Dysphagia with recurrent severe aspiration due to cervical diffuse idiopathic skeletal hyperostosis (Forestier's disease).

Dysphagia is a common symptom in patients presenting to the gastroenterologist. However, extraluminal causes of dysphagia may be missed by endoluminal diagnosis alone. This case report presents a 72-year-old man with slowly progressive dysphagia that occurred with the ingestion of certain solid foods and was intermittently associated with severe aspiration. Esophagogastroduodenoscopy and barium swallow study were both normal. However, a conventional x-ray and computed tomography (CT) scan of the neck revealed diffuse idiopathic skeletal hyperostosis (Forestier's disease) of the anterior cervical spine (C2-C7). Fiber endoscopic evaluation of swallowing (FEES) revealed functionally incomplete emptying of the oral cavity during swallowing, and the patient reported dysphagia score (EAT-10) was 23 (normal < 3). Surgical removal of the hyperostosis (C3-C6) resulted in immediate and sustained improvement in dysphagia at 3 months.

Digital cholangioscopy: the diagnostic yield and impact on management of patients with biliary stricture.

OBJECTIVES: Biliary strictures frequently present a diagnostic challenge. The aim of this study was to evaluate the impact of digital single-operator cholangioscopy (DSOC) on subsequent treatment of patients with biliary stricture. METHODS: Consecutive patients undergoing DSOC for biliary stricture were enrolled. Gold standard for final diagnosis included histology from surgical resection. In patients without surgery, clinical evaluation methods and repeated imaging studies were used for comparison of DSOC findings and final diagnosis. Patients were followed-up prospectively focusing on subsequent treatment. RESULTS: Among 30 enrolled patients, final diagnosis was malignant in 13 (43%) and benign in 17 (57%). The sensitivity and specificity of visual impression in diagnosing malignant stricture were 100% (95% CI: 75 - 100) and 76% (95% CI: 50 - 93), respectively. The sensitivity and specificity for biopsy were 92% (95% CI: 62 - 100) and 100% (95% CI: 78 - 100), respectively. One (3%) case of complicating cholangitis with fatal outcome occurred. Final treatment included surgery in 7 (23%), endoscopy in 18 (60%) and chemotherapy in 3 (10%) of patients. CONCLUSIONS: In this study, favorable operating characteristics of DSOC were confirmed. Absolute negative predictive value of visual impression provided reassurance to patients with benign strictures who avoided unnecessary surgery in 53%. One (3%) case of cholangitis with fatal outcome occurred.

Promoter methylation of Wnt-antagonists in polypoid and nonpolypoid colorectal adenomas.

BACKGROUND: Nonpolypoid adenomas are a subgroup of colorectal adenomas that have been associated with a more aggressive clinical behaviour compared to their polypoid counterparts. A substantial proportion of nonpolypoid and polypoid adenomas lack APC mutations, APC methylation or chromosomal loss of the APC locus on chromosome 5q, suggesting the involvement of other Wnt-pathway genes. The present study investigated promoter methylation of several Wnt-pathway antagonists in both nonpolypoid and polypoid adenomas. METHODS: Quantitative methylation-specific PCR (qMSP) was used to evaluate methylation of four Wnt-antagonists, SFRP2, WIF-1, DKK3 and SOX17 in 18 normal colorectal mucosa samples, 9 colorectal cancer cell lines, 18 carcinomas, 44 nonpolypoid and 44 polypoid adenomas. Results were integrated with previously obtained data on APC mutation, methylation and chromosome 5q status from the same samples. RESULTS: Increased methylation of all genes was found in the majority of cell lines, adenomas and carcinomas compared to normal controls. WIF-1 and DKK3 showed a significantly lower level of methylation in nonpolypoid compared to polypoid adenomas (p < 0.01). Combining both adenoma types, a positive trend between APC mutation and both WIF-1 and DKK3 methylation was observed (p < 0.05). CONCLUSIONS: Methylation of Wnt-pathway antagonists represents an additional mechanism of constitutive Wnt-pathway activation in colorectal adenomas. Current results further substantiate the existence of partially alternative Wnt-pathway disruption mechanisms in nonpolypoid compared to polypoid adenomas, in line with previous observations.

Cap-assisted water immersion for minimal sedation colonoscopy: prospective, randomized, single-center trial.

