Piyapan Prueksapanich

Endoscopic ultrasound-guided needle-based confocal laser endomicroscopy for diagnosis of solid pancreatic lesions (ENES): a pilot study

Background and study aims: Endoscopic ultrasound-guided needle-based confocal laser endomicroscopy (EUS-nCLE) has been shown to aid in the diagnosis of cystic pancreatic lesions. This is a pilot project to study its findings in patients with solid pancreatic lesions (SPLs) with a prospective single-blinded study design. Methods: Patients with SPLs undergoing trans-gastric EUS fine needle aspiration (EUS-FNA) from July 2013 to March 2014 were prospectively enrolled. The nCLE diagnoses were compared with the final diagnoses. Researchers learned about the EUS-nCLE findings from previously published studies and applied it to diagnose SPLs. In the meantime, the findings were recorded. Results: In total, 22 patients were recruited (mean age 62.7 years, SD 13.8 years; 14 men and eight women). The mean maximal tumor diameter was 36.0 mm (SD 10.9 mm). EUS-nCLE yielded satisfactory images in all patients during the first EUS procedure and diagnosed benign and malignant SPLs in 3 and 19 patients, respectively. Final diagnoses of malignant SPLs were made in 19 patients. Benign SPLs were eventually diagnosed in three patients, with confirmed the cytology and disease stability during the 12-month follow-up period. At the end of the project, based on the results of this current study, EUS-nCLE findings for malignant SPLs were dark clumping with or without dilated vessels (> 40 μm). There were two criteria for diagnosing benign lesions which were white fibrous bands and normal acini cells. The accuracy rate of EUS-nCLE was 90.9 % (20/22). One falsely diagnosed malignant SPL was an inflammatory mass from a recent acute pancreatitis. Another one with a pancreatic neuroendocrine tumor presenting with a symptomatic pseudocyst was incorrectly diagnosed as an inflammatory mass. This was likely from sampling error of the EUS-nCLE probe in an inflammatory area. Only one patient had post EUS-FNA bleeding but did not require a blood transfusion. The inter-observer agreement among three blinded endoscopists was almost perfect (Kappa 0.82). Conclusion: EUS-nCLE is a promising technique for the diagnosis of SPLs with good inter-observer agreement. Study registration‎: TCTR20140402001

Liver Fluke-Associated Biliary Tract Cancer

Cholangiocarcinoma (CCA) is an aggressive cancer arising from epithelial cells of the bile duct. Most patients with CCA have an unresectable tumor at the time of diagnosis. In Western countries, the risk of CCA increases in patients with primary sclerosing cholangitis, whereas liver fluke infection appears to be the major risk factor for CCA in Asian countries. A diagnosis of liver fluke infection often relies on stool samples, including microscopic examination, polymerase chain reaction-based assays, and fluke antigen detection. Tests of serum, saliva and urine samples are also potentially diagnostic. The presence of liver fluke along with exogenous carcinogens magnifies the risk of CCA in people living in endemic areas. The “liver fluke-cholangiocarcinoma” carcinogenesis pathways consist of mechanical damage to the bile duct epithelium, immunopathologic and cellular reactions to the liver fluke’s antigens and excretory/secretory products, liver fluke-induced changes in the biliary tract microbiome and the effects of repeated treatment for liver fluke. A vaccine and novel biomarkers are needed for the primary and secondary prevention of CCA in endemic areas. Importantly, climate change exerts an effect on vector-borne parasitic diseases, and awareness of liver fluke should be enhanced in potentially migrated habitat areas.

Aloe vera attenuated gastric injury on indomethacin-induced gastropathy in rats.

