胰管支架安置在胰管狭窄中的治疗作用

目的采用胰管支架安置治疗胰管狭窄病例,以缓解胰管梗阻症状,同时对胰管支架的适应证及操作技术进行探讨。方法对诊断明确的胰腺癌及慢性胰腺炎伴胰管狭窄的病例,先行内镜下逆行胰胆管造影及胰管腔内超声检查,确定狭窄长度及距乳头的距离,选择合适的胰管支架,在导丝的引导下,用推送器将支架送到目的部位,然后摄片定位。结果该组18例安置顺利,支架都超过狭窄的远端,吸引后胰液外流,患者症状很快缓解。结论胰管支架是治疗各种原因引起的胰管狭窄的有效的姑息治疗措施,对于胰管阻塞的病例能起到缓解症状、提高生活质量的目的,尤其是塑料胰管支架安置及取出较方便,并发症少。

Randomized controlled trial of pancreatic stenting to prevent pancreatitis after endoscopic retrograde cholangiopancreatography

AIM:To determine the effectiveness of pancreatic duct(PD) stent placement for the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography(ERCP) in high risk patients.METHODS:Authors conducted a single-blind,randomized controlled trial to evaluate the effectiveness of a pancreatic spontaneous dislodgement stent against post-ERCP pancreatitis,including rates of spontaneous dislodgement and complications.Authors defined high risk patients as having any of the following:sphincter of Oddi dysfunction,difficult cannulation,prior history of post-ERCP pancreatitis,pre-cut sphincterotomy,pancreatic ductal biopsy,pancreatic sphincterotomy,intraductal ultrasonography,or a procedure time of more than 30 min.Patients were randomized to a stent group(n = 60) or to a non-stent group(n = 60).An abdominal radiograph was obtained daily to assessspontaneous stent dislodgement.Post-ERCP pancreatitis was diagnosed according to consensus criteria.RESULTS:The mean age(± standard deviation) was 67.4 ± 13.8 years and the male:female ratio was 68:52.In the stent group,the mean age was 66 ± 13 years and the male:female ratio was 33:27,and in the non-stent group,the mean age was 68 ± 14 years and the male:female ratio was 35:25.There were no significant differences between groups with respect to age,gender,final diagnosis,or type of endoscopic intervention.The frequency of post-ERCP pancreatitis in PD stent and non-stent groups was 1.7%(1/60) and 13.3%(8/60),respectively.The severity of pancreatitis was mild in all cases.The frequency of post-ERCP pancreatitis in the stent group was significantly lower than in the non-stent group(P = 0.032,Fisher's exact test).The rate of hyperamylasemia were 30%(18/60) and 38.3%(23 of 60) in the stent and non-stent groups,respectively(P = 0.05,χ2 test).The placement of a PD stent was successful in all 60 patients.The rate of spontaneous dislodgement by the third day was 96.7%(58/60),and the median(range) time to dislodgement was 2.1(2-3) d.The rates of stent migration,hemorrhage,perforation,infection(cholangitis or cholecystitis) or other complicationss were 0%(0/60),0%(0/60),0%(0/60),0%(0/60),0%(0/60),respectively,in the stent group.Univariate analysis revealed no significant differences in high risk factors between the two groups.The pancreatic spontaneous dislodgement stent safely prevented post-ERCP pancreatitis in high risk patients.CONCLUSION:Pancreatic stent placement is a safe and effective technique to prevent post-ERCP pancreatitis.Therefore authors recommend pancreatic stent placement after ERCP in high risk patients.

Study on chronic pancreatitis and pancreatic cancer using MRS and pancreatic juice samples

AIM:To investigate the markers of pancreatic diseases and provide basic data and experimental methods for the diagnosis of pancreatic diseases.METHODS:There were 15 patients in the present study,among whom 10 had pancreatic cancer and 5,chronic pancreatitis.In all patients,pancreatic cancer or chronic pancreatitis was located on the head of the p-a-ncrea-s.Pa-thology da-ta-of a-ll p-a-tients wa-s confirmed by biopsy and surgery.Among the 10 patients with pancreatic cancer,3 people had a medical history of longterm alcohol consumption.Of 5 patients with chronic pancreatitis,4 men suffered from alcoholic chronic pancreatitis.Pancreatic juice samples were obtained from patients by endoscopic retrograde cholangiopancreatography.Magnetic resonance spectroscopyn was performed on an 11.7-T scanner (Bruker DRX-500) using Call-Purcell-Meiboom-Gill pulse sequences.The parameters were as follows:spectral width,15 KHz;time domain,64 K;number of scans,512;and acquisition time,2.128 s.RESULTS:The main component of pancreatic juice included leucine,iso-leucine,valine,lactate,alanine,acetate,aspartate,lysine,glycine,threonine,tyrosine,histidine,tryptophan,and phenylalanine.On performing 1D 1H and 2D total correlation spectroscopy,we found a triplet peak at the chemical shift of 1.19 ppm,which only appeared in the spectra of pancreatic juice obtained from patients with alcoholic chronic pancreatitis.This triplet peak was considered the resonance of the methyl of ethoxy group,which may be associated with the metabolism of alcohol in the pancreas.CONCLUSION:The triplet peak,at the chemical shift of 1.19 ppm is likely to be the characteristic metabolite of alcoholic chronic pancreatitis.

