

目的　对比塑料胆管支架3种末端开口留置方式在解除不可切除肝门部胆管癌梗阻性黄疸方面的临床应用效果。方法　回顾性分析2014年4月—2020年12月在中国医学科学院肿瘤医院内镜科行塑料胆管支架置入减黄治疗的不可切肝门部除胆管癌患者61例，其中胆管支架末端开口胃内留置18例（胃内留置组），十二指肠乳头留置31例（十二指肠乳头留置组），十二指肠水平部留置12例（十二指肠水平部留置组）。对随访2周发热率、围手术期死亡率、术后90 d支架梗阻率、支架中位通畅时间进行分析。结果　胃内留置组、十二指肠乳头留置组和十二指肠水平部留置组3组患者术后2周内发热率比较［66.7%（12/18），58.1%（18/31）和16.7%（2/12），χ2=7.30，P=0.026］差异有统计学意义，围手术期死亡率［0（0/16），3.2%（1/31）和0（0/10），χ2=1.09，P=1.000］、术后90 d内支架梗阻率［52.9%（9/17），48.3%（14/29）和40.0%（4/10），χ2=1.91，P=0.589］和支架中位通畅时间（66.0 d，91.5 d和94.0 d，Z=4.96，P=0.084）比较差异无统计学意义。结论　与胆管支架末端开口胃内留置和十二指肠乳头留置比较，十二指肠水平部留置术后2周发热率低，但支架中位通畅时间、术后90 d支架梗阻率及围手术期死亡率相似。支架末端开口留置于十二指肠水平部可作为首选置入方式。     

超细推送系统金属支架在肝门胆管恶性狭窄中的应用

目的　探讨超细金属支架治疗肝门胆管恶性狭窄的可行性、有效性和安全性。方法　2014年1月—2021年6月在东方肝胆外科医院消化内科根据影像学或组织学和（或）细胞学诊断为Bismuth Ⅱ型以上肝门胆管恶性狭窄的30例患者,使用超细推送系统金属支架,采用同步并行置入法置入胆管双侧金属支架。分析其技术成功率、临床疗效及并发症发生率。结果　技术成功率为100.0%（30/30）,临床成功率为93.3%（28/30）,操作时间（55.7±20.7）min, 金属支架置入时间（28.3±18.2） min。早期不良事件包括轻度急性胰腺炎2例和胆管炎5例。支架半数通畅时间为243 d （95%CI： 186.6~299.4 d）,患者半数生存期为237 d （95%CI：149.0~325.0 d）。晚期胆管炎发生率为36.7% （11/30）。14例患者出现支架失效,其中5例接受内镜下再介入。双侧金属支架腔内再置入支架技术成功率为4/5,操作时间为（49.8±6.9）min。结论　内镜下同步并行放置双侧超细金属支架治疗肝门胆管恶性狭窄是安全、可行、有效的。 结果 技术成功率100%（30/30例）,临床成功率93.3%(28/30例),操作时间55.7±20.7分, 金属支架置入时间28.3±18.2分。早期不良事件包括轻度急性胰腺炎2例和胆管炎5例。支架中位通畅时间为243 d (95% CI 186.6-299.4 d),中位生存期为237 d (95% CI 149.0-325.0 d)。晚期胆管炎发生率为36.7% (11/30)。14例患者出现支架失效,其中5例受内镜下再介入。双侧金属支架腔内再置入支架技术成功率为80%（4/5）,操作时间为49.8±6.9分。 结论 内镜下同步并行放置双侧超细推送系统金属支架治疗肝门胆管恶性狭窄是安全、可行、有效的。     

胆管狭窄患者塑料支架移位致十二指肠损伤的危险因素研究

目的　研究胆管狭窄患者置入胆管塑料支架后发生移位致十二指肠损伤的危险因素。方法　回顾性分析2017年1月—2021年12月在杭州市第一人民医院行胆管塑料支架置入术的1 408例胆管狭窄患者（2 607例次操作）的病例资料。统计术后出现胆管支架移位致十二指肠损伤的情况,将2 607例次操作分为移位损伤组（n=23例次）和非移位损伤组（n=2 584例次）两组,比较移位损伤组和非移位损伤组在基线资料和手术情况方面的差异,利用logistic回归分析探究胆管狭窄患者置入胆管塑料支架后支架移位致十二指肠损伤的独立危险因素。结果　1 408例胆管狭窄患者先后置入塑料支架2 607例次,共发生23例次支架移位导致的十二指肠损伤。logistic回归分析提示,胃肠手术史（OR=4.278,95%CI：1.332~13.737,P=0.015）、经内镜乳头括约肌切开术（endoscopic sphincterotomy, EST）手术史（OR=8.128,95%CI：2.382~27.738,P=0.001）、高位胆管狭窄（OR=4.457,95%CI：1.722~11.539,P=0.002）、使用长度≥7 cm的塑料支架（OR=4.701,95%CI：1.708~12.938,P=0.003）和圣诞树型支架（OR=6.890,95%CI：1.540~30.830,P=0.012）是胆管塑料支架移位致十二指肠损伤的独立危险因素。结论　高位胆管狭窄、使用长度≥7 cm的塑料支架和圣诞树型支架、有胃肠手术史及EST手术史会增加胆管狭窄患者置入塑料支架后支架移位致十二指肠损伤的危险。     