AIM To evaluate the protective effects of Aloe vera on gastric injury in rats with indomethacin (IMN)-induced gastropathy. METHODS Male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control, n = 6) was given distilled water (DW) orally. Group 2 (IMN, n = 6) was given oral IMN (150 mg/kg) dissolved in 5% sodium bicarbonate (NaHCO3 (-)) at time 0 and 4 h. Group 3 (Aloe vera-treated, n = 6) was given oral Aloe vera (150 mg/kg) dissolved in DW and IMN at time 0 and 4 h. Eight hours later, the stomach was removed to determine gastric malondialdehyde (MDA), the number of interleukin (IL)-18 positive stained cells (%) by immunohistochemistry, and for histopathological examination. Then, the serum was collected to determine tumor necrosis factor (TNF)-α and cytokine-induced neutrophil chemoattractant (CINC)-1 by sandwich enzyme linked immunosorbent assay method. RESULTS In the IMN group, serum TNF-α, CINC-1 and gastric MDA were significantly increased when compared to the control group (27.78 ± 1.52 pg/mL vs 85.07 ± 49.11 pg/mL, P = 0.009; 104.55 ± 45.80 pg/mL vs 1054.70 ± 20.38 pg/mL, and 1.74 ± 0.21 nmol/mg vs 9.36 ± 1.07 nmol/mg protein, P = 0.000, respectively). The mean level of TNF-α, CINC-1 and gastric MDA in the Aloe vera-treated group were improved as compared with the IMN group (85.07 ± 49.11 pg/mL vs 35.19 ± 1.61 pg/mL, P = 0.021; 1054.70 ± 20.38 pg/mL vs 813.56 ± 239.04 pg/mL, P = 0.025; and 9.36 ± 1.07 nmol/mg vs 2.67 ± 0.64 nmol/mg protein, P = 0.000, respectively). The number of IL-18 positive stained cells (%) in the gastric epithelial cells of the IMN group was significantly higher than the control group (5.01% ± 3.73% vs 30.67% ± 2.03%, P = 0.000, respectively). In contrast, Aloe vera treatment decreased the number of IL-18 positive stained cells (%) significantly when compared with the IMN group (30.67% ± 2.03% vs 13.21% ± 1.10%, P = 0.000, respectively). Most rats in the IMN group developed moderate to severe gastric inflammation and erosions. The gastric erosions and neutrophil infiltration scores were significantly reduced in the Aloe vera-treated group. CONCLUSION Aloe vera attenuated IMN-induced gastropathy in rats by the reduction of oxidative stress, inflammation, and improvement of gastric histopathology.

Value of probe-based confocal laser endomicroscopy (pCLE) and dual focus narrow-band imaging (dNBI) in diagnosing early squamous cell neoplasms in esophageal Lugol’s voiding lesions

Background and study aims: Lugol’s chromoendoscopy provides excellent sensitivity for the detection of early esophageal squamous cell neoplasms (ESCN), but its specificity is suboptimal. An endoscopy technique for real-time histology is required to decrease the number of unnecessary biopsies. This study aimed to compare the ESCN diagnostic capability of probed-based confocal laser endomicroscopy (pCLE) and dual focus narrow-band imaging (dNBI) in Lugol’s voiding lesions. Patients and methods: Patients with a history of head and neck cancer without dysphagia were recruited. Lugol’s voiding lesions larger than 5 mm were sequentially characterized by dNBI and pCLE by two independent operators. Finally, all lesions larger than 5 mm were biopsied followed by histological analysis, which is considered to be the gold standard in cancer diagnosis. The primary outcomes were the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the accuracy of the two techniques. Results: In total, 44 patients were enrolled with a mean age of 60 years; 80 % were male. Twenty-one Lugol’s voiding lesions larger than 5 mm were detected in 12 patients. Seven lesions (33 %) from four patients were histologically diagnosed as ESCNs (four with high grade dysplasia and three with low grade dysplasia). The other 14 lesions were histologically confirmed as non-neoplastic: active esophagitis, glycogenation with inflammation, acute ulcer, inlet patch, and unremarkable changes. The sensitivity, specificity, PPV, NPV, and accuracy of pCLE vs. dNBI were 83 % vs. 85 %, 92 % vs. 62 %, 83 % vs. 54 %, 92 % vs. 89 %, and 89 % vs. 70 %, respectively (NS). Conclusions: Asymptomatic patients with a history of head and neck cancer underwent Lugol’s chromoendoscopy based ESCN surveillance. Further characterization of the Lugol’s voiding lesions by advanced imaging showed that both pCLE and dNBI provided good sensitivity in diagnosing ESCN, and pCLE tended to provide higher specificity, PPV, and accuracy than dNBI. Perhaps the trend of lower specificity of dNBI in this study was possibly because of the interference from Lugol’s stain on the interpretation of intrapapillary capillary loops (IPCLs). Further study is required to seek a significant difference in the performance of dNBI and pCLE in a larger group of patients.

Persistent duodenal ulcers bleeding in postkidney transplant patient treated by infliximab

A 50-year-old woman with end-stage kidney disease was admitted for a living-donor kidney transplantation. On post-transplantation day 6, she developed antibody-mediated rejection and was treated with plasmapheresis, rituximab and intravenous immunoglobulin. 1 week later, she developed severe upper gastrointestinal bleeding from multiple duodenal ulcers along the bulb and the third part of the duodenum. She underwent 11 sessions of endoscopic and interventional therapies comprised with the combination of various techniques including bipolar coaptation, hemoclipping, band ligation and angiogram with coil embolisation of duodenal branch of gastroduodenal artery. Histopathology showed neither any organism nor any feature of graft-versus-host disease. However, empiric treatments with intravenous proton pump inhibitor and broad-spectrum antibiotics/antifungal were given but failed to heal the ulcer, and bleeding recurred from the new developed ulcers. Finally, a single dose of intravenous infliximab was administered to stop bleeding. The patient responded dramatically with rapid ulcers healing and there was no recurrent bleeding during a 3-month follow-up.

