Zhendong Jin

Assessment of morbidity and mortality associated with EUS-guided FNA: a systematic review

BACKGROUND EUS-guided FNA (EUS-FNA) permits both morphologic and cytologic analysis of lesions within or adjacent to the GI tract. Although previous studies have evaluated the accuracy of EUS-FNA, little is known about the complications of EUS-FNA. Moreover, the frequency and severity of complications may vary from center to center and may be related to differences in individual experience. OBJECTIVE To systematically review the morbidity and mortality associated with EUS-FNA. DESIGN MEDLINE and EMBASE were searched to identify relevant English-language articles. MAIN OUTCOME MEASUREMENTS EUS-FNA-specific morbidity and mortality rates. RESULTS We identified 51 articles with a total of 10,941 patients who met our inclusion and exclusion criteria; the overall rate of EUS-FNA-specific morbidity was 0.98% (107/10,941). In the small proportion of patients with complications of any kind, the rates of pancreatitis (36/8246; 0.44%) and postprocedure pain (37/10,941; 0.34%) were 33.64% (36/107) and 34.58% (37/107), respectively. The mortality rate attributable to EUS-FNA-specific morbidity was 0.02% (2/10,941). Subgroup analysis showed that the morbidity rate was 2.44% in prospective studies compared with 0.35% in retrospective studies for pancreatic mass lesions (P=.000), whereas it was 2.33% versus 5.07% for pancreatic cysts (P=.036). LIMITATIONS Few articles reported well-designed, prospective studies and few focused on overall complications after EUS-FNA. CONCLUSIONS EUS-FNA-related morbidity and mortality rates are relatively low, and most associated events are mild to moderate in severity.

Endoscopic ultrasonography-guided interstitial implantation of iodine 125-seeds combined with chemotherapy in the treatment of unresectable pancreatic carcinoma: a prospective pilot study.

BACKGROUND AND STUDY AIMS Intraoperative and transdermal ultrasonography-mediated brachytherapy has been proved to be effective in postponing the development of abdominal carcinomas. The main purpose of this study was to evaluate the clinical efficacy and safety of endoscopic ultrasonography (EUS)-guided interstitial implantation of radioactive iodine 125 seeds in advanced pancreatic cancer. PATIENTS AND METHODS In total, 22 patients with advanced pancreatic cancer and positive fine-needle aspiration results underwent EUS-guided interstitial implantation of iodine seeds. All enrolled patients received routine gemcitabine-based 5-fluorouracil chemotherapy 1 week after brachytherapy. RESULTS All 22 patients were successfully implanted with 125I seeds via EUS, with a median of 10 seeds and a maximum of 30 seeds per procedure. The median follow-up time of patients was 9.3 months, and the estimated median survival time was 9.0 months (95 % confidence interval 6.7 - 11.3 months). Partial remission was achieved in three cases (13.6 %) during the 4-week period, and disease in 10 patients (45.5 %) remained stable. Cancer finally progressed in 20 patients, all of whom died during 2 years of follow-up. Visual analog scale pain score dropped from 5.07 +/- 2.63 to 1.73 +/- 1.91 ( P< 0.01) 1 week after brachytherapy but increased again to 3.53 +/- 1.51 1 month later ( P< 0.05 vs. baseline). There were no obvious complications following therapy. CONCLUSIONS EUS-guided interstitial implantation of 125I seeds may represent a safe alternative treatment option for locally advanced pancreatic cancer. Our preliminary data suggest improvement in pain, but no long-term survival benefit.

Diagnostic value of mucins (MUC1, MUC2 and MUC5AC) expression profile in endoscopic ultrasound-guided fine-needle aspiration specimens of the pancreas.

