肠道微生态影响动脉粥样硬化发生发展的机制

动脉粥样硬化(AS)不仅是一种炎症性疾病,而且属于一种代谢性疾病。肠道微生态的改变可对AS的发生发展产生双面影响。一方面,肠道菌群紊乱可以通过影响机体的胆碱代谢、氧化应激、炎症反应等机制直接促进AS产生发展,此外,可通过导致AS危险因素肥胖、高脂血症、糖尿病等的产生这些间接机制促AS的进展。另一方面,益生菌及益生元的增加则可有效地降低肠道微生物内毒素产生、增强肠道屏障、减轻机体质量、缓解炎症反应、改善胰岛素抵抗,进而在AS的进展方面发挥重要作用。因此,合理调控机体肠道微生态环境成为AS防治的新型重要手段。     

瓣膜性房颤定义及抗凝治疗研究进展

现阶段对于"瓣膜病变型"房颤(AF)与"非瓣膜病变型"AF的定义尚未达成共识,不仅如此,各指南在表述这些概念时也存在差异。临床试验对于"瓣膜病变型"AF与"非瓣膜病变型"AF定义的阐述不甚理想。两类AF血栓栓塞风险差异较大,抗凝治疗策略也有所不同。本文将对瓣膜性AF定义及抗凝治疗的研究进展予以综述。     

PNPLA3 I148M polymorphism and progressive liver disease

The 148 Isoleucine to Methionine protein variant(I148M)of patatin-like phospholipase domain-containing 3(PNPLA3),a protein is expressed in the liver and is involved in lipid metabolism,has recently been identified as a major determinant of liver fat content.Several studies confirmed that the I148M variant predisposes towards the full spectrum of liver damage associated with fatty liver:from simple steatosis to steatohepatitis and progressive fibrosis.Furthermore,the I148M variant represents a major determinant of progression of alcohol related steatohepatitis to cirrhosis,and to influence fibrogenesis and related clinical outcomes in chronic hepatitis C virus hepatitis,and possibly chronic hepatitis B virus hepatitis,hereditary hemochromatosis and primary sclerosing cholangitis.All in all,studies suggest that the I148M polymorphism may represent a general modifier of fibrogenesis in liver diseases.Remarkably,the effect of the I148M variant on fibrosis was independent of that on hepatic steatosis and inflammation,suggesting that it may affect both the quantity and quality of hepatic lipids and the biology of non-parenchymal liver cells besides hepatocytes,directly promoting fibrogenesis.Therefore,PNPLA3 is a key player in liver disease progression.Assessment of the I148M polymorphism will possibly inform clinical practice in the future,whereas the determination of the effect of the 148M variant will reveal mechanisms involved in hepatic fibrogenesis.     

Acute kidney injury spectrum in patients with chronic liver disease:Where do we stand?

Acute kidney injury (AKI) is a common complication of liver cirrhosis and is of the utmost clinical and prognostic relevance. Patients with cirrhosis, especially decompensated cirrhosis, are more prone to develop AKI than those without cirrhosis. The hepatorenal syndrome type of AKI (HRS–AKI), a spectrum of disorders in prerenal chronic liver disease, and acute tubular necrosis (ATN) are the two most common causes of AKI in patients with chronic liver disease and cirrhosis. Differentiating these conditions is essential due to the differences in treatment. Prerenal AKI, a more benign disorder, responds well to plasma volume expansion, while ATN requires more specific renal support and is associated with substantial mortality. HRS–AKI is a facet of these two conditions, which are characterized by a dysregulation of the immune response. Recently, there has been progress in better defining this clinical entity, and studies have begun to address optimal care. The present review synopsizes the current diagnostic criteria, pathophysiology, and treatment modalities of HRS–AKI and as well as AKI in other chronic liver diseases (non-HRS–AKI) so that early recognition of HRS–AKI and the appropriate management can be established.     

