Albumin and Neutrophil-to-Lymphocyte Ratio Score in Neoadjuvant Concurrent Chemoradiotherapy for Esophageal Cancer: Comparison With Prognostic Nutritional Index.

BACKGROUND/AIM: Neoadjuvant concurrent chemoradiotherapy (CCRT) for esophageal cancer is often overwhelming due to its toxic effects. This study aimed to establish a prognostic indicator based on pretreatment albumin and neutrophil-to-lymphocyte (NLR) ratio score (ANS) in comparison to the Prognostic Nutritional Index (PNI) in patients with esophageal cancer. PATIENTS AND METHODS: A total of 123 patients who received neoadjuvant CCRT for esophageal cancer were prospectively and consecutively recruited between August 2016 and December 2017 from three medical institutes in Taiwan. Patients were assigned to ANS 0, 1, and 2 groups based on their pretreatment albumin and NLR values. ANS and PNI performances were compared for prediction of survival outcome. RESULTS: Compared with ANS 0 (39 patients) and ANS 1 (51 patients), ANS 2 (33 patients) cases showed worse overall survival (hazard ratio=2.96; 95% confidence interval=1.45-6.05; log-rank p=0.003; hazard ratio=3.79; 95% confidence interval=1.79-8.02, p<0.001, respectively). ANS had better performance in overall survival evaluation and discrimination ability than PNI and individual albumin and NLR. Patients in the ANS 0, 1, and 2 had radiotherapy incompletion rates of 2.6%, 3.9%, and 18.2%, respectively, and chemotherapy incompletion rates of 5.1%, 7.8%, and 30.3%, respectively. Patients in the ANS 2 group were significantly associated with a higher incidence of infection (30.3%) than those in the ANS 0 (10.3%) and ANS 1 groups (9.8%). CONCLUSION: Pre-treatment ANS was significantly associated with CCRT safety profiles, CCRT completion rate, and survival outcome in patients with esophageal cancer with excellent performance compared to PNI and NLR.

Utility of Palliative Prognostic Index in Predicting Survival Outcomes in Patients With Hematological Malignancies in the Acute Ward Setting.

BACKGROUND: The palliative prognostic index (PPI) predicts the life expectancy of patients with terminally ill cancer in hospice settings. This study aimed to evaluate PPI as a prognostic tool for predicting the life expectancy of patients with hematological malignancies admitted to the acute ward. METHODS: A total of 308 patients with hematological malignancies admitted to the hematological ward at a medical center between January 2016 and December 2017 were consecutively enrolled. PPI was scored within 24 h of admission. All patients were categorized into 3 groups by PPI for comparing survival and in-hospital mortality rates. RESULTS: The median survival times were 38.4, 3.6, and 1.1 months for patients with good, intermediate, and poor prognostic group, respectively. The hazard ratio was 2.31 (95% CI 1.59-3.35, p < 0.001) when comparing the intermediate and good prognosis groups, and 3.90 (95% CI 2.52-6.03, p < 0.001) when comparing the poor and good prognosis groups. Forty-five (14.6%) patients died at discharge; in-hospital mortality rates among the good, intermediate, and poor prognostic groups were 9.0%, 23.4%, and 46.4%, respectively. The adjusted odds ratio for in-hospital mortality was 1.96 (95% CI, 0.80-4.82, p = 0.14) and 5.25 (95% CI, 2.01-13.7, p < 0.001) for patients in the intermediate and poor prognostic groups compared to those in the good prognostic group. CONCLUSION: PPI is an accurate prognostic tool for predicting survival times and in-hospital mortality rates in patients with hematological malignancies in an acute ward setting. PPI could assist clinicians in discussing end-of-life issues and in referring patients with hematological malignancies to palliative care.

Endoscopic ultrasound-directed transgastric ERCP (EDGE): a retrospective multicenter study.

BACKGROUND: Endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (ERCP; EDGE) is an alternative to enteroscopy- and laparoscopy-assisted ERCP in patients with Roux-en-Y gastric bypass anatomy. Although short-term results are promising, the long-term outcomes are not known. The aims of this study were: (1) to determine the rates of long-term adverse events after EDGE, with a focus on rates of persistent gastrogastric or jejunogastric fistula; (2) to identify predictors of persistent fistula; (3) to assess the outcomes of endoscopic closure when persistent fistula is encountered. METHODS: This was a multicenter retrospective study involving 13 centers between February 2015 and March 2019. Adverse events were defined according to the ASGE lexicon. Persistent fistula was defined as an upper gastrointestinal series or esophagogastroduodenoscopy showing evidence of fistula. RESULTS: 178 patients (mean age 58 years, 79 % women) underwent EDGE. Technical success was achieved in 98 % of cases (175/178), with a mean procedure time of 92 minutes. Periprocedural adverse events occurred in 28 patients (15.7 %; mild 10.1 %, moderate 3.4 %, severe 2.2 %). The four severe adverse events were managed laparoscopically. Persistent fistula was diagnosed in 10 % of those sent for objective testing (9/90). Following identification of a fistula, 5 /9 patients underwent endoscopic closure procedures, which were successful in all cases. CONCLUSIONS: The EDGE procedure is associated with high clinical success rates and an acceptable risk profile. Persistent fistulas after lumen-apposing stent removal are uncommon, but objective testing is recommended to identify their presence. When persistent fistulas are identified, endoscopic treatment is warranted, and should be successful in closing the fistula.

