从郁论治胆结石

胆结石的发病多与情志不疏有关,情志不疏,气机运行失畅,遂生郁滞,进而产生六郁之邪及其他变证。郁证贯穿胆结石的整个发病过程。七情作为外因而致郁,又可因郁而致内在因素如气血阴阳等物质的改变,进而产生六郁,即气郁、湿郁、痰郁、热郁、血郁及食郁,六郁证候各有不同,又相互影响,相互为病,故临床立法当以疏理气机为先,进而根据气郁所致之痰郁、血郁、热郁等不同辨证治疗,用药当以理气药为主,配合活血药、清热药、祛痰祛湿药等共奏标本兼治之效。笔者在辨证选方的基础上,灵活运用对药,如茵陈配金钱草,石菖蒲配远志,瓜蒌仁配瓜蒌皮,白茅根配芦根,柴胡配白芍,桔梗配枳壳,百合配生地黄、天花粉、煅牡蛎等,发挥药物相使或相须的配伍之效,增强了疗效。另外,应嘱患者注意调节情绪,在配合治疗同时放松心情,才有助于减少胆结石的复发。     

Ceftriaxone‐associated biliary pseudolithiasis in children: do we know enough?

Ceftriaxone is an antibiotic agent frequently used in paediatric hospital practice for the treatment of severe bacterial infections. The use of this agent can result in cholelithiasis and/or biliary sludge, more commonly in children than in adults. This systematic review was aimed at analysing available literature concerning ceftriaxone‐associated biliary pseudolithiasis in paediatric patients, with a special emphasis on the clinical aspects. A literature analysis was performed using Medline and Embase electronic databases (articles published in English up to December 2019), with the search terms and combinations as follows:’ceftriaxone’, ‘cholelithiasis’, ‘biliary sludge’ ‘gallstones’ ‘neonates’ ‘children’ ‘clinical aspects’ ‘management’. Several case reports, case series and prospective/retrospective studies have documented a relationship between ceftriaxone treatment and biliary pseudolithiasis in the paediatric population, even though literature data regarding neonates and infants are scarce. Ceftriaxone‐associated biliary pseudolithiasis is dose‐dependent and usually asymptomatic but, sometimes, it may present with abdominal pain, nausea and emesis. Abdominal ultrasonography should be performed when this complication is suspected. Generally, ceftriaxone‐associated cholelithiasis resolves over a variable period of time (days to months) after cessation of therapy. Therefore, a conservative approach to this condition is advocated, but a prolonged follow‐up may be necessary. A personalized assessment of factors predisposing to ceftriaxone‐associated biliary pseudolithiasis before prescribing the drug can allow to minimize the risk of developing it, with significant advantages in terms of human and economic costs.     

能谱CT多参数成像评估胆结石成分的应用价值

目的 探究能谱CT多参数成像评估胆固醇结石和非胆固醇结石的应用价值。方法 收集125枚胆结石置入猪肝模型中行CT能谱模式扫描,并重建普通螺旋CT图像,测量所有胆结石单能量40 keV、100 keV时的CT值（HU_{40 keV}、HU_{100 keV}）、有效原子序数（Eff-Z）和普通螺旋CT值（HU_{120 kVp like}）,并计算40～100 keV区间能谱衰减斜率（K）,根据红外光谱分析结果分为胆固醇结石组56枚和非胆固醇结石组69枚。采用秩和检验比较两组各参数差异,利用多因素Logistic回归分析判断胆结石成分的独立影响参数,绘制受试者工作特征（ROC）曲线,分析评估影响效能及截断值。招募胆结石患者80例,术前行CT能谱模式扫描并重建普通螺旋CT图像,分别预测术前胆结石成分,术后取出86枚胆结石行红外光谱分析,分析各参数预测结果的准确性。结果 体外非胆固醇结石组HU_{40 keV}、HU_{100 keV}、Eff-Z、K值及HU_{120 kVp like}与胆固醇结石组比较,差异有统计学意义（P <0.05）,非胆固醇结石组高于胆固醇结石组。多因素Logistic回归分析结果显示仅Eff-Z［R=12.57（95% CI：5.38,29.35）］是胆固醇和非胆固醇结石的影响因素,其ROC曲线下面积为0.962（95% CI：0.928,0.997）,对应截断值为7.27。体内验证结果显示,以术后红外光谱分析为参照,能谱CT预测胆结石成分的总准确率为91.86%（95% CI：0.831,0.967）,而普通螺旋CT预测的总准确率仅为77.9%（95% CI：0.690,0.872）,能谱CT与红外光谱分析结果具有较高的一致性（κ =0.832,P <0.05）。而普通螺旋CT值预测胆结石成分结果与红外光谱分析结果一致性一般（κ =0.561,P <0.05）。结论 能谱CT多参数成像可较准确地评估胆结石成分,尤其以Eff-Z参考价值为佳,优于普通螺旋CT扫描。     

