Background: The WHO classified pancreatic neuroendocrine neoplasms (pNEN) in 2010 as G1, G2, and neuroendocrine carcinoma (NEC), according to Ki67 labeling index (LI). However, the clinical behavior of NEC is still not fully studied. We aimed to clarify the clinicopathological and molecular characteristics of NECs. Methods: We retrospectively evaluated the clinicopathological characteristics, KRAS mutation status, treatment response, and the overall survival of eleven pNEC patients diagnosed between 2001 and 2014 according to the WHO 2010. We subclassified WHO-NECs into well-differentiated (WDNEC) and poorlydifferentiated NEC (PDNEC), the latter further subdivided into large and small cell type. Results: The median Ki67 LI was 69.1% (range, 40% - 95%) and the median tumor size was 35 mm. 11 WHO-NECs were subclassified 4 WDNEC and 7 PDNEC, and further separated PDNEC into 3 large cell and 4 small cell subtypes. Comparisons of WDNEC vs. PDNEC revealed hypervascularity on CT, 50% (2/4) vs. 0% (0/7) (P = 0.109); median Ki67 LI, 46.3% (40% - 53%) vs. 85% (54% - 95%) (P = 0.001); KRAS mutations, 0% (0/4) vs. 85.7% (6/7) (P = 0.015); response rates to platinum-based chemotherapy, 0% (0/2) vs.100% (4/4) (P = 0.067) and median survival, 227 vs. 186 days (P = 0.227). Conclusions: The WHO-NEC category may be composed of heterogeneous disease entities, namely WDNEC and PDNEC. These subgroups tended to exhibit differing Ki67 and KRAS mutation profiles, and distinct response to chemotherapy. Further studies for the re-evaluation of the current WHO 2010 classification is warranted.

BACKGROUND: We evaluated whether the addition of a small dose of ketamine or fentanyl would lead to a reduction in the total dose of propofol consumed without compromising the safety and recovery of patients having endoscopic ultrasonography (EUS). METHODS: A total of 210 adult patients undergoing elective EUS under sedation were included in the study. Patients were randomized into three groups. Patients were premedicated intravenously with normal saline in group 1, 50 µg fentanyl in group 2, and 0.5 mg/kg ketamine in group 3. All patients received intravenous propofol for sedation. Propofol consumption in mg/kg/h was noted. The incidence of hypotension, bradycardia, desaturation, and coughing was noted. The time to achieve a Post Anesthesia Discharge Score (PADS) of 10 was also noted. RESULTS: There were 68 patients in group 1, 70 in group 2, and 72 in group 3. The amount of propofol consumed was significantly higher in group 1 (9.25 [7.3–13.2]) than in group 2 (8.8 [6.8–12.2]) and group 3 (7.6 [5.7–9.8]). Patient hemodynamics and oxygenation were well maintained and comparable in all groups. The time to achieve a PADS of 10 was significantly higher in group 3 compared to the other two groups. CONCLUSIONS: The use of 50 µg fentanyl or 0.5 mg/kg ketamine in a single dose during EUS reduces the dose of propofol required for sedation. However, unlike the addition of fentanyl, the addition of ketamine increased the time to recovery. Thus, 50 µg fentanyl is a good additive to propofol infusion for sedation during EUS to reduce the requirement for propofol without affecting the time to recovery.
Adult ; Anesthesia ; Bradycardia ; Cough ; Endosonography ; Fentanyl ; Hemodynamics ; Humans ; Hypotension ; Incidence ; Ketamine ; Oxygen ; Propofol

Background: The WHO classified pancreatic neuroendocrine neoplasms (pNEN)in 2010 as G1, G2, and neuroendocrine carcinoma (NEC), according to Ki67labeling index (LI). However, the clinical behavior of NEC is still not fully studied.We aimed to clarify the clinicopathological and molecular characteristics ofNECs.Methods: We retrospectively evaluated the clinicopathological characteristics,KRAS mutation status, treatment response, and the overall survival of elevenpNEC patients diagnosed between 2001 and 2014 according to the WHO 2010.We subclassified WHO-NECs into well-differentiated (WDNEC) and poorlydifferentiatedNEC (PDNEC), the latter further subdivided into large and smallcell type.Results: The median Ki67 LI was 69.1% (range, 40% - 95%) and the mediantumor size was 35 mm. 11 WHO-NECs were subclassified 4 WDNEC and 7PDNEC, and further separated PDNEC into 3 large cell and 4 small cell subtypes.Comparisons of WDNEC vs. PDNEC revealed hypervascularity on CT, 50% (2/4)vs. 0% (0/7) (P = 0.109); median Ki67 LI, 46.3% (40% - 53%) vs. 85% (54% -95%) (P = 0.001); KRAS mutations, 0% (0/4) vs. 85.7% (6/7) (P = 0.015); responserates to platinum-based chemotherapy, 0% (0/2) vs.100% (4/4) (P = 0.067) andmedian survival, 227 vs. 186 days (P = 0.227).Conclusions: The WHO-NEC category may be composed of heterogeneousdisease entities, namely WDNEC and PDNEC. These subgroups tended to exhibitdiffering Ki67 and KRAS mutation profiles, and distinct response to chemotherapy.Further studies for the re-evaluation of the current WHO 2010 classification iswarranted.