Predicting Postoperative Events in Patients With Gastric Cancer: A Comparison of Five Nutrition Assessment Tools.

BACKGROUND/AIM: We compared the adequacy of five nutrition assessment tools with respect to their predictive value in patients with locally advanced gastric cancer (GC) receiving radical surgery. PATIENTS AND METHODS: Five nutrition assessment tools-Glasgow prognostic score (GPS), malnutritional universal screening tool (MUST), nutritional risk screening, patient generated subjective global assessment (PG-SGA), and prognostic nutritional index (PNI)-were assessed preoperatively for stage III GC patients. The correlation between postoperative events and nutritional status was further analyzed. RESULTS: Most of the nutritional tools accurately predicted length of hospital stay and grade 3 or higher surgical complications, while only the GPS correlated with 30-day readmission and surgical complications. The PG-SGA performed the poorest among the five tools and failed to predict any postoperative event. CONCLUSION: The application of GPS is recommended as a prognostic index for patients with locally advanced GC prior to radical surgery.

Beta-sitosterol-induced Acute Pancreatitis: A Case Report and Review of the Literature.

While drug-induced pancreatitis from corticosteroids has been well described in the medical literature, the exact mechanism is unclear. We present the first reported case of drug-induced pancreatitis from beta-sitosterol, a naturally occurring plant sterol structurally similar to cholesterol, obtained primarily through Western diet and supplementation. A 57-year-old male with a history of situs inversus and benign prostatic hyperplasia presented from an outside facility with a two-day history of worsening epigastric pain radiating to the right upper quadrant. Lipase was markedly elevated at 572 U/L. CT scan and ultrasound of the abdomen were remarkable for acute pancreatitis with acute necrotic collections and normal appearing gallbladder and bile ducts without the presence of gallstones. The patient was managed with aggressive intravenous hydration and supportive management and had resolution of symptoms. At his follow-up appointment, the patient disclosed that he had started a new herbal supplement, beta-sitosterol, on the morning after his symptoms began. Abdominal magnetic resonance cholangiopancreatography obtained at follow-up appointment showed interval resolution of pancreatitis and normal biliary anatomy. In the absence of classical risk factors for acute pancreatitis, a diagnosis of drug-induced pancreatitis secondary to beta-sitosterol was made. The patient was advised to avoid beta-sitosterol, and thus continued to remain asymptomatic. We describe the first reported case of drug-induced pancreatitis from beta-sitosterol, a common phytosterol found in many over the counter supplements worldwide. After a thorough workup to exclude other causes, our case demonstrates consistent resolution of symptoms and pancreatic enzymes along with normal imaging following discontinuation of the offending agent.

Endoscopic ultrasound-guided drainage of pancreatic walled-off necrosis using 20-mm versus 15-mm lumen-apposing metal stents: an international, multicenter, case-matched study.

BACKGROUNDS: Endoscopic ultrasound (EUS)-guided placement of lumen-apposing metal stents (LAMSs) has gained popularity for the treatment of pancreatic walled-off necrosis (WON). We compared the 20-mm and 15-mm LAMSs for the treatment of symptomatic WON in terms of clinical success and adverse events. METHODS: We conducted a retrospective, case-matched study of 306 adults at 22 tertiary centers from 04/2014 to 10/2018. A total of 102 patients with symptomatic WON who underwent drainage with 20-mm LAMS (cases) and 204 patients who underwent drainage with 15-mm LAMS (controls) were matched by age, sex, and drainage approach. Conditional logistic regression analysis was performed to compare clinical success (resolution of WON on follow-up imaging without reintervention) and adverse events (according to American Society for Gastrointestinal Endoscopy criteria). RESULTS: Clinical success was achieved in 92.2 % of patients with 20-mm LAMS and 91.7 % of patients with 15-mm LAMS (odds ratio 0.92; P = 0.91). Patients with 20-mm LAMS underwent fewer direct endoscopic necrosectomy (DEN) sessions (mean 1.3 vs. 2.1; P < 0.001), despite having larger WON collections (transverse axis 118.2 vs. 101.9 mm, P = 0.003; anteroposterior axis 95.9 vs. 80.1 mm, P = 0.01). There was no difference in overall adverse events (21.6 % vs. 15.2 %; P = 0.72) and bleeding events (4.9 % vs. 3.4 %; P = 0.54) between the 20-mm and 15-mm LAMS groups, respectively. CONCLUSIONS: The 20-mm LAMS showed comparable clinical success and safety profile to the 15-mm LAMS, with the need for fewer DEN sessions for WON resolution.