Endoscopic resection techniques for colorectal neoplasia:Current developments

Endoscopic polypectomy and endoscopic mucosal resection(EMR) are the established treatment standards for colorectal polyps. Current research aims at the reduction of both complication and recurrence rates as well as on shortening procedure times. Cold snare resection is the emerging standard for the treatment of smaller(< 5 mm) polyps and is possibly also suitable for the removal of noncancerous polyps up to 9 mm. The method avoids thermal damage, has reduced procedure times and probably also a lower risk for delayed bleeding. On the other end of the treatment spectrum, endoscopic submucosal dissection(ESD)offers en bloc resection of larger flat or sessile lesions. The technique has obvious advantages in the treatment of high-grade dysplasia and early cancer. Due to its minimal recurrence rate, it may also be an alternative to fractionated EMR of larger flat or sessile lesions. However, ESD is technically demanding and burdened by longer procedure times and higher costs. It should therefore be restricted to lesions suspicious for high-grade dysplasia or early invasive cancer.The latest addition to endoscopic resection techniques is endoscopic fullthickness resection with specifically developed devices for flexible endoscopy.This method is very useful for the treatment of smaller difficult-to-resect lesions,e.g., recurrence with scar formation after previous endoscopic resections.     

Lymph node staging in colorectal cancer:Old controversies and recent advances

Outcome prediction based on tumor stage reflected by the American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC)tumor node metastasis(TNM)system is currently regarded as the strongest prognostic parameter for patients with colorectal cancer.For affected patients,the indication for adjuvant therapy is mainly guided by the presence of regional lymph node metastasis.In addition to the extent of surgical lymph node removal and the thoroughness of the pathologist in dissecting the resection specimen,several parameters that are related to the pathological work-up of the dissected nodes may affect the clinical significance of lymph node staging.These include changing definitions of lymph nodes,involved lymph nodes,and tumor deposits in different editions of the AJCC/UICC TNM system as well as the minimum number of nodes to be dissected.Methods to increase the lymph node yield in the fatty tissue include methylene blue injection and acetone compression.Outcome prediction based on the lymph node ratio,defined as the number of positive lymph nodes divided by the total number of retrieved nodes,may be superior to the absolute numbers of involved nodes.Extracapsular invasion has been identified as additional prognostic factor.Adding step sectioning and immunohistochemistry to the pathological work-up may result in higher accuracy of histological diagnosis.The clinical value of more recent technical advances,such as sentinel lymph node biopsy and molecular analysis of lymph nodes tissue still remains to be defined.     

Role of endoscopic ultrasound in the screening and follow-up of high-risk individuals for familial pancreatic cancer

Managing familial pancreatic cancer(FPC)is challenging for gastroenterologists,surgeons and oncologists.High-risk individuals(HRI)for pancreatic cancer(PC)(FPC or with germline mutations)are a heterogeneous group of subjects with a theoretical lifetime cumulative risk of PC over 5%.Screening is mainly based on annual magnetic resonance imaging(MRI)and endoscopic ultrasound(EUS).The goal of screening is to identify early-stage operable cancers or high-risk precancerous lesions(pancreatic intraepithelial neoplasia or intraductal papillary mucinous neoplasms with high-grade dysplasia).In the literature,target lesions are identified in 2%-5%of HRI who undergo screening.EUS appears to provide better identification of small solid lesions(0%-46%of HRI)and chronicpancreatitis-like parenchymal changes(14%-77%of HRI),while MRI is probably the best modality to identify small cystic lesions(13%-49%of HRI).There are no specific studies in HRI on the use of contrast-enhanced harmonic EUS.EUS can also be used to obtain tissue samples.Nevertheless,there is still limited evidence on the accuracy of imaging procedures used for screening or agreement on which patients to treat.The cost-effectiveness of screening is also unclear.Certain new EUS-related techniques,such as searching for DNA abnormalities or protein markers in pancreatic fluid,appear to be promising.     