多序列MRI检查在胆系结石诊断中的应用价值

目的:探讨胆系结石MRI检出的适宜序列,评价MRI推测胆系结石类型的可行性。方法:回顾性分析临床诊断胆石症,且手术取出最大径＞8 mm的胆囊或胆管结石的30例患者。术前行上腹部轴面三维脂肪抑制快速扰相梯度回波（3D-FSPGR-FS T1WI）、脂肪抑制快速扰相梯度回波（FSPGR-FS T1WI）、稳态采集快速成像（FIESTA）和脂肪抑制快速自旋回波（FSE-FS T2WI）序列扫描。30例患者中,胆色素石16例,胆固醇石14例。观察各序列结石的信号特点,测量信号强度,计算结石检出率。采用 McNemar′s检验对各序列胆系结石的检出率差异进行组间比较。采用Mann-Whitney U 检验比较胆色素石与胆固醇石各序列信号强度之间的差异。结果:3D-FSPGR-FS T1WI和FIESTA序列对胆系结石的检出率分别为93.33%（28/30）和96.67%（29/30）。胆色素石在3D-FSPGR-FS T1WI上表现特征性高信号, 绝大部分胆固醇石在所有MRI序列中为均匀或混杂的低信号。3D-FSPGR-FS T1WI上,胆色素石的信号强度高于胆固醇石[146.3（42.12）vs.32.15（35.61）,P<0.000 1]。结论:3D-FSPGR-FS T1WI和FIESTA序列对胆系结石的检出率高,3D-FSPGR-FS T1WI有助于结石的分类。     

Glucuronidation of bilirubin and the occurrence of pigment gallstones in patients with chronic haemolytic diseases

A group of thirty-seven patients with increased haem catabolism has been studied to gain insight in their bilirubin conjugating capacity. Bilirubin UDP-glucuronyl transferase activity (GlcATa) in the liver and bilirubin monoconjugates in bile were measured and the hepatic bilirubin clearance was calculated from the radio-chromium-survival data. In the present group, 41% of the patients clearly had a deficiency in bilirubin conjugation similar to what is classically found in Gilbert's syndrome. The association may facilitate detection of these patients as serum bilirubin levels were higher (65.8 microM +/- 19) (m +/- 1 SD) in the fifteen patients with associated Gilbert's syndrome versus thirteen having only haemolysis (43.6 microM +/- 15). A fair correlation was found between the percentage of monoconjugates in bile and the GlcATa levels in the liver as well as with the calculated hepatic bilirubin clearance, although some discrepancies exist. Using these determinations, a clearcut separation from normal values was not obtained, suggesting at least in the present group of patients that Gilbert' syndrome represents only one end of a continuum of bilirubin conjugation rates and not a separate entity. Pigment stones in the gall-bladder were documented in 51% of the patients and usually at an early age. There was no relationship towards sex, serum bilirubin, GlcATa in liver, total bilirubin or monoconjugates in bile. Age played some role as well as the type of haemolysis as all patients with congenital dyserythropoiesis (n = 4) or acquired haemolysis (n = 3) had lithiasis. Moderate chronic cholecystitis was present, whereas an accumulation of iron and bile pigment was evident in the liver.     

Enterohepatic cycling of bilirubin as a cause of 'black' pigment gallstones in adult life

