Early detection of necrosis in low-enhanced pancreatic parenchyma using contrast-enhanced computed tomography was a better predictor of clinical outcomes than pancreatic inflammation: A multicentric cohort study of severe acute pancreatitis.

OBJECTIVES: We aim to assess the early use of contrast-enhanced computed tomography (CECT) of patients with severe acute pancreatitis (SAP) using the computed tomography severity index (CTSI) in prognosis prediction. The CTSI combines quantification of pancreatic and extrapancreatic inflammation with the extent of pancreatic necrosis. METHODS: Post-hoc retrospective analysis of a large, multicentric database (44 institutions) of SAP patients in Japan. The area under the curve (AUC) of the CTSI for predicting mortality and the odds ratio (OR) of the extent of pancreatic inflammation and necrosis were calculated using multivariable analysis. RESULTS: In total, 1097 patients were included. The AUC of the CTSI for mortality was 0.65 (95 % confidence interval [CI:] [0.59-0.70]; p < 0.001). In multivariable analysis, necrosis 30-50 % and >50 % in low-enhanced pancreatic parenchyma (LEPP) was independently associated with a significant increase in mortality, with OR 2.04 and 95 % CI 1.01-4.12 (P < 0.05) and OR 3.88 and 95 % CI 2.04-7.40 (P < 0.001), respectively. However, the extent of pancreatic inflammation was not associated with mortality, regardless of severity. CONCLUSIONS: The degree of necrosis in LEPP assessed using early CECT of SAP was a better predictor of mortality than the extent of pancreatic inflammation.

Postprocedure serum amylase or lipase levels predict postendoscopic retrograde cholangiopancreatography pancreatitis: Meta-analysis of diagnostic test accuracy studies and utility assessment.

OBJECTIVES: We aimed to clarify the clinical utility of measuring serum pancreatic enzymes after endoscopic retrograde cholangiopancreatography (ERCP) for the purpose of predicting post-ERCP pancreatitis (PEP) by a meta-analysis of diagnostic test accuracy studies. METHODS: Studies on the prediction accuracy of PEP by serum amylase or lipase measured at 2, 3, and 4 h after ERCP were collected. A literature search was performed in PubMed and the Cochrane Library database for studies published between January 1980 and March 2023. The quality of individual studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2. Data were analyzed using Meta-DiSc 2.0 software. RESULTS: We searched the databases and identified 20 observational studies (12,313 participants). PEPs were defined according to criteria by Cotton or modified Cotton, revised Atlanta criteria, or the Japanese criteria. Meta-analysis of eight studies (4389 participants) showed a pooled sensitivity of 71.1% (95% confidence interval [CI] 56.1-82.5) and pooled specificity of 91.2% (95% CI 85.9-94.6) for the serum amylase cut-off value at 3 times the upper limit of normal (ULN). Another meta-analysis of five studies (1970 participants) showed a pooled sensitivity of 85.8% (95% CI 61.9-95.7) and pooled specificity of 85.3% (95% CI 81.9-88.1) for the serum lipase cut-off value at 3 times ULN. CONCLUSION: Despite a high risk of bias due to various reference standards, this updated meta-analysis and the utility assessment by a decision tree showed the utility of serum amylase or lipase levels more than 3 times ULN measured 2-4 h after ERCP for predicting PEP.

A prospective multicenter study of endoscopic ultrasound-guided fine needle biopsy using a 22-gauge Franseen needle for pancreatic solid lesions.