BACKGROUND AND AIM: Water immersion insertion is able to reduce discomfort and need for sedation during colonoscopy. A cap attached to the colonoscope tip may improve insertion during air insufflation colonoscopy. According to several reports, both techniques alone may result in higher detection of neoplastic lesions. Our study was designed to evaluate the efficacy of cap-assisted water immersion compared to water immersion colonoscopy in minimally sedated patients. METHODS: A total of 208 consecutive outpatients were randomized to either cap-assisted water immersion (Cap Water) or water immersion colonoscopy (Water). The primary endpoint was cecal intubation time. RESULTS: Cecal intubation time was 6.9 ± 2.9 min in Cap Water and 7.4 ± 4.2 min in the Water arm (P = 0.73). Success rate of minimal sedation colonoscopy was equal in both groups (92.9%, P = 1.00). From the endoscopist's point of view, there were non-significant trends towards lower discomfort (P = 0.06), less need for abdominal compression (P = 0.06) and lower difficulty score (P = 0.05) during Cap Water colonoscopy. Adenoma detection rate was similar in both arms (44% in Cap Water vs 45% in the Water group, P = 0.88). There were no complications recorded in the present study. CONCLUSIONS: In comparison with water immersion without cap, cap-assisted water immersion colonoscopy was not able to shorten the cecal intubation time. However, it has the possibility of reducing patient discomfort and difficulty of colonoscope insertion. Potential impact on improved detection of neoplastic lesions has to be evaluated by further studies.

Isolated Gastric Metastases of Pancreatic Ductal Adenocarcinoma following Radical Resection-Impact of Endosonography-Guided Fine Needle Aspiration Tract Seeding.

BACKGROUND: Endosonography-guided fine needle aspiration biopsy (EUS-FNA)-associated metachronous gastric seeding metastases (GSM) of pancreatic ductal adenocarcinoma (PDAC) represent a serious condition with insufficient evidence. METHODS: Retrospective analysis of PDAC resections with a curative-intent, proven pathological diagnosis of PDAC, preoperative EUS-FNA and post-resection follow-up of at least 60 months. The systematic literature search of published data was used for the GSM growth evaluation using Pearson correlation and the linear regression analyses. RESULTS: The inclusion criteria met 59/134 cases, 16 (27%) had retained needle tract (15 following distal pancreatectomy, 1 following pylorus-sparing head resection). In total, 3/16 cases (19%) developed identical solitary GSM (10-26th month following primary surgery) and were radically resected. A total of 30 published cases of PDAC GSM following EUS-FNA were identified. Lesion was resected in 20 distal pancreatectomy cases with complete information in 14 cases. A correlation between the metastasis size and time (r = 0.612) was proven. The regression coefficient b = 0.72 expresses the growth of 0.72 mm per month. CONCLUSIONS: The GSM represent a preventable and curable condition. A remarkably high number of GSM following EUS-FNA was identified, leading to follow-up recommendation of EUS-FNA sampled patients. Multimodal management (gastric resection, adjuvant chemotherapy) may prolong survival.

High-frequency ultrasound probe sonography staging for colorectal neoplasia with superficial morphology: its utility and impact on patient management.

BACKGROUND: This prospective study aimed to evaluate the impact of high-frequency ultrasound probe sonography (HFUPS) staging on the management of patients with superficial colorectal neoplasia (SCN) as determined by the endoscopic characteristics of lesions. METHODS: Consecutive patients referred for endoscopic treatment of nonpedunculated SCN were enrolled in this study. A lesion was considered high risk if a depressed area or invasive pit pattern was present. The gold standard for final staging included histology from endoscopic or surgical resection. The impact on treatment was defined as any modification of the therapeutic algorithm based on the result of the HFUPS examination compared with that based on endoscopy alone. RESULTS: In this study, 48 lesions in 48 patients were evaluated. Of these, 28 (58%) were considered high risk, and the remaining 20 (42%) were regarded as low risk. A total of seven lesions (15%) that could not be examined with HFUPS and another non-neoplastic lesion were excluded from final analysis. For the remaining 40 lesions, the overall accuracy of the HFUPS examination to predict the correct T-stage was 90% (95% confidence interval [CI], 77-96%). The HFUPS examination had a positive impact on the treatment of 0 low-risk and 11 high-risk (42%) lesions. CONCLUSION: The impact of HFUPS on the treatment of SCN depends on their endoscopic characteristics. It is negligible for low-risk SCNs, and these lesions can be treated on the basis of their endoscopic appearance alone. Nevertheless, compared with endoscopy alone, HFUPS changed the subsequent therapeutic approach in a positive way for up to 42% of high-risk lesions, including those with a depressed component and an invasive pit pattern. These endoscopic features can therefore be recommended as the entry criteria for an HFUPS examination.