Prophecy about post-endoscopic retrograde cholangiopancreatography pancreatitis:From divination to science

One unresolved issue of endoscopic retrograde cholangiopancreatography(ERCP)is post-ERCP pancreatitis (PEP),which occurs in up to 40%of patients.Identification of risk factors for PEP is especially important in the field of ERCP practice because it may assist physicians in taking protective measures in situations with high risk.A decade ago,Freeman et al meticulously evaluated a large number of potentially relevant risk factors for PEP,which can be divided into patient-relat-ed and procedure-related issues.In this commentary, we summarize this classic article and reevaluate the risk factors for PEP from the current point of view.This is followed by assessment of strategies for prevention of PEP that can be divided into mechanical and pharmacologic methods.     

Issues and controversies in esophageal inlet patch

The proximal esophagus is rarely examined,and its inspection is often inadequate.Optical chromoendoscopy techniques such as narrow band imaging improve the detection rate of inlet patches in the proximal esophagus,a region in which their prevalence is likely underestimated.Various studies have reported correlations between these esophageal marks with different issues such as Barrett’s esophagus,but these findings remain controversial.Conflicting reports complicate the process of interpreting the clinical features of esophageal inlet patches and underestimate their importance.Unfortunately,the limited clinical data and statistical analyses make reaching any conclusions difficult.It is hypothesized that inlet patches are correlated with various esophageal and extraesophageal symptoms,diagnoses and the personalized therapeutic management of patients with inlet patches as well as the differential diagnosis for premalignant lesions or early cancers.Due to its potential underdiagnosis,there are no consensus guidelines for the management and follow up of inlet patches.This review focuses on questions that were raised from published literature on esophageal inlet patches in adults.     

Endoscopic management of difficult common bile duct stones

Endoscopy is widely accepted as the first treatment option in the management of bile duct stones.In this review we focus on the alternative endoscopic modalities for the management of difficult common bile duct stones.Most biliary stones can be removed with an extraction balloon,extraction basket or mechanical lithotripsy after endoscopic sphincterotomy.Endoscopic papillary balloon dilation with or without endoscopic sphincterotomy or mechanical lithotripsy has been shown to be effective for management of difficult to remove bile duct stones in selected patients.Ductal clearance can be safely achieved with peroral cholangioscopy guided laser or electrohydraulic lithotripsy in most cases where other endoscopic treatment modalities have failed.Biliary stenting may be an alternative treatment option for frail and elderly patients or those with serious co morbidities.     

Anal manometric findings in symptomatic hemorrhoids

Anal manometric findings were studied in 50 patients with symptomatic hemorrhoids and an equal number of age- and sex-matched control subjects. Manometry was performed with a continuously perfused catheter by the continuous pull-through technique. Both the control subjects and patients had significant negative collerations between age and basal pressure;i.e., basal pressure was lower with advancing age. Patients with symptomatic hemorrhoids had significantly higher maximal basal pressure (P<0.02) and maximal voluntary contraction pressure (P<0.05) as compared to controls. There was no correlation between the anal manometric findings and the degree of hemorrhoids or duration of symptoms. Those patients who had bleeding as the predominant symptom had higher basal pressures; (P<0.05) than those who had prolapsing hemorrhoids as the predominant symptom.     

Tumor Site Predicts Outcome After Radiochemotherapy in Squamous-Cell Carcinoma of the Anal Region: Long-Term Results of 101 Patients