BACKGROUND AND AIM: While encouraging data of endoscopic ultrasound (EUS)-guided fine-needle biopsy (EUS-FNB) using a 22-gauge Franseen needle have been reported, large-scale data of per pass and quantitative analyses are still lacking. METHODS: This was a multicenter prospective study of EUS-FNB using the 22-gauge Franseen needle for a pancreatic solid lesion. Cytological and histological analyses per pass were evaluated and semi-quantitative analyses were performed on core tissue and blood contamination. Primary end-point was diagnostic accuracy per session. Prognostic factors were analyzed for diagnostic accuracy, sensitivity, core tissue, and blood contamination. RESULTS: A total of 629 passes were performed in 244 cases at 14 centers between 2018 and 2019. The median tumor size was 29 mm, and the puncture was transduodenal in 43%. The median pass number was 2. Diagnostic accuracy per session, at a first pass, and per pass were 93%, 90%, and 88%. In 198 cases with pancreatic cancer, diagnostic sensitivity per session, at a first pass, and per pass were 94%, 89%, and 89%. The rates of core tissue score of 4 and blood contamination score of 3 were 50% and 47%. The adverse event rate was 1.6%. In the multivariate analysis, tumor size ≤20 mm (odds ratio [OR] of 0.46, P = 0.03), transduodenal puncture (OR of 0.53, P = 0.04), and suction (OR of 0.16, P = 0.01) were associated with lower diagnostic accuracy. CONCLUSIONS: The EUS-FNB using the 22-gauge Franseen needle for pancreatic solid lesions showed high per pass and overall diagnostic accuracy.

Etiology and mortality in severe acute pancreatitis: A multicenter study in Japan.

BACKGROUND/OBJECTIVES: Severe acute pancreatitis (SAP) has a high mortality rate despite ongoing attempts to improve prognosis through a various therapeutic modalities. This study aimed to delineate etiology-based routes that may guide clinical decisions for the treatment of SAP. METHODS: Using data from a recent retrospective multicenter study in Japan, we analyzed the association between clinical outcomes, mainly in-hospital mortality and pancreatic infection, and various etiologies while considering confounding factors. We performed additional multivariate analyses and built decision tree models. RESULTS: The 1097 participating patients were classified into the following groups by etiology: alcohol (n = 436, 39.7%); cholelithiasis (n = 230, 21.0%); idiopathic (n = 227, 20.7%); and others (n = 204, 18.6%). Mortality at hospital discharge was 8.4%, 12.2%, 16.7%, and 16.2% in the alcohol, cholelithiasis, idiopathic, and others groups, respectively. According to multivariable analysis, early enteral nutrition (EN) was significantly associated with reduced in-hospital mortality only in the cholelithiasis group. However, there was a consistent association between age and the need for mechanical ventilation and increased mortality, regardless of etiology. Our decision tree models presented different contributing factors depending on the etiology and patient background. Interaction analysis showed that EN and the use of prophylactic antibiotics may influence these results differently according to etiology. CONCLUSIONS: No study has yet used comprehensive models to investigate etiology-related prognostic factors for SAP; our results can, therefore, be used as a reference for improving clinical decisions.

Large Volume Fluid Resuscitation for Severe Acute Pancreatitis is Associated With Reduced Mortality: A Multicenter Retrospective Study.

BACKGROUND AND AIMS: Although fluid resuscitation is critical in acute pancreatitis, the optimal fluid volume is unknown. The aim of this study is to evaluate the association between the volume of fluid administered and clinical outcomes in patients with severe acute pancreatitis (SAP). METHODS: We conducted a multicenter retrospective study at 44 institutions in Japan. Inclusion criteria were age 18 years or older, and diagnosed with SAP from 2009 to 2013. Patients were stratified into 2 groups: administered fluid volume <6000 and ≥6000 mL in the first 24 hours. We evaluated the association between the 2 groups and clinical outcomes using multivariable logistic regression analysis. The primary outcome was in-hospital mortality. Secondary outcomes included the incidence of pancreatic infection and the need for surgical intervention. RESULTS: We analyzed 1097 patients, and the mean fluid volume administered was 5618±3018 mL (mean±SD), with 708 and 389 patients stratified into the fluid <6000 mL and fluid ≥6000 mL groups, respectively. Overall in-hospital mortality was 12.3%. The fluid ≥6000 mL group had significantly higher mortality than the fluid <6000 mL group (univariable analysis, 15.9% vs. 10.3%; P<0.05). In multivariable logistic regression analysis, administration of ≥6000 mL of fluid within the first 24 hours was significantly associated with reduced mortality (odds ratio, 0.58; P<0.05). No significant association was found between the administered fluid volume and pancreatic infection, or between the volume administered and the need for surgical intervention. CONCLUSIONS: In patients with SAP, administration of a large fluid volume within the first 24 hours is associated with decreased mortality.