Endoscopic ultrasound-guided fine needle aspiration of pancreatic masses: the utility and impact on management of patients.

OBJECTIVE: It is controversial whether endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is beneficial in all patients with suspected pancreatic cancer. The aim of this study was to assess diagnostic yield, safety and impact of EUS-FNA on management of patients with solid pancreatic mass. MATERIAL AND METHODS: Consecutive patients undergoing EUS-FNA of solid pancreatic mass were enrolled. Gold standard for final diagnosis included histology from surgical resection. In patients without surgery, clinical evaluation methods and repeated imaging studies were used for the comparison of initial cytology and final diagnosis. Patients were followed-up prospectively focusing on subsequent treatment. RESULTS: Among 207 enrolled patients, final diagnosis was malignant in 163 (78.6%) and benign in 44 (21.4%). The sensitivity, specificity and accuracy of EUS-FNA in diagnosing pancreatic cancer were 92.6% (95% CI: 87.20-95.96), 88.6% (95% CI: 74.64-95.64) and 91.8% (95% CI: 87.24-94.81), respectively. No major and five (2.4%) minor complications occurred. Of 151 true-positive patients by EUS-FNA, 57 (37.7%) were surgically explored, of whom 28 (49.1%) underwent resection. Ten of 12 patients with false-negative cytology were explored based on detection of mass on EUS, of whom two had a delay due to false-negative cytology without curative treatment. From the whole study cohort, EUS-FNA had positive and negative impacts on subsequent management in 136 (65.7%) and 2 (0.9%) patients, respectively. CONCLUSIONS: EUS-FNA provides accurate diagnosis in 92% and has positive therapeutic impact in two-thirds of patients with solid pancreatic mass. Despite negative cytology, surgical exploration is recommended in clinical suspicion for pancreatic cancer and solid mass on EUS.

Endosonography-Guided Fine-Needle Aspiration versus "Key-Hole Biopsy" in the diagnostics of upper gastrointestinal subepithelial tumors. A prospective randomized interventional study.

BACKGROUND: The management and prognosis of subepithelial tumors (SETs) of the upper gastrointestinal tract depend on the correct preoperative evaluation, including tissue diagnosis in selected cases. Several methods providing deep tissue sampling for cytological and/or histological examinations have been described but their diagnostic yield and precise position in the diagnostic algorithm remain to be established. This prospective randomized study aims to compare the Endosonography-Guided Fine-Needle Aspiration (EUS-FNA) to Key-Hole Biopsy (KHB) in cytological or histological diagnostics of upper gastrointestinal SETs. PATIENTS AND METHODS: This study was conducted in a single tertiary endoscopy center in Ostrava, Czech Republic between November 2010 and October 2015. Patients with endoscopically detected SETs of the upper gastrointestinal tract with a diameter ≥ 2 cm, were randomized to either the EUS-FNA with 22G needle, or to the Key Hole biopsy (forceps biopsy through mucosal incision) groups. The main study outcomes were success rate of tissue diagnostics and, in the cases of Gastrointestinal Stromal Tumours (GIST), possibility of determining mitotic activity. A cross-over examination was performed in situations where the first method had failed. RESULTS: A total of 46 consecutive patients were randomized. Of these, 24 (52%) and 22 (48%) were randomized to EUS-FNA group and KHB arm, respectively. 5 SETs (11%) were detected in the esophagus, 40 (87%) in the stomach and 1 (2%) in the duodenum. The definitive diagnosis was established by the first sampling method in 42 (91%) patients, including 22 (92%) in the EUS-FNA group and 20 (91%) in the KHB group (P=0.999), and after a cross-over in another 3 (7%) patients. The most prevalent SET was GIST (70%). Although some mitotic activity could be observed in 11 patients, the mitotic index could be diagnosed in none of them. Of a total of 20 surgically treated patients, preoperative and postoperative tissue diagnosis corresponded in 19/20 (95%) cases, including 100% in FNA group and 91% in KHB group (P=0.999). No adverse events of tissue sampling occurred in the study. CONCLUSIONS: Deep tissue sampling by EUS-FNA and KHB are equally effective in the diagnostics of SETs of the upper gastrointestinal tract ≥ 2 cm. However, neither EUS-FNA nor KHB provided adequate tissue sample to determine mitotic index. TRIAL REGISTRATION: Clinicaltrials.gov (NCT02025244).