PURPOSE This study was designed to assess the long-term results following radiochemotherapy in patients with anal squamous-cell carcinoma and to evaluate the impact of tumor location on response, survival, and colostomy-free survival.PATIENTS AND METHODS Between 1985 and 2001, a total of 101 patients with anal carcinoma were registered for curative treatment, of whom 77 had involvement of the anal canal alone, 10 cases had extension into the perianal skin, and 14 patients had pure anal margin tumors. Small tumors of the anal margin were not included since they were treated by surgical excision only. Among the 101 patients were 74 women and 27 men with a median age of 62 (range, 26–84) years. T categories (International Union against Cancer) were T1 (15), T2 (36), T3 (34), and T4 (16). Seventy-one patients had no evidence of nodal disease, whereas 30 presented with involved regional nodes. Radiation treatment was directed to the primary tumor region and to the inguinal, perirectal, and internal iliac nodes using a three-field to four-field box technique with 10MV photons up to a total dose of 5040 cGy. Lesions greater than 5 cm received an additional boost by interstitial or external radiation depending on circumferential extension of the residual tumor. All patients were scheduled for simultaneous chemotherapy with two cycles of 5-fluorouracil at a dose of 1000 mg/m ²/day as 120 hours of continuous intravenous infusion on Days 1 to 5 and 29 to 33 and mitomycin C at 10 mg/m ²/day on Days 1 and 29. Median follow-up time was was 7.5 (range, 1–16) years.RESULTS Overall survival and colostomy-free survival rates for patients with anal canal cancer were 75 percent and 87 percent at five years, respectively. Patients with anal margin cancer had a less favorable outcome with five-year-overall and colostomy-free survival rates of 54 percent and 69 percent, respectively. After correction for imbalance between anal canal and anal margin tumors, i.e., exclusion of T1 tumors of the anal canal, difference in overall survival remained significant (73 percent vs. 54 percent, P = 0.01). Following multivariate analysis, tumor location (anal canal vs. anal margin, P = 0.02), age (P = 0.003), and dose intensity of chemotherapy (≤75 percent vs. >75 percent, P = 0.03) remained independent significant factors for overall survival. Initial tumor response at six weeks (P = 0.03) was predictive for colostomy-free survival.CONCLUSIONS With colostomy-free survival rates around 85 percent, long-term treatment results for anal canal carcinoma have reached a satisfactory level. However, patients with larger lesions of the perianal skin are at high risk for locoregional recurrence and possible treatment intensification in this subgroup seems desirable.Supported by Grant No. D 15 from the Interdisciplinary Center for Clinical Research of the Medical Faculty of the University of Erlangen-Nuremberg.Presented at the meeting of the American Society for Therapeutic Radiology and Oncology, Denver, Colorado, October 16 to 20, 2005.     

Infiltrating adenocarcinoma arising in a villous adenoma of the anal canal

Primary neoplasms arising in the anal canal are relatively unusual. In particular, adenomas and adenocarcinomas are distinctly rare entities in this region. We describe an infiltrating, well-differentiated adenocarcinoma arising in a villous adenoma from the distal anal canal, in an otherwise healthy patient at low risk for gastrointestinal malignancy. This is the case of an octogenarian man with a several year history of hemorrhoids and intermittent rectal bleeding, more recently complaining of continuous hematochezia. Examination revealed a blood-covered pedunculated mass with a long stalk protruding from the anus. The lesion was amputated at the bedside. Microscopic evaluation revealed an infiltrating well-differentiated adenocarcinoma, arising from a villous adenoma. This was further evaluated under anesthesia and complete excision of distal anal tissue was performed. Our report is the first describing the possible malignant degeneration of a villous adenoma in the anal canal.     

The external anal sphincter

Anal manometry and anal electromyography (EMG) were performed in 45 patients to evaluate the external anal sphincter. Their symptoms were soiling (N=6), incontinence (N=10), and obstipation (N=10). Clinical diagnoses were previous anal surgery (N=16), rectal prolapse—partial, total, intussusception (N=16), puborectalis syndrome (N=4), neurologic disorders (N=3), and others (N=6). The relationship between the maximum squeeze pressure (MSP) measured with anal manometry and the maximum (voluntary) contraction pattern (MCP) and signs of denervation (DEN) measured with anal EMG were examined. The correlation coefficient between MSP and MCP was 0.55 (P<.001) and between MSP, and DEN 0.13 (NS). A normal MSP always showed a normal MCP, a normal MCP showed an abnormal MSP in 43 percent only. In conclusion, the clinical value of anal EMG seems limited. Assessment of an additional anal EMG seems indicated in incontinent patients with previous anal surgery with a low MSP to estimate muscle function, whenever anal surgery is considered. Anal EMG during straining can easily confirm the clinical diagnosis of puborectalis syndrome. Presented in part at the meeting of the Dutch Society of Gastroenterology, Noordwijkerhout, The Netherlands, October 2–3, 1987.     