Evaluation of clinical relevance of examining K-ras, p16 and p53 mutations along with allelic losses at 9p and 18q in EUS-guided fine needle aspiration samples of patients with chronic pancreatitis and pancreatic cancer

AIM： To establish an optimum combination of molecular markers resulting in best overall diagnostic sensitivity and specificity for evaluation of suspicious pancreatic mass. METHODS： Endoscopic ultrasound （EUS）-guided fine needle aspiration cytology （FNA） was performed on 101 consecutive patients （63 males, 38 females, 60 ± 12 years; 81 with subsequently diagnosed pancreatic cancer, 20 with chronic pancreatitis） with focal pancreatic mass. Samples were evaluated on-site by an experienced cytopathologist. DNA was extracted from Giemsa stained cells selected by laser microdissection and the presence of K-ras, p53 and p16 somatic mutations was tested by cycling-gradient capillary electrophoresis （CGCE） and single-strand conformation polymorphism （SSCP） techniques. In addition, allelic losses of tumor suppressor genes p16 （INK4, CDKN2A） and DPC4 （MADH4, SMAD4） were detected by monitoring the loss of heterozygosity （LOH） at 9p and 18q, respectively. RESULTS： Sensitivity and specificity of EUS-guided FNA were 75% and 85%, positive and negative predictive value reached 100%. The remaining 26% samples were assigned as inconclusive. Testing of molecular markers revealed sensitivity and specificity of 70% and 100% for K-ras mutations （P 〈 0.001）, 24% and 90% for p53 mutations （NS）, 13% and 100% for p16 mutations （NS）, 85% and 64% for aUelic losses at 9p （P 〈 0.001） and 78% and 57% for allelic losses at 18q （P 〈 0.05）. When tests for different molecular markers were combined, the best results were obtained with K-ras ＋ LOH at 9p （92% and 64%, P 〈 0.001）, K-ras ＋ LOH at 18q （92% and 57%, P 〈 0.001）, and K-ras ＋ LOH 9q ＋ LOH 18q （96% and 43%, P 〈 0.001）. When the molecular markers were used as complements to FNA cytology to evaluate inconclusive samples only, the overall sensitivity of cancer detection was 100% in all patients enrolled in the study. CONCLUSION： EUS-guided FNA cytology combined with screening of K-ras mutations and allelic losses of tumor suppressors p16 and DPC4 represents a very sensitive approach in screening for pancreatic malignancy. Molecular markers may find its use particularly in cases where FNA cytology has been inconclusive.

Pancreatic carcinoma coexisting with chronic pancreatitis versus tumor-forming pancreatitis:Diagnostic utility of the time-signal intensity curve from dynamic contrast-enhanced MR imaging

AIM: To evaluate the ability of the time-signal intensity curve (TIC) of the pancreas obtained from dynamic contrast-enhanced magnetic resonance imaging (MRI) for differentiation of focal pancreatic masses, especially pancreatic carcinoma coexisting with chronic pancreatitis and tumor-forming pancreatitis. METHODS: Forty-eight consecutive patients who underwent surgery for a focal pancreatic mass, including pancreatic ductal carcinoma (n = 33), tumor-forming pancreatitis (n = 8), and islet cell tumor (n = 7), were reviewed. Five pancreatic carcinomas coexisted with longstanding chronic pancreatitis. The pancreatic TICs were obtained from the pancreatic mass and the pancreatic parenchyma both proximal and distal to the mass lesion in each patient, prior to surgery, and were classified into 4 types according to the time to a peak: 25 s and 1, 2, and 3 min after the bolus injection of contrast material, namely, type-Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively, and were then compared to the corresponding histological pancreatic conditions. RESULTS: Pancreatic carcinomas demonstrated type-Ⅲ (n = 13) or Ⅳ (n = 20) TIC. Tumor-forming pancreatitis showed type-Ⅱ (n = 5) or Ⅲ (n = 3) TIC. All islet cell tumors revealed type-Ⅰ. The type-Ⅳ TIC was only recognized in pancreatic carcinoma, and the TIC of carcinoma always depicted the slowest rise to a peak among the 3 pancreatic TICs measured in each patient, even in patients with chronic pancreatitis.CONCLUSION: Pancreatic TIC from dynamic MRI provides reliable information for distinguishing pancreatic carcinoma from other pancreatic masses, and may enable us to avoid unnecessary pancreatic surgery and delays in making a correct diagnosis of pancreatic carcinoma, especially, in patients with longstanding chronic pancreatitis.