In contrast to bile salts, which undergo a highly efficient enterohepatic circulation with multiple regulatory and physiologic functions, glucuronic acid conjugates of bilirubin are biliary excretory molecules that in health do not have a continuing biologic life. Intestinal absorptive cells are devoid of recapture transporters for bilirubin conjugates, and their large size and polarity prevent absorption by passive diffusion. However, unconjugated bilirubin, the beta-glucuronidase hydrolysis product of bilirubin glucuronides can be absorbed passively from any part of the small and large intestines. This can occur only if unconjugated bilirubin is kept in solution and does not undergo rapid bacterial reduction to form urobilinoids. Here we collect, and in some cases reinterpret, experimental and clinical evidence to show that in addition to the well-known occurrence in newborns, enterohepatic cycling of unconjugated bilirubin can reappear in adult life. This happens as a result of several common conditions, particularly associated with bile salt leakage from the small intestine, the most notable ileal dysfunction resulting from any medical or surgical cause. We propose that when present in excess, colonic bile salts solubilize unconjugated bilirubin, delay urobilinoid formation, prevent calcium complexing of unconjugated bilirubin and promote passive absorption of unconjugated bilirubin from the large intestine. Following uptake, reconjugation, and resecretion into bile, this source of 'hyperbilirubinbilia' may be the important pathophysiological risk factor for 'black' pigment gallstone formation in predisposed adult humans.     

Jaundice

Jaundice is a yellow discoloration of body tissues usually observed in the skin secondary to excess bilirubin in the serum. This occurs due to imbalance between production and clearance of bilirubin. It is important to understand the pathophysiology of jaundice to understand its aetiology. Careful history and physical examination, together with appropriate urine and blood tests will guide further investigations to obtain an appropriate diagnosis. It is important to assess and address associated sepsis, dehydration, electrolyte imbalance and clotting abnormality to reduce morbidity prior to instituting any treatment plan. This often involves specialists from the multidisciplinary team.     

消炎利胆片与经胆道镜取石术治疗老年肝胆结石对患者血清Ins、C－P、HA水平的影响比较

目的：比较消炎利胆片与经胆道镜取石术治疗老年肝胆结石对患者血清胰岛素（ Ins）、C－肽（ C－P）、透明质酸（ HA）水平的影响。方法将老年胆结石患者212例随机分为试验组和对照组各106例。试验组采用经胆道镜取石术,对照组给予包括消炎利胆片口服在内的药物治疗。于治疗前后检测2组患者血清Ins、C－P及HA水平,并比较2组临床疗效。结果治疗后2组患者Ins和HA水平均显著低于治疗前,且试验组降低幅度大于对照组,差异均有统计学意义（P＜0．05）。但2组患者治疗后C－P水平差异无统计学意义（P＞0．05）。试验组的总有效率96．23％高于对照组的82．08％,差异有统计学意义（P＜0．05）。结论经胆道镜取石术治疗老年肝胆结石患者可显著降低血清Ins和HA水平,对C－P水平无影响,较药物治疗具有更好的治疗效果。     

Diminished gallbladder motility in Rotund leptin-resistant obese mice

Background. Obesity is a risk factor for cholesterol gallstone formation, but the pathogenesis of this phenomenon remains unclear. Most human obesity is associated with diabetes and leptin-resistance. Previous studies from this laboratory have demonstrated that diabetic leptin-resistant (Lep^db) obese mice have low biliary cholesterol saturation indices, enlarged gallbladders and diminished gallbladder response to neurotransmitters. Recently, a novel leptin-resistant mouse strain Lepr^db-rtnd (Rotund) has been discovered. Rotund mice are also obese, diabetic, and have an abnormal leptin receptor. Therefore, we tested the hypothesis that leptin-resistant obese Rotund mice would have large gallbladders and reduced biliary motility.Methods. Eight-week-old control (C57BL/6J, N=12) and Rotund leptin-resistant (Lepr^db-rnd, N=9) mice were fed a non- lithogenic diet for four weeks. Animals were fasted and underwent cholecystectomy. Gallbladder volumes were recorded, and contractile responses (N/cm²) to acetylcholine (10⁻⁵ M), Neuropeptide Y (10^{−8,−7,−6} M), and cholecystokinin (10^{−10,−9,−8,−7} M) were measured. Results were analyzed using the Mann-Whitney Rank Sum Test.Results. Compared to control mice, Rotund mice had larger body weights, higher serum glucose levels, and greater gallbladder volumes (p<0.05). Rotund gallbladders had less contractility (p<0.05)) to acetylcholine and cholecystokinin than control mice. Responses to Neuropeptide Y were also less, but not statistically significant, in the Rotund mice.Conclusions. These data suggest that leptin-resistant Rotund mice have (1) enlarged gallbladders with (2) diminished contractility compared to lean control mice. Therefore, this study confirms that leptin-resistance is associated with abnormal biliary motility and may lead to gallstone formation in leptin-resistant obesity.