Anal cancer in renal transplant patients

Purpose A comprehensive literature review was performed to examine the prevalence of anal cancer, anal intraepithelial neoplasia (AIN) and anal human papillomavirus (HPV) infection in renal transplant recipients who are at risk of anal cancer due to iatrogenic immunosuppression.Methods Pertinent articles were identified from searches performed on the National Center for Biotechnology Information database using the following keywords: anal cancer, AIN, screening, renal transplant (or kidney transplant), organ transplant recipients and post-transplant malignancies.Results The prevalence of AIN is 20% in renal transplant patients. The prevalence of anal HPV infection in established transplant patients is 47%, and the prevalence of anal HPV infection in new transplant patients is 23%. The relative risk for anal cancer in renal transplant patients is 10.Conclusions As compared to HIV-positive male patients who practise anal intercourse, renal transplant patients showed a modest rise in relative risk for anal cancer. Screening programmes to detect AIN in HIV-positive patients who practise anal intercourse have been introduced on a preliminary basis in sexual health clinics in the US and may become standard practise in this population. The case for screening in renal transplant patients is unclear and would merit further investigation, especially with reference to the prevalence of anal HPV infection in this population. It may transpire that renal transplant patients would benefit more from HPV prophylaxis rather than screening for AIN.     

Patient satisfaction and symptom relief after anal dilatation

Anal dilatation is used as a simple method of treatment and has been used for both anal fissure and haemorrhoids. This study examined longer-term results among a cohort of 162 patients, 132 of whom responded to a detailed questionnaire, an 82% response (66 patients were male; age range 17–75 years, median 42 years). Follow-up ranged from 16 months to 36 months (median 27 months) after anal dilatation (68 patients for fissure, 32 for haemorrhoids, and 32 for both). In the early months after dilatation, 83% had symptomatic improvement and 76% remained improved. Five (7%) patients with fissure and 11 with haemorrhoids (17%) required further hospital treatment, while 10% and 17%, respectively, had received further treatment from their general practitioners (GPs). Seventy-one percent said they would have a further anal dilation if symptoms recurred. There was no difference in results obtained by surgeons of different seniority. Complications – bleeding (29%) and difficulty controlling flatus (15%) or faeces (8%) – resolved in all cases. The results of anal dilatation for fissure are generally satisfactory in the longer term, with a trend toward better symptom relief in patients with fissure compared with those with haemorrhoids. We do not recommend anal dilatation as the sole treatment of patients with haemorrhoids, but it may be a useful adjunct to other treatments such as banding or sclerotherapy. Morbidity was generally acceptable and the majority of our patients would be prepared to have this procedure again if their symptoms were to return. Accepted: 14 September 1998     

A study to determine the nitroglycerin ointment dose and dosing interval that best promote the healing of chronic anal fissures