Transcatheter Examination of the Peritoneal Dialysis Catheter with the SpyGlass Direct Visualization System: A New Aid in Diagnosis and Salvation of Ultrafiltration Failure from Partial Catheter Obstruction

Mechanical complications in peritoneal dialysis (PD), including intraluminal clogging of the PD catheter by fibrin, omentum, or blood clot, are major causes of outflow problems and, in rare cases, lead to technical failure. To visualize an intraluminal image of patients undergoing PD with ineffective ultrafiltration (UF), a SpyGlass fiber optic probe was inserted into the catheter, together with SpyBite biopsy forceps, should the removal of clogging materials be needed. Applying these transcatheter devices in 2 PD patients with unexplained UF failure led to the demonstration of omental plugging at the catheter tip in the first patient and demonstration of intraluminal blood clots in the second patient from whom clots were removal successfully. Both patients achieved better UF volume thereafter without procedure-related complications.

Bimodal Chromoendoscopy with Confocal Laser Endomicroscopy for the Detection of Early Esophageal Squamous Cell Neoplasms

Background/Aims This study aimed to evaluate the diagnostic accuracy of dual-focus narrow-band imaging (dNBI) and Lugol’schromoendoscopy (LCE) combined with probe-based confocal laser endomicroscopy (pCLE) to screen for esophageal squamous cell neoplasms (ESCNs) in patients with a history of head and neck cancer. Methods From March to August 2016, dNBI was performed. Next, LCE was performed, followed by pCLE and biopsy. Histology has historically been the gold standard to diagnose ESCN. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of dNBI and LCE adjunct with pCLE were determined. Results Twenty-four patients were included. Ten ESCNs were found in 8 patients (33%). Forty percent of high-graded intraepithelial neoplasias and all low-grade intraepithelial neoplasias were overlooked by dNBI. The sensitivity, specificity, PPV, NPV, and accuracy of dNBI vs. LCE combined with pCLE were 50% vs. 80%, 62% vs. 67%, 36% vs. 44%, 75% vs. 91%, and 83% vs. 70%, respectively. Conclusions The use of dNBI to detect ESCN was suboptimal. LCE with pCLE following dNBI had additional value for detecting esophageal dysplasia not detected by dNBI. The use of pCLE to detect dNBI-missed lesions yielded a high NPV, while pCLE-guided biopsy could reduce the number of unnecessary biopsies.

Reply to Xavier S and colleague: “Hemospray use in upper gastrointestinal bleeding from tumor – is it the answer?”

We appreciated the comments from Dr. Sofia Xavier and colleagues and read their case with great interest. This case is an elderly male patient who presented with acute recurrent tumor bleeding in the pre-pyloric area which was treated with adrenaline injection followed by bipolar coaptation 4 days prior to experiencing recurrent bleeding. Hemospray was applied to the blood clot on the lesion and hemostasis was achieved. The duration of hemostasis control was not described; however, we believed that it would be a temporary effect according to our previous experience [1]. We totally agree that Hemospray may be a promising first-line treatment for upper gastrointestinal bleeding from tumor because no other techniques have proven to be effective [1,2]. However, presence of blood on the lesion is required to activate Hemospray cohesion [3]. The initial endoscopic finding in the current case was Forrest IIa (non-bleeding visible vessel) ulcer in which there was no blood to trigger activation of Hemospray. Therefore, Hemospray might not have been suitable for their case initially. According to either the American [4] or the recent European [5] guideline for management of upper gastrointestinal bleeding, a lesions suspicious for malignancy should be biopsied for pathologic diagnosis regardless of bleeding activity [4,5.] Hemospray may play an important role in that circumstance. Patients with suspected upper gastroinestinal bleeding from cancer may benefit from a biopsy and the temporary hemostasis that could be achieved with Hemospray. Hemospray has several advantages in treatment of upper gastrointestinal bleeding from tumor. First, application of Hemospray is simple and it can be performed easily even in patients with anatomical distortion, as demonstrated in this case. Second, Hemospray did not cause further damage to the friable surface of the bleeding tumor and could also be beneficial even in the presence of thrombocytopenia or coagulopathy. Moreover, the Hemospray powder overlying the surface of the tumor could protect the vulnerable gastric tissue from acid and might provide additional time for tissue healing. In contrast, were a coaptation technic such as bipolar coaptation used, the heat from it could cause further necrosis to the tumor surface, resulting in recurrent bleeding [1]. Finally, Hemospray can applied as many times as needed in case of recurrent bleeding. We would like to recommend using Hemospray as a bridging hemostasis technique when there is obvious blood on the lesion. Practically, it can be used as a firsttier intervention as a bridging hemostatic technique for malignant upper gastrointestinal bleeding. However, it should be followed by further definitive hemostasis.