Laterally spreading tumors--experience based on 138 consecutive cases.

BACKGROUND/AIMS: Laterally spreading tumors (LST) are flat elevated neoplastic lesions with diameters equal to or greater than 10 mm. The treatment results of 138 lesions in 131 patients are presented here as a part of a retrospective analysis. METHODOLOGY: Two gastroenterology centers participated in the study in the period from 1/2002-12/2006. During colonoscopy, each superficial lesion was classified according to the Paris endoscopic classification. Endoscopic mucosal resection (EMR) lift and cut was employed. Treatment was considered successful when both endoscopic and histo-pathological criteria of complete resection were fulfilled. RESULTS: A total of 138 LST in 131 patients were diagnosed. Average LST diameter was 25 mm. A total of 5 (3.6%) lesions in 4 patients were referred for primary surgery. One patient was treated with argon plasma coagulation only. EMR was attempted for 132/138 (95.7%) of all LST and was successful in 125 (90.6%) cases. Complications occured in 16/132 (12.1%) patients. Severe complications, defined as decession, emergency surgery, emergency endoscopy and transfusion of eryhrocyte concentrate occured in 5/132 (3.8%). One (0.7%) 69 year-old-male patient died on the third day following EMR due to complications of acute myocardial infarction. CONCLUSION: LST lesions could be efficiently treated with EMR lift and cut method with a reasonable rate of complications.

Local residual neoplasia after endoscopic treatment of laterally spreading tumors during 15 months of follow-up.

BACKGROUND: Among superficial neoplastic lesions of the colon and rectum, a laterally spreading tumor (LST) is a flat elevated type at least 10 mm in size. It can be treated by conventional endoscopic resection (CER). Nevertheless, local residual neoplasia (LRN) may occur during follow-up. The aim of this prospective study was to evaluate the occurrence of LRN and the risk factors for its presence. METHODS: Consecutive patients referred for CER of an LST were included. Follow-up colonoscopies were performed after 3 and 15 months. LRN was defined histologically as the presence of neoplastic tissue in the post-CER site. RESULTS: Of a total of 127 patients with 127 lesions, follow-up could not be completed in 48 (37.8%). Of the remaining 79 (62.2%) patients (64.6% men, mean age 66.1±9.7 years), 63 (79.7%) were negative and 16 (20.3%) were positive for the presence of LRN after 15 months. Of 62 (78.5%) patients without LRN after 3 months, 55 (88.7%) remained negative after 15 months. Of 17 (21.5%) patients with LRN after 3 months, eight (47.1%) were negative after 15 months. In a multivariate analysis, LST size of at least 20 mm was found to be a significant risk factor after 3 months (odds ratio, 5.837; 95% confidence interval 1.199-28.425; P=0.029). After 15 months, the only significant risk factor was the presence of LRN observed after 3 months (odds ratio, 6.0; 95% confidence interval, 1.793-20.073; P=0.004). CONCLUSION: This prospective study shows that the occurrence of LRN is frequent and its treatment is less effective than reported previously. These are important limitations of CER and should be taken into consideration for the management of patients with LSTs.

Combination of water immersion and carbon dioxide insufflation for minimal sedation colonoscopy: a prospective, randomized, single-center trial.