Multicenter study of endoscopic preoperative biliary drainage for malignant hilar biliary obstruction: E-POD hilar study.

BACKGROUND AND AIM: Endoscopic nasobiliary drainage (ENBD) is often recommended in preoperative biliary drainage (PBD) for hilar malignant biliary obstruction (MBO), but endoscopic biliary stent (EBS) is also used in the clinical practice. We conducted this large-scale multicenter study to compare ENBD and EBS in this setting. METHODS: A total of 374 cases undergoing PBD including 281 ENBD and 76 EBS for hilar MBO in 29 centers were retrospectively studied. RESULTS: Extrahepatic cholangiocarcinoma (ECC) accounted for 69.8% and Bismuth-Corlette classification was III or more in 58.8% of the study population. Endoscopic PBD was technically successful in 94.6%, and adverse event rate was 21.9%. The rate of post-endoscopic retrograde cholangiopancreatography pancreatitis was 16.0%, and non-endoscopic sphincterotomy was the only risk factor (odds ratio [OR] 2.51). Preoperative re-intervention was performed in 61.5%: planned re-interventions in 48.4% and unplanned re-interventions in 31.0%. Percutaneous transhepatic biliary drainage was placed in 6.4% at the time of surgery. The risk factors for unplanned procedures were ECC (OR 2.64) and total bilirubin ≥ 10 mg/dL (OR 2.18). In surgically resected cases, prognostic factors were ECC (hazard ratio [HR] 0.57), predraiange magnetic resonance cholangiopancreatography (HR 1.62) and unplanned re-interventions (HR 1.81). EBS was not associated with increased adverse events, unplanned re-interventions, or a poor prognosis. CONCLUSIONS: Our retrospective analysis did not demonstrate the advantage of ENBD over EBS as the initial PBD for resectable hilar MBO. Although the technical success rate of endoscopic PBD was high, its re-intervention rate was not negligible, and unplanned re-intervention was associated with a poor prognosis in resected hilar MBO.

Practical prognostic index for survival in patients with unresectable pancreatic cancer treated with gemcitabine or S-1.

BACKGROUND/AIMS: We performed this retrospective cohort study to identify prognostic factors for unresectable pancreatic cancer treated with current standard therapy using gemcitabine (GEM) or S-1 and to stratify patients prior to treatment using a prognostic index (PI). METHODOLOGY: We analyzed 182 patients with unresectable pancreatic cancer, who had received GEM or S-1 as first-line chemotherapy. Factors that contributed to the prognosis were identified by univariate and multivariate analysis using a Cox proportional hazards model. The PI was constructed using the factors identified in the multivariate analysis. RESULTS: By multivariate analysis, performance status (PS), stage, and absolute neutrophil count (ANC) were identified as factors that independently contributed to the prognosis of unresectable pancreatic cancer (P < 0.05). The hazard ratios were 1.69, 3.33, and 1.18, respectively. In addition, PI was calculated using these three factors. Patients were classified into three groups according to the PI values. A significant difference was observed among the survival curves of these three groups (P < 0.05). CONCLUSIONS: We identified three prognostic factors in the population after the introduction of S-1, and have created a simple and useful PI. This index demonstrates the ability to accurately classify advanced pancreatic cancer patients before the start of treatment.

Gastroduodenal Stenting with a Flexible Stent Demonstrates Favorable Clinical Effectiveness despite Gradual Expansion: A Multicenter Prospective Study.

AIMS: This study aimed to evaluate the effectiveness and safety of stenting with a flexible braided self-expandable metal stent (SEMS) for unresectable malignant gastric outlet obstruction (GOO). METHODS: Palliative stenting was prospectively carried out at seven university hospitals between October 2017 and August 2020. All procedures were performed using a flexible branded SEMS of the same brand. The primary endpoint was clinical success rate at 7 days after stenting. Secondary endpoints were procedural success rate, adverse events, recurrent gastric outlet obstruction (RGOO), and patient survival time. RESULTS: Sixty patients were enrolled. The procedural and clinical success rates were 100% and 90%, respectively. RGOO occurred in 15 cases (25%). Adverse events other than RGOO were found in seven cases (12%). The 50% survival time was 75.5 days (range: 52-97 days). Median expansion rates at 1, 3, and 7 days after stenting were 55%, 65%, and 75%, respectively. CONCLUSIONS: A flexible braided stent woven with relatively thin wires was used for malignant GOO. Despite a gradual expansion with slightly lower expansile force, the stent functioned sufficiently well and showed favorable results. Clinical Trials Registry ID: UMIN000029496.