Contrast-enhanced endoscopic ultrasound in discrimination between focal pancreatitis and pancreatic cancer

AIM： To evaluate the contrast-enhanced endosonography as a method of differentiating inflammation from pancreatic carcinoma based on perfusion characteristics of microvessels. METHODS： In 86 patients with suspected chronic pancreatitis （age： 62± 12 years; sex： f/m 38/48）, pancreatic lesions were examined by conventional endo- scopic B-mode, power Doppler ultrasound and contrastenhanced power mode （Hitachi EUB 525, SonoVue, 2.4 mL, Bracco） using the following criteria for malignant lesions： no detectable vascularisation using conventional power Doppler scanning, irregular appearance of arterial vessels over a short distance using SonoVue contrastenhanced technique and no detectable venous vessels inside the lesion. A malignant lesion was assumed if all criteria were detectable [gold standard endoscopic ultrasound （EUS）-guided fine needle aspiration cytology, operation]. The criteria of chronic pancreatitis without neoplasia were defined as no detectable vascularisation before injection of SonoVue, regular appearance of vessels over a distance of at least 20 mm after injection of SonoVue and detection of arterial and venous vessels. RESULTS： The sensitivity and specifidty of conventional EUS were 73.2% and 83.3% respectively for pancreatic cancer. The sensitivity of contrast-enhanced EUS increased to 91.1% in 51 of 56 patients with malignant pancreatic lesion and the specificity increased to 93.3% in 28 of 30 patients with chronic inflammatory pancreatic disease.CONCLUSION： Contrast-enhanced endoscopic ultrasound improves the differentiation between chronic pancreatitis and pancreatic carcinoma.

Overexpression of c-met in the early stage of pancreatic carcinogenesis; altered expression is not sufficient for progression from chronic pancreatitis to pancreatic cancer

AIM： To investigate c-met expression during early pancreatic carcinogenesis. METHODS： We used 46 bulk tissues and 36 microdissected samples, including normal pancreas, chronic pancreatitis, and pancreatic cancer, for quantitative realtime reverse transcription-polymerase chain reaction. RESULTS： In bulk tissue analyses, pancreatic cancer tissues expressed significantly higher levels of c-met than did chronic pancreatitis and normal pancreas tissues. c-met levels did not differ between chronic pancreatitis and normal pancreas tissues. In microdissection-based analyses, c-met was expressed at higher levels in microclissected pancreatic cancer cells and pancreatitisaffected epithelial cells than in normal ductal epithelial cells （both, P 〈 0.01）. Interestingly, pancreatitis-affected epithelial cells expressed levels of c-met similar to those of pancreatic cancer cells. CONCLUSION： Overexpression of c-met occurs during the early stage of pancreatic carcinogenesis, and a single alteration of c-met expression is not sufficient for progression of chronic pancreatitis-affected epithelial cells to pancreatic cancer cells.

Difficulty with diagnosis of malignant pancreatic neoplasms coexisting with chronic pancreatitis

Chronic pancreatitis is a relatively common disease. We encountered two different cases of belatedly demonstrated pancreatic carcinoma featuring underlying chronic pancreatitis. The first case was one that was highly suspected as that of a malignancy based upon imaging study, but unfortunately, it could not be confirmed by intra-operative cytology at that time. Following this, the surgeon elected to perform only conservative bypass surgery for obstructive biliary complication. Peritoneal carcinomatosis was later noted and the patient finally died. The second case, a malignant mucinous neoplasm,was falsely diagnosed as a pseudocyst, based upon the lesion's sonographic appearance and associated elevated serum amylase levels. After suffering repeated hemoptysis,the patient was found to exhibit lung metastasis and peritoneal seeding. We reviewed some of the literature,including those studies discussing chronic pancreatitis predisposing to a malignant change. These two case analyses illustrate clearly that the diagnosis for such conditions, which is simply based upon imagery or pathological considerations may end up being one of a mistaken malignancy. Some of our suggestions for the treatment of such malignancies as revealed herein include,total pancreatomy for univocal mass lesion, and needle aspiration of lesion-contained tissue for amylase, CA199and CEA levels for a suspicious cystic pancreatic mass.