胆管支架联合光动力和（或）射频消融治疗在肝外胆管癌中的应用

为探讨内镜下胆管支架置入后行光动力治疗（photodynamic therapy,PDT）和（或）射频消融术（radiofrequency ablation,RFA）在不可切除肝外胆管癌（extrahepatic cholangiocarcinoma,EHCC）姑息治疗中的应用,回顾性分析了2017年1月至2023年1月在青岛大学附属医院消化内科治疗的5例EHCC患者的临床资料。5例患者均先接受胆管支架置入治疗,支架置入后6个月内接受PDT和（或）RFA。5例患者手术均成功。治疗后,5例患者血清胆红素水平均明显下降,术后恢复良好,1~3 d即好转出院。1例患者出现感染性并发症,其余均未发生不良事件。胆管支架治疗先于PDT和（或）RFA对EHCC进行姑息治疗,为后续PDT和（或）RFA顺利进行创造良好条件,可明显提高手术成功率,快速有效解除管腔梗阻,减少术后不良事件的发生,缩短术后恢复时间。     

金属支架联合三维适形放疗治疗晚期胆管癌的临床研究

目的探讨金属支架联合三维适形放疗对晚期胆管癌的疗效。方法 2005年8月～2009年7月,我院收治的51例不能手术治疗的晚期胆管癌患者,联合组29例行胆管金属支架联合三维适形放疗,单纯组22例仅行胆管金属支架置入治疗。结果 联合组与单纯组平均生存时间分别为（376.38±47.60）d和（238.82±67.30）d（P〈0.05）,中位生存期分别为（387.00±6.28）d和（202.00±8.21）d。结论金属支架联合三维适形放疗是治疗晚期胆管癌的有效方法。     

塑料胆管支架置入方式对不可切除肝门部胆管癌伴梗阻性黄疸治疗效果的影响

目的对比塑料胆管支架3种末端开口留置方式在解除不可切除肝门部胆管癌梗阻性黄疸方面的临床应用效果。方法回顾性分析2014年4月—2020年12月在中国医学科学院肿瘤医院内镜科行塑料胆管支架置入减黄治疗的不可切肝门部除胆管癌患者61例, 其中胆管支架末端开口胃内留置18例(胃内留置组), 十二指肠乳头留置31例(十二指肠乳头留置组), 十二指肠水平部留置12例(十二指肠水平部留置组)。对随访2周发热率、围手术期死亡率、术后90 d支架梗阻率、支架中位通畅时间进行分析。结果胃内留置组、十二指肠乳头留置组和十二指肠水平部留置组3组患者术后2周内发热率比较[66.7%(12/18), 58.1%(18/31)和16.7%(2/12), χ2=7.30, P=0.026]差异有统计学意义, 围手术期死亡率[0(0/16), 3.2%(1/31)和0(0/10), χ2=1.09, P=1.000]、术后90 d内支架梗阻率[52.9%(9/17), 48.3%(14/29)和40.0%(4/10), χ2=1.91, P=0.589]和支架中位通畅时间(66.0 d, 91.5 d和94.0 d,...     

经皮穿刺内支架置入联合区域性动脉化疗栓塞治疗恶性梗阻性黄疸

目的 观察经皮肝穿刺胆管内支架置入联合区域性动脉化疗的方法进行栓塞治疗恶性梗阻性黄疸的疗效.方法 梗阻性黄疸患者68例,采用经皮肝穿刺支架置入术(PTCD)联合肝动脉灌注化疗栓塞(TACE)观察治疗成功率、并发症及临床效果.结果 PTCD成功率100%,Ⅰ期支架置入成功率78.6%(44/56),Ⅱ期支架置入成功率100%(12/12).术后并发PTCD引流管脱落2例,腹腔出血2例.随访62例(6个月～3 a),平均生存时间为18.2个月.结论 采用PTCD联合TACE治疗恶性梗阻性黄疸,成功率高,并发症少,可延长患者生存期.     

内镜支架引流治疗肝细胞肝癌所致肝门部胆管恶性梗阻的疗效分析

目的　评估无法手术切除的肝细胞肝癌所致肝门部胆管恶性梗阻患者的内镜支架引流疗效。方法　回顾性分析2012年1月—2019年1月在海军军医大学第三附属医院因无法手术切除的肝细胞肝癌导致肝门部胆管恶性梗阻而行内镜支架引流的106例患者的临床资料。根据置入支架类型的不同，分为金属支架组（30例）和塑料支架组（76例）。观察指标包括临床成功率、并发症发生率、支架通畅期及总体生存时间。采用多因素Cox回归模型分析患者支架通畅期和总体生存时间的独立预测因素。结果　患者的总体临床成功率为67.9%（72/106），术后胆管炎发生率为29.2%（31/106）。金属支架组与塑料支架组的临床成功率分别为93.3%（28/30）和57.9%（44/76） （χ2=12.40，P<0.001），术后胆管炎发生率分别为13.3%（4/30）和35.5% （27/76）（χ2=5.12，P=0.024）。中位支架通畅期为5.2（95%CI：3.7~6.0）个月，中位总体生存时间为3.0（95%CI：2.5~3.7）个月。多因素Cox回归分析显示肝脏引流体积<30%是支架通畅期的独立预测因素（HR=2.12， 95%CI：1.01~4.46，P=0.048）。BismuthⅣ型（HR=2.06， 95%CI：1.12~3.77，P=0.020）、Child⁃Pugh C级（HR=4.09， 95%CI：2.00~8.39，P<0.001）、塑料支架（HR=1.87，95%CI：1.21~2.90，P=0.005）是总体生存时间的独立预测因素。结论　肝细胞肝癌一旦累及肝门部胆管预后不良。与塑料支架相比，金属支架引流在临床成功率、术后胆管炎发生率方面均具有一定优势。肝脏引流体积<30%是支架通畅期的独立预测因素，而Bismuth Ⅳ型、Child⁃Pugh C级、塑料支架为总体生存时间的独立预测因素。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.