Factors involved in resistance to early treatment of acute cholangitis patients.

BACKGROUND/AIMS: Severity-based treatment is not homogenously effective for acute cholangitis patients and some are resistant to early treatment. We performed a retrospective cohort study involving acute cholangitis patients and analyzed factors strongly associated with resistance to early treatment. METHODOLOGY: The subjects were 94 patients admitted to the Department of Gastroenterology, Showa University Hospital and diagnosed with acute cholangitis. The endpoint was set as the presence or absence of resistance to early treatment. Background and blood test results of the patients immediately after admission were surveyed and significant factors independently contributing to resistance to early treatment were extracted from the surveyed factors employing a logistic regression model. RESULTS: The mean age of the patients was 73.2 ± 11.6 years and 58 were male (61.7%). Jaundice, fever and abdominal pain were observed in 46 (48.9%), 66 (70.2%) and 85 patients (90.4%), respectively. Twenty-eight patients (29.8%) were resistant to early treatment. On multivariate analysis, 3 factors (fever, serum amylase level and systolic blood pressure (below 100 mm Hg)) were extracted as significant factors independently contributing to resistance to early treatment (p<0.05). CONCLUSIONS: If such resistance can be predicted before treatment, appropriate treatment may be selected to shorten the persistence of symptoms, improving the patient's QOL.

Morphological study of the gastrointestinal tract around the ligament of Treitz using upper gastrointestinal radiography: Fundamental data for EUS-guided gastrojejunostomy.

BACKGROUND/PURPOSE: We developed EUS-guided double-balloon occluded gastrojejunostomy (EPASS) for gastric drainage tract obstruction. The success of EPASS depends on the proximity of the stomach and the gastrointestinal (GI) tract near the ligament of Treitz. The aim of this study is to clarify the GI anatomy near the ligament of Treitz. METHODS: One thousand and sixteen cases imaged upper GI radiography using barium were retrospectively evaluated. Morphologically, the GI tract running near the ligament of Treitz was divided in three types: Type I: The 4th portion of the duodenum (D4) approaches the stomach; Type II: D4 does not approach the stomach; Type III: D4 forms a loop to the jejunum. The minimum distance between the stomach and the GI tract near the ligament of Treitz was measured. RESULTS: Based on the morphological classification, 74.6% in the study group was classified in Type I, 22.0% in Type II, and 3.3% in Type III, respectively. The median minimum distance in Type II/III group were significantly longer, compared with the Type I (P < .01). CONCLUSIONS: The GI anatomy near the ligament of Treitz was clarified using upper GI radiography. It is divided into three patterns, and one-fourth of cases may have difficulty in EUS-guided gastrojejunostomy.

Successful and Safe Reinstitution of Chemotherapy for Pancreatic Cancer after COVID-19.

Cancer patients are regarded as highly vulnerable to severe acute respiratory syndrome coronavirus (SARS-CoV)-2. However, little is known regarding how cancer treatments should be restarted for cancer patients after coronavirus disease (COVID)-19. We herein report a pancreatic cancer case in which chemotherapy was able to be reinstituted after COVID-19. The patient was a 67-year-old man diagnosed with pancreatic cancer. On day 7 after first chemotherapy, he was infected with COVID-19. A SARS-CoV-2 test was negative after one month of treatment, and we reinstituted chemotherapy. The patient has received three cycles of chemotherapy without recurrence of COVID-19. It may be feasible to reinstitute chemotherapy for cancer patients after a negative SARS-CoV-2 test.

A case of juvenile eosinophilic cholangitis: Rapid peripheral blood hypereosinophilia after admission leading to diagnosis.