Strategy to differentiate autoimmune pancreatitis from pancreas cancer

Autoimmune pancreatitis (AIP) is a newly described entity of pancreatitis in which the pathogenesis appears to involve autoimmune mechanisms. Based on histological and immunohistochemical examinations of various organs of AIP patients, AIP appears to be a pancreatic lesion reflecting a systemic "IgG4-related sclerosing disease". Clinically, AIP patients and patients with pancreatic cancer share many features, such as preponderance of elderly males, frequent initial symptom of painless jaundice, development of new-onset diabetes mellitus, and elevated levels of serum tumor markers. It is of uppermost importance not to misdiagnose AIP as pancreatic cancer. Since there is currently no diagnostic serological marker for AIP, and approach to the pancreas for histological examination is generally difficult, AIP is diagnosed using a combination of clinical, serological, morphological, and histopathological features. Findings suggesting AIP rather than pancreatic cancer include:fluctuating obstructive jaundice; elevated serum IgG4 levels; diffuse enlargement of the pancreas; delayed en- hancement of the enlarged pancreas and presence of a capsule-like rim on dynamic computed tomography; low apparent diffusion coefficient values on diffusion-weighted magnetic resonance image; irregular narrowing of the main pancreatic duct on endoscopic retrograde cholangiopancreatography; less upstream dilatation of the main pancreatic duct on magnetic resonance cholangiopancreatography, presence of other organ involvement such as bilateral salivary gland swelling, retroperitoneal fibrosis and hilar or intrahepatic sclerosing cholangitis; negative work-up for malignancy including endoscopic ultrasound-guided fine needle aspiration; and steroid responsiveness. Since AIP responds dramatically to steroid therapy, accurate diagnosis of AIP can avoid unnecessary laparotomy or pancreatic resection.

Expression of Ki-67,p53,and K-ras in chronic pancreatitis and pancreatic ductal adenocarcinoma

AIM： To examine surgical specimens of pancreas with either chronic pancreatitis or pancreatic cancer in order to study whether ductal hyperplasia and dysplasia in pancreas represent precursor lesions for pancreatic cancer. METHODS： We examined expression of Ki-67, CEA, p53, and K-ras, in the surgical specimens of pancreas with adenocarcinomas （n = 11） and chronic pancreatitis （n = 12）. Cellular proliferation was assessed by Ki-67 proliferation index using the proliferation marker Ki-67. In specimens with pancreas cancer, we divided pancreas epithelium into normal （n = 7）, ductal hyperplasia （n = 3）, dysplasia （n = 4）, and cancerous lesion （n = 11） after hematoxylin and eosin staining, Ki-67, and CEA immunohistochemical staining. In cases with chronic pancreatitis, the specimen was pathologically examined as in cases with pancreas cancer, and they were also determined as normal （n = 10）, ductal hyperplasia （n = 4）, or dysplasia （n = 5）. p53 and K-ras expression were also studied by immunohistochemical staining. RESULTS： In pancreatic cancer, the Ki-67 index was 3.73±3.58 in normal site, 6.62±4.39 in ductal hyperplasia, 13.47：1：4.02 in dysplasia and 37.03±10.05 in cancer tissue, respectively. Overall, p53 was positive in normal ducts, ductal hyperplasia, dysplasia, and carcinoma cells in 0 of 14 （0%）, 0 of 7 （0%）, 7 of 9 （78%）, and 10 of 11 （91%）, respectively, and K-ras was positive in 0 of 8 （0%）, 1 of 3 （33%）, 4 of 6 （67%）, 4 of 5 （80%）, respectively. CONCLUSION： Our results favorably support the hypothesis that ductal hyperplasia and dysplasia of the pancreas might be precursor lesions for pancreas cancer. Further evaluation of oncogenes by the molecular study is needed.

Role of endoscopic ultrasound in idiopathic pancreatitis

Recurrent acute pancreatitis(RAP) is defined based on the occurrence of two or more episodes of acute pancreatitis. The initial evaluation fails to detect the cause of RAP in 10%-30% of patients, whose condition is classified as idiopathic RAP(IRAP). Idiopathic acute pancreatitis(IAP) is a diagnostic challenge for gastroenterologists. In view of associated morbidity and mortality, it is important to determine the aetiology of pancreatitis to provide early treatment and prevent recurrence. Endoscopic ultrasound(EUS) is an investigation of choice for imaging of pancreas and biliary tract. In view of high diagnostic accuracy and safety of EUS, a EUS based management strategy appears to be a reasonable approach for evaluation of patients with a single/recurrent idiopathic pancreatitis. The most common diagnoses by EUS in IAP is biliary tract disease. The present review aims to discuss the role of EUS in the clinical management and diagnosis of patients with IAP. It elaborates the diagnostic approach to IAP in relation to EUS and other different modalities. Controversial issues in IAP like when to perform EUS, whether to perform after first episode or recurrent episodes, comparison among different investigations and the latest evidence significance are detailed.