Mucins are aberrantly expressed in various malignancies. We immunohistochemistrically tested mucins expression (MUC1, MUC2 and MUC5AC) in EUS‐FNA samples from pancreatic occupying lesions for the diagnostic utility. The prevalence of MUC1, MUC2 and MUC5AC expression in pancreatic cancers were 77.5% (31/40), 10.0% (4/40) and 80.0% (32/40), respectively, and in the benign pancreatic diseases 25% (4/16), 31.3% (5/16) and 43.8% (7/16). MUC1 and MUC5AC significantly overexpressed in pancreatic cancer, and MUC1 negatively related with tumor differentiation degree (p < 0.05). The prevalence of MUC1, MUC2 and MUC5AC expression in pancreatic mucinous neoplasms were 66.7% (12/18), 38.9% (7/18) and 88.9% (16/18), respectively, and in the pancreatic nonmucinous neoplasms 60.5% (23/38), 5.3% (2/38) and 57.9% (22/38). MUC2 and MUC5AC significantly overexpressed in pancreatic mucinous neoplasms, especially MUC2 in benign mucinous neoplasms (p < 0.05). Compared with cytology alone, the combination test of MUC1+cytology, and MUC5AC+cytology could achieve higher sensitivity (85 vs. 65%, 100 vs. 65%) and accuracy (89.3% vs. 73.2%, 91.1% vs. 73.2%) for pancreatic cancer diagnosis; the combination test of MUC2 + cytology, and MUC5AC + cytology could achieve higher sensitivity (77.8% vs. 38.9%, 100% vs. 38.9%), and specificity (97.4% vs. 60.5%, 71.1% vs. 60.5%) accuracy (100% vs. 51.8%, 80.4% vs. 51.8%) for mucinous neoplasm diagnosis. The panel MUC1+/MUC2−/MUC5AC+/ was higher specific in pancreatic cancer diagnosis, as well as MUC1−/MUC2+/MUC5AC+/ in pancreatic mucinous neoplasms. Our observations suggest the mucins expression profile in EUS‐FNA specimens has higher value for the diagnosis of pancreatic cancer and mucinous neoplasms.

Alarm features and age for predicting upper gastrointestinal malignancy in Chinese patients with dyspepsia with high background prevalence of Helicobacter pylori infection and upper gastrointestinal malignancy: an endoscopic database review of 102 665 patients from 1996 to 2006

Objective Patients with dyspepsia with alarm features are suspected of having upper gastrointestinal (GI) malignancy; however, the true value of alarm features in predicting an underlying malignancy for patients with dyspepsia with high background prevalence of Helicobacter pylori infection and upper GI malignancy is uncertain. The aim of the present study was to determine the diagnostic accuracy of alarm features in predicting upper GI malignancy by reviewing an endoscopic database consisting of >100 000 Chinese patients. Methods A retrospective analysis of prospectively collected data was conducted in a single tertiary medical centre. Consecutive patients who underwent oesophagogastroduodenoscopy (OGD) for dyspepsia in 1996–2006 were enrolled. The data including gender, age, symptoms, and endoscopic and pathological findings were analysed. The main outcome measure was the diagnostic accuracy of individual alarm feature. Results 102 665 patients were included in the final analysis. Among all the 4362 patients with malignancy, 52% (2258/4362) had alarm features. Among 15 235 patients who had alarm features, 2258 (14.8%) were found to have upper GI malignancy. The pooled sensitivity and specificity of the alarm features were 13.4% and 96.6%, respectively. Only the feature of dysphagia in patients between 36 and 74 years old had a positive likelihood ratio (PLR) >10 for malignancy prediction, while all other alarm features in other age groups had a PLR <10. Conclusions For uninvestigated Chinese patients with dyspepsia with high background prevalence of H pylori infection and upper GI malignancy, alarm features and age, except for dysphagia in patients between 36 and 74 years old, had limited predictive value for a potential malignancy; therefore, prompt endoscopy may be recommended for these patients. However, less invasive, inexpensive screening methods with high diagnostic yield are still needed to reduce unnecessary endoscopy workload.