A 15-year-old boy was referred to our hospital with elevated hepatobiliary enzyme levels and jaundice. Magnetic resonance cholangiopancreatography performed at the previous medical facility revealed a stricture of the intrahepatic and extrahepatic bile duct. Computed tomography showed dilatation and wall thickness of the intrahepatic bile ducts. Primary sclerosing cholangitis or cholangiocarcinoma was suspected. Endoscopic retrograde cholangiopancreatography (ERCP) showed stricture in the intrahepatic and extrahepatic bile duct. On admission, the eosinophil count in the peripheral blood was normal; however, rapid hypereosinophilia in the peripheral blood was observed after admission, leading us to suspect eosinophilic cholangitis (EC). A bile duct biopsy showed inflammatory cells and eosinophil infiltration during a second ERCP. The patient was diagnosed with EC based on histopathology.

Impact of Enteral Nutrition Within 24 Hours Versus Between 24 and 48 Hours in Patients With Severe Acute Pancreatitis: A Multicenter Retrospective Study.

OBJECTIVES: In patients with severe acute pancreatitis (SAP), early enteral nutrition (EN) is recommended by major clinical practice guidelines, but the exact timing for the initiation of EN is unknown. METHODS: We conducted a post hoc analysis of the database for a multicenter (44 institutions) retrospective study of patients with SAP in Japan. The patients were classified into 3 groups according to the timing of EN initiation after the diagnosis of SAP: within 24 hours, between 24 and 48 hours, and more than 48 hours. The primary outcome was in-hospital mortality. RESULTS: Of the 1094 study patients, 176, 120, and 798 patients started EN within 24 hours, between 24 and 48 hours, and more than 48 hours after SAP diagnosis, respectively. On multivariable analysis, hospital mortality was significantly better with EN within 48 hours than with more than 48 hours (adjusted odds ratio, 0.49; 95% confidence interval, 0.29-0.83; P < 0.001) but did not significantly differ between the groups with EN starting within 24 hours and between 24 and 48 hours (P = 0.29). CONCLUSIONS: Enteral nutrition within 24 hours may not confer any additional benefit on clinical outcomes compared with EN between 24 and 48 hours.

Prediction of the progression of walled-off necrosis in patients with acute pancreatitis on whole pancreatic perfusion CT.

BACKGROUND/PURPOSE: This study investigated whether measuring pancreatic blood volume (PBV) on whole pancreatic perfusion computed tomography (P-CT) can predict the progression of walled-off necrosis (WON) in patients with acute pancreatitis (AP). METHODS: A single-center, retrospective cohort study was conducted between December 2015 and December 2016. The participants were divided into two groups: 14 patients with WON and 15 patients without WON. PBV was measured within 72 hours after the diagnosis of AP, and the final diagnosis of WON was made by contrast-enhanced CT (CE-CT) or endoscopic ultrasonography (EUS) 4 weeks after the onset of AP. RESULTS: The minimum CT value did not differ significantly between the two groups. On the other hand, the minimum PBV was significantly lower in the WON group than in the without WON group (1.4 (0.9-9.9) vs 19.8 (8.2-21.7) mL/100 mL, respectively; P = .02). The cutoff value of the minimum PBV for WON was 16.5 mL/100 mL (sensitivity 100%, specificity 67%, AUC 0.85; P = .001). CONCLUSIONS: Whole pancreatic P-CT can evaluate pancreatic ischemia visually and quantitatively. The minimum PBV measurement on whole pancreatic P-CT within 72 hours after the diagnosis of AP contributes to the prediction of progression of WON.

Continuous regional arterial infusion versus intravenous administration of the protease inhibitor nafamostat mesilate for predicted severe acute pancreatitis: a multicenter, randomized, open-label, phase 2 trial.