PURPOSE: The aim of this study was to determine the optimal dose and dosing interval of nitroglycerin ointment to heal chronic anal fissures. METHOD: A randomized, double-blind study of intra-anally applied nitroglycerin ointment (Anogesic) was conducted in 17 centers in 304 patients with chronic anal fissures. The patients were randomly assigned to one of eight treatment regimens (0.0, 0.1, 0.2, 0.4 percent nitroglycerin ointment applied twice or three times per day), for up to eight weeks. A dose-measuring device standardized the delivery of 374 mg ointment. Healing of fissures (complete reepithelialization) was assessed by physical examination using an observer unaware of treatment allocation. The subjects assessed pain intensity daily by completing a diary containing a visual analog scale for average pain intensity for the day, the worst pain intensity for the day, and pain intensity at the last defecation. RESULTS: There were no significant differences in fissure healing among any of the treatment groups; all groups, including placebo had a healing rate of approximately 50 percent. This rate of placebo response was inexplicably higher than previously reported in the literature. Treatment with 0.4 percent (1.5 mg) nitroglycerin ointment was associated with a significant (P < 0.0002) decrease in average pain intensity compared with vehicle as assessed by patients with a visual analog scale. The decreases were observed by Day 4 of treatment. At 8 weeks the magnitude of the difference between 0.4 percent nitroglycerin and control was a 21 percent reduction in average pain. Treatment was well tolerated, with only 3.29 percent of patients discontinuing treatment because of headache. Headaches were the primary adverse event and were dose related. CONCLUSION: Nitroglycerin ointment did not alter healing but significantly and rapidly reduced the pain associated with chronic anal fissures.     

Keratoacanthoma of the anus

Three cases of keratoacanthomas localized to the anal region are reported-one in the anal canal and two at the anal margin. The duration of the tumors before treatment was very short (three to nine weeks). Treatment consisted of local excision or curettage and electrocaagulation. No recurrence of the tumors was found at follow-up four to six years after treatment.     

Continence disorders after anal surgery—a relevant problem?

Subject  Anal incontinence is a well-known and feared complication following surgery involving the anal sphincter, particularly if partial transection of the sphincter is part of the surgical procedure. Methods  The literature was reviewed to evaluate the risk of postoperative incontinence following anal dilatation, lateral sphincterotomy, surgery for haemorrhoidal disease and anal fistula. Results  Various degrees of anal incontinence are reported with frequencies as follows: anal dilatation 0–50%, lateral sphincterotomy 0–45%, haemorrhoidal surgery 0–28%, lay open technique of anal fistula 0–64% and plastic repair of fistula 0–43%. Results vary considerably depending on what definition of “incontinence” was applied. The most important risk factors for postoperative incontinence are female sex, advanced age, previous anorectal interventions, childbirth and type of anal surgery (sphincter division). Sphincter lesions have been reported following procedures as minimal as exploration of the anal canal via speculum. Conclusions  Continence disorders after anal surgery are not uncommon and the result of the additive effect of various factors. Certain risk factors should be considered before choosing the operative procedure. Since options for surgical repair of postoperative incontinence disorders are limited, careful indications and minimal trauma to the anal sphincter are mandatory in anal surgery.     

Anorectal pressure gradient and rectal compliance in fecal incontinence

To study whether anorectal pressure gradients discriminated better than standard anal manometry between patients with fecal incontinence and subjects with normal anal function, anorectal pressure gradients were measured during rectal compliance measurements in 36 patients with fecal incontinence and in 22 control subjects. Anal and rectal pressures were measured simultaneously during the rectal compliance measurements. With standard anal manometry, 75% of patients with fecal incontinence had maximal resting pressure within the normal range, and 39% had maximum squeeze pressure within the normal range. Anorectal pressure gradients did not discriminate better between fecal incontinence and normal anal function, since, depending on the parameters used, 61%–100% of the incontinent patients had anorectal pressure gradients within the normal range. Patients with fecal incontinence had lower rectal volumes than controls at constant defecation urge (median 138 ml and 181 ml, P<0.05) and at maximal tolerable volume (median 185 ml and 217 ml, P<0.05). We conclude that measurements of anorectal pressure gradients offer no advantage over standard anal manometry when comparing patients with fecal incontinence to controls. Patients with fecal incontinence have a lower rectal volume tolerability than control subjects with normal anal function. Accepted: 5 June 1998