A Long-Term Follow-Up Study on Endoscopic Management of Children and Adolescents With Chronic Pancreatitis

OBJECTIVES:Data on therapeutic endoscopic retrograde cholangiopancreatography (ERCP) for chronic pancreatitis (CP) in children and adolescents, especially with long-term follow-up of consequences, are rarely reported. The aim of this study was to determine the long-term follow-up results of therapeutic ERCP for CP in children and adolescents.METHODS:All patients with CP who received therapeutic ERCP at Changhai Hospital from January 1997 to May 2009, with the age at first onset of pain being less than 18.0 years, were included. Attempts were made to contact all adolescents and follow-up data were recorded. Clinical data were assessed before and after every ERCP.RESULTS:Follow-up information was available in 42 (91.3%) of the 46 patients who received therapeutic ERCP. There were 20 boys and 22 girls, with the age at first onset being 11.8±4.5 years. A total of 110 therapeutic ERCP sessions were performed in the 42 patients. The post-ERCP complication rate was 17.3%, including mild and moderate pancreatitis (n=17) and mild cholangitis (n=2). The mean follow-up period of time was 61.4 (range: 24–132) months. Five patients underwent subsequent surgery because of refractory abdominal pain after endotherapy. Of the remaining 37 patients who received therapeutic ERCP alone, abdominal pain improved in 30 (81.1%) patients, and was completely relieved in 24 (64.9%) patients during the period of follow-up.CONCLUSIONS:Therapeutic ERCP may offer long-term improvement in pain in children and adolescents with CP.

EUS-guided celiac ganglion irradiation with iodine-125 seeds for pain control in pancreatic carcinoma: a prospective pilot study

BACKGROUND Celiac plexus neurolysis for the palliative reduction of pain in unresectable pancreatic carcinoma (PC) is safe but provides limited relief. In a previous study, we found that EUS-guided implantation of iodine-125 ((125)I) around the celiac ganglia is a safe procedure and can induce apoptosis of local neurons in a porcine model. OBJECTIVE To evaluate the safety and efficacy of direct celiac ganglion irradiation with (125)I seeds for the relief of moderate to severe pain secondary to unresectable PC. DESIGN Prospective study. SETTING Single, tertiary care referral center. PATIENTS This study enrolled consecutive patients who had moderate to severe pain resulting from biopsy-proven unresectable PC. INTERVENTION All patients underwent EUS-guided direct celiac ganglion irradiation with (125)I seeds. Follow-up was conducted at least once weekly until death. MAIN OUTCOME MEASUREMENTS Blood parameters, Visual Analog Scale (VAS) score, mean analgesic (MS Contin [morphine sulfate]) consumption, and complications were evaluated during follow-up. RESULTS Twenty-three patients with unresectable PC underwent the procedure. The mean number of seeds implanted in the celiac ganglion per patient was 4 (range 2-6). Immediately after the procedure, pain relief and analgesic consumption showed no significant changes compared with preoperative values. Six patients (26%) reported pain exacerbation. Two weeks later, the VAS score and mean analgesic consumption were significantly less than preoperative values. No procedure-related deaths or major complications occurred. LIMITATIONS Uncontrolled study. CONCLUSIONS EUS-guided direct celiac ganglion irradiation with (125)I seeds can reduce the VAS score and analgesic drug consumption in patients with unresectable PC.

Gastroesophageal Reflux Disease Questionnaire (GerdQ) in real‐world practice: A national multicenter survey on 8065 patients

Recently, Gastroesophageal Reflux Disease Questionnaire (GerdQ) has been developed for diagnosis of GERD. However, no study investigated its value in real‐world practice. This study aimed to investigate whether GerdQ can be used for diagnosis of GERD in China.

Occurrence of and risk factors for diabetes mellitus in Chinese patients with chronic pancreatitis.

Objectives: The aim of the study was to determine the occurrence and the risk factors of diabetes mellitus (DM) in Chinese patients with chronic pancreatitis (CP), with particular emphasis on those with endoscopic or surgical therapy for CP. Methods: Four hundred forty-five contacted CP patients in our hospital between January 1, 1997, and July 31, 2007, were followed up. Risk factors for DM were determined in a multivariate analysis after exclusion of 58 patients. Results: The cumulative rate of DM was 51.5% (SD, 8%) at 20 years after the onset of CP and 27.8% (SD, 6%) at 10 years after endotherapy or surgery, without significant difference between the 2 therapies (P = 0.243). The age at the onset of CP (hazard ratio, 1.032; 95% confidential interval, 1.012-1.052), smoking (2.859, 1.448-5.645), chronic pain (0.412, 0.180-0.945), and pancreatic calcifications (2.326, 1.203-4.496) were identified as independent risk factors for developing DM in the patients before any invasive therapy. Smoking (2.203, 1.153-4.209) and distal pancreatectomy (5.412, 2.506-11.690) were the independent risk factors for DM development in patients after invasive therapy. Conclusions: The risk of DM seems to be mainly caused by progression of CP because it increased with older age, absence of chronic pain, and pancreatic calcifications, whereas this risk is influenced by smoking and distal pancreatectomy.