BACKGROUND: We evaluated whether the addition of a small dose of ketamine or fentanyl would lead to a reduction in the total dose of propofol consumed without compromising the safety and recovery of patients having endoscopic ultrasonography (EUS). METHODS: A total of 210 adult patients undergoing elective EUS under sedation were included in the study. Patients were randomized into three groups. Patients were premedicated intravenously with normal saline in group 1, 50 µg fentanyl in group 2, and 0.5 mg/kg ketamine in group 3. All patients received intravenous propofol for sedation. Propofol consumption in mg/kg/h was noted. The incidence of hypotension, bradycardia, desaturation, and coughing was noted. The time to achieve a Post Anesthesia Discharge Score (PADS) of 10 was also noted. RESULTS: There were 68 patients in group 1, 70 in group 2, and 72 in group 3. The amount of propofol consumed was significantly higher in group 1 (9.25 [7.3–13.2]) than in group 2 (8.8 [6.8–12.2]) and group 3 (7.6 [5.7–9.8]). Patient hemodynamics and oxygenation were well maintained and comparable in all groups. The time to achieve a PADS of 10 was significantly higher in group 3 compared to the other two groups. CONCLUSIONS The use of 50 µg fentanyl or 0.5 mg/kg ketamine in a single dose during EUS reduces the dose of propofol required for sedation. However, unlike the addition of fentanyl, the addition of ketamine increased the time to recovery. Thus, 50 µg fentanyl is a good additive to propofol infusion for sedation during EUS to reduce the requirement for propofol without affecting the time to recovery.

Endoscopic ultrasonography (EUS) combines endoscopy and intraluminal ultrasonography, and allows imaging with a high-frequency transducer over a short distance to generate high-resolution ultrasonographic images. EUS is now a widely accepted modality for diagnosing pancreatobiliary diseases. EUS-guided fine-needle aspiration (EUS-FNA) using a curved linear-array echoendoscope was initially described more than 20 years ago, and since then many researchers have expanded its indications to sample diverse lesions and have also used it for various therapeutic purposes. EUS-guided biliary drainage (EUS-BD) is one of the therapeutic procedures that has been developed using a curved linear-array echoendoscope. Technically, EUS-BD includes rendezvous techniques via transesophageal, transgastric, and transduodenal routes, EUS-guided choledochoduodenostomy (EUS-CDS), and EUS-guided hepaticogastrostomy (EUS-HGS). Published data have demonstrated a high success rate, albeit with a comparatively high rate of nonfatal complications for EUS-CDS and EUS-HGS, and a comparatively low success rate with a low complication rate for the rendezvous technique. At present, these procedures represent an alternative to surgery or percutaneous transhepatic biliary drainage (PTBD) for patients with obstructive jaundice when endoscopic biliary drainage (EBD) has failed. However, these procedures should be performed in centers with extensive experience in linear EUS and therapeutic biliary ERCP. Large prospective studies are needed in the near future to establish standardized EUS-BD procedures as well as to perform controlled comparative trials between EUS-BD and PTBD, between rendezvous techniques and direct-access techniques (EUS-CDS and EUS-HGS), and between EBD and EUS-BD.
Biopsy, Fine-Needle ; Cholangiopancreatography, Endoscopic Retrograde ; Choledochostomy ; Dioxolanes ; Drainage ; Endoscopy ; Endosonography ; Fluorocarbons ; Humans ; Jaundice, Obstructive ; Transducers

Background/Aims: Liver cirrhosis is an important cause of morbidity and mortality globally. Every episode of decompensation and hospitalization reduces survival. We studied the clinical profile and long-term outcomes comparing alcohol-related cirrhosis (ALC) and non-ALC.
Methods: Cirrhosis patients at index hospitalisation (from January 2010 to June 2017), with ≥1 year follow-up were included.
Results: Five thousand and one hundred thirty-eight cirrhosis patients (age, 49.8±14.6 years; male, 79.5%; alcohol, 39.5%; Child-A:B:C, 11.7%:41.6%:46.8%) from their index hospitalization were analysed. The median time from diagnosis of cirrhosis to index hospitalization was 2 years (0.2–10). One thousand and seven hundred seven patients (33.2%) died within a year; 1,248 (24.3%) during index hospitalization. 59.5% (2,316/3,890) of the survivors, required at least one readmission, with additional mortality of 19.8% (459/2,316). ALC compared to non-ALC were more often (P<0.001) male (97.7% vs. 67.7%), younger (40–50 group, 36.2% vs. 20.2%; P<0.001) with higher liver related complications at baseline, (P<0.001 for each), sepsis: 20.3% vs. 14.9%; ascites: 82.2% vs. 65.9%; spontaneous bacterial peritonitis: 21.8% vs. 15.7%; hepatic encephalopathy: 41.0% vs. 25.0%; acute variceal bleeding: 32.0% vs. 23.7%; and acute kidney injury 30.5% vs. 19.6%. ALC patients had higher Child-Pugh (10.6±2.0 vs. 9.0±2.3), model for end-stage liver-disease scores (21.49±8.47 vs. 16.85±7.79), and higher mortality (42.3% vs. 27.3%, P<0.001) compared to non-ALC.
Conclusions One-third of cirrhosis patients die in index hospitalization. 60% of the survivors require at least one rehospitalization within a year. ALC patients present with higher morbidity and mortality and at a younger age.