BACKGROUND: Continuous regional arterial infusion (CRAI) of protease inhibitor nafamostat mesilate (NM) is used in the context of predicted severe acute pancreatitis (SAP) to prevent the development of pancreatic necrosis. Although this therapy is well known in Japan, its efficacy and safety remain unclear. METHODS: This investigator-initiated and -driven, multicenter, open-label, randomized, controlled trial (UMIN000020868) enrolled 39 patients with predicted SAP and low enhancement of the pancreatic parenchyma on computed tomography (CT). Twenty patients were assigned to the CRAI group, while 19 served as controls and were administered NM at the same dose intravenously (IV group). The primary endpoint was the development of pancreatic necrosis as determined by CT on Day 14, judged by blinded central review. RESULTS: There was no difference between the CRAI and IV groups regarding the percentages of participants who developed pancreatic necrosis (more than 1/3 of the pancreas: 25.0%, range 8.7-49.1% vs. 15.8%, range 3.4-39.6%, respectively, P = 0.694; more than 2/3 of the pancreas: 20%, range 5.7-43.7% vs. 5.3%, range 0.1-26.0%, respectively, P = 0.341). The early analgesic effect was evaluated based on 24-h cumulative fentanyl consumption and additional administration by intravenous patient-controlled analgesia. The results showed that the CRAI group used significantly less analgesic. There were two adverse events related to CRAI, namely bleeding and splenic infarction. CONCLUSIONS: CRAI with NM did not inhibit the development of pancreatic necrosis although early analgesic effect of CRAI was superior to that of IV. Less-invasive IV therapy can be considered a viable alternative to CRAI therapy.

The Effect of an Invasive Strategy for Treating Pancreatic Necrosis on Mortality: a Retrospective Multicenter Cohort Study.

BACKGROUND: Infected acute necrotic collections (ANC) and walled-off necrosis (WON) of the pancreas are associated with high mortality. The difference in mortality between open necrosectomy and minimally invasive therapies in these patients remains unclear. METHODS: This retrospective multicenter cohort study was conducted among 44 institutions in Japan from 2009 to 2013. Patients who had undergone invasive treatment for suspected infected ANC/WON were enrolled and classified into open necrosectomy and minimally invasive treatment (laparoscopic, percutaneous, and endoscopic) groups. The association of each treatment with mortality was evaluated and compared. RESULTS: Of 1159 patients with severe acute pancreatitis, 122 with suspected infected ANC or WON underwent the following treatments: open necrosectomy (33) and minimally invasive treatment (89), (laparoscopic three, percutaneous 49, endoscopic 37). Although the open necrosectomy group had a significantly higher mortality on univariate analysis (p = 0.047), multivariate analysis showed no significant associations between open necrosectomy or Charlson index and mortality (p = 0.29, p = 0.19, respectively). However, age (for each additional 10 years, p = 0.012, odds ratio [OR] 1.50, 95% confidence interval [CI] 1.09-2.06) and revised Atlanta criteria-severe (p = 0.001, OR 7.84, 95% CI 2.40-25.6) were significantly associated with mortality. CONCLUSIONS: In patients with acute pancreatitis and infected ANC/WON, age and revised Atlanta criteria-severe classification are significantly associated with mortality whereas open necrosectomy is not. The mortality risk for patients undergoing open necrosectomy and minimally invasive treatment does not differ significantly. Although minimally invasive surgery is generally preferred for patients with infected ANC/WON, open necrosectomy may be considered if clinically indicated.

[Two cases of gastric cancer expressing Glypican 3, but producing AFP with different lectin affinity].

We encountered 2 cases of AFP-producing gastric cancer. In the first patient, an 82-year-old man was found to have advanced type II advanced carcinoma in the stomach with a massive tumor embolus in the portal vein. In the second case, an 80-year-old man was given a diagnosis of multiple liver metastases of gastric cancer with portal vein thrombosis. Our diagnosis of gastric cancer in both cases was AFP-producing. It was supposed that the elevation of serum level of AFP might be caused by enteroblastic differentiation in the first case and hepatoid differentiation in the second case. Although, in both cases, the biopsy specimens of the gastric neoplasm proved moderately to poorly differentiated adenocarcinoma without hepatoid differentiation, the localization of Glypican 3 in gastric cancer cells was observed using immunostaining with a monoclonal antibody. In both cases, Glypican 3 was a sensitive and useful marker for AFP-producing gastric cancer with or without hepatoid differentiation.