Detection of KRAS gene mutations in endoscopic ultrasound-guided fine-needle aspiration biopsy for improving pancreatic cancer diagnosis.

OBJECTIVES:Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) is a useful tool in the diagnosis of pancreatic masses. Genetic analysis of these samples could increase the sensitivity and specificity of diagnosis. This study aimed to evaluate the usefulness of a novel method for the detection of mutations in the KRAS (Kirsten rat sarcoma-2 virus) gene for the diagnosis of pancreatic cancer.METHODS:EUS-FNABs were performed on 82 patients with pancreatic masses, including 54 cases of pancreatic ductal adenocarcinoma and 28 of non-malignant pancreatic masses. The biopsies were histopathologically and cytopathologically evaluated, and the detection of KRAS gene mutations (codons 12 and 13) was performed through peptide nucleic acid-directed polymerase chain reaction clamping and DNA sequencing.RESULTS:In the pancreatic cancer cases, 88.9% (48/54; 95% confidence interval (CI): 80.5–97.2%) had KRAS mutations, while 61.1% (33/54; 95% CI: 48.1–74.1%) were unequivocally diagnosed by histo/cytopathology. In the indeterminate patients (n=49; diagnosed by EUS-FNA as either insufficient material to make a diagnosis, no malignancy, or suspicion of malignancy), there were 10 cases of pancreatic cancer with low serum carbohydrate antigen 19-9 (CA19-9) (<37 U/l) and 6 of these were KRAS mutations. The sensitivity of detection by KRAS mutations (76.2%) and the combination of KRAS mutations and serum CA19-9 (81%) were significantly higher than for serum CA19-9 alone (52.4%). A logistic regression model showed that the KRAS mutation was significant (odds ratio=5.830; CI: 1.531–22.199, P=0.01), but not serum CA19-9. In the non-malignant pancreatic masses (n=28), KRAS mutations were detected in nine precancerous lesions.CONCLUSIONS:Our method for the detection of KRAS gene mutations may be useful to supplement histo/cytopathologic evaluations for pancreatic cancer, and is superior to serum CA19-9 in EUS-FNAB histo/cytopathology-indeterminate patients. Results warrant further verification in other patient populations.

Endoscopic ultrasound-guided ethanol ablation therapy for tumors.

Endoscopic ultrasonography (EUS) has evolved into a useful therapeutic tool for treating a broad range of tumors since being introduced into clinical practice as a diagnostic modality nearly three decades ago. In particular, EUS-guided fine-needle injection has proven a successful minimally invasive approach for treating benign lesions such as pancreatic cysts, relieving pancreatic pain through celiac plexus neurolysis, and controlling local tumor growth of unresectable malignancies by direct delivery of anti-tumor agents. One such ablative agent, ethanol, is capable of safely ablating solid or cystic lesions in hepatic tissues via percutaneous injection. Recent research and clinical interest has focused on the promise of EUS-guided ethanol ablation as a safe and effective method for treating pancreatic tumor patients with small lesions or who are poor operative candidates. Although it is not likely to replace radical resection of localized lesions or systemic treatment of metastatic tumors in all patients, EUS-guided ablation is an ideal method for patients who refuse or are not eligible for surgery. Moreover, this treatment modality may play an active role in the development of future pancreatic tumor treatments. This article reviews the most recent clinical applications of EUS-guided ethanol ablation in humans for treating pancreatic cystic tumors, pancreatic neuroendocrine tumors, and metastatic lesions.