The EDGI new take on EDGE: EUS-directed transgastric intervention (EDGI), other than ERCP, for Roux-en-Y gastric bypass anatomy: a multicenter study.

Background and study aims Indications for accessing the duodenum, and/or excluded stomach in Roux-en-Y gastric bypass (RYGB) patients extend beyond diagnosis and treatment of pancreaticobiliary maladies. Given the high technical and clinical success of EUS-directed transgastric ERCP (EDGE) in RYGB anatomy, we adopted this transgastric (anterograde) approach to evaluate and treat luminal and extraluminal pathology in and around the excluded gut in RYGB patients. EUS-directed transgastric intervention ("EDGI"), other than ERCP, is the terminology we have chosen to describe this heterogenous group of transgastric diagnostic and/or interventional endoscopic procedures (transgastric interventions) performed via a lumen-apposing mental stent (LAMS) in select patients with RYGB. Patients and methods A multicenter (n = 4), retrospective study of RYGB patients with suspected luminal or extraluminal pathology, in or around the duodenum and/or excluded stomach, underwent EDGI using LAMS between December 2015 and January 2019. Results A total of 14 patients (78.6 % women; mean age, 55.7 + 12.4 years) underwent EDGI via LAMS. Technical and clinical success rates of EDGI were 100 %. The most common transgastric interventions were diagnostic EUS of extraluminal pathology (n = 6, 42.7 %) and endoscopic biopsy of gastroduodenal luminal abnormalities (n = 5, 35.7 %). Two moderate-severity adverse events due to LAMS maldeployment occurred during EUS-JG creation (14.3 %), and each instance was successfully rescued with a bridging stent. Conclusions A variety of gastroduodenal luminal and extraluminal disorders in RYGB patients can be effectively diagnosed and managed using EDGI via LAMS.

Use of Lumen-Apposing Stents for the Treatment of Postsurgical Fluid Collections: A Case Series and a Review of Literature.

Lumen-apposing metal stents (LAMS) use in gastrointestinal endoscopy has been on the rise for various indications for the last few years. Currently, LAMS is a well-established treatment for post-pancreatitis peri-pancreatic fluid collections and walled-off necrosis (WON), but it is still not a standard of care in the treatment of post-surgical fluid collections (PSFC). Most of the earlier studies for treatment of PSFC utilized double pigtail plastic stents (DPS). We present a series of 3 cases where LAMS was successfully used for PSFC drainage. The cases include a patient with perigastric abscess after Whipple's procedure, a case of peri-pancreatic collection after distal pancreatectomy, and a patient with peri-pancreatic fluid collection after right partial hepatectomy and splenectomy due to lacerations from a motor vehicle accident.

Leaky Ca2+ release channel/ryanodine receptor 2 causes seizures and sudden cardiac death in mice.

The Ca2+ release channel ryanodine receptor 2 (RyR2) is required for excitation-contraction coupling in the heart and is also present in the brain. Mutations in RyR2 have been linked to exercise-induced sudden cardiac death (catecholaminergic polymorphic ventricular tachycardia [CPVT]). CPVT-associated RyR2 mutations result in "leaky" RyR2 channels due to the decreased binding of the calstabin2 (FKBP12.6) subunit, which stabilizes the closed state of the channel. We found that mice heterozygous for the R2474S mutation in Ryr2 (Ryr2-R2474S mice) exhibited spontaneous generalized tonic-clonic seizures (which occurred in the absence of cardiac arrhythmias), exercise-induced ventricular arrhythmias, and sudden cardiac death. Treatment with a novel RyR2-specific compound (S107) that enhances the binding of calstabin2 to the mutant Ryr2-R2474S channel inhibited the channel leak and prevented cardiac arrhythmias and raised the seizure threshold. Thus, CPVT-associated mutant leaky Ryr2-R2474S channels in the brain can cause seizures in mice, independent of cardiac arrhythmias. Based on these data, we propose that CPVT is a combined neurocardiac disorder in which leaky RyR2 channels in the brain cause epilepsy, and the same leaky channels in the heart cause exercise-induced sudden cardiac death.