Background/Aims: High-grade pancreatic intraepithelial neoplasia and invasive pancreatic duc-tal adenocarcinoma ≤10 mm are targets for early detection of pancreatic cancer. However, their imaging characteristics are unknown. We aimed to identify endoscopic ultrasound findings for the detection of these lesions. Methods: Patients diagnosed with high-grade pancreatic intraepithelial neoplasia (n=29), pan-creatic ductal adenocarcinoma ≤10 mm (n=11) (who underwent surgical resection), or benignmain pancreatic duct stenosis (n=20) between January 2014 and January 2021 were retrospectively included. Six features differentiating these lesions were examined by endoscopic ultraso-nography: main pancreatic duct stenosis, upstream main pancreatic duct dilation, hypoechoic areas surrounding the main pancreatic duct irregularities (mottled areas without demarcation or round areas with demarcation), branch duct dilation, prominent lobular segmentation, and atrophy. Interobserver agreement was assessed by two independent observers. Results: Hypoechoic areas surrounding the main pancreatic duct irregularities were observedmore frequently in high-grade pancreatic intraepithelial neoplasia (82.8%) and pancreatic ductal adenocarcinoma ≤10 mm (90.9%) than in benign stenosis (15.0%) (p<0.001). High-grade pan-creatic intraepithelial neoplasia exhibited mottled hypoechoic areas more frequently (79.3% vs 18.9%, p<0.001), and round hypoechoic areas less frequently (3.4% vs 72.7%, p<0.001), than pancreatic ductal adenocarcinoma ≤10 mm. The sensitivity and specificity of hypoechoic areas for differentiating high-grade pancreatic intraepithelial neoplasia, pancreatic ductal adenocarci-noma ≤10 mm, and benign stenosis were both 85.0%, with moderate interobserver agreement. Conclusions The hypoechoic areas surrounding main pancreatic duct irregularities on endo-scopic ultrasound may differentiate between high-grade pancreatic intraepithelial neoplasia, pan-creatic ductal adenocarcinoma ≤10 mm, and benign stenosis (Trial Registration: UMIN Clinical Trials Registry (UMIN000044789).

Neurodegenerative diseases are the consequences of imbalance between the production of oxidative stress and its nullification by cellular defense mechanisms. Hydrogen peroxide (HO), a precursor of deleterious reactive oxygen species, elicits oxidative stress, resulting in severe brain injuries. Bacopa monnieri is well known for its nerve relaxing and memory enhancing properties. The present study was designed to evaluate the protective effects of extracts from Bacopa monnieri against HO induced oxidative stress using a cellular model, neuroblastoma IMR32 cell line. The protective potential of methanolic, ethanolic, and water extracts of B. monnieri (BM-MEx, BM-EEx, and BM-WEx) was evaluated using MTT assay. Although, all the B. monnieri extracts were found to protect cells against HO-mediated stress but BM-MEx showed significantly greater protection. UPLC analysis of BM-MEx revealed various polyphenols, including quercetin, catechin, umbelliferone, and caffeic acid predominance. Further, BM-MEx was found to possess considerable greater neuroprotective potential in comparison to the standard polyphenols such as quercetin, catechin, umbelliferone, and caffeic acid. The levels of antioxidant enzymes were significantly elevated after the pretreatment of BM-MEx and quercetin. The expression levels of oxidative stress markers, such as NF200, HSP70, and mortalin, were significantly alleviated after the pretreatment of BM-MEx as shown by immunofluorescence and RT-PCR. In conclusion, the present study demonstrated the protective effects of BM-MEx, suggesting that it could be a candidate for the development of neuropathological therapeutics.
Antioxidants ; metabolism ; pharmacology ; Bacopa ; chemistry ; Cell Line ; Humans ; Hydrogen Peroxide ; Neuroblastoma ; Neurodegenerative Diseases ; metabolism ; Neuroprotective Agents ; pharmacology ; Oxidative Stress ; drug effects ; Plant Extracts ; pharmacology ; Polyphenols ; analysis ; pharmacology ; Reactive Oxygen Species ; metabolism