OBJECTIVE: Water immersion insertion and carbon dioxide (CO2) insufflation, as alternative colonoscopic techniques, are able to reduce patient discomfort during and after the procedure. We assessed whether the combination of water immersion and CO2 insufflation is superior in efficacy and patient comfort to other colonoscopic techniques. METHODS: In a prospective, randomized study, a total of 420 patients were randomized to either water immersion insertion and CO2 insufflation during withdrawal (water/CO2), water insertion and air insufflation during withdrawal (water/air), CO2 insufflation during both insertion and withdrawal (CO2/CO2), or air insufflation during both insertion and withdrawal (air/air). The main outcome was the success of minimal sedation colonoscopy, which was defined as reaching the cecum without switching to another insertion method and without additional sedation beyond the initial 2 mg of midazolam. Patient comfort during and after the procedure was assessed. RESULTS: A total of 404 patients were analyzed. The success rate of minimal sedation colonoscopy in the water insertion arm (water/CO2 and water/air) was 97% compared with 83.3% in the gas insertion arm (CO2/CO2 and air/air; P<0.0001). Intraprocedural pain and bloating were significantly lower in the water/CO2 group than in all other groups. Patient discomfort in the water/CO2 group during 24 h after the procedure was comparable with that in the CO2/CO2 group and significantly lower than that in the air groups (water/air and air/air). No complications were recorded during the study. CONCLUSION: The combination of water immersion and CO2 insufflation appears to be an effective and safe method for minimal sedation colonoscopy. Overall patient discomfort was significantly reduced compared with that in other techniques.

Chromosome 5q loss in colorectal flat adenomas.

PURPOSE: Flat adenomas are a subgroup of colorectal adenomas that have been associated with a more aggressive clinical behavior compared with their polypoid counterparts. Here, we aimed to compare one of the molecular changes most explicitly associated with adenoma to carcinoma progression, that is, chromosomal instability, between flat and polypoid colorectal adenomas. EXPERIMENTAL DESIGN: Consecutive series of 83 flat and 35 polypoid adenomas were analyzed for DNA copy number changes using a high-resolution array comparative genomic hybridization platform, microsatellite instability (MSI) status, and for mutations in the adenomatous polyposis coli (APC) gene. Immunohistochemical stainings for CD3, CD8, and FoxP3 expression were carried out. RESULTS: Patterns of DNA copy number changes differed between the two phenotypes, with significantly more frequent loss of 5q14.3 and 5q15-q31.1 in flat adenomas, whereas losses of 1p36.32-p35.3, 10q25.3, 17p12, and chromosome 18 were more frequent in polypoid adenomas (false discovery rate < 0.2). MSI was observed in one flat adenoma. As the 5q15-q31.1 region harbors the APC locus, APC mutation status was investigated, showing significantly less mutations in flat adenomas (P = 0.04). An initial exploration of a possible association of 5q loss with inflammation indicated that tumor-infiltrating lymphocytes were more abundant in the stroma of flat adenomas compared with that of polypoid adenomas. CONCLUSION: Flat and polypoid adenomas have partially distinct chromosomal profiles, consistent with differences in the biology underlying these phenotypes. Alterations more specific to flat adenomas, in particular 5q loss, may be associated with inflammation.

Comprehensive mutation analysis in colorectal flat adenomas.

BACKGROUND: Flat adenomas are a subgroup of colorectal adenomas that have been associated with a distinct biology and a more aggressive clinical behavior compared to their polypoid counterparts. In the present study, we aimed to compare the mutation spectrum of 14 cancer genes, between these two phenotypes. METHODS: A consecutive series of 106 flat and 93 polypoid adenomas was analyzed retrospectively for frequently occurring mutations in "hot spot" regions of KRAS, BRAF, PIK3CA and NRAS, as well as selected mutations in CTNNB1 (ß-catenin), EGFR, FBXW7 (CDC4), PTEN, STK11, MAP2K4, SMAD4, PIK3R1 and PDGFRA using a high-throughput genotyping technique. Additionally, APC was analyzed using direct sequencing. RESULTS: APC mutations were more frequent in polypoid adenomas compared to flat adenomas (48.5% versus 30.3%, respectively, p = 0.02). Mutations in KRAS, BRAF, NRAS, FBXW7 and CTNNB1 showed similar frequencies in both phenotypes. Between the different subtypes of flat adenomas (0-IIa, LST-F and LST-G) no differences were observed for any of the investigated genes. CONCLUSION: The lower APC mutation rate in flat adenomas compared to polypoid adenomas suggests that disruption of the Wnt-pathway may occur via different mechanisms in these two phenotypes. Furthermore, in contrast to previous observations our results in this large well-defined sample set indicate that there is no significant association between the different morphological phenotypes and mutations in key genes of the RAS-RAF